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Meta-Analysis
. 2021 Jul;35(7):3492-3505.
doi: 10.1007/s00464-020-07806-y. Epub 2020 Jul 17.

Early diagnosis is associated with improved clinical outcomes in benign esophageal perforation: an individual patient data meta-analysis

Bram D Vermeulen  1   2 , Britt van der Leeden  3 , Jawad T Ali  4 , Tomas Gudbjartsson  5 , Michael Hermansson  6 , Donald E Low  7 , Douglas G Adler  8 , Abraham J Botha  9 , Xavier B D'Journo  10 , Atila Eroglu  11 , Lorenzo E Ferri  12 , Christoph Gubler  13 , Jan Willem Haveman  14 , Lileswar Kaman  14 , Richard A Kozarek  15 , Simon Law  16 , Gunnar Loske  17 , Joerg Lindenmann  18 , Jung-Hoon Park  19 , J David Richardson  20 , Paulina Salminen  21 , Ho-Yong Song  19 , Jon A Søreide  22   23 , Manon C W Spaander  24 , Jeffrey N Tarascio  25 , Jon A Tsai  26 , Tim Vanuytsel  27 , Camiel Rosman  28 , Peter D Siersema  3 ; Benign Esophageal Perforation Collaborative Group
Collaborators, Affiliations
Meta-Analysis

Early diagnosis is associated with improved clinical outcomes in benign esophageal perforation: an individual patient data meta-analysis

Bram D Vermeulen et al. Surg Endosc. 2021 Jul.

Abstract

Background: Time of diagnosis (TOD) of benign esophageal perforation is regarded as an important risk factor for clinical outcome, although convincing evidence is lacking. The aim of this study is to assess whether time between onset of perforation and diagnosis is associated with clinical outcome in patients with iatrogenic esophageal perforation (IEP) and Boerhaave's syndrome (BS).

Methods: We searched MEDLINE, Embase and Cochrane library through June 2018 to identify studies. Authors were invited to share individual patient data and a meta-analysis was performed (PROSPERO: CRD42018093473). Patients were subdivided in early (≤ 24 h) and late (> 24 h) TOD and compared with mixed effects multivariable analysis while adjusting age, gender, location of perforation, initial treatment and center. Primary outcome was overall mortality. Secondary outcomes were length of hospital stay, re-interventions and ICU admission.

Results: Our meta-analysis included IPD of 25 studies including 576 patients with IEP and 384 with BS. In IEP, early TOD was not associated with overall mortality (8% vs. 13%, OR 2.1, 95% CI 0.8-5.1), but was associated with a 23% decrease in ICU admissions (46% vs. 69%, OR 3.0, 95% CI 1.2-7.2), a 22% decrease in re-interventions (23% vs. 45%, OR 2.8, 95% CI 1.2-6.7) and a 36% decrease in length of hospital stay (14 vs. 22 days, p < 0.001), compared with late TOD. In BS, no associations between TOD and outcomes were found. When combining IEP and BS, early TOD was associated with a 6% decrease in overall mortality (10% vs. 16%, OR 2.1, 95% CI 1.1-3.9), a 19% decrease in re-interventions (26% vs. 45%, OR 1.9, 95% CI 1.1-3.2) and a 35% decrease in mean length of hospital stay (16 vs. 22 days, p = 0.001), compared with late TOD.

Conclusions: This individual patient data meta-analysis confirms the general opinion that an early (≤ 24 h) compared to a late diagnosis (> 24 h) in benign esophageal perforations, particularly in IEP, is associated with improved clinical outcome.

Keywords: Esophageal rupture; Individual patient data meta-analysis; Time of diagnosis.

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Conflict of interest statement

Peter D. Siersema declares that he currently receives research support from EllaCS (Czech Republic) and Pentax (Japan). He previously received research support from Boston Scientific (US), Cook Medical (Ireland) and EndoStim (US/The Netherlands). Manon C.W. Spaander declares that she has received research grants from Boston Scientific and Pyromed. Jon A. Tsai declares that he is an employee of Sanofi Genzyme. Bram D. Vermeulen, Britt van der Leeden, Jawad T. Ali, Tomas Gudbjartsson, Michael Hermansson, Donald E. Low, Douglas G. Adler, Abraham J. Botha, Xavier B. D’Journo, Atila Eroglu, Lorenzo E. Ferri, Christoph Gubler, Jan Willem Haveman, Lileswar Kaman, Richard A. Kozarek, Simon Law, Gunnar Loske, Joerg Lindenmann, Jung-Hoon Park, J. David Richardson, Paulina Salminen, Ho-Yong Song, Jon A. Søreide, Jeffrey N. Tarascio, Tim Vanuytsel, Camiel Rosman declares they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Flow chart of study and patient inclusion for the IPD meta-analysis. IPD individual patient data, IEP iatrogenic esophageal perforation, BS Boerhaave’s syndrome
Fig. 2
Fig. 2
Survival differences between patients with IEP and BS during 3 months of follow-up. Hazard ratio is adjusted for age, gender, etiology, perforation location and initial treatment strategy. IEP iatrogenic esophageal perforation, BS Boerhaave’s syndrome
Fig. 3
Fig. 3
Forest plots depicting odds ratio of late TOD for overall mortality, ICU admission and re-intervention in patients with IEP and BS. Values represent odds ratios with 95% confidence intervals. Odds ratios are adjusted for treatment center, etiology, age, gender, perforation location and initial treatment approach. A Late (> 12 h) TOD and outcome in patients with IEP. B Late (> 24 h) TOD and outcome in patients with IEP. C Late (> 12 h) TOD and outcome in patients with BS. D Late (> 24 h) TOD and outcome in patients with BS. E Late (> 12 h) TOD and outcome in patients with IEP and BS. F Late (> 24 h) TOD and outcome in patients with IEP and BS. TOD time of diagnosis, IEP iatrogenic esophageal perforation, BS Boerhaave’s syndrome, ICU intensive care unit, h hour. *Indicates a statistically significant association
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