Mary Koshy, Natia Esiashvilli, Jerome C. Landry, Charles R. Thomas, Jr. and Richard
Presentation and Progression, Work-up, and Surgical Approaches
Multiple Management Modalities in Esophageal Cancer: Epidemiology,
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Multiple Management Modalities in Esophageal Cancer:
Epidemiology, Presentation and Progression, Work-up,
and Surgical Approaches
MARY KOSHY,aNATIA ESIASHVILLI,aJEROME C. LANDRY,aCHARLES R. THOMAS JR.,b
RICHARD H. MATTHEWSc,d
aEmory University School of Medicine, Department of Radiation Oncology, Atlanta, Georgia, USA;
bUTHSCSA/San Antonio Cancer Institute, Department of Radiation Oncology, San Antonio, Texas, USA;
cBeth Israel/Deaconess Medical Center, Harvard Medical School, Department of Radiation Oncology, Boston,
Massachusetts, USA; dBoston VA Health Care Radiation Oncology Service, Boston, Massachusetts, USA
Key Words. Esophageal carcinoma · Multimodal treatment · Survival · Surgeries
Annually, approximately 13,200 people in the U.S. are
diagnosed with esophageal cancer and 12,500 die of this
malignancy. Of new cases, 9,900 occur in men and 3,300
occur in women. In part I of this two-part series, we
explore the epidemiology, presentation and progression,
work-up, and surgical approaches for esophageal cancer.
In the 1960s, squamous cell cancers made up greater than
90% of all esophageal tumors. The incidence of
esophageal adenocarcinomas has risen considerably over
the past two decades, such that they are now more preva-
lent than squamous cell cancer in the western hemisphere.
Despite advances in therapeutic modalities for this dis-
ease, half the patients are incurable at presentation, and
overall survival after diagnosis is grim. Evolving knowl-
edge regarding the etiology of esophageal carcinoma may
lead to better preventive methods and treatment options
for early stage superficial cancers of the esophagus. The
use of endoscopic ultrasound and the developing role of
positron emission tomography have led to better diagnos-
tic accuracy in this disease. For years, the standard of care
for esophageal cancer has been surgery; there are several
variants of the surgical approach. We will discuss
combined modality approaches in part II of this series.
The Oncologist 2004;9:137-146
The Oncologist 2004;9:137-146
Correspondence: Richard H. Matthews, M.D., Ph.D., Beth Israel/Deaconess Medical Center, Harvard Medical School, 330
Brookline Avenue, Boston, Massachusetts 02215, USA. Telephone: 617-232-9500, ext 4457 or ext 5628; Fax: 617-524-
0643; e-mail: RHMatthews@comcast.netReceived May 13, 2003; accepted for publication September 18, 2003.
©AlphaMed Press 1083-7159/2004/$12.00/0
After completing this course, the reader will be able to:
1. Describe the epidemiology, work-up, and staging of esophageal cancer.
2. Identify the disease presentation, progression, and prognostic factors for esophageal cancer.
3. Discuss the surgical approach and management of esophageal cancer.
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Koshy, Esiashvilli, Landry et al.
It has been estimated that in 2001 there were 13,200
new cases and 12,500 deaths attributable to esophageal
carcinoma in the U.S. . Table 1 presents new cancer
cases and deaths in the U.S. for a few selected sites for
comparison. We use the ratio of deaths to new cases as a
rough index of the overall degree of success of treatments
for various cancers. We can, thus, anticipate that, nation-
wide and for all presentations and all management
approaches, the curative success in dealing with cancer of
the esophagus is less than 10%. Cancer of the esophagus
occurs much less frequently than cancers of the breast,
prostate, lung, or rectum (Table 1). With reference to ratios
of deaths to new cases, roughly 80% of cancers of the
breast, prostate, and rectum can be treated successfully in
the U.S. Lung cancer, however, resembles esophageal can-
cer in that less than 10% of patients in our country are
treated successfully. Lung cancer occurs less commonly
than breast or prostate cancers, but accounts for more can-
cer deaths than the other four sites combined.
There is an approximate 3:1 male predominance in
esophageal cancer incidence and death. One factor in the
poor results obtained for the treatment of esophageal carci-
nomas is that half the cases are unresectable or metastatic at
The cervical esophagus begins at the cricopharyngeus
muscle at the level of the cricoid cartilage and extends 6 cm
to enter the thoracic inlet. The intrathoracic esophagus
extends for another 20-25 cm to the gastroesophageal junc-
tion. The American Joint Committee on Cancer (AJCC)
divides the esophagus into four regions: cervical, upper tho-
racic, midthoracic, and lower thoracic .
The predominant histological types of esophageal car-
cinoma are squamous cell carcinoma (SCC) and adenocar-
cinoma (AC). Less common histologies include adenoid
cystic, mucoepidermoid, adenosquamous, undifferentiated,
and malignant melanoma, all of which have poor prog-
noses. Small cell carcinoma can also occur in the esopha-
gus, and it has a course similar to that in the lung .
Nonepithelial tumors in the esophagus are rare; the most
common type is leiomyosarcoma and the most common
metastatic source to the esophagus is the breast . In the
1960s, more than 90% of all esophageal tumors were SCCs.
The incidence of esophageal AC has risen considerably
over the past two decades such that it is now more preva-
lent than SCC in the western hemisphere. The rise in
esophageal AC, particularly in the distal esophagus, has
been paralleled by a rise in gastric cardia AC. This leads to
the concept of gastroesophageal junction AC.
The standard of care for esophageal cancer had been
surgery alone for many years. There are several different
surgical approaches in use, with various advantages and
disadvantages and with differences in procedure preference
in different parts of the world. We review the epidemiol-
ogy, etiology, presentation and work-up, and surgical
approaches for esophageal cancer in this paper.
EPIDEMIOLOGY AND ETIOLOGY
The incidence of esophageal cancer varies considerably
with geographic location and also, to some extent, among
ethnic groups within a common area. Some of the highest
rates occur in northern China and northern Iran, where inci-
dence exceeds 100 in 100,000 individuals; in the U.S., the
incidence is less than 5 per 100,000, although rates are
nearly quadruple for African Americans . In Linxian,
Hunan province, China, esophageal cancer is endemic and
has been directly related to nitrosamines and inversely
related to consumption of riboflavin, nicotinic acid, magne-
sium, and zinc . SCC predominates in African Americans
over Caucasians by a ratio of 6:1, and AC has the opposite
preponderance, occurring in Caucasians over African
Americans at a ratio of 4:1 . Nearly 30 years ago, AC
accounted for only 15% of cases of esophageal cancer, but
the incidence of AC has increased more than 350% since
1970, surpassing SCC since 1990; this increase is also seen,
to a lesser extent, in African Americans [7, 8]. In the Far
East, no increase in AC has been observed, and SCC con-
tinues to be the more common histology . In the western
world, there is less impact from dietary factors, such as
nitrosamines, due to different food preservation techniques,
and the primary etiology of esophageal cancer is the use of
tobacco and alcohol, which have a synergistic effect; they
are very strong risk factors for SCC and moderate risk fac-
tors for AC . Tobacco exposure has been linked to a ten-
fold higher risk for esophageal SCC in heavy smokers
relative to nonsmokers, and the risk is directly related to the
duration of exposure [7, 11]. In contrast, smoking has been
linked to only a two- to threefold greater risk for esophageal
AC in smokers relative to nonsmokers [8, 12]. There is a
greater than multiplicative effect between smoking and
alcohol consumption that occurs in SCC; for AC, the effect
Table 1. Comparison of new cases and deaths for selected cancer
sites, 2001 
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is only additive . The exception to this may be the con-
sumption of hard liquor, which has been found to have a
stronger association with AC than with SCC . The rela-
tive risk of esophageal AC remains high up to 30 years after
smoking cessation, in contrast to the significant decline in
risk of SCC within a decade of smoking cessation .
Several studies have linked obesity to the risk for
esophageal AC. Increasing body mass index (obesity) corre-
lates with increasing risk for esophageal AC, but decreasing
risk for esophageal SCC . Obesity promotes gastroe-
sophageal reflux disease (GERD) by increasing intra-abdom-
inal pressure; GERD, in turn, promotes the formation of
Barrett’s esophagus (BE)—a metaplastic precursor of AC
[16, 17]. Multiple studies have shown that the bacterium
Helicobacter pylori has an inverse relationship with the risk
for esophageal cancer but causes a greater risk for gastric
cancer . H. pylori is thought to protect against the risk of
esophageal AC because it promotes achlorhydria, implying
lower acid production and reflux . As rates of H. pylori
infection have decreased in the U.S. and Europe, there has
been a parallel rise in the incidence of GERD (an indepen-
dent risk factor for esophageal AC) and BE . Prior aerodi-
gestive tract malignancies predispose to a higher risk for
esophageal cancer, primarily through field cancerization.
Ten percent of second primary cancers in patients with prior
oropharyngeal cancer or lung cancer occur in the esophagus
[19, 20]. Chronic inflammation and stasis, which occur with
strictures caused by caustic injury and achalasia, are long-
term risks for esophageal SCC; in addition, patients with
tylosis, which is inherited in an autosomal dominant fashion,
and Plummer Vinson syndrome have a definite greater risk
for esophageal SCC .
The definition of BE has evolved from simply a colum-
nar-lined esophagus to at least 3 cm of columnar lining or
metaplasia in the esophagus [21, 22]. Approximately 0.5%-
2% of adults in the western world have BE, with prevalences
greater in Caucasians and men and with increasing age until
the eighth decade of life [23, 24]. In a review of 51,311
patients at the Mayo Clinic, the length of BE epithelium did
not increase significantly with age, suggesting that BE does
not progress with age and is latent for several years before
being discovered . GERD affects up to 44% of the gen-
eral population in the U.S., but only 10% of people with
GERD develop BE [25, 26]. Recurrent symptoms of reflux
have been associated with a 7.7 times greater risk for
esophageal AC, with more frequent, more severe, and
longer-lasting reflux resulting in a 43.5 times higher risk for
esophageal AC . Patients with BE have a 40-fold greater
risk or 0.5% risk per patient year of developing esophageal
AC . A middle-aged patient who develops BE has a 10%-
15% risk of developing esophageal AC during his lifetime
. Specific risk factors that predispose for the progression
of BE to AC include hiatal hernia of at least 3 cm in length,
length of BE, and the presence of dysplasia . In addition,
increased bile acid exposure is thought to exacerbate
esophageal mucosal injury and to promote the neoplastic
process [23, 30].
Esophageal cancers, both SCC and AC, typically have
aberrant cell-cycle regulation. Mutations occur in onco-
genes such as EGFR, erbB-2, and cyclin D1, and in tumor
suppressors such as 3p(FHIT), Rb, p53, p16, p14ARF, and
telomerase, which affect the G1restriction point. Cyclin D1
directly regulates phosphorylation of the Rb protein at the
G1restriction point facilitating G1/S transit. About 40%-
60% of esophageal carcinomas and 30% of premalignant
lesions overexpress cyclin D1. Cancers that retain normal
Rb expression typically overexpress cyclin D1, whereas
those that lack normal Rb have normal cyclin D1 levels.
The p53 gene product regulates cell-cycle progression,
DNA repair, neovascularization, and apoptosis; 50%-80%
of esophageal carcinomas have p53 mutations. Malignancy
is facilitated by inactivation of the growth constraints
imposed by the Rb and p53 suppressor pathways, but also
requires activation of telomerase, a ribonucleoprotein that
adds hexamer DNA repeats to the ends of chromosomes to
prevent loss of telomere length in DNA replication.
Elevated telomerase expression is found in high-grade dys-
plasia as well as virtually all esophageal carcinomas.
Several of the individual aforementioned factors have been
shown to carry prognostic significance .
Part of the problem in dealing with esophageal carcino-
mas is that half the patients present with unresectable or
metastatic cancers; if a screening program could detect dis-
ease at an earlier stage, there could be a greater possibility
of cure. In comparison, there is considerable evidence that
the combination of physical examination with mammogra-
phy used as a screening tool decreases the death rate from
breast cancer . However, several studies have failed to
demonstrate the benefit of a decreased death rate due to
lung cancer from screening chest x-rays and physical exam-
inations . Unfortunately, the value and cost-effective-
ness of endoscopic surveillance for esophageal cancers has
not been demonstrated. In 11 screening studies with 1,127
patients with BE, only 3.5% actually progressed to cancer
. To date, there is no solid evidence that screening
reduces the esophageal AC death rate .
Proponents argue that screening, to be productive, should
be focused on patients with multiple risk factors: GERD,
Caucasian race, male gender, age greater than 50 years, and
long duration of symptoms. Small studies have suggested
that surveillance can identify neoplasms that are at an ear-
lier stage and, thus, potentially curable [35-38]. However,
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Koshy, Esiashvilli, Landry et al.
these hopeful results may be confounded by lead time bias,
length time bias, and pseudodisease . Furthermore,
even if surveillance were effective, it is unlikely to impact
mortality soon because few patients with esophageal cancer
are diagnosed via surveillance programs. Less than 5% of
patients with esophageal cancer were known to have had BE
before they sought help for symptoms of cancer, and up to
40% had no prior history of GERD [39, 40]. Most patients
with BE die from unrelated causes, and the presence of BE
does not change life expectancy or overall survival [41, 42].
Currently, the American College of Gastroenterology recom-
mends that surveillance endoscopy for BE be guided by the
presence of dysplasia. If dysplasia is not present, endoscopy
is recommended every 3 years, and if low-grade dysplasia is
present, it is recommended that endoscopy be done every 6
months for 1 year and yearly thereafter if no progression is
seen . If high-grade dysplasia is present, this finding
should be confirmed by an experienced pathologist and the
patient should be offered either esophagectomy or intensive
surveillance (endoscopy every 3 months) . The technique
of four-quadrant biopsies taken every 2 cm of BE segment
during endoscopy is optimal . Dysplasia is currently the
best pathological predictor of cancer development.
DISEASE PRESENTATION, PROGRESSION, AND
The most common presenting symptoms of esophageal
cancer are dysphagia and weight loss. Less common symp-
toms include odynophagia, cachexia, melena, retrosternal
pain, and hoarseness . Cancers of the esophagus must
involve at least 75% of the circumference before the sensa-
tion of food “sticking” or blockage is experienced. As noted
above, about one-half of esophageal cancer patients present
with locally advanced unresectable disease or distant
metastasis. The extent of wall penetration and lymph node
metastases are more important prognosticators of survival
than tumor length or functional obstruction .
Esophageal AC spreads via transverse penetration
through the full thickness of the wall, whereas SCC tends to
spread linearly in a submucosal fashion . Esophageal
cancer spreads through extensive lymphatic channels with an
erratic pattern including “skip metastases” being observed in
autopsy specimens; in addition, up to 71% of frozen tissue
sections classified as tumor free by conventional histopathol-
ogy have been positive for lymphatic micrometastases when
tested by immunohistochemistry . This micrometastatic
disease has been shown to be a significant independent
adverse prognostic factor for relapse-free survival and over-
all survival . Routine use of immunohistochemistry in
conjunction with extensive lymph node sampling has been
advocated as an advance over the traditional staging work-up.
Histologic tumor type is an independent prognostic fac-
tor in esophageal cancer patients who have had surgical
treatment. Siewert et al. analyzed 1,059 patients who had
undergone resection and found that overall survival at 5 years
was 46.8% for the AC group versus 37.4% for the SCC
group; patients with early-stage AC had a much lower inci-
dence of lymph node involvement than their SCC counter-
parts, and it was hypothesized this was due to occlusion of
lymphatic channels secondary to the inflammatory changes
of GERD in AC . Tumor size less than 5 cm, upper
third esophageal location, female sex, and age less than 65
years have all been noted to positively influence outcome
[50, 51]. Conversely, weight loss, low Karnofsky perfor-
mance status, deep ulceration of tumor, sinus tract forma-
tion, and fistula formation have all been found to be poor
prognostic factors [21, 50].
STAGING AND WORK-UP
The AJCC has established a staging system for
esophageal cancer that is based on the tumor-node-metasta-
sis (TNM) system and is, in essence, a pathological staging
system . Table 2 illustrates the AJCC staging classifica-
tion of esophageal cancer. Only the depth of penetration is
taken into account for the T staging, not the length of the
tumor, extent of involved circumference, or degree of
lumen narrowing. Clinical staging takes into account the
amount of disease that is present before treatment and is
based on history, physical examination, biopsy, laboratory
studies, endoscopic examination, and imaging such as
endoscopic ultrasound (EUS), computed tomography (CT)
scan and positron emission tomography (PET) scan.
Pathologic staging is based on examination of the surgically
resected esophagus and lymph nodes. Spread to the celiac
lymph nodes is considered a site of distant metastasis, as
are cervical nodes occurring with an esophageal primary
elsewhere than in the cervical esophagus .
The appropriate work-up for a patient suspected of hav-
ing esophageal cancer should include a thorough history and
physical exam with special attention to the supraclavicular
and cervical lymph nodes. Fine-needle aspiration should be
performed on any palpable cervical lymph node to rule out
extrathoracic spread of disease. Blood tests, a chest x-ray,
and a double-contrast barium swallow should follow. CT
scans of the chest and upper abdomen should be obtained to
further characterize the lesion and evaluate for metastatic dis-
ease. Esophagoscopy, with the intent of tissue biopsy and
detailed characterization of the lesion, should be pursued
with an emphasis on how far the lesion is from the incisors
and the squamocolumnar junction; in addition, the presence
of esophagitis or BE should be noted . Brushings should
be obtained before biopsy, and these two procedures together
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achieve a diagnostic accuracy of 99% . In lesions that
appear borderline for the endoscopist, the use of Lugol’s
iodine can help distinguish normal mucosa by selectively
staining it and leaving the abnormal mucosa identifiable for
biopsy . Finally, patients with upper- or middle-third
esophageal cancers or symptoms of hoarseness or hemopty-
sis should have a bronchoscopy to rule out laryngeal nerve
involvement or tracheobronchial fistula .
Conventional CT scans can accurately determine
resectability 65%-88% of the time [54, 55]. CT accurately
predicts T stage in 70% of cases and N stage in about 50%-
70% of cases [54-56]. Secondary to poor sensitivity, CT may
not be the optimal modality to evaluate celiac lymph nodes
and T4 disease or response to neoadjuvant chemoradiother-
apy. The sensitivity and specificity of CT for pathologically
positive celiac lymph nodes are 30% and 93%, respectively,
and for T4 disease, are 25% and 94%, respectively [57, 58].
With respect to assessing response after chemotherapy, no
correlation has been found between tumor volume reduction
on serial CT examinations and pathological assessment of
tumor response or patient survival .
EUS has improved the preoperative staging of
esophageal cancer, particularly in regard to T and N staging
. In a meta-analysis of 27 studies, the accuracy of EUS
for T staging was 90% and for N staging was 80%, and a
further review of the literature supports an overall accuracy
for EUS of approximately 85% for T staging and 75% for N
staging [59-61]. However, the utility of EUS in detecting dis-
tant metastases other than celiac metastases is low, secondary
to limited depth of penetration, and therefore, CT is still a
necessary and complementary part of the staging work-up
. EUS detection of celiac lymph node disease correlates
with overall survival and has a sensitivity of 70%-80% and a
specificity of 97% [57, 63-65]. EUS has also been useful in
evaluating recurrence after resection; in a study evaluating 40
patients with suspected recurrence, the sensitivity and speci-
ficity of EUS were found to be 95% and 80%, respectively
. One problem with EUS specificity in that study of pos-
sible recurrences were the false positives reported for anasto-
motic thickening because of inflammation. Other limitations
to EUS include its decreased sensitivity in the presence of
stenosis and its unreliability in assessment of the response to
neoadjuvant therapy [67, 68]. In three studies involving 196
patients, the accuracy of EUS after neoadjuvant therapy
ranged from 27%-48% for T staging and 38%-71% for N
staging [68-70]. This significantly lower accuracy is attribut-
able to the failure of EUS to distinguish between tumor and
postradiation fibrosis and inflammation.
Fluorodeoxyglucose (FDG)-PET is rapidly evolving as
an important tool in the noninvasive staging of patients with
esophageal cancer. Kole et al. prospectively evaluated 26
patients and found the diagnostic accuracies in determining
Table 2. AJCC staging classification of esophageal cancer
Primary tumor (T)
TX: Primary tumor cannot be assessed
Regional lymph nodes
NX: Regional lymph nodes cannot be assessed
Distant metastasis (M)
MX: Presence of distant metastasis cannot
M0: No distant metastasis
M1: Distant metastasis
T0: No evidence of primary tumor N0: No regional lymph node metastasis
N1: Regional lymph node metastasis
Tis: Carcinoma in situ
T1: Tumor invades lamina
T2: Tumor invades muscularis propria
T3: Tumor invades adventitia
T4: Tumor invades adjacent structures
Stage I: T1N0M0
Stage IIA: T2N0M0; T3N0M0
Stage IIB: T1N1M0; T2N1M0
Stage III: T3N1M0; T4, any N, M0
Stage IV: Any T, any N, M1
Stage IVA: Any T, any N, M1a
Stage IVB: Any T, any N, M1b
Tumors of the lower thoracic esophagus
M1a: Metastasis to celiac lymph nodes
M1b: Other distant metastasis
Tumors of the midthoracic esophagus
M1a: Not applicable
M1b: Nonregional lymph nodes and/or
other distant metastasis
Tumors of the upper thoracic esophagus
M1a: Metastasis in cervical lymph nodes
M1b: Other distant metastasis
For the cervical esophagus, the cervical nodes (including the supraclavicular nodes) are considered regional; for the intrathoracic esophagus, the
mediastinal and perigastric lymph nodes (excluding the celiac nodes) are considered regional.
T1 has been further subdivided into T1m, cancer confirmed to the mucosa, and T1sm, cancer invading the submucosa.
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Koshy, Esiashvilli, Landry et al.
resectability to be 65% for CT and 88% for PET; for CT and
PET together, an accuracy of 92% was achieved . The
accuracy of PET in detecting primary tumors is 78%; nodal
metastases are visualized by PET in 86% of cases [71, 72].
A particular advantage of FDG-PET has been its greater accu-
racy in detecting distant metastatic disease than CT alone or
combined with EUS (86% versus 62%), but it has a lower
accuracy in detecting local nodal disease than CT alone or
combined with EUS (48% versus 69%) [73-75]. FDG-PET
has also demonstrated greater accuracy than other methods in
detecting recurrences other than perianastomotic recurrences
. The quantitative decrease in FDG uptake seen after
neoadjuvant therapy has been correlated with histopathologic
assessment of viable tumor cells, time to disease progression,
and overall survival [77-79]. FDG-PET may assist in deter-
mining response to neoadjuvant therapy, which subsequently
could aid in the selection of patients who will benefit from
surgery and avoid excess morbidity and mortality in those
who are unlikely to respond . Minimally invasive staging,
including thoracoscopic and laparoscopic methods, remains
the most accurate method to detect distant metastases and
determine resectability. Although PET had a better accuracy
than CT in detecting distant metastases (84% versus 63%),
minimally invasive staging was even better, determining
resectability with an accuracy of 97%, compared with only
61% with EUS and CT [81, 82].
Esophagectomy remains the standard of care for the
treatment of early-stage tumors confined to the esophagus
and paraesophageal region. There is controversy about
whether en bloc resection with extended lymph node dis-
section confers any advantage in curative management. The
two most common approaches for definitive resection are
the transthoracic esophagectomy (TTE) and the transhiatal
esophagectomy (THE). TTE is the most common approach
used worldwide, whereas THE is more common in the
western world. Advantages of TTE include better visual-
ization, access, and resection of the upper two-thirds of the
esophagus and mediastinal disease and avoidance of blind
blunt dissection with tumors of the midthoracic esophagus
. The rate of resectability of esophageal cancer is
reported to range from 60%-90%, hospital mortality after
resection ranges from 1.4%-23%, and the resulting 5-year
overall survival rate ranges from 10%-25% [83-86]. Five-
year survival rates reported for stage I esophageal cancer
range from 80%-94% and, for stage III, rates range from
10%-14% [83, 84]. Advantages of THE include the avoid-
ance of morbidity, including the respiratory compromise
associated with thoracotomy, and the fact that if a leak does
occur it will be in the neck where it is more accessible .
Operative mortality has ranged from 1% to 4%, and the 5-
year survival rate has ranged from 20%-25% overall, with
that of stage I as high as 65% and that of stage III as low as
10% [87-91]. Two randomized trials and a meta-analysis
concluded that there were no significant differences
between TTE and THE with respect to overall morbidity,
operative mortality, and long-term survival [87, 92].
For tumors below the tracheal bifurcation, radical en bloc
esophagectomy or two-field dissection has been recom-
mended [93, 94]. The surgical objective is to achieve exten-
sive margins, with removal of the upper abdominal,
retroperitoneal, and mediastinal lymph nodes, the peri-
cardium, periaortic tissue, bilateral pleura, azygous vein, and
thoracic duct [93, 95]. Proponents of this radical operation
argue that the technique is a better attempt to obtain the
benefits of a resection with no residual disease (R0).
Achievement of R0 status has been reported to be a prognos-
tic factor for long-term survival [96, 97]. In a study of 500
patients undergoing TTE, patients with an R0 resection had
a 5-year survival rate of 29% in contrast to those with micro-
scopic residual (R1) or macroscopic residual (R2) disease,
none of whom survived 5 years . Some have doubted the
value of the en bloc approach, theorizing that esophageal
cancer systemically spreads at onset and lymphatic dissec-
tion is, therefore, palliative rather than curative . The
counter argument from those viewing the disease progression
as sequential, from primary site to lymph nodes and then to
distant sites, is that dramatically low rates of local recurrence
are better achieved with en bloc resection, which results in
better long-term survival [94, 99, 100]. Local recurrence
rates after en bloc resection have ranged from 1%-8%, oper-
ative mortality rates have ranged from 3%-6%, and the 5-
year overall survival rate has ranged from 30%-52% [98,
100, 101]. A survival advantage for patients with advanced
primary and nodal disease with en bloc resection has been
claimed in small retrospective studies [94, 101, 102]. The
superior survival evinced in node-positive patients lends cre-
dence to the theory that disease progression is sequential and
that removal of the involved nodal groups is therapeutic and
potentially curative. Reservations in asserting a superiority
for the en bloc resection include dependence on retrospective
rather than randomized study data, with selection bias and
stage migration as a result of more accurate staging (Will
Rogers effect). In a study by Hagen et al., patients selected
to undergo en bloc resection were chosen based on the pres-
ence of limited disease and “good general health,” while
those with “poor physiologic reserve” and more advanced
disease underwent THE, clearly a selection bias . The
selection of young patients with limited disease and excel-
lent performance statuses for en bloc resection has been
corroborated by others .
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Japanese surgeons routinely extend the en bloc or two-
field dissection into the neck, mediastinum, and upper
abdomen, creating a three-field dissection. This is based on
the finding that cervical nodal metastases occur in up to
46.3% of upper-third tumors and in up to 27% of lower-
third tumors in patients undergoing three-field lymph node
dissection . Two randomized trials have been done in
Japan comparing three-field radical surgery with two-field
radical surgery. In one study, the 5-year survival rate was
significantly better with the three-field procedure (48% ver-
sus 33%) and, in the other study, a survival difference was
not noted; however, in both studies, there was a selection
bias toward younger, earlier stage patients being allocated
to three-field radical surgery [105, 106]. In the western
world, three-field surgery has also been investigated in the
institutional setting. Lerut et al. analyzed 37 patients under-
going three-field radical resection and found that the extended
field improved staging accuracy (30% of patients had patho-
logic cervical nodes and 17% of gastroesophageal junction
tumors had positive cervical nodes) but did not change over-
all survival . Altorki et al., in the largest western study of
three-field radical resection, prospectively analyzed 80
patients undergoing the procedure and found an operative
mortality of 5%, cervical nodal involvement of 36%, and a 5-
year survival rate of 51% (88% in node-negative patients and
25% in node-positive patients) . Differences in dissec-
tion technique around the recurrent laryngeal nerve may
account for the low rates of recurrent laryngeal nerve injury,
only 6% in that study, dramatically lower than the up to 70%
observed in Japanese reports [96, 108].
An impairment to quality of life with respect to speech
and swallowing has been chronicled in up to 20% of
patients for up to 5 years postoperatively and must also be
a serious consideration. Both en bloc dissection and three-
field resection may offer a survival benefit but, before these
techniques can be widely adopted, we need more experi-
ence and randomized studies to substantiate the benefit of
such radical surgery.
The overall results of treatment for esophageal cancer in
our country continue to be poor, with over 90% of the new
cases each year eventually succumbing to this disease. In part
I of this two-part series we have covered the issues of epi-
demiology, work-up and staging, prognostic factors, and sur-
gical treatment. More radical surgical approaches may have
the potential of gaining an advantage in local-regional control,
and perhaps ultimately survival, although perhaps at a cost in
terms of the morbidity of the procedure. In part II we will
explore the integration of chemotherapy and radiation therapy
into multimodal management approaches to the disease.
The authors disclaim any proprietary interest and
acknowledge that there have been no grants, equipment, or
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