9 Esophagus 9

9 Esophagus

(Sarcomas are not included.)

9

INTRODUCTION

Occurring more often in males, cancer of the esophagus accounts for 5.5% of all malignant tumors of the gastrointestinal tract and for less than 1% of all cancers in the United States. However, during the past 20 years, there has been a dramatic shift in the epidemiology of esophageal cancer in North America and most Western countries, characterized by a very rapid rise in the incidence of this disease and a marked shift from squamous cell carcinomas occurring pre- dominantly in the middle third and distal esophagus and the esophagogastric (EG) junction. Predisposing factors for squamous cell carcinomas include a high alcohol intake and heavy use of tobacco or nutritional deficiencies of vitamins and minerals. In contrast, EG junction adenocarcinomas arise most frequently in Barrett’s epithelium. The underlying causes for this marked epidemiologic change remain undefined.

Esophageal cancers, regardless of histologic type, may extend over wide areas of the mucosal surface. Squamous cell carcinomas often arise as multifocal tumors, presumably as a result of field carcinogenesis. Adenocarci- nomas may have varying lengths of mucosal and submucosal disease, particu- larly in patients with long segments of Barrett’s mucosa. However, only the depth of penetration into the esophageal wall and nodal status are considered in staging.

Many patients are asymptomatic during the early stages of disease. Early symptoms include those related to gastroesophageal reflux and associated Barrett’s esophagus or odynophagia caused by esophageal ulceration. Unfortu- nately, the most common clinical symptom for all lesions is dysphagia, which occurs with large tumors that obstruct the lumen and deeply invade the esophageal wall. Therefore, most patients already have locally advanced or metastatic disease at diagnosis.

C15.0 Cervical esophagus C15.1 Thoracic esophagus C15.2 Abdominal esophagus C15.3 Upper third of

esophagus

C15.4 Middle third of esophagus C15.5 Lower third of

esophagus

C15.8 Overlapping lesion of esophagus C15.9 Esophagus, NOS

SUMMARY OF CHANGES

• The definitions of TNM and the Stage Grouping for this chapter have not changed from the Fifth Edition.

78

Primary Site. Beginning at the hypopharynx, the esophagus lies posterior to the trachea and the heart, passing through the posterior mediastinum and enter- ing the stomach through an opening in the diaphragm called the hiatus. Figure 9.1 illustrates the anatomical subsites of the esophagus, including the average measurement of each region from the incisors (front teeth).

Histologically, the esophagus has four layers: mucosa, submucosal, muscle coat or muscularis propria, and adventitia. There is no serosa.

16-20 cm Thoracic

C15.0

C15.3

C15.4

C15.5

22-26 cm Tracheal

bifurcation

30-34 cm

38-42 cm Esophagogastric

junction

FIGURE 9.1. The anatomical subsites of the esophagus, including the average measurement of each region from the incisors. The exact measurement is body size/height dependent.

For classification, staging, and reporting of cancer, the esophagus is divided into four regions. Because the behavior of esophageal cancer and its treatment vary with the anatomic divisions, these regions should be recorded and reported separately. The location of esophageal cancer at the time of endoscopy is often measured from the incisors (front teeth).

Cervical Esophagus. The cervical esophagus begins at the level of the lower border of the cricoid cartilage and ends at the thoracic inlet (the suprasternal notch), approximately 18 cm from the upper incisor teeth.

Intrathoracic and Abdominal Esophagus. This region is divided into two por- tions: The upper thoracic portion extends from the thoracic inlet to the level of the tracheal bifurcation, approximately 24 cm from the upper incisor teeth. The midthoracic portion of the esophagus lies between the tracheal bifur- cation and the distal esophagus just above the esophagogastric junction.

The lower level of this portion is approximately 32 cm from the upper incisor teeth.

Lower Thoracic and Abdominal Portion. Approximately 3 cm in length, the lower esophagus also includes the intraabdominal portion of the esophagus and the EG junction, which is located approximately 40 cm from the upper incisor teeth. Most adenocarcinomas arise from the EG junction and involve both the distal esophagus and the proximal stomach. Controversy exists over how to dis- tinguish proximal gastric cancers involving the EG junction from distal esophageal and EG junction adenocarcinomas extending inferiorly to involve the gastric cardia. In the absence of underlying Barrett’s mucosa, making this distinction can be difficult. Siewert has proposed classifying EG junction cancers into types I, II, and III, depending on the relative extent of involvement of either the esophagus or the stomach. Further validation of this classification is needed to determine whether it is reliable for staging or for prognosis. In clinical prac- tice, tumors arising within the EG junction and gastric cardia that have minimal (2 cm or less) involvement of the esophagus are considered primary gastric cancers.

Regional Lymph Nodes. Figure 9.2 illustrates the regional lymph nodes of the esophagus. Specific regional lymph nodes are listed as follows:

Cervical esophagus Scalene Internal jugular Upper and lower cervical Periesophageal

Supraclavicular

Intrathoracic esophagus—upper, middle, and lower Upper periesophageal (above the azygous vein) Subcarinal

Lower periesophageal (below the azygous vein)

9

80

Lower esophageal (below the azygous vein) Diaphragmatic

Pericardial Left gastric Celiac

Involvement of more distant lymph nodes (such as cervical or celiac axis nodes for intrathoracic tumors) is currently considered distant metastasis (M1a). However, recent analyses suggest that extensive nodal disease is associ- ated with a better overall survival than visceral metastases and with an approx- imately 10% chance of cure at 5 years after surgical resection. On this basis, it has been suggested that the involvement of distant lymph nodes be classified as

C77.0

Cervical esophagus

Intra-thoracic esophagus C77.1, 2

(partly)

FIGURE 9.2. For intrathoracic tumors involvement of more distant lymph nodes (such as cervical or celiac axis nodes) is currently considered distant metastasis (M1a).

N2 disease rather than M1a, but such a change in classification requires further study.

The nomenclature used to indicate the location of involved lymph nodes has most frequently been that shown above, which provides a general anatom- ical description. More recently, a lymph node map that extends the nomencla- ture and numbering system used for the staging of non–small cell lung cancer has been developed and used in clinical trials. This map, which is shown in Figure 9.1, makes possible the more precise identification of involved lymph nodes.

Metastatic Sites. The liver, lungs, and pleura are the most common sites of distant metastases. Occasionally, the tumor may extend directly into mediasti- nal structures before distant metastasis is evident. This occurs most frequently with tumors of the intrathoracic esophagus, which may extend directly into the aorta, trachea, and pericardium.

DEFINITIONS Primary Tumor (T)

TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ

T1 Tumor invades lamina propria or submucosal (Figure 9.3) T2 Tumor invades muscularis propria (Figure 9.3)

T3 Tumor invades adventitia (Figure 9.4) T4 Tumor invades adjacent structures (Figure 9.5)

Regional Lymph Nodes (N)

NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis

N1 Regional lymph node metastasis (Figures 9.6, 9.7, 9.8, 9.9)

Distant Metastasis (M)

MX Distant metastasis cannot be assessed M0 No distant metastasis

M1 Distant metastasis (Figure 9.6)

Tumors of the lower thoracic esophagus:

M1a Metastasis in celiac lymph nodes (Figure 9.7) M1b Other distant metastasis (Figure 9.7)

Tumors of the midthoracic esophagus:

M1a Not applicable

Mlb Nonregional lymph nodes and/or other distant metastasis (Figure 9.8)

Tumors of the upper thoracic esophagus:

M1a Metastasis in cervical nodes (Figure 9.9) M1b Other distant metastasis (Figure 9.9)

9

82

T1T2 Epithelium Muscularis mucosaeLamina propria Submucosa Muscularis propria Adventitia

Mucosa FIGURE9.3.On the left,two views ofT1,tumor which is defined as tumor that invades lamina propria (left side ofT1 illustration) or submucosa (right side ofT1 illustration).T2 tumor invades muscularis propria as illustrated on the right.

9

T3

FIGURE 9.4. T3 tumor invades adventitia.

T4

Figure 9.5. T4 tumor that invades adjacent structures (tracheobronchial involvement is shown).

Cervical including supra-clavicular

Mediastinal

Celiac

Perigastric N1

Carcinoma of Cervical Esophagus

M1

Figure 9.6. For carcinomas of the cervical esophagus, lymph node involvement outside the cervical and supraclavicular region, as illustrated here in the mediastinal region, is defined as M1 disease.

9

Cervical including supra-clavicular

Mediastinal

Celiac

Perigastric M1b

Carcinoma of Lower Thoracic Esophagus

N1

M1a

Figure 9.7. Lymph node involvement outside the regional lymph nodes of the lower thoracic esophagus, as illustrated here, is defined as M1a for metastasis in celiac lymph nodes and M1b for other distant metastasis.

86

Cervical including supra-clavicular

Mediastinal

Celiac

Perigastric M1b

Carcinoma of Mid-thoracic Esophagus

N1

M1b

Figure 9.8. In carcinoma of the mid-thoracic esophagus, any nonregional lymph node involvement and/or other distant metastasis is defined as M1b disease.

9

Cervical including supra-clavicular

Mediastinal

Celiac

Perigastric M1a

Carcinoma of Upper Thoracic Esophagus

N1

M1b

Figure 9.9. Lymph node involvement outside the regional lymph nodes of the upper thoracic esophagus, as illustrated here, is defined as M1a for metastasis in cervical lymph nodes and M1b for other distant metastasis.

88

0 Tis N0 M0

I T1 N0 M0

IIA T2 N0 M0

T3 N0 M0

IIB T1 N1 M0

T2 N1 M0

III T3 N1 M0

T4 Any N M0

IV Any T Any N M1

IVA Any T Any N M1a

IVB Any T Any N M1b