Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2019; 25(3): 356-366
Published online Jan 21, 2019. doi: 10.3748/wjg.v25.i3.356
Incidence and treatment of mediastinal leakage after esophagectomy: Insights from the multicenter study on mediastinal leaks
Uberto Fumagalli, Gian Luca Baiocchi, Andrea Celotti, Paolo Parise, Andrea Cossu, Luigi Bonavina, Daniele Bernardi, Giovanni de Manzoni, Jacopo Weindelmayer, Giuseppe Verlato, Stefano Santi, Giovanni Pallabazzer, Nazario Portolani, Maurizio Degiuli, Rossella Reddavid, Stefano de Pascale
Uberto Fumagalli, Department of Digestive Surgery, IEO European Institute of Oncology IRCCS, Milano 20141, Italy
Gian Luca Baiocchi, Nazario Portolani, Department of Clinical and Experimental Studies, Surgical Clinic, University of Brescia, Brescia 25123, Italy
Andrea Celotti, Stefano de Pascale, General Surgery 2, ASST Spedali Civili di Brescia, Brescia 25123, Italy
Paolo Parise, Andrea Cossu, Department of Gastrointestinal Surgery, San Raffaele Hospital, Vita-Salute San Raffaele University, Milano 20132, Italy
Luigi Bonavina, Daniele Bernardi, Department of Surgery, IRCCS Policlinico San Donato, University of Milan, Milano 20122, Italy
Giovanni de Manzoni, Jacopo Weindelmayer, General and Upper GI Surgery Division, University of Verona, Verona 37134, Italy
Giuseppe Verlato, Department of Diagnostics and Public Health, University of Verona, Verona 37134, Italy
Stefano Santi, Giovanni Pallabazzer, Esophageal Surgery Unit, Tuscany Regional Referral Center for the Diagnosis and Treatment of Esophageal Disease, Cisanello Hospital, Pisa 56124, Italy
Maurizio Degiuli, Rossella Reddavid, University of Turin, Department of Oncology, Surgical Oncology and Digestive Surgery, San Luigi University Hospital, Orbassano 10043, Italy
Author contributions: Fumagalli U and de Pascale S conceived and designed the study; Fumagalli U implemented the study and drafted the article; Celotti A made substantial contributions to the acquisition and analysis of data; Baiocchi GL made substantial contributions to the analysis and interpretation of data; Verlato G reviewed the statistical analysis. All authors substantially contributed to the interpretation of data, made critical revisions related to important intellectual content of the manuscript, and approved the final version of the manuscript.
Institutional review board statement: The publication of this manuscript has been reviewed and approved by the institutional review board of the Department of Clinical and Experimental Sciences of the University of Brescia, Brescia, Italy.
Informed consent statement: Patients were not required to provide informed consent to this study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All authors have received no funding and declare no conflicts of interest in relation to this specific work.
Data sharing statement: No additional data are available.
Open-Access: This is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Uberto Fumagalli, MD, Director, Surgical Oncologist, Department of Digestive Surgery, IEO European Institute of Oncology IRCCS, Via Ripamonti 435, Milano 20141, Italy.
Telephone: +39-2-57489680 Fax: +39-2-57489930
Received: October 22, 2018
Peer-review started: October 22, 2018
First decision: November 29, 2018
Revised: January 4, 2019
Accepted: January 9, 2019
Article in press: January 9, 2019
Published online: January 21, 2019
Research background

Cancer of the esophagus is a highly malignant disease with a poor prognosis. Esophagectomy is still a highly invasive surgical procedure, with significant morbidity rates and mortality rates. Minimally invasive esophagectomy was introduced with the aim of improving postoperative morbidity rates, yet possibly affecting the leakage rate. In fact, anastomotic mediastinal leakage (ML) represents one of the most feared complications of esophageal resection, being associated with mediastinitis, sepsis, acute respiratory distress syndrome, prolonged hospitalization, decreased quality of life, and reduced life expectancy.

Research motivation

A standard strategy for both the diagnosis and treatment of MLs remains difficult to establish because the incidence, the underlying risk factors, the associated mortality rates, and the treatment strategies of MLs reported in the literature vary widely. This heterogeneity in the reported findings is partly explained by the fact that different series and studies use different definitions of ML, which make it difficult to compare their findings, and, hence, to derive clear indications regarding the best strategy for the diagnosis and treatment of MLs.

Research objectives

The aim of our retrospective study was to evaluate the incidence, predictive factors, treatments, and associated mortality rates of ML after transthoracic esophagectomy using a standardized and commonly agreed upon definition of ML recently proposed by the Esophagectomy Complications Consensus Group (ECCG) and relying on a large, multicenter and comprehensive dataset of esophagectomies.

Research methods

The data include all transthoracic esophagectomies intrathoracic esophagogastric anastomosis performed from 2014 to 2017 in seven Italian surgical centers (5 high-volume and 2 low-volume), which form a representative sample of Italian centers with surgical teams having significant expertise in esophageal resection. A total of 501 patients were identified by retrospective review of the prospectively maintained medical databases. MLs, patient ASA score and body mass index (BMI), tumor histology and stage, use of neoadjuvant treatment, pyloric procedure, duration of surgery, surgical approach, and anastomotic technique were coded. The Mann-Whitney U test was used to compare continuous variables not normally distributed [presented as the median and interquartile range (IQR)]. The normality of the distribution of variables was determined using the D’Agostino-Pearson test. Chi-square or Fisher’s exact tests, when appropriate, were used to compare categorical variables.

Research results

The overall incidence of ML was 11.8%, with a leakage rate varying across centers from 1.6% to 20%. Leakage incidence did not correlate with center volume. The 30- and 90-d total mortality rates were 1.4% and 3.2%. Meanwhile, the 30- and 90-d leak-related mortality rates were 0.6% and 1.8%. The ASA score, tumor histology and stage, use of preoperative (neoadjuvant) treatment, and duration of surgery did not correlate with the occurrence of ML. BMI was significantly correlated with an increased risk of ML (P = 0.032). The surgical approach significantly influenced the incidence rate of ML: the proportion of leakages was 10.5% and 9% after open Ivor Lewis esophagectomy and hybrid esophagectomy, respectively, and doubled (20%) after total minimally invasive esophagectomy (P = 0.016). Conservative treatment was the first-line treatment in 13.6% of ML cases. Endoscopy was the first-line treatment in 49% of ML cases. Surgery, as a first-line treatment, consisting of surgical debridement with or without stent placement, re-anastomosis or demontage, was performed in 37.3% of patients. Endoscopy had the highest rate of retreatment (17.2%) but the lowest mortality rate (6.9%).

Research conclusions

The main novel finding from the analysis of our series is that technical aspects of esophageal resection, more specifically the use of a minimally invasive approach, seem to be one of the two predictive factors for the occurrence of ML (BMI being the other). In contrast, other factors, such as tumor histology and stage, multimodality treatment, and duration of surgery, did not seem to influence the occurrence of this postoperative surgical complication.

Research perspectives

Our series shows that ML occurred mainly in the group of patients undergoing totally minimally invasive esophagectomy, suggesting that technical problems during the initial phase of the learning curve are likely the main drivers behind the occurrence of ML. The take-home message of our study is that early treatment of severe leaks, presenting either directly as severe or causing persistent sepsis after initial conservative treatment, is mandatory, and that there should be no hesitation before reoperation if the first attempt of conservative management fails. Further studies using large and comprehensive datasets from other countries yet relying on the same standardized definition of ML recently proposed through international consensus by the ECCG will enable to compare different series in a meaningful way. This in turn will significantly improve the understanding of the risk factors, incidence and treatment strategies for mediastinal leaks after esophageal resection.