Epidemiology and Diagnosis of Oesophageal Adenocarcinoma

Epidemiology and Diagnosis of Oesophageal Adenocarcinoma

Dr. Reda Elwakil, MD

Emeritus Professor of Tropical Medicine

Ain Shams University

President Elect of the African Middle East Association for Gastroenterology (AMAGE)

Member of the American Gastroenterology Association (AGA)

Member of the American Society for Gastrointestinal Endoscopy (ASGE)

Esophageal cancer (EC) is the eighth most common malignant tumor worldwide. In 2010 an estimated 16,640 new cases and 14,500 deaths due to EC occurred in the US. It is associated with a 5-year survival rate of 15 to 20%. The lifetime risk of developing this cancer is 0.8% for men and 0.3% for women. The risk increases with age and the mean age at diagnosis is 67 years .Esophageal cancers include squamous cell carcinomas which are similar to head and neck cancer in their appearance and association with tobacco and alcohol consumption ,adenocarcinomas which are often associated with a history of GERD and Barrett’s (BE). A general rule is that a cancer in the upper two-thirds is a squamous cell carcinoma and one in the lower one-third is an adenocarcinoma. Rare histologic types of esophageal cancer are non-epithelial tumors, such as leiomyosarcoma , malignant melanoma, rhabdomyosarcoma and lymphoma

Esophageal Adenocarcinoma (EAC) Epidemic

Edgren et al.,(2013) ,collected data on incident cases of EAC from population-based cancer registries in Australia, Europe, North America and Asia. They calculated age-standardized incidence rates and assessed annual rate of increase since 1985.They found a consistent dramatic increase in incidence with an observed or estimated start between 1960 and 1990. The average annual increase ranged from 3.5% in Scotland to 8.1% in Hawaii with a maintained three to six-fold higher incidence among men.

Epidemiology of adenocarcinoma

Although squamous cell carcinoma is the most common histo-type, over the past three decades a slight decline in its prevalence and, conversely, a dramatic increase in the prevalence of adenocarcinoma have been recorded, especially in the US, UK and Western Europe. Patients with Barrett’s esophagus have a 30 to 40 times higher risk of developing esophageal cancer. In the US, approximately 1.52- million people are affected with Barrett’s esophagus, and its prevalence in people without symptoms of GER is about 0.4–6%.

Barrett’s esophagus and esophageal adenocarcinoma (AC) risk

The risk of malignant progression has been examined in over 8,500 patients with BE using the Northern Ireland BE Registery and followed-up for a mean of 7 years. Incidence of EC or gastric cardia cancer or high-grade dysplasia combined was found to be 0.22% per year. In patients with specialized intestinal metaplasia (SIM), the combined incidence was 0.38% per year. A statistically significant elevation of cancer risk was observed in patients with vs. those without SIM at index biopsy .

In a population-based, cohort study that included all patients with BE collected in Denmark in the period 1992 through 2009, the relative risk of AC among patients with BE, compared with the risk in the general population, was 11.3.Low-grade dysplasia on the index endoscopy was associated with an incidence rate for AC of 5.1 cases per 1,000 person-years, whereas the incidence rate for patients without

dysplasia was 1.0 case per 1,000 person-years.

A major risk factor for BE is GERD, whose prevalence is estimated to be 10–20% in the Western world. However, only 10–15% of patients with chronic GERD develop BE, indicating that additional genetic and/or environmental factors are likely to be involved. Other risk factors associated with the development of EAC include advanced age, male gender, white race and elevated body mass index.

An inverse association has been described between the presence of BE and H. pylori infection.

Screening and Surveillance for EAC

The prognosis for symptomatic and advanced EAC in patients who are suitable for radical surgical intervention is very poor, with a median survival of 1 year and a 5-year survival rate of 10%. Lymph node metastases were seen in 18% of patients with surveillance-detected cancer compared with in 56% of patients with symptoms. Surveillance-detected cancers were at a significantly earlier stage than symptomatic cancers. This translated into significantly better survival rates: 80% (surveillance) vs 31% (symptomatic) at 3 years. These observations suggest that patients enrolled in surveillance programs have a better actuarial survival and have helped define the current recommendations for surveillance. However, patients who will enter surveillance programs may be different from those who present with advanced EAC. They are often younger and generally in better health. Thus, the value of surveillance is still subject to considerable debate and much controversy.

Risk factors for the development of EAC within a segment of BE

Age greater than 45 years, male sex, long segments (> 8 cm),long duration of reflux history , early onset of reflux and the presence of ulceration or stricture.

Current guidelines for screening and surveillance for Barrett’s esophagus

AGA technical review on the management of BE concluded that inadequate evidence exists to endorse endoscopic screening for BE based solely on the presence of GERD symptoms, and decisions on when to recommend endoscopic screening should continue to be individualized. Endoscopic surveillance with 4 quadrant biopsies at distance of 12- cm of BE segment at intervals of:

Three to five years for patients without dysplasia, six to twelve months for those with low-grade dysplasia (LGD), and every 3 months for high-grade dysplasia (HGD) patients. Because there are no controlled trials that examine the efficacy of surveillance, the question of whether the current strategies to detect and diagnose Barrett's esophagus are optimal or justified still remains unanswered

Diagnosis of adenocarcinoma

The diagnosis of esophageal cancer is usually established by endoscopy. Early esophageal cancer may appear as a superficial plaque or ulceration. Advanced lesions may appear as a stricture, an ulcerated mass or circumferential mass or a large ulceration.

The Role of New Imaging Techniques in Improving Diagnosis of EAC

Narrow Band Imaging: Refers to an imaging technique, where light of specific blue and green wavelengths is used to enhance the detail of certain aspects of the surface of the mucosa. A special filter is electronically activated by a switch in the endoscope leading to the use of ambient light of wavelengths of 440 to 460 nm (blue) and 540 to 560 nm (green). Because the peak light absorption of hemoglobin occurs at these wavelengths, blood vessels will appear very dark, allowing for their improved visibility and in the improved identification of other surface structures. It allows for better detection of early neoplastic lesions by visualizing the patterns produced by subsurface vascular changes. It can detect significantly more patients with dysplasia and higher grades of dysplasia with fewer biopsy samples compared with standard resolution white light endoscopy Chromo-endoscopy:

involves the application of a solution that contains a stain (methylene blue) or potassium iodide and iodine through a spray catheter. The dye stains the glycogen in normal squamous epithelium a dark brown color in case of iodine. Areas that are unstained, particularly those that are larger than 5 mm in size, are likely to be dysplasic or malignant and can be readily targeted for endoscopic biopsy. Smaller unstained areas (less than 5 mm) may result from inflammatory change.

Confocal laser endomicroscopy (CLE): Is an endoscopic modality developed to obtain very high magnification and resolution images of the mucosal layer of the GI tract. CLE is based on tissue illumination with a low-power laser with subsequent detection of the fluorescence of light reflected from the tissue through a pinhole. The term confocal refers to the alignment of both illumination and collection systems in the same focal plane. The laser light is focused at a selected depth in the tissue of interest and reflected light is then refocused onto the detection system by the same lens. Confocal imaging can be based on tissue reflectance or fluorescence. Confocal devices based on tissue reflectance do not require any contrast agents, but current prototypes strategies have relatively low resolution, which significantly compromise in vivo imaging and clinical utility. CLE by using topical and/or intravenous fluorescence contrast agents generates images with resolution similar to traditional histological examination. CLE systems have included through-the-scope probes or dedicated endoscopes with integrated CLE systems.

In conclusion , early detection of esophageal adenocarcinoma markedly improved the prognosis of this serious disease.