Ann. N.Y. Acad. Sci.

ISSN 0077-8923

A N N A L S O F T H E N E W Y O R K A C A D E M Y O F SC I E N C E S
Special Issue: Global Perspectives and Novel Technologies for Esophageal Diseases

Review

Esophageal cancer surgery: review of complications and

their management
Mickael Chevallay,1 Minoa Jung,1 Seung-Hun Chon,2 Flavio Roberto Takeda,3
Junichi Akiyama, and Stefan Mönig1
4
1
Division of Visceral Surgery, Department of Surgery, Geneva University Hospital, Geneva, Switzerland. 2 Department of
General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany. 3 Gastroenterology
Department, University of São Paulo, São Paulo, Brazil. 4 Division of Gastroenterology and Hepatology, National Center for
Global Health and Medicine (NCGM), Tokyo, Japan

Address for correspondence: Dr. Mickael Chevallay, Division of Visceral Surgery, Department of Surgery, Geneva University
Hospital, 4 Rue Gabrielle-Perret-Gentil, 1205 Genève, Switzerland. Mickael.Chevallay@hcuge.ch

Esophagectomy, even with the progress in surgical technique and perioperative management, is a highly special-
ized surgery, associated with a high rate of complications. Early recognition and adequate treatment should be a
standard of care for the most common postoperative complications: anastomotic leakage, pneumonia, atrial fib-
rillation, chylothorax, and recurrent laryngeal nerve palsy. Recent progress in endoscopy with vacuum and stent
placement, or in radiology with embolization, has changed the management of these complications. The success
of nonoperative treatments should be frequently reassessed and reoperation must be proposed in case of failure.
We have summarized the clinical signs, diagnostic process, and management of the frequent complications after
esophagectomy for esophageal cancer.

Keywords: complications; esophagectomy; anastomotic leakage; chylothorax; nerve palsy

Introduction opening of the esophagus into the neck, and

gastrostomy.5 Since then, several organs have
Esophageal cancer is an oncological burden that
been used as substitutes for the resected esoph-
requires multidisciplinary support. In 2018, it was
agus (stomach, colon, and jejunum). Different
the cause of death in 508,585 patients and ranked
surgical techniques are now available: Ivor Lewis
sixth in worldwide cancer-related deaths.1 Late
esophagectomy (abdominal and right thoracic
diagnosis of advanced disease is one explana-
incisions), McKeown (abdominal, right thoracic,
tion for this poor prognosis.2 Despite the intro-
and cervical incisions), Sweet procedure (single
duction of multimodal neoadjuvant treatment,
left-sided thoracotomy), abdominal resection with
such as chemoradiotherapy or chemotherapy,
left thoracotomy, and transhiatal esophagectomy.
esophagectomy—the surgical removal of the
Several anastomotic methods have been
esophagus—remains the only curative treatment.3
described with hand-sewn anastomoses, stapling,
Several studies concluded that better outcome
or combined methods. The numerous approaches
(surgical and survival) is clearly related to treat-
and anastomotic techniques reflect the complexity
ment in high-volume centers, which can perform a
of the esophageal surgery. Despite these options,
systematic complex procedure and recognize early
no approach or anastomotic technique is devoid of
signs of complications.4
complications, and technical factors can affect the
In 1942, Sweet described one of the first
integrity of the anastomosis.6 Esophagectomy is a
esophagectomies with an esophagostomy, the
major procedure associated with consistently high
doi: 10.1111/nyas.14492
Ann. N.Y. Acad. Sci. xxxx (2020) 1–17 © 2020 New York Academy of Sciences. 1
Management of esophagectomy complications
complication rates (more than 50%).7 On the other
hand, the mortality rate has decreased from 71% in
19908 to 4.5% in recent audits,7 and improvement
of perioperative management has contributed to
this decrease. Currently, minimally invasive surgery
is a preferred option since it has an equal overall
survival rate and causes less morbidity and fewer
pulmonary complications compared with open
surgery.9
Standardization of the definitions of complica-
tions is necessary. The Esophageal Complications
Consensus Group (ECCG),10 a panel of interna-
tional experts, proposed a definition for periop-
erative complication after esophagectomy. Early
recognition and appropriate treatment for each
of these complications is fundamental to improve
patient outcome.
Below, we review the management and pre-
vention of four common complications after
esophagectomy for esophageal cancer: anasto-
motic leakage, cardiopulmonary complications,
chylothorax, and recurrent laryngeal nerve palsy
(RLNP).
Anastomotic leakage
Failure of the anastomosis to heal is the most
severe complication after esophageal surgery. A
unanimous definition of anastomotic leakage was
lacking until recently. A meta-analysis11 analyzing
postoperative complications after esophagectomy
included 98 publications and noted an absence of
the definition of complication in 63% of them. In
2015, the ECCG proposed a definition for the most
frequent complications after esophagectomy.10 In
this consensus, anastomotic leakage was defined
as a full thickness gastrointestinal defect involving
the esophagus, anastomosis, staple line, or con-
duit, irrespective of presentation or method of
identification. Three types were proposed (Table 1).
Conduit necrosis was another serious condition
identified. It involves a vascular compromise of the
Table 2. Standardized definition of conduit necrosis after esophagectomy
Type of conduit necrosis Endoscopic description
Type 1 Conduit necrosis focal
Type 2 Conduit necrosis focal
Type 3 Conduit necrosis extensive
Note: Adapted from Low et al.10
2 Ann. N.Y. Acad. Sci. xxxx (2020) 1–17 © 2020 New York Academy of Sciences.
Chevallay et al.
Table 1. Standardized definition of anastomotic leakage
after esophagectomy
Type of anastomotic
leakage Extent and treatment
Type 1 Localized defect that was treated
using medical therapy or by
observation alone
Type 2 Localized defect requiring
intervention but not surgical
therapy
Type 3 Localized defect requiring
surgical intervention
Note: Adapted from Low et al.10
stomach conduit. A different classification was pro-
posed by the ECCG group (Table 2).
Despite the progress in perioperative manage-
ment and improvement of surgical techniques,
the rate of leakage still ranges from 10% to 21.2%
(Table 3).7–9,12,13 The ECCG proposed a benchmark
of 11.4% for the anastomotic leakage rate, which
was derived from the results of 24 high-volume
centers.7
Compared with other digestive anastomosis,
esophageal anastomosis is risky due to several fac-
tors. The organ used for reconstruction is brought
from a distant position, inside or through the tho-
racic cavity. The blood supply length is extended to
the maximum that is possible. For the stomach con-
duit, vascularization relies on one artery, the right
gastroepiploic, and for the esophagus, the submu-
cosal arteries. Mechanical factors also play a role
since the esophagus does not possess a serosa. The
suture through this delicate tissue is associated with
high dehiscence rates; the use of surrounding tis-
sue (omentum, pleura, or pericardium) to reinforce
this fragile anastomosis has been described.14 Risk
factors identified for anastomotic leakage are obe-
sity, heart failure, coronary disease, vascular disease,
renal disease, and tobacco use.8
Treatment
Additional monitoring or nonsurgical therapy
Surgical therapy not involving esophageal diversion
Treated with conduit resection and diversion
Chevallay et al. Management of esophagectomy complications

Figure 1. Diagram of the location of the various esophageal anastomoses. (A) Cervical anastomosis. (B) Intrathoracic anasto-
mosis. (C) Colonic interposition with cervical and intrabdominal anastomoses.

The localization and type of anastomosis is an
important factor for the comprehension and man-
agement of anastomotic leakage. In esophagectomy,
the anastomosis could lie in three different posi-
tions: cervical, thoracic, or abdominal (Fig. 1).
For cervical anastomosis, the stomach conduit
is brought through the thoracic cavity. This anas-
tomosis has a higher rate of leakage than thoracic.
Studies and systematic reviews report a rate of
12–14% for cervical anastomosis compared with 3–
9.3% for thoracic localization.8,15,16 This higher rate
is explained by an anastomosis with more tension
and which experiences more stress from neck move-
ments. The anastomosis is usually performed at the
very end of the stomach conduit where vascular-
ization is at its more distant location. The diagnosis
of cervical anastomotic leakage can be clinical. The
cervical wound will develop an erythema, indura-
tion, or fluctuance.17 The appearance of saliva or air
in the surgical drain should raise suspicion of a leak-
age. Even if cervical anastomosis is at higher risk for
leakage, its consequence is different. If the leakage is
confined to the cervical soft tissue, mediastinitis will
not appear, improving the patient outcome. Cervi-
cal leakage can be managed by opening the wound
and packing it. A small disruption can be treated
completely with observation, including wound
care, delayed oral intake, parenteral nutrition,
and antibiotics.18 Some patients with prominent
cervical leaks may recover with these measures. If

Table 3. Rate of anastomotic leakage and mortality in large review and cohort studies

Number of Mortality at 30 days

References Year patients Rate of anastomotic leakage postoperative Site of anastomosis

Low et al.7 2017 2704 Anastomotic leak: 308 (11.4%) 65 (2.4%) Cervical: 1025 (37.9%)
Conduit necrosis: 35 (1.3%) Thoracic: 1641 (60.7%)
Other: 37 (1.4%)
Kassis et al.8 2013 7595 804 (10.6%) 270 (3.6%) Cervical: 934 (12.3%)
58 (7.2%) in patients Thoracic: 706 (9.3%)
with leakage
Price et al.12 2013 432 50 (11%) 16 (3.7%) Cervical: 164 (38%)
Thoracic: 268 (62%)

Wright et al.13 2009 2315 261 (11%) 63 (2.7%) Cervical: 879 (38%)
Thoracic: 1435 (62%)

Ann. N.Y. Acad. Sci. xxxx (2020) 1–17 © 2020 New York Academy of Sciences. 3
Management of esophagectomy complications
Figure 2. X-ray with an oral soluble contrast swallow for suspected anastomotic leakage. Red arrow: contrast leak confirming
the diagnosis.
the leak is uncontained or cannot be controlled by
drainage, or if intrathoracic complications occur, a
more aggressive approach should be implemented
with decortication, resection, and diversion. If the
cervical leaks extend to the thoracic cavity, the time
to recovery has been shown to be longer and require
more reoperation, compared with leaks confined to
the neck.19
For thoracic anastomosis, the healing conditions
are more favorable than in cervical anastomosis, but
the consequences of the leakage are more serious.
A negative pressure environment from the tho-
racic cavity tends to promote aspiration of gastric
fluid with anaerobic bacteria through anastomotic
sutures. This contaminates the pleural and medi-
astinal space, which affects the negative intratho-
racic pressure, compromising respiratory function
and eventually leading to death. Early recognition
is a key step. Clinical signs can be obvious with
tachycardia, fever, and enteric fluid from the chest
tube. Signs can be more subtle, such as change in
mental status, tachypnea, or cardiac arrhythmia.
Development of unilateral pleural effusion should
be considered an anastomotic leakage until proven
otherwise. A low threshold for prompt investigation
is mandatory. Patient prognosis after an anasto-
motic leak depends on the extent of contamination.
This is directly related to the time interval to diag-
nosis. Management of intrathoracic anastomotic
4 Ann. N.Y. Acad. Sci. xxxx (2020) 1–17 © 2020 New York Academy of Sciences.
Chevallay et al.
leaks should be individualized to each patient.
Surgical intervention is warranted if the leak is
uncontained and for those who fail conservative
management.
The use of an interposition organ other than
the stomach (most frequently the colon) adds
further complexity to the surgery. The colon is a
suitable organ replacement for the esophagus and
the left or right colon has been used for esophageal
reconstruction.20 For the left colon, the large bowel
is transected at the right flexure, then passed behind
the stomach and through the hiatus to create a
mediastinal interposition with an esophagocolonic
anastomosis.21 The reconstruction is completed
after transection of the proximal portion of the
descending colon and after anastomosing the graft
to the stomach. During this procedure, three anas-
tomoses are created: esocolonic, gastrocolonic, and
colocolic. To ensure a sufficient length of the colon
interposition, a meticulous vascular dissection
is necessary. The vascularity of the graft usually
depends on one terminal arterial branch and thus an
injury to it will lead to graft necrosis. The reported
rate of colon necrosis or ischemia is around 5%,
and for an anastomotic leak, 12–14%.20,22,23 To
detect leakage, a thoracic-abdominal computed
tomography (CT) scan with contrast medium per
oral is generally the first diagnostic examination.
This will detect a contrast leak or collection that
Chevallay et al.
Figure 3. Endoluminal vacuum therapy for an esophagogastric anastomotic leak. Left picture: a small defect on the anastomosis.
Middle picture: the endoscopic placement of the vacuum. Right picture: the final result with complete healing of the leak.
may require drainage. Based on imaging studies,
the leak can be categorized as contained (small area
of contrast extravasation contained by surrounding
structures) or uncontained (large leak with contrast
freely flowing).24
Endoscopy is also a part of the initial evaluation
during a suspected anastomotic leakage. It allows
a visual assessment of the anastomosis and the
vascularization of the conduit. X-ray with an oral
soluble contrast swallow is an option to test the
anastomosis on the 6th to 8th day after the surgery
in asymptomatic patients only (Fig. 2). In the early
postoperative period, a CT scan with oral contrast
evaluation is sometimes not possible due to several
factors (e.g., mechanical ventilation and dyspha-
gia), and endoscopy appears to be superior in the
detection of anastomotic leakage.25 Endoscopy
within 1 week of esophagectomy has been attested
by several studies to be safe for the anastomosis.26,27
Management of an anastomotic leakage has sev-
eral goals: closure or coverage of the defect, contain-
ment of the leak, and drainage of the contaminated
space.28 The treatment should match the magni-
tude of the leak. If the leak occurs within 72 h, a
technical error is presumed. If the general condi-
tion of the patient is acceptable, exploration and
repair are appropriate. Most leaks, however, occur
at 2 weeks after the surgery and present an inflam-
matory condition, which is unsuitable for a direct
repair. For a minor leakage, the infected area (tho-
racic or neck wound) should be drained, with a
delay of oral intake and introduction of a large spec-
trum of antibiotics. Adequate nutritional status, as
judged by preoperative albumin, and a contained
leak have been demonstrated to be associated with
Ann. N.Y. Acad. Sci. xxxx (2020) 1–17 © 2020 New York Academy of Sciences.
Management of esophagectomy complications
successful observational management.29 If the leak-
age is major or the initial management fails, a step-
up treatment should be considered.
Endoscopic treatment of anastomotic leakage
An endoscopic management plan is used for either
primary closure of the defect (clips, endoscopic
suturing, or fibrin glue) or secondary closure (stents
and endoscopic vacuum therapy). Primary closure
is a good option when the leakage is detected early
and the patient in a stable condition. The limitations
include difficulty in grasping the edge of the defect
and poor results if the leak is large (more than 3 cm)
or asymmetrical.
For stenting or endoscopic vacuum therapy, the
patient should also be clinically stable, and the
peri-anastomotic collections should be drained.
The limitations are the potential migration of the
stents and the need for regular changes for the
vacuum therapy. Oral feeding is also limited with
this treatment. Dasari et al.30 reviewed 27 case
series with 340 patients treated with metal or plastic
self-expanding stents. Endoscopic placement of
stents for the management of an anastomotic leak
was reported as successful in 91.4% of cases, with no
difference according to the stent type. The average
time for a stent to be left in place was 6–8 weeks.
The overall migration rate was 20.8%. Stent-related
complications (bleeding and perforation) occurred
in 3% of cases, with a mortality rate of 13% in all
patients. Stenting for esophageal anastomotic leaks
is potentially beneficial for leaks involving less than
30% of the anastomotic circumference and without
extensive necrosis. Patients with extensive devi-
talization of esophageal anatomy, large leaks, or a
5
Management of esophagectomy complications
nonviable conduit are in the contraindication group
for this treatment. The stent placement should be
performed during the initial diagnosis. Serial
surveillance with chest radiography is required to
monitor stent migration. In their study, Dai et al.31
reported a stent migration in 35% of patients.
A self-expandable metallic stent (SEMS) should
be used for aggressive nonsurgical management and
should be considered when developing a treatment
plan. Plum et al.32 studied cases of anastomotic
leakage after an Ivor Lewis esophagectomy. In this
approach, the anastomosis is intrathoracic, and a
leakage has a significant deleterious potential for
respiratory function. In this subgroup of patients,
the authors reported a sealing success rate of 70%
(n = 49) with a median treatment of 28 days (range
7–87).
The timing for the stent removal is crucial: not
too soon before the anastomosis heals and not too
late to avoid stent-related complications. In their
retrospective study, Freeman et al.33 observed the
time of removal in 45 patients with an anastomotic
leak treated with a stent. They showed that patients
treated for an intrathoracic anastomotic leak after
esophagectomy had a significantly reduced compli-
cation rate related to an esophageal stent when the
stent was removed at 14 days compared with later
removal. This was not associated with a continued
leak in patients with an earlier stent removal. They
concluded that a stent could be removed as early as
14 days after its placement, with no increased risk of
leak recurrence.
Endoscopic endoluminal vacuum therapy is a
recently developed treatment option. The first appli-
cation of an endoluminal vacuum was described by
Loske in 2007 for anastomotic leakage after upper
gastrointestinal surgery, and it showed promising
results.34 The negative pressure applied on the tissue
promotes angiogenesis, removes the accumulating
secretions, and reduces the size of the wound cavity.
It has been used for esophageal anastomotic leakage
since 2010.35
The treatment involves the insertion of a sponge
directly into the defective area under endoscopic
guidance (Fig. 3). The end of the drain is then
connected to an electronic pump, which cre-
ates a negative pressure. There is still a lack of
evidence for when the sponge system needs to be
exchanged. The accepted time frame varies between
3 and 6 days. In some high-volume institutions,
6 Ann. N.Y. Acad. Sci. xxxx (2020) 1–17 © 2020 New York Academy of Sciences.
Chevallay et al.
sponge systems are renewed every 2–4 days. This
interval was chosen based on the availability of
the endoscopy service for routine procedures on
weekends. Other studies reported a mean treatment
duration of 11–27 days, with a sponge exchange rate
of 2.75–6 times.36–40 Schniewind et al.41 showed
that endoscopic treatment had a lower mortality
in critically ill patients. They compared different
regimen therapies for anastomotic leakage (surgical
revision, endoscopic endoluminal vacuum, endo-
scopic stent, and conservative management) and
found that in-hospital mortality was lowest in the
endoluminal vacuum group. When compared with
stenting treatment, the two endoscopic options
seem to be equivalent. A retrospective study42
compared the results of a self-expanding metal
stent (n = 76) with endoscopic vacuum therapy
(n = 35). They found a comparable success rate
in both groups (85.7% in the stent group versus
72.4% in the vacuum group, P = 0.152). The
median ICU and hospital stay lengths were similar.
A recently published meta-analysis by Scog-
namiglio et al.43 showed a significantly higher
success rate in the healing of esophageal leaks,
a shorter duration of treatment, and a lower in-
hospital mortality rate for endoscopic vacuum
therapy compared with SEMS. No difference in
the length of hospital stay was observed. The type
of treatment did not seem to affect the incidence
of major or short-term complications. However,
owing to the limitations of the underlying trials,
a clear recommendation without restrictions can-
not be made for the treatment of an esophageal
anastomotic leak.
Surgical management of anastomotic leakage
Indications for surgical reintervention depend on
several aspects:
r Condition of the patient, when signs of uncon-
trolled sepsis are present.
r Step-up after the failure of an initiated treat-
ment.
r Early leakage (within the first 72 hours).
r Uncontained intrathoracic anastomostic
leaks.
Options for surgical intervention include pri-
mary repair of the anastomosis if the leak is small
and there is no extensive contamination. Rein-
forcement with a flap, such as chest wall muscle,
Chevallay et al. Management of esophagectomy complications

Table 4. Results of studies with endoscopic vaccum therapy, self-expandable metal stent, or surgical treatment
for anastomotic leakage
References Year Type study Number of patients Success rate Complications rate

Berlth et al.42 2018 Retrospective EVT: 27 EVT: 23/27 (85.7%) EVT: 4 (14.8%)
E-SEMS: 69 E-SEMS: 51/69 (74%) E-SEMS: 18 (26%)
Hwang et al.36 2016 Retrospective EVT: 7 EVT: 100% EVT: 0%
E-SEMS: 11 E-SEMS: 7/11 (63.6%) E-SEMS: 6/11; 54.5%
Mennigen et al.40 2015 Retrospective EVT: 15 EVT: 14/15 (93.3%) Mortality
E-SEMS: 30 E-SEMS: 19/30 (63.3%) EVT: 1/15 (6.7%)
E-SEMS: 8/30 (26.7%)
Martin et al.45 2005 Retrospective Surgical treatment: 13 11 (85%) Mortality
2 (15%)
Page et al.50 2005 Retrospective Surgical treatment: 17 15 (88%) Mortality
2 (12%)
EVT, endoscopic vacuum therapy; E-SEMS, endoscopic stent implantation with self-expandable metal stent.

omentum, pleura, or pericardial fat, generally com-
pletes the procedure. If the leak is large or there
is clear necrosis of the conduit, the repair of an
anastomosis in such a hostile environment is rarely
possible. Complete excision of the anastomosis with
the creation of an end-esophagostomy and gastros-
tomy is recommended. If the patient survives, a
delayed reconstruction can be planned in a second
operation. In either procedure, a feeding jejunos-
tomy is required as these patients will have delayed
oral feeding. This will provide enteral nutrition,
which improves the recovery of gastrointestinal
function, prevents the translocation of bacteria,
and appears to lower the rate of complications.44 In
2005, a retrospective study showed that mortality
after reintervention for anastomotic leaks was not
higher than mortality without leaks. They reported
a 3.3% mortality-associated leak.45 Even if the
short-term mortality was comparable, the 5-year
survival was reduced in patients with anastomotic
leakage.46 In their cohort of 128 patients, Kofoed
et al.47 found that the 5-year survival rate was 23%
in patients with leakage and 36% in those without.
A delay in the decision to perform a reoper-
ation in patients with persistent sepsis can have
fatal consequences. This failure to rescue patients
with persistent sepsis was shown first in colorectal
surgery.48 Despite similar surgical complication
rates, variability in outcome following the man-
agement of postoperative complications occurred
between high- and low-mortality hospitals. In
upper gastrointestinal cancer surgery, this effect has
also been studied in England.49 The authors showed
that there was variability in outcomes following
serious surgical complications, necessitating reop-
erations among gastroesophageal cancer surgical
units. Units with lower overall mortality intervened
more often and were subsequently more successful
than units with higher overall mortality. A more
aggressive and appropriate reintervention seems to
confer better outcomes.50 Table 4 summarizes the
results of large studies on the treatment (endoscopic
vaccum, self-expandable metal stent, or surgical) of
anastomotic leakage.
Cardiopulmonary complications
Pulmonary complications
Pneumonia is frequent after esophageal surgery. It
increases mortality and prolongs hospital stay. Low
et al.10 pointed out the lack of a standardized def-
inition for pneumonia. In 56 studies included in a
meta-analysis on postoperative complications, only
18 defined pneumonia, and 16 different definitions
were given.11 This has resulted in a wide range of
pneumonia incidences (2–39%) in previous reports
of esophagectomy outcomes.
This led to an effort to create a scoring system
to define pneumonia after an esophagectomy for
cancer. Van der Sluis et al.51 analyzed the patients
treated for postoperative pneumonia after an
esophagectomy. They looked at the criteria used in
the decision to introduce treatment for suspected
pneumonia and from these results, they created
a scoring system named the Utrecht Pneumonia
Scoring System. The score consists of three vari-
ables: leukocytes, temperature, and pulmonary

Ann. N.Y. Acad. Sci. xxxx (2020) 1–17 © 2020 New York Academy of Sciences. 7
Management of esophagectomy complications
Table 5. Rate of postoperative pneumonia and associated mortality in key studies
Rate of postoperative
References Year Number of patients
Van der Sluis et al.51 2014 185
Weijs et al.52 2016 201
Booka et al.54 2015 284
radiography. A sum score of 2 points or higher,
with at least 1 point assigned to infiltrative findings
on pulmonary radiography, indicates treatment
for pneumonia. This score was then validated
on a U.S. patient cohort52 and revised to create
the Uniform Pneumonia Score. There are still
approximately 25–40% of patients who will suf-
fer from pulmonary complications following an
esophagectomy (Table 5).15,53 It is the leading cause
of postoperative mortality. Pneumonia has been
proven to be a risk factor for in-hospital and long-
term survival. In a retrospective study that included
284 patients, postoperative pneumonia increased
postoperative mortality by 10% and diminished
5-year overall survival by 12%.54 Identification of
risk and protective factors is important to improve
short- and long-term outcomes. The known risk
factors for postoperative pneumonia are age, heavy
smoking history, chronic obstructive pulmonary
disease, operative blood loss, postoperative pain,
and advanced clinical stage.53,55
The surgical approach influences the incidence of
pulmonary complications. Several trials have com-
pared open and minimally invasive approaches.
The TIME trial56 was a randomized trial that com-
pared open and minimally invasive esophagectomy.
Minimally invasive esophagectomy was performed
through a right thoracoscopy and abdominal
laparoscopy. They found that 19 (34%) patients in
the open esophagectomy group had pulmonary
infection in-hospital, compared with 7 (12%) in the
minimally invasive group.
The MIRO trial57 was another randomized trial
that compared the hybrid approach (abdominal
laparoscopic with right thoracotomy) with the
open approach for esophageal cancer. A total of
207 patients were randomized and 31 (30.1%)
patients in the open group had major pulmonary
8 Ann. N.Y. Acad. Sci. xxxx (2020) 1–17 © 2020 New York Academy of Sciences.
Chevallay et al.
pneumonia Mortality
70 (37.8%) 4.5% of patients with pneumonia
2.7% of all patients
80 (40%) 4% of patients with pneumonia
64 (22.5%) Overall survival at 12 months:
76.6% of patients with pneumonia;
85.5% of patients without
pneumonia
complications compared with 18 (17.7%) in the
hybrid approach group, corresponding to a 50%
relative risk reduction. The ROBOT trial,58 a
randomized controlled trial that compared open
esophagectomy versus robot-assisted minimally
invasive esophagectomy (RAMIE), also demon-
strates the benefits of the robotic approach. Pul-
monary complications occurred in 17 out of 54
patients in the RAMIE group (32%) and in 32 out
of 55 patients in the open group (58%). The evi-
dence from these randomized studies showed that
minimally invasive surgery decreased the rate of
pulmonary complications and therefore should be
favored for patients at risk.
Patients should be encouraged to quit smoking,
as smoking cessation more than 1 month before an
esophagectomy seems to significantly reduce pul-
monary postoperative complications.59
Preoperative inspiratory muscle training has
been another field of interest to reduce pulmonary
complications. Several programs are described;
instruction by a physiotherapist and daily inspira-
tory exercise is the most common,60,61 but more
intense programs exist, with three supervised train-
ing periods during the week.62
A systematic review summarized the actual evi-
dence for respiratory prehabilitation. They con-
cluded that inspiratory muscle training showed
improvements in functional status preoperatively,
with three studies showing improvements in respi-
ratory complications, but the heterogeneity of the
studies prevented a strong conclusion.63
Perioperative antibiotic prophylaxis was stud-
ied in a retrospective German study. The authors
did not find any advantage in the prophylaxis
group in terms of pulmonary infection incidence or
mortality.64 Two retrospective studies65,66 showed
that there was no significant correlation between
Chevallay et al.
the detection of pathogenic bacteria in a perioper-
ative routine bacteriological culture (endotracheal
and gastric juice) and the incidence of postoper-
ative pneumonia. Identification of the pathogenic
bacteria is mandatory and endotracheal aspiration
or sputum should be sampled and sent for bacteri-
ological culture. Broad-spectrum antibiotics should
be introduced and adapted according to the bacteria
resistance profile.
Improved pain and perioperative fluid man-
agement have contributed to the decrease in
respiratory complications during the past decade.67
A retrospective analysis on 516 patients iden-
tified independent predictors for postoperative
pulmonary complications.53 They developed a
scoring system based on lung function, age, and
performance status that identified the risk of pul-
monary complications and was relatively accurate
in quantifying the risks. To reduce the risk of devel-
oping postoperative pulmonary complications,
adequate breathing and early mobilization should
be facilitated with appropriate pain control. Epidu-
ral analgesia is the current gold standard following
esophageal surgery, as it is associated with better
pain control, less pneumonia, and a lower mortality
rate compared with intravenous opioids.68
Since its development in 2001, the principles of
enhanced recovery after surgery (ERAS)69 aim to
minimize surgical stress and promote early ambu-
lation and early resumption of oral food intake.
The ERAS protocol aims to optimize perioperative
care by minimizing surgical stress and complica-
tions and accelerating recovery. ERAS guidelines
were published for several gastrointestinal surgical
procedures, including colonic surgery, pancreatico-
duodenectomy, rectal surgery, bariatric surgery, and
gastrectomy. A new ERAS guideline for esophagec-
tomy was published by Low et al.70 This consen-
sus of international experts produced 39 sections for
the perioperative management of patients with an
esophageal resection and could improve outcomes.
Cardiac complications
Atrial fibrillation (AF) is a frequently encoun-
tered complication after esophagectomy and can be
explained by the proximity of the esophagus to the
left atrium.71 In a meta-analysis by Schizas et al.72
that included 53 studies with 9087 patients, the
authors found an overall incidence of 16.5% for AF
in the postoperative period. Coronary artery dis-
Ann. N.Y. Acad. Sci. xxxx (2020) 1–17 © 2020 New York Academy of Sciences.
Management of esophagectomy complications
ease and hypertension were the risk factors. Patients
with AF had a significantly higher risk of over-
all postoperative adverse events than those without
fibrillation (odds ratio (OR) = 5.50), including
30-day mortality (OR = 2.49), anastomotic leak
(OR = 2.65), and pneumonia (OR = 3.42). AF is
a complication that is rarely seen in isolation; it
is therefore advisable to have a low threshold for
initiation of additional diagnostic workup in the
case of cardiac arrhythmia. In a series that involved
473 patients,73 direct consequences of AF were rare,
seen in just four (0.8%) patients, two from ischemic
bowel and two from cerebrovascular accidents. By
discharge, 88 (92%) of the AF patients had reverted
to a sinus rhythm.
Two randomized trials have studied the impact
of preventive rhythm control in patients with an
esophagectomy. The first trial74 randomized the
patients into two groups: one group received amio-
darone for 96 h after the induction of anesthe-
sia, and the other group received no prophylaxis.
Forty patients were randomized to each group.
The incidence of AF was 40% versus 15% in
the control group. There were no significant dif-
ferences between the groups in median hospi-
tal stay, median intensive care unit stay, or post-
operative adverse events. The second random-
ized trial75 used beta-blockers to prevent AF after
an esophagectomy. They randomized 50 patients
to each group. Postoperative AF occurred in 15
patients (30%) who received a placebo versus 5
(10%) who received a beta-blocker (P = 0.012).
There was no difference in the rates of vocal cord
paralysis (P = 0.585), pneumonia (P = 0.318),
anastomotic leakage (P = 0.160), and chylothorax
(P = 0.495). The prevention of AF is feasible in
postoperative patients. The actual evidence does not
show any improvement in short-term outcomes.
However, the onset of AF requires the introduc-
tion of anticoagulation for the prevention of car-
dioembolic events. The preventive strategy would
avoid the introduction of therapeutic anticoagula-
tion after a major surgery.
Chylothorax
The thoracic duct arises from the cisterna chyli at
the level of the second lumbar vertebra, lateral to
the aorta. It generally crosses to the left side of the
body at the fifth thoracic vertebra. The thoracic
duct drains 75% of the body’s lymph. Around 4 L
9
Management of esophagectomy complications
of lymph per day flows from the lower extremities
and abdominal organs back to the brachiocephalic
vein. Its close location to the esophagus in the
thoracic region places it at risk during esophageal
surgery. When injured, the chylothorax can appear
with the accumulation of chyle in the pleural space.
The reported incidence of a chyle leak after an
esophagectomy ranges from 0.9% to 18.6%.76–78
A lower body mass index, high intraoperative
fluid balance, and neoadjuvant chemoradiotherapy
are known risk factors for thoracic duct injury.79,80
Due to the loss of lymphocyte- and lipid-rich fluid,
these patients will suffer from hypovolemia, malnu-
trition, and immunosuppression.
Diagnosis can be done easily via the milky
appearance of the thoracic drainage. If the patient
is malnourished, the concentration of triglycerides
could be lower and change the fluid aspect. A
threshold of triglyceride level >110 mg/dL was set
based on the results of one study conducted 30 years
ago.81 In a study from 2009,82 44% of chylous pleu-
ral effusions had a triglyceride level of lower than
50 mg/dL. The gold standard is the presence of chy-
lomicrons in the effusion and should be tested if a
diagnostic doubt persists.
The ECCG group defined chylothorax10 accord-
ing to its treatment (Type I, with enteric dietary
modifications; Type II with total parenteral nutri-
tion; and Type III with interventional or surgical
therapy) and its severity. (Severity Level A: daily
output <1 L, Severity Level B: >1 L).
The goals for chylothorax management are ces-
sation of the leak, evacuation of the pleural space,
and reduction in nutritional losses. The initial step
to improve respiratory function and monitor the
leak output is the insertion of a chest drain. A con-
servative treatment can then be initiated with a
low-fat diet or total parenteral nutrition and
introduction of subcutaneous octreotide to slow
down the lymph duct flow. A previous treat-
ment for chylothorax was the use of medium-
chain triglycerides.83 Long-chain fats are digested
and absorbed in the jejunum. They are processed
into chylomicrons that enter the lymphatic system.
Medium-chain triglycerides are directly absorbed
through the intestinal mucosa into the portal
vein. A diet composed of medium-chain triglyc-
erides provides the daily fat requirement with sol-
uble vitamins without increasing the chyle leak
output.
10 Ann. N.Y. Acad. Sci. xxxx (2020) 1–17 © 2020 New York Academy of Sciences.
Chevallay et al.
Several factors were identified as predictors for
the failure of conservative management.84 The-
ses factors are related to the chest drain output:
1000 mL/day before treatment with octreotide or an
output of more than 1000 mL/day after 2 days of
treatment with octreotide. The initial output and its
response after introduction of the treatment are pre-
dictors for the success of medical therapy. Pleurode-
sis with instillation of a high concentratation glu-
cose perfusion via the chest tube has been described
with varying success rates in case series and small
series.85
An interventional method for chylothorax man-
agement would be to perform lymphoscintigraphy
with coils embolization. Cope et al.86 described this
percutaneous technique first in 1997 for the occlu-
sion of the thoracic duct. This process is technically
challenging and involves catheterization of the tho-
racic duct percutaneously and embolization (Fig. 4).
In two series,87,88 the success rate for thoracic
duct embolization was between 71% and 74%. The
success rate was related to the ability to catheter-
ize the thoracic duct. If this was technically pos-
sible, the success rate was high, with a cure rate
of 90%. The overall success of catheterization was
between 62% and 67%. The reported complications
were leg edema, wound infection, and emboliza-
tion of the pulmonary artery. When medical or
lymphatic embolization fails, a reoperation with lig-
ation of the thoracic duct is required. The first
description of this procedure was made in 1948.89
In 1973, Selle et al.90 recommended surgery rather
than conservative treatment whenever the daily out-
put of chylous fluid exceeded 1500 mL in adults.
With the improvement of radiological interven-
tion, embolization should be attempted first when
the dietary measure fails. If technically nonfeasible,
reoperation is the second option.
Reoperation is indicated in cases of persistent
leak rates greater than 1000 mL/day over 5 days of
strict starvation or radiological management failure.
The success rate ranges from 87.5% to 100%.77,91
The most difficult part of the procedure is to identify
the leak. Administration of substances, such as but-
ter, cream, or methylene blue, prior to administer-
ing anesthesia may facilitate direct visualization of
the leak site. Video-assisted thoracoscopic surgery
is recommended as the first approach, as it is associ-
ated with less postoperative pain, quicker recovery,
and shorter hospital stay. If the leak is not identified,
Chevallay et al.
Figure 4. Thoracic duct embolization for postoperative chylothorax. Left picture: lymphangiography with puncture in inguinal
lymph node. Middle picture: catheterization of the thoracic duct. Right picture: embolization with coils (arrow).
experts advocate the application of fibrin glue to the
suspected leak site. A German retrospective study
summarized the experience of a high-volume cen-
ter for esophageal surgery in the optimal manage-
ment of chylothorax. A total of 906 patients under-
went an esophageal resection. Chylothorax after an
esophagectomy was identified in 17 (1.9%) patients.
Repeat ligation of the thoracic duct was successful
in 14 (93.3%) patients. The authors recommended
that immediate reoperation should be discussed to
expedite recovery and minimize hospital stay if the
chest tube drainage was more than 500 mL during
the first 24 h after the complete oral intake cessation
and total parenteral nutrition.92
One debate is whether the systematic ligation
of the thoracic duct should be routine during an
esophagectomy. A randomized study of 653 patients
undergoing an Ivor Lewis esophagectomy, who
were separated into either routine or no thoracic
duct ligation, showed a minimized risk of post-
operative chylothorax in patients who had routine
dissection and ligation of the thoracic duct (1.2%
versus 2.1% in the no ligation group).93 In another
study,94 patients were prospectively assigned to two
groups: en masse ligation of the thoracic duct (55
patients) or selective ligation if it appeared injured
(241 patients). In the latter group, 8.7% of the
patients underwent selective en masse ligation of
the thoracic duct. Incidence of chylothorax-related
reoperation was significantly lower in the selective
ligation (0%) than in the systematic ligation (3.6%).
Ann. N.Y. Acad. Sci. xxxx (2020) 1–17 © 2020 New York Academy of Sciences.
Management of esophagectomy complications
The administration of preoperative liquid rich in
lipid nutrition could help identify the thoracic duct
or its injury.95,96 The surgeon can avoid inadver-
tent damage in this setting, identify a potential chyle
leakage, and perform selective ligation. Table 6 sum-
marizes the results of the principal studies on the
management of postoperative chylothorax.
Recurrent laryngeal nerve palsy
The recurrent laryngeal nerve (RLN) plays an
important role in vocal cord coordination. The
RLN originates from the vagus nerve and provides
ipsilateral motor innervation to the intrinsic mus-
cles of the larynx except for the cricothyroid. These
muscles play a major role in speech, swallowing,
and breathing. An anatomical difference exists
between the left and right nerves. The left loops
around the aortic arch from front to back and
returns to the neck. The right nerve has a shorter
pathway and loops around the right subclavian
artery.
Its injury during an esophagectomy is com-
mon during either the thoracic paratracheal lymph
node dissection or the cervical dissection. The
most frequent injuries arise in a cervical anas-
tomosis. In the cervical esophagus, the recurrent
nerves are closer to the esophagus in the upper
part. The risk of injury to the nerve is diminished
if the anastomosis is done at the lowest possible
location.97 The incidence of RLN injury after an
esophagectomy has been reported from 0% to 29.3%
11
Management of esophagectomy complications Chevallay et al.

Table 6. Results of large studies on radiological and surgical treatment of postoperative chylothorax

Nonsurgical treatment Surgical treatment

Total
number of Number of Number of Number of Number of
References Year patients patients (%) resolved cases (%) patients (%) resolved cases (%)

Cope and 2002 42 Thoracic duct 21 (73.8%) 7 7 (100%)

Kaiser87 embolization
29 (69%)
Itkin et al.88 2010 109 Thoracic duct 64 (90%)
embolization
71 (65%)
Schumacher 2007 10 9 (90%) 8 (88%)
et al.91
Merigliano 2000 19 NPO and 4 (36.4%) 15 (%) 14 (93.3%)
et al.77 observation
11 (58%)
Dugue 1998 23 NPO and 14 (100%) 9 (39%) 7 (77.8%)
et al.76 observation
14 (61%)
NPO, nil per os.

(Table 7).98 The transthoracic approach seems to
have a lower incidence. The incidence of RLN injury
was reported to be 0.9% in 220 patients with an
Ivor Lewis esophagectomy.99 Hulscher et al. showed
a relative risk reduction of 0.36 for RLN injury
in an Ivor Lewis esophagectomy compared with
the transhiatal approach, with a rate of 3.5% in
the transthoracic approach compared with 9.5% in
the transhiatal approach.100 RLNP results in glot-
tic incompetence due to the inability of the affected
vocal fold to adduct completely and oppose the nor-
mally mobile vocal fold during tasks that require
glottis closure, such as voicing, swallowing, and
coughing. Impaired coughing and airway clearance
lead to an increased rate of pneumonia, up to 10-
fold, after an esophagectomy.101
The most common processes for this type of
injury are direct thermal injury, stretching injuries,
compression, or vascular compromise. Several
authors proposed intraoperative monitoring with
neural stimulation and laryngeal electrode. The
monitoring was concluded as being feasible and safe
with a good rate of identification (87%),102 but stud-
ies did not find any diminution of RLNP incidence
in the group with monitoring compared with the
nonmonitored group.102,103
When RLNP is diagnosed, the outcome is dif-
ficult to predict and three different outcomes are
possible: full recovery of motion, no return of vocal
fold motion but adequate compensation, and no
regaining of motion with flaccid paralysis. The
treatment includes three options. Observation can
be chosen for spontaneous return of function or
voice improvement with voice therapy to stimu-
late recovery. Injection medialization consists of
a temporary injection in the paraglottic space to
medialize the edge of the paralyzed vocal cord;
this can be done with topical local anesthesia.
This procedure allows recovery of limited func-
tion of the vocal cord, but it is temporary. The
injection material is resorbed over time, with most
preparations lasting 3–6 months. Some authors
hypothesized that the temporary injection material
promotes better positioning of the immobile vocal
fold during the initial period after a nerve injury.
Yung et al. in their retrospective study found that
patients with early temporary injection medializa-
tion were less likely to undergo permanent medi-
alization compared with patients with conservative
management (26% versus 65%, P = 0.013).104 Fried-
man et al. in their cohort found a similar propor-
tion of patients with early injection that did not
require additional treatment; 65% of the patients
with early injection did not require additional treat-
ment when the injection was performed within
6 months of the procedure.105 Early vocal fold

12 Ann. N.Y. Acad. Sci. xxxx (2020) 1–17 © 2020 New York Academy of Sciences.
Chevallay et al.
Table 7. Rate of recurrent laryngeal nerve paralysis (RLNP), its treatment, and its recovery rate in large cohorts
Number of
References Year patients Rate of RLNP
Scholtemeijer 2017 451 47 (10%)
et al.108 Transhiatal: 3/127 (2%)
McKewon: 44/324 (14%)
Yung et al.104 2011 54
Hulscher et al.100 2000 140 31 (22%)
injection seems to create a more favorable vocal
fold position that was maintained by reinnerva-
tion. The prognosis for return of vocal function is
poor if motion and voice have not recovered by
9–12 months from onset.106 In two studies,107,108 the
median time between an esophagectomy and recov-
ery from RLNP was 6 months and the rate of recov-
ery at 12 months ranged between 50% and 61.7%.
Definitive treatment is usually postponed until this
period to allow for potential recovery. If the paral-
ysis persists, transcervical permanent medialization
is recommended.
The thyroplasty proposed by Isshiki et al. in
1974 revolutionized the permanent treatment of
RLNP.109 Under local anesthesia and sedation, a car-
tilaginous window is created at the level of the vocal
fold and a material (usually polytetrafluoroethy-
lene, silastic, hydroxyapatite, titanium, or Gore-Tex)
is implanted to medialize the vocal fold. Other
adjunction techniques can be used during the pro-
cedure (arytenoid adduction and cricothyroid sub-
luxation) to enhance the vocal quality. The use of
early permanent treatment has been questioned by
several authors. Abraham et al.110 examined a series
of 23 patients who underwent permanent medi-
alization for unilateral vocal cord paralysis within
2 weeks following surgical resections for pulmonary
or esophageal malignancies and found improve-
ment postoperatively in all measured outcomes,
including hoarseness and dysphagia. The advantage
of intervening early in the course of injury could
offer protection against respiratory complications.
Two studies examined outcomes at 6–9 months
and found no significant differences in terms of
short-term outcomes between injection laryngo-
plasty and medialization thyroplasty.111,112 Many
authors advocate initial treatment with temporary
Ann. N.Y. Acad. Sci. xxxx (2020) 1–17 © 2020 New York Academy of Sciences.
Management of esophagectomy complications
Secondary
Number of surgical
Treatment recoveries medialization
Observation: 21 (47.7%) 41/47 (87%) 6 (13%)
Speech language
therapy: 36 (81.8%)
Observation: 35 (65%) 12 (34%) 28 (51%)
Temporary injection: 19 14 (73%)
(35%)
Observation: 31 (100%) 25 (75%) 6 (20%)
injectable materials, followed by a period of watch-
ful waiting, before proceeding to laryngeal surgery
if no improvement is observed at 6 months.
Conclusion
Despite progress being made to improve periopera-
tive morbidity and mortality, the complication rate
after an esophagectomy in patients with esophageal
cancer is still high in the modern era. Minimally
invasive surgery and the desire to develop enhanced
postoperative care could lower the morbidity asso-
ciated with this major procedure. The surgeon and
the team participating in the patient care should
know how to recognize early signs of these com-
plications. A delay in management can have seri-
ous consequences as the success of therapeutic
options depends on how quickly the treatment is
started. A sign as subtle as new-onset AF may be
the only manifestation of an anastomotic leakage.
The endoscopic technique has evolved, and this
modality would be the first-line therapy if an anas-
tomotic leakage is suspected. Management deci-
sions should be taken by a multidisciplinary team of
experts, including surgeons, anesthetists, gastroen-
terologists, and oncologists. This proactive attitude
toward the identification of potential complications
will benefit the patient and improve postoperative
outcomes.
Competing interests
The authors declare no competing interests.
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