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ESOPHAGUS
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49
FIG. 4 Hypercontractile disorders. (A) Jackhammer esophagus. Extremely elevated contractile vigor (DCI in this case ranged from 12,000–50,000).
(B) Nutcracker esophagus. Peristaltic, vigorous contractions with DCI 5000 to 8000. DCI, Distal contractile integral. (Courtesy The Oregon Clinic.)
The Chicago Classification additionally addresses clinical
entities of absent contractility and ineffective esophageal motility.
Absent contractility is defined as HRM with hypocontractility
and failed peristalsis in 100% of swallows in the setting of an
EGJ with normal relaxation pressure. Premature hypocontractile
swallows with failed peristalsis are grouped here. In cases with
borderline EGJ relaxation and evidence of esophageal pressurization, achalasia should be considered and the patient managed
accordingly.
Systemic sclerosis (scleroderma) falls into the absent con-
tractility category (Fig. 5). This figure demonstrates complete
hypocontraction of esophageal smooth muscle, with preserved
skeletal muscle contraction in the upper esophageal sphincter and
diaphragm. Therapeutic options specific to diminished esophageal motility are limited, so treatment is directed primarily at the
underlying systemic disorder as well as relief of symptoms. Unfortunately, no specific pharmacologic therapy improves contractility
and function of esophageal smooth muscle. Prokinetic agents are
fraught with side effects and are primarily avoided. GERD has
been identified frequently in these patients and should be treated
aggressively with PPIs. Antireflux surgery can be considered carefully for refractory GERD cases in this setting, but it should be
approached with caution at the risk of exacerbating dysphagia.
Because connective tissue disorders such as scleroderma also can
affect gastric motility, one should be aware that GERD symptoms
may be a result of overflow reflux and should not be treated by
fundoplication alone. A small retrospective review of scleroderma
patients treated with fundoplication or Roux-en-Y gastric bypass
(RYGBP) revealed improvement in control of reflux and dysphagia in the RYGBP group compared with fundoplication. In very
carefully selected cases, RYGBP may be considered for primary
management of refractory GERD in scleroderma. Less-invasive
endoscopic procedures such as suture plication or radiofrequency
ablation may be more appealing for GERD in such fragile patients
but are less effective at reducing reflux.
FIG. 5 Absent contractility. This is a case of scleroderma with complete
hypomotility of esophageal smooth muscle; note preserved function of
skeletal muscle of the upper esophageal sphincter (asterisk) and diaphragm
(circumflex). (Courtesy The Oregon Clinic.)
50 MANAGEMENT OF DISORDERS OF ESOPHAGEAL MOTILITY
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Ineffective esophageal motility (IEM) is a minor esophageal
motility disorder defined by a significant number of weak or failed
swallows. Presentation may include heartburn and regurgitation with
or without dysphagia, and symptoms tend to be mild. GERD often
plays a significant role in the underlying cause of IEM because many
of these patients are found to have underlying abnormal esophageal
acid exposure. IEM is redefined by HRM criteria in CC v4.0 as at least
50% failed peristalsis, or more than 70% ineffective swallows. Inef-
fectiveswallowsareindicatedbyDCIlessthan450mmHg•s•cm,
failedperistalsisindicatedbyDCIlessthan450mmHg•s•cm,or
fragmented peristalsis (Fig. 6). Interestingly, symptom-free healthy
patients may also exhibit a manometric pattern consistent with IEM.
In the patient with IEM, the manometry technician may elect to perform additional provocative testing with multiple repetitive swallow
(MRS) assessment. Deglutitive inhibition of the esophageal body and
EGJ occurs during MRS, usually followed by augmented esophageal
contraction vigor and improved bolus transit. Augmented contraction with MRS may be reassuring to the physician who is considering
an antireflux procedure to treat underlying GERD while avoiding
iatrogenic postoperative dysphagia. When MRS does not augment
subsequent contraction, it is predictive of late dysphagia after fundoplication. Although evidence would indicate that there is a relatively
low risk of postoperative dysphagia with Nissen fundoplication for
patients with IEM, many surgeons choose to carefully tailor a partial
fundoplication to avoid the risk of postoperative dysphagia. Clinical
implications of MRS findings in this setting have yet to be defined
clearly and require further study because these provocative maneuvers are used more frequently with HRM.
Therapeutic options are limited for IEM patients. Because many,
if not most, IEM cases are related to chronic reflux disease, correction of GERD may result in correction of the motility disorder. Reassurance and antacid medications along with dietary and
behavioral modifications may be helpful. As in other motility disorders, prokinetic drugs generally are not recommended. Low-dose
antidepressants, especially tricyclic antidepressants or trazodone,
may reduce functional chest discomfort, heartburn, and globus sensation but may not be effective for dysphagia.
Nonoperative Management
The main goals of any treatment for patients with esophageal motility
disorders include reduction of chest pain and dysphagia. Treatment
is focused on reducing spasm, GERD, and outflow obstruction to
facilitate esophageal emptying. Reassurance alone can be beneficial.
Reassurance not only helps relieve anxiety but also has been shown
to reduce the severity of chest pain and the frequency of healthcare
use.
Dietary and Behavioral Modifications
Dietary and behavioral modifications can be very helpful for avoiding chest pain or dysphagia. These modifications include sitting
upright and allowing plenty of time for meals, taking small bites,
chewing thoroughly, and taking sips of liquid between bites. Foods
such as bread, meat, and rice are notorious for worsening dysphagia
and should be ingested with caution or minimized. Extremely hot or
cold foods can exacerbate esophageal spasm. Choosing soft or liquefied foods can be helpful during symptom flares.
Pharmacologic Therapy
Before pharmacologic therapy is initiated, it is important to carefully
review the patient’s home medications and minimize those that affect
esophageal motility. DES in particular is associated with chronic
opioid use and has been shown to improve with opioid cessation. A
few classes of drugs have been used with some success in providing
symptomatic relief of esophageal spasm. Smooth muscle–relaxing
agents (nitrates or calcium channel blockers) taken 15 minutes
before meals may provide some symptomatic relief in spastic or
hypercontractile disorders, including DES, some cases of EGJOO,
FIG. 6 Minor disorders of peristalsis. (A) Ineffective esophageal motility, weak peristalsis (DCI <450). (B) Fragmented peristalsis. Large breaks (>5 cm)
with preserved contractile vigor (DCI >450). DCI, Distal contractile integral. (Courtesy The Oregon Clinic.)
and jackhammer esophagus. Phosphodiesterase-5 inhibitors such as
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sildenafil, which acts by blocking degradation of nitric oxide, also
can be effective. These drugs may be tolerated poorly because of
lightheadedness, headache, or other side effects, and tachyphylaxis
has been noted. The cost of sildenafil may be prohibitive, and effects
of daily long-term use of this agent in various populations of patients
are unknown. Low-dose antidepressants, including tricyclic agents
and trazodone, may provide pain modulation and anxiety relief for
noncardiac chest pain. As previously discussed, GERD is frequently
part of the clinical syndrome of esophageal dysmotility, although its
role in pathogenesis is not understood completely. A trial of PPIs
is warranted and may help reduce inflammation, pain, and spasm
related to abnormal esophageal acid exposure.
Endoscopic Therapy
PD has been used to treat spastic esophageal motility disorders
affecting the EGJ, including EGJOO, DES, and nutcracker esophagus, with variable success. In small studies, 26% to 70% of DES
and nutcracker patients had a favorable response with PD, although
there is concern that some of these cases may have been classified
more accurately as achalasia. From the achalasia literature, there is
a known risk of perforation with pneumatic dilation in the range of
about 2% to 5% of cases performed by expert endoscopists. This rate
of perforation is unacceptable to many endoscopists, who no longer
use PD as first-line therapy.
Endoscopic injection of botulinum toxin (Botox) may be temporarily effective in relief of spasm in EGJOO, DES, or jackhammer
disorders. The technique for administration of botulinum toxin has
not been standardized; some report injection of the EGJ alone, and
others include the esophageal body. Botox to the esophageal body
may be helpful in cases such as DES or jackhammer, although it is
uncertain exactly where and how much drug should be injected.
Infection is an uncommon but serious risk of Botox injections.
One death resulting from mediastinitis has been reported in a DES
case treated with Botox, although other serious adverse events have
been rare. Endoscopists may elect to use EUS to guide positioning
and depth of injections into the thinner-walled esophageal body. In
small studies of patients with EGJOO and DES, successful relief of
symptoms with botulinum toxin injections was achieved in more
than 50% of patients at 6 months, with further improvement from
serial on-demand treatments thereafter. This was comparable to
efficacy in achalasia. Fall-off of symptom relief is present in each of
these disorders with time, which may require repeat treatments or
escalation to surgical intervention. Prominent symptoms and spastic
features may predict early recurrence of symptoms. Botulinum toxin
before surgical myotomy has been noted to cause submucosal fibrosis and increase difficulty in identifying and maintaining the proper
dissection plane. Prior Botox is not an absolute contraindication
to surgery, however, and may be useful as a trial to determine if a
patient may respond well to surgical myotomy. Long-term studies
are not available evaluating the efficacy of repeated botulinum toxin
injection for spasm.
Surgical Management
Surgical therapy is an option for nonachalasia esophageal motility disorders, but optimal timing and approach are controversial.
Surgery generally has been reserved for medically refractory cases
because outcomes are variable, somewhat unpredictable, and may
be associated with surgical morbidity. As mentioned earlier, IEM
patients with GERD, whether they also have dysphagia, tolerate
antireflux surgery with a tailored fundoplication well, and treatment
of the reflux often corrects the motility disorder as well. Classically,
these patients have a partial fundoplication, most commonly a
270-degree posterior wrap (Fig. 7). Nissen fundoplication also has
been shown to be well tolerated in select patients; a full wrap should
be reserved for IEM patients with minimal symptoms of dysphagia
before surgery and significant reflux disease. Endoluminal antireflux
ESOPHAGUS
FIG. 7 Completed laparoscopic 270-degree posterior Toupet fundoplication.
procedures such as Stretta (radiofrequency) and transoral incisionless fundoplication, which provide less-aggressive valve reconstructions, also may be good options for these patients.
Data on surgical outcomes for EGJOO, DES, and other hypercontractile disorders are limited to a few series, mostly small and
nonrandomized over the past 50 years. As diagnostic modalities have
improved and disease classifications have evolved, these data become
even more difficult to interpret. In general, outcomes for surgery are
better for relief of chest pain and dysphagia compared with medical
or endoscopic therapies. In DES, which is the most frequently studied
esophageal motility disorder aside from achalasia, favorable symptomatic outcomes are reported in about 70% of cases treated with
surgical myotomy via an abdominal or thoracic approach at highly
skilled centers. These outcomes are notably less successful than those
for surgical myotomy for achalasia, so surgery often is reserved as a
last resort for patients with nonachalasia motility disorders. Symptoms of chest pain are less reliably improved than dysphagia in these
patients, and prior series have reported only 50% reduction in chest
pain for patients with nutcracker esophagus. Therefore, many of
these patients endure long courses of medical or endoscopic therapy
because there is no clear definition of “medical failure.”
Surgical techniques for esophageal myotomy are varied. Traditional open surgery largely has been replaced by minimally invasive
techniques, and new endoscopic options are available. Length of the
esophageal body myotomy, inclusion of the EGJ in the myotomy, and
addition of a concomitant antireflux procedure are variable from surgeon to surgeon. Previous authors in this text have recommended a
long thoracic myotomy for the treatment of DES or other esophageal
body motility disorders and have described the technique in detail
(Fig. 8). Thoracic access allows myotomy extension for the full length
of the esophageal body, which is not possible with laparoscopic
Heller myotomy. However, thoracic myotomy has the disadvantage of
requiring single lung ventilation, chest tube placement, and typically
a longer length of stay. The thoracic approach is complicated further
if the surgeon desires a fundoplication or extended gastric myotomy.
POEM offers several advantages for esophageal myotomy and
is preferred as a less invasive technique for patients with hypercontractile/spastic esophageal motility disorders. This natural orifice
transluminal endoscopic surgery procedure is completely endoscopic
51
52 MANAGEMENT OF DISORDERS OF ESOPHAGEAL MOTILITY
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FIG. 8 (A) Thoracic myotomy and (B) Belsey fundoplication. Courtesy Corinne Sandone. (From Cameron JL, Sandone C. Atlas of Gastrointestinal Surgery,
vol 1. 2nd ed. Shelton, CT: People’s Medical Publishing; 2007.)
and incisionless. It provides the ability to tailor the length and location of the myotomy with ease because the entire affected esophageal
body and EGJ are accessible. POEM allows the surgeon to produce a
selective circular myotomy and avoids the risk of vagus nerve injury
or disruption of the diaphragmatic crural component of the EGJ.
Single lung ventilation, lateral or prone positioning, and chest tubes
are not required. Moreover, postoperative pain is usually minimal.
POEM was first applied clinically for achalasia by Inoue in
2008, and since then more than 4000 cases have been performed
worldwide with an excellent safety profile and good clinical results,
mostly for patients with achalasia. Until recently, studies of POEM
for nonachalasia esophageal motility disorders included only a few
such cases and have not always been stratified by subtype. POEM is
also used for spastic esophageal disorders such as DES, jackhammer
esophagus, and EGJOO (including cases of nutcracker esophagus
and HTLES as classified before CC v3.0) with favorable results.
POEM has reported success rates of more than 80% for these disorders with relatively low morbidity at expert centers. In a meta-analysis by Khan et al. examining the clinical success of POEM in spastic
esophageal disorders including type III spastic achalasia, DES, and
nutcracker esophagus, 179 patients were pooled for analysis from 8
observational studies. Clinical success for all types of spastic esophageal disorders was 87%. Although these studies are small, they
suggest comparable outcomes for extended POEM with low morbidity compared with traditional open or laparoscopic/thoracoscopic
approaches for extended esophageal myotomy.
Given the subsequent weakening of peristalsis after esophageal
body myotomy, it is recommended to extend the myotomy through
the EGJ onto the stomach to prevent relative outflow obstruction and
postoperative dysphagia, even in the setting of a normally relaxing
EGJ. POEM myotomy length should be tailored based on HRM
topography and endoscopic measurement of the high-pressure zone
and has been extended proximally anywhere between 6 and 23 cm
above the gastric cardia in such cases. POEM with variable length of
myotomy was comparable to other surgical techniques for relief of
dysphagia and chest pain and had less morbidity.
A disadvantage of POEM is the requisite learning curve, which
is about 20 cases for experienced endoscopists as demonstrated by
Kurian and colleagues. GERD is also a long-term risk of POEM,
currently with a 20% to 46% risk based on cumulative data. This is
in fact comparable to Heller myotomy with partial fundoplication,
which has a postoperative rate of GERD between 21% and 42%,
depending on the fundoplication technique. Postoperative GERD is
asymptomatic in one-half of patients, so routine follow-up pH testing
or endoscopy is prudent. Patients identified with GERD have been
treated successfully with PPIs with avoidance of long-term sequelae
of reflux thus far. POEM results in a low rate of clinically significant
leak or stricture and has been shown to be safe and effective in revision after Heller myotomy, Botox, and PD. POEM does not preclude
subsequent endoscopic, laparoscopic, or thoracoscopic procedures
should they be required. Because of these benefits, extended myotomy by POEM should be the preferred approach for primary spastic
motility disorders requiring intervention.
Peroral Endoscopic Myotomy Operative Technique
Previous chapters in this and other texts have described esophageal
myotomy with or without fundoplication via abdominal and thoracic
approaches, so these are not repeated in detail here.
POEM is performed in the operating room under general anesthesia. The procedure requires a high-definition endoscope for optimal visualization and CO
profile than room air. The patient is placed in the supine position to
allow access to the abdomen or chest. For a few days before the procedure, patients are given a Nystatin rinse prophylactically to clear
any Candida esophagitis related to esophageal stasis and allowed
only a liquid diet for 1 day to allow clearance of retained food. A
preoperative antibiotic and a single preoperative dose of intravenous
steroid are administered to prevent development of mucosal edema.
Upper endoscopy is performed to evaluate the anatomy, rule out
Candida spp., and clear any fluid or food debris within the esophagus before proceeding. An endoscopic functional lumen imaging
probe (EndoFLIP) is used to measure baseline esophageal diameter,
pressure, cross-sectional area, distensibility, and compliance. An
overtube is used for distal myotomy to stabilize the scope from
overtorquing. No overtube is used for extended myotomy. The gastric wall is tattooed with indigo carmine 2 cm distal to the EGJ in
the anterior position along the lesser curvature, marking the target
for the distal extent of the myotomy. The location and extent of the
myotomy and mucosotomy are calculated based on careful evaluation of the preoperative manometry and intraoperative evaluation of
the high-pressure zone. An angled dissecting cap is attached to the
high-definition endoscope to facilitate dissection and visualization.
A mucosal lift is created with injectable saline with dilute indigo carmine in the anterior esophagus 2 to 4 cm proximal to the proximal
extent of the planned myotomy (Fig. 9).
An endoscopic cautery knife is used to create a 1.5-cm longitudinal mucosal incision to expose the submucosa. Using the dissecting
cap, the surgeon advances the endoscope through the mucosotomy
and into the submucosal plane. Once inside, spray cautery and serial
injections of lifting solution are used to create a submucosal tunnel,
separating the mucosa from the circular muscle. Visible vessels are
coagulated with the dissecting knife or grasped with hot biopsy
insufflation because it has a better safety
2
ESOPHAGUS
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53
A
FIG. 9 Peroral endoscopic myotomy. (A) Entry into submucosal plane. (B) Creation of submucosal tunnel (mucosa is inferior, circular muscle is superior).
(C) Myotomy of circular muscle. (D) Closure of mucosal entry site with clips. (From Inoue H, Sato H, Ikeda H, etal. Per-oral endoscopic myotomy: a series of 500
patients. J Am Coll Surg. 2015;221:256–264).
forceps. The submucosal tunnel is extended distally across the GEJ
and onto the gastric wall until the distal darker blue tattoo is reached.
Once satisfied with the extent of the tunnel, the endoscope is
brought back, and the myotomy is created by selectively dividing the
circular muscle layers. The thin longitudinal muscle layer is left intact
whenever possible. Full-thickness breaches of the muscle are usually
not critical as the mediastinal adventitial tissue is left intact. The
myotomy is extended across the EGJ and onto the proximal gastric
wall. During the procedure, exiting the tunnel to deflate insufflated
gas from the stomach may be required to relieve gastric distension.
Capnoperitoneum may develop in up to 30% of cases; it is often
minor and self-limited but is evacuated easily with a Veress needle
if abdominal overdistension or respiratory compromise develops.
After the myotomy is completed, the surgeon withdraws the
endoscope, checking for hemostasis. Completion endoscopy identifies any inadvertent mucosal injuries, which are treated with endoscopic clips. The EndoFLIP catheter is replaced, and measurements
are compared with those obtained before surgery to ensure adequacy
of the myotomy before closure. Endoscopic clips then are used to
close the proximal mucosotomy in a longitudinal fashion from distal
to proximal.
B
Postoperative Care
The patient is kept NPO overnight, and a routine contrast esophagram is obtained on the first postoperative day. If no leaks or
obstruction are identified, the patient is allowed clear liquids and
crushed medications. The patient may be discharged on postoperative day 1 if liquids are tolerated and should maintain a puree-consistency diet for 1 week to avoid disruption of the mucosal closure
clips. In most cases, postoperative pain is minimal and usually does
not require narcotics.
Complications
Acute postoperative complications can include intratunnel bleeding,
mucosal leak or dehiscence, or mediastinitis. No deaths have been
C
reported. Bleeding may require transfusion and repeat endoscopy
to achieve hemostasis. Mucosal leaks or dehiscence may seal with
conservative management but often require repeat endoscopy and
repair with additional clips or suturing. Mediastinitis is treated
with antibiotics and may require percutaneous or surgical drainage.
Postprocedure adverse events in the meta-analysis reported by Khan
et al. for all types of spastic esophageal disorders were 14%. Most of
the adverse events (74%) were managed conservatively. Five patients
required prolonged hospitalization and/or an intervention for pneumothorax, pulmonary embolism, capnoperitoneum, or bleeding.
D
CONCLUSION
There is work to be done in the realm of nonachalasia esophageal
motility disorders as HRM diagnostics and treatment options evolve.
To achieve the best possible outcome, therapeutic options should be
considered carefully and individually tailored. Patients should be
advised on expectations because treatment outcomes are somewhat
unpredictable and may be disappointing in some cases. POEM is a
promising, minimally invasive treatment option for hypercontractile
and spastic disorders and perhaps will be considered as an early
surgical intervention rather than salvage therapy, given its relative
success and safety profile. For hypomotility disorders associated with
GERD, partial fundoplications remain the gold standard, although
Nissen fundoplication also has been shown to be well tolerated in
many cases of at least partially preserved peristalsis. There also may
be a role for newer endoscopic antireflux procedures, although there
are insufficient data at this time to define their application for these
relatively rare disorders.
ACKNOWLEDGMENT
We acknowledge the work of Kristin Wilson Beard, MD, in conjunction with Lee L. Swanstrom, MD, on the comprehensive content in
previous editions of this text.
54 MANAGEMENT OF ESOPHAGEAL CANCER
T1a
T1b
pTNM Adenocarcinoma pTNM Squamous Cell Carcinoma
AB
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S u g g e S t e d R e a d i n g S
Almansa C, Hinder RA, Smith CD, et al. A comprehensive appraisal of
the surgical treatment of diffuse esophageal spasm. J Gastrointest Surg.
2008;12:1133–1145.
Inoue H, Sato H, Ikeda H, etal. Per-oral endoscopic myotomy: a series of 500
patients. J Am Coll Surg. 2015;221:256–264.
Khan MA, Kumbhari V, Ngamruengphong S, etal. Is POEM the answer for
management of spastic esophageal disorders? A systematic review and
meta-analysis. Dig Dis Sci. 2017;62:35–44.
Roman S, Kahrilas PJ. Distal esophageal spasm. Curr Opin Gastroenterol.
2015;31:328–333.
Samo S, Qayed E. Esophagogastric junction outflow obstruction: Where
are we now in diagnosis and management? World J Gastroenterol.
2019;25(4):411–417.
Management of
Esophageal Cancer
Fatima G. Wilder, MD, and Stephen C. Yang, MD
EPIDEMIOLOGY
Esophageal cancer is the eighth deadliest cancer in the world as
reported by the World Health Organization in 2020. The two predominant histologic types are adenocarcinoma (most common in the
United States) and squamous cell carcinoma (most common worldwide). Notable risk factors include gastroesophageal reflux, smoking,
alcohol consumption, nutritional deficiencies, environmental carcinogens, long-standing achalasia, and caustic injury.
CLINICAL PRESENTATION
Commonly reported symptoms at the time of presentation include
regurgitation, odynophagia, weight loss, and hematemesis. Dysphagia is the most common presenting symptom in patients with
esophageal cancer. In the early phases of obstruction, patients typically compensate for their symptoms by adjusting their diet and
consuming semisolid and liquid nutrition as tolerated. Dysphagia
does not typically present until the tumor occludes two-thirds of the
Schlottmann F, Shaheen NJ, Madanick RD, Patti MG. The role of Heller
myotomy and POEM for non-achalasia motility disorders. Dis Esophagus.
2017;30(4):1–5.
Sharata A, Dunst C, Pescarus R, etal. Peroral endoscopic myotomy (POEM)
for esophageal primary motility disorders: analysis of 100 consecutive
patients. J Gastrointest Surg. 2015;19:161–170.
Vanuytsel T, Bisschops R, Farré R, etal. Botulinum toxin reduces dysphagia
in patients with nonachalasia primary esophageal motility disorders. Clin
Gastroenterol Hepatol. 2013;11:1115–1121 e2.
Woltman TA, Oelschlager BK, Pellegrini CA. Surgical management of esoph-
ageal motility disorders. J Surg Res. 2004;117:34–43.
Yadlapati R, Kahrilas PJ, Fox MR, et al. Esophageal motility disorders
on high-resolution manometry: Chicago classification version 4.0.
Neurogastroenterol Motil. 2020;33:e14058.
lumen. A notable component of the patient’s past medical history
is often a long-standing history of gastroesophageal reflux disease
with or without a hiatal hernia. Due to the fact that symptoms often
present late, patients are typically at an advanced stage at the time
of diagnosis. However, those with a history of reflux disease may be
diagnosed earlier on surveillance endoscopy.
DIAGNOSIS/STAGING
Diagnosis and staging should be carried out in an expeditious manner to avoid delay in therapy, potentially compromising outcome.
The eighth edition of the American Joint Committee on Cancer
(AJCC) staging of epithelial cancers of the esophagus and esophagogastric junction (EGJ) presents separate classifications for clinical
(cTNM), pathologic (pTNM), and postneoadjuvant (ypTNM) stage
groups, and differs slightly between adenocarcinoma and squamous
cell histologies (Fig. 1).
Barium swallow should be the first study in the diagnostic workup
of esophageal cancer, as it will provide critical information regarding
the source of obstruction. However, esophagogastroduodenoscopy
(EGD) remains the gold standard for evaluation and tissue diagnosis
when there is a concern for malignancy. It allows for identification
of anatomical location of the mass, tumor characteristics, relation
to surrounding structures, and tumor grade. Evidence of Barrett’s
esophagus should be characterized according to the Prague criteria.
N0
0
Tis
G1
G2
G3
G1
G2
G3
G1
T2
G2
G3
T3
T4a
T4b
FIG. 1 Staging of esophageal cancer, American Joint Committee on Cancer Manual, eighth edition. Pathologic stage groups (pTNM) for (A) adenocarcino-
ma and (B) squamous cell carcinoma. (From Rice TW, Ishwaron H, Ferguson MK, Blackstone EH, Goldstraw P. Cancer of the esophagus and esophagogastric junction:
an eighth edition staging primer. J Thoracic Oncol. 2017;12[1]:36–42.)
IA
IB
IC
IB
IC
IC
IIA
IIB
IIIB IIIB
IVA
N1 N2 N3 M1
IIB
IIB
IIIA
IIIB IIIB
IVAIVA
IIIA
IIIA
IIIB
IVAIVA
IVA IVB
IVA
IVA
IVA
IVB
IVB
IVB
IVB
IVBIVA
T1a
Tis
0
G1
G2-3
T1b
G1
T2
G2-3
G1
T3
G2-3
T4a
T4b
N0
L U/M N1 N2 N3 M1
IA IA
IB IB
IB
IB IB
IIA
IIA
IIA
IVAIVA IVAIVA
IIA
IIA
IIB
IIB
IIB
IIIA
IIIBIIIB
IIIA
IIIA
IIIB
IIIBIIIB
IVAIVA
IVA
IVA
IVA
IVA
IVB
IVB
IVB
IVB
IVB
IVB
ESOPHAGUS
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TABLE 1 Siewert Classification
Siewert Type Description
I Adenocarcinoma of the lower
esophagus with the epicenter
located within 1 to 5 cm above
the anatomic GEJ
II True carcinoma of the cardia with
the tumor epicenter within 1 cm
above and 2 cm below the EGJ
III [Considered gastric
cancer; utilize gastric
cancer algorithm for
management guidelines]
All suspicious lesions should be biopsied simultaneously. Based on
the Seattle protocol, six to eight four-quadrant biopsies of the mass
utilizing standard size endoscopy forceps should be obtained along
every centimeter of gross disease.
If available at the time of EGD, endoscopic ultrasound (EUS) is
important as an early staging modality and to determine the Siewert
classification (Table 1), as location will determine optimal treatment
pathways. EUS will also assess tumor invasion (T stage), presence of
suspicious lymph nodes (N stage), and, at times, presence of regional
metastases (M stage). The addition of fine-needle aspiration (FNA)
aids in the accuracy of diagnosis.
Endoscopic mucosal resection (EMR) can be considered therapeutic especially in patients with early-stage disease (T1a or T1b).
This typically correlates with small, nodular lesions ≤2 cm. Focal
nodules should be completely excised and sent for pathology.
Tumor samples should be assessed for depth of invasion, degree of
differentiation, and presence of vascular and/or lymphatic invasion.
Presence of poor differentiation, deep submucosal invasion, and/or
lymphovascular invasion (LVI) are associated with greater risk of
lymph node involvement.
Additional workup including computed tomography (CT) of the
chest, abdomen, and pelvis with oral and IV contrast is indicated
Subcardial carcinoma with the
tumor epicenter between 2 and
5 cm below the EGJ, which infiltrates the EGJ and lower esophagus from below
to evaluate for metastatic disease, assess the locoregional extent of
the disease, and evaluate for issues of unresectability. CT is poorly
sensitive for early-stage disease, type of Siewert location, and limited
in its ability to distinguish T3 from T4 lesions. However, esophageal thickening of more than 5 mm clearly is considered abnormal.
Whole body
(FDG-PET)/CT is done to assess for metastatic disease. In patients
with tumor that is at or above the carina, with no evidence of M1
disease, bronchoscopy should be performed.
Symptom management in the preoperative settings includes
esophageal dilation for those with obstructive symptoms. Tumor
ablation with Nd:YAG laser, photodynamic therapy (PDT), and
cryoablation can be utilized for long-term ablation. Expandable metal
or plastic stents can also be utilized to relieve obstructive disease but
should not be placed if radiation therapy is offered for local control.
18
F-fluorodeoxyglucose positron emission tomography
STAGE-BASED TREATMENT STRATEGIES/
ALGORITHMS
There are subtle differences in the treatment of esophageal cancer based
on stage depending on the histology; these are briefly listed in Table 2.
T1 tumors involving the mucosa and superficial submucosa may
be addressed with EMR or endoscopic submucosal dissection; deeper
submucosal lesions may be treated with esophagectomy. Data regarding treatment of squamous cell carcinoma with EMR are limited.
Optimal management of T2N0M0 disease is somewhat controversial. Due to unreliable clinical staging modalities, a significant
percentage of patients are under- and overstaged. Although historical evidence supports induction therapy for this group, there
are a growing number of studies that suggest induction therapy is
not beneficial in those with node-negative disease. Current NCCN
guidelines suggest that, for patients who are medically fit, there are a
variety of treatment possibilities including definitive chemoradiation
and esophagectomy with or without induction or adjuvant therapy.
Treatment selections also take into consideration low- versus
high-risk lesions. cT1b-cT2, N0 low-risk lesions that are <3 cm in
size and well-differentiated should be resected with esophagectomy
(including for noncervical squamous cell cancer). Generally, higher
risk lesions (LVI, ≥3 cm, poorly differentiated), cT1b-cT2N+, or
cT3-cT4aN+ should undergo preoperative chemoradiation (for
noncervical squamous cell) or definitive chemoradiation (for cervical squamous cell). In patients with adenocarcinoma, preoperative
TABLE 2 Treatment Strategies for Adenocarcinoma and Squamous Cell Carcinoma in Medically Fit Patients
Tumor Classification Adenocarcinoma Squamous Cell
pTis ER ± ablation
pT1a ER ± ablation
Superficial pT1b ER ± ablation
cT1bN0-cT2N0 (low-risk lesions: <3 cm,
well differentiated)
cT2N0 (high-risk lesions: LVI, ≥3 cm,
poorly differentiated)
cT1b-cT2N+ or
cT3-cT4a, any N
cT4b Definitive chemoradiation therapy or che-
ER, Endoscopic resection; LVI, lymphovascular invasion; Tis, tumor in situ.
Adapted from National Comprehensive Cancer Network treatment guidelines, August 3, 2021.
ER and/or ablation
Esophagectomy
Esophagectomy
Esophagectomy
Esophagectomy Esophagectomy (noncervical esophagus)
Induction chemoradiation therapy
Definitive chemoradiation therapy (for
those who decline surgery)
Induction chemotherapy
motherapy alone
Esophagectomy
ER and/or ablation
Esophagectomy
Esophagectomy
Induction chemoradiation therapy
(noncervical esophagus)
Definitive chemoradiation (for cervical
esophagus)
Definitive chemoradiation therapy or
chemotherapy alone
56 MANAGEMENT OF ESOPHAGEAL CANCER
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chemoradiation is preferred. Definitive chemoradiation should be
reserved for patients who decline surgery, have poor performance
status, and those with bulky, multistation nodal involvement.
Approximately 32% of patients with esophageal cancer are found
to have regional disease at the time of diagnosis. Survival is found
to only be in the 10% to 30% range. Management of patients with
T3-4aN0, T1-4aN1M0 is highly variable. NCCN guidelines suggest
a variety of combinations of esophagectomy and chemoradiation as
opposed to definitive chemoradiation. Recent studies suggest that
induction chemoradiation followed by surgery is the optimal treatment for patients with T3-4a tumors or nodal disease. Additionally, a
recently published randomized trial demonstrated a survival benefit
to induction chemoradiation after surgery compared with surgery
alone for esophageal or EGJ cancer.
OPERATIVE APPROACHES TO
ESOPHAGEAL CANCER
Surgical Resection
Before any operative planning, patients should be assessed for their
ability to undergo general anesthesia and major surgery. One must
take into account a patient’s age and performance status in making this decision. Although no defined number of lymph nodes
has been definitively established, NCCN guidelines suggest that
patients who have not received induction chemoradiation should
have at least 15 lymph nodes resected and assessed for adequate
staging. Cervical or cervicothoracic esophageal carcinomas located
less than 5 cm from the cricopharyngeus should be treated with
definitive chemoradiation. Consideration should be given to placement of a feeding tube (jejunostomy tube preferred) before induction therapy if the patient is near totally obstructed and cannot
tolerate any oral liquids.
Approaches to resection of esophageal cancer include (open
versus minimally invasive) Ivor Lewis, McKeown, transhiatal, or
left transthoracic/thoracoabdominal approach with the anastomosis
in the chest or neck. Selection of the operative approach depends
on tumor location and surgeon expertise. Options for a conduit
are the stomach (preferred), colon, or jejunum. NCCN guidelines
recommend definitive chemoradiotherapy for patients with cervical
esophageal squamous cell carcinoma. Minimally invasive techniques
include laparoscopy, thoracoscopy, and robotic approaches; there are
hybrid approaches that combine open/minimally invasive, but available data show no superiority for any specific technique.
Ivor Lewis Esophagectomy
Ivor Lewis esophagectomy is the most commonly performed method
of esophageal resection worldwide in patients with esophageal
cancer. Although open resection is still utilized by some, minimally invasive esophagectomy (MIE) has rapidly become the more
common approach. Data have suggested decreased morbidity and
faster recovery times with this approach when compared with open
resection. Ivor Lewis esophagectomy is ideal for intraabdominal and
intrathoracic exposure in patients with cancer in the mid- and distal
esophagus. With either the open or minimally invasive approach,
resection begins with the patient in the supine position. In MIE,
the patient is placed in a split-leg position with moderate reverse
Trendelenburg. Intraperitoneal access is obtained by standard upper
midline laparotomy for open resection. In the MIE approach, five
intraabdominal ports and an atraumatic liver retractor for the left
hepatic lobe are positioned to expose the hiatus. The intraperitoneal
space should be carefully inspected to rule out any metastatic disease.
Once this is confirmed, dissection is started at the gastrohepatic
ligament, exposing the right crus. Care is taken to preserve a large
accessory or replaced left hepatic artery. A complete D2 lymph node
dissection is performed starting at the celiac trunk and following
the hepatic and left gastric artery, the superior margin of the portal
vein, and the peripancreatic tissue. The left gastric vascular pedicle
is divided with a stapling device or suture ligation. A thorough
node dissection is particularly important for adenocarcinoma of the
cardia, which has higher propensity to metastasize to these lymph
nodes. Equally important is an en bloc dissection of the distal mediastinum, which is easily done from the laparoscopic approach. The
gastrocolic ligament is then divided just distal to the gastroepiploic
arcade taking care not to injure the perigastric vascular structures,
which might compromise the blood flow to the newly formed gastric
conduit (Fig. 2). In situations where there is difficulty with identifi-
cation of the right gastroepiploic artery, fluorescence imaging and
Doppler at this stage can facilitate identification and determine the
adequacy of perfusion at the distal conduit.
The dissection is carried out medially to the level of the duodenum and then extended to the fundus by dividing the short gastric
vessels and the lateral phrenoesophageal ligament. The stomach
is then lifted anteriorly, and the retroperitoneal attachments are
divided. Pyloroplasty or botulinum toxin injection of the pylorus is performed at this stage to aid the emptying of the conduit.
Transhiatal dissection of the esophagus is then performed dividing
the phrenoesophageal ligament and dissecting the paracardial and
lower paraesophageal nodes and dividing the peritoneum from
the crurae bilaterally. A Penrose drain is used to encircle the distal
esophagus for retraction during both the abdominal and thoracic
phase. A 3 to 5 cm-wide gastric conduit is then created by dividing
the stomach with multiple findings of a linear stapler, starting at the
level of the incisura on the medial side all the way proximal to the
fundus leaving the last 5 cm of stomach undivided to allow retrieval
during the thoracic phase (Figs. 3 and 4). The staple line can be
reinforced either with a running or interrupted Lembert suture. As a
final step, a feeding jejunostomy tube is inserted in the small bowel.
After the abdominal portion is complete and the incisions are
closed, the patient is re-positioned in the left lateral decubitus
position. While this is the traditional approach, there are centers
that complete the thoracic portion with the patient in the prone
position. Anesthesia is asked to collapse the right lung either by use
of a double lumen endotracheal tube or capnothorax with minimally
invasive ports. A posterolateral thoracotomy incision is made in the
fifth intercostal space and access is gained to the thorax. In the MIE
approach, four trocars are placed in the thoracic wall in a diamond
pattern. The pulmonary ligament is divided to the level of the inferior pulmonary vein. A retractor (fan retractor if MIE) is placed to
improve visualization of the posterior mediastinal pleura at the level
of the azygos vein. The azygos vein is divided with a vascular stapler
to allow exposure of the entire esophagus (Fig. 5).
The Penrose drain left around the esophagus is retrieved and used
to retract the esophagus and facilitate dissection. The esophagus is
dissected out of the mediastinum, being extremely careful using
energy devices in the subcarinal and paratracheal areas to avoid
injury to the airway. Proximal dissection should be carried out to
provide a margin of 5 cm from the tumor’s edge. The esophagus is
then divided and the proximal margin is sent for frozen section to
assess for the presence of Barrett’s esophagus and tumor.
With the esophagus mobilized from the mediastinum, lymph
node dissection is performed in the paratracheal, subcarinal, and
inferior pulmonary ligament regions. Some surgeons also prophylactically ligate the thoracic duct by passing sutures at the T9 and/or
T10 level in the prevertebral tissues.
The gastric conduit is then gently pulled up into the chest up to
the level of the staple line that was previously created, making sure
no twists are present. A transoral circular end-to-end anastomotic
(EEA) stapler is then inserted through the patient’s mouth into the
esophageal stump. The nasogastric tube connected to the anvil is
passed through a small opening next to the staple line and removed
through one of the trocars. At this point, fluorescence imaging can
be used again to determine appropriate perfusion of the conduit.
This can be trimmed to a point of maximal perfusion, making sure
that excessive tension is avoided. The EEA stapler is introduced
ESOPHAGUS
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57
Lesser
curve vessels
Greater
Right
gastroepiploic
FIG. 2 Division of gastrocolic ligament with preservation of the right
gastroepiploic vessels during the abdominal portion of the esophagectomy.
(From Khatri V. Atlas of Advanced Operative Surger y. Philadelphia: Elsevier;
2012.)
omentum
Lesser
curve vessels
Pylorus
FIG. 3 Creation of the conduit. (From Khatri V. Atlas of Advanced Operative
Surgery. Philadelphia: Elsevier; 2012.)
Specimen
Gastric
tube
6SHFLPHQ
*DVWULFWXEH
FIG. 4 Creation of the conduit. (From Khatri V. Atlas of Advanced Operative
Surgery. Philadelphia: Elsevier; 2012.)
'HIODWHGOXQJ
'LYLGHGD]\JRVYHLQ
7UDFKHD
(VRSKDJXV
FIG. 5 Thoracic mediastinal exposure after division of the azygos vein.
(From Khatri V. Atlas of Advanced Operative Surger y. Philadelphia: Elsevier;
2012.)
58 MANAGEMENT OF ESOPHAGEAL CANCER
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tr
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through an opening made in the proximal gastric conduit. The conduit is pulled over the stapler to allow the piston to come out next
to the greater curvature of the stomach in the area chosen for the
anastomosis (Fig. 6). The anvil and the stapler are engaged, and the
stapler is fired to complete the anastomosis. Using a linear stapler,
the specimen is trimmed from the conduit (Fig. 7). The specimen
is then extracted with the help of a wound protector and the gastric
margin is checked. If excess perigastric fat is available from the conduit, this is placed around the anastomosis to decrease the chance of
an anastomotic leak.
McKeown
The McKeown (three-field) esophagectomy is utilized for patients
with a proximal thoracic tumor located near the airways, with
extensive Barrett’s esophagus, or if there is a concern for attaining an adequate proximal margin that is tumor free. A McKeown
esophagectomy has a cervical anastomosis that may represent a
better option for proximal esophageal disease. The steps of the
operation are the same as for an Ivor Lewis esophagectomy except
that the thoracic portion is performed first. After the abdominal
portion is complete, through an oblique incision anterior to the sternocleidomastoid muscle, the thoracic inlet is then dissected and the
specimen is extracted through this incision. A single-layer esophagogastric anastomosis is constructed using interrupted 3-0 silk sutures.
Alternatively, if there is enough overlap of the esophagus and gastric
conduit, the posterior row can be made with a GIA 30 stapler, and the
remaining closed with interrupted sutures in two layers, as originally
described by Orringer.
Transhiatal
A transhiatal esophagectomy should be the procedure of choice for
lower esophageal early-stage disease. With this approach, a right
thoracotomy is avoided. The transhiatal approach includes an initial
abdominal approach, similar to the Ivor Lewis esophagectomy, with
preparation of the gastric conduit. Following this, the patient remains
in the supine position and a cervical anastomosis is created, after
the blunt transhiatal dissection. Transhiatal MIE uses laparoscopic
abdominal dissection and preparation of the gastric conduit followed
by a cervical anastomosis in the left neck as previously described.
Mediastinal dissection of periesophageal lymph nodes, including those
in the subcarinal station, can be accessed through the hiatus, using the
lighting and magnification afforded by the laparoscope. The esophageal specimen is removed through the neck. The transhiatal operation
is the least invasive esophagectomy, requires less operative time, and
has excellent functional outcomes. The chest need not be violated for
early-stage disease, unless there is concern for an inadequate gastric
conduit length to perform a safe cervical anastomosis. Although longterm survival differences have not been demonstrated, many experts
believe this operation has a lower oncologic yield, although this has
not been analyzed for the minimally invasive approach where en bloc
dissection of the distal mediastinum is possible.
FIG. 6 Insertion of the EEA stapler and creation of the anastomosis. (From
Zwischenberger JB. Atlas of Thor acic Sur gical Techniques. Philadelphia: Elsevier;
2010.)
COMPLICATIONS
Some of the most common postesophagectomy complications can be
related to respiratory events, chyle leak, anastomotic/conduit complications, and atrial fibrillation.
Atrial fibrillation is a common complication after esophageal
Esophagus
resection. It is reportedly more common in older patients and those
who have undergone neoadjuvant therapy. The occurrence of atrial
fibrillation should prompt a workup for possible anastomotic leak.
Standard atrial fibrillation management includes electrolyte correction, medical management with antiarrhythmics, and defibrillation
Gastri
tube
Excess stomach
immed and closed
if needed.
Respiratory complications are additionally a common event after
esophagectomy. Aspiration and subsequent pneumonia increases a
patient’s risk for worse outcome, including an increased mortality
risk. Aspiration precautions should be strictly followed in the postoperative period.
Chyle leak is another well-documented complication. Low-volume
chyle leaks can be managed by making the patient nil per os (NPO),
initiating parenteral nutrition and conservative management until
chest tube output declines. If output remains high despite these
changes, one can consider invasive management, either with thoracic
duct embolization by interventional radiology or by surgical ligation.
FIG. 7 Trimming of the excess conduit at the esophago-gastric anastomo-
sis. (From Zwischenberger JB. Atlas of Thoracic Surgical Techniques. Philadelphia:
Elsevier; 2010.)
Anastomotic complications include anastomotic leak and stricture. In the setting of anastomotic leak, management depends on the
approach to the primary surgery. If the patient has undergone Ivor
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