6
Treatment of early oesophageal cancer
The prevalence of early oesophageal cancer
is increasing due to the rising incidence of
adenocarcinoma (ACA) in the West, persistent high
incidence of squamous cell carcinoma (SCC) in the
East, along with improving methods of endoscopic
diagnosis and surveillance strategies identifying high-
risk changes in the mucosa. The management of early
oesophageal cancer has evolved, with consensus that
selected patients should be treated with endoscopic
therapy consisting of resection of localised neoplasia
with ablation of associated high-risk mucosa with
curative intent aiming to avoid an oesophagectomy.
Definition of early
oesophageal cancer
A cancer in the oesophagus is considered ‘early’ if
it is contained within the superficial components
of the epithelial lining and there is no lymph node
involvement. Using the AJCC staging criteria, for
both SCC and ACA, this would include oesophageal
cancer diagnosed at stages 0 or IA.1 Stage 0 includes
Tis or high-grade dysplasia (HGD) of the epithelium.
This had previously been called carcinoma in situ.2
Stage I includes cancers that are T1–2 and relates
to the depth of invasion into the oesophageal
mucosa/submucosa (T1) and muscularis propria
(T2), with no lymph nodes involved. However, the
true pathological stage can only be diagnosed after
resection of the oesophagus. A clear definition of T
stage is vital when assessing a patient thought to
have an ‘early’ oesophageal cancer, as the deeper the
invasion into the mucosa and submucosa, the higher
the incidence of nodal metastasis.
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B. Mark Smithers
Iain Thomson
The T1 stage can be subclassified into cancer that
is restricted to the mucosa, T1a, or extends to the
submucosa, T1b. T1a carcinoma is intramucosal
carcinoma (IMC) and can be subclassified
according to the level of invasion, such as: confined
to the epithelium (m1), the lamina propria (m2)
or the muscularis mucosae (m3).1 Patients with
Barrett’s oesophagus may have duplication of the
muscularis mucosae but they are still m3 so long
as the muscularis mucosae has not been breached.
Cancers infiltrating into the submucosa (T1b), may
be subclassified into sm1 (inner third), sm2 (middle
third) and sm3 (outer third)1 (Fig. 6.1).
The relevance of subclassification relates to the
risk of lymphatic invasion. The lymphatic network
in the oesophagus is concentrated in the submucosa;
however, there are lymphatic channels in the lamina
propria. There is a higher risk of nodal involvement
if the cancer invades to T1b level compared with T1a
cancers.3–12 There are subtle differences between
patients with ACA and SCC. HGD in Barrett’s
epithelium and in squamous epithelium as well as
ACA or SCC involving m1 have not been reported
to develop nodal disease.3,5,6,9,12 A large review
reported the overall lymph node-positive rate for
T1a, ACA to be 1.93% (95%CI 1.19–2.66), with
only patients with m3 invasion being positive in
8/170 patients (4.7%).3
For patients with SCC to the m2 level, there have
been reports of patients with positive lymph nodes
found in 3.3%5 and 5.6%,12 although others have
reported no evidence of positive nodes with this level
of invasion.6–11 If the tumour extends to m3, the node-
positive rate has been reported to be 18% in a large
single-centre series12 and 12.2% in a review of 1740
89
Chapter 6
T1a – ACA 2%,3 T1b – ACA 26%,13
SCC 18%12 SCC 45%13
m1 m2 m3 sm1 sm2 sm3 T2
m ACA = 0
5,12
SCC = 3.5−5.6%
ACA = 2%
3 Muscularis
5,12
SCC = 12−18%
ACA = 10%
SCC = 27%
13
ACA = 21%
sm SCC = 36%
13
ACA = 49%
13
SCC = 55%
Figure 6.1 • Anatomical layers of the oesophagus with
risk of lymph node involvement.
patients with early SCC.5 The histological finding of
lymphatic invasion in association with m3 invasion
has been shown to increase the risk of positive lymph
nodes from 10% to 42%.7,12
For either ACA or SCC invading into the submucosa
(T1b) the potential for nodal metastasis increases
from sm1 to sm3.13 A review of articles from 1997
to 2011 reported an overall lymph node-positive rate
for patients with T1b cancer to be higher in patients
with SCC (45%) compared with ACA (26%). For
sm1 disease, the presence of lymphatic invasion on
histology increases the risk of positive lymph nodes
from 11% to 65%.7 Comparing each level for the
risk of nodal positivity for SCC compared with ACA
the risk for sm1 was 27% vs 10%; sm2, 36% vs 21%
and for sm3, 55% vs 49%13 (Fig. 6.1).
One report of 85 patients with T1 ACA analysed
four subgroups with differing nodal involvement
and prognosis. Patients with T1a disease had no
nodes and 100% disease-specific survival (DSS).
Those with T1b cancers were split into three groups:
well-differentiated and no lymphovascular invasion
(LVI) – 4% nodal involvement, 85% 5-year DSS;
poorly differentiated and no LVI – 22% nodal
involvement, 65% 5-year DSS; and any cancer with
LVI – 46% nodal involvement, 40% 5-year disease-
specific survival.4 This highlights the reasons for the
difference in recommendations when it comes to
management of the disease.
In patients with ACA with sm1 invasion, the risk
of lymph node metastasis is minimal if the disease
is well or moderately well differentiated, less than
20 mm, has no evidence of lymphovascular invasion
and is not ulcerated.14 Rather than use sm1, some
authors have used the depth of invasion into the
submucosa as a guide, with nodal metastasis shown
to be low if invasion is less than 500 μm as measured
by the pathologist.14,15 These data are relevant, with
90
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a focus on the role of endoscopic therapy in patients
with submucosal invasion of the cancer.
The reason for the difference between histologic
Epithelial layer subtypes is not clear but explanations include: fewer
lymphatic channels in the lamina propria in the lower
Lamina propria oesophagus (where ACA occurs)16 and that SCC is
more biologically aggressive at an earlier stage.12,17
mucosae
Patients with HGD or intramucosal ACA (T1a) have
Submucosa a very low risk for lymph node involvement and are
suitable for endoscopic ablative therapies as definitive
treatment.
Patients with squamous HGD and SCC with
Muscularis invasion to m1 and m2 disease are unlikely to have
propria
nodal metastasis and thus are suitable for endoscopic
therapy.
The other T stages in patients with ACA (early sm1
or SCC m3, early sm) have a higher rate of lymph node
involvement, which must be taken into consideration
along with patient factors when deciding appropriate
definitive treatment.
The risk of lymph node involvement in patients with
submucosal involvement (sm2, sm3) and any histology
is high enough to recommend treatment of the primary
and the associated lymphatics as definitive therapy.
Investigations/staging
The patient will have had a biopsy reporting either
HGD, carcinoma in situ or invasive carcinoma
in either the squamous epithelium or Barrett’s
glandular epithelium.
Endoscopic assessment and local
staging
Barrett’s neoplasia
Patients with the diagnosis of HGD or IMC in
Barrett’s epithelium should have the endoscopy
repeated according to a protocol of four quadrant
biopsies one centimetre apart and targeted biopsies
of macroscopically suspect lesions. Two independent
experienced gastrointestinal pathologists should
review the pathology to confirm the diagnosis.
Squamous neoplasia
Patients with a diagnosis of HGD in squamous
epithelium or suspected early invasive carcinoma
should have the endoscopy repeated to clearly
establish the extent of the disease process. The use
of Lugol’s iodine staining has traditionally been
recommended as the areas of mucosa that do not
stain are most likely to be neoplastic, allowing
targeted biopsies. Knowledge of the extent of
the mucosal change is important when planning
treatment as very long segments may only be treated

with oesophagectomy. If endoscopic therapy is to be
considered, the non-stained areas outline the targets
for endoscopic resection or ablation.
More recently, the use of narrow banded imaging
(NBI) has been reported to be reliable18 and not
inferior to Lugol’s staining.19 In a RCT comparing
NBI with magnification endoscopy and Lugol’s
staining, the NBI technique took a shorter time,
with similar accuracy, no difference in sensitivity
and it was less invasive.20 This technique has been
recommended as the optimum technique to use for
screening patients at high risk for developing SCC.18
Endoscopic mucosal resection (EMR)
This is the removal of the mucosa and a varying
degree of submucosa. In patients with HGD or
suspected IMC this is the most accurate and
definitive method of confirming the histology and
defining the T stage of the abnormal mucosa or
any mucosal lesion. An EMR has been reported
to change the clinical T classification in 53% of
patients with ACA and 39% of patients with early
SCC.13 Endoscopic mucosal resection offers better
T staging than EUS and CT scanning21 (Fig. 6.2).
Patients with squamous epithelial neoplasia should
have abnormalities targeted with EMR. A study of
51 patients who had an EMR for squamous HGD
reported 31% to be m2/3 with over a third of these
lesions being flat such that they were unrecognisable
from HGD alone.22 This also stresses the need for
extensive mapping biopsies of squamous epithelial
neoplasia, if endoscopic therapies are to be
considered.
Endoscopic submucosal dissection (ESD)
This technique is widely used in Asia, notably by
the Japanese for definitive treatment of patients
with superficial gastric cancer. It has been used for
a b
Figure 6.2 • Intramucosal carcinoma in a segment of Barrett’s epithelium (a) pre-endoscopic mucosal resection and
(b) post-endoscopic mucosal resection.
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Treatment of early oesophageal cancer
squamous neoplasia because it entails a formal
dissection in the submucosal plane to remove a
complete segment of mucosa and submucosa. The
advantage is that the whole abnormal segment
of oesophagus may be removed en bloc, with less
margin involvement compared with EMR in the
tubular oesophagus.23 However, this technique
requires a higher degree of expertise than EMR.
Endoscopic ultrasound
The accuracy of differentiating the layers of the
mucosa has been reported to be 85–100% with
the use of the higher frequency (15 and 20 MHz)
miniprobes;24 however, the numbers in these studies
are small and these are expert centres. A systematic
review assessing the accuracy of EUS in assessing
early oesophageal ACA and SCC reported a large
degree of heterogeneity due to site of the lesion,
method of use and the frequency of the ultrasound
probe and experience of the operator, to differentiate
a T1a and T1b lesion. The main role for EUS was
considered to be to define a T2 lesion and to assess
lymph nodes.25
In a review evaluating the role of EUS to change
management in patients with early oesophageal
cancer the proportion of patients with more advanced
disease, not amenable to endoscopic therapy, based
on T stage was 14%. In the absence of nodules,
stricture or ulceration, the potential to change
management was 4%. The ability to predict T1sm
had a sensitivity of 56%, specificity of 89%, positive
predictive value of 63% and negative predictive
value of 85%. EUS over-diagnosed patients with
submucosal disease, so that it was recommended
this procedure should not be considered alone when
deciding a treatment approach for these patients.26
91
Chapter 6
Patients with invasive disease being considered for
oesophagectomy should have anatomical imaging
with CT scanning and functional imaging with
proton emission tomography, usually in combination.
Endoscopic mucosal resection of defined
mucosal abnormalities offers the most sensitive
method of obtaining a T stage for early oesophageal
neoplasia and should be considered before defining
the overall treatment of the patient.
Management of early
oesophageal cancer
The definitive management of an invasive
oesophageal cancer is the complete eradication of the
primary lesion with a margin of normal epithelium
along with the draining lymph nodes. Patients with
HGD in Barrett’s oesophagus may have an associated
carcinoma and patients with superficial SCC of the
oesophagus have a higher potential for lymph node
involvement, making surgical resection the definitive
therapy for these patients. Oesophagectomy has
been the gold standard; however, more recently
endoscopic therapy for lesions confined to the
mucosa is considered safe and, in selected patients, to
be the optimal therapy, with comparison to surgical
outcomes confirming the efficacy of this approach.
Radiotherapy targeting the primary lesion with
or without chemotherapy can be an alternative to
oesophageal resection.
Endoscopic therapy
For mucosal carcinoma, endoscopic therapies
are the default option, accepting surgery as the
alternative. To be acceptable as the definitive
treatment, endoscopic therapy must completely
eradicate the neoplastic epithelium in a situation
where the risk of positive lymph nodes should be
zero or very low.
Endoscopic mucosal resection
Aside from diagnosis and T stage assessment, this
technique may be therapeutic by removing the
lesion completely. The techniques used result in
piecemeal segments of mucosa and submucosa
being removed. The procedures include ‘inject,
suck, and cut’(ER-cap) and ‘band and snare’ (ER-
MBM), and these have been shown to provide the
pathologist with equivalent and adequate depths
of mucosa and submucosa.27 A randomised study
assessing the two techniques has shown that ER-
cap produces specimens of larger diameter but with
equivalent amount of submucosa. ER-MBM was
92
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quicker, less costly and had a similar safety profile.28
Short segments of neoplastic epithelium (Barrett’s
or squamous) can be completely removed in up to
80–94% of patients.29 However, the recurrence rate
increases with the length of follow-up because the
treatment may not have dealt with all the Barrett’s
epithelium, some of which may not be visible. When
EMR alone is used to eradicate the Barrett’s segment,
the complete eradication rate may reach 97% but
the incidence of stricture can be as high as 37%.30
For patients with Barrett’s neoplasia, the optimal
use of EMR is for focal resection of the HGD or
mucosal cancer segment with associated use of
ablative techniques. This approach has been shown
to be safe, with a low incidence of complications
such as bleeding (0–1.5%), perforation (0.3–0.5%)
and stricture formation if segmental regions are
treated (7–9%).
For squamous epithelial neoplasia the results from
EMR are similar to Barrett’s neoplasia. The rates of
recurrence have been reported to be 10–26%.31–33
More specifically, when the recurrence rate was
assessed in association with depth of invasion the
incidence was reported to be 13–18% in lesions that
were m1/2.32
Endoscopic submucosal dissection
This is a technically demanding procedure with a
higher risk of perforation and a higher incidence
of stricture formation when compared with EMR
because of the deeper resection plane and larger
segments removed. In a review of the role of ESD
compared with EMR in eight studies, all from Asia,
ESD was reported to give a higher en bloc and
curative rate compared with EMR for superficial
SCC. There was a longer operating time and higher
perforation rate but a lower local recurrence
rate.23 A review of ESD for both histologic
subtypes reported a resection rate of 99%, which
was complete in 90% (95% CI 87–93%). The
perforation rate was 1% and the stricture rate was
5%, being 9% before 2011 and 2% after 2011 and
related to the extent of resection.34 A systematic
review of six cohort studies assessing ESD for
oesophagogastric carcinoma reported a complete
resection rate of 87% with a 7% stenosis rate.35 All
studies were from Japan.
This technique has not been readily taken up in
the West for the management of Barrett’s neoplasia
although there have been European reports of the
technique used for SCC.31,36 The European Society
of Gastro-intestinal Endoscopy has recommended
EMR for lesions less than 10 mm. The evidence in
Barrett’s oesophagus is that ESD is not superior to
EMR but may be considered for lesions greater than
15 mm and for those with poor lifting following
submucosal injection of saline, suggestive of a
higher risk of submucosal invasion.37

Mucosal ablation
If the focal mucosal carcinoma has been completely
removed endoscopically the residual high-risk
mucosa should be eradicated by either endoscopic
resection or ablative techniques. Radiofrequency
ablation (RFA) is the gold standard ablative
technique, with other options including argon
plasma coagulation (APC), photodynamic therapy
(PT) and cryotherapy (CT).
Radiofrequency ablation (RFA) is a balloon-
based radiofrequency device that will ablate the
mucosal layer of the tubular oesophagus to the
submucosa. There is also a separate device that will
treat distinct residual patches of Barrett’s mucosa.
The UK RFA registry (HGD 72%, IMC 24%) has
reported the outcomes from 335 patients who had
a focal lesion removed with RFA or RFA alone for
HGD. At 12  months the complete eradicaton rate
for HGD and intestinal metaplasia was 86% and
62%, respectively, and the incidence of invasive
carcinoma 3%.38 Patients typically will require
a number of procedures. Stricture rates between
7% and 13% have been reported. A systematic
review of RFA has concluded that following focal
EMR of endoscopic nodules and known IMC,
RFA is the endoscopic treatment of choice for
dysplastic Barrett’s epithelium.39 Residual disease is
typically seen as small islands or tongues and can
be treated separately. Complete eradication cannot
be guaranteed, with newly detected metaplasia at
1 year seen in up to 26%, with 8.5% reported to
have dysplasia.40
Ablative therapies for Barrett’s carry the risk of
the presence of subsquamous intestinal metaplasia,
which carries a risk of malignant transformation.
RFA has the lowest risk, being 0.9%, in a review of
1004 patients who had Barrett’s ablation.41
There are very few data available relating to the
use of RFA for squamous neoplasia. In a study
of 29 patients with dysplasia,18 HGD10 and SCC,
m11 treated with RFA, after a single treatment,
at 3  months the complete response rate (CR) was
86%. At 12 months, with further RFA treatments,
the CR was 83% (14% LGD).42 The UK RFA
registry reported 20 patients who had an EMR of a
visible lesion (5 patients) and RFA of the neoplastic
squamous epithelium. At 12  months 30% of the
patients had progressed to invasive SCC.38
Photodynamic therapy is very intensive and only
performed in specialist units. It has high complication
rates such as photosensitisation and high stricture
rates with lower efficacy rates. The remission rate
from PT, with replacement by squamous epithelium,
was 50–80% of patients.43 PT has been replaced by
RFA. Some centres use APC and CT.
Argon plasma coagulation (APC) will eradicate
the superficial Barrett’s mucosa to a variable depth
allowing complete eradication in 38–99% of patients,
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Treatment of early oesophageal cancer
with recurrence rates of 3–16%.44–47 APC has a
better ablation rate when compared with PDT.47
Cryotherapy destroys tissue with cycles of rapid
freezing and slow thawing. Typically, multiple
treatments are required to achieve ablation of the
Barrett’s segment with recurrences higher if the
segment is greater than 3 cm.48
Results from endoscopic therapy
for early oesophageal cancer
Adenocarcinoma
A large single-centre experience of 1000 patients
treated for HGD and or IMC in Barrett’s epithelium
using focal EMR and Barrett’s ablation reported
complete eradication of the neoplasia in 96% at
5 years.49 In a review of studies assessing the role of
Barrett’s ablation, after EMR of HGD patients who
had Barrett’s ablation were compared with those who
did not have the Barrett’s ablated. The long-term cancer
risk was reduced by ablation but not abolished. After
ablation the risk of malignant change was 16.66/1000
patient years compared with 65.8/1000 patient years
in those who had observation only.50 A systematic
review of the role of focal EMR and RFA reported
the worse progression to cancer rate of 0.9%. For
patients with associated dysplastic epithelium treated
with RFA the progression to cancer rate was 0.1% per
year.51 Once a complete eradication has been obtained
patients still require close endoscopic follow-up.
There has been one case-controlled comparative
study assessing oesophagectomy compared with EMR
and ablation in patients with ACA, IMC (T1a).52 The
resection group had a median follow-up of 4  years
with no tumour recurrence. The major complication
rate was 32% and 90-day mortality 2.6%. Following
endoscopic therapy there was no major morbidity
or mortality, and 6.6% of patients needed further
local therapy, during the median follow-up time of
3.7 months.52
The use of EMR has been reported in a cohort
of 21 patients having endoscopic therapy for ‘low-
risk’ T1b adenocarcinoma. Low risk was defined as:
invasion of the upper sm1; absence of lymphatic/
vascular invasion; grade I/II; polypoid or flat lesion
(not ulcerated). APC was used for Barrett’s ablation
in 73%. At a median follow-up of 62 months there
was an initial 90% complete resection rate with 28%
recurrence of metachronous carcinoma. There were
no tumour-related deaths. For this subset of patients
one needs to consider this treatment as experimental
and more suitable for patients not considered to be
surgical candidates until more data are available.53
Squamous cell carcinoma
The majority of the studies are from Japan using
EMR or ESD.5,33,54,55 A study from Japan assessed
93
Chapter 6
the outcome from EMR in 351 patients and reported
a 5-year disease-free survival of 98%. At a median
follow-up of 9 months the local recurrence rate was
2% in patients with m1/2 disease, 7% with m3/sm1
and 7% sm2/3. The only patients who developed
metastasis had sm1/2 disease.56 The largest single-
centre series has 300 patients with m1 to m3 (m3
15%) disease in whom 184 had EMR and 116 ESD.33
A positive margin was seen in 3% who had ESD and
22% who had an EMR. However, the stricture rate
was 17% for ESD compared with 9% who had an
EMR. Local recurrence was 10% following an EMR
that removed the disease as a piecemeal resection.
Recurrence may also manifest as recurrent nodes
or systemic disease. This is more likely to occur in
patients who had lesions that were m3 or submucosal
treated with EMR or ESD.31,54,55
Patients with early oesophageal neoplasia including
HGD, stage 0 and stage I disease have a potential
for cure of their disease. Patients and those treating
them must commit to a diligent protocol of regular
follow-up endoscopy, accepting that this approach
carries a risk of recurrence of the metaplastic and/
or dysplastic epithelium and that long-term acid
control is very important, particularly in those
patients with ACA.
For patients with intramucosal ACA, endoscopic
therapy is an appropriate alternative to resection of
the oesophagus. This should be complemented by
endoscopic ablation of associated Barrett’s dysplasia
and intestinal metaplasia. RFA ablation is the gold
standard. Recurrence of the intestinal metaplasia
and/or dysplasia can occur along with a small risk of
malignancy.
For patients with squamous neoplasia or IMC
(m1/2), EMR is an option or for larger segments, in
experienced hands, ESD is an option if the disease
can be completely removed. For patients with m3/
sm1 (without LVI): EMR/ESD is an option if the patient
is unwilling or unfit for resection. The role of ablation
techniques for squamous neoplasia is uncertain.
It is essential that patients who have undergone
endoscopic ablation techniques undergo careful and
vigilant endoscopic follow-up.
For submucosal disease there will be very few
patients for whom endoscopic therapy is a suitable
treatment unless they are not fit for surgery or refuse
resection.
Oesophageal resection
The clear advantage of complete removal of the
disease process provided by an oesophageal resection
must be weighed against the potential mortality and
morbidity of the procedure.
94
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In a review from 2007 of 29 series of patients
having a resection for Barrett’s HGD, it was reported
that cancer was found in the specimen in 37% of
cases with 60% of this group (22% of the total)
invading beyond the mucosa.57 However, this review
consists of a number of older series where patients
were unlikely to have had a systematic approach
to biopsy of the Barrett’s mucosa, and none of
the patients underwent an EMR of the abnormal
mucosa, offering a better histological assessment
with improved T staging. The factors that have been
reported to be associated with a coexisting cancer
in HGD are a visible lesion, ulceration and HGD at
multiple levels.58,59 With the addition of a targeted
EMR of focal lesions the potential for an unexpected
finding of invasive cancer should be small.
For patients confirmed to have squamous
dysplasia, the potential for the development of an
invasive cancer increases with time. For low-grade
intraepithelial neoplasia (LGIN), the risk at 3.5 years
and 13.5 years has been reported to be 5% and
24%, respectively; moderate grade intraepithelial
neoplasia (MGIN) 27% and 50% and high-grade
intraepithelial neoplasia (HGIN) 65% and 74%.60
Definitive treatment should be directed towards
HGD with careful observation in patients with
lower levels of dysplasia.
For patients with HGD and IMC, the short-term
cancer mortality is low so that if surgery is contemplated
the outcomes must be optimal. The operative mortality
for oesophageal resection in high-volume centres has
been reported to be 2–4%, with rates of 0–1% when
the resection was for HGD or IMC.57,61 The long-
term disease-specific survival (DSS) following an
oesophagectomy for HGD should be 100% and for
early invasive oesophageal cancer (stage I) for ACA
80–90%16,62 and SCC 3-year survival of 85%63 and
5-year DSS of 53–77%64,65 have been reported.
Because of the associated high morbidity, mortality
and effects on the quality of life, alternatives to a
traditional oesophagectomy and lymphadenectomy
have been explored. For lesser procedures to be
successful a degree of predictability of the lymph
node drainage is necessary. For stage I disease, in
one study, patients with ACA had the majority
of positive nodes below the tracheal bifurcation,
locally associated with the primary cancer in all
but 2% of patients. For SCC the nodal site was
not predictable, with the positive nodes widely
distributed in the chest and upper abdomen.16
For early ACA this had led to groups attempting
variations for resection of the diseased segment. Two
variations described for patients with Barrett’s HGD
and IMC are a limited resection of the oesophagogastric
junction66 and vagal sparing oesophagectomy.67 The
resection of the oesophagogastric junction with jejunal
interposition (Merendino operation) is performed
using a transabdominal approach, with splitting of the

oesophageal hiatus to access the lower oesophagus. The
dissection can be carried out through the hiatus, to the
level of the tracheal bifurcation, incorporating a lower
mediastinal and upper abdominal lymphadenectomy
with or without preservation of the vagal innervation
of the distal stomach. Following resection of the
distal oesophagus, cardia and proximal stomach, the
gastrointestinal continuity is restored by means of
interposition of an iso-peristaltic, pedicled, jejunal loop
to prevent postoperative reflux.66 The outcome of over
100 procedures for early Barrett’s cancer was reported
to be similar in terms of long-term survival compared
with a radical oesophagectomy. The advantages
were lower peri- and postoperative morbidity, and
a good postoperative quality of life. The procedure
has been reported to be technically challenging and
requires attention to detail to achieve good long-term
functional results.66
A vagal-sparing oesophagectomy (VSO), has
been described for resection of HGD and T1a adeno­
carcinoma of the lower oesophagus. Reconstruction
is via the use of a gastric tube or colon pull-up. The
authors report a reduction in side-effects attributed to
the vagal resection that occurs with a more aggressive
resection,67 with an operative mortality of 2% and
a major complication rate of 35%. Although there
was a reduction in post-vagotomy symptoms such
as diarrhoea and dumping symptoms, these were not
abolished.67
Other approaches include the trans-hiatal dissection
and minimally invasive methods of oesophagectomy.
The trans-hiatal approach has been reported to
reduce respiratory complications compared with
an open oesophagectomy.68 Although suitable for
ACA, the trans-hiatal approach does not address
the issue of the unpredictable lymphatic drainage of
SCC so that a systematic lymphadenectomy should
be performed with the benefits of a cervical and
upper mediastinal lymphadenectomy being weighed
against the added morbidity in this group.6,16,69
Minimally invasive approaches to oesophagectomy
aim to reduce the trauma of the abdominal and/
or the thoracic incisions. A randomised controlled
trial comparing an open approach to a combined
thoracoscopic oesophageal mobilisation and a
laparoscopic approach to the gastric mobilisation
reported a significant reduction in respiratory
complications from the minimally invasive
approach.70 This was also the case in a comparative
study examining open surgery with a hybrid
approach consisting of a laparoscopic abdominal
gastric mobilisation and an open thoracotomy.71
There does not appear to be any detrimental
oncological impact using the minimally invasive
approaches, compared with an open resection for
invasive cancer, with a meta-analysis, including
studies from the East and the West, reporting no
difference in the 1- to 5-year cancer survival.72
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Treatment of early oesophageal cancer
Sentinel node biopsy offers a targeted approach to
lymphadenectomy. The literature consists of small
cohort studies with a review suggesting this technique
is not reasonable for use in current practice, but
there may be a role in patients with early stage
oesophagogastric junction ACA.73 For T1 tumours
there was a 17% higher detection rate compared
with T3/4 cancers, with no difference between SCC
and ACA, but the sensitivity was higher for ACA due
to the more predictable lymphatic drainage.74
Oesophagectomy does have an effect on the quality
of life of patients. There have been reports that claim
the long-term functional outcomes from a resection
are at least equivalent to the general population.75,76
However, despite these conclusions there are patients
that have significant gastro-oesophageal reflux
(59–68%), dysphagia (38%), dumping (15%),
diarrhoea (55%) and bloating (45%).75,76 Others
have confirmed a higher incidence of functional
symptoms such as dumping syndrome, bloat, reflux
and diarrhoea, which do not settle in the long term.77
Aside from cancer invading into the submucosa
(T1b), the more definitive indications for an
oesophagectomy instead of endoscopic therapy alone
include: patient preference after a full discussion
about the alternatives; positive margins after EMR/
ESD for T1a IMC; difficult to eradicate Barrett’s
neoplasia such as multifocal disease or long segment
neoplasia; poor oesophageal body function such as
achalasia and a patient who is not committed to
long-term surveillance with repeated endoscopy
with or without further endoscopic therapy.78
Resection offers the most definitive treatment
aimed at cure for early oesophageal neoplasia,
taking away the need for long-term endoscopic
surveillance.
Resection is the definitive approach for T1b
early oesophageal cancer. However, surgery has a
potential for mortality and unpredictable effects on
short- and long-term quality of life.
Endoscopic therapy compared
with oesophagectomy
There have been three meta-analyses and one review
assessing and comparing the outcomes of the two
approaches,13,14,79,80 three in cohorts with Barrett’s
neoplasia14,79 and one assessing both histologic
variants,13 along with two published consensus
conference reports78,81 and one international
consensus statement.82 All have concluded that
endoscopic therapy consisting of EMR of the HGD/
IMC segment with endoscopic ablation of any
metaplastic/dysplastic epithelium is safe and should
be the first line of therapy for HGD/IMC (T1a).
95
Chapter 6
In one review the mortality from endoscopic therapy
was 0.2% compared with 1.4% from surgery. The
neoplasia-specific mortality from endoscopic therapy
was zero. The 1-, 3- and 5-year survival rates were
the same. The baseline patient morbidities were the
main long-term cause of death. Compared to surgery
the endoscopic therapy major adverse event rate was
0.38 (95% CI 0.2–0.75).79
Patients require lifelong follow-up and should
accept the possibility of re-intervention if there
is recurrent neoplasia or intestinal metaplasia.
Using a decision analysis model for surgery to be
the preferred option in this group of patients, the
endoscopic procedure mortality would need to be
2% and the risk of positive lymph nodes more than
50%.83
Endoscopic therapy is less likely to be successful
for long segment Barrett’s greater than 8 cm; poorly
differentiated ACA; lesions greater than 2 cm; large
hiatus hernia and if there is poorly controlled
gastro-oesophageal reflux.78
For T1b cancer all agree that resection is the
standard of care, with endoscopic therapy suitable
for only a select few or in those where surgery is not
possible, or is rejected by the patient.
Definitive radiotherapy with or
without chemotherapy
Most often this modality is offered when patients are
unfit for resection or refuse an operation. In patients
with invasive SCC (stage II/III), there is evidence
from a randomised trial for the use of definitive
chemoradiation (CRT)84 over radiation (RT) alone
and, in a trial with low numbers, that definitive
chemoradiation has a similar 2-year survival compared
with resection alone.85 For adenocarcinoma, there are
no data from randomised trials for the use of definitive
radiation with or without chemotherapy and so the
evidence is extrapolated from the histologic responses
that may occur in the primary tumour in phase II and
III trials of neoadjuvant therapy followed by resection
of the oesophagus.86
A Cochrane analysis of CRT compared with RT
alone reports the value of CRT to be a reduction
in local persistence/recurrence of 12%.87 Assessing
local control of disease following definitive CRT for
stage I disease, two studies from Japan report initial
complete responses of 93%88 and 87%.89 After CRT
the incidence of recurrence has been reported to be
20%88 to 30%.64 Salvage may be possible with EMR
or resection.64,88 The more recent studies examining
outcomes from CRT in patients with stage 1 SCC,
have reported 3-year DSS of 85%,63 4-year DSS of
80%90 and 5-year DSS of 77%88 and 76%.64 The
5-year DSS survival for T1a was 84% compared with
50% for patients who were T1b.64
96
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There has been one institutional study that
has compared the outcomes from a three-field
oesophagectomy for stage I SCC with definitive
CRT.63 Patients with clinical stage 1 disease, not
considered candidates for endoscopic resection,
were offered resection or definitive CRT. The
criteria for exclusion from endoscopic therapy
were disease >5 cm and more than two-thirds of
the circumference. There was a bias towards CRT
for the elderly and longer lesions. In the 54 patients
who had CRT there was a complete endoscopic
response in 53. Local recurrence occurred in 21%.
Primary resection had a complication rate of 34%,
some very serious. The 1- and 3-year disease-
specific survivals were 98.1% and 88.75 for CRT
and 97.4% and 85.5% for oesophagectomy,
respectively. Adjusting for age, sex and tumour size
the hazard ratio for CRT for overall survival was
0.95 (95% CI 0.37–2.47).63
In Japan, CRT and surgery is considered
equivalent for stage 1a SCC (T1,N0,M0).91 For
patients with IMC (m3) and T1b SCC a cohort
study assessed the outcome of patients treated
directly with CRT and those who had an ESD
then CRT. The dose of CRT was lower in the ESD
group. The overall disease recurrence rate was
29% for definitive CRT and 6.3% for ESD and
CRT. The local recurrence rate for CRT was 9%
and for combined ESD and CRT 0 (0/16). The
higher dose of RT caused pericardial effusions
in 9.7% of the CRT compared to zero for the
combined treatment.92 We await the results of a
RCT comparing definitive CRT with surgery for
patients who have had an EMR for a T1B tumour
(Japanese Clinical Oncology Group JCOG 0502).
As previously stated, the data relating to the
use of radiation for early adenocarcinoma of the
oesophagus are not clear. Thus this modality is an
option for patients not suitable for surgery but who
are considered suitable candidates for a definitive
therapy. This is particularly the case if the patient
is considered to be high-risk for residual primary
disease or localised lymph node metastasis. As such
the guidelines used for SCC as stated above would
appear reasonable. However, for both histologic
subtypes, it is yet to be proven that the addition of
chemotherapy to patients having treatment for T1a
and sm1 disease without LVI is worthwhile, given
the potential increase in the side-effect profile.
CRT is an alternative to oesophagectomy for T1a,
SCC.
The role of CRT for T1b, SCC is yet to be defined
from trials but is considered an alternative to resection.
For patients with ACA, CRT is an option if the
patient has failed endoscopic therapy, and is unfit or
refuses surgery.
 Treatment of early oesophageal cancer

Role of a multidisciplinary with specialist interventional endoscopists who

team
Because of the evidence for multimodality therapy
for locally advanced oesophageal cancer, patient
management decisions are now typically made
in a multidisciplinary environment, including
the surgeon, radiation oncologist and medical
oncologist. It is clear that for early oesophageal
cancer the management discussions should include
an interventional endoscopist, allowing all the
alternatives for therapy to be considered in the
same multidisciplinary, collaborative environment.
It is clear that improved oesophagectomy outcomes
occur in specialist high-volume centres; however,
the technical expertise of the surgeon is only one
component in the operative and cancer outcomes
for these patients. For endoscopic therapies, it is
likely the better neoplasia eradication figures and
procedural outcomes will be optimal in centres
that have a specific interest in this problem
have strict follow-up endoscopy protocols in a
multidisciplinary environment.
Conclusion
The choice of management for patients with early
oesophageal cancer has improved in the last decade.
In appropriately selected patients with HGD and
IMC, endoscopic therapy is the treatment of choice
as it has the potential to achieve the same curative
effect as surgery with low complication rates along
with retention of the oesophagus. Surgery remains
the definitive choice for complicated, extensive
HGD, SCC in situ, deep mucosal SCC and any
cancer with submucosal infiltration. There is a
role for definitive radiotherapy, typically with
concurrent chemotherapy, in selected patients with
SCC and possibly adenocarcinoma where surgery
is not an option. Multidisciplinary assessment and
planning is important to achieve optimal outcomes.

Key points
• Oesophageal mucosal cancer has a very low risk for lymph node metastasis but it is slightly higher
for SCC compared with ACA.
• Endoscopic mucosal resection (EMR) provides the best method of T staging early oesophageal cancer.
• For localised mucosal ACA, endoscopic therapy is the gold standard.
• The definitive endoscopic therapy of early ACA in Barrett’s mucosa consists of complete EMR of the
mucosal cancer and ablation of the residual intestinal metaplasia.
• Radiofrequency ablation provides the most efficient, durable ablation outcomes for intestinal
metaplasia with associated low morbidity from the procedure.
• Endoscopic resection for localised intramucosal SCC is acceptable therapy so long as complete
resection is possible. The role of ablative therapies is unclear.
• Oesophagectomy for early cancer is reserved for fit patients with submucosal extension of the
cancer and/or extensive mucosal neoplasia not suitable for endoscopic ablation.
• Radiotherapy typically with concurrent chemotherapy is an option for patients with early
oesophageal SCC but its role in treatment for early ACA is not clear. It remains an option for unfit
patients not suitable for endoscopic therapy or surgery.

Recommended video:
Key references
• Radiofrequency ablation (RFA) of Barrett’s
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iu4kv90cOII
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Chapter 6
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 Treatment of early oesophageal cancer

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99
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