DISPACT Trial

In Review

Diener MK, et al. "Efficacy of stapler versus hand-sewn closure after distal pancreatectomy (DISPACT): a randomised, controlled multicentre trial". The Lancet. 2011. 377(9776):1514-1522.
PubMed • Full text

Clinical Question

In patients with disease of the pancreatic tail and body do hand sewn or stapled closure of the remnant pancreas result in a lower incidence of pancreatic fistula and mortality?

Bottom Line

The pancreatic fistula rate, serious adverse events, and mortality did not differ between patients who had hand sewn or stapler closure of the pancreatic remnant.

Major Points

One of the major and most common (0-40%) of distal pancreatectomies are pancreatic fistulas . Distal pancreatectomies are defined as surgical resection of the pancreas occurring to the left of the superior mesenteric vein. Pancreatic fluid consists of 90% digestion enzymes. After a resection this fluid can leak from the remnant pancreas and be activated in the surrounding abdominal cavity. Fistulas commonly lead to collections, abscesses, wound infection, delayed gastric emptying, respiratory complications, sepsis and bleeding. Often fistulas are difficulty to diagnose and to manage. They significantly increase morbidity and prolong hospital stays; often requiring further surgical or interventional treatment, which has serious implications for patients and for the health care system .

In this trial the team evaluated the effectiveness stapled vs. hand sewn closure of the pancreatic remnant; the two most common surgical techniques for distal pancreatectomy. At the time of this trial there was no literature to suggest which technique was associated with decreased morbidity. Through their analysis the researchers demonstrated that there was no difference in morbidity (fistula rate, serious adverse event, and mortality) between staple and hand-sewn techniques. The authors also found that 36% of patients will develop a fistula by day 30, and up to 25% will experience a serious adverse event. Both groups also experienced intraabdominal abscesses and fluid collections at a rate of 19%. These adverse events mean increased morbidity for patients, and more money spent on interventions (surgical and interventional) to remediate them.

The authors ultimately concluded that stapler and hand sewn closure are equally safe in distal pancreatectomy. The formation of fistulas therefore remains clinically relevant and unsolved for patients.

Guidelines

Cited by The Association of the Scientific Medical Societies in Germany Guidelines for Chronic Pancreatitis on 31 Aug 2012

Design

• Multicenter, double-blind, stratified and randomized, controlled trial
• N=223
  • Hand Sewn (n=146)
  • Stapler (n=150)
• Setting: 21 centers in Germany
• Enrollment: November 16 2006- July 3 2009
• Mean follow-up: 12 months
• Analysis: Intention-to-treat
• Primary outcome: The development of a postoperative pancreatic fistula and/or death due to any cause.

Population

Inclusion Criteria

• Age ≥ years
• Expected survival time more than 12 months
• Patients with at least one of the following pathological diseases scheduled for elective resection:
  • Resectable malignancies of the pancreatic tail
  • Resectable chronic pancreatitis of the tail
  • Resectable benign tumors of the pancreas including neuroendocrine tumors
  • Pseudocyst of the pancreatic tail

Exclusion Criteria

• Current immunosuppressive therapy
• Chemotherapy 2 weeks or less before operation
• Radiotherapy completed more than 8 weeks before operation
• Curative resection not feasible
• Severe psychiatric or neurologic diseases
• Drug and/or alcohol abuse according to local standards
• Participation in another intervention trial with interference of a primary or secondary endpoint of this study
• Inability to follow the instructions given by the investigator
• Lack of compliance
• Lack of informed consent

Baseline Characteristics

• Stapler Group
  • Male: 48%
  • Female 52%
  • Age (years): 59.8
  • BMI (kg/m²): 25.2
  • Indication for operation
    • Malignant disease: 51%
    • Benign tumors: 37%
    • Chronic pancreatitis: 10%
    • Pseudocyst: 10%
    • Other: 6%
  • Risk levels (as randomized):
    • High (malignant, non-malignant, neuroendocrine tumours): 84%
    • Low (chronic pancreatitis and pseudocysts): 16%
  • Risk levels (as documented):
    • High: 86%
    • Low: 14%
  • Concomitant treatment:
    • Immunosuppressive treatment: 2%
    • Analgesic treatment: 9%
  • Somatostatin analogues: 0%
  • Neoadjuvant chemotherapy: <1%
  • Comorbidity:
    • Diabetes mellitus: 16%
    • Never smoked: 69%
    • Previous smoker: 19%
    • Current smoker: 12%
  • Surgical skills:
    • Low: 21%
    • Medium: 10%
    • High: 69%
  • Surgeon's experience:
    • 1-3 years: 0%
    • 4-6 years: 6%
    • 7-9 years: 16%
    • ≥10 years: 78%
  • Technique of laparotomy:
    • Midline: 44%
    • Transverse: 46%
    • Other: 10%
  • Splenectomy: 82%
  • Lymph-node dissection: 61%
  • Somatostatin during surgery: 41%
  • Somatostatin after surgery: 49%

Interventions

• Standardized surgical abdominal approach:
  • Midline or transverse laparotomy in keeping with local standards
  • complete exploration of the abdomen, including frozen sections, in order to determine if curative resection is possible
  • The surgeon decides if splenectomy is indicated based on the patient's disease and curative intention
  • No additional treatment or covering of the pancreatic remnant is permitted

• Intraabdominal drainage
  • Each patient must receive at least one intraabdominal drainage tube in order to measure amylase and output to assess the primary outcome
  • The drain(s) should remain in place until post operative day 3
  • The use of soft, non rigid drainage tubes is recommended

• Hand sewn group:
  • Complete mobilization of the pancreatic tail (up to the region of the superior mesenteric vein or at least 2-3 cm central of the planned resection margin)
  • Resection performed with a surgical scalpel
  • Closure of the remnant with a separately stitched ligation of the pancreatic duct, followed by a single stitched or running suture of the entire remnant
  • Suture material should be slowly absorbable monofilament such as PDS^TM or MonoPlus^TM
  • Recommended suture strength is USP 4/0 and USP 5/0
  • Non absorbable sutures are not permitted for the closure of the pancreas

• Staple closure group:
  • Pancreatic resection and transsection of the pancreatic body will be done using a linear stapling device (Ethicon TL 60 1.0-2.5 mm) with a 60 mm magazine
  • The depth of individual staple can be chosen as needed, ranging from 1.0-2.5 mm

Outcomes

Comparisons are stapler vs. hand sewn interventions.

Primary Outcomes

Pancreatic fistula (day 3-7) and death (until day 7)

32% vs. 28% (OR 0.84; 95% CI 0.53-1.33; P=0.56)

Mortality (until day 7)

0% vs. 0006% (P=0.31)

Secondary Outcomes

Pancreatic fistula (30 days)

36% vs. 37% (OR 1.94; 95% CI 0.68-1.61; P=0.84)

Mortality (30 days)

0.006% vs. 1% (OR 2.04; 95% CI 0.18-22.7; P=0.55)

Total operating time (min)

187.7 vs. 192.4 (OR 1.00; 95% CI 1.00-1.00; P=0.70)

Resection time for distal pancreatectomy (min)

68.4 vs. 70.8 (OR 1.00; 95% CI 1.00-1.01; P=0.43)

Wound dehiscence

0.006% vs. 1% (OR 2.0.4; 95% CI 0.18-22.7; P=0.55)

Wound infection

6% vs. 5% (OR 0.82; 95% CI 0.33-2.03; P=0.66)

Intraabdominal fluid collection or abscess

19% vs. 19% (OR 1.01; 95% CI 0.60-2.03; P=0.95)

Concomitant occurrence of pancreatic fistula and fluid collection or abscess

9% vs. 8% (OR 1.14; 95% CI 0.54-2.42; P=0.73)

New onset of diabetes mellitus

9% vs. 13% (OR 1.52; 95% CI 0.78-2.99; P=0.22)

Length of hospital stay (days)

15.1 vs. 15.7 (OR 1.00; 95% CI 0.99-1.02; P=0.86)

Mortality (90 days)

3% vs. 3% (P=0.98)

Mortality (12 months)

9% vs. 10% (P=0.69)

Patients with at least one serious adverse event

49% vs. 40% (P=0.08)

Serious adverse event resulting in death

13% vs. 15% (P=0.69)

Pancreatic fistula

20% vs. 22% (P=0.25)

Delayed gastric emptying

2% vs. 0% (P=0.25)

Bleeding

7% vs. 9% (P=0.25)

Abscess or fluid colection

16% vs. 9% (P=0.25)

Cholangitis

2% vs. 1% (P=0.25)

Other surgical morbidity

17% vs. 18% (P=0.25)

Cardiocirculatory

7% vs. 5% (P=0.25)

Pulmonary

3% vs. 7% (P=0.25)

Pancreatic cancer or metastasis

13% vs. 8% (P=0.25)

Renal

2% vs. 3% (P=0.25)

Criticisms

• The authors identified the following limitations in their trial:
  • The choice to have the endpoint for the primary outcome of pancreatic fistula up to day 7 might have been too short, as there was a significant increase in the rate of fistulas up to day 30
  • Randomization should be done intraoperatively as opposed to preoperatively, there would have been less exclusions (i.e. the patients in which distal pancreatectomy was not done)

Funding

• The authors did not declare any conflicts of interest
• German Federal Ministry of Education and Research