Screening and Case Finding for Gastrointestinal Cancers

Cancers of the digestive tract present a major challenge, because early-stage disease, though potentially curable, is typically asymptomatic and later-stage disease is often refractory to treatment. Such frustrating characteristics have raised interest in early detection through screening as a means of improving survival. However, for population screening to be cost-effective, prevalence has to be high; diagnostic testing has to be affordable, acceptable, and accurate; and treatment in the early stage has to produce a demonstrable improvement in survival (see Chapter 3). Of the gastrointestinal cancers affecting US adults, only colorectal cancer meets all these criteria and is discussed in a separate chapter (see Chapter 56).

Case finding, an alternative to screening that involves testing selected high-risk persons for early-stage disease or premalignant change, represents an alternative strategy for detection of potentially preventable or curable digestive tract cancers in asymptomatic persons when prevalences are too low to warrant mass screening. A number of gastrointestinal cancers (e.g., esophageal, gastric, hepatic, pancreatic) have biologic characteristics (e.g., a premalignant state, identifiable risk factors) that make them potential targets for case finding, an approach of increasing interest stimulated by advances in diagnostic methods. However, improved survival associated with such case finding has been difficult to study and definitively demonstrate, often triggering controversy and impeding consensus, leaving the question of case finding to the individual patient and physician.

Although currently not sufficiently evidence based to be recommended as a standard of care for routine use, the primary care physicians should be aware of these case-finding efforts because they may be worth considering in selected patients and may be suggested to patients or family members by specialty physicians.

ESOPHAGEAL CANCER (1, 2 and 3)

Of the approximately 14,000 new cases of esophageal cancer diagnosed annually in the United States, less than 10% of patients survive 5 years, focusing interest on improvements in prevention and early detection. Symptoms of early disease may be absent or nonspecific, but the association with chronic reflux and Barrett esophagus and the widespread availability of upper endoscopy have raised interest in selective case finding for detection at a premalignant or early stage of disease.

Risk Factors and Premalignant States (see also Chapter 61)

Prolonged, severe, symptomatic gastroesophageal reflux is a wellestablished risk factor for adenocarcinoma of the esophagus by virtue of its association with development of Barrett esophagus (metaplastic columnar epithelialization of the distal esophagus due to chronic exposure to gastric acid, pepsin, and bile—see Chapter 61). Dysplastic transformation may ensue and eventually lead to adenocarcinoma. Risk is highest in older white males, especially those with a history of alcohol excess and smoking. Initial estimates of cancer risk were high, triggering considerable enthusiasm for surveillance (see below), but more recent data suggest a rate of 0.12% (one case per 860 patient-years) for the development of esophageal cancer in patients with Barrett esophagus. Moreover, life expectancy is similar to the general population, and esophageal cancer is actually an uncommon cause of death in persons with Barrett regardless of the cancer screening strategy.

Case Finding

As noted, the impetus for case finding in esophageal cancer derives from the poor survival for patients with esophageal adenocarcinoma and the presence of a detectible premalignant state, which might respond to therapy (see Chapter 61). Endoscopy with biopsy provides a safe and accurate, though somewhat expensive, means of detecting premalignant and very early-stage disease. Although the value of case finding has not yet been proven in randomized trial, current consensus guidelines from endoscopists recommend periodic upper endoscopy in persons with chronic severe gastroesophageal reflux disease (GERD) symptoms. Those with more than 5 years of severe GERD symptoms, particularly older white men with a history of smoking and alcohol excess, are at greatest risk and the best candidates for at least a single case-finding endoscopy. Complicating the recommendation is the demonstration of Barrett epithelium in some patients with no heartburn symptoms.

Surveillance

Endoscopic biopsy and surveillance are recommended for those persons found to have Barrett esophagus changes. The recommended surveillance interval depends on the presence and grade of dysplasia:

No dysplasia on two consecutive annual biopsies: endoscopy every 3 years
Low-grade dysplasia (confirmed by expert pathologist and by repeat examination within 6 months): endoscopy every 12 months
High-grade dysplasia: endoscopy every 3 months and ablative therapy (e.g., endoscopic mucosal resection—see Chapter 61) if high-grade dysplasia with mucosal irregularity is identified

GASTRIC CANCER (4, 5, 6 and 7)

There are approximately 23,000 new cases of gastric cancer in the United States each year and 14,000 deaths attributable to it annually, reflecting a poor response to treatment. In Asia and some countries of Latin America, it is one of the leading causes of cancer death. Over the last century, the incidence has decreased markedly in the United States, attributed in part to improved food handling and refrigeration. Mass screening has been tried in countries where disease incidence is very high, such as Japan and Korea; initial results suggest detection of earlier-stage disease and improved outcomes, but lead-time bias and other factors put these results in question. In countries such as the United States where disease incidence is low, case finding has been suggested as a more cost-effective alternative, with particular interest in detection of premalignant states and very early-stage disease.

Risk Factors and Premalignant States

Gastric adenocarcinoma is a heterogeneous condition with a host of subtypes and associated risk factors. Cancers that arise in the proximal stomach (cardia) and gastroesophageal junction often exhibit an association with chronic gastroesophageal reflux (see Chapter 61), while more distal cancers typically occur in the setting of chronic atrophic gastritis and achlorhydria, often induced by long-standing Helicobacter pylori infection. Those cancers with intestinal-type histology (the most common form) may occur proximally as well as distally and appear to follow an evolution from chronic superficial gastritis (as seen with H. pylori infection, high-salt diet, pernicious anemia, and or Billroth II anastomosis) to malignancy with intermediate states of atrophic gastritis, metaplasia, and dysplasia. The less common and more aggressive diffuse-type gastric adenocarcinomas show no such precursor gastric pathology, but may exhibit a genetic pathogenesis in a hereditary subset (e.g., mutation in the CDH1 gene affecting production of cadherin, a cell adhesion molecule).

Environmental Risk Factors

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