Adenocarcinoma of the Stomach: A Review

Austria, Dr. Theodor Billroth performed the first successful operation for gastric cancer.Two previous attempts by other surgeons had resulted in early postoperative deaths; Dr. Billroth's patient survived the surgery but died a few months later from metastatic disease (1).Today surgeons are still challenged by similar obstacles in gastric cancer, notably the dismal result of incomplete resection. INCIDENCE AND ETIOLOGYWorldwide, gastric cancer is the fourth most common cancer (2).In the West, the incidence of gastric cancer has steadily decreased since the 1930s due to better living conditions and dietary changes.It is now the eighth most common cause of cancer death (Figure 1).The incidence in the USA is 5.2 per 100,000 vs 12 to 15 per 100,000 in Europe and 93 per 100,000 in Japan (3-5).In 2002, there were 21,600 newly diagnosed gastric cancers and 12,400 deaths due to gastric cancer in the USA (6, 7).The median age of diagnosis is 70 years for men and 74 years for women (3, 8).The incidence is twice as high in men as in women and increases with age (9).The vast majority of gastric cancers are attributed to environmental factors, the most common being infection with Helicobacter pylori.H. pylori was discovered in 1984 by Drs.Marshall and Warren as an inciting cause for peptic ulcer disease and has since been linked to gastric cancer (10).This organism is found in 72% of antral gastric cancers and results in a 9-fold increased risk of developing cancer.Inoculation most likely occurs in childhood through the oral-fecal pathway and is transmitted person to person (11), which partially explains why the incidence decreases as countries become more developed.Palayo Correa theorizes that preexisting infection with H. pylori causes inflammation and atrophy, leading to reduced acid and bacterial overgrowth.Chronic atrophic gastritis can progress to metaplasia, then to dysplasia, and finally to carcinoma (12-14).It is also possible that more virulent strains of H. pylori (i.e., the Cag A strain) may cause cancer (15).This mechanism is more likely to apply to distal cancers compared with more proximal cancers.Food intake is thought to be con-tributory as well; diets high in salt and preserved, smoked foods as well as low in fresh fruits and vegetables appear to be a risk factor.A Swedish population-based case-control study evaluated the absolute risk reduction from changes in diet.It was estimated that 25,000 people would have to eat a high-fruit diet to prevent one gastric cancer (16).However, certain carcinogens in foods, such as nitrosamines and nitrosamides, in the presence of achlorhydria along with the decreased antioxidant effect of fruits and vegetables may enhance the risk of developing chronic atrophic gastritis.Proximal tumors, however, appear to have a different mechanism, as many pathology specimens fail to demonstrate dysplasia or metaplasia (17, 18).Genetic factors have been difficult to prove.Although many molecular studies have been and are being performed to uncover the genetic basis for gastric cancer formation, no causal