Endoscopic ultrasound (EUS) is a minimally invasive advanced imaging procedure using high-frequency sound waves to produce detailed images of the esophageal wall with fine-needle aspiration to biopsy adjacent lymph nodes. The role of EUS is well established in patients with locally advanced Barrett esophagus neoplasia. The utility of EUS in the evaluation of Barrett esophagus patients is controversial. This is a review of the evidence using EUS in BE patients. The assessment is that EUS may be a powerful tool in managing patients with BE neoplasia.
Key points
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Endoscopic ultrasound (EUS) is safe and widely available.
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Evidence suggests that EUS can accurately change the management strategy in 14% of patients referred for evaluation of Barrett neoplasia.
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EUS has suboptimal specificity and a high rate of overstaging early tumors.
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EUS is especially useful to exclude advanced disease and nodal involvement.
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Cost-effectiveness of EUS for this indication has not been established.
Introduction
Esophageal adenocarcinoma (EAC) continues to be a major cause of cancer mortality in Western populations. The incidence of EAC seems to be increasing. Although several risk factors have been identified for EAC, Barrett esophagus (BE), which is intestinal metaplasia of squamous esophageal mucosa, is the only treatable factor. The risk of progression to EAC among patients with BE varies by degree to dysplasia. As with most cancers, local staging of neoplasia is of critical importance and dictates treatment options and patient outcomes. The current staging of EAC follows the TNM staging ( Table 1 ). Superficial cancers are those arising in the mucosa (T1m) or submucosa (T1sm). Current practice includes endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) for patients with superficial neoplasia (T1m) and some T1sm ( Fig. 1 ). This is followed by radiofrequency ablation (RFA) to eradicate the remaining BE segment. Such therapy, referred to as endoscopic eradication therapy (EET), has been shown efficacious and safe in management of those superficial cancer patients. EET, however, is not risk-free. There are risks to EMR and ESD, including perforation, bleeding, and stricture formation. Thus, among patients with advanced disease, T1sm or beyond or N1 or beyond, EMR and ESD are not indicated. Instead, these patients are normally referred to surgeons for consideration of esophagectomy with or without neoadjuvant chemoradiotherapy. Accurate staging for disease is, therefore, essential. Cross-sectional imaging with modalities, such as CT and MRI, are limited in their ability to stage EAC at local levels, especially in early stages. Therefore, EUS has been proposed and used as a better diagnostic test for this indication. This review discusses the usefulness of EUS in identifying those patients and better examining the role of EUS for this frequently encountered clinical scenario. Given the availability of several studies on the topic, best evidence-based recommendations are used to inform the discussion and conclusions.
| Primary Tumor (T) | |
|---|---|
| TX | Primary tumor cannot be assessed |
| T0 | No evidence of primary tumor |
| Tis | High-grade dysplasia |
| T1 | Tumor invades lamina propria, muscularis mucosae, or submucosa |
| T1a or T1m | Tumor invades lamina propria or muscularis mucosae |
| T1b or T1sm | Tumor invades submucosa |
| T2 | Tumor invades muscularis propria |
| T3 | Tumor invades adventitia |
| T4 | Tumor invades adjacent structures |
| T4a | Resectable tumor invading pleura, pericardium, or diaphragm |
| T4b | Unresectable tumor invading other adjacent structures, such as the aorta, vertebral body, and trachea |
| Regional Lymph Nodes (N) | |
|---|---|
| NX | Regional lymph node(s) cannot be assessed |
| N0 | No regional lymph node metastasis |
| N1 | Metastasis in 1–2 regional lymph nodes |
| N2 | Metastasis in 3–6 regional lymph nodes |
| N3 | Metastasis in 7 or more regional lymph nodes |
| Distant Metastasis (M) | |
|---|---|
| M0 | No distant metastasis |
| M1 | Distant metastasis |
Introduction
Esophageal adenocarcinoma (EAC) continues to be a major cause of cancer mortality in Western populations. The incidence of EAC seems to be increasing. Although several risk factors have been identified for EAC, Barrett esophagus (BE), which is intestinal metaplasia of squamous esophageal mucosa, is the only treatable factor. The risk of progression to EAC among patients with BE varies by degree to dysplasia. As with most cancers, local staging of neoplasia is of critical importance and dictates treatment options and patient outcomes. The current staging of EAC follows the TNM staging ( Table 1 ). Superficial cancers are those arising in the mucosa (T1m) or submucosa (T1sm). Current practice includes endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) for patients with superficial neoplasia (T1m) and some T1sm ( Fig. 1 ). This is followed by radiofrequency ablation (RFA) to eradicate the remaining BE segment. Such therapy, referred to as endoscopic eradication therapy (EET), has been shown efficacious and safe in management of those superficial cancer patients. EET, however, is not risk-free. There are risks to EMR and ESD, including perforation, bleeding, and stricture formation. Thus, among patients with advanced disease, T1sm or beyond or N1 or beyond, EMR and ESD are not indicated. Instead, these patients are normally referred to surgeons for consideration of esophagectomy with or without neoadjuvant chemoradiotherapy. Accurate staging for disease is, therefore, essential. Cross-sectional imaging with modalities, such as CT and MRI, are limited in their ability to stage EAC at local levels, especially in early stages. Therefore, EUS has been proposed and used as a better diagnostic test for this indication. This review discusses the usefulness of EUS in identifying those patients and better examining the role of EUS for this frequently encountered clinical scenario. Given the availability of several studies on the topic, best evidence-based recommendations are used to inform the discussion and conclusions.
| Primary Tumor (T) | |
|---|---|
| TX | Primary tumor cannot be assessed |
| T0 | No evidence of primary tumor |
| Tis | High-grade dysplasia |
| T1 | Tumor invades lamina propria, muscularis mucosae, or submucosa |
| T1a or T1m | Tumor invades lamina propria or muscularis mucosae |
| T1b or T1sm | Tumor invades submucosa |
| T2 | Tumor invades muscularis propria |
| T3 | Tumor invades adventitia |
| T4 | Tumor invades adjacent structures |
| T4a | Resectable tumor invading pleura, pericardium, or diaphragm |
| T4b | Unresectable tumor invading other adjacent structures, such as the aorta, vertebral body, and trachea |
| Regional Lymph Nodes (N) | |
|---|---|
| NX | Regional lymph node(s) cannot be assessed |
| N0 | No regional lymph node metastasis |
| N1 | Metastasis in 1–2 regional lymph nodes |
| N2 | Metastasis in 3–6 regional lymph nodes |
| N3 | Metastasis in 7 or more regional lymph nodes |
| Distant Metastasis (M) | |
|---|---|
| M0 | No distant metastasis |
| M1 | Distant metastasis |
Management goals
Defining the exact management goals for EUS in patients with BE is paramount to this discussion. In the performance of EUS for patients with BE, the authors and colleagues believe that the main goal is the accurate identification of advanced disease. If a patient has superficial disease, then EMR is indicated and potentially provides curative treatment. If a patient has advanced disease, however, the only curative option may be esophagectomy. In such patients, EMR is not indicated and may increase risk of morbidity from adverse outcomes like perforation or bleeding. Therefore, being able to stratify patients based on their disease stage is essential. Accurate identification of advanced disease deals with 2 specific issues:
- 1.
Definition of advanced disease
- 2.
Test characteristics, which include sensitivity, specificity, and accuracy
Definition of Advanced Disease
EAC is staged based on the TNM classification (see Table 1 ). The difference between mucosal (T1m) and submucosal (T1sm) disease is subtle and requires high image resolution ( Fig. 2 ). Cross-sectional imaging modalities, such as CT and MRI, do not have the sufficient imaging resolution to stage EAC at the T1 to T1sm levels. For this reason, EUS, which has a higher resolution, has been used to stage EAC for years. Most experts agree that neoplasia invasive into the submucosa, or involvement of lymph nodes, classifies as advanced disease. In those patients, EMR is not curative, and esophagectomy with or without neoadjuvant chemoradiotherapy is the only curative option. There continues to be some debate on the classification of T1sm. Some expert pathologists can subdivide the submucosa into 3 zones. Sm1 is defined at the upper third of the submucosa within less than 500 μm. In patients with T1sm1, EMR may be curative. This approach has been mostly accepted in several European centers. In the United States, most centers refer patients to surgery on finding T1sm. For the purposes of this review, advanced disease is defined as disease at or beyond T1sm or N1.
Related posts:
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The Troublesome Epidemiology of Barrett’s Esophagus and Esophageal Adenocarcinoma
Who Deserves Endoscopic Screening for Esophageal Neoplasia?
Management of Nodular Neoplasia in Barrett’s Esophagus
Radiofrequency Ablation of Barrett’s Esophagus
Radiofrequency Ablation of Barrett’s Esophagus
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