Same admission vs. Interval cholecystectomy for
mild gallstone pancreatitis
- the PONCHO trial -
David da Costa
No conflict of interest or disclosures
David da Costa
SIS-, Amsterdam
2-6-2016
Introduction
Introduction
• Acute pancreatitis is a common emergency admission
diagnosis
– Usually caused by gallstones1
– Mild disease course in 85% of cases2
• Cholecystectomy to reduce the risk of recurrence
• Median waiting period to surgery 6 weeks3,4
– Early surgery more difficult?
– Logistical reasons
1Yadav
Gastro 2013; 2Banks Gut 2012; 3Bakker BJS 2011; 4 van Baal Ann Surg 2012
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Safety of early cholecystectomy
Introduction
• Increased morbidity and mortality after severe pancreatitis1,2
• Difficulty of dissection after mild pancreatitis appears to increase
with time…
1Kelly
Surgery 1988, 2Nealon Annals of Surg 2004
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Logistical aspects
Introduction
• Large variation in performing cholecystectomy
– 4.5 - 45%1
1 Johnstone, the Surgeon 2013
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The problem…
Introduction
• Risk of new biliary complications during waiting period
– Up to 60% readmissions prior to surgery
• Guidelines: same admission cholecystectomy
– International Association of Pancreatology / American
Pancreatic Association (IAP / APA) 1
– American College of Gastroenterology2
• Available evidence is limited
– Mostly retrospective
1IAP/APA
Pancreatology 2013; 2Tenner Gastro 2013
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PONCHO trial
Introduction
Same-admission vs. interval cholecystectomy for mild gallstone
pancreatitis
A multicenter randomised controlled trial
David da Costa*, Stefan Bouwense*, Nicolien Schepers, Sandra van Brunschot, Marc
Besselink, Hjalmar van Santvoort, Olaf Bakker, Marja Boermeester, Thomas Bollen, Koop
Bosscha, Menno Brink, Marco Bruno, Esther Consten, Cornelis Dejong, Peter van
Duijvendijk, Casper van Eijck, Jos Gerritsen, Harry van Goor, Joos Heisterkamp, Ignace de
Hingh, Philip Kruyt, Quintus Molenaar, Vincent Nieuwenhuijs, Jacco van Unen, Marcel
Spanier, Sijbrand Hofker, Eric Manusama, Annet Voorburg, Laurens van der Waaij, Camiel
Rosman, Alexander Schaapherder, Joris Scheepers, Marcel Spanier, Robin Timmer, Bas
Weusten, Ben Witteman, Bert van Ramshorst, Marcel Dijkgraaf,
Hein Gooszen, Djamila Boerma
for the Dutch Pancreatitis Study Group
David da Costa // [email protected] // www.pancreatitis.nl
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PONCHO trial: study question
Introduction
• Does same admission cholecystectomy, compared with
interval cholecystectomy, reduce the number of biliary
complications without increasing surgical risk in patients
with mild biliary pancreatitis?
David da Costa // [email protected] // www.pancreatitis.nl
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Methods: design
Methods
• Randomized, controlled, multicenter, superiority trial
• 23 Dutch hospitals
– 7 university medical centers
– 16 non-academic teaching hospitals
David da Costa // [email protected] // www.pancreatitis.nl
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Methods: eligibility
Methods
Exclusion
Inclusion
• First episode of pancreatitis
• Pancreatic necrosis
• Biliary origin
• (Peri)pancreatic collections
• Age 18 years or older
• Organ failure
• ASA class III and > 75 years
• ASA class IV and V
• Pregnancy
• Alcohol abuse
• Chronic pancreatitis
David da Costa // [email protected] // www.pancreatitis.nl
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Methods: randomization
Methods
•
Randomization
– 1-2 days before anticipated discharge
– Oral diet, no need for opioid analgesics, declining CRP levels
•
Stratification
– Per center and for sphincterotomy
•
Intervention:
– Cholecystectomy within 3 days of randomization [same-admission]
•
Control:
– Discharge and cholecystectomy after 25-30 days [interval]
David da Costa // [email protected] // www.pancreatitis.nl
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Methods: end points
Methods
• Primary end point
– Biliary complication requiring acute readmission or mortality
• Recurrent pancreatitis
• Cholecystitis
• Symptomatic choledocholithiasis requring ERCP
• Biliary colics
David da Costa // [email protected] // www.pancreatitis.nl
12
Methods: end points (2)
Methods
• Secondary end points
– Individual components of the primary end point
– Difficulty of cholecystectomy (scale 0-10)
– Need for conversion
– Patient reported biliary colics in gallstone questionnaire
– Total length of stay
• Safety end points
– Bile duct injury
– Bleeding requiring intervention
David da Costa // [email protected] // www.pancreatitis.nl
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Results: CONSORT
Results
David da Costa // [email protected] // www.pancreatitis.nl
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Results: CONSORT (2)
Results
David da Costa // [email protected] // www.pancreatitis.nl
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Results: baseline
Results
Same admission
(N=128)
Interval
(N=136)
Age in years; median (IQR)
53 (38-66)
54 (41-68)
Female sex; No. (%)
76 (59%)
84 (62%)
Body Mass Index (kg/m2); median (IQR)
27 (24-32)
28 (25-31)
I (healthy patient)
43 (34%)
51 (38%)
II (mild systemic disease)
72 (56%)
74 (54%)
III (severe systemic disease)
13 (10%)
11 (8%)
Endoscopic sphincterotomy; No. (%)
36 (28%)
42 (31%)
ASA; No. (%)
David da Costa // [email protected] // www.pancreatitis.nl
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Results: time to surgery
Results
• Median number of days between randomization and surgery
– Same admission:
1 (IQR 1-2)
– Interval:
27 (IQR 26-29)
David da Costa // [email protected] // www.pancreatitis.nl
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Results: primary end point
Results
Same admission
(N=128)
Interval
(N=136)
Risk Ratio (95% CI)
P value
6 (5%)
23 (17%)
0.28 (0.12-0.66)
0.002
Recurrent pancreatitis
3 (2%)
12 (9%)
0.27 (0.08-0.92)
0.03
Colics
2 (1%)
7 (5%)
0.3 (0.06-1.43)
0.11
Choledocholithiasis
1 (1%)
2 (1%)
0.53 (0.05-5.79)
0.6
0
2 (1%)
0.5
1 (1%)
0
0.30
Primary end point
Biliary complications
or mortality
Biliary complications
Cholecystitis
Mortality
David da Costa // [email protected] // www.pancreatitis.nl
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Results: secondary end points
Results
Same admission
(N=128)
Interval
(N=136)
P value
5.5 ± 2.1
5.5 ± 2.1
0.78
Conversions; No. (%)
5 (4%)
4 (3%)
0.7
Colics during waiting period; No. (%)
3 (2%)
62 (51%)
<0.001
Total length of stay in days; median (IQR)
3 (2-4)
3 (2-5)
0.99
Secondary end points
Difficulty of cholecystectomy; mean ± SD
David da Costa // [email protected] // www.pancreatitis.nl
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Results: safety end points
Results
Same admission
(N=128)
Interval
(N=136)
P value
Cystic duct leakage
1 (1)
1 (1)
0.99
Bleeding
1 (1)
1 (1)
0.99
Safety end points
David da Costa // [email protected] // www.pancreatitis.nl
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Timing of primary endpoints
Results
• Same admission group
– All primary end points occurred after surgery within three weeks
following discharge
• Interval group
– 21/23 primary end points (91%) before surgery
David da Costa // [email protected] // www.pancreatitis.nl
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PONCHO trial conclusions
Conclusion
• Same admission cholecystectomy reduced the rate of
– Biliary complications requiring readmission
– Recurrent biliary pancreatitis
– Biliary colics during waiting period
• Very few surgical complications
David da Costa // [email protected] // www.pancreatitis.nl
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Implications
Conclusion
• Shift from elective to acute care
– Mindset towards semi-acute cholecystectomy
– Organizational adjustments
David da Costa // [email protected] // www.pancreatitis.nl
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Thank you
David da Costa // [email protected] // www.pancreatitis.nl
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Recommendation
Conclusion
•In patients with mild biliary pancreatitis cholecystectomy
should be performed during the same admission
– The elderly… sphincterotomy enough?
•Severe pancreatitis: delay of cholecystectomy until all
symptoms have resolved
– Sphincterotomy as bridge to surgery?
David da Costa // [email protected] // www.pancreatitis.nl
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Results: Subgroup
sphincterotomy
Conclusion
Subgroup analysis: endoscopic sphincterotomy
• no interaction between ES and primary endpoint
Same admission
(N=128)
Interval
(N=136)
P value
ES (N=78)
1 (3%)
7 (17%)
0.07
No ES (N=185)
5 (5%)
16 (17%)
0.02
David da Costa // [email protected] // www.pancreatitis.nl
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Results: subgroup analysis
Results
• Tests for interaction not significant
• Primary end point per subgroup:
Same admission
Interval
P value
ES (N=78)
1 (3%)
7 (17%)
0.07
No ES (N=185)
5 (5%)
16 (17%)
0.02
Age under 75 years (N=233)
5 (4%)
18 (21%)
0.002
Age over 75 years (N=31)
1 (7%)
2 (13%)
1
David da Costa // [email protected] // www.pancreatitis.nl
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Results: health care utilization
Results
Same admission
Interval
P value
179
200
ns
Emergency room visits
5
10
ns
Endoscopy
11
18
ns
Radiology
65
57
ns
6385
8249
ns
Outpatient clinic
Productivity loss (hours, total)
David da Costa // [email protected] // www.pancreatitis.nl
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