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DOI:10.4251/wjgo.v6.i5.112 © 2014 Baishideng Publishing Group Inc. All rights reserved.

REVIEW

Esophageal cancer: A Review of epidemiology,

pathogenesis, staging workup and treatment modalities

Kyle J Napier, Mary Scheerer, Subhasis Misra

Kyle J Napier, Mary Scheerer, Subhasis Misra, Department of of current treatment include surgery, radiation and
Surgery, Texas Tech University Health Science Center School of chemotherapy. Tumor markers of esophageal cancer
Medicine, Amarillo, TX 79106, United States are an advancing area of research that could potentially
Subhasis Misra, Division of Surgical Oncology, Chief of Gas- lead to earlier diagnosis as well as playing a part in as-
troIntestinal and Hepato-Pancreato-Biliary Surgery, Texas Tech
sessing tumor response to therapy.
University Health Science Center School of Medicine, Amarillo,
TX 79106, United States
© 2014 Baishideng Publishing Group Inc. All rights reserved.
Author contributions: Napier KJ and Scheerer M contributed
equally to the writing of this paper and should be deemed both
first authors; Misra S was the senior author and guide for this Key words: Esophageal cancer; Esophageal cancer
paper. staging; Esophageal squamous cell carcinoma; Esopha-
Correspondence to: Subhasis Misra, MD, MS, FACCWS, geal adenocarcinoma; Surgery
FACS, Associate Professor, Division of Surgical Oncology,
Chief of GastroIntestinal and Hepato-Pancreato-Biliary Surgery, Core tip: Esophageal carcinoma is a serious malignancy
Texas Tech University Health Science Center School of Medi- with regards to mortality and prognosis, and is ex-
cine, 1400 S Coulter St.Amarillo, Amarillo, TX 79106,
pected to increase in incidence over the next 10 years.
United States. [email protected]
Squamous cell carcinoma is the most common histolog-
Telephone: +1-806-3545563 Fax: +1-806-3545561
Received: November 17, 2013 Revised: December 31, 2013 ical type of esophageal cancer worldwide but the inci-
Accepted: April 11, 2014 dence of esophageal adenocarcinoma has dramatically
Published online: May 15, 2014 increased in the past 40 years. Esophageal cancer is
staged according to the TNM system. Common imaging
modalities used in staging include computed tomog-
raphy, endoscopic ultrasound and positron emission
tomography scans. Current treatment options include
Abstract multimodality therapy. Including surgery, radiation and
Esophageal cancer is a serious malignancy with regards chemotherapy. Tumor markers of esophageal cancer
to mortality and prognosis. It is a growing health con- are an advancing area of research that could potentially
cern that is expected to increase in incidence over the lead to earlier diagnosis.
next 10 years. Squamous cell carcinoma is the most
common histological type of esophageal cancer world-
wide, with a higher incidence in developing nations. Napier KJ, Scheerer M, Misra S. Esophageal cancer: A Review of
With the increased prevalence of gastroesophageal re- epidemiology, pathogenesis, staging workup and treatment mo-
flux disease and obesity in developed nations, the inci- dalities. World J Gastrointest Oncol 2014; 6(5): 112-120 Available
dence of esophageal adenocarcinoma has dramatically from: URL: http://www.wjgnet.com/1948-5204/full/v6/i5/112.htm
increased in the past 40 years. Esophageal cancer is DOI: http://dx.doi.org/10.4251/wjgo.v6.i5.112
staged according to the widely accepted TNM system.
Staging plays an integral part in guiding stage specific
treatment protocols and has a great impact on overall
survival. Common imaging modalities used in staging
INTRODUCTION
include computed tomography, endoscopic ultrasound
and positron emission tomography scans. Current treat- Esophageal cancer is considered a serious malignancy
ment options include multimodality therapy mainstays with respect to prognosis and mortality rate. Account-

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 Napier KJ et al . Esophageal cancer

ing for more than 400000 deaths worldwide in 2005[1]. and melanomas may arise in the esophagus.
Esophageal carcinoma is the eighth most common can-
cer, and the sixth most common cause of cancer related
deaths worldwide with developing nations making up PATHOGENESIS OF SCC
more than 80% of total cases and deaths[2]. Over 490000 SCC is the most common type of esophageal cancer
new cases of esophageal cancer were reported in 2005. worldwide. The overall incidence increases with age,
While many other types of cancer are expected to de- reaching a peak in the seventh decade. SCC occurs equal-
crease in incidence over the next 10 years by 2025 the ly as often in the middle and lower esophagus, with an in-
prevalence of esophageal cancer is expected to increase cidence that is three times higher in blacks in comparison
by 140%[1]. According to the National Cancer Institute, in to whites[11].
the United States there will be approximately 17990 new Major risk factors include alcohol consumption and
cases and 15210 deaths in 2013[3]. Despite many advances tobacco use. Most studies have shown that alcohol is the
in diagnosis and treatment, the 5-year survival rate for all primary risk factor but smoking in combination with al-
patients diagnosed with esophageal cancer ranges from cohol consumption may have a synergistic effect and in-
15% to 20%[4]. The epidemiology of esophageal cancer crease the relative risk. The relative risk in men who used
in developed nations has dramatically changed over the both heavy tobacco and alcohol was 35.4 in white males
past forty years. Forty years ago squamous cell carci- and 149.2 in black males compared to men of the same
noma (SCC) was responsible for greater than 90% of race and region who were non-smokers or drinkers[12].
the cases of esophageal carcinoma in the United States. The mechanism of how tobacco and alcohol in combi-
Adenocarcinoma has now become the leading cause of nation lead to increased risk of esophageal cancer has
esophageal cancer in the United States, representing 80% been extensively studied. Alcohol can damage the cellular
of cases[5]. In 1975 esophageal adenocarcinoma (EAC) DNA by decreasing metabolic activity within the cell and
affected four people per million, in 2001 the rate had in- therefore reduce detoxification function while promoting
creased to twenty-three people per million. Making it the oxidation[13]. Alcohol is a solvent, specifically of fat-sol-
uble compounds. Therefore, the hazardous carcinogens
fastest-growing cancer in United States, according to the
within tobacco are able to penetrate the esophageal epi-
National Cancer Institute[6]. Considerable differences of
thelium easier[14]. Some of the carcinogens in tobacco in-
incidence of esophageal cancer exist on the basis of geo-
clude aromatic amines, nitrosamines, polycyclic aromatic
graphic and racial differences, which can be linked to dif-
hydrocarbons, aldehydes and phenols.
ferences in exposure to risk factors. This review discusses
Other carcinogens, such as nitrosamines found in cer-
epidemiology, pathogenesis, etiology and treatment mo- tain salted vegetables and preserved fish, have also been
dalities available for esophageal cancer. implicated in SCC of the esophagus. The pathogenesis
appears to be linked to inflammation of the squamous
EPIDEMIOLOGY epithelium that leads to dysplasia and in situ malignant
change[15].
Worldwide SCC is the most prevalent histological type
of esophageal cancer, while in certain developed nations
including Australia, Finland, France, United States and PATHOGENESIS OF ADENOCARCINOMA
United Kingdom adenocarcinoma of the esophagus pre- Adenocarcinoma of the esophagus occurs in the distal
dominates[7]. Esophageal cancer incidence and histologi- esophagus approximately three-fourths of the time[16]
cal type is highly variable based upon geographic loca- and has a distinct link to gastroesophageal reflux disease
tion. Incidence rates of SCC of the esophagus have been (GERD). Untreated GERD can progress to Barrett’s
reported as high as 100 cases per 100000 annually in an esophagus (BE), where the stratified squamous epithe-
area referred to as the “Asian esophageal cancer belt” and lium that normally lines the esophagus is replaced by a
this region extends from northeast China to the Middle columnar epithelium. The chronic reflux of gastric acid
East[8]. In the United States the National Cancer Institute and bile at the gastroesophageal junction and the sub-
estimates close to 18000 new cases and more than 15000 sequent damage to the esophagus has been implicated
deaths from esophageal cancer in 2013[3]. From 1975 in the pathogenesis of Barrett metaplasia[17]. The exact
to 2004, the incidence of EAC among white American nature of the metaplasia still remains to be determined.
males increased by more than 460% and in the same Diagnosis of Barrett esophagus can be confirmed by
period, the incidence among white American females in- biopsies of the columnar mucosa during an upper en-
creased by 335%[9]. doscopy. According to the requirements set forth by
the United States gastroenterology societies, the biopsy
specimen should contain the characteristic columnar
PATHOGENESIS epithelium metaplasia with goblet cells for a definitive
The two most common histological types of esophageal diagnosis. Barrett esophagus incidence increases with age
carcinoma include SCC and adenocarcinoma. Less than and is uncommon in children. It is more common in men
1% to 2% of all esophageal cancers are sarcomas or than women and more common in whites in comparison
small cell carcinomas[10]. Rarely lymphomas, carcinoids, to Asian or African American populations.

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 Napier KJ et al . Esophageal cancer

Some studies have shown that the risk of adenocarci- the overall 5-year survival rate for the adenocarcinoma
noma of the esophagus may be affected by the extent of group was 47% in comparison to 37% for the group with
esophagus lined by esophageal metaplasia[18]. The longer SCC.
the segment of esophagus affected the higher the risk
of adenocarcinoma. However, given the fact that short
segment esophageal metaplasia is more common in the ROUTES OF ESOPHAGEAL CANCER
general population, many cases of adenocarcinoma occur SPREAD
in patients with short-segment metaplasia. Less than five
Prognosis in esophageal cancer is greatly dependent on
percent of patients diagnosed with adenocarcinoma of local invasion as well as spread to regional and distant
the esophagus had a prior diagnosis of BE[19]. The risk of structures within the body. Esophageal cancer is noto-
developing esophageal cancer is 50-100 times more likely riously aggressive in nature, spreading by a variety of
in those patients with BE[15]. However, a majority of pa- pathways including direct extension, lymphatic spread
tients with BE will not develop EAC, the annual risk in and hematogenous metastasis. The lack of serosa in the
patients with BE has been reported as 0.12%[20]. esophageal wall plays an integral role in the local exten-
Screening for BE via endoscopy is controversial and sion of esophageal cancer. With no anatomical barrier,
challenging. Currently no definitive screening protocol the primary tumor is able to extend rapidly into the adja-
has been formulated due to lack of documentation that cent structures of the neck and thorax including the thy-
screening effects EAC mortality. A large number of pa- roid gland, trachea, larynx, lung, pericardium, aorta and
tients with BE will not have reflux symptoms therefore diaphragm[25]. The lymphatic drainage of the esophagus
predicting which patients will have BE prior to endos- is extensive. It is drained by two separate lymphatic plex-
copy is very challenging. Despite no definitive data for uses, with one lymphatic plexus arising within the muco-
universal recommendation, most gastroenterological sal layer and a second plexus arising within the muscular
associations consider endoscopic surveillance “reason- layer. A majority of the lymphatic fluid from the upper
able” and “desirable” in patients with diagnosed BE[21]. two-thirds of the esophagus tends to flow upward, and
The primary goal of surveillance is to identify dysplasia the lymph from the lower third of the esophagus flows
before it progresses to an invasive malignancy. Current relatively downward, but all the lymphatic channels of
endoscopic technique consists of four quadrant biopsies the esophagus communicate. Therefore, lymphatic fluid
taken every 2 cm in the columnar-lined esophagus for from any portion of the esophagus may spread in either
histological evaluation. The American College of Gas- direction and spread to the intrathorax or intra-abdo-
troenterology has recommendation guidelines for how menal lymph nodes[26]. Esophageal cancer also spreads
often surveillance should take place based upon the pres- hematogenously,, in order of decreasing frequency, to the
ence or absence of dysplasia and grade of dysplasia if liver, lungs, bones, adrenal glands, kidney and brain. This
present. Surveillance endoscopy is recommended every method of spread is more common with more advanced
2-3 years in patients with no dysplasia. In patients with stages of esophageal cancer[27].
low-grade dysplasia, surveillance is recommended every
6 mo for the first year. If the dysplasia has not pro-
gressed in the first year, yearly surveillance is applicable. STAGING OF ESOPHAGEAL CANCER
In patients diagnosed with high-grade dysplasia (HGD), The clinical staging of esophageal cancer is assessed
two alternatives have been proposed. One option is to with the widely accepted TNM system developed by the
continue intensive endoscopic surveillance every 3 mo American Joint Committee on Cancer (AJCC). Pretreat-
until intramucosal cancer is detected. The other alterna- ment staging of esophageal cancer will directly affect
tive is for the patient with HGD to undergo endoscopic overall treatment options available to each patient and
mucosal resection[20]. Although the natural history of their prognosis, so accurate staging is essential.
HGD is variable, > 30% of patients with HGD will T staging of esophageal cancer focuses on identifying
develop EAC within 5 years[22]. Due to the high risk of the depth of invasion of the primary tumor. A critical
cancer most patients with HGD are evaluated as if can- aspect of T staging focuses on establishing if the primary
cer is present. tumor has invaded the surrounding mediastinal struc-
Another risk factor for EAC is obesity, specifically in tures, given that these patients would no longer be con-
those individuals with predominately abdominal centered sidered surgical candidates. Table 1 describes the TNM
fat distribution. Hypertrophied adipocytes and inflam- system, specifically referring to depth of invasion in T
matory cells within fat deposits create an environment staging[28]. This aspect of staging is essential in determin-
of low-grade inflammation and promote tumor develop- ing stage-specific protocols for treatment (Table 2[28]).
ment through the release of adipokines and cytokines[23]. For example, for T3 or T4 tumors the oncology team will
Adipocytes in the tumor microenvironment supply energy use preoperative chemotherapy or combination radia-
production and support tumor growth and progression[22]. tion and chemotherapy in order to render the primary
Long-term prognosis after resection is better for ad- tumor resectable by surgical excision. In contrast, T1 or
enocarcinoma compared to SCC. A study by Siewert et T2 tumors are treated primarily with surgical resection[29].
al[24]. Of 1059 patients who underwent resection showed Given the importance of T Staging in treatment options

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 Napier KJ et al . Esophageal cancer

Table 1 TNM system, specifically referring to depth of

accuracy improved as the T stage of the primary tumor
invasion in T staging increased. Accuracy ranged from 75%-82% for the T1
disease state to 88%-100% for the T4 disease state[41].
Category Description EUS is a useful tool in assessing the extent of disease
Tis Carcinoma in situ as well as response to chemotherapy, when the dimen-
T1 Tumors invade lamina propria or submucosa sions of the tumor are analyzed as the primary variable.
T2 Tumors invade muscularis propria
However, EUS is unreliable for staging esophageal cancer
T3 Tumors invade adventitia
T4 Tumors invade adjacent structures after neoadjuvant chemoradiation[42]. Other potential limi-
N0 No regional lymph node metastases tations of EUS do exist. With any form of ultrasound
N1 Regional lymph node metastases the accuracy of the study is operator dependent. Also, in
M0 No distant metastasis cases of esophageal cancer where the esophageal lumen
M1a, M1b Distant metastasis
has been narrowed by strictures or stenosis, it may not be
possible to pass the endoscope through to visualize the
and overall prognosis, many modalities have been utilized entire tumor[30].
to accurately establish T Stage. These options include
computer tomography (CT), endoscopic ultrasound (EUS) N STAGE OF ESOPHAGEAL CANCER
and 18F-fluorodeoxyglucose positron emission tomogra-
phy (FDG-PET scan)[30]. In esophageal cancer, N Staging can be defined by the in-
volvement (N1) or absence of involvement (N0) of peri-
esophageal lymph nodes. Sensitivity and specificity of CT
T STAGE OF ESOPHAGEAL CANCER scans to detect periesophageal lymph node involvement
When assessing the esophagus by CT, a basic starting depends on the size of the lymph nodes. Most studies,
point to consider is the esophageal wall thickness. A wall used the common size criteria of 1 cm to define a lymph
thickness greater than 5mm is considered abnormally node as enlarged. Sensitivity was reported as 30%-60%
thick[31] given that the distended wall of the esophagus while specificity was 60%-80%[43]. An obvious limitation
is usually less than 3 mm[32]. Esophageal wall thickness of CT imaging in the ability to detect nodal involvement,
asymmetry is a classic but nonspecific CT finding of comes from the possibility that a normal sized lymph
esophageal cancer and esophageal wall thickness sym- node may contain metastatic foci without an obvious
metry should always be considered when evaluating the increase in the size of the lymph node. Also, an enlarged
esophagus by CT. CT has been shown to be less accurate lymph node does not necessarily mean metastasis, given
when compared to other assessment modalities such as that benign enlargement and inflammation may occur[43].
EUS[33]. CT assessment of the esophagus is also unable to Accuracy to detect N stage by CT imaging was reported
accurately differentiate between T1, T2 and T3 stages of as 46%-58%[39].
the primary tumor invasion. This information is essential EUS has been shown to be more accurate in deter-
in order to guide stage-specific protocols of treatment. mining nodal involvement in esophageal cancer, with an
The most useful aspect of CT imaging in determination accuracy of 72%-80%[44]. Accuracy has increased greatly
of T status is evaluating if the primary tumor invades with the use of EUS in combination with United States
into adjacent structures. Obliteration of the fat planes be- guided fine-needle aspiration to evaluate for lymph node
tween the primary tumor and the adjacent structures on metastasis.
CT would establish the primary tumor as a T4 stage can- FDG-PET has also been utilized in determining
cer. The sensitivity and specificity of CT to detect medi- nodal involvement in esophageal cancer. Assessment of
astinal invasion ranges between 85%-100%[34,35]. It should local and regional lymph nodes for uptake of FDG is
be noted that while obliteration of the fat planes between difficult to determine given the intense uptake of FDG
the primary esophageal tumor and adjacent structures is by the primary esophageal tumor. However, PET is quite
usually reliable in the establishment of a T4 stage tumor, useful in detecting distant metastasis, including metasta-
it can occur in patients with prior radiation therapy or ca- sis to the abdomen and cervical lymph nodes. Sensitivi-
chectic patients. ties were reported as high as 90% in distant lymph node
EUS is now considered the most accurate imagining metastasis[45].
modality available to establish T staging of esophageal
cancer. In comparison to CT, EUS is more accurate
to differentiate between T1, T2 and T3 tumors[36]. In M STAGE OF ESOPHAGEAL CANCER
comparing the two imaging modalities, EUS was able to Esophageal cancer is notoriously aggressive and invasive
determine the preoperative T stage 76%-89% in com- in nature. In fact 20%-30% of patients with esophageal
parison to 49%-59% when CT imaging was utilized[37-39]. cancer will have distant metastasis at time of initial diag-
This differentiation is essential in guiding stage-specific nosis[27]. The presence or absence of distant metastasis
treatment protocols and the overall prognosis. Overall will be essential in guiding treatment options and in de-
in a study conducted by Rösch[40], EUS was able to cor- termining operability. Common sites of distant metastasis
rectly stage esophageal cancer 84% of the time, and the include liver, lung and bones[30].

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 Napier KJ et al . Esophageal cancer

Table 2 Aspect of staging is essential in determining stage-specific protocols for treatment

Stage Tumor Node Metastasis Therapeutic options

0 Tis N0 M0 Local ablative therapy
Ⅰ T1 N0 M0 Surgery
ⅡA T2 N0 M0 Surgery
T3 N0 M0
ⅡB T1 N1 M0 Neoadjuvant therapy with or without surgery
T2 N1 M0
Ⅲ T3 N1 M0 Neoadjuvant therapy with or without surgery
T4 Any N M0
ⅣA Any T Any N M1a Chemotherapy or radiation therapy with or without surgery
ⅣB Any T Any N M1b Palliative treatment

In the classification system of metastasis set forth metastasis, lymph node metastasis, higher clinical stage,
by the AJCC, distant metastasis can be subdivided into and a shorter survival rate. This study demonstrated the
M1a and M1b. Each of these classifications is crucial in possibility of using H2 RLN as a serum prognostic fac-
determining possible treatment options. M1a includes tor for ESCC[50]. A Japanese study, investigated the prog-
metastasis to celiac and cervical lymph node groups. nostic value of the tumor marker p53 in ESCC. They
This classification is associated with a better prognosis observed no correlation between a p53 aberration and
compared to M1b. Patients classified as M1a often times any clinical, pathological, or epidemiology of ESCC[51].
complete a course of neoadjuvant therapy followed by Another study investigated the marker gene, WDR66
surgical resection. Patients with M1b include those with through genome-wide expression profiling. Other WD
distant site metastasis. This classification usually carries a proteins have been used as tumor markers in other can-
worse prognosis given that surgical resection with cura- cers, such as hepatocellular carcinoma. WDR66 has a
tive intent is not indicated in these cases[46]. higher concentration in ESCC tissue than healthy tissue.
CT is the most commonly used imaging modality to WDR66 was found to have a role in the growth, motility,
rule out distant metastasis in patients with esophageal and epithelial-mesenchymal transition of ESCC. Poor
cancer. The most common areas of distant metastasis survival was noted with high levels of WDR66 in the tu-
can be quickly assessed using contrast-enhanced CT. Sen- mor tissue[52]. In a Chinese study, the gene marker phos-
sitivity for spiral CT to detect masses ≥ 1 cm has been pholipase A2 group ⅡA (PLA2G2A) was investigated to
reported as high as 90%[47]. determine its usefulness as a prognostic factor of ESCC.
EUS is limited in its ability to assess for distant me- PLA2G2A catalyzes multiple fatty acids, including ara-
tastasis. In general, CT or FDG-PET is preferred over chidonic acid and is expressed in colorectal, pancreatic,
endoscopic United States for M staging of esophageal prostate, gastric and lung cancer. Low expression of
cancer. PLA2G2A in tumor tissue correlated to high-grade tu-
FDG PET most distinct role in esophageal cancer mors, metastasis, increased depth of invasion, lymphatic
staging is in the detection of distant metastasis. In com- invasion, and poorer overall survival rate[53].
parison to CT, PET has been shown to be more accurate
in detecting distant metastasis[48]. One study showed that
PET was able to detect distant metastasis 15% of the PROGNOSTIC FACTORS
time in patients that were believed to only have primary Platelet count has been used to help determine the prog-
esophageal cancer by other imaging modalities[49]. If pres- nosis of other cancers because platelets are an integral
ent, distant metastasis places the patient in M1b category component of the inflammation processes. Platelet count
and surgery with curative intent is no longer recommend- is inversely related to the cancer prognosis, as in a higher
ed. Accurate M staging is imperative in guiding treatment platelet count correlates to a poorer prognosis. The ab-
options. solute cut off for platelet count as a prognostic factor
has been debated. In one study of ESCC, platelet counts
were higher in patients with large tumors. It was deter-
TUMOR MARKERS mined that those patients with platelet counts ≤ 205000
Serum human relaxin 2 (H2 RLN) is made in the corpus had a better 5-year survival rate than patients with plate-
luteum of females and the prostate of males. It helps lets > 205000 especially when nodes were involved[54].
remodel various tissue components such as extracellular Tumor length is used as a prognostic factor in ESCC
matrix, collagen, and matrix metalloproteinase. There is but the length cutoff point in predicting survival has
supporting evidence that RLN is a tumor growth fac- been contested. Researchers in China looked at tumor
tor and has been shown in vitro to enhance invasiveness length in the elderly population (over 70 years old) and
of breast cancer cells. A study measuring RLN levels in the cutoff point was calculated to be 4.0 cm. Patients
patients with esophageal SCC (ESCC) discovered that with a tumor length of ≤ 4.0 cm had a better 5-year sur-
patients with higher levels of H2 RLN had more distant vival than those with a tumor length of > 4.0 cm, espe-

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 Napier KJ et al . Esophageal cancer

cially with a T3-4 grade or nodal-negative patients[55]. ach conduit[60].

Cancer causes a hypercoagulable state and this envi- Another critical component of esophagectomy is the
ronment encourages tumors to grow and produce more lymph node dissection. There is debate about which surgi-
pro-coagulants. D-dimers are the end product of fibrin cal approach is appropriate based upon access, adequacy
and fibrinolysis and have been reported to be associated of the lymph node retrieval, and the lymph node dissec-
with tumor prognosis, tumor stage, lymph node involve- tion[54]. Each surgical technique have different lymph node
ment, and overall survival. One study looked at the retrieval rates based on the surgical exposure of open,
plasma D-dimer levels in patients with esophageal cancer laparoscopic or laparoscopic assisted surgery. Laparoscop-
before and after surgery as well as patients without can- ic surgery offers less blood loss and more patient comfort
cer. Their research showed that high levels of D-dimers but not as many lymph nodes can be retrieved compared
in the pre-operative state correlated with a higher tumor to the open approach. Placement of a thorascopic port
stage and surgery caused more patients to have a hyper- has been shown to provide more exposure into the chest
coagulable state which shortened their survival time[56]. cavity allowing for a more thorough dissection. One study
Nutrition is an important factor that influences pa- looked at the difference between open and laparoscopic
tients with esophageal cancer during their perioperative THE without a thorascopic port and found that while the
period. Early enteral nutrition was noted to protect the open procedure yielded more lymph nodes this did not
intestinal mucosa, improved the nutritional status, and affect the patient’s overall prognosis[61].
increased the immune status patients undergoing esopha- The differences between transthoracic and THE have
gectomy. Enteral nutrition protected the intestinal mucosa been extensively debated. A meta-analysis of 52 studies
by maintaining the intestinal barrier against plasma en- was performed in 2011 comparing the 5 years survival,
dotoxins[57]. Another study looked at immunonutrition in postoperative morbidity and mortality between transtho-
patients with head and neck cancer and esophageal cancer racic and transhiatal esophagectomy. The analysis showed
undergoing chemoradiotherapy. Plasma levels of argi- that transhiatal method is associated with reduced operat-
nine, eicosapentaenoic acid, docosahexaenoic acid, and ing time, length of stay in hospital, postoperative respira-
nucleotides were measured in patients undergoing chemo- tory complications, and decreased early mortality. The
radiotherapy, who received either an Immune modulating transthoracic method is associated with fewer anastomo-
Enteral Nutrition formula (IEN) or an isocaloric, isoni- sis leaks, anastomotic strictures, and vocal cord paralysis.
trogenous formula, Standard Enteral Nutrition (SEN). There was no significant difference between transhiatal
IEN patients had less weight loss, increased antioxidants, and transthoracic method in 5-year survival rates [62].
and maintained their functional capacities compared to These findings agree with two previous meta-analysis
those with the SEN formula[58]. conducted in 1999 and 2001[63-64]. This data suggest that
the outcome of the esophagectomy does not depend on
TREATMENT the surgical method chosen but more on the surgeon’s
and hospital’s experience in dealing with these complex
Surgery can be a definitive treatment for Tis, T1 and oncological cases[65].
some T2 carcinoma of the esophagus. There is some Another treatment option for high grade dysplasia
debate on whether neoadjuvant chemoradiotherapy or is esophageal mucosal resection (EMR) or esophageal
surgery be performed first on T2 esophageal cancer mucosal dissection. EMR dissects the esophageal sub-
because staging difficulties[59]. There are different surgi- mucosa to better evaluate and stage early carcinoma[66].
cal techniques for esophagectomy but the main two are It has been suggested the EMR be performed on lesions
transhiatal esophagectomy (THE) and transthoracic with a diameter ≤ 2 cm and only occurs in less than one
esophagectomy. THE does not include a thoracotomy third of the esophageal wall circumference. EMR is used
and instead the stomach is mobilized from the surround- in conjuction with radiofrequency ablation therapy and
ing omentum and blood vessels through a midline su- cryotherapy ablation to eradicate BE[67]. In one trial, EMR
praumbilical incision during the abdominal phase[56]. The with radiofrequency ablation eradicated 90% of dysplasia
esophagus is removed from a small cervical incision usu- and metaplasia in patients[68].
ally on the left side of the neck during the cervical phase. One study investigated the hemodynamic changes
The transthoracic esophagectomy uses the Ivor Lewis during surgery between patients who underwent a trans-
method, the McKeown Modification (3 hole approach), thoracic vs THE and their post-operative changes. It was
or the left transthoracic approach. Surgeons choose the found that there was no statistical significance between
method based on tumor location and size. The McK- transthoracic and THE in their intraoperative hemody-
eown modification is performed more for middle and namic changes. However more vasopressors were used
upper esophageal cancer while tumors in the lower third during surgery in patients with transthoracic esophagec-
of the esophagus are best approached using the left tomy due to increased hemodynamic liability[69].
transthoracic approach[56]. The abdominal phase of the
transthoracic esophagectomy is identical to the THE and
the thoracic phase is accomplished with a posterolateral MEDICAL AND RADIOLOGICAL
thoracotomy in the fifth intercostals space. The McK-
eown modification also includes a cervical phase where
TREATMENT
the proximal esophagus can be anastomosed to the stom- Chemotherapy and radiotherapy are other critical modali-

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 Napier KJ et al . Esophageal cancer

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P- Reviewers: Muguruma N, Watari J S- Editor: Qi Y

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