Issues in the Management of the Upper Third Gastric Cancer
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According to the nationwide survey of gastric cancer in Korea conducted by Korean Gastric Cancer Association, the upper third gastric cancer was not increased significantly from 1995 (10.0%) to 1999 (11.7%), unlike the Western countries where there has been an continuing rise in the incidence of gastric cancer in cardia (1,2). But, interestingly, the proportion of performing proximal gastrectomy was increased significantly (0.3% in 1995; 3.6% in 1999), especially in the large volume hospitals in Korea. This could be explained by the relatively increased proportion of early gastric cancer in the upper one third gastric cancer.
There has been confusion with the definition of the upper third gastric cancer, gastric carcinoma of the cardia, and adenocarcinoma of the esophagogastric junction. Siewert et al. defined the adenocarcinoma of esophagogastric junction as adenocarcinoma that has its center within 5 cm proximal and distal of the anatomical esophagogastric junction, and this definition was approved at the consensus conference during the second International Gastric Cancer Congress in 1997 (3). Furthermore, it has been subdivided into those with the center located more than 1cm above the anatomical esophagogastric junction (type I: adenocarcinoma of the distal esophagus), those with the center located within 1 cm oral and 2 cm aboral of the junction (type II: true carcinoma of the cardia), and those with the center located more than 2 cm below the junction (type III: subcardial carcinoma) (4). Gastric carcinoma of the cardia is very ambiguous term because it may refer to any cancer in the proximity of the esophagogastric junction. Generally, this disease entity is considered as Siewert's type II and III esophagogastric junction cancer. On the other hand, the Japanese Research Society for Gastric Cancer recommended that the stomach be separated into an upper, middle, and lower third by dividing the lesser and greater curvature into thirds and drawing lines between corresponding points at the two curvatures (5). This Japanese classification is thought to be very clear for communicating each other about the location of gastric cancer. Therefore, this system has been accepted as a standard descriptive tool for gastric cancer by Korean Gastric Cancer Association.
It is generally accepted that the prognosis of patients with the upper third gastric cancer is worse than that of patients with more distally located gastric cancers (6). In the past, the upper third gastric cancer is sometimes considered as a distinct disease category from the middle or lower third gastric cancer, but recent studies indicates that the poor prognosis usually associated with this tumor is mainly due to late presentation and advanced tumor stages (7,8).
Nowadays, one of the hottest issues in the management of the upper third gastric cancer is the role of proximal gastrectomy for early gastric cancer. In this issue of Cancer Research and Treatment, Yoo, et al. presented the long-term results of proximal vs. total gastrectomy for the upper third gastric cancer (9). In this retrospective study including sufficient number of patients, they concluded that the extent of resection for the upper third gastric cancer did not affect long-term survival, but that proximal gastrectomy was associated with an increased risk of reflux esophagitis, anastomotic stricture, and local recurrence. Until now, the prospective randomized trial comparing proximal vs. total gastrectomy for the upper third gastric cancer has never been conducted. But, many retrospective studies demonstrated that proximal gastrectomy for early gastric cancer in the upper third of stomach showed a comparable long-term result to total gastrectomy (10,11).
As discussed in this article, in surgical viewpoint, proximal gastrectomy has some limitation for sufficient lymph node dissection around the pylorus. In addition, some patients who underwent proximal gastrectomy have been found to experience gastroesophageal reflux and consequent esophagitis. Jejunal interposition was one of the most promising techniques for reducing postoperative gastroesophageal reflux (11), but this procedure was complicated and time-consuming (12). Due to limited lymph node dissection, proximal gastrectomy has not been performed as a standard procedure for all of the upper third gastric cancer. Previous report conducted by Yoo et al. revealed that the risk factors for local recurrence following proximal gastrectomy were diffuse type tumor, greater than 5 cm in tumor size, and serosal invasion (13). Therefore, proximal gastrectomy for advanced gastric cancer in the upper third of stomach should be considered very carefully until the result of prospective randomized trials have been available.
This finding is quite different from the treatment result of distal gastric cancer. In distal gastric cancer, 3 prospective randomized trials confirmed that total gastrectomy did not improve survival rates comparing to the distal subtotal gastrectomy as long as clear resection margin were achievable with subtotal gastrectomy (14~16).
Another possible explanation for the relatively frequent local recurrence pattern after proximal gastrectomy can be the role of gastrin for cancer recurrence. Gastrin is known as a growth factor for cancer cells of the gastrointestinal tract. Half of proximal gastrectomy patients exhibit hypergastrinemia and more than half of gastric cancer tissues express gastrin/CCKB receptor and gastrin can stimulate growth of gastric cancer cells with gastrin/CCKB receptor (17). Hypergastremia induced by proximal gastrectomy may enhance recurrence of gastric cancer.
In summary, although we can save distal stomach by performing proximal gastrectomy for the upper third gastric cancer, it should be considered only in early gastric cancer because of the insufficient regional lymph node dissection, relatively high postoperative complication rate.