Diagnosis and Treatment of Superficial Gastric Neoplasms

Introduction

The incidence and mortality of gastric cancer have decreased in recent decades because of the reduction of Helicobacter pylori infection, development of endoscopic equipment, and refinement of endoscopic diagnostic and treatment techniques. However, it still remains among the most common malignancies, particularly in Asian countries. Although the prognosis of advanced gastric cancer is poor, the long-term outcome of early gastric cancer is favorable, so it is very important to endoscopically recognize cancers in the early phase. Therefore, endoscopists and gastroenterologists must have sufficient knowledge to provide a better quality of life and prognosis for patients with gastric cancer.

Epidemiology

Almost 1 million new cases of gastric cancer were estimated to have occurred in 2012 (952,000 cases, 6.8% of the total), making it the fifth most common malignancy in the world after cancers of the lung, breast, colorectum, and prostate. More than 70% of cases occur in developing countries, and half the world total occurs in Eastern Asia. Age-standardized incidence rates are approximately twice as high in men as in women, ranging from 3.3 in Western Africa to 35.4 in Eastern Asia for men, and from 2.6 in Western Africa to 13.8 in Eastern Asia for women ( Fig. 32.1 ).

Gastric cancer is the third leading cause of cancer death in both sexes worldwide (723,000 deaths, 8.8% of the total). The highest estimated mortality rates are in Eastern Asia (24 per 100,000 in men, 9.8 per 100,000 in women), with the lowest in Northern America (2.8 and 1.5, respectively). High mortality rates are also present in both sexes in Central and Eastern Europe, and in Central and South America.

Helicobacter pylori

In 1994, International Agency for Research on Cancer clarified H. pylori as a definite carcinogen of gastric cancer, and it is well known that most gastric cancer patients are positive for H. pylori infection. H. pylori contributes to the development and progression of chronic gastritis that is present in most cases of gastric cancer, and it is associated with an increased cancer risk. In fact, approximately 99% of Japanese gastric cancer patients are positive for H. pylori , and there is very low risk of gastric cancer in individuals that are negative for H. pylori infection. The rates of incidence of and mortality from gastric cancer are still high in Japan, but there is a tendency to decrease both of these because of the recent reduction of H. pylori infection cases and the widespread use of eradication therapy for H. pylori ( Fig. 32.2 ). In addition, it has been reported that eradication therapy reduces the risk of gastric cancer as well as occurrence of metachronous gastric cancer after endoscopic resection.

Background of Diagnosis for Early Gastric Cancer

Treatment of gastric cancer remains a major clinical challenge. Survival of patients with early gastric cancer (EGC) is excellent, so early detection is essential for providing a more favorable prognosis. The 5-year disease-specific survival rate for surgical cases of intramucosal and submucosal invasive cancer is 99.3% and 96.7%, respectively. It is also important for ensuring a better overall quality of life because endoscopic treatment provides a minimally invasive local resection for EGC with a negligible risk of lymph node metastasis, thereby preserving the patient's stomach.

Japan has had a well-organized mass screening program for gastric cancer as an integral part of the public health service since the mid-1960s. The Japanese mass screening program, however, most often utilizes gastrophotofluorography, which has comparatively poor resolution, and thus the sensitivity for EGC has been quite low (39%) despite the sensitivity for advanced gastric cancer being high (92%). Recent advances in endoscopy have had a substantial impact on improving early diagnosis, and EGC now accounts for approximately 50% of all gastric cancers treated at major medical facilities in Japan. In fact, most cases (78%) of EGC at the National Cancer Center Hospital (NCCH) in Tokyo were recently detected by endoscopy. A preponderance of those patients with EGC were asymptomatic, and therefore it is extremely important to motivate adults to undergo an endoscopy examination even if they are asymptomatic. It has been reported that the results of a community-based, case–control study by endoscopic screening suggest a 30% reduction in gastric cancer mortality by endoscopic screening compared with no screening within 36 months before the date of diagnosis of gastric cancer. Consequently, the guidelines for screening of upper gastrointestinal tract malignancies have been revised to allow the usage of endoscopy, which is expected to increase the early detection of gastric cancer.

Description of EGC

It is vital to describe tumors accurately using defined terminology to facilitate effective communications among endoscopists, surgeons, and pathologists.

Tumor Location

The stomach is anatomically divided into three parts: the upper, middle, and lower thirds, as determined by lines connecting the trisected points on the lesser and greater curvatures ( Fig. 32.3 ). The stomach's cross-sectional circumference is divided into four equal sections: the lesser and greater curvatures and the anterior and posterior walls.

Macroscopic Type

Macroscopic types are defined as polypoid (0-I) and non-polypoid (0-II and 0-III). The polypoid (0-I) type is subdivided into protruded sessile (0-Is) and protruded pedunculated (0-Ip) subtypes. The non-polypoid type is subdivided into superficial elevated (0-IIa), flat (0-IIb), superficial depressed (0-IIc), and excavated (0-III) subtypes. A mixed type (e.g., 0-IIa+IIc, 0-IIc+IIa) is diagnosed whenever a lesion consists of at least two distinct macroscopic types and/or subtypes ( Fig. 32.4 ).

Endoscopic Diagnosis of EGC

EGC is usually characterized by only a slight change on the surface mucosa, particularly when the tumor invasion depth is intramucosal, so careful observation is paramount for detection.

Preparation

Optimal mucosal visualization is required for a thorough endoscopic examination. Mucosal flushing techniques have become standard practice in Japan to decrease foam and mucus that can obscure the field of view ( Fig. 32.5 ). Anti-foaming agents such as simethicone have been used since the 1950s, and more recent studies have shown that the addition of a mucolytic agent such as proteases further improves mucosal visualization. Flushing the entire stomach is time-consuming, but the early detection of EGC is difficult when large volumes of mucus and foam are present on the surface of the mucosa. Optical digital chromoendoscopy (e.g., narrow-band imaging [NBI, Olympus, Tokyo, Japan], etc.) and magnifying endoscopy are not helpful without this basic step. In addition, patients are routinely instructed to drink 100 mL of water containing 2 mL of simethicone and 20,000 units of Pronase (Sigma-Aldrich, St. Louis, MI) (a commercially available mixture of proteases) 10 minutes prior to endoscopy examination at NCCH to shorten flushing time.

Systematic Examination

A systematic recording routinely produces 30 to 40 endoscopic images of the whole stomach, including suspected lesions as well as normal-appearing areas ( Fig. 32.6 ; Video 32.1 ). It is very important to maintain an adequate bend of the endoscope and to use the retroflexion view for the gastric body and cardia, as various angles and views are useful to detect the tiny abnormalities. Moreover, cloudiness of the lens also interferes with a careful observation, so one should use a lens cleaner just before endoscopy. Some EGCs involve only a slight mucosal change that may be misdiagnosed as gastritis or erosions, so it is important to review the database of endoscopic images cautiously. Such endoscopic images are also useful for educational purposes and especially helpful for less experienced endoscopists. During endoscopy, adequate air insufflation is necessary, particularly to detect lesions located between folds ( Fig. 32.7 ).