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ESOPHAGUS
artery
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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
c
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
ESOPHAGUS
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59
Lewis esophagectomy, an anastomotic leak can be handled by placement of a metallic or plastic stent (if small and contained), or reoperation. In the setting of a cervical anastomosis with a McKeown or
transhiatal esophagectomy, an anastomotic leak is more easily managed
with a bedside neck washout and negative pressure therapy, if needed.
Patients should be treated with antibiotics if systemic signs of illness
appear and repeat assessment of the leak should be completed at an
interval time.
Recurrent laryngeal nerve injury has been reported more commonly in patients with cervical anastomoses and three-field lymph
node dissections. There is an increased risk of pulmonary complications in the postoperative period in patients with recurrent laryngeal
nerve injury. Swallow evaluation should be carried out and, if necessary, vocal cord medialization can be performed.
CONCLUSION
The management of esophageal cancer continues to evolve. Minimally
invasive interventions such as ablation, EMR, and ESD are increasingly common as improved screening tools have led to earlier diagnosis. With these less invasive techniques, up to 90% cure rates have been
seen. Detailed preoperative workup and staging remains paramount
to appropriate management. Minimally invasive surgical approaches
are quickly becoming the gold standard for surgical treatment in most
centers, as the data are trending toward better functional outcomes
and quality of life compared with totally open procedures.
Perhaps one of the most impactful recent advances that has
been instituted as standard of care is the addition of nivolumab as
adjuvant therapy for patients with resected esophageal (or gastroesophageal junction) cancers with residual pathologic disease if
they had received induction chemoradiation therapy. In the recently
completed CheckMate-577 trial, nivolumab given postoperatively
doubled the median disease-free survival versus placebo (22 vs. 11
months, respectively), translating to a 31% reduction in the risk of
disease recurrence. Better understanding of the patient-specific risk
factors for treatment failures as well as patient-specific tumor profiling and treatments has ushered in an era of minimally invasive and
precision therapeutics that holds a promise of improved outcomes
for this highly lethal disease.
S u g g e S t e d R e a d i n g S
Berry MF. Esophageal cancer: staging system and guidelines for staging and
treatment. J Thorac Dis. 2014;6(Suppl 3):S289–S297.
Kelly RJ, Ajani JA, Kuzdzal J, etal. Adjuvant nivolumab in resected esophageal or
gastroesophageal junction cancer. N Engl J Med. 2021;384(13):1191–1203.
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines):
esophageal and esophagogastric junction cancers. V. 4.2021, Aug. 3, 2021.
https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1433.
Shapiro J, van Lanschot JB, Hulshof Marten CCM, etal. Neoadjuvant chemo-
radiotherapy plus surgery versus surgery alone for oesophageal or junc-
tional cancer (CROSS): long-term results of a randomized controlled trial.
Lancet Oncol. 2015;16(9):1090–1098.
Multimodality Therapy
in Esophageal Cancer
Brooks V. Udelsman, MD, MHS, and
Uma M. Sachdeva, MD, PhD
OVERVIEW
In patients with locally advanced esophageal adenocarcinoma and
esophageal squamous cell carcinoma, optimal treatment involves
multimodal therapy. This rapidly evolving field includes surgery,
chemotherapy, radiotherapy, and more recently immunotherapy. The
goal of this multimodal approach is to increase R0 resection rates,
decrease local and systemic recurrence, and improve disease-specific
and overall survival. With current treatment regimens, 5-year survival has increased to nearly 50% in patients with resectable disease;
however, risk of recurrence remains high in individuals without a
complete pathologic response to neoadjuvant therapy. In this chapter, we review the current status of multimodal therapy in treatment
of locally advanced esophageal cancer, with special focus on the
emerging role of immunotherapy in resectable disease and new
approaches to oligometastatic disease. This chapter is intended to
provide an overview of the key studies driving current practice rather
than serve as an exhaustive review of all multimodal combinations
currently in trials for esophageal cancer.
DEFINITIONS OF MULTIMODAL THERAPY
AND INDICATIONS IN ESOPHAGEAL
CANCER
Multimodal therapy refers to the use of surgery in combination with
chemotherapy, radiotherapy, and immunotherapy in the oncologic
treatment of malignant disease. Surgery involves esophagectomy
with reconstruction, which can be performed using open, minimally
invasive, or robotic-assisted techniques. The procedural conduct of
esophagectomy is discussed in detail in the chapter entitled “Management of Esophageal Cancer” and therefore will not be reviewed
here. Oncologic treatment occurring before surgery is termed
neoadjuvant therapy, while treatment occurring after surgery is
termed adjuvant therapy. Both neoadjuvant and adjuvant therapy
may include chemotherapy alone or chemotherapy combined with
radiotherapy (i.e., chemoradiotherapy). Similarly, immunotherapy
may be delivered in the neoadjuvant or adjuvant setting, alone or
in combination with chemotherapy or chemoradiotherapy. In some
publications, the term induction therapy is used interchangeably with
neoadjuvant therapy; however, induction specifically refers to the
delivery of chemotherapy before radiation therapy, in contrast with
concurrent chemoradiotherapy. In this chapter, we will refer to all
treatment before surgical resection simply as neoadjuvant therapy.
The success of multimodal therapy regimens is determined
through quantified improvements in overall survival and disease-specific survival. Surrogate markers of successful response
include increased R0 resection rate, decreased time to recurrence, and increased likelihood of obtaining a complete pathologic
response, meaning the absence of residual disease identified in the
resection specimen following neoadjuvant treatment. These surrogates are highly correlated with improved survival and are often
reported after a shorter follow-up time, allowing for clinical practice
to be influenced by interim trial results while awaiting results of the
primary survival endpoints.
The two main histologic subtypes of esophageal cancer are esophageal adenocarcinoma and esophageal squamous cell carcinoma.
Together they represent 19,000 new cases per year in the United
States alone and are associated with 15,000 deaths annually. Worldwide, squamous cell carcinoma is the more common subtype, with
high prevalence in Asia and Africa. Esophageal squamous cell carcinoma has well-defined and strongly associated risk factors, including
use of tobacco, alcohol, and betel quid and ingestion of very hot
60 MULTIMODALITY THERAPY IN ESOPHAGEAL CANCER
pTis
T
Adenocarcinoma or
Esophageal Squamous Cell
Carcinoma in medically fit
patients
y in
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reatment of Esophageal
FIG. 1 Treatment algorithm for adenocarcinoma and squamous cell carcinoma in medically fit patients. (Data from National Comprehensive Cancer Network.)
temperature liquids, as well as some genetic predisposition. In contrast, adenocarcinoma is the dominant histology in Western Europe
and the United States, with risk factors including gastroesophageal
reflux disease, Barrett’s esophagus, and obesity, without clearly
defined genetic predisposition. Both types of esophageal cancer are
significantly more common in men than in women.
In both histologic subtypes, multimodal therapy in the neoadjuvant setting has demonstrated survival benefits and is now
standard-of-care for patients with locally advanced disease (Fig. 1).
This includes patients with at least clinical T3 disease or clinical N1
disease. Neoadjuvant multimodal treatment for patients with clinical
T2N0 esophageal cancer is controversial and nuanced. Up to 50%
of patients with clinical T2 disease will have occult nodal disease
not identified on staging computed tomography–positron emission
tomography. These patients with occult nodal disease stand to benefit from neoadjuvant treatment, while those without nodal disease
may not. Factors supporting the upstaging of T2N0 disease and use
of neoadjuvant therapy in this setting include tumor length ≥3cm,
poorly differentiated histology, and evidence of lymphovascular
invasion on biopsy. Consideration for neoadjuvant multimodal therapy in patients with T2N0 disease should be discussed in a multidisciplinary tumor board within the context of the patient’s unique risk
factors and tolerance for multimodal therapy before surgery.
Traditional Multimodal Treatment
Esophageal Adenocarcinoma and Gastroesophageal
Junction Adenocarcinoma
Current multimodal treatment of esophageal adenocarcinoma and
gastroesophageal junction adenocarcinoma involves concurrent
perioperative chemotherapy and radiotherapy. The benefit of perioperative chemotherapy as a single modality was definitively demonstrated through the randomized controlled MAGIC trial in 2006
(Table 1). A regimen of three preoperative cycles of epirubicin,
cisplatin, and fluorouracil (5-FU) (ECF) followed by three postoperative cycles of the same was compared with surgery alone in patients
with resectable adenocarcinoma of the stomach, gastroesophageal junction, and lower esophagus, and demonstrated substantial
improvements in both R0 resection rate and 5-year survival (36% vs.
29%) with neoadjuvant chemotherapy. Ychou et al. reported similar
pT1a, N0
pT1b, N0
cT2, N0
cT1b-T2, N+
cT3-T4a, N0-N+
cT4b Definitive chemoradiation
Endoscopic treatment or esophagectomy (T1b)
Esophagectomy or neoadjuvant therapy. Lower
threshold for multimodal neoadjuvant therap
patients with high-risk features (tumor length
≥3cm, poorly differentiated, lymphovascular
invasion on biopsy)
Multimodal neoadjuvant therapy followed by
esophagectomy. Adjuvant immunotherapy if
evidence of residual disease after
esophagectomy
results in 2011 comparing a regimen of three cycles each of preoperative and postoperative cisplatin with 5-FU with surgery alone.
More recently, the FLOT4 trial demonstrated the superiority of four
preoperative and postoperative cycles of docetaxel, oxaliplatin, leucovorin, and 5-FU (FLOT) compared with ECF dosed according to
the MAGIC protocol, with an increase in median survival from 35
months to 50 months with FLOT4. The major downside to these regimens has been the number of patients (almost 50% in some series)
who are unable to complete the postoperative chemotherapy because
of operative complications, patient deconditioning, or intolerance.
Given this limitation, there has been a push toward total neoadjuvant
treatment, with active studies using FLOT4 and FOLFOX (folinic
acid, 5-FU, oxaliplatin) regimens in the preoperative setting. The
use of chemotherapy alone in the neoadjuvant setting tends to be
more common in European and Asian centers, while North American centers tend to favor delivery of chemotherapy with concurrent
radiation, with or without an initial induction phase of chemotherapy in a total neoadjuvant approach, before surgical resection for
locally advanced disease. The use of concurrent chemoradiation in
the neoadjuvant setting for gastroesophageal adenocarcinoma dates
to the 1990s, when Bass et al. performed a randomized controlled
trial comparing surgery alone against a treatment regimen of two
cycles of neoadjuvant 5-FU and cisplatin along with external beam
radiation on days 1 to 5, 8 to 12, and 15 to 19. Patients with adenocarcinoma who received this regimen demonstrated an increase in
overall survival to 76 months compared with 23 months for patients
treated with surgery alone. Tepper et al. replicated these results using
a similar regimen of neoadjuvant cisplatin, 5-FU, and radiotherapy,
demonstrating a 5-year survival of 39% in the multimodal treatment
arm versus 16% in the surgical monotherapy arm (P
tunately, this study was closed early because of poor patient accrual.
In a direct comparison of neoadjuvant chemoradiotherapy to
neoadjuvant chemotherapy alone, Stahl et al. demonstrated significantly higher rates of pathologic complete response and negative
lymph nodes at time of resection in patients who received two cycles
of cisplatin, 5-FU, and folinic acid in conjunction with 30 Gray of
radiation as compared with patients who received 2.5 cycles of neoadjuvant chemotherapy alone. However, this study was also closed
early because of poor patient accrual, and no significant survival
benefit was demonstrated. Using a similar regimen, Burmeister et al.
= 0.002). Unfor-
ESOPHAGUS
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TABLE 1 Summary of Landmark Randomized Controlled Trials Using Traditional Multimodal Treatment of
Esophageal Adenocarcinoma/Gastroesophageal Junctional Adenocarcinoma and Squamous Cell Carcinoma
Overall Survival
Publication
Study
Ancona etal.
1
Year N Histology Control Regimen Experimental Regimen
2001 94 ESCC Surgery alone 2–3 preoperative cycles of cisplatin
and 5-FU
MRC Oesophageal
Cancer Working Party
Cunningham etal.
(MAGIC)
3
2002 802 ESCC Surgery alone 2 preoperative cycles of cisplatin
2
and 5-FU
2006 503 EAC Surgery alone 3 preoperative and 3 postoperative
cycles of epirubicin, cisplatin,
and 5-FU
Lv etal.
4
2010 238 ESCC Surgery alone 2 preoperative cycles of paclitaxel
and cisplatin with concurrent
radiotherapy OR 2 postoperative
cycles of paclitaxel and cisplatin
with concurrent radiotherapy
Boonstra etal.
5
2011 169 ESCC Surgery alone 2–4 preoperative cycles of cisplatin
and etoposide
Ychou etal.
6
2011 224 EAC Surgery alone 3 preoperative and 3 postoperative
cycles of cisplatin and 5-FU
Alderson etal. (0E05)
7
2017 897 EAC 2 preoperative
cycles of cispla-
4 preoperative cycles of epirubicin,
cisplatin, and capecitabine
tin and 5-FU
Yang etal.
(NEOCRTEC5010)
2018 451 ESCC Surgery alone 2 preoperative cycles of vinorelbine
8
and cisplatin with concurrent
radiotherapy
9
Al-Batran (FLOT4)
2016, 2019 716 EAC 3 preoperative
and 3 postop-
4 preoperative and 4 postoperative
cycles of FLOT
erative cycles of
ECF/ECX
van Hagen (CROSS)
2012, 2015,
2021
368 EAC/
ESSC
Surgery alone 5 preoperative cycles of carbopla-
tin, paclitaxel, and concurrent
10,11
radiotherapy
5-FU, Fluorouracil; EAC, esophageal adenocarcinoma; ECF, epirubicin/cisplatin/Fluorouracil; ECX, epirubicin/cisplatin/capecitabine; ESCC, esophageal squa-
mous cell carcinoma; FLOT, docetaxel/oxaliplatin/leucovorin/fluorouracil; MRC, Medical Research Council.
1
Ancona E, Ruol A, Santi S, etal. Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients
with resectable esophageal squamous cell carcinoma. Cancer. 2001;91:2165–2174.
2
Medical Research Council Oesophageal Cancer Working Group. Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a ran-
domised controlled trial. Lancet. 2002;359(9319):1727–1733.
3
Cunningham D, Allum WH, Stenning SP, etal.; MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal
cancer. N Engl J Med. 2006;355(1):11–20.
4
Lv J, Cao XF, Zhu B, Ji L, Tao L, Wang DD. Long-term efficacy of perioperative chemoradiotherapy on esophageal squamous cell carcinoma. World J
Gastroenterol. 2010;16(13):1649–1654.
5
Boonstra JJ, Kok TC, Wijnhoven BP, etal. Chemotherapy followed by surgery versus surgery alone in patients with resectable oesophageal squamous cell car-
cinoma: long-term results of a randomized controlled trial. BMC Cancer. 2011;11:181.
6
Ychou M, Boige V, Pignon JP, etal. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC
and FFCD multicenter phase III trial. J Clin Oncol. 2011;29(13):1715–1721.
7
Alderson D, Cunningham D, Nankivell M, etal. Neoadjuvant cisplatin and fluorouracil versus epirubicin, cisplatin, and capecitabine followed by resection in
patients with oesophageal adenocarcinoma (UK MRC OE05): an open-label, randomised phase 3 trial. Lancet Oncol. 2017;18(9):1249–1260.
8
Yang H, Liu H, Chen Y, etal.; AME Thoracic Surgery Collaborative Group. Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for
Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial. J Clin
Oncol. 2018;36(27):2796–2803.
9
Al-Batran SE, Homann N, Pauligk C, etal.; FLOT4-AIO Investigators. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and
docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019;393(10184):1948–1957.
10
van Hagen P, Hulshof MC, van Lanschot JJ, etal.; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med.
2012;366(22):2074–2084.
11
Shapiro J, van Lanschot JJB, Hulshof MCCM, etal. 2015. Neoadjuvant Chemoradiotherapy plus Surgery versus Surgery Alone for Oesophageal or Junctional
Cancer (CROSS): Long-Term Results of a Randomised Controlled Trial. Lancet Oncol. 16(9):1090–1098.
12
Eyck BM, van Lanschot JJB, Hulshof MCCM, etal.; CROSS Study Group. Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for
Esophageal Cancer: The Randomized Controlled CROSS Trial. J Clin Oncol. 2021;39(18):1995–2004.
(Control vs.
Experimental)
5 year: 22% vs. 34%
Median: 13.3 months
vs. 16.8 months
5 year: 29% vs. 36%
5 year: 33.8% (con-
trol) vs. 43.5% (preoperative) vs. 42.3%
(postoperative)
5 year: 17% vs. 26%
5 year: 24% vs. 38%
Median: 23.4 months
vs. 26.1 months
Median: 66.5 months
vs. 100.1 months
5 year: 36% vs. 45%
5 year: 33% vs. 47%
61
62 MULTIMODALITY THERAPY IN ESOPHAGEAL CANCER
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showed an improvement in histopathologic response in patients who
received neoadjuvant chemoradiotherapy over patients who received
neoadjuvant chemotherapy alone.
More recently, the CROSS trial demonstrated significantly
improved overall and progression-free survival with neoadjuvant
chemoradiotherapy as compared with surgery alone using a regimen
of six cycles of carboplatin and paclitaxel in combination with 41.4
Gray of radiation given in 23 fractions. This survival benefit was
seen in both adenocarcinoma and squamous cell carcinoma, but it
was more pronounced in the latter group, which also demonstrated
a higher rate of pathologic complete response following neoadjuvant therapy. In long-term follow-up of the CROSS trial, 5-year and
10-year survival have been 47% and 38%, respectively. Given the
durable success of this neoadjuvant chemoradiotherapy regimen,
it has become standard-of-care at many centers. Ongoing trials of
additional regimens, including neoadjuvant FOLFOX, neoadjuvant
FLOT, induction chemotherapy before the CROSS regimen, use of
Herceptin for Her2-positive tumors, and proton beam therapy rather
than traditional radiation, are currently underway.
Esophageal Squamous Cell Carcinoma
Treatment of esophageal squamous cell carcinoma with chemotherapy and chemoradiotherapy in conjunction with surgical resection
has been studied for the past several decades. In 2001, a randomized
controlled trial published by Ancona et al. failed to demonstrate an
overall survival benefit with neoadjuvant chemotherapy using two to
three cycles of cisplatin and 5-FU, but did report a significant survival advantage in subgroup analysis among patients whose tumors
responded to preoperative chemotherapy. The overall survival benefit for preoperative chemotherapy in squamous cell carcinoma was
subsequently demonstrated in two separate randomized controlled
trials conducted by the medical research council on esophageal cancer working party and Boonstra et al. using regimens of cisplatin and
5-FU and cisplatin and etoposide, respectively.
Over the past decade, several randomized controlled trials have
demonstrated a survival benefit to preoperative chemoradiotherapy
compared with surgery alone. These studies include the CROSS
trial, the NEOCRTEC5010, and a separate analysis by Lv et al. In
the NEOCRTEC5010 trial, 2 cycles of neoadjuvant vinorelbine
and cisplatin delivered concurrently with 40 Gray of radiation in
20 fractions was compared with surgery alone. In contrast, Lv et
al. randomized patients to either neoadjuvant or adjuvant delivery
of two cycles of cisplatin/paclitaxel concurrently with 40 Gray of
radiation in 20 fractions. Meanwhile, the CROSS trial, as described
earlier, demonstrated the greatest relative benefit for the subgroup of
patients with squamous cell carcinoma, with median survival of 81.6
months in the neoadjuvant group versus 21.1 months in the surgery
alone group. Despite the differences in neoadjuvant regimens used,
all three studies demonstrated a significant benefit to neoadjuvant
chemoradiation in both overall and disease-free survival in patients
with locally advanced squamous cell carcinoma (Table 1).
There have been few published studies directly comparing neoadjuvant chemoradiotherapy to neoadjuvant chemotherapy, though
this is an ongoing area of study. Early results from Wang et al. directly
comparing a regimen of cisplatin and paclitaxel with or without 40
Gray of concurrent radiation have shown an improvement in complete pathologic response among those receiving chemoradiotherapy,
although it remains to be seen whether this will translate into an
overall or disease-specific survival benefit.
Immunotherapy in Neoadjuvant and Adjuvant
Settings
Immunotherapy is an increasingly important tool in medical oncology that utilizes the body’s natural defense mechanisms to fight
cancer cells. Common targets of immunotherapy agents include
the programmed cell death protein (PD-1) and the associated pro-
expressed on activated immune cells, including T cells, B cells, and
myeloid cells, while PD-L1 is expressed on the surface of some cancer cells to trigger immune evasion. When PD-1 is bound to PD-L1,
an immune checkpoint is activated, preventing the T cells from
targeting cancer cells for death. Novel immunotherapeutic medications include monoclonal antibodies that bind either PD-1 on the
surface of T cells (nivolumab, pembrolizumab, and toripalimab) or
PD-L1 on the surface of tumor cells (atezolizumab, avelumab, and
durvalumab) to block this immune checkpoint and thus reactivate
the T-cell–mediated antitumor immune response. This targeted
approach can lead to more effective tumor targeting and cytotoxic
response with less systemic side effects than traditional chemotherapeutic agents.
Although better tolerated than traditional chemotherapy, immunotherapy-related toxicities can occur. Most commonly this involves
an autoimmune response that can affect the gastrointestinal tract,
skin, endocrine glands, and liver. More serious, but less common,
adverse immune responses can include myocarditis, pneumonitis,
and disorders of the central nervous system. These events may require
cessation of immunotherapy and treatment with glucocorticoids.
The benefits of immunotherapy regimens utilizing checkpoint
inhibitors have been demonstrated in several cancers, including
malignant melanoma and non–small cell lung cancer. The efficacy
of these agents as first-line therapy in esophageal adenocarcinoma
has been shown in advanced unresectable disease and in recurrent
or metastatic disease.
Recently, the CheckMate 577 trial demonstrated the efficacy of
immunotherapy in multimodal treatment through use of adjuvant
nivolumab in patients with locally advanced esophageal adenocarcinoma and esophageal squamous cell carcinoma. Patients treated with
total neoadjuvant chemoradiotherapy with residual pathologic disease after resection were randomized to treatment with nivolumab
versus placebo. Patients in the treatment arm demonstrated a significant improvement in median disease-free survival compared with
placebo (22.4 months vs. 11.0 months). The success of this trial has
led to additional studies exploring the potential benefits of immunotherapy in the neoadjuvant setting (Table 2). As the results of these
trials are reported, the multimodal treatment of esophageal cancer,
both adenocarcinoma and squamous cell carcinoma, may change
rapidly in the next several years.
Multimodal Therapy for Recurrent and
Oligometastatic Disease: A New Frontier for
Surgery?
Despite improvements in the treatment of resectable locally advanced
esophageal cancer, patients who present with recurrent or oligometastatic disease continue to have an extremely poor prognosis. In
patients with distant organ metastasis, 5-year survival is less than
5%, even in the setting of aggressive chemotherapy regimens. In an
effort to improve these outcomes, several groups have evaluated the
potential benefit of multimodal therapy in patients with recurrent
and/or oligometastatic disease. For these patients, there is potential
benefit to definitive local therapy (e.g., resection or radiation) to the
oligometastatic site in conjunction with systemic therapy.
Data supporting the local treatment of oligometastatic disease
have been reported by Li et al. In their retrospective analysis of 576
patients with oligometastatic disease, radiotherapy or chemoembolization to the metastatic site were independent factors associated with
improved progression-free and overall survival. Similarly, Port et al.
demonstrated prolonged survival in patients who underwent surgical
resection followed by adjuvant chemoradiation for recurrent nodal
disease or oligometastatic solid organ metastasis as compared with
definitive chemoradiation alone. These results have been replicated
in several other publications demonstrating improved survival in
patients treated with chemoradiotherapy or surgical resection for
recurrent oligometastatic disease in individuals who had previously
undergone esophagectomy. Moreover, the site of oligometastatic
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TABLE 2 Summary of Completed and Active Trials Utilizing Adjuvant and Neoadjuvant Immunotherapy
Regimens
Primary
Study Histology Inclusion Criteria Control Regimen Experimental Regimen
CheckMate 5771EAC/ESSC Neoadjuvant
Placebo Adjuvant nivolumab Disease-free surchemotherapy
with incomplete pathologic
response in
esophagectomy
specimen
FRONTiER
HCHTOG1909
Hong etal.
2
4
ESSC Locally advanced
disease
3
ESSC Locally advanced
disease
ESSC Locally advanced
disease
NA Neoadjuvant chemotherapy
plus nivolumab
Neoadjuvant
Chemotherapy
Neoadjuvant chemotherapy
plus toripalimab
NA Neoadjuvant chemora-
diotherapy plus neoadjuvant pembrolizumab
followed by adjuvant
pembrolizumab
PROCEED
5
EAC/ESSC Locally advanced
disease
NA Neoadjuvant chemora-
diotherapy plus neoadjuvant pembrolizumab
followed by adjuvant
pembrolizumab
Outcome* Status
Completed
vival (11.0 vs.
22.4 months;
P < 0.001)
Dose-limiting
Active trial
toxicity
Event-free
Active trial
survival
Complete patho-
Completed
logic response
(46.1%)
Complete patho-
Active trial
logic response
63
EAC, Esophageal adenocarcinoma; ESCC, esophageal squamous cell carcinoma; NA, not applicable
*Control versus experimental.
1
Kelly RJ, Jaffer A, Ajani JA, Kuzdzal J, etal. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N Engl J Med.
2021;384(13):1191–1203.
2
Yamamoto S, Kato K, Daiko H, etal. Feasibility study of nivolumab as neoadjuvant chemotherapy for locally esophageal carcinoma: FRONTiER
(JCOG1804E). Future Oncol. 2020;16(19):1351–1357.
3
Zheng Y, Liu XB, Sun HB, etal.; written on Henan Cancer Hospital Thoracic Oncology Group (HCHTOG). A phase III study on neoadjuvant chemotherapy
versus neoadjuvant toripalimab plus chemotherapy for locally advanced esophageal squamous cell carcinoma: Henan Cancer Hospital Thoracic Oncology
Group 1909 (HCHTOG1909). Ann Transl Med. 2021;9(1):73.
4
Hong MH, Kim H, Park SY, etal. 2019. A Phase II trial of preoperative chemoradiotherapy and pembrolizumab for locally advanced esophageal squamous
cell carcinoma (ESCC).” J Clin Oncol. 2019;37(15_suppl):4027–4027.
5
Pembrolizumab, Radiotherapy, and Chemotherapy in Neoadjuvant Treatment of Malignant Esophago-Gastric Diseases (PROCEED).” 2017. Clinicaltrials.gov.
February 27, 2017. https://clinicaltrials.gov/ct2/show/NCT03064490.
disease plays a role, with improved survival associated with lung
metastasis as compared with brain or liver metastasis.
Although promising, all of these studies are limited by retrospective study design and/or a lack of randomization. For patients who
present with limited metastatic gastroesophageal junction adenocarcinoma, a survival benefit to neoadjuvant therapy followed by surgical resection of the primary tumor and all metastatic sites has been
shown in the FLOT3 trial. Although there is much still unknown,
these studies indicate a potential benefit to aggressive systemic and
local treatment of limited metastatic and recurrent disease.
complexity of surgery, and many surgeons may feel more comfortable with open surgical approaches in this setting. Frailty, sarcopenia,
and malnutrition limit the ability of patients to complete multimodal
treatment and increase the risk for postoperative complications and
postdischarge institutionalization. This is exacerbated by symptomatic dysphagia, which often accompanies locally advanced esophageal cancers.
To improve the likelihood of successful completion of multimodal therapy, several adjunctive measures have been utilized. First,
there has been a shift toward total neoadjuvant therapy. By giving
all chemoradiotherapy during the preoperative period, delays in
Additional Considerations to Multimodal Therapy
The success of a multimodal approach for the treatment of locally
advanced esophageal cancers, both adenocarcinoma and squamous
cell carcinoma, is dependent on the patient’s ability to tolerate the
effects of chemotherapy and radiotherapy and to recover from major
surgery. Although minimally invasive approaches can decrease surgical morbidity, aggressive neoadjuvant protocols can also increase the
treatment that may occur as a result of postoperative complications
or deconditioning are eliminated. Moreover, total neoadjuvant treatment increases the likelihood of obtaining a complete pathologic
response and can give a better indication of expected prognosis at
the time of surgery. A summary of current neoadjuvant and total
neoadjuvant treatment regimens is included in Table 3.
To improve patient fitness for major surgery, the concept of
prehabilitation has gained traction. Prehabilitation has shown early
64 MULTIMODALITY THERAPY IN ESOPHAGEAL CANCER
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TABLE 3 Summary of Current Neoadjuvant and Total Neoadjuvant Treatment Regimens
Neoadjuvant with Adjuvant
Preoperative Cycles of
Regimen Tumor Type
Chemotherapy
Cisplatin, 5-FU EAC/ESCC 3 cycles of Cisplatin and 5-FU 3 cycles of Cisplatin and 5-FU
FLOT4 EAC 4 Cycles of Docetaxel, Oxaliplatin,
Leucovorin, 5-FU
Total Neoadjuvant
Regimen Tumor Type Induction Chemotherapy Chemoradiation Trial Status
FOLFOX Plus
Radiotherapy
FLOT4 Plus
Radiotherapy
EAC 8 Cycles of Folinic Acid, 5-FU
Oxaliplatin
EAC 8 Cycles of Docetaxel, Oxaliplatin,
Leucovorin, 5-FU
CROSS EAC/ESCC None 41.4 Gray with Concurrent Carboplatin/
EAC, Esophageal adenocarcinoma; ESCC, esophageal squamous cell carcinoma; 5-FU, fluorouracil
1
Ychou M, Boige V, Pignon JP, etal. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC
and FFCD multicenter phase III trial. J Clin Oncol. 2011;29(13):1715–1721.
2
Al-Batran SE, Homann N, Pauligk C, etal.; FLOT4-AIO Investigators. 2019. chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus
fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a
randomised, phase 2/3 trial. Lancet. 2019;393(10184):1948–1957.
3
Roeland E, Kanter K, Jennifer Yon-Li Wo J, etal. 2020. Preliminary analysis of total neoadjuvant therapy for patients with locally advanced gastric (G) and
gastroesophageal (GE) adenocarcinoma. J Clin Oncol. 2020;38:(4_suppl):393–393.
4
Shapiro J, van Lanschot JJB, Hulshof MCCM, etal. 2015. Neoadjuvant Chemoradiotherapy plus Surgery versus Surgery Alone for Oesophageal or Junctional
Cancer (CROSS): Long-Term Results of a Randomised Controlled Trial. Lancet Oncol. 16(9):1090–1098.
5
Eyck BM, van Lanschot JJB, Hulshof MCCM, etal.; CROSS Study Group. Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal
Cancer: The Randomized Controlled CROSS Trial. J Clin Oncol. 2021;39(18):1995–2004.
Postoperative Cycles of
Chemotherapy Chemoradiation
1
4 Cycles of Docetaxel, Oxaliplatin,
Leucovorin, 5-FU
2
50.4 Gray with Concurrent Carboplatin/
Paclitaxel
3
50.4 Gray with Concurrent Carboplatin/
Paclitaxel
4
None
None
Ongoing
Ongoing
Published
Paclitaxel (5 cycles)
5
promise in patients with esophageal cancer and other malignancies
that require major operations and prolonged multimodal treatment
in either the neoadjuvant or adjuvant setting. Often, these multimodal treatments are described as a marathon, with the idea that pretreatment “training” may improve outcomes and reduce associated
morbidity and mortality. Prehabilitation regimens include aerobic
exercise, strength-based exercise, and inspiratory muscle training.
Unfortunately, well-designed studies evaluating the effectiveness of
these interventions are limited at present. The strongest evidence
for use of preoperative training regimens has been reported by
Minella et al. In a randomized controlled trial of patients undergoing
multimodal treatment for esophageal cancer, they demonstrated
a significant improvement in functional capacity both before and
after surgery in the treatment group that underwent preoperative
home-based aerobic and strength training as compared with a control group without prehabilitation. Although prehabilitation seems
instinctively beneficial, additional trials are needed to optimize
training programs and resource allocation.
An additional challenge in the multimodal treatment of esophageal
cancer is the associated difficulty in maintaining adequate nutrition.
Because the stomach is most often used as the conduit for reconstruction after esophagectomy, gastric feeding tubes are generally avoided
in the preoperative setting. Patients who need additional preoperative
or postoperative nutritional supplementation often undergo jejunal
feeding tube placement, either before neoadjuvant therapy, during
neoadjuvant treatment, or at the time of esophagectomy. Less desirable
alternatives include total parenteral nutrition (TPN) or nasoenteral
feeding tubes. The optimal feeding strategy for patients undergoing
esophagectomy for esophageal cancer has been explored in multiple studies. In several randomized controlled trials, jejunostomy
tube feeding demonstrated superiority both to TPN and long-term
nasoenteric tube feeding. Studies comparing enteral feeding without a
jejunostomy tube to jejunostomy tube feeding have had more mixed
results, and the optimal strategy remains unclear. Although jejunal
feeding tube placement certainly benefits a subset of the population,
they are also associated with an up to 30% complication rate. Determining which patients may benefit from a jejunal feeding tube and the
optimal timing of placement is an area of active investigation. For now,
the decision regarding placement of a jejunal feeding tube remains
dependent on specific patient, operative, and institutional factors.
CONCLUSIONS
The past two decades have brought major advances in the treatment
of locally advanced esophageal cancer, including both adenocarcinoma and squamous cell carcinoma. Multimodal therapy involving neoadjuvant chemotherapy or chemoradiotherapy has become
standard-of-care for locally advanced disease and has led to major
improvements in the prognosis of patients with this disease. Outcomes have dramatically improved, and patients and clinicians can
expect a 5-year survival approaching 50% with current regimens.
The role of surgery and localized radiation or radiofrequency ablation in patients with recurrent disease or oligometastatic disease is
an area of active investigation, and there is evidence that multimodal
therapy can benefit well-selected patients within this high-risk
patient subgroup that was previously considered unresectable.
In the next 5 to 10 years, the field is expected to undergo a second
revolution with the addition of immunotherapy to current treatment
regimens in both the adjuvant and neoadjuvant settings. This will
come along with continued refinement and direct comparison of
current in-trial neoadjuvant chemotherapy and chemoradiotherapy
regimens.
ESOPHAGUS
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65
Finally, as the arsenal of the surgical oncologist has grown, there
is even greater need for patient optimization before surgery, as
patients must now endure major surgery involving esophageal resection and reconstruction after completing often-grueling neoadjuvant
regimens, with the potential for additional adjuvant treatments after
recovery from surgery. To reap the maximal benefit from these
ongoing advances in multimodal therapy, concomitant work will be
needed to combat frailty and malnutrition and to maintain patient
quality of life along with enhanced survival.
S u g g e S t e d R e a d i n g S
Al-Batran SE, Homann N, Pauligk C, et al.; FLOT4-AIO Investigators.
2019. chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and
docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubi-
Use of Esophageal
Stents
Matthew D. Grunwald, MD, Anthony N. Kalloo, MD, and
Dmitriy O. Khodorskiy, MD
irst described by French surgeon Leroy D’Etiolles in 1845, esoph-
ageal stenting (ES) was, at its inception, reserved mainly for the
F
palliation of severe dysphagia in advanced esophageal cancer (EC).
Over the years, the use of esophageal stent has steadily increased
with an expansion of its indications to include benign disease.
Improvement in stent design, endoscopic techniques, and complication rates have made it an attractive therapeutic option for patients
with either mechanical or functional dysphagia, perforations, leaks,
or fistulas. ES generally has one of two main goals: (1) to maintain
luminal patency and relieve severe dysphagia in the setting of benign
or malignant strictures and (2) to stave off potentially fatal luminal
contamination of the mediastinum. For patients with debilitating
disease, ES offers the prospect of improved oral intake, symptomatic
relief of dysphagia or aspiration, and the avoidance of morbid surgical interventions.
This chapter reviews the evolution of ES, currently available
stents, most current indications for ES, stent placement techniques,
and complications.
STENTS THROUGH THE AGES
D’Etiolles’ stents, which were made of decalcified ivory, were unfortunately unsuccessful. Over the next 4 decades, several attempts by
the likes of Sir Morrell Mackenzie in England yielded similarly disappointing results. The first successful esophageal stent was designed
by Sir Charters Symonds in 1885. Symonds’ stent, which was blindly
inserted, featured an esophageal tube affixed to a boxwood funnel
by a silver wire and was secured to the ear by a silk thread passing
through the mouth or nose. Over the next decades, as interest in
plastic polymers grew, stent design evolved. The first stents widely
used in the esophagus were constructed from silicon rubber. These
early stents were inserted with the assistance of a rigid esophagoscope but had a high rate of stent misplacement and migration. In
the late 1950s, Celestin successfully palliated a malignant esophageal
stricture using a plastic stent inserted via an open gastrostomy. The
next few years would see an evolution in stent placement technique
as endoscopic tools evolved. In the 1970s, Atkinson introduced an
cin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet.
2019;393(10184):1948–1957.
Eyck BM, van Lanschot JJB, Hulshof MCCM, et al.; CROSS Study Group.
Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for
Esophageal Cancer: The Randomized Controlled CROSS Trial. J Clin
Oncol. 2021;39(18):1995–2004.
Kelly RJ, Jaffer A, Ajani JA, Kuzdzal J, etal. Adjuvant nivolumab in resect-
ed esophageal or gastroesophageal junction cancer. N Engl J Med.
2021;384(13):1191–1203.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines
in Oncology (NCCN Guidelines): Esophageal and Esophagogastric
Junction Cancers. JNCCN. March 2021.
Port JL, Abu Nasar MS, Lee PC, etal. Definitive therapy for isolated esopha-
geal metastases prolongs survival. Ann Thoracic Surg. 2012;94(2):413–419
discussion 419–420.
endoscopically inserted plastic prosthesis. Unfortunately, a significant drawback of the Atkinson stent was its small internal diameter,
which proved rate limiting when patients resumed a regular diet.
High complication rates plagued many of these early plastic endoprostheses. Because of their rigidity and fixed internal as well as
external diameters, most stents required endoscopic dilation, which
invariably led to perforations. Additionally, their inability to conform
intimately to the strictural morphology caused frequent stent migrations requiring intervention. In 1983, the modern era of esophageal
stent innovation was ushered in when Frimberger published the first
description of the endoscopic placement of a self-expanding metal
stent (SEMS) for a patient with a malignant esophageal stricture. In
the 1990s, SEMS grew in popularity, in part fueled by the results of
a series of trials conducted by Knyrim etal., which demonstrated
that SEMS had higher patency rates, successful placement rates, and
a better safety profile than available rigid plastic endoprostheses.
Over the next few years, stent design and materials would continue
to evolve. The modern esophageal stent is self-expanding and made
of either plastic, Nitinol (a metal alloy), or biodegradable material. It
may also come fully or partially covered. Table 1 reviews currently
available stents and their characteristics.
STENT SELECTION
Selecting the appropriate stent for a given lesion—a critical step in
preprocedural planning and a significant determinant of outcome—
requires an understanding of the mechanical and physical properties
of the various stents models (Fig. 1).
The majority of SEMS are made of Nitinol, a nickel-titanium
alloy, that has superelasticity and shape memory. This property
allows a metal’s shape to be easily modulated by small temperature
variations, but there is also a spontaneous return to the original
shape when the temperature is outside of the transformative range.
These unique characteristics are exploited in SEMS as they expand at
body temperature to fit the morphology of a given lesion. Nitinol is
also resistant to corrosion and hypoallergenic. Although biologically
inert, it triggers a mild inflammatory response with resulting fibrosis
that is useful in reducing stent migration. Unfortunately, this same
property can be a major drawback of uncovered SEMS (uc-SEMS),
fostering stent stenosis by allowing fibrotic tissue ingrowth through
the openings in the mesh material. To counter this phenomenon,
fully covered and partially covered stents were developed. These
stents feature proximal and distal ends that remain bare and uncovered to provide additional luminal anchorage. Covered stents are
believed to have less tumor ingrowth but can potentially be more
66 USE OF ESOPHAGEAL STENTS
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TABLE 1 Selected Overview of Currently Available Esophageal Stents and Relevant Characteristics for
Clinical Practice
Diameter Stent
Product Manufacturer Placement Material
Alimaxx-ES Merit Medical OTW Nitinol 12/14/16/18/22 7/10/12 FC
EndoMAXX Merit Medical OTW Nitinol 19/23 7/10/12/15 FC
Choostent M.I. Tech OTW Nitinol 18/20/22/24 6/17 FC
Evolution Cook OTW Nitinol 18/20 8/10/12 FC/PC
HILZO BCM TTS/OTW Nitinol 20/22 10/12/15 FC/PC
Hanarostent M.I. Tech TTS/OTW Nitinol 18/20/22/24 6/8/10/12/15 FC/PC
Niti-S: single-layered Taewoong Medical TTS/OTW Nitinol 16/18/20/22/24/28 6/8/10/12/14/15 FC/PC
Niti-S: double-layered Taewoong Medical OTW Nitinol 16/18/20/22/24/28 6/8/10/12/14/15
SX-ELLA-HV Ella-CS OTW Nitinol 18/20 8.5/11/13.5/15 FC
SX-ELLA-BD Ella-CS OTW Biodegradable 18/20/23/25 6/8/10/13.5 UC
Flexella Plus Ella-CS OTW Nitinol 18/20 8.5/11/13.5/15 FC
Ultraflex Boston Scientific OTW Nitinol 18/23 10/12/15 PC
Wallflex Boston Scientific OTW Nitinol 18/23 10/12/15 FC/PC
Agile Boston Scientific TTS Nitinol 14/18 6.2/10.2/11.9/14.8/ FC/PC
Polyflex Boston Scientific Polyester/silicone FC
Body (mm) Length (cm) Cover
FC + UC
FC, Fully covered; OTW, over-the-wire; PC, partially covered; TTS, through-the-scope; UC, uncovered. Modified from Vermeulen BD, Siersema PD.
Esophageal stenting in clinical practice: an overview. Curr Treat Options Gastroenterol. 2018;16:260–273.
Considering that their internal diameter tends to decrease under
tension, SEPS are easily retrieved endoscopically, making them ideal
for short-term stenting.
Introduced in the mid-2000s, biodegradable stents (BDS) are
mainly used in the setting of benign strictures, as they negate the
need for retrieval. These are made of plaited polydioxanone, a monofilament that undergoes hydrolytic degradation over 8 to 12 weeks.
These maintain their mechanical strength for 4 to 6 weeks.
PATIENT SELECTION
Careful clinical evaluation and characterization of the lesion of interest are necessary to optimize clinical outcome in patients receiving
ES. Baseline assessment of dysphagia, nutritional status, and quality
of life (QOL) will provide a reference point from which the efficacy
of the intervention can be measured. The Dysphagia Scoring Scale
by Ogilvie etal. (Table 2) is a simple and effective tool to assess dys-
phagia in patients with strictures. Combining radiographic modalities such as esophagram, positron emission tomography, computed
tomography (CT), and endoscopy can provide invaluable information about the lesion’s location, size, morphology, and relationship to
adjacent extrinsic structures and thus inform stent selection.
INDICATIONS
The Food and Drug Administration (FDA) has approved ES for the
FIG. 1 Self-expanding metal stent.
susceptible to stent migration, especially in high-risk areas such as at
the distal esophagus.
Self-expandable plastic stents (SEPS) are double-layered, featuring polyester mesh on their external surface with an embedded
silicon layer forming a smooth inner surface. To prevent migration, flared distal and proximal ends facilitate luminal anchorage.
preservation of luminal patency in the setting of intrinsic or extrinsic
malignant strictures, and the occlusion of concurrent esophageal
fistula. In practice, however, the list of lesions amenable to ES has
increased, owing to better stent design, improved safety profile,
and sophisticated endoscopic techniques. In the United States and
other developed nations, stenting for malignant esophageal strictures has decreased because of improved outcomes with single-dose
brachytherapy. Conversely, ES for the management of various benign
conditions, such as refractory benign esophageal strictures (RBES),
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