Early gastric cancer: From basic knowledge to understanding how to find it by endoscopy: Review

Early gastric cancer is defined as invasive gastric cancer that invades no more deeply than the submucosa, irrespective of lymph node metastasis (T1, any N). The need for better approaches to the treatment of early gastric cancer has led to the development of advanced endoscopic techniques to diagnosis and resect early gastric cancer.

EARLY GASTRIC CANCER: FROM BASIC KNOWLEDGE TO UNDERSTANDING HOW TO FIND IT BY ENDOSCOPY: REVIEW

Dao Truong Giang 1 ; Duong Xuan Nhuong 1

SUMMARY

Early gastric cancer is defined as invasive gastric cancer that invades no more deeply than the submucosa, irrespective of lymph node metastasis (T1, any N) The need for better approaches to the treatment of early gastric cancer has led to the development of advanced endoscopic techniques to diagnosis and resect early gastric cancer This review aims: To guide gastrointestinal doctor to understand early gastric cancer from basic histologic knowledge and the usefulness of conventional endoscopy to advanced endoscopy to diagnose early gastric cancer

* Keywords: Gastric cancer; Endoscopy

DEFINITION

The concept of early gastric cancer

(EGC) was originated in Japan in 1962 At

that time, an EGC was defined as a

neoplasm that could be successfully

treated with surgery EGC is now defined

more specifically as an adenocarcinoma

that is restricted to mucosa or submucosa,

irrespective of lymph node metastasis

(T1, any N)

These cancers have a significantly better

prognosis (approximately 90% five-year

survival rate) than do more advanced

stages of gastric cancer In Japan, gastric

cancer screening began in the 1960s, and

was continued to be the leading cause of

cancer mortality

There has been a transition to

magnification chromo-endoscopy with

indigo-carmine spray in experienced centers in Eastern Asia In addition, there

is variation in screening practices by country and region Methods used to screen for

gastric cancer include endoscopy, H pylori

serology, and serum pepsinogen testing

HISTOLOGICAL CLASSIFICATION

Gastric cancers can be classified in a number of ways, according to both histological and macroscopic findings

1 Lauren classification

Histologically, gastric cancers are classified

as intestinal (well-, moderately-, poorly-differentiated) or diffuse (unpoorly-differentiated) subtypes based on the Lauren classification [1] These two types of gastric cancer have distinct morphologic appearances, epidemiology, pathogenesis, and genetic profiles

1 103 Military Hospital

Corresponding author: Nguyen Truong Giang (giangle127@yahoo.com)

Date received: 24/07/2018

Date accepted: 28/09/2018

2 Recently histologic classification

There are differences in gastric histologic

interpretation between Japanese and

Western pathologists to the higher

proportion of EGCs among Japanese

patients The disagreement is centered in

the characterization of high-grade dysplasia

and intra-mucosal adenocarcinoma [2]

Western pathologists have typically required

invasion of the lamina propria for

diagnosis of cancer, whereas Japanese

pathologists have based on the diagnosis

of cytologic and architectural changes

alone, without requiring invasion of the

lamina propria As a result, lesions

classified as high-grade dysplasia by

Western pathologists, may be classified

as intramucosal carcinoma by Japanese

pathologists

However, these differences in classification

are usually not clinically meaningful

because of the following reasons:

- Patients with severe dysplasia or EGC

are usually managed by endoscopic resection,

since both diagnosis are associated with

a low risk of lymph node metastasis

- Invasion of the lamina propria, which

is the threshold for diagnosing cancer

among Western pathologists, may be

difficult to identify on histology

3 The Vienna classification

In an attempt to close the gap between

the Japanese and Western views and

reporting schemes, consensus groups have formulated the Vienna classification

of gastrointestinal epithelial neoplasia and the Padova international classification of dysplasia [2] The Vienna classification recognizes the following categories:

- Category 1: Negative for neoplasia/dysplasia

- Category 2: Indefinite for neoplasia/ dysplasia

- Category 3: Noninvasive low-grade neoplasia (low-grade adenoma/dysplasia)

- Category 4: Noninvasive high-grade neoplasia

+ High-grade adenoma/dysplasia + Noninvasive carcinoma (carcinoma

in situ)

+ Suspicion of invasive carcinoma

- Category 5: Invasive neoplasia: + Intramucosal carcinoma (invasion into the lamina propria or muscularis mucosae) + Submucosal carcinoma or beyond

4 Macroscopic classification [3]

- Basic classification: Gross tumor morphology is categorized as either superficial or advanced type Superficial type is typical of T1 tumors while T2 - 4 tumors usually manifest as advanced types From the mucosal surface, gross tumor appearance is categorized into 6 types

Table 1:

Type 0

(superficial)

Typical of T1 tumors

from the surrounding mucosa Type 2

(ulcerative)

Ulcerated tumors with raised margins surrounded by a thickened gastric wall with clear margins

Type 3

(infiltrative

ulcerative)

Ulcerated tumors with raised margins, surrounded by a thickened gastric wall without clear margins

Type 4 (diffuse

infiltrative)

Tumors without marked ulceration or raised margins, the gastric wall is thickened and indurated and the margin

is unclear Type 5

(unclassifiable)

Tumors that cannot be classified into any of the above types

Type 0 is subdivided according to the macroscopic classification of EGC Table below shows subclassification of type 0

Table 2:

elevation or depression relative to the surrounding mucosa

Type 0 - Iia (superficial

Slightly elevated tumors

Type 0 - Iib (superficial

flat)

Type 0 - Iic (superficial

depressed)

depression

Slightly depressed tumors

(*: Tumors with ≤ 3 mm elevation are usually classified as 0 - IIa, with more elevated tumors being classified as 0 - I)

BASIC PRINCIPLES FOR DETECTING EGC

BY CONVENTIONAL ENDOSCOPY

In order to detect suspicious lesions for

EGC, doctor should familiarize themselves

with the basic principles of technique and

knowledge

1 Preparation

- Ideal preparation:

The aim of right preparation: To

minimize time and remove mucus and

froth from the mucosal surface 30

minutes before the procedure, patients

drink a mixture of water with mucolytic

and defoaming agents:

+ 100 mL of water with 20,000 U pronase,

1 g of sodium bicarbonate, and 10 mL of

dimethylpolysiloxane (20 mg/mL)

+ Or 100 mL of water mixed with 2 mL

of acetylcysteine and 0.5 mL activated

dimethicone

- Use of an antiperistaltic agent:

In the physiological state, the gastric

wall always moves due to peristalsis, for

administering an anticholinergic agent

such as:

+ 10 to 20 mg of scopolamine

butylbromide (buscopan) intramuscularly

or intravenously just before inserting the

endoscopy

+ Or 1 mg of glucagon if there are contraindications to the use of anticholinergic agents

2 Avoiding blind spots [4]

The first step in diagnosing EGC endoscopically is to detect any suspicious lesions, to characterize them and make

an accurate diagnosis [5] First of all, use white light endoscopy (WLE) During the endoscopy, in order to avoid blind spots, doctor should employ a standardized procedure to map the entire stomach

- A basic technique for avoiding blind spots:

+ Extending the gastric wall by air insufflation

+ Rinsing mucus and the froth from the gastric mucosa through irrigation with water and a defoaming agent

+ Mapping the entire stomach

- Use SSS system protocol (Systematic Screening protocol for the Stomach): This

is very useful, as shown in figure 1 In the SSS, pictures are arranged according to the order of the procedure, and take pictures of 4 or 3 quadrant views in either

a clockwise or counter-clockwise manner

If you find lesions, additional pictures can

be taken

Figure 1: Systematic screening protocol for the stomach

(Q: Quadrant; L: Lesser curvature; A: Anterior wall; G: Greater curvature; P: Posterior wall)

3 Knowledge of the endoscopist

- Determining the risk of development

of EGC:

As soon as inserting the scope into the

stomach, defining whether risk factors

for gastric cancer are present in the

background mucosa, such as Helicobacter

pylori-associated gastritis, gastric atrophy

or intestinal metaplasia [6] If the

appearance of gastric mucosa is normal,

with none of the abovementioned risk

factors, suspicious lesions for gastric cancer

are less likely Magnified endoscopic

observation, if available, is useful for

determining whether the gastric mucosa

is accompanied by such risk factors

- Awareness of signs of suspicious lesions:

+ With polypoid and ulcerative types (early gastric neoplasias) are easily detected

if doctors follow the SSS with optimum preparation

+ With superficial mucosal lesions that mimic gastritis (gastritis-like lesions) are very difficult to detect Accordingly, the key signs for detecting superficial mucosal neoplasia are the two distinct markers for detection on surface and color change, other markers changes in light reflection and spontaneous bleeding

(figure 2)

Figure 2: Endoscopic findings of

superficial depressed (0 IIc)

type EGC in the gastric cardia

4 Basic principles for characterization

of detected lesions

- Characterization using conventional

white light imaging (C-WLI) or chromoendoscopy

(CE):

After detecting a suspicious lesion through

careful SSS using conventional endoscopy,

doctor needs to differentiate between

cancerous and non-cancerous lesions

(characterization) For characterization, two

distinct markers, namely color and surface

morphology, should be applied to the

interpretation of the C-WLI endoscopic

findings CE using indigo carmine is useful

in enhancing the surface pattern [7]

Differential diagnosis using the following

criteria:

+ Well-demarcated border

+ Irregularity in color/surface pattern

If the C-WLI or CE findings fulfill both

criteria, we make the endoscopic diagnosis

of EGC

However, it is difficult to correctly diagnose minor gastric cancers (≤ 5 mm) or superficial flat (0 IIb) gastric cancers using C-WLI or

CE, because these lesion types yield only non-specific findings using conventional endoscopy alone In such cases, the following advanced imaging is useful in differentiating between small/flat cancers and focal gastritis

Figure 3: Endoscopic findings of

superficial elevated (0 IIa) type EGC in

the gastric antrum

(A: C-WLI shows a slightly elevated lesion The light reflection suggests something different in surface morphology B: Indigo carmine CE demonstrates a well-demarcated superficial elevated lesion with an irregular surface pattern)

- Characterization using advanced

endoscopy (magnifying endoscopy with

narrow-band imaging (M-NBI)):

According to Pasechnikov V et al,

there are several advanced endoscopic

techniques like magnifying endoscopy,

CE, novel high resolution virtual CE

techniques with narrow-band imaging

(NBI) with or without magnification

(NBI-ME), flexible spectral imaging color

enhancement (FICE) endoscopy with or

without magnification (FIME) and confocal

laser endomicroscopy (CLE), have been

tested for the diagnosis of EGC, with

promising results The most investigated

endoscopic technique seems to be NBI,

which has given promising results Since

M-NBI can help clearly visualize both the

microvascular pattern and microsurface

pattern [8] They developed the M-NBI

technique and proposed a comprehensive

diagnostic system, the vessel plus surface

(VS) classification system [9]

- Three categories of microvascular

pattern are defined:

+ Regular microvascular pattern: The

mucosal capillaries have a uniform shape

that can be closed-looped (polygonal) or

open-looped They have a homogeneous

morphology, have symmetrical distribution

and regular arrangement

+ Irregular microvascular pattern: The

vessels differ in shape, being

closed-looped (polygonal), open-closed-looped, tortuous,

branched, or bizarrely shaped, with or without

a network They have a heterogeneous

morphology, asymmetrical distribution and

irregular arrangement

+ Absent microvascular pattern: The subepithelial microvascular pattern is obscured by the presence of a white opaque substance (WOS) within the superficial part of the mucosa

- Three categories of microsurface pattern are defined:

+ Regular microsurface pattern: The morphology of the marginal crypt epithelium shows a uniform linear/curved/oval/circular structure It shows a homogeneous morphology, symmetrical distribution and regular arrangement When WOS

is present, regular WOS can be an additional marker of a regular microsurface pattern, defined as a well-organized and symmetrical distribution of WOS in a regular reticular/maze-like/speckled pattern + Irregular microsurface pattern: The morphology of the marginal crypt epithelium shows an irregular linear/curved/oval/ circular/villous structure It shows a heterogeneous morphology, asymmetrical distribution and irregular arrangement When WOS is present, irregular WOS can be an additional marker of an irregular microsurface pattern, defined as

a disorganized and asymmetrical distribution

of WOS in an irregular reticular/speckled pattern

+ Absent microsurface pattern: Neither the marginal crypt epithelial structure nor WOS are visible using M-NBI According

to the VS classification system, the characteristic M-NBI findings of EGC are

a clear demarcation line between the background noncancerous mucosa and the cancerous mucosa, and an irregular microvascular pattern and/or irregular

microsurface pattern within the demarcation

line Accordingly, we set the criteria for

making a diagnosis of gastric cancer as

follows: If the endoscopic findings fulfill

either or both, make the diagnosis of cancer, and make the diagnosis of non-cancer if neither is fulfilled And 97% of EGCs fit the above criteria [10]

Figure 4: VS classification

CONCLUSIONS

In conclusion, to find EGC in endoscopy,

we would like to stress that:

- Should have knowledge about histologic

classification of EGC

- Need to know how to have good

preparation, avoid blind spots when doing

endoscopy

- Need to familiarize ourselves with the

basic principles, firstly for detection and

secondly for characterization, using both

conventional endoscopy and advanced

endoscopic techniques (mostly as M-NBI

endoscopy)

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