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Original Investigation
May 12, 2021

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

Author Affiliations
  • 1Department of Surgery, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
  • 2Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands
  • 3Department of Surgery, Amsterdam UMC, location AMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
  • 4Department of Surgery, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands
  • 5Department of Operating Rooms, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
  • 6Department of Surgery, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
  • 7Department of Surgery, Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands
  • 8Department of Surgery, Ziekenhuisgroep (Hospital Group) Twente, Almelo, the Netherlands
  • 9Department of Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands
  • 10Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
  • 11Department of Surgery, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands
JAMA Surg. 2021;156(7):601-610. doi:10.1001/jamasurg.2021.1555
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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    1 Comment for this article
    EXPAND ALL
    Esophagectomy: Western and Eastern differences
    FLAVIO ROBERTO TAKEDA, Professor | Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo
    We read with great interest the article by van Workum that compared intrathoracic with cervical anastomosis concerning anastomotic leakage requiring reinterventions in patients with esophageal carcinoma.
    The epidemiology of esophageal carcinoma differs from western to eastern countries. Forty years ago, the esophagectomy with lymphadenectomy technique in three dissection fields (cervical, thoracic, and abdominal) and cervical anastomosis proposed by Hiroshi Akiyama in 1981 showed an increased survival of patients with esophageal neoplasia associated with extensive lymphadenectomy, currently representing the primary type of esophagectomy performed in the East, where the squamous cell carcinoma is more frequent. In the West, where adenocarcinoma
    is more frequent, surgeons are more familiar with the Ivor-Lewis esophagectomy. However, both procedures’ morbidity rate was around 60%, with mortality of around 7%. The advent of minimally invasive surgery in the late 1990s led to declining rates of postoperative complications, especially those of respiratory complications, without interfering with overall survival confirmed by randomized prospective trial study.
    Thus, in recent years, the relationship between the results of complications in high volume centers and the occurrence of anastomotic leakage has been discussed. This study was conducted in a European high-volume center, used to perform intrathoracic anastomosis, which could be why the leakage rate was around 30%, recently confirmed by a Dutch trial. However, despite the implementation of minimally invasive techniques, the rates of esophagogastric anastomosis fistula in eastern centers remain at around 10-15%, regardless of the technique employed (manual, circular, or linear stapling) and some surgical maneuvers (epiploplasty, pleural reconstruction, and use of surgical glue).
    Another technical argument is that the final location of cervical anastomosis could be inferior to sternal manubrium (simulating an intra-thoracic anastomosis), which might contribute to descending mediastinal contamination, causing additional rates of surgical interventions after anastomotic leakage instead of benign spontaneous drainage to cervicotomy. In our view, the main problem from cervical anastomosis is leakage and stenosis (dysphagia-related), related to anastomotic tissue perfusion. We recently proposed a surgical standardization following esophagectomy for revascularization of the gastric tube transposed by the posterior mediastinum using neck vessels, reducing the incidence of fistula and stenosis.





    REFERENCES:
    1- van Workum F et al. Intrathoracic vs Cervical Anastomosis After Totally or Hybrid Minimally Invasive Esophagectomy for Esophageal Cancer: A Randomized Clinical Trial. JAMA Surg. 2021 May 12:e211555. doi: 10.1001/jamasurg.2021.1555. Epub ahead of print. PMID: 33978698; PMCID: PMC8117060.
    2- Akiyama H, et al. Ann Surg. 1981 Oct;194(4):438-46. doi: 10.1097/00000658-198110000-00007.
    3- Mariette C, et al. Hybrid Minimally Invasive Esophagectomy for Esophageal Cancer. N Engl J Med. 2019 Jan 10;380(2):152-162.
    4- Kataoka K, et al. Prognostic Impact of Postoperative Morbidity After Esophagectomy for Esophageal Cancer: Exploratory Analysis of JCOG9907. Ann Surg. 2017 Jun;265(6):1152-1157. doi: 10.1097/SLA.0000000000001828. PMID: 27280509.

    5- Takeda FR, et al. Supercharged cervical anastomosis for esophagectomy and gastric pull-up. J Thorac Cardiovasc Surg. 2020 Jun 26:S0022-5223(20)31737-2. doi: 10.1016/j.jtcvs.2020.06.021
    CONFLICT OF INTEREST: None Reported
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