- •Contents
- •1. Introduction
- •5. Comments on the Variability of the Diagnoses
- •II. Vienna Consensus Criteria for Pathological Diagnosis
- •1. Vienna Consensus Criteria for Pathological Diagnosis
- •III. Early Neoplasia in Barrett’s Esophagus
- •1. Early Neoplasia in Barrett’s Esophagus
- •1. Gastric Cancer
- •2. Colorectal Cancer
- •3. Esophageal Cancer
- •4. Gastrointestinal Tract Cancer in Europe
- •5. New Trends in Endoscopic Ultrasonography
- •V. Endoscopic Treatment
- •1. Gastric Cancer
- •2. Colorectal Cancer
- •3. Management of Colorectal Cancer by “Hot Biopsy” and Snare Resection
- •4. Esophageal Cancer: Photodynamic Therapy
- •VI. Natural Course of Early Cancer
- •1. Gastric Cancer
- •4. Colorectal Cancer: The Importance of Depressed Lesions in the Development of Colorectal Cancer
- •Index
1. Gastric Cancer
RIKIYA FUJITA, HIROSHI TAKAHASHI, and JUNKO FUJISAKI
1. Introduction |
2. Endoscopic Diagnosis |
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
159
160 IV. Detection of Early Cancer: Is Endoscopic Ultrasonography Effective
Fig. 1. Early gastric cancer. Well differentiated adenocarcinoma. 0-I protruded lesion
Fig. 2. Early gastric cancer. Well differentiated adenocarcinoma. 0-IIa slightly elevated lesion
Fig. 3. Early gastric cancer. Well differentiated adenocarcinoma. 0-IIa+IIc slightly elevated and depressed lesion
1. Gastric Cancer |
161 |
Fig. 4. Early gastric cancer. Poorly differentiated adenocarcinoma. 0-IIb flat lesion
Fig. 5. Early gastric cancer. Poorly differentiated adenocarcinoma. 0-IIc slightly depressed lesion without converging folds
Fig. 6. 0-IIc+III slightly depressed and excavated lesion with converging folds
162 IV. Detection of Early Cancer: Is Endoscopic Ultrasonography Effective
A
B
Fig. 7. A Early gastric cancer. Well differentiated adenocarcinoma. 0-IIc slightly depressed lesion with chromoscopy and narrow band imaging (NBI). B Endoscopy. Well differentiated adenocarcinoma. 0-IIc slightly depressed lesion with magnifying endoscopy and histopathology
Table 1. Incidence and types of early gastric cancer
Types |
1962~71 |
1979~2003 |
|
(Japan survey) |
(Cancer Institute H) |
|
N=7,617 |
N=4,029 |
I |
14.0% |
2.9% |
IIa |
13.1% |
14.1% |
IIa+IIc |
11.0% |
n.d. |
IIb |
2.6% |
8.3% |
IIc |
55.4% |
74.2% |
III |
4.0% |
0.5% |
Total |
100.0% |
100.0% |
|
|
|
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
1. Gastric Cancer |
163 |
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].
164 IV. Detection of Early Cancer: Is Endoscopic Ultrasonography Effective
5. Magnifying Endoscopy |
Table 2. Proportions of correct diagnosis obtained using |
|||||
|
|
|
three-dimensional endoscopic ultrasonography |
|||
With the aid of magnifying endoscopy, observation of |
m cancer |
95% |
(115/121) |
|||
EGC and its differential diagnosis, establishment of a |
sm cancer |
77% |
(47/61) |
|||
advanced cancer |
57% |
(12/21) |
||||
demarcation line for EMR, and examination of cancer |
||||||
mp cancer |
0% |
(0/2) |
||||
recurring after EMR are performed under magnifica- |
||||||
ss cancer |
69% |
(9/13) |
||||
tions of 40–100 power. The rate at which EGC is dia- |
s cancer |
60% |
(3/5) |
|||
gnosed by magnifying endoscopy is not as high as |
si cancer |
0% |
(0/1) |
|||
compared with the rate at which early colon cancer is |
|
|
|
|||
|
|
|
||||
diagnosed under magnified observation. However, it is |
|
|
|
|||
gradually being accepted that magnifying endoscopy |
|
|
|
|||
is useful when used in combination with chromoscopy |
|
|
|
|||
or narrow band imaging. The routine use of magnifying |
|
|
|
|||
endoscopy does not appear to be necessary. The fol- |
recently developed makes it easy to identify the stage |
|||||
lowing types of magnifying endoscope are available |
of cancer in patients. It should be further determined, |
|||||
now on the market. |
|
however, whether EUS is really indispensable to detect |
||||
Fujinon |
EG450ZW5 |
100 ¥ zoom |
early cancers. Since |
mucosal cancers treatable with |
||
EMR (endoscopic mucosal resection) are equally diag- |
||||||
Olympus |
Q240Z |
80 ¥ zoom |
||||
nosed with either EUS or conventional endoscopy, EUS |
||||||
|
|
|
||||
|
|
|
does not seem to be indispensable. The rate at which |
|||
6. Narrow Band Imaging |
advanced cancers are diagnosed with EUS is not much |
|||||
different from that at which they are diagnosed with |
||||||
|
|
|
||||
Narrow band imaging (NBI) is a recently developed |
conventional endoscopy. The notion that EUS is truly |
|||||
valuable may not be accepted widely unless EUS makes |
||||||
method. It |
has attracted |
considerable attention as a |
||||
differential diagnosis among sm1, sm2, and sm3 possi- |
||||||
technique that allows the detection of abnormal pat- |
||||||
ble [5] (Table 2). |
|
|
||||
terns of superficial capillary vessels. Although this |
|
|
||||
|
|
|
||||
method should be used in combination with a magnify- |
|
|
|
|||
ing endoscope, the use of NBI is beginning to be used |
References |
|
|
|||
alone in examination of the esophagus, stomach, and |
|
|
||||
colon. According to our experience, we can differenti- |
|
|
|
|||
ate patterns of capillary vessels in the superficial layer |
1. The Paris endoscopic classification of superficial neoplastic |
|||||
of the mucosa. The consistency rate between patholog- |
lesions: esophagus, stomach, and colon (2003) Gastrointest |
|||||
ical diagnoses and diagnoses obtained with NBI has |
Endosc 58(Suppl 6):S3–S43 |
|
||||
been established. NBI is gaining attention as a new |
2. Schlemper RJ, Hirata I, Dixon MF (2002) The macroscopic |
|||||
method that occupies an important role in optic biopsy. |
classification of early neoplasia of |
the digestive tract. |
||||
Endoscopy 34:163–168 |
|
|||||
|
|
|
|
|||
|
|
|
3. Schlemper RJ, Itabashi M, Kato Y, et al (1997) Differences |
|||
7. Endoscopic Ultrasonography |
in diagnostic criteria for gastric carcinoma between Japan- |
|||||
ese and Western pathologists. Lancet 349:1725–1729 |
||||||
(EUS) |
|
|
4. Dixon MF (2002) |
Gastrointestinal |
epithelial neoplasia: |
|
|
|
Vienna revisited. Gut 51:130–131 |
|
|||
|
|
|
|
5. Ida M, et al (2002) Endosc Digest 14:624–632
Nowadays, EUS examination using a miniature probe is performed widely. The 3D (three-dimensional)-EUS