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ESOPHAGUS
artery
https://t.me/med1917
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
*DVWULFWXEH
FIG. 4 Creation of the conduit. (From Khatri V. Atlas of Advanced Operative
Surgery. Philadelphia: Elsevier; 2012.)
'HIODWHGOXQJ
'LYLGHGD]\JRVYHLQ
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
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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, etal. 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, etal. 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 etal.
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 etal.
(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 etal.
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 etal.
5
2011 169 ESCC Surgery alone 2–4 preoperative cycles of cisplatin
and etoposide
Ychou etal.
6
2011 224 EAC Surgery alone 3 preoperative and 3 postoperative
cycles of cisplatin and 5-FU
Alderson etal. (0E05)
7
2017 897 EAC 2 preoperative
cycles of cispla-
4 preoperative cycles of epirubicin,
cisplatin, and capecitabine
tin and 5-FU
Yang etal.
(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, etal. 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, etal.; 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, etal. 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, etal. 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, etal. 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, etal.; 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, etal.; 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, etal.; 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, etal. 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, 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.
(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 etal.
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, etal. 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, etal. 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, etal.; 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, etal. 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, etal. 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, etal.; 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, etal. 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, etal. 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, 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.
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, etal. 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, etal. 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 etal., 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 etal. (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),