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

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.

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.. 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.. 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.