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362 Part III Esophagus
5
TABLE 17-8: DIVISIONS OF T1 TUMORS
ACCORDING TO THE JAPAN ESOPHAGEAL
I
1
II
III
A
0
2
5
SOCIETY
TX Depth of tumor invasion cannot be assessed
T0 No evidence of primary tumor
T1a Tumor invades mucosa
T1a-EP Carcinoma in situ (Tis)—formerly corresponds to M1
T1a-LPM Tumor invades lamina propria mucosa (LPM)—
formerly corresponds to M2
T1a-MM Tumor invades muscularis mucosa (MM)—formerly
corresponds to M3
T1b Tumor invades submucosa
SM1 Tumor invades the upper third of the submucosal
layer
SM2 Tumor invades the middle third of the submucosal
layer
SM3 Tumor invades the lower third of the submucosal layer
In endoscopically resected specimens, because the full thickness of the submucosa
extending into the muscularis propria is not available for examination, a tumor
invading the submucosa to a depth of 200 µm is classi ed as SM1, while a tumor
invading more than 200 µm is classi ed as SM2.
proximal dilation of the esophagus ( Fig. 17-5 ). Tortuosity,
angulation, axis deviation from the midline, sinus formation,
and stulization to the bronchial tree are signs indicative of
advanced tumor that has traversed the adventitia and involved
59
the neighboring xed organs.
staging modalities, barium studies are becoming less essential.
With the availability of other
B
C
FIGURE 17-4 A. Classi cation of adenocarcinomas around the
gastroesophageal junction (GEJ) according to Siewert. Type I,
esophageal; type II, cardiac; type III, subcardiac. B. A type I adeno-
carcinoma arising from Barrett’s esophagus. e large arrow points at
the gastroesophageal junction (GEJ) while the small arrow points at
the squamocolumnar junction. C. A type II cardia cancer removed as
a total gastrectomy specimen and its corresponding barium contrast
study. ere is no evidence of Barrett’s esophagus.
Bronchoscopy
Use of the beroptic endoscope allows histologic con rmation of the cancer by biopsy or brush cytology. Flexible bronchoscopy is performed to assess tumor involvement of the
tracheobronchial tree, especially for tumors in the middle
and upper esophagus. Signs of involvement include a widened carina, external compression, tumor in ltration, and
stulization. e last two signs contraindicate resection.
60
Gross macroscopic bronchoscopic appearance may not be
accurate, and biopsy and brush cytology is recommended.
61
Computer Tomography Scan
e main value of CT scan in staging of esophageal cancer
lies with its ability to detect distant disease, such as that in
liver, lungs, bone, and kidneys. When metastasis to the liver
is more than 2 cm, sensitivity is 70–80% although it drops
to approximately 50% when it is less than 1 cm.
lung metastases are rare in patients presenting with esopha-
63
geal carcinoma
and thus, when seen on CT, are more likely
to be primary lung cancers or benign nodules and should be
investigated as such.
62
Solitary
Chapter 17 Cancer of the Esophagus 363
In the diagnosis of T4 disease, obliteration of the fat plane
between the esophagus and the aorta, trachea and bronchi, and
pericardium is suggestive of invasion, but the paucity of fat in
cachectic patients makes this criterion unreliable. When the
area of contact between the esophagus and the aorta extends
for more than 90 degrees of the circumference, an 80% accu-
64
racy of inltration was reported,
but this is by no means abso-
lute and the accuracy is inferior to that of EUS.
e sensitivity of detecting mediastinal and abdominal
nodal involvement is suboptimal with CT scans because
only size alone can be used as diagnostic criterion. However,
normal-sized lymph nodes may contain metastatic deposits
and enlargement of lymph nodes may be due to reactive and
inammatory hyperplasia. Studies using high-resolution helical CT scanning have demonstrated sensitivities of 11–77%
as well as specicities of 71–95% for detection of regional
65,66
nodal disease.
CT scanning is nowadays commonly performed together with PET scanning; a composite picture is
created in the same setting to correlate more accurate anatomy
with metabolic uptake (Fig. 17-6). Experience with magnetic
those of CT.
67
FIGURE 17-5 Barium contrast study showing a stenotic tumor.
Mucosal irregularities and proximal dilation with retention of
contrast material is evident. A sinus often indicates inltrative
disease (arrow).
Endoscopic Ultrasound and
Percutaneous Ultrasound
Endoscopic ultrasound (EUS) is the only imaging modality
able to distinguish the various layers of the esophageal wall,
usually seen as ve alternating hyper- and hypoechoic layers
FIGURE 17-6 Combined PET and CT image: in addition to size of lymph nodes, the standard uptake value often will help to determine if
the lymph node is involved by cancer. A right pulmonary hilar node identied with its corresponding PET image. Standard uptake value (SUV)
uptake was 3.1.
364 Part III Esophagus
in 30.8% of patients (160/519). e sensitivity, specicity,
and accuracy of US diagnosis in patients who underwent
subsequent cervical lymphadenectomy were 74.5%, 94.1%,
and 87.6%, respectively. In those who did not undergo neck
dissection, the chance of cervical nodal recurrence was low, at
less than 5%.
78
Information gained by combining preoperative cervical
ultrasound and EUS can be highly prognostic. In one study,
when the number of metastatic nodes was stratied into
subdivisions of 0, 1–3, 4–7, and 8 or more, the number of
involved lymph nodes was prognostically similar to the eventual subdivisions as determined by histological diagnosis.
79
However, both percutaneous and EUS are highly operatordependent, and their meticulous application is required to
produce these results.
FDG-PET Scans
FIGURE 17-7 Endoscopic ultrasound (EUS) picture of an early
tumor conned to the mucosa. Five layers of the esophagus could be
seen; the two dark layers are the muscularis mucosae (inner layer) and
muscularis propria (outer layer). In this tumor, the hyperechoic layer
of the submucosa has not been reached. e tumor is at 6 o’clock. is
lesion was removed with endoscopic submucosal dissection (ESD)
technique.
(Fig. 17-7). e accuracy of EUS for tumor and nodal staging
averages 85 and 75%, respectively, compared to 58 and 54%
68
for CT scanning.
One problem with EUS is the nontra-
versable tumor stricture, which occurs in about one-third of
69,70
patients.
in up to a 25% chance of perforation.
Early studies showed that predilation may result
71,72
More recent results
suggest that predilation is safe, and the success rate of complete examination depends on the size of dilation—36% for
73
11–12.8 mm, and 87% for 14–16 mm.
An alternative is to
use miniaturized ultrasound catheter probes passed through
the working channel of a conventional endoscope, which can
achieve comparable accuracy to conventional EUS.
74
Echo features of lymph nodes that suggest malignant
involvement include echo-poor (hypoechoic) structure,
sharply demarcated borders, rounded contour, and size
75
greater than 10 mm, in increasing order of importance.
A
collective review showed that the overall accuracy of staging
68
nodal disease was 77%.
e accuracy of EUS may dier for
dierent lymph node locations and is related to the depth
of penetration of EUS (about 3 cm). It is best for detecting
paraesophageal nodes, and sensitivity varies inversely with the
76
axial distance of the nodes from the esophageal axis.
e
ability to perform EUS-guided FNA cytology of suspicious
nodes (such as celiac nodes) is another factor that makes EUS
superior to CT scanning.
77
Percutaneous ultrasound is particularly useful for obtaining FNA biopsies of cervical lymph nodes. In one large study
in 519 patients, cervical lymph node metastasis was detected
PET scan is gaining popularity in esophageal cancer staging
80,81
(see Fig. 17-6).
For the detection of the primary tumor,
the sensitivity of PET ranges from 78 to 95% with most
false-negative tests occurring in patients with T1 or small T2
65,82
tumors.
Adenocarcinomas of the GEJ and proximal stomach sometimes show limited or absent FDG accumulation
regardless of tumor volume (FDG nonavidity). Some investigators observed this phenomenon in as many as 20% of these
patients, which seems to be related to the diusely growing
subtype and poorly dierentiated tumors.
83
PET does not provide denition of the esophageal
wall and thus has no value in T stage. For locoregional
nodal metastases, its spatial resolution is also insucient
to separate the primary tumor with juxtatumoral lymph
nodes because of interference from the primary tumor,
and thus most studies demonstrated poor sensitivity.
82,84
is is especially true for nodes in the middle and lower
mediastinum, where most primary tumors are found. In
one study, the sensitivities of PET for detecting cervical,
upper thoracic, and abdominal nodes were 78%, 82%, and
60%, respectively, but was only 38 and 0% respectively for
65
the mid- and lower mediastinum.
Specicity of PET in
detecting regional nodes is usually much better, reaching
82,84
95–100% in some studies.
e low rate of false-positive
ndings is important in preoperative staging.
A meta-analysis of 12 publications on PET scanning in
esophageal cancer showed that the pooled sensitivity and
specicity for the detection of locoregional metastases were
0.51 (95% CI, 0.34–0.69) and 0.84 (95% CI, 0.76–0.91),
respectively. For distant metastases, the corresponding gures
were 0.67 and 0.97. When two studies (out of 11) that had
particularly low sensitivities for detection of distant metastases were excluded (probably because they included more early
tumors), the pooled sensitivity improved to 0.72 and speci-
85
city to 0.95.
is study highlights again that the accuracy
of PET in locoregional nodes is only moderate. EUS-FNA
is superior in this regard. PET is more useful for picking up
distant metastases.
Chapter 17 Cancer of the Esophagus 365
A multi-institutional trial with a primary objective to evaluate whether PET could detect metastatic disease that would
preclude esophagectomy was recently published. Patients
who had operable disease after conventional staging (including CT scan) were evaluated with PET scan. Of 189 patients,
only 9 (4.8%) had M1b disease found and conrmed as true
positives and were excluded from surgery. An additional 3.7%
had unconrmed M1b disease. However, apparent M1 ndings by PET were also found in at least 3.7% of patients.
86
e true value of PET scan may therefore be limited and costeectiveness should be evaluated further.
Thoracoscopy and Laparoscopy
oracoscopy and laparoscopy have their advocates. oracoscopic staging usually involves a right-sided approach, with
opening of the mediastinal pleura from below the subclavian
vessels to the inferior pulmonary vein with lymph node sampling. Laparoscopic staging can include celiac lymph node
biopsy and the use of laparoscopic ultrasound for detecting
liver metastases. One multi-institutional study (CALGB 9380)
reported results in 113 patients, and the strategy was feasible
in 73% of patients. oracoscopy and laparoscopy identied nodes or metastatic disease missed by CT scan in 50% of
deaths or major complications occurred, it did involve a general anesthesia, one-lung anesthesia, a median operating time of
87
210 minutes, and a hospital stay of 3 days.
Laparoscopy could
be used in diagnosing metastases (especially peritoneal spread)
or identifying unsuspected cirrhosis, which may contraindicate
resection, and it could be performed as a preliminary
procedure during the time of planned esophagogastrectomy.
Its main contribution would be in lower esophageal and cardial
adenocarcinoma, while its value is expected to be minimal for
88
more proximally located tumors.
Given their invasiveness,
thoracoscopy and laparoscopy should be reserved for cases in
whom positive conrmation of metastatic disease not otherwise obtainable is essential in deciding on treatment.
TREATMENT
Stage-Directed Therapy
In the past, esophageal cancer was treated by surgical resection alone, radiotherapy, or use of a plastic stent for palliation.
Increasing choices and combinations of therapeutic options
have made staging important; the treatment for early and
advanced cancers should be individualized.
Treatment for Early Squamous
Cell Cancers
Early tumors include T1a-EP, LMP, MM and T1b-SM1,
SM2, and SM3 lesions as dened in Table 17-8. e distinction is important because of the risk of nodal metastases.
e incidence of lymph node involvement in T1a-EP, T1aLMP, and T1a-MM tumors are 0%, 3.3%, and 12.2%, respectively. For T1b-SM1, SM2, and SM3 lesions, the respective
incidences of lymph node involvement are 26.5, 35.8, and
89
45.9%, respectively.
For mucosal cancers 5-year survival rates
are 80–100% and for submucosal cancers 50–65%.
T1a-EP or LMP tumors are amenable to endoscopic resection because they carry a very small risk of nodal metastases and
endoscopic resection is a suciently radical treatment. Because
circumferential resection is likely to be associated with cicatricial
stenosis, this procedure is indicated for lesions not exceeding
two-thirds of the circumference. Lesions reaching T1a-MM or
T1b-SM1 (200 µm deep from the muscularis mucosa) may be
associated with nodal metastases, but endoscopic mucosal resec-
lymph node metastasis (relative indication). Lesions showing
deep invasion (T1b-SM2 or SM3) are associated with metastasis at a frequency of about 30–50% and are treated in the
Japan Esophageal Society with regards to endoscopic resection
90
are shown in Fig. 17-8.
Other unfavorable features for endoscopic resection in addition to depth of inltration and extent
of involvement include poorly dierentiated tumor and ndings of lymphovascular inltration in the resected specimen.
-
tted forward-viewing endoscope, saline is injected into the
submucosal layer in order to raise the lesion from the deeper
wall layer. e lesion is sucked into the cap and a snare wire
that has been prelooped is used to snare the lesion. e strangulated mucosa is cut by blend-current electrocautery. In a
series of 250 patients, 72% had absolute indications when
patients, no local or distant metastases occurred during follow-up. e 5-year survival rate was 95%. All those who died
within 5 years died of non–cancer-related causes.
Endoscopic submucosal dissection (ESD) techniques are
now preferred by many endoscopists. In this method, the
injection is carried out. Various types of uid have been used
for injection to delay dispersion, for example glycerol, hyaluronic acid, hypertonic saline, and mannitol. rough-thescope “knives” such as hook, needle, ex, or insulated tip (with
ceramic) knives are used to cut out the lesions. is technique
be used to remove large lesions of substantial length in one
piece, thus achieving the aim of en bloc removal. e depth of
resection can also be deeper and controlled, often revealing the
underlying muscularis propria. Positive margins are less likely,
and an en bloc specimen is more suitable for more complete
pathological examination. e skill to perform ESD, however,
(which is usually minor), perforation (which can be prevented
by adequate submucosal saline injection and can be treated
sometimes with hemoclip), and stenosis (which tends to occur
when the lesion is large).
91
366 Part III Esophagus
Investigational stateRelative indicationsAbsolute indications
EP or LPM lesions not
exceeding two-thirds of the
circumference
Clinical and histopathological evaluation
Follow-up
observation
FIGURE 17-8
Guidelines for diagnosis and treatment of carcinoma of the esophagus part I. Japan Esophageal Society. Esophagus. 2008;5:61–73, with kind permission from Springer Science +
Business Media.)
Treatment for High-Grade Dysplasia and
Early Adenocarcinoma
Barrett’s high-grade dysplasia, synonymous with intra epithelial
cancer, is the last preinvasive stage in the metaplasia-dysplasia-cancer
sequence. Options of treatment include intensive surveillance,
MM or SM 1 lesions not
accompanied by clinical evidence
of lymph node metastasis, or EP or
LPM lesions exceeding two-thirds
of the circumference
Determination of radicality
Additional treatments (radical surgery, radiotherapy, chemotherapy)
SM2 or deeper lesions
targeted for local control
mucosa, endoscopic resection is recommended to ensure no
48
invasive cancer is present.
If surveillance is to be carried
out, the American College of Gastroenterology recommends
48
three-monthly surveillance.
e intensity that is required in
surveillance of patients with high-grade dysplasia does make
this an unattractive option.
mucosal ablation, and esophagectomy.
INTENSIVE SURVEILLANCE
Proponents of endoscopic surveillance claim that such a
strategy can diagnose invasive cancer at an early stage and
treatment can be delayed until then without compromising
prognosis. e high morbidity and mortality rate of esophagectomy is also thought by some to be a deterrent to immediate surgical resection. Opponents of surveillance observe that
most patients with high-grade dysplasia will have an invasive adenocarcinoma identied during the following 5 to 10
years, in approximately 25% of patients at 1.5 years, 50% at
31
3 years, and up to 80% 8 years later.
High-grade dysplasia is currently the only reliable marker in preinvasive cancer detection, but interobserver concordance is suboptimal
92
in distinguishing invasive and noninvasive lesions.
esophagectomy is carried out in patients who have highgrade dysplasia, invasive cancer is identied in the surgical
When
specimen in up to 42% of patients, even when patients have
93
been recruited in surveillance programs.
More recent evidence, however, suggests that this gure is an overestimation;
a meta-analysis of histologic ndings after esophagectomy
for high-grade dysplasia revealed invasive adenocarcinoma
(at least submucosal cancer) in 12.7% and most of these had
visible lesions at endoscopy, a known risk for invasive can-
94
In the absence of visible lesions, this gure is as low as
cer.
95
Most would regard the nding of high-grade dyspla-
6.7%.
sia as a threshold for intervention. In patients who have visible lesions, such as raised nodules and not just a at Barrett’s
ENDOSCOPIC THERAPIES
e rationale of endoscopic mucosal treatments is that the
incidence of nodal metastases is low in high-grade dysplasia or
T1a (intramucosal) cancers, and therefore treating the mucosal disease alone will result in cure. In T1a lesions, the rate of
nodal metastases is low, reported as 0–6%. Once the submucosa
is invaded (T1b lesions), this gure rises to around 20%.
96,97
Barrett’s esophagus. e largest series on the use of localized
were treated; all had mucosal lesions of a diameter up to 20
mm, without lymphovascular invasion proven by histology of
the resected specimen and histologic grades G1 and G2 arising
in Barrett’s metaplasia. Complete local remission was achieved
in 99% of patients, 11% developed recurrence (6% locally and
5% at dierent locations), but successful repeated treatments
were possible in all. Calculated 5-year survival rate was 98%.
98
One problem about Barrett’s metaplasia is multifocality of
dysplasia and potential malignant transformation. us, in
addition to localized resection of suspicious lesions, ablation
of the whole Barrett’s mucosa is desirable. Mucosal ablative
therapies consist of various methods for ablating the metaplastic mucosa combined with high-dose acid-suppressive
therapy so that normal squamous mucosa will replace the
ablated metaplastic mucosa in a pH-neutral environment.
tery, argon beam coagulation, photodynamic therapy (PDT),
and radiofrequency ablation.
Chapter 17 Cancer of the Esophagus 367
cedure is usually necessary to lessen the chance of stricture
formation. In a series of 41 Barrett’s patients who had highgrade dysplasia or early adenocarcinoma, circumferential
metachronous early cancer was found in 12% of patients.
99
not en bloc. Barrett’s epithelium could be missed and grow
mucosal ablative therapy is that specimens are available for
histopathologic examination.
PDT has been demonstrated in a randomized trial to
reduce the cancer risk in Barrett’s esophagus. In this study,
208 patients with high-grade dysplasia were randomized
comparing PDT using pormer sodium plus a PPI against
PPI only. High-grade dysplasia was eliminated in 77% of
the PDT group, although 39% in the PPI group also lost
high-grade dysplasia on subsequent biopsies. Barrett’s epithelium elimination was achieved in 52% in the PDT compared to 7% in the PPI group. Adenocarcinoma developed
in 15% of the PDT group compared with 29% in the PPI
group, with a longer time to progression to cancer favor-
100
ing PDT.
e problems with PDT treatment include the
need for repeated sessions, photosensitivity, stricture formation (6% in the series just described), and the phenomenon
of buried glands or pseudoregression; residual metaplastic
mucosa beneath the regenerated squamous mucosa can be
present, which makes continual surveillance necessary. is
101
incidence can be as high as 51%.
Because PDT does not
treat nodal disease and there is not specimen histological
examination, accurate pretherapy diagnosis of noninvasiveness is necessary.
be eective in treating both nondysplastic and dysplastic Barrett’s esophagus. It is a balloon-based circumferential endoscopic radiofrequency device (HALO360); 60 tightly spaced
bipolar electrodes that deliver radiofrequency are wrapped
around the balloon. A sizing balloon is rst introduced into
the esophagus; an appropriately sized radiofrequency frequency balloon is then used to ablate the mucosa. Ablation
is based on frictional heating of cellular water molecules.
e advantages of the system are that it is easy to use, and,
because of its controlled depth of injury up to 500–1000 µm
(to the muscularis mucosae), stricture formation is uncommon. A more focal device (HALO90) mounted on the tip of
a gastroscope is also available. e upper surface of the device
is a 20-mm-long × 13-mm-wide articulated platform with
an electrode array identical in pattern to the circumferential
device. It is best used for ablating residual Barrett’s mucosa
after initial HALO360 treatment.
e Ablation Intestinal Metaplasia-II (AIM-II) trial examined the use of the HALO system in ablating nondyplastic
Barrett’s esophagus up to 6 cm in length. HALO360 treatment was performed at baseline and repeated at 4 months
if there was residual intestinal metaplasia. Focal ablation
with HALO90 was carried out after 12 months if needed. At
12months complete remission of metaplasia was achieved in
48 of 69 patients (70%) and at 30 months 60 of 61 patients
(98%). No stricture or buried glands were found.
Another trial recently published examined the use of
HALO system in ablating dysplastic Barrett’s esophagus; 127
patients were randomly assigned in a 2:1 ratio to radiofre-
stratied according to the grade of dysplasia and the length
of Barrett’s esophagus. Primary outcomes at 12 months
included eradication rates of dysplasia and intestinal metaplasia. In the intention-to-treat analyses, among patients
with low-grade dysplasia, complete eradication of dysplasia
occurred in 90.5% of those in the ablation group as compared with 22.7% of those in the control group. Among
patients with high-grade dysplasia, the respective gures
were 81 and 19%. Overall, 77.4% of patients in the ablation group had complete eradication of intestinal metaplasia,
compared with 2.3% in the control group. Patients in the
ablation group had less disease progression (3.6 vs 16.3%)
and fewer cancers (1.2 vs 9.3%). Stricture only developed in
6% of ablated patients.
103
ESOPHAGECTOMY
Surgical resection is the only method to ensure complete
eradication of the dysplastic mucosa, and the frequently
undetected invasive cancer. Surgical resection was considered a standard treatment because of the high frequency of
invasive cancers found in surgical specimens when resection was performed for high-grade dysplasia (up to 42%),
though more recent evidence suggests that this gure
94
is much lower at 13%.
e supposedly high morbidity
and mortality rates of esophagectomy are also deterrents
against surgical resection. However, in specialized centers,
the mortality rate from esophagectomy, especially in this
group of patients, is minimal. Minimally invasive surgical
methods, including thoracoscopy, laparoscopy, or esophageal stripping, further reduce the trauma of surgical access.
Excellent long- term survival with good quality of life is
reported.
104,105
Vagal-sparing esophagectomy leaves the vagi intact, is
another approach aimed at preserving quality of life, and has
been shown to result in much fewer postvagotomy symptoms.
In the Merendino procedure, limited surgical resection of the
distal esophagus and GEJ, together with lymphadenectomy of
the lower mediastinum and upper abdominal compartment,
has also been advocated. An isoperistaltic jejunal interposition
graft is used to restore intestinal continuity. is method combines the adequacy of nodal dissection and improved quality
of life, as the jejunal loop prevents gastroesophageal reux.
In summary, in patients with high-grade dysplasia or early
intramucosal cancer, there is a denite risk of progression to
invasive cancer, treatment needs to be individualized. e
choice between intensive surveillance, mucosal ablative therapies, and esophagectomy needs to be considered based on
available expertise and patient’s preference.
102
107
106
368 Part III Esophagus
Treatment For Advanced Esophageal
Cancer
SURGICAL RESECTION FOR ESOPHAGEAL
CANCER
Surgical resection remains the mainstay treatment for
patients with localized esophageal cancer. In dedicated highvolume centers, mortality rate from surgery of 2–3% can
be achieved.
dent.
also improves outcome.
Important aspects to enhance better outcome after esophagectomy are (1) selecting appropriate patients for resection,
(2) choice of surgical techniques and their execution, and (3)
enhancing perioperative care.
Patient Selection for Esophagectomy. How stringent
one selects patients for esophagectomy will inuence the
resection rate. Selection depends on many factors, including
(1) the referral pattern of individual centers, (2) the prevailing treatment philosophy, (3) the availability of alternative
therapies, and (4) the possible mortality that the surgeon and
from 21 to 70–80%.
able prereferral bias or a high prevalence of early cancers in
those with high resection rates.
In studies that report on improvement of surgical results
over time, more stringent patient selection often comes into
play, either by excluding high-risk patients or by treating
advanced disease by nonoperative means.
a clear aim for palliation is becoming uncommon, and most
would only operate on patients for potential cure.
Factors often cited as being predictive of morbidity and
mortality after esophagectomy include advanced age,
performance status,
more proximally located tumor,
cirrhosis,
ing from adenocarcinoma and squamous cell cancers also have
dierent risk proles. Patients with squamous cell cancers are
more likely to be malnourished, have high alcohol intake, are
smokers, and have more impairment of pulmonary and hepatic
function. Patients with adenocarcinomas on the other hand are
more likely to be overweight and are more at risk from cardiovascular diseases.
Assessing a patient’s tness is often based on the surgeons’
experience and intuition and is not an exact science. Objective scores can help assess operative risk and patient selec-
116,118,121
tion.
based on compromised general status and poor cardiac,
hepatic, and respiratory function as independent predictors of postoperative death, 30% of patients with otherwise
resectable tumors were excluded from surgery. When this was
applied in prospective patient selection, it led to decrease in
postoperative mortality rates from 9.4 to 1.6%
It is uncertain if patient selection based on a strict mathematical scoring system is better than one based on surgeon
56,108–112
111,113
Centralization of service to high-volume hospitals
119
and abnormal cardiac evaluation.
A volume-outcome relationship is evi-
114
110,115
is wide variation suggests prob-
116
116
nutritional depletion
120
112
poor pulmonary function,
117
and weight loss,
116
Patients suer-
In one series of studies using a scoring system
116
112
poor
118
and anesthesiologist assessments alone. ey are more likely
to be complementary to each other.
Choice of Surgical Approaches. ere are many impor-
tant variables in esophagectomy, suchas surgical access, the
extent of resection and lymphadenectomy, the type and the
method of preparation of the esophageal substitute, the route
of reconstruction, and the technique of esophageal anastomosis. Many of these variables are interrelated and could aect
immediate morbidity and mortality rates, long-term quality
of life, and survival. Tumor location and stage, patient’s risk
prole, and surgeon’s preference and experience are important variables in deciding the surgical procedure. e surgeon
should be versatile and well versed with the many dierent
techniques to adapt to dierent clinical situations.
Cervical Esophageal Cancer. In 1960, Ong and Lee rst
described the procedure of pharyngolaryngoesophagectomy
(PLE) as a one-stage, three-phase operation that involved cer-
122
vical and abdominal incisions and a thoracotomy.
Tumors
involving the hypopharyngeal and upper cervical esophageal
region were resected together with the whole esophagus, and
the stomach was delivered via the posterior mediastinum to
the neck for pharyngogastric anastomosis. A terminal tracheostome was constructed. e thoracotomy was later replaced
by transhiatal esophageal mobilization. oracoscopic esophageal mobilization has become another and our preferred
123
alternative.
PLE is associated with signicant morbidity
and mortality, partly related to the fact that the procedure
is often performed as a last resort for salvage when no other
123
means of palliation exists.
So despite improvements in surgical care, results remain worse compared to patients with
intrathoracic cancers. At the authors’ institution, of 317 PLE
performed from 1966 to 1995, mortality rate decreased from
31 to 9%.
124
For tumors conned to the proximal portion of the
cervical esophagus with sucient distal margin, free jejunal
interposition graft or deltopectoral or pectoralis major
myocutaneous aps are options for reconstruction after resection. e use of a free jejunal graft is advantageous because it
avoids mediastinal dissection, though expertise in performing
microvascular anastomosis is essential. Graft necrosis, stula
formation, and late graft strictures are specic problems.
When compared with gastric pull-up, graft survival and leak
rates are similar. Stricture was the most common late complication for free jejunal transfers, whereas reux was most
common in gastric pull-ups, both occurring in approximately
125
20% of patients.
swallowing mechanism in all patients.
is also tolerant to postoperative radiotherapy.
Functional study showed a satisfactory
126
e jejunal graft
127
e need to
sacrice the larynx does make surgical resection an unattractive option, and chemoradiation has been used up-front in
many series, with surgery reserved for salvage.
128
Intrathoracic Esophageal Cancer. For tumors in the
upper thoracic esophagus, obtaining a sucient proximal
resection margin dictates an anastomosis placed in the neck.
Chapter 17 Cancer of the Esophagus 369
For this reason, resection is best carried out by a three-phase
129
esophagectomy or the McKeown approach.
In this procedure a right thoracotomy is rst carried out to mobilize the
thoracic esophagus together with lymphadenectomy; this is
followed by abdominal and neck incisions for the mobilization of the esophageal substitute, placing the anastomosis
in the neck. e split-sternum approach is an alternative,
especially for tumors close to the thoracic inlet.
130,131
e majority of intrathoracic cancers are squamous esophageal cancers located in the middle and lower esophagus, and Barrett’s adenocarcinomas in the lower esophagus. e most widely
3
used approach was that described independently by Lewis
4
Tanner.
e operation begins with an abdominal phase, in
and
which the stomach is prepared, followed by a right thoracotomy
and resection of the tumor together with lymphadenectomy. e
stomach is then brought up into the chest for anastomosis with
the proximal esophagus at the apex of the pleural cavity.
An alternative approach involves a single left thoracotomy incision. rough a left thoracotomy and incision in
the diaphragm, both the esophagus and stomach could be
mobilized and resection carried out, and stomach delivered
into the chest for anastomosis, either below or above the aortic arch. Proximally the aortic arch does hinder surgical access,
making mobilization of the proximal esophagus and subsequent anastomosis dicult. e approach is therefore more
suitable for cancer of the cardia or the distal esophagus where
an adequate resection margin is obtained below the aortic arch.
A transhiatal approach, whereby the thoracic part of the
esophagus is mobilized by blunt and often blind dissection
through the enlarged esophageal hiatus, and the mobilized
stomach is then delivered to the neck and anastomosed to the
cervical esophagus is is advocated especially for distal esophageal tumor or early-stage tumors of other parts of the esophagus.
Abdominal Esophagus and Gastric Cardia Tumors.
For cancers that are limited to the abdominal esophagus or
gastric cardia cancers, an abdominal-right thoracic approach
as in a Lewis-Tanner esophagectomy is one option, with the
proximal stomach also resected in order to gain an adequate
distal resection margin. A left thoracoabdominal incision
through the seventh or eighth rib space also gives excellent
exposure of the low mediastinum and upper abdomen. A
single left thoracotomy with opening up of the diaphragm is
also an option. is gives reasonable exposure of the upper
abdomen. However, lymphadenectomy toward the hepatoduodenal ligament is hampered. When a thoracotomy is
not desired, opening the hiatus widely by splitting the crura
laterally and the diaphragm anteriorly can gain access to
the low posterior mediastinum, and distal esophagectomy
can be performed with the anastomosis performed from the
abdomen without the need for a thoracic incision. e anas-
stapler designed with a transoral placement of the anvil into
the distal esophagus makes construction of a lower mediastinal anastomosis easier. When the proximal stomach is
reconstruction is preferred by many.
Transthoracic Versus Transhiatal Resection. is con-
tinues to be controversial. Proponents of transhiatal resection believe that surgical resection for esophageal cancer is
mostly palliative and a cure is a chance phenomenon for
only those with very early tumors. More thorough lymphadenectomy through a thoracotomy merely improves staging but does not aect prognosis. e operating time is also
shorter and postoperative morbidity is less with the transhia-
132
tal approach.
Conversely, surgeons who practice transtho-
racic esophagectomy (TTE) consider the open approach to
133
be safer, with dissection under direct vision.
A more thor-
ough lymphadenectomy leads to better staging and survival.
Population data from the Surveillance, Epidemiology, and
from 1992 to 2002 who underwent either transhiatal or
transthoracic approach were studied in one recent study; 225
underwent transhiatal and 643 received TTE. Lower operative mortality rate was observed after a transhiatal than transthoracic approach (6.7 vs 13.1%). Survival was not dierent
after adjusting for tumor stage, patient, and provider factor.
134
e largest randomized controlled trial comparing the two
approaches studied 106 patients who underwent transhiatal
esophagectomy and 114 patients who had the transthoracic
approach for mid-lower third/cardia adenocarcinomas. Pulmonary complication rates were 27% in the former group
compared to 57% in the later. Ventilation time, intensive care,
and hospital stay were longer in the transthoracic group. ere
were, however, no signicant dierences in in-hospital mortality at 2 and 4%. Signicantly more lymph nodes were dissected
in the transthoracic group (16 vs 31). Overall 5-year survival
was 34% (transhiatal) and 36% (transthoracic). Importantly, it
showed that in individuals with limited nodal spread (one to
eight positive lymph nodes), TTE imparted a survival advantage (64 vs 23%). Survival was not dierent in patients with
no nodal metastases or in those with more nodal metastases.
135
e location and stage of the primary tumor has bearing on
which surgical approach is selected. From a purely safety point
of view, transhiatal resection is not suitable for patients with
advanced middle- or upper-third tumors, especially in patients
with tumors closely related to the tracheobronchial tree and after
neoadjuvant radiation therapy; tumor inltration or brosis
may obliterate tissue planes and make blind dissection unsafe.
As such, its application is more suitable for lower esophageal
tumors for which much of the mobilization can be performed
under vision. From an oncological standpoint, the philosophy
toward lymphadenectomy dictates the surgical approach.
Minimally Invasive Esophagectomy (MIE). Various
combinations of minimally invasive approaches including
thoracoscopy, laparoscopy, mediastinoscopy, hand-assisted
laparoscopy, and open laparotomy and thoracotomy have
136
been explored.
e myriad of surgical methods implies a
lack of consensus on which is superior.
Large single-center series are few; some have experience
137–140
of over 100 patients.
been published
136,141–144
Several reviews on MIE have
; none could conclusively show that
MIE is better or worse than that of the open approach,
370 Part III Esophagus
and no randomized controlled trial has been undertaken.
Conversion rate is approximately 5%, respiratory complications 13–22%, and a very low mortality rate of 3% is
142,143
achieved.
Biere and colleagues examined 10 comparative studies comparing MIE with open esophagectomy,
comprising 1061 patients. ree comparative groups were
created for meta-analysis: (1)total MIE versus open TTE;
(2) thoracoscopy and laparotomy versus open TTE; (3)
laparoscopy versus open transhiatal esophagectomy. ere
was a trend toward less mortality with MIE in groups 1 and
2, and fewer anastomotic leaks with MIE in group 2 were
found. Again, denitive conclusions could not be reached
because of selection bias and the variety of techniques
144
used.
Potentially serious intraoperative complications can
occur with MIE, such as bleeding from the azygous vein
146
and from intercostal vessels,
tracheobronchial tree,
149–151
injury to the aorta,
and recurrent laryngeal nerve,
145
147,148
152
but certainly they are not specic for these methods. e
increased magnication and excellent visualization oered by
thoracoscopy might help lessen complications.
Whether MIE could reduce morbidity and mortality rates remains controversial. is is partly because of the
number of patients studied generally was too small to have
enough statistical power to demonstrate a dierence. ere
are also other reasons why benets are dicult to conrm.
With modern analgesic methods, such as epidural analgesia,
153
postoperative pain control is less critical a problem.
e
genesis of cardiopulmonary complications is multifactorial
and does not depend solely on the size of the incisions. Surgical trauma from mediastinal dissection is independent of
the incision size. e benet of smaller port sites compared
with open thoracotomy may be oset by the lengthened
time of single-lung anesthesia. A learning curve obviously
154,155
exists for such complicated procedures.
e duration of
the thoracoscopic procedure, blood loss, and the incidence
of postoperative pulmonary infection were all less, and the
number of mediastinal nodes retrieved was more, in the latter
half of a group of 80 patients who had thoracoscopic esopha-
154
gectomy.
us, for most series, the full technical potential
may not have been realized. e number of procedures that
need to be performed before the learning curve is overcome
is uncertain.
Patient selection is evident in many series, and in some
studies most subjects had early-stage disease or high-grade
138,156
dysplasia in Barrett’s esophagus.
e most important
test will be long-term survival by stage-by-stage comparison,
but stage migration may be hard to eliminate. Most series
do not report on survival data and, in those that do, there
is no reported dierence compared with historical controls.
Existing data, however, do show that nodal harvesting can be
136
equivalent to that of open surgery.
e place of MIE thus
remains controversial without a well-conducted randomized
controlled trial.
Extent of Resection: Axial and Lateral Margin. One
of the most controversial aspects of treating gastrointestinal
malignancies is the appropriate extent of resection, and this
debate is exemplied by esophageal cancer.
157
resection results in total removal of the tumor mass (primary
and lymph nodes) with clear proximal, distal, and lateral
margins. e need to obtain clear axial and lateral margins
is less controversial. e propensity of esophageal cancer to
spread intramurally and to have multiple separate tumors in
the esophagus is well recognized. e prevalence of intraepithelial, subepithelial, or intramural spread was as high as
158,159
46 and 54%,
around 30% of patients.
and multiplicity of tumor was found in
159,160
e deeper the wall penetra-
tion of the primary tumor, the farther away such spread can
158
take place.
positive margin declines with increasing distance at which
the esophagus is transected away from the tumor edge, and
that the frequency of anastomotic recurrence is a function of
It is clear that the chance of a histologically
the length of proximal resection margin attained. Taking into
account shrinkage of the specimen after resection, as a guide
to surgery, an in situ margin of 10 cm (fresh contracted specimen of approximately 5 cm) should be aimed at, to allow
a less than 5% chance of anastomotic recurrence.
operative frozen section is one method to ensure a negative
margin. However, a histologically involved resection margin does not necessarily lead to denite anastomotic recurrence, and a negative margin does not preclude anastomotic
recurrence. e occurrence of skip lesions or submucosal
spread can be missed even by a conscientious pathologist;
hence margins may be falsely negative. Extramural recurrence with inltration back to the anastomosis may also be
indistinguishable from true anastomotic recurrence. Patients
who have positive histologic margins are those likely to have
more advanced disease, and early recurrences at more distant
sites may make anastomotic recurrence less relevant. In our
study, a positive histologic margin (diagnosed with denitive
histology and not with frozen section) occurred in 7.5% of
patients who had esophagectomy, which had an anastomotic
recurrence rate of 10.3% compared to 4.9% in those with
a negative margin. e dierence, however, did not reach
statistical signicance.
161
Microscopic involvement of the lateral margin (macro-
scopically clear) results in increased chance of local recurrence
162
and worse survival.
Obtaining a clear lateral margin is dicult with esophageal cancer because of its anatomical position
and adjacent indispensable structures. Neoadjuvant therapy
may help achieve this. Some Western centers advocate the
concept of “en bloc” resection, which aims at removing the
primary tumor together with the pericardium, thoracic duct,
azygous vein, intercostal vessels, and bilateral pleurae overlying the primary tumor and a surrounding cu of crura (where
the primary tumor is abutting) to enhance lateral clear-
108,163
ance.
Obviously this type of resection is less suitable for
upper esophageal cancers in close proximity to the trachea.
e concept of “en bloc” resection is thus more applicable for
Western patients, where most tumors are adenocarcinomas of
the lower esophagus.
161
Intra-
Chapter 17 Cancer of the Esophagus 371
A
FIGURE 17-9 e extent of mediastinal lymphadenectomy: A. Standard mediastinal lymphadenectomy includes removing the paraesophageal
nodes and subcarinal and right and left bronchial nodes below the tracheal bifurcation. B. Extended mediastinal lymphadenectomy involves
standard lymphadenectomy plus right apical nodes, right recurrent laryngeal nerve nodes, and right paratracheal nodes.
Extent of Lymphadenectomy: Squamous Cell Cancers.
As discussed previously, the ability to perform lymphadenectomy is closely related to the surgical approach utilized, and an
open transthoracic or thoracoscopic approach is necessary,
unless only a limited lower mediastinal dissection is planned.
In countries where squamous cell cancers are prevalent,
transhiatal resection is uncommonly performed based on
safety concerns, as well as because the value of lymphadenectomy is less questioned.
Conventional lymph node dissection for esophageal cancer usually involves a “standard two-eld” lymphadenectomy,
which entails removing the nodes and periesophageal tissue
below the level of the carina, and the lymph node stations
around the celiac trifurcation. When superior mediastinal
lymph node dissection is performed, it is sometimes known
as “extended two-eld lymphadenectomy.” “ree-eld”
B
lymphadenectomy involves additional bilateral cervical
lymph node clearance (Figs. 17-9 to 17-14). For intrathoracic
squamous cell cancers, detailed lymph node mapping of metastatic disease in Japan shows that lymph nodes can spread
to the neck, mediastinum, and upper abdomen around the
celiac trifurcation. e overall rate of cervical lymph node
metastases is approximately 30%. In relation to the level of
primary tumor, cervical lymph nodes are involved in 60,
20, and 12.5% of upper-, middle-, and lower-third tumors,
respectively. When nodes along the recurrent laryngeal nerves
from the superior mediastinum are considered together with
the cervical nodes as one entity, this “cervicothoracic” group
nodes are involved in up to 63.4% of proximal-third, 45.2%
164
of middle-third, and 42.0% of lower-third cancers.
ese
data provide the rationale behind “three-eld” lymphadenectomy, where the true value of extended lymphadenectomy