The management of walled off pancreatic necrosis in 2023 – Lessons learned from the past two decades

Piramanayagam Paramasivan

doi:10.4103/ghep.ghep_39_22

REVIEW ARTICLE

Year : 2023 | Volume : 3 | Issue : 2 | Page : 49-53

The management of walled off pancreatic necrosis in 2023 – Lessons learned from the past two decades

Piramanayagam Paramasivan
Department of Medical Gastroenterology, Apollo Hospitals, Chennai, Tamil Nadu, India

Date of Submission	09-Dec-2022
Date of Acceptance	16-Jan-2023
Date of Web Publication	09-Mar-2023

Correspondence Address:
Piramanayagam Paramasivan
Room 106, Apollo Hospitals, Greams Lane (Off Graeams Road), Chennai - 600 006, Tamil Nadu
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ghep.ghep_39_22

Abstract

Acute necrotizing pancreatitis is associated with the formation of acute necrotic collection which eventually becomes encapsulated to form walled-off pancreatic necrosis (WOPN) in 4 weeks. Good quality randomized controlled trials published in the past two decades have helped us understand and refine the management of WOPN. This review summarizes the lessons learned from these trials. Sterile pancreatic necrosis is managed conservatively unless they cause symptoms. Infected pancreatic necrosis leads to organ failure and mortality. The treatment paradigm for infected pancreatic necrosis has shifted from early open necrosectomy to initial intensive medical management, followed by interventions. Step-up approach with initial drainage followed by minimally invasive necrosectomy, in selected patients who do not improve with drainage, has been shown to have better short-term and long-term outcomes. Endoscopic step-up approach has been associated with a lower incidence of pancreaticocutaneous fistula and similar mortality or organ failure as compared to surgical step-up approach. Dedicated endoscopic accessories for performing necrosectomy are undergoing validation studies, which hopefully will help perform necrosectomy with less complications.

Keywords: Lumen-apposing metal stents, necrosectomy, step-up approach, walled-off necrosis

How to cite this article:
Paramasivan P. The management of walled off pancreatic necrosis in 2023 – Lessons learned from the past two decades. Gastroenterol Hepatol Endosc Pract 2023;3:49-53

How to cite this URL:
Paramasivan P. The management of walled off pancreatic necrosis in 2023 – Lessons learned from the past two decades. Gastroenterol Hepatol Endosc Pract [serial online] 2023 [cited 2023 Mar 27];3:49-53. Available from: http://www.ghepjournal.com/text.asp?2023/3/2/49/371280

Introduction

Acute pancreatitis is associated with significant necrosis of pancreatic parenchyma or peripancreatic tissue in 20% of patients. About ~90% of patients with necrotizing pancreatitis develop acute necrotic collection (ANC), which lack a well-defined wall. About 55%–60% of patients with ANC develop a wall around the collection containing both solid and liquid necrotic contents, usually in 4 weeks, and are termed as walled-off pancreatic necrosis (WOPN).^[1] The treatment paradigm of WOPN has evolved with the introduction and refinement of less invasive surgical and endoscopic treatment options. This review will focus on the evolution of treatment strategies for WOPN, based on the key good quality randomized controlled trials published in the past two decades.

Prognosis of Walled-off Pancreatic Necrosis

The primary determinant of the outcomes of patients who develop WOPN is the development of infection. Infected WOPN carries a high risk of mortality (15%–35%) as compared to sterile WOPN, which carries ~10% of mortality risk.^[2] Infected WOPN results in sepsis with multiorgan failure and death. Sterile necrosis can cause symptoms due to pressure effect on adjacent organs due to its enlarging size causing gastric outlet obstruction or biliary obstruction. Hemorrhage into the collection can occur due to bleeding from pseudoaneurysm or venous collaterals in the wall of the cavity formed as a result of splenic or portal venous thrombosis.

Indications for Intervention in Walled-off Pancreatic Necrosis

The indications for intervention in WOPN are (i) infection; (ii) pressure symptoms due to large collection causing early satiety with poor intake, gastric outlet obstruction, or biliary obstruction; and (iii) hemorrhage into collection. The diagnosis of infected WOPN relies mainly on clinical features of infection – fever, abdominal pain, or new-onset organ failure in patients with WOPN. Gas in the pancreatic parenchyma is also considered a sign of infection, though this can also be seen after spontaneous communication of WOPN with adjacent gut lumen. Image-guided aspiration from WOPN to culture the organism helps in choosing appropriate antibiotic therapy. However, it is not widely practiced due to the perceived risk of introducing infection in a sterile necrosis. Retrospective studies have shown that microbial culture evidence of infection was similar in those groups of patients diagnosed to have infected WOPN based on either clinical signs or radiological evidence of gas in collection or image-guided fine-needle aspiration, and the outcomes were not different between these groups.^[3]

The initial management of infected WOPN includes the initiation of broad-spectrum antibiotic, directed by local antibiotic protocol and enteral nutrition. Empirical antibiotic therapy should include antibiotics which are presumed to penetrate necrotic pancreatic tissue – preferably carbapenems or combination of quinolone and metronidazole.^[4] About 30% of patients respond to antibiotic therapy alone. Antibiotics are used till ANC becomes encapsulated, which enable safer (less risk of free perforation or bleeding) and less interventions. Most would require further interventions in the form of drainage and/or debridement.^[5]

Timing of Surgery in Walled-off Pancreatic Necrosis

WOPN can be drained by either one or combination of modalities – percutaneous catheter drainage or endoscopic stents or surgery. Historically, laparotomy and necrosectomy was the treatment, which was associated with high morbidity and mortality. A trial comparing early open surgical necrosectomy (<72 h after onset of necrotizing pancreatitis) with delayed necrosectomy (>12 days after onset) was halted midway as the odds ratio of mortality was three times higher in the early necrosectomy group.^[6] In a retrospective analysis of patients undergoing open surgical necrosectomy, it was noted that the mortality rate in patients undergoing early surgery (<14 days after onset of pancreatitis) was 75% as compared to 8% in patients undergoing delayed surgery (>30 days onset of pancreatitis).^[7] These data have changed the management strategy from early surgery to intensive medical management in the initial phase followed by delayed intervention.

Comparison of Open Surgical Necrosectomy and Step-up Surgical Approach

As open surgical necrosectomy carried significant adverse events including mortality, a “step-up” approach involving percutaneous drainage of necrotic collection as the initial step, followed by minimally invasive necrosectomy (video-assisted retroperitoneal debridement [VARD]) along the tract created by the initial percutaneous drainage, has been advocated. PANTER trial included 88 patients with infected WOPN who were randomized to step-up approach or open necrosectomy. The primary composite endpoint was the incidence of major complication or death. It was shown that step-up approach had a lower incidence of new-onset organ failure (12% vs. 42%, P < 0.001), while the mortality rate was similar in both the groups (19% vs. 16%). On follow-up at 6 months, new-onset diabetes mellitus and need for pancreatic enzyme supplement were also significantly lower in step-up approach. It was also noted that one-third of patients in step-up approach recovered with percutaneous drainage alone and did not require necrosectomy. This trial has changed the paradigm in favor of minimally invasive step-up approach, when anatomically feasible.^[8]

Comparison of Endoscopic and Surgical Step-up Approach

Since surgical procedures carried increased morbidity and mortality, it was postulated that endoscopic approaches to necrosectomy would not be associated with added “trauma” to patients who were already sick and would result in better outcomes. PENGUIN trial studied proinflammatory marker serum interleukin-6 (IL-6) levels, postintervention in twenty patients who were randomized to endoscopic transgastric necrosectomy or surgical necrosectomy (open and step-up approach included). There were significantly reduced IL-6 levels in endoscopic transgastric necrosectomy group as compared to surgical necrosectomy. The secondary endpoints in the form of major organ failure and death were also less in endoscopic group.^[9]

The hypothesis of whether endoscopic step-up approach was superior to surgical step-up approach was evaluated in TENSION trial. Initial drainage with endoscopic ultrasound-guided transgastric stent placement for drainage followed by endoscopic necrosectomy constituted “endoscopic step-up approach.” Initial percutaneous catheter drainage followed by VARD constituted “surgical step-up approach.” TENSION trial included 98 patients with infected WOPN who were randomized to either endoscopic or surgical step-up approach. Fifty percent of patients included in the trial had <30% pancreatic necrosis. Plastic pigtail stents were used in this trial for endoscopic drainage. This trial showed that endoscopic step-up approach was not superior to surgical step-up approach with regard to composite endpoint of death and major organ failure (43% in endoscopic step-up vs. 45% in surgical step-up). The number of necrosectomy sessions was higher in endoscopic step-up group compared to surgical step-up group. This was possibly due to delayed step-up to VARD in surgical step-up group (mean interval from drainage to necrosectomy: 23 days vs. 10 days) as compared to endoscopic step-up group.^[10]

Comparison of Endoscopic Step-up Therapy with Minimally Invasive Surgical Necrosectomy

In MISER trial, minimally invasive surgery was compared with endoscopic step-up approach in 66 patients at a single center in the US. Minimally invasive surgery group underwent either direct laparoscopic transgastric necrosectomy (80%) or VARD (20%). About ~28% of patients in minimally invasive surgery group underwent “step-up approach” with preoperative percutaneous catheter placement. Interestingly, 40% of patients in endoscopic group also had percutaneous catheter placement before endoscopic intervention. Nearly half of patients (47%) in endoscopy group had lumen-apposing metal stents (LAMSs), while the rest had plastic stent placement. The primary composite endpoint of major complications or death was significantly higher (40%) in minimally invasive surgery group as compared to 11% in endoscopic step-up group. Although there was no difference in mortality or major organ complication between the two groups, the proportion of patients with pancreaticocutaneous fistula, which was included as a part of the primary composite endpoint, was higher in the minimally invasive group (28%) as compared to none in endoscopic group. The secondary endpoints such as health-related quality of life and costs favored endoscopic step-up approach.^[11]

There are some key lessons to be learned from these trials. In both trials, endoscopic step-up approach was not superior to surgical step-up approach or minimally invasive surgery in terms of mortality or major organ complications, which determine outcome. The difference in the primary composite endpoint noted in MISER trial was mainly attributable to proportion of patients developing pancreaticocutaneous fistula. Pancreaticocutaneous fistula was not included in the primary composite endpoint in TENSION trial. If step-up approach is adopted, 40%–66% of patients will respond to drainage alone and will not require necrosectomy. The decreased need for necrosectomy in step-up approach is consistent with other studies as well.^[12] When step-up approach is adopted, additional percutaneous drainage is likely to be required in ~15%–20% of patients after primary intervention. About 15%–20% of patients with infected WOPN will not be amenable for step-up approach and will require open surgical necrosectomy.

Endoscopic Drainage – Plastic or Lumen-apposing Metal Stents

Plastic stent with smaller internal diameter frequently get clogged with thick necrotic debris resulting in incomplete drainage and infection, requiring reintervention [Figure 1]. If necrosectomy was required, tract had to be dilated after removal of the plastic stents to allow the passage of endoscope. Covered biliary metal stents (10 mm diameter) were used to provide better drainage with an increased risk of migration. LAMS was approved for the drainage of pancreatic WOPN with >70% fluid content in 2013. The larger diameter of WOPN (10–20 mm) was expected to provide better drainage as well as serve as a conduit for necrosectomy. Electrocautery-enhanced delivery system along with stent (Hot Axios™, Boston Scientific, USA) enabled the placement of LAMS as a single-step procedure without a need for guidewire exchange, thereby shortening the procedure duration. As LAMS provided a larger diameter for the drainage of solid necrotic content, it was hypothesized that there will be reduced need for necrosectomy and shorter procedure duration. However, randomized controlled trials^[13] and comparative studies of LAMS with historical-matched plastic stent cohorts^[14] have not shown a superiority of LAMS over plastic stent in reducing the need for reinterventions or necrosectomy.

Figure 1: Technique of endoscopic necrosectomy. (a) Imaging of WOPN by EUS, (b) EUS-guided puncture of WOPN followed by passage of guidewire into the cavity, (c) Transmural tract dilatation using controlled release expansion balloon, (d) Visualization of necrotic contents by passing endoscope into the necrotic cavity, (e) Necrosectomy done using snare and depositing it in the stomach, (f) Placement of multiple double-pigtail plastic biliary stents across the wall of the stomach at the end of necrosectomy session. WOPN: Walled-off pancreatic necrosis, EUS: Endoscopic ultrasound

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LAMS was associated with an increased risk of bleeding and migration after 3 weeks of placement. Due to the collapse of WOPN cavity, distal biflanged stent erodes the vessels of the cavity and results in pseudoaneurysm formation and bleeding. LAMS can migrate into the cavity or into the lumen or be buried in the wall of lumen due to partial migration. Biliary stricture has been reported to LAMS causing compression over the lower bile duct, while migration into the lumen has been associated with gastric outlet, intestinal obstruction. Hence, it is recommended to remove LAMS within 3 weeks of insertion, if WOPN has resolved or replace with plastic stents if persistent WOPN is noted on CT at the end of 3 weeks.

The recurrence of fluid collection after removal of LAMS is seen in 13%–25% at 1 year. One of the key factors associated with the recurrence of fluid collection is disconnected pancreatic duct (DPD) (>90%). DPD is defined as a complete disruption of main pancreatic duct with the isolation of viable pancreatic parenchyma upstream.^[15] In a large retrospective study of patients with WOPN drained by LAMS, who underwent endoscopic retrograde cholangiopancreatography (ERCP) (before LAMS removal), DPD was observed in 73%. Thirteen percent of patients in the study had the recurrence of fluid collection at 5 months, with ~50% being symptomatic requiring reintervention. The risk of recurrence of fluid collection was higher in those with DPD (17% vs. 1%).^[16] Some centers exchange LAMS for permanent indwelling transmural plastic stent as a treatment modality to reduce the risk of recurrence of fluid collections in patients with DPD. A randomized trial of this strategy compared with no stent showed a similar recurrence rate at 3 months (5%) and lower, though not statistically significant risk of the recurrence at 6 (13% vs. 19%, P > 0.05) and 12 months (13 vs. 25%, P > 0.05).^[17]

Role of Multiple Transluminal Gateway Technique

There have been some technical modifications of transluminal drainage, which include multiple transluminal gateway technique, wherein multiple transluminal tracts are created with the deployment of stents (plastic or metal) to help drain the contents better. It was shown in retrospective series that placing multiple transluminal gateway technique (using plastic stents) was better at achieving treatment success as compared to conventional single transluminal plastic stent in patients with WOPN.^[18]

Role of Percutaneous Necrosectomy

Percutaneous necrosectomy (PEN) or sinus tract necrosectomy is the modification of percutaneous step-up approach, in which endoscope is used for necrosectomy after dilatation of percutaneous catheter tract instead of VARD. It has certain advantages over transluminal endoscopic necrosectomy as PEN can be done in areas inaccessible to endoscope such as paracolic gutters and can be done at bedside and avoid general anesthesia. The use of flexible endoscope allows more effective necrosectomy as the scope can be better maneuvered than nephroscope or laparoscope for the removal of debris. It has been shown in a retrospective cohort study to be 62% effective in managing infected pancreatic necrosis (including both WOPN and ANC). Necrosis >50% and early-onset organ failure are known to be independent predictors of unsuccessful percutaneous step-up approach.^[19]

Dual-Modality Drainage

Combined percutaneous catheter and transluminal stent placement (dual-modality drainage) has been shown in single-center retrospective studies to have a shorter length of hospital stay, shorter time until the removal of percutaneous drains, fewer computed tomography scans, and ERCP. Dual-modality drainage was associated with ~88% clinical response rate in retrospective series.^[20],[21]

Role of Hydrogen Peroxide Irrigation

The ancillary use of hydrogen peroxide for irrigation has been reported to be safe and useful in two systematic reviews and meta-analyses of case series.^[22],[23] No large-scale randomized controlled trials have been done to evaluate the role of hydrogen peroxide in WOPN.

Revisiting the Timing of Necrosectomy in the Era of Endoscopic or Minimally Invasive Necrosectomy

The current treatment paradigm to delay intervention after 4 weeks in infected pancreatic necrosis was based on the increased mortality associated with early necrosectomy (<4 weeks) in open necrosectomy era. As step-up approach has been proven to be superior to and safer than open necrosectomy, it was hypothesized if step-up approach can be applied safely in ANC (<4 weeks) even when the collection has not been encapsulated completely. The retrospective analysis of early (<4 weeks) endoscopic step-up approach was shown to be feasible without additional complications when compared with delayed endoscopic step-up necrosectomy (>4 weeks).^[24] POINTER trial was done to assess if early drainage (percutaneous or endoscopic) within 24 h of diagnosing infected pancreatic necrosis was superior to delaying drainage till the stage of walled-off necrosis was achieved. The primary endpoint, comprehensive complication index over 6 months, was similar in both groups. However, early drainage group had more interventions (4.4 vs. 2.6) and necrosectomy (50% vs. 22%). In addition, one-third of patients in delayed drainage group responded to antibiotics alone and did not require drainage. Hence, early drainage, though safe, did not result in improved outcomes.^[5]

Endoscopic Devices for Necrosectomy

Endoscopic attempts at necrosectomy have been hampered by a lack of dedicated devices for the same. Removal of necrosum with the currently available devices such as snares, rat tooth forceps, and baskets is inefficient, laborious, and time-consuming. A new powered endoscopic debridement system has been evaluated for safety outcomes in a multicenter trial recently.^[25] More data from randomized trials evaluating its efficacy will be required.

Summary

The management of necrotizing pancreatitis has evolved in the past two decades. There has been a gradual shift from early surgical intervention to early intensive medical management and delaying surgical intervention till necrotic collections become walled off. Step-up approach with initial drainage by either percutaneous or endoscopic techniques followed by necrosectomy, in selected patients, is preferred over open necrosectomy. Up to one-third of patients may not require a second step of necrosectomy if step-up approach is adopted. Endoscopic step-up approach is associated with the less frequency of pancreaticocutaneous fistula and is comparable to surgical step-up approach in terms of mortality or major organ failure. Refinement in endoscopic techniques of transmural drainage is a work in progress as is the development of dedicated accessories for endoscopic necrosectomy. Open necrosectomy still has a place in the management of WOPN, in up to 15% of patients in whom the location of collections is not suitable for endoscopic or percutaneous drainage. The management of WOPN requires a multidisciplinary approach with intensivists, medical gastroenterologists, intervention radiologists, and surgeons to achieve good outcomes.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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