Endoscopic Cancer Screening and Surveillance

Esophagus

• 3.

  Endoscopic cancer screening of the esophagus is primarily undertaken for what two types of esophageal cancers? What risk factors are associated with these two types of cancers?

  • Esophageal adenocarcinoma (EAC) is the most common type of esophageal cancer in the United States; it is increasing in prevalence and is highly associated with BE, gastroesophageal reflux disease (GERD), and obesity.

  • Squamous cell carcinoma (SCC) is a less frequent cause of esophageal cancer in the United States. The risk factors for esophageal SCC include alcohol, tobacco smoking, achalasia, caustic injury, tylosis, prior or concurrent head and neck SCC, and Plummer-Vinson syndrome. A new review links infection with human papillomavirus to a threefold greater chance of developing esophageal SCC.

• 4.

  What is Barrett Esophagus (BE, metaplasia)? Is endoscopic screening and surveillance for BE necessary?

  BE is the development of specialized intestinal metaplasia (SIM) of the distal tubular esophagus, which has been identified as a premalignant precursor to EAC. The incidence of EAC is currently increasing at a rate greater than that of any other cancer in the Western world. The 5-year survival rate for late-stage EAC is poor and the only hope for improved survival is early detection. Screening for BE remains controversial, however, because of a lack of randomized controlled trials documenting a decreased effect on mortality.

• 5.

  Which patients should undergo endoscopic screening for BE?

  Screening for BE in the general population is not recommended at this time but should be considered in selected male patients older than 50 with frequent heartburn (several times per week) and long-standing GERD. The primary purpose of surveillance of BE is to identify dysplasia and early EAC. Patients at increased risk for BE are typically white men older than 50 years and those with nocturnal reflux. After a negative screening examination, surveillance endoscopy is not indicated.

• 6.

  What techniques are used to perform endoscopic screening in BE?

  A complete direct visual examination (esophagogastroduodenoscopy [EGD]) of the esophagus with high-resolution and high-definition white-light endoscopy is the standard for endoscopic screening of BE. Esophageal capsule endoscopy may provide a noninvasive assessment of suspected BE; however, studies demonstrate varying sensitivity with the device.

• 7.

  How is BE histologically graded?

  BE is histologically graded as:

  • Nondysplastic

  • Indeterminate-grade dysplasia

  • Low-grade dysplasia (LGD)

  • High-grade dysplasia (HGD)

• 8.

  What is the rationale for endoscopic surveillance in BE?

  Decisions about endoscopic surveillance and treatment for BE are based on the presumption that SIM may advance to LGD, that LGD may advance to HGD, and that HGD may progress to intramucosal carcinoma. BE surveillance programs attempt to detect adenocarcinoma or HGD at an earlier, potentially curable, stage and have been shown to significantly improve 5-year survival compared with similar patients not undergoing routine endoscopic surveillance.

• 9.

  What techniques are used to perform endoscopic surveillance in BE?

  Surveillance endoscopy should only be performed after patients have their reflux aggressively controlled with a proton pump inhibitor because any inflammation may interfere with the endoscopic and microscopic identification of dysplasia. Endoscopic surveillance involves systematic four-quadrant biopsies at 1- to 2-cm intervals along the entire length of the Barrett segment. Biopsies should also specifically target any luminal irregularity in the Barrett segment (e.g., ulceration, erosion, nodule, or stricture) because there is an association of such lesions with underlying cancer. The use of jumbo biopsy forceps may improve the yield of the biopsies and should be considered, especially in patients with previous dysplasia. Newer brushing techniques (WATS, FISH etc) may provide greater sensitivity compared to biopsy for detecting high-grade lesions/dysplasia and neoplasia.

• 10.

  How often should patients with BE undergo endoscopic surveillance?

  Endoscopic surveillance intervals are determined by the presence and grade of dysplasia found in patients with BE ( Table 62-1 ).

  Table 62-1

  2012 ASGE Guidelines: Endoscopic Management Strategies for Barrett’s Esophagus

  Histologic Characteristics	Surveillance	Intervention options
  Nondysplastic Barrett’s esophagus	Consider no surveillance. If surveillance is elected, perform EGD every 3 to 5 years with 4-quadrant biopsies every 2 cm.	Consider endoscopic ablation in select cases.
  Indeterminate for dysplasia	Clarify presence and grade of dysplasia with expert GI pathologist. Increase antisecretory therapy to eliminate esophageal inflammation. Repeat EGD and biopsy to clarify dysplasia status.	No therapeutic intervention recommended
  Low-grade dysplasia	Confirm with expert GI pathologist. Repeat EGD in 6 months to confirm LGD. Perform surveillance EGD every year, 4-quadrant biopsies every 1 to 2 cm.	Consider endoscopic resection or ablation.
  High-grade dysplasia	Confirm with expert GI pathologist. Consider surveillance EGD every 3 months in select patients, 4-quadrant biopsies every 1 cm.	Consider endoscopic resection or mucosal ablation. Consider EUS for local staging and lymphadenopathy. Consider surgical resection.

  EGD, esophagogastroduodenoscopy; EUS, endoscopic ultrasound; GI, gastrointestinal; LGD, low-grade dysplasia.

• 11.

  How is LGD managed in patients with BE?

  LGD must be confirmed on a repeat EGD within 6 months, and an expert GI pathologist is also required to review the biopsy samples before the initiation of annual endoscopic surveillance. Surveillance endoscopy continues until there is no dysplasia on two consecutive endoscopic examinations. Some experts assert that aggressive ablation of LGD is an option and patients can be reassured that 60% of patients with LGD will regress to no dysplasia after a mean follow-up of 4 years.

• 12.

  How do you manage HGD in patients with BE?

  HGD is associated with 30% risk of developing EAC. If HGD is confirmed by an expert GI pathologist, there is currently no agreement on the most appropriate management of these patients. Treatment options available to patients include intensive endoscopic surveillance with four-quadrant biopsies every 1 cm performed every 3 months, endoscopic ablation therapy, or surgical resection. All of these treatment options have produced similar outcomes for patients in retrospective cohort studies performed at expert centers. Optimal treatment is therefore determined on a case-by-case basis, taking into account the patient’s age, comorbidities, and ability to comply with an aggressive surveillance program, as well as the available local endoscopic and surgical expertise.

• 13.

  What is the principal role of endoscopic ultrasound (EUS) in evaluating patients with HGD?

  EUS can be used to exclude the presence of occult cancer, submucosal invasion, and malignant lymphadenopathy in patients with BE of HGD. This information is particularly important when determining the appropriate selection of patients if endoscopic management is considered. Routine application of EUS in BE with LGD or without dysplasia is not recommended because the risk of malignancy is so low.

• 14.

  Describe the workup once EAC is identified while performing endoscopic surveillance for BE?

  Once EAC is confirmed by an expert GI pathologist, staging of the cancer is performed with a computed tomography (CT) scan, preferably with integrated positron emission tomography, to evaluate for the presence of metastatic disease. Next, patients without evidence of metastatic disease by CT would undergo EUS for regional staging to provide detailed images of the esophageal masses and their relationship within the structure of the esophageal wall. EUS with fine-needle aspiration (FNA) can also be used for lymph node staging. Finally, depending on the stage of the cancer, the patient should be referred to oncology, radiation oncology, or surgery for treatment. The use of endoluminal stenting may be considered.

• 15.

  What other imaging modalities are available for BE endoscopic screening and surveillance?

  Confocal laser endomicroscopy (CLE) imaging of the GI mucosa enables endoscopists to obtain immediate real-time histologic images without biopsies as well as enhance the guidance of mucosal biopsies, leading to a higher dysplasia and neoplasia detection rate. BE and associated neoplasia can be predicted with a sensitivity of 98.1% and 92.9%, and a specificity of 94.1% and 98.4%, respectively, with CLE (overall accuracy: 96.8% and 97.4%), which may lead to decreased biopsies and lower associated cost.

  Narrowband imaging (NBI) is a technique that filters the illuminating white light on the endoscope into two colors (blue and green), which are avidly absorbed by blood vessels to allow for better visualization of the mucosa. In one study of patients with BE, the sensitivity of NBI detection for an irregular mucosal pattern was 100% with a specificity of 98.7%. Chromoendoscopy has also been used to stain the esophagus with agents like methylene blue, crystal violet, indigo carmine, and acetic acid that are applied to the mucosa to enhance the detection of abnormal mucosal patterns in BE.

• 16.

  Do patients with achalasia have an increased risk of esophageal cancer?

  Yes. Individuals with achalasia have as much as a thirty-threefold greater risk of developing SCC of the esophagus compared with the general population. On average, patients with achalasia will have had at least 15 years of symptoms prior to the diagnosis of esophageal cancer.

• 17.

  What is the role of endoscopic cancer surveillance in patients with achalasia?

  Currently, there is insufficient data to support routine endoscopic surveillance in patients with achalasia. Endoscopic surveillance in patients with achalasia has not been found to be cost effective but may be considered 15 years after the onset of symptoms. All surface abnormalities of esophagus identified during the examination should undergo biopsy, and the recommended timing of any surveillance endoscopy has not been defined.

• 18.

  Is there a link between caustic ingestion and the development of esophageal cancer?

  Yes. A caustic injury to the esophagus, most commonly after lye ingestion, appears to be associated with an increased risk of developing SCC of the esophagus. A history of caustic ingestion is present in 1% to 4% of patients with esophageal cancer.

• 19.

  What are the clinical characteristics of patients who develop esophageal cancer after a caustic injury?

  • The mean age of onset is 35 to 51 years.

  • The average interval between caustic injury and development of esophageal cancer is approximately 40 years.

  • Cancers are located in the midesophagus.

• 20.

  What rare genetic disorder is associated with a high incidence of SCC of the esophagus?

  Tylosis is an uncommon autosomal dominant disorder that is distinguished by thickening of the skin (hyperkeratosis) on the palms and soles. The syndrome is associated with a 27% incidence of SCC of the esophagus. The average age at onset of esophageal cancer is 45 years, and death from esophageal cancer can occur in patients as young as 30 years.

• 21.

  What type of endoscopic surveillance is recommended in patients with tylosis?

  Patients with tylosis should begin endoscopic surveillance at the age of 30. Most cases of esophageal cancer in these patients have been noted in the distal esophagus, so attention should be focused in this area during the examination. Repeat endoscopy should not be conducted more frequently than every 1 to 3 years in these patients.