PANTER

Published

van Santvoort HC, et al. "A Step-up Approach or Open Necrosectomy for Necrotizing Pancreatitis". The New England Journal of Medicine. 2010. 362(16):1491-502.
PubMed • Full text • PDF

Clinical Question

Among patients with necrotizing pancreatitis with infected necrosis, what are the differences in outcomes between a minimally invasive step-up approach and primary open necrosectomy?

Bottom Line

A minimally invasive step-up approach reduced complications or death by 43% compared with primary open necrosectomy, among patients with necrotizing pancreatitis and infected necrosis.

Major Points

Secondary infection of pancreatic necrosis remains a leading cause of death in necrotizing pancreatitis, and is treated with percutaneous drainage and/or surgical debridement. However, the choice of initial procedure has remained controversial. The Minimally Invasive Step Up Approach versus Maximal Necrosectomy in Patients with Acute Necrotising Pancreatitis (PANTER) trial randomized 88 patients with necrotizing pancreatitis and infected necrosis to either a minimally invasive step-up approach or primary open necrosectomy. The step-up approach utilized percutaneous or endoscopic transgastric drainage followed by video-assisted retroperitoneal debridement if necessary. It found a 43% reduction in the composite primary outcome, major complications or death. Significant reductions were seen in the rate of long-term complications, health care utilization, and total cost. Minimally invasive approaches to necrotizing pancreatitis are now rapidly becoming the standard of care, with open surgery being generally reserved for cases of simultaneous intraabdominal complications.

Guidelines

The findings have been adopted in guidelines established in 2013 by the American College of Gastroenterology for the Management of Acute Pancreatitis

• In symptomatic patients with infected necrosis, minimally invasive methods of necrosectomy are preferred to open necrosectomy.

Design

• Multicenter, parallel-group, randomized, controlled trial
• N=88
  • Step-up approach (n=43)
  • Primary open necrosectomy (n=45)
• Setting: 7 university centers and 12 large teaching hospitals in The Netherlands
• Enrollment: 2005-2008
• Analysis: Intention-to-treat
• Follow-up: 6 months

Population

Inclusion Criteria

• Age ≥18 years
• Pancreatic and/or peripancreatic necrosis on contrast CT
• Decision for procedure must be based on suspected infected necrosis
• Ability to place drain in necrotic collection(s)

Exclusion Criteria

• Acute-on-chronic pancreatitis
• Prior exploratory laparotomy during current episode of pancreatitis
• Prior drainage or surgery for infected necrosis
• Pancreatitis due to abdominal surgery
• Post-abdominal surgery necrotizing pancreatitis
• Other indications for procedure: bleeding, abdominal compartment syndrome, or perforated viscus

Baseline Characteristics

Comparisons are step-up approach vs. primary open necrosectomy.

• Age: 57-78 years
• Males: 72-73%
• Cause of pancreatitis
  • Gallstones: 26 vs. 29%
  • Alcoholic: 7 vs. 11%
  • Other: 33% vs. 24%
• Coexisting condition
  • CV disease: 44% vs. 47%
  • Pulmonary disease: 9%
  • CKD: 7% vs. 4%
  • DM: 12% vs. 9%
• ASA class at admission
  • I (healthy): 26% vs. 24%
  • II (mild systemic disease): 44%
  • III (severe systemic disease): 30% vs. 31%
• BMI at admission: 28 vs. 27 kg/m²
• CT severity index: 8
• Extent of pancreatic necrosis
  • <30%: 40% vs. 42%
  • 30-50%: 33% vs. 22%
  • >50% 28% vs. 36%
• Necrosis >5 cm down paracolic gutter: 56% vs. 60%
• Retroperitoneal access to necrosis possible: 93% vs. 89%
• Disease severity
  • SIRS: 98% vs. 100%
  • ICU at time of randomization: 54% vs. 47%
  • ICU at any time before randomization: 65% vs. 64%
  • Single organ failure: 49%
  • Multiple organ failure: 35% vs. 29%
  • Positive blood culture in prior 7 days: 33%
  • Positive blood culture before randomization: 51% vs. 56%
• APACHE II score: 15
• APACHE II score ≥20: 23% vs. 20%
• MODS: 2 vs. 1
• SOFA score: 3 vs. 2
• CRP: 214 vs. 216 mg/L
• WBC: 18 vs. 16
• Time since symptom onset: 30 vs. 29 days
• Antibiotics before randomization: 86% vs. 84%
• Nutritional support before randomization:
  • Enteral only: 54% vs. 51%
  • Parenteral only: 7% vs. 9%
  • Both: 28% vs. 24%
  • Oral: 12% vs. 16%
• Tertiary referral: 49% vs. 51%
• Confirmed infected necrosis: 91% vs. 93%

Interventions

• Randomized to minimally invasive step-up approach or primary open necrosectomy
• Open necrosectomy consisted of laparotomy through bilateral subcostal incision, blunt removal of necrosis, insertion of two large-bore drains for postoperative lavage, and closure of abdomen
• Step-up approach began with percutaneous or endoscopic transgastric drainage (preferred approach via left retroperitoneum)
  • If no improvement within 72h and drain(s) position inadequate/insufficient, then second drainage procedure performed
  • If not possible or if no improvement within additional 72h, video-assisted retroperitoneal debridement (VARD) and perioperative lavage was performed
• Follow-up visits at 3 and 6 months post-discharge

Outcomes

Comparisons are step-up approach vs. primary open necrosectomy.

Primary Outcome

Major complications or death

40% vs. 69% (RR 0.57; 95% CI 0.38-0.87; P=0.006; NNT=3)

Secondary Outcomes

Death

19% vs. 16% (RR 1.20; 95% CI 0.48-3.01; P=0.70)

Major Complication

New-onset multiple organ failure or systemic complications

12% vs. 42% (RR 0.28; 95% CI 0.11-0.67; P=0.001)

Multiple organ failure

12% vs. 40%

Multiple systemic complications

0% vs. 2%

Intraabdominal bleeding requiring intervention

16% vs. 22% (RR 0.73; 95% CI 0.31-1.75; P=0.48)

Enterocutaneous fistula or perforation requiring intervention

14% vs. 22% (RR 0.63; 95% CI 0.25-1.58; P=0.32)

Other Outcomes

Pancreatic fistula

28% vs. 38% (RR 0.74; 95% CI 0.40-1.36; P=0.33)

Incisional hernia

7% vs. 24% (RR 0.29; 95% CI 0.09-0.95; P=0.03)

New-onset diabetes

16% vs. 38% (RR 0.43; 95% CI 0.20-0.94; P=0.02)

Use of pancreatic enzymes

7% vs. 33% (RR 0.21; 95% CI 0.07-0.67; P=0.002)

Health Care Utilization

Necrosectomies

0: 40% vs. 0

1: 44% vs. 69%

2: 14% vs. 18%

≥3: 2% vs. 13%

Number of operations

53 vs. 91 (P=0.004)

Number of drainage procedures

82 vs. 32 (P=0.004)

New ICU admission after first intervention

16% vs. 40% (RR 0.41; 95% CI 0.19-0.88; P=0.01)

ICU days

9 vs. 11 (P=0.26)

Hospital days

50 vs. 60 (P=0.53)

Criticisms

• Not powered to demonstrate mortality difference.
• No direct comparison of open necrosectomy and video-assisted retroperitoneal necrosectomy.
• No direct comparison between percutaneous drainage and endoscopic transgastric drainage.

Funding

Funding through a grant from the Dutch Organization for Health Research and Development.