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Intrathoracic vs Cervical Anastomosis After Totally or Hybrid Minimally Invasive Esophagectomy for Esophageal CancerA Randomized Clinical Trial

Educational Objective To study to what extent the location of the esophageal anastomosis is associated with leakage requiring reintervention in patients with transthoracic minimally invasive esophagectomy.
1 Credit CME
Key Points

Question  Is an intrathoracic or cervical anastomosis the preferable location of the anastomosis after a transthoracic, minimally invasive esophagectomy, in terms of anastomotic leakage requiring reintervention?

Findings  In this randomized clinical trial of 245 patients, anastomotic leakage necessitating reintervention occurred in 15 of 122 patients (12.3%) with intrathoracic anastomosis and 39 of 123 patients (31.7%) with cervical anastomosis.

Meaning  In this study, intrathoracic anastomosis resulted in better outcome for patients treated with transthoracic minimally invasive esophagectomy for midesophageal to distal esophageal or gastroesophageal junction cancer.

Abstract

Background  Transthoracic minimally invasive esophagectomy (MIE) is increasingly performed as part of curative multimodality treatment. There appears to be no robust evidence on the preferred location of the anastomosis after transthoracic MIE.

Objective  To compare an intrathoracic with a cervical anastomosis in a randomized clinical trial.

Design, Setting, and Participants  This open, multicenter randomized clinical superiority trial was performed at 9 Dutch high-volume hospitals. Patients with midesophageal to distal esophageal or gastroesophageal junction cancer planned for curative resection were included. Data collection occurred from April 2016 through February 2020.

Intervention  Patients were randomly assigned (1:1) to transthoracic MIE with intrathoracic or cervical anastomosis.

Main Outcomes and Measures  The primary end point was anastomotic leakage requiring endoscopic, radiologic, or surgical intervention. Secondary outcomes were overall anastomotic leak rate, other postoperative complications, length of stay, mortality, and quality of life.

Results  Two hundred sixty-two patients were randomized, and 245 were eligible for analysis. Anastomotic leakage necessitating reintervention occurred in 15 of 122 patients with intrathoracic anastomosis (12.3%) and in 39 of 123 patients with cervical anastomosis (31.7%; risk difference, −19.4% [95% CI, −29.5% to −9.3%]). Overall anastomotic leak rate was 12.3% in the intrathoracic anastomosis group and 34.1% in the cervical anastomosis group (risk difference, −21.9% [95% CI, −32.1% to −11.6%]). Intensive care unit length of stay, mortality rates, and overall quality of life were comparable between groups, but intrathoracic anastomosis was associated with fewer severe complications (risk difference, −11.3% [−20.4% to −2.2%]), lower incidence of recurrent laryngeal nerve palsy (risk difference, −7.3% [95% CI, −12.1% to −2.5%]), and better quality of life in 3 subdomains (mean differences: dysphagia, −12.2 [95% CI, −19.6 to −4.7]; problems of choking when swallowing, −10.3 [95% CI, −16.4 to 4.2]; trouble with talking, −15.3 [95% CI, −22.9 to −7.7]).

Conclusions and Relevance  In this randomized clinical trial, intrathoracic anastomosis resulted in better outcome for patients treated with transthoracic MIE for midesophageal to distal esophageal or gastroesophageal junction cancer.

Trial Registration  Trialregister.nl Identifier: NL4183 (NTR4333)

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: April 21, 2021.

Published Online: May 12, 2021. doi:10.1001/jamasurg.2021.1555

Corresponding Author: Camiel Rosman, MD, PhD (camiel.rosman@radboudumc.nl), and Moniek H. P. Verstegen, MD (moniek.verstegen@radboudumc.nl), Department of Surgery, Radboud Institute of Health Sciences, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, the Netherlands.

Author Contributions: Dr Rosman had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs van Workum and Verstegen contributed equally to this article and are co–first authors.

Concept and design: van Workum, Verstegen, Bouwense, van Berge Henegouwen, Daams, Gisbertz, Hannink, Heisterkamp, Jansen, van Lanschot, Nieuwenhuijzen, van der Peet, Polat, Rovers, Rosman.

Acquisition, analysis, or interpretation of data: van Workum, Verstegen, Klarenbeek, van Berge Henegouwen, Daams, Gisbertz, Hannink, Haveman, Heisterkamp, Kouwenhoven, van Lanschot, van der Peet, Ubels, Wijnhoven, Rovers, Rosman.

Drafting of the manuscript: van Workum, Verstegen, Bouwense, Hannink, Jansen, van der Peet, Ubels, Rosman.

Critical revision of the manuscript for important intellectual content: van Workum, Verstegen, Klarenbeek, Bouwense, van Berge Henegouwen, Daams, Gisbertz, Hannink, Haveman, Heisterkamp, Kouwenhoven, van Lanschot, Nieuwenhuijzen, van der Peet, Polat, Ubels, Wijnhoven, Rovers, Rosman.

Statistical analysis: van Workum, Verstegen, Bouwense, Hannink, Ubels, Rosman.

Obtained funding: van Workum, Rovers, Rosman.

Administrative, technical, or material support: van Workum, Verstegen, Bouwense, van Berge Henegouwen, Daams, Gisbertz, Heisterkamp, Jansen, Kouwenhoven, Polat, Ubels, Wijnhoven.

Supervision: van Workum, Klarenbeek, Gisbertz, Hannink, Haveman, Heisterkamp, van der Peet, Polat, Rovers, Rosman.

Conflict of Interest Disclosures: Dr Verstegen reported grants from Netherlands Organization for Health Research (ZonMw) during the conduct of the study. Dr van Berge Henegouwen reported personal fees to his institution from Mylan, Alesi Surgical, Johnson & Johnson, and Medtronic outside the submitted work and grants paid to his institution from Olympus and Stryker outside the submitted work. Dr Ubels reported grants from ZonMw during the conduct of the study and grants from Medtronic outside the submitted work. Dr Rovers reported grants from ZonMw during the conduct of the study and outside the submitted work and grants from Siemens Healthineers outside the submitted work. Dr Rosman reported grants from ZonMw during the conduct of the study. No other disclosures were reported.

Funding/Support: The Netherlands Organization for Health Research Development Health Care Efficiency Research program (ZonMw; grant 843002607) financially supported this trial.

Role of the Funder/Sponsor: ZonMw had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The members of the ICAN collaborative research group appear in Supplement 4.

Data Sharing Statement: See Supplement 3.

Additional Contributions: We thank Tjarda Tromp, research nurse, and Marianne Stenstra, MD, Radboud University Medical Center, for their support in coordinating this trial and Marja Bulte-ter Meer, PhD, Radboud University Medical Center, for designing the figure used in the visual abstract. We thank Henk Hartgrink, MD, PhD, Leiden University Medical Center, Ton de Haan, MSc, Radboud University Medical Center, and Hein Gooszen, MD, PhD, Radboud University Medical Center, for their role as member of the data safety monitoring board.

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