Paradigm shift away from open surgical necrosectomy toward endoscopic interventions for necrotizing pancreatitis

Abstract

Introduction

Acute pancreatitis (AP) is a dynamic inflammatory process with a benign clinical course and low mortality. However, 10–20% of patients experience severe AP, which can result in an intense in-flammatory response, a prolonged hospital course, and variety of local and systemic complications that carry a significant risk of morbidity and mortality.1–4 Necrosis of the pancreas itself is defined by nonenhancement of the parenchyma on dynamic computed tomography scan, and approximately 5–10% of patients with AP develop necrotizing pancreatitis. Necrosis of peripancreatic/pancreatic tissue can progress to liquefaction with subsequent organization without epithelial lining, and eventual evolution into a walled-off pancreatic necrosis (WOPN) over 4 weeks. This may be related to secondary infection or symptomatic sterile necrosis. Because the mortality rate of infected WOPN is as much as approximately 39% compared to 15% of sterile WOPN, patients with infection generally need to undergo an intervention, which has shifted from primary open necrosectomy to a step-up approach. Currently, step-up approach is a widely used treatment modality consisting of percutaneous catheter drainage (PCD), endoscopic transmural drainage (ETD), and endoscopic transmural necrosectomy (ETN). Of these, ETN provides a targeted approach with a reduction in the systemic inflammatory response and avoidance of wound complications5; its use is increasingly widespread and now accepted as a first line treatment for this condition. In this review, we aim to determine the risk and benefits of ETN for management of necrotizing pancreatitis.

Indications and strategies of intervention for WOPN

The primary indications for intervention in WOPN are similar regardless of different intervention routes, such as endoscopic, percutaneous, or surgical approach. The indications for intervention in WOPN are as follows: (1) clinical suspicion or documented infected WOPN with clinical deterioration; (2) ongoing organ failure in the several weeks after the onset of acute pancreatitis; (3) symptomatic sterile WOPN including intractable pain, persistent unwellness, ongoing gastrointestinal obstruction; and (4) disconnected pancreatic duct syndrome with WOPN.

Among various treatment modalities, surgical debridement, either open or laparoscopic, may be associated with prolonged recovery, the need for repeat operations, external fistula, and abdominal wall hernias.6,7 Percutaneous debridement techniques have been used as an alternative to operative management; however, these methods are not universally successful and additional combination treatment is required.8–10 Endoscopic interventions, such as ETD and ETN, have also been introduced in an effort to overcome the aforementioned limitations; however, there are some problems of accessibility and complication. Therefore, combination treatments using PCD, ETD, ETN, and surgery by a step-up manner have recently been advocated. Endoscopic or percutaneous drainage is first recommended, and followed, if necessary, by endoscopic or minimally invasive surgical necrosectomy. As a targeted minimally invasive approach, ETN with mechanical debridement was demonstrated to be an efficacious and reproducible technique with an acceptable safety profile.11,12 The ideal goal of ETN is excision of all dead and devitalized pancreatic and peripancreatic tissue while preserving a viable functioning pancreas, and controlling surgery related complications.

Overview of ETN

Necrotizing pancreatitis is a dynamic disease process that evolves in local and systemic inflammation; consequently, endoscopic/percutaneous drainage alone often proves inadequate, and additional endoscopic/surgical necrosectomy is required. The optimal time for intervention of necrotizing pancreatitis is important in order to reduce the occurrence of procedure related complications, and it should be delayed by approximately 4 weeks after the onset of pancreatitis, when vascular inflammation has decreased, organization of the process has occurred, and delineation of live from dead tissue is complete. At this point, the retroperitoneal inflammatory response decreases and the necrotic areas are demarcated from the surrounding viable tissue, which may permit definitive endoscopic debridement.

Endoscopic interventions require proximity to the gastroduodenal lumen and WOPN, whereas percutaneous drainage may be suitable for collections distant from the gut lumen and those with less demarcation. Necrosis closely adhering to the posterior gastric wall or medial duodenal wall is considered an ideal access route for ETN; thus it is typically performed via a transgastric or transduodenal approach. Under conscious sedation or anesthesia, a puncture site is identified by locating a bulge into the gastrointestinal lumen using endoscopic ultrasound or visual assessment. The fluid collection is then entered, a sample of fluid is aspirated and cystenterostomy is created using wire-guided balloon dilators up to 15–20 mm. Once the entry site is established, direct endoscopic debridement using endoscopic accessories, including snare, baskets, and stone retrieval balloons, can be performed using a conventional upper or water-jet endoscope. When ETN extends into the fat of the mesocolon or small bowel mesentery, meticulous care should be taken to avoid vascular injury, particularly to the colic, superior, or inferior mesenteric vessels. After mechanical removal of necrotic debris, large-bore double pigtail plastic stents or a fully covered self-expandable metallic stent (SEMS) are inserted into the cavity; a nasocystic tube may occasionally be placed for postinterventional lavage. ETD can be performed during the index procedure, but it is usually repeated on a regular basis until the cavity is clean by direct visualization. As many as 3–10 sessions may be necessary for complete debridement of the necrotic cavity; however, the number of sessions depends on disease severity (Fig. 1).

Figure 1

Sequential endoscopic images showing walled off pancreatic necrosis (WOPN) cavity. (A) Initial finding after entry into complicated WOPN; (B) net snare removal of necrotic material; and (C) clean cavity after ...

Outcomes of endoscopic intervention

Endoscopic interventions for WOPN carry significant additive risks, and there are a few comparative data to document increased success. Published studies of ETD and ETN are summarized in Table 1.5,11–23 The Dutch Pancreatitis Group compared endoscopic intervention (n = 10) and surgical necrosectomy (n = 10), and showed that ETN reduced the proinflammatory response as well as the composite clinical end point compared with surgical necrosectomy.5 Factors that predict failure of endoscopic therapy have not been well studied. A major determinant for the feasibility of ETN is the location of the target collection and other risk factors for failure of endoscopic intervention are the size of the necrotic cavity (>15 cm), deep retroperitoneal extension, presence of diabetes mellitus, and comorbid conditions. Early aggressive adjuvant therapy, such as PCD with or without sinus tract endoscopy or video-assisted retroperitoneal debridement, in addition to endoscopic treatment, was required in patients with more extensive necrotic debris, severe pancreatic duct disruption, or deep retro-peritoneal necrotic extension.17 In cases of inaccessible necrotic collections, a variety of other minimally invasive retroperitoneal approaches, including PCD, sinus tract endoscopy, and video-assisted retroperitoneal debridement procedure may be either preferable or serve as adjuncts to endoscopic therapy.

Several novel approaches were recently introduced. First, the multigateway approach uses more than one transmural entry site created in order to facilitate rapid drainage in large (>80 mm) symptomatic WOPN.24 One tract may serve as a channel for irrigation, whereas the other acts as an exit conduit for drainage of necrotic contents.25 Second, esophageal fully covered SEMS has been used for drainage of peripancreatic/pancreatic collections26,27; however, potential stent migration and uncertainty regarding cost-effectiveness preclude widespread adoption in clinical practice. Third, a novel type of antimigration SEMS for cystenterostomy has been developed.28,29 These stents have a wide lumen (16 mm diameter), allowing insertion of the endoscope through the stent lumen for direct necrosectomy. In addition, novel methods including hydrogen peroxide, vacuum sponge, and newly developed grasping type of scissors for debridement are under continuous investigation.30–32 Although their advantages and safety are unclear compared to conventional methods, further studies using newly developed devices and accessories for endoscopic necrosectomy are anticipated.

Complications and limitations

A complication rate of ETN of up to approximately 30% has been reported. In a recent systematic review including >1100 endoscopic necrosectomy procedures in 260 patients, procedure-related morbidity rate was 27% and all-cause mortality rate was 5%.33 Bleeding is the most common complication and it may occur during the index puncture or direct debridement of the necrotic material. Sometimes, incidental mechanical injury of retroperitoneal vessels such as the portal vein may result in a drastic hemorrhage requiring emergent angiography or even surgery. Perforation, another severe complication, might occur during initial cystenterostomy, repeated dilation of the access route, or disruption of the cavity wall. In general, surgical management is required in many cases of perforation however, Gardner et al11 reported successful nonoperative management of five patients with perforation. In addition, many complications, including infection of necrotic materials, air embolism, gallbladder puncture, stent migration, fistula, and bowel obstruction may occur during ETN. Among them, air embolism, which is likely from dissection of insufflated air through exposed retroperitoneal vessels, may sometimes lead to fatal consequences. Carbon dioxide is now very strongly recommended for air insufflation during ETN, as it theoretically minimizes the chance of air embolism.

ETN is the one of the most aggressive endoscopic interventions; avoidance of all complications is impossible. Therefore, the most important thing is the early recognition of these potential life-threatening complications, and endoscopists should immediately take an appropriate action for them in collaboration with interventional radiology and surgery.

ETD and ETN are regarded as important therapeutic procedures for management of complicated and symptomatic WOPN; however, many controversies remain. Contrary to opinion with regard to preference of ETD or ETN, several reports have suggested the possibility of treatment of WOPN without formal drainage, either by antibiotics alone or more commonly by use of selective percutaneous drainage. Mouli et al34 recently published a meta-analysis involving 324 patients, which showed that primary nonoperative management of infected necrosis without necrosectomy was successful in 64% of cases and was associated with a lower mortality and obviated the need for surgical necrosectomy. However, it remains unclear as to which patients with WOPN can be safely and effectively managed with or without any forms of intervention, and which method is better for management of cases. Considering the high likelihood of success with ETD or transpapillary pancreatic stent placement (in properly selected patients) alone, combined procedures should probably be limited to special situations in order to minimize complications.

Moreover, it is still not known whether endoscopic ultrasound is necessary in every initial puncture for cystenterostomy and whether the optimal strategy involves a step-up approach with initial drainage followed by on-demand ETN versus scheduled ETN. It is also unclear whether necrosectomy, once started, should be carried to completion in every case. In addition, there is uncertainness of optimal timing, number of sessions, and completeness of endoscopic debridements, and we do not have knowledge of the optimal interval between sessions and how to remove the necrotic tissue. In terms of medical devices for drainage and debridement, there is a lack of dedicated instruments available for necrosectomy, many of which are borrowed from other endoscopic applications. In addition, the optimal stent for cystenterostomy also remains unsettled, although the trend seems to be toward increasingly large tissue-apposition-type removable SEMS.

Conclusion

As a targeted minimally invasive approach, ETN with mechanical debridement was suggested to be an efficacious and reproducible technique with an acceptable safety profile. Despite the possibility of severe procedure related complications, including perforation, hemorrhage, infection, and air embolism, ETN with mechanical debridement is regarded as a primary therapeutic method for complicated and symptomatic WOPN. Considering the inherent properties and the procedure related risks, ETN should be performed by experienced interventional endoscopists who are well-versed in management of necrotizing pancreatitis at specialized centers, and the optimal treatment should be tailored to the individual patient by a multidisciplinary approach including a gastroenterologist, interventional radiologist, and surgeon. Given the complexity and risk associated with ETN, specific comprehension of pathogenesis of necrotizing pancreatitis, specialized training of interventional endoscopic techniques and multidisciplinary approach to patients are essential to improving the therapeutic outcomes of complicated WOPN.

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