Gastroenterology and Hepatology Board Review: Pearls of Wisdom, Third Edition

Section II ESOPHAGUS

CHAPTER 12. Esophageal Tumors

Eric B. Goosenberg, MD

Image True/False: Esophageal papillomas have been associated with squamous cell cancer and should be removed endoscopically when identified.

True.

Image True/False: Esophageal inlet patches are biologically similar to Barrett’s esophagus and should be managed (eg, undergo routine endoscopic surveillance) similarly.

False.

Image What are risk factors for squamous cell carcinoma of the esophagus?

Excessive alcohol use, smoking (of cigarettes more so than cigars or pipes) or chewing tobacco, ingestion of nitrosamines (from grilled meats, etc), pre-existing head and neck cancer, radiation exposure from prior cancer treatment, history of lye-induced esophageal strictures, long-standing achalasia, Plummer–Vinson syndrome, and tylosis. Tobacco and alcohol increase the risk in a dose-dependent manner and use of both is associated with a much higher incidence than with either substance alone. For unknown reasons, neither smoking nor alcohol is associated with esophageal cancer outside the United States. Family history only seems to be significant in regions of higher incidence of esophageal cancer.

Image What are the most significant risk factors for adenocarcinoma of the esophagus?

Barrett’s esophagus is the strongest risk factor. Severe gastroesophageal reflux disease (independent of the presence of Barrett’s), smoking, obesity (especially central obesity), older age, male sex, and low dietary intake of fruits and vegetables are other risk factors in the United States. Alcohol ingestion does not appear to be a risk factor, and wine ingestion may be protective.

Image What demographic features are associated with squamous cell esophageal cancer in Americans?

Males are more often affected than are females (ratio 3:1), African-Americans more often than Caucasians (ratio 4:1) and individuals of lower socioeconomic status have a greater incidence.

Image True/False: The incidence and mortality related to esophageal cancer are highest in portions of China, Iran, and Africa.

True. Environmental risk factors such as ingestion of foods and drinks (particularly tea) of higher temperatures are assumed but not proven to be responsible.

Image True/False: People with tylosis have approximately a 50% likelihood of developing esophageal cancer during their lifetime.

False. This rare condition presents with hyperkeratosis of the skin on the palms and soles and papillomas of the esophagus that progress to squamous cell cancer in virtually 100% of cases.

Image How does achalasia influence the age of onset of esophageal cancer?

It occurs 10 to 20 years earlier (mean age 52 years) than in patients without achalasia. The esophageal malignancy is squamous cell carcinoma in over 90% of achalasia patients and typically occurs about 20 years after the diagnosis of achalasia is made. The risk of squamous cell carcinoma in achalasia is about 10- to 30-fold greater than in the general population.

Image When squamous cell esophageal cancer is diagnosed after the development of related symptoms, what can be predicted about its stage?

Distant metastases will be present in 25%–30% of cases, lymph nodes will be affected in up to two-thirds of cases and it will be limited to the mucosa in only 2% of cases.

Image What are the most common causes of hematemesis in patients with known esophageal cancer?

Tumor ulceration and aorto-esophageal fistulization.

Image True/False: The incidence of squamous cell carcinoma of the esophagus has fallen dramatically over the past several decades, such that squamous cell carcinoma and adenocarcinoma are now equally common in the United States.

False. While it is true that these two cancers of the esophagus are now of roughly equal frequency in the United States, the incidence of squamous cell carcinoma has remained steady, but adenocarcinoma has increased markedly.

Image What endoscopic tests can be done to distinguish benign from malignant esophageal masses?

Endoscopic biopsies and brush cytology are the most commonly used techniques for confirmation of cancer. Endoscopic ultrasound (EUS) with or without fine needle aspiration is particularly useful. Endoscopically applied vital stains such as Lugol’s solution may be helpful (with only normal tissue taking up stain) and concurrent magnification endoscopy may allow detection of features suggestive of metaplasia or dysplasia in Barrett’s mucosa. Newer techniques such as optical coherence tomography (OCT) and spectroscopy have shown promise but are not widely available in clinical practice.

Image True/False: When Barrett’s esophagus without dysplasia is initially diagnosed and surveillance is planned, endoscopy should initially be repeated in 3 years.

False. Endoscopy should be repeated in 1 year to confirm the absence of dysplasia. If this is confirmed, then the current recommendation is that endoscopy should be repeated at 3-year intervals.

Image What tests should be done in the initial diagnosis and staging of esophageal cancer?

Initial diagnosis should be made by endoscopy with biopsies (six are recommended). Cytologic brushings may be helpful in stenotic tumors where biopsies may be difficult to obtain. A barium swallow may be helpful in demonstrating high-grade luminal obstruction and in identifying esophagotracheal fistulae. A CT scan of the chest and upper abdomen should be done to look for distant metastatic disease or for contiguous involvement of adjacent structures. If distant disease is not detected, then positron emission tomography (PET) scanning is often utilized if available. PET scanning or combination “PET-CT” scans will identify distant metastatic disease in up to 20% of patients who otherwise might have unwarranted surgery based on the absence of metastases on CT scanning alone. If metastatic disease is not found with CT or PET scanning, then EUS is employed for local staging and, if necessary, for deeper biopsies of the primary tumor or of suspicious paraesophageal or celiac lymph nodes.

Image True/False: If EUS demonstrates a very early tumor that is small (< 2 cm), polypoid, elevated, and appears to be a T1a tumor (confined to the mucosa), then endoscopic mucosal resection (EMR) can be performed.

True. EMR in this scenario may be curative in removing the tumor in its entirety, or may allow determination that the muscularis mucosae are involved, necessitating more aggressive treatment.

Image What are the roles of EUS in esophageal cancer?

Radial endosonography can determine the depth of esophageal wall invasion of cancer (T stage in the TNM system), the presence or absence of malignant paraesophageal lymph nodes (N stage) and to evaluate for celiac adenopathy (part of the M stage). Linear array instruments can be used to perform fine needle aspirates of submucosal lesions and of accessible lymph nodes. Endoscopic catheter probes are also available and may be used instead of or in addition to conventional EUS, particularly in the staging of stenotic tumors. The role of EUS to evaluate for evidence of malignancy in Barrett’s esophagus is controversial. It does not seem to be an effective technique in evaluating the esophagus after radiation therapy because fibrosis can be difficult to distinguish from recurrent or residual cancer.

Image What are the histologic equivalents of the five esophageal layers found by endoscopic ultrasonography?

Image

Image What is the likely ultrasound T stage of the stenotic esophageal cancer shown in the figure?

Image

Figure 12-1 See also color plate.

Stenotic tumors are usually locally advanced—either T3 (invading the adventitia and paraesophageal fat) or T4 (invading adjacent organs).

Image What is the EUS appearance (echogenicity, layer, or layers) of esophageal varices?

Anechoic lesion of the submucosa (third ultrasonic layer).

Image What is the EUS appearance (echogenicity, layer, or layers) of an esophageal lipoma?

Hyperechoic lesion of the submucosa (third layer).

Image What is the EUS appearance (echogenicity, layer, or layers) of an esophageal leiomyoma or leiomyosarcoma?

Hypoechoic lesion of the muscularis propria (fourth layer).

Image What is the EUS appearance (echogenicity, layer, or layers) of an esophageal gastrointestinal stromal tumor (GIST)?

Fewer than 1% of GIST tumors occur in the esophagus (up to 60% occur in the stomach and 25%–30% are in the jejunum or ileum), but their EUS appearance is the same as that of a smooth muscle tumor, that is, an hypoechoic lesion of the muscularis propria (fourth layer).

Image True/False: Smooth muscle tumors of the esophagus that cause dysphagia and bleeding are virtually always malignant (leiomyosarcomas).

False. These symptoms, as well as chest pain, are indicators of a large tumor, but not necessarily of malignancy.

Image How do squamous cell carcinomas and adenocarcinomas of the esophagus differ in terms of their natural history?

Squamous cell carcinoma is more likely to be widespread at the time of diagnosis. Adenocarcinoma tends to progress by local extension. Accordingly, surgery has a more limited role in squamous cell carcinoma.

Image Which form of endoscopic palliation would be most useful in the management of a tight stricture due to a leiomyosarcoma of the mid-esophagus?

Stent placement is the only treatment mode that is useful in extrinsic stenoses due to submucosal or extrinsic tumors (such as lung cancer). Dilatation is usually ineffective, typically providing only transient relief of symptoms. Thermal devices have no role.

Image Which form of endoscopic palliation would be most useful in the management of an esophageal carcinoma causing severe dysphagia before initiation of neoadjuvant chemotherapy and radiation?

Dilatation with either Savary or hydrostatic balloon dilators often provides effective palliation before and during therapy. If there is a significant volume of exophytic tumor causing luminal stenosis, then a potentially removable self-expandable metal or plastic stent, or photodynamic therapy (PDT) are options. Fully covered metal stents can be removed, although they have a tendency to migrate. PDT has generally superceded endoscopic laser therapy because the former is easier to perform and is better tolerated.

Image True/False: The palliative method shown in the figure represents the preferred management of tracheoesophageal fistulae in esophageal cancer.

Image

Figure 12-2 See also color plate.

True. Covered self-expanding metal stents are probably the best intervention in this setting. Low doses of radiation may also be effective, although larger doses may result in enlargement of a fistula.

Image What are the most common complications of radiation therapy to the esophagus?

Esophagitis (early) and esophageal strictures (late).

Image What potentially curative endoscopic treatment options are available for early-stage esophageal cancer?

EMR and PDT.

Image How should nutritional support be provided to a patient with a resectable esophageal cancer during neoadjuvant therapy?

In patients who cannot eat, a feeding jejunostomy tube is preferable to a gastrostomy tube because it will not affect the segment of the gut that needs to be mobilized (eg, gastric pull-up) after esophagectomy.

Image True/False: Columnar epithelium with specialized intestinal metaplasia in the esophagus is associated with an increased risk of adenocarcinoma.

True. This type of metaplastic mucosa is characterized histologically by the presence of goblet cells and defines “Barrett’s esophagus.”

Image True/False: Short-segment Barrett’s esophagus is not associated with an increased risk of adenocarcinoma.

False. Short-segment Barrett’s esophagus has been shown to be a risk factor for adenocarcinoma, although it appears to be of lesser relative risk compared to long-segment Barrett’s (3 cm or longer).

Image Describe an appropriate approach for a patient who has Barrett’s esophagus and low-grade dysplasia (LGD)?

Biopsies should be reviewed by a second expert pathologist and then, if the finding of LGD is confirmed, endoscopy with multiple biopsies should be repeated within 6 months. More recently, treatment with radiofrequency ablation (RFA) has shown good results with elimination of the dysplasia; however, the low rate of progression from low-grade dysplasia to cancer (less than 1% per patient-year) makes the subgroup that should be so treated difficult to determine.

Image Describe an appropriate approach for a patient who has Barrett’s esophagus and high-grade dysplasia (HGD).

Confirmation of the diagnosis by a second expert pathologist is the first step. Because of the strong possibility that adenocarcinoma will already be present in patients whose biopsies show only HGD, patients who are surgical candidates should consider esophagectomy. Patients who refuse or cannot tolerate surgery should either be surveyed endoscopically every 3 months or undergo ablation with radio frequency ablation (RFA) or photodynamic therapy (PDT), preceded by EMR if there is a nodule with HGD or even intramucosal cancer.

Image True/False: A potential limitation of ablative therapy in the management of Barrett’s esophagus is that nonneoplastic mucosa may be restored over persistent submucosal neoplasia.

True.

Image What is the likelihood that endoscopic biopsies showing Barrett’s esophagus and HGD but no cancer will contain cancer in an esophagectomy specimen?

Up to 40%, historically. Recent data suggest the incidence to be much lower.

Image What should be offered to a patient with nondysplastic Barrett’s esophagus to reduce the likelihood of developing cancer?

At present, only endoscopic surveillance, every 3 years, can be offered. Currently, there is no convincing evidence that any antireflux therapy will eliminate Barrett’s esophagus or the risk of adenocarcinoma. The role of ablative therapy in this setting remains controversial given the low risk of progression, but it is generally not recommended.

• • • SUGGESTED READINGS • • •

Wang KW, Wingkeesong M, Buttar NS. American Gastroenterological Association Technical Review on the Role of the Gastroenterologist in the Management of Esophageal Carcinoma. Gastroenterology. 2005;128:1471-1505.

Spechler SJ, Pharma P, Souze FR, Inadomi JM, Shaheen NJ. American Gastroenterological Association Technical Review on the Management of Barrett’s Esophagus. Gastroenterology. 2011;140(3):e18-e52.