Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2020 Jan 21;323(3):237-247.
doi: 10.1001/jama.2019.20967.

Effect of Early Surgery vs Endoscopy-First Approach on Pain in Patients With Chronic Pancreatitis: The ESCAPE Randomized Clinical Trial

Yama Issa  1 , Marinus A Kempeneers  1 , Marco J Bruno  2 , Paul Fockens  3 , Jan-Werner Poley  2 , Usama Ahmed Ali  1 , Thomas L Bollen  4 , Olivier R Busch  1 , Cees H Dejong  5   6 , Peter van Duijvendijk  7 , Hendrik M van Dullemen  8 , Casper H van Eijck  9 , Harry van Goor  10 , Muhammed Hadithi  11 , Jan-Willem Haveman  12 , Yolande Keulemans  13 , Vincent B Nieuwenhuijs  14 , Alexander C Poen  15 , Erik A Rauws  3 , Adriaan C Tan  16 , Willem Thijs  17 , Robin Timmer  18 , Ben J Witteman  19 , Marc G Besselink  1 , Jeanin E van Hooft  3 , Hjalmar C van Santvoort  20   21 , Marcel G Dijkgraaf  22 , Marja A Boermeester  1 ; Dutch Pancreatitis Study Group
Affiliations
Randomized Controlled Trial

Effect of Early Surgery vs Endoscopy-First Approach on Pain in Patients With Chronic Pancreatitis: The ESCAPE Randomized Clinical Trial

Yama Issa et al. JAMA. .

Abstract

Importance: For patients with painful chronic pancreatitis, surgical treatment is postponed until medical and endoscopic treatment have failed. Observational studies have suggested that earlier surgery could mitigate disease progression, providing better pain control and preserving pancreatic function.

Objective: To determine whether early surgery is more effective than the endoscopy-first approach in terms of clinical outcomes.

Design, setting, and participants: The ESCAPE trial was an unblinded, multicenter, randomized clinical superiority trial involving 30 Dutch hospitals participating in the Dutch Pancreatitis Study Group. From April 2011 until September 2016, a total of 88 patients with chronic pancreatitis, a dilated main pancreatic duct, and who only recently started using prescribed opioids for severe pain (strong opioids for ≤2 months or weak opioids for ≤6 months) were included. The 18-month follow-up period ended in March 2018.

Interventions: There were 44 patients randomized to the early surgery group who underwent pancreatic drainage surgery within 6 weeks after randomization and 44 patients randomized to the endoscopy-first approach group who underwent medical treatment, endoscopy including lithotripsy if needed, and surgery if needed.

Main outcomes and measures: The primary outcome was pain, measured on the Izbicki pain score and integrated over 18 months (range, 0-100 [increasing score indicates more pain severity]). Secondary outcomes were pain relief at the end of follow-up; number of interventions, complications, hospital admissions; pancreatic function; quality of life (measured on the 36-Item Short Form Health Survey [SF-36]); and mortality.

Results: Among 88 patients who were randomized (mean age, 52 years; 21 (24%) women), 85 (97%) completed the trial. During 18 months of follow-up, patients in the early surgery group had a lower Izbicki pain score than patients in the group randomized to receive the endoscopy-first approach group (37 vs 49; between-group difference, -12 points [95% CI, -22 to -2]; P = .02). Complete or partial pain relief at end of follow-up was achieved in 23 of 40 patients (58%) in the early surgery vs 16 of 41 (39%)in the endoscopy-first approach group (P = .10). The total number of interventions was lower in the early surgery group (median, 1 vs 3; P < .001). Treatment complications (27% vs 25%), mortality (0% vs 0%), hospital admissions, pancreatic function, and quality of life were not significantly different between early surgery and the endoscopy-first approach.

Conclusions and relevance: Among patients with chronic pancreatitis, early surgery compared with an endoscopy-first approach resulted in lower pain scores when integrated over 18 months. However, further research is needed to assess persistence of differences over time and to replicate the study findings.

Trial registration: ISRCTN Identifier: ISRCTN45877994.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Ahmed Ali reports receipt of grants from ZonMW (governmental agency, nonprofit, Ministry of Health), MLDS (nongovernmental organization, national gastrointestinal disease association, nonprofit), and Alvleeskliervereniging (patient association of pancreatic disease, nongovernmental organization, nonprofit) during the conduct of the study. Dr Boermeester reports receipt of grants from Mylan, Acelity/KCI, Johnson & Johnson, Bard, New Compliance, and Alvleeskliervereniging; and other from Acelity/KCI (speaker, instructor, advisory board), Johnson & Johnson (speaker and advisory board), Bard (speaker), Gore (speaker and instructor), and Smith & Nephew outside the submitted work. Dr Bruno reports receipt of grants for investigator-initiated studies from Cook Medical, Pentax Medical, 3M, and Mylan; grants for industry and investigator-initiated studies from Boston Scientific; and personal fees for consultancies and lectures from Boston Scientific, from Cook Medical, Pentax Medical, 3M, and Mylan outside the submitted work. Dr Fockens reports receipt of grants from Boston Scientific and personal fees from Olympus, Cook, and Ethicon Endosurgery outside the submitted work. Dr Poley reports receipt of personal fees and other from Cook Endoscopy, Boston Scientific, and Pentax outside the submitted work. Dr van Hooft reports receipt of grants from Cook Medical and Abbott and personal fees from Boston Scientific outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of Enrollment, Randomization, and Follow-up
aTo see in which step an exclusion took place, see eTable 9 in Supplement 2. bOne patient underwent no extracorporeal shock-wave lithotripsy (ESWL) despite having stones greater than 7 mm, and this same patient also underwent endoscopies for too long (>1 year of stenting).
Figure 2.
Figure 2.. Mean Izbicki Pain Score During 18 Months of Follow-up
Mean difference during follow-up for the early surgery group vs the endoscopy-first approach group: −12 (95% CI, −22 to −2); P = .02. The scale for the Izbicki pain score ranges from 0 to 100 points (increasing score indicates more pain severity). Questions consist of 4 items regarding frequency of pain, intensity of pain, use of pain medication, and disease-related inability to work (see eFigure 2 in Supplement 2 for scoring details).
Figure 3.
Figure 3.. Pain Relief During 18 Months of Follow-up
Complete relief is defined as having an Izbicki pain score of 10 or less; partial relief is a score of greater than 10 but decreased by more than 50% when compared with baseline. Average pain relief during follow-up was 44% in the early surgery group and 30% in the endoscopy-first approach group (difference, 14% [95% CI, −7% to 35%]; P = .18). Other pain relief scenarios at the end of follow-up are presented in eTable 10 in Supplement 2.
See this image and copyright information in PMC

Comment in

References

    1. Ammann RW, Muellhaupt B. The natural history of pain in alcoholic chronic pancreatitis. Gastroenterology. 1999;116(5):1132-1140. doi:10.1016/S0016-5085(99)70016-8 - DOI - PubMed
    1. Gardner TB, Kennedy AT, Gelrud A, et al. . Chronic pancreatitis and its effect on employment and health care experience: results of a prospective American multicenter study. Pancreas. 2010;39(4):498-501. doi:10.1097/MPA.0b013e3181c5c693 - DOI - PubMed
    1. Drewes AM, Bouwense SAW, Campbell CM, et al. ; Working group for the International (IAP–APA–JPS–EPC) Consensus Guidelines for Chronic Pancreatitis . Guidelines for the understanding and management of pain in chronic pancreatitis. Pancreatology. 2017;17(5):720-731. doi:10.1016/j.pan.2017.07.006 - DOI - PubMed
    1. Forsmark CE. Management of chronic pancreatitis. Gastroenterology. 2013;144(6):1282-1291 e3. doi:10.1053/j.gastro.2013.02.008 - DOI - PubMed
    1. Löhr JM, Dominguez-Munoz E, Rosendahl J, et al. ; HaPanEU/UEG Working Group . United European gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU). United European Gastroenterol J. 2017;5(2):153-199. doi:10.1177/2050640616684695 - DOI - PMC - PubMed

Publication types

Substances