1. Gastric Cancer

When early gastric cancer (EGC) was diagnosed for the first time a little more than 40 years ago, abnormal regions were detected by fluoroscopic barium examination and by photographs from a gastrocamera. With regard to the use of endoscopes for diagnosis, the gastrocamera was replaced by the fiberscope in the 1970s. The latter was then replaced with the electronic endoscope in the 1980s. Since the latter half of the 1990s, capsule endoscopes have come into use. In addition to conventional endoscopy, the following endoscopic examinations are now available: chromoscopy, endoscopic ultrasonography (EUS), magnifying endoscopy, and narrow band imaging etc. It is also worth noting that a definite diagnosis of EGC is impossible without biopsy.

The study of EGC was prompted by the fact that the 5- year survival rate of patients with mucosal and submucosal cancers was high. Because mucosal cancer formerly was detected infrequently, “EGC” was defined as mucosal cancer with or without infiltration up to the submucosal layer.A cancer fulfilling the above criterion was defined to be an EGC even though it may have been accompanied by metastases to lymph nodes [JGES (Japan Gastroenterological Endoscopy Society) classification]. This definition was probably derived from the desire to detect as many EGCs as possible. In Japan, the number of EGCs accounts for 60%–80% of the sum of all currently detected cancers. Endoscopic treatment of EGC has also developed from the initial types of treatment, to endoscopic mucosal resection (EMR), and then to endoscopic submucosal dissection (ESD), which now attracts considerable attention in the field of endoscopic surgery. In addition, the laparoscope is used for local resection of cancer in combination with the endoscope. The survival rate of patients with EGC is as high as above 90% after surgical resection. Correct diagnosis of EGC is becoming more and more important not only in Japan but also internationally. There is a trend that early cancers are integrated and classified as superficial carcinomas, since they exist on or in the superficial layer. In “The Paris Endoscopic Classification of Superficial Neoplastic Lesions: Esophagus, Stomach, and Colon” published recently [1], the criteria for the classification of EGC were applied to the classification of early cancers in the esophagus and colon [2]. Cancers in these regions are explained individually as superficial neoplastic lesions (type 0) in the publication.

Lesions can be classified into three fundamental types: protruded type (0-I), superficial type (0-II), and excavated type (0-III). The superficial type is further divided into three subtypes: slightly elevated (0-IIa), flat (0-IIb), and slightly depressed (0-IIc). Some lesions can be divided into classes described by combinations of types and/or subtypes, such as IIa+IIc and IIc+III (see Figs. 1–7).

Because the criteria for the classification described above are subjective, there are surely individual variations in the classification of each lesion among examiners. For instance, type I (protruded type) cannot be definitely differentiated from type IIa (slightly elevated type). To differentiate these two types, it was proposed that the height (2.5 mm) of the closed cups of the biopsy forceps should be used as a standard. Therefore, lesions less elevated than the standard are classified into type IIa and those more protruded than the standard are classified as type I. Even if lesions are considerably protruded, extensive lesions are often classified into type I+IIa rather than into type I when the lesion as a whole is taken into consideration. This may be one reason for individual variations in the classification of lesions. With regard to the classification of EGC, the proportion of patients with type IIc is highest, as shown in Table 1. Patients with type IIc and its combined types account for 75% of all patients suffering from EGC. The proportion of patients with type IIb is increasing slightly, probably because small lesions are detected more easily. In contrast, the proportion of patients with type III (excavated type) has recently decreased.

The following points are used to detect and classify cancerous lesions during endoscopy.

1.Color changes (redness, erosion, discoloration, paleness, milky-colored, etc.) are found in superficial lesions, particularly in depressed lesions (0-IIc). Slightly elevated lesions (0-IIa) can be easily detected by chromoendoscopy. On the other hand, it is difficult to detect flat lesions (0-IIb) based on color changes.

2.Convergence of folds (abnormal folds, enlargement of folds, moth-eaten appearance of folds, thinning

of folds, fusion of folds, etc.) are frequently found in excavated lesions (types 0-III, 0-IIc+III) and slightly depressed lesions (type 0-IIc). Because such lesions are often confused with benign ulcer scars, examiners with

Table 1. Incidence and types of early gastric cancer

little experience with EGC fail to detect these lesions. Consequently, biopsies are not performed for these lesions, and cancers easily pass undetected. Chromoscopy performed in combination with conventional endoscopy reveals slight depressions, abnormal changes in folds, and slight elevations more clearly. The rate at which EGC is diagnosed by biopsy ranges from 80% to 90%.

3. Protruded lesions (type 0-I) or slightly elevated lesions (type 0-IIa) can be diagnosed correctly if biopsy of the lesions is made without exception. The rate at which EGC is diagnosed by biopsy is over 95%,

which is higher than the corresponding value for excavated lesions.

4.Minute cancer. Gastric cancers smaller than 5 mm in diameter are called minute cancers. Minute cancers have no characteristic appearance of malignant tumors, such as an irregular margin. Clues to identify lesions of this type are a slightly uneven surface, paleness in color, an irregular pattern, disappearance of superficial blood vessels, and redness. An isolated erosive lesion is a feature of cancer of this type. Minute cancers can be detected and diagnosed with the aid of chromoscopy, magnifying endoscopy or NBI (narrow band imaging) and biopsy.

5.Comparison with histopathology. Well-differenti- ated and undifferentiated adenocarcinomas have been known to exhibit different endoscopic appearances from each other. Well-differentiated lesions exhibit redness whereas undifferentiated lesions exhibit paleness and discoloration. The former are not sharply demarcated, whereas the latter are well circumscribed. The most serious problem concerning the pathological diagnosis is inconsistency in the diagnostic criteria. Presently, there is international discussion to establish unified criteria. Readers are referred to the corresponding chapters.

3.Chromoscopy

The contrast method using indigo carmine (0.2%–0.5% in concentration) is most frequently applied now. The method is performed as follows. After conventional endoscopic observation, a target point is sprayed with a dye solution through a spraying catheter in such a manner that the solution spreads thinly over a wide region that includes the target point. Simple injection of the solution through the biopsy channel is also possible, but using a spraying catheter is much better. After spraying of the solution, recordings and target biopsy are made as quickly as possible. Although chromoscopy cannot make all invisible sites visible, it is a convenient method to differentiate a target point from the surrounding tissue easily. Particularly, it facilitates to determine a site for biopsy and provides a clear border between pathological and normal sites. The procedure takes only 2–3 min. According to our survey of three institutions, the detection rate of EGC did not increase with the rate at which the contrast method was used in individual institutions.

4. Pitfalls of Biopsy Diagnosis

Detection of cancerous lesions is first required. The rate at which EGCs are diagnosed with biopsy is higher than

the rate at which advanced cancers are diagnosed with biopsy. Among EGCs, protruded or slightly elevated cancers are diagnosed at a higher rate than slightly depressed or excavated cancers. If a cancer passes undetected by endoscopy and accordingly biopsy is not performed, the cancer remains unnoticed until the next endoscopic examination. Lesions of type IIb and minute lesions of types IIa and IIc are missed very often.

The level of competence of individual endoscopic examiners also influences the detection rate of EGC. We once compared diagnoses from the endoscopic observation with diagnoses provided by subsequent biopsy in routine examinations in order to assess the differences among examiners in the ability to diagnose EGC. We considered a cancer was missed when the endoscopic diagnosis provided was ulcer scar or erosion and then a cancerous lesion was found on biopsy. On the other hand, we considered that an endoscopic diagnosis was correct when it was a suspected cancer and a cancerous lesion was found on biopsy. As a result of such comparisons, we found that the rate of correct endoscopic diagnosis was distributed between 20% and 100% among individual examiners. The personal variations in the rate of correct diagnosis did not depend markedly on the length of experience. The detection rate among upper gastrointestinal tract endoscopists was higher than the detection rate among other specialists in gastroenterology.

The next problem concerns clinical pathologists. The difference in diagnostic criteria among clinical pathologists in Japan, European countries, and the United States is a concern. Schlemper et al. [3] reported their experience where they requested Japanese, European, and American pathologists to examine and provide a diagnosis for the same histopathological preparations. Diagnoses of the same lesion provided by the pathologists varied widely among cancer and high-grade or low-grade adenoma/dysplasia. As with the revised Vienna classification [4], an effort should be continued hereafter to obtain a consensus about the criteria for biopsy diagnosis. Readers are referred to the corresponding chapters regarding pathological diagnostic standards.The diagnostic standard in Japan is shown below.

Group I: Normal mucosa and benign lesions with no atypia

Group II: Lesions showing atypia but diagnosed as benign (non-neoplastic)

Group III: Borderline lesions between benign (nonneoplastic) and malignant lesions

Group IV: Lesions strongly suspected of carcinoma Group V: Carcinoma

The Paris classification reported in 2003 [1] was based on the Japanese classification [2].