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□ Fig. 108a-d. Female patient Zh., age 63. Diagnosis: gastric cancer. a Stomach roentgenogram (tight filling, vertical position, anterior projection): stomach cavity decreased, lesser curvature shortened and depressed, walls of the sinus are uneven (arrows). b Stomach roentgenogram (double contrast, horizontal position, anterior projection): the walls are rigid and thickened due to circular intramural infiltration (arrows). Conclusion: Infiltrative cancer of the stomach. c Macrospecimen of a resected stomach: the wall is firm over the entire length due to intramural infiltration. d Fragment of the macrospecimen (strip): the wall is thickened, white tumor tissue infiltrating the stomach wall is seen (arrows). Histologically, signet-ring cell carcinoma.

The endoscopic picture depends largely on localization of the tumor. In cases where the tumor is found mainly on the lesser curvature of the stomach body or in the antral part, slightly elevated sites of infiltration with indistinct margins are also revealed, firm (to instrumental palpation) and sometimes covered with a grayish coat (□ Fig. 109). Small flat ulcers in the center of the »infiltrate« are not infrequent.

If the affected region is limited largely to the greater curvature of the stomach, markedly thick-

▲ Fig. 109 d.

D Fig. 109a-d. Patient E., age 55. Diagnosis: gastric cancer. a Stomach roentgenogram (tight filling, vertical position, anterior projection) at the moment of contrast medium passage through the gastroesophageal junction: the lower third of the esophagus is irregularly narrowed, the contours are uneven (white arrows); the stomach cavity is markedly decreased, the stomach is disfigured (rigid tube), its contours are uneven (black arrows). b Stomach roentgenogram (double contrast, horizontal position, anterior projection): the cavity is decreased significantly, the walls are rigid due to diffuse circular intramural infiltration (arrows). Conclusion: Infiltrative cancer of the stomach with invasion of the esophagus. c Macrospecimen of the resected stomach: the inner surface of the stomach is occasionally covered with a grayish coat, the wall is firm over the entire length due to tumor infiltration which invades the esophagus. d Fragment of the macrospecimen (strip): wall is thickened, white tumor tissue is seen over entire length, which infiltrates the stomach wall (arrows). Histologically, adenocarcinoma with the signet-ring cell component.

□ Fig. 110a-c. Female patient S., age 64. Diagnosis: gastric cancer. a Stomach roentgenogram (tight filling, vertical position, anterior projection): the angular notch is straightened, the lesser curvature is depressed (arrow). b Stomach roentgenogram (double contrast, horizontal position, anterior projection): the wall of the notch is thickened due to intramural infiltration (arrow); the folds converge toward the involved site of the wall. Conclusion: Infiltrative cancer of the angular notch. c Endophotograph: mucous membrane is grayish pink, dull, with uneven surface; occasional scarlet papillary growths with a fibrin coat can be seen on the anterior wall and the lesser curvature of the stomach body. Stomach lumen is disfigured and narrowed. Histologically, adenocarcinoma with the signet-ring cell component

□ Fig. 110a-c. Female patient S., age 64. Diagnosis: gastric cancer. a Stomach roentgenogram (tight filling, vertical position, anterior projection): the angular notch is straightened, the lesser curvature is depressed (arrow). b Stomach roentgenogram (double contrast, horizontal position, anterior projection): the wall of the notch is thickened due to intramural infiltration (arrow); the folds converge toward the involved site of the wall. Conclusion: Infiltrative cancer of the angular notch. c Endophotograph: mucous membrane is grayish pink, dull, with uneven surface; occasional scarlet papillary growths with a fibrin coat can be seen on the anterior wall and the lesser curvature of the stomach body. Stomach lumen is disfigured and narrowed. Histologically, adenocarcinoma with the signet-ring cell component ened infiltrated rigid folds (sometimes eroded) do not stretch after intensive inflation of the stomach with air. In some cases, changes on the mucous membrane amount to only a small, shallow ulcer that looks benign, but during surgery, the infiltration can be seen to spread to the submucous and muscular coats. Regardless of the location of tumors, they have one property in common. Obvious changes on the surface of the mucous membrane must be visualized by endoscopy (□ Fig. 110). If the changes show only slightly on the surface of the mucous membrane, and the growth is mainly in the submucous coat, endoscopic examination proves ineffective.

In most cases, the changes revealed by endoscopy must be differentiated from various hyperplasias of the mucous membrane and post-ulcer deformities of the stomach, which are known to interfere with X-ray examination. Here, findings of histological examination ofbioptates obtained during fiber-gastroscopy become of special importance. In view of the specific nature of spreading in infiltrative cancer, multiple target biopsy is one of the most important requirements. At least five to seven specimens of tissues should be taken from the parts of the stomach wall which are in question based on X-ray examination and endoscopy. Target endoscopy of the mucous membrane is reasonable only when it is based on the findings of a preliminary roentgenological examination, which suggests that a particular part of the stomach should be visualized endoscopically (□ Fig. 111) [241, 259].

In explaining the reasons for the inappropriate use of endoscopy in Russia, most authors indicate a lack of adequate attention on the part of the endoscopist. As an example, they cite the results of gastric cancer control in Japan, where endoscopy is widely used for diagnostic purposes. In our opinion, however, the reason for late diagnosis of gastric cancer may not be connected with the endoscopists' lack of attention. In order to understand the inability of en-doscopy alone to reveal gastric cancer, it suffices to compare the results of gastric cancer diagnosis (a) by stages, (b) by the 5-year survival, and (c) by the death rates in USA and Japan, where high-quality endoscopy is available everywhere. An analysis of published data shows that in Japan, where endoscopy is preceded by an X-ray examination, the results

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are better by several orders of magnitude than in the USA, where endoscopy alone is normally used.

X-ray examination of the stomach prior to endo-scopic inspection ensures qualitative performance in two stages [24]:

1. Chromogastroscopy, i.e., intravital staining of the stomach mucosa during endoscopic examination

2. Endoscopic resection of the stomach mucosa from the area of pathological change, which was revealed preliminarily by X-ray or fiber-gastroscopy

The following two methods are mainly used to stain gastric mucosa: a 0.5% methylene blue solution (the dye method) or a 0.2% solution of indigo carmine (the contrast method). Both are based on visual contrast between the pathologically changed tissues and intact surrounding tissues. The method of staining with methylene blue is based on the active absorption of the stain in the foci of intestinal metaplasia and dysplasia of the gastric epithelium (stain diffusion through the membrane of malignant tu mor cells). The method employing indigo carmine, which does not stain the cells of the stomach mucosa, is based on distribution of the stain over the surface of the mucous membrane, giving a contrast image of its relief and pathologically changed parts.

Thus, target chromogastroscopy helps to visualize in detail pathological changes in the mucous membrane of the stomach, to locate them and determine their size, to verify changes in the relief and structure of the mucosal surface, and to take the necessary tissue specimens. However, as we have already said, target biopsy is unable to solve the diagnostic problem in all cases, especially in detecting early forms of infiltrative cancer of the stomach by examining a small number of specimens. Very often it is unable to establish a correct diagnosis of early gastric cancer or to estimate the extent of tumor invasion. A much larger fragment is often needed for a reliable conclusion.

Endoscopic resection of the mucous membrane from the suspected region can provide such large specimens. At present, the following two methods are most popular and widely used in clinical practice:

1. A standard loop excision

2. Aspiration of a specimen using a distal cap

Appropriately conducted endoscopy based on preliminary X-ray findings has far greater diagnostic value and a lower probability of possible complications during the procedure.

The reason for unsatisfactory diagnosis of gastric cancer should be sought in quite a different field. In infiltrative tumor growth the gastroscopic picture is far less conspicuous; this impedes not only verification of the nature of affection, but also visualization of its manifestations. In addition, there is the strong tendency toward an increasing proportion of endophytic new growths in the overall picture of gastric cancer and the decreasing number (or almost complete lack) of roentgenological examinations. Thus the absolute majority of tumors are revealed only in their far advanced stages, despite the expanding network of endoscopic units.

Unfortunately, the results of microscopic examination of specimens taken during target endosco-

▲ Fig.111 b.
▲ Fig.111 d.

py often turn out to be of low informative value. Errors in morphological verification of the nature of infiltrative tumors of the stomach are connected to a great extent with their structure. There is a strikingly large proportion of diffuse forms of tumors compared with other histological versions of malignant new growths of gastric mucosa. According to some authors, scirrhous cancers alone account for 41- 65% of all gastric carcinomas [97, 131,156, 157, 174]. The microscopic picture of this type of new growth is characterized by the presence of a marked fibro-plastic component. It appears as the spread of connective tissue, which surrounds occasional cancer cells or their small aggregations with strong ridges. This explains the serious difficulties we face while establishing the character of a pathology. According to M. Kanter et al. (1985) and Evans et al. (1986), up to one fourth of all diagnostic errors are due to incorrect interpretation of the revealed changes. The complexity of identifying tumor infiltration is confirmed indirectly by the old and persistent concept of the inflammatory genesis of linitis plastica - a form of diffuse cancer.

While discussing the reason for decreasing effectiveness of histological and cytological studies in revealing the endophytic form of gastric cancer, it is necessary to note such factors as the incorrect choice of the site for taking tissue specimens, technical difficulties in conducting biopsy, and the predominantly submucous spread of the process.

D Fig. 111a-d. Patient I., age 48. Diagnosis: gastric cancer. a Target stomach roentgenogram (tight filling, vertical position, anterior projection): the angular notch is straightened, its contour is uneven (arrow). b Stomach roentgenogram (double contrast, horizontal position, anterior projection): the contour is uneven, the wall is rigid, folds converge toward the affected part of the angular notch (arrow). c Stomach roentgenogram (double contrast, horizontal position, right half-oblique projection): with the optimal projection during roentgenotelescopy thickened wall of the notch due to intramural infiltration is visualized (arrow) with converging folds. Conclusion: Infiltrative cancer of the angular notch. d Endophotograph: a portion of mucous membrane with a diameter of about 3 cm, slightly elevated over the surrounding tissues is seen in the lower third of the stomach body at the border of the anterior wall and the lesser curvature; some mucosal folds converging toward the affected site do not straighten on inflation of the stomach with air. The mucous membrane in this region is scarlet, rough, with two eccentrically placed flat ulcers to 0.3 cm in diameter. Histologically, adenocarcinoma with the signet-ring cell component.

According to data in the literature, the best way to avoid mistakes in selecting the site for taking tissue specimens is to take many samples. The accuracy of morphological diagnosis increases from 70% to 98% if the number of bioptates increases from one to six or seven [201, 224].

It is more difficult to get around another cause of incorrect verification of the nature of pathology: mostly submucous spread of the tumor. In such cases, in addition to correct selection of the site for biopsy, it is necessary to take a tissue specimen from the submucous coat. However, the small (0.2 x 0.2 cm) branches of biopsy forceps can take only specimens of the mucous membrane. The situation is even more aggravated by the fact that even »sophisticated« methods of biopsy, such as loop biopsy, needle aspiration biopsy, artificial electro-ulceration with subsequent taking of the material from the ulcer using common forceps, or using »gigantic« forceps, are effective in not more than 50% of cases (Kaneki et al. 1983, Iishu et al. 1986, Graham et al. 1989, Levin et al. 1990). The results of our observations are more optimistic: Using »gigantic« forceps of our own design enhanced the efficacy of biopsy to 65-70% [37, 222].

In our opinion, standardization of the method could improve endoscopic identification of infiltra-tive tumors. Experience with radiological diagnosis of gastrointestinal pathologies, malignant tumors included, shows that using standardized programs

(other conditions being the same) increases the efficacy of examinations. Nevertheless, an obliterated and atypical visual picture, characteristic mostly of the early stages of gastric cancer or of later stages of the disease with submucous spread of the tumor, may significantly decrease the efficacy of fibergas-troscopy (D Fig. 112).

The accumulated experience indicates that an examination done in compliance with all current requirements can give us highly accurate information on the nature of the disease, and in some situations can outline the extent of spread. This is because even at the very early stages of cancer there may be a marked tendency to mostly submucous spread of tumor infiltration, giving a specific X-ray picture of uneven contours (with tight filling), wall thickening, and local decrease of elasticity (with double contrast). Traditional X-ray examination with filming gives the endoscopist additional information on the nature of the revealed changes and also on the best site for target biopsy using the relevant methods and appropriate tools.

Our vast experience in diagnosing the pathology in question indicates that many errors and difficulties in identifying minor forms of cancer may be avoided by using a complex of the traditional radiological and endoscopic examinations. Mutual exchange of information obtained by either of the methods increases the efficacy of early detection of infiltrative new growths with correct interpretation of the obtained results. Opposition to any of these methods can only harm the patient.

D Fig. 112a-d. Female patient M., age 68. Diagnosis: gastric cancer. a Stomach roentgenogram (tight filling, vertical position, anterior projection): stomach body is disfigured (rigid tube), gastroesophageal junction is wide open. b Stomach roentgenogram (tight filling, vertical position, left lateral projection): stomach body is disfigured (rigid tube), uneven contours of the posterior wall of the body (arrows). c, d Stomach roentgenograms (double contrast, horizontal position, left oblique projection, lateral projection): stomach cavity is decreased, walls of the stomach body and its upper part are thickened and rigid due to diffuse circular intramural infiltration (arrows). Conclusion: Infiltrative cancer of the stomach body with invasion of the esophagus. The patient was operated. Histologically, signet-ring cell carcinoma.

▲ Fig. 112 c.

No less complicated is endoscopic identification of the nature of so-called organic stenosis of the pyloric part of the stomach. In the presence of exacerbation of the primary disease, endoscopy of ulcer-caused stenosis detects some features of malignancy: hyperemia, edema of the mucous membrane, vulnerability to physical contacts, and the like. Or the tumor tends to mostly submucous spread. Valuable information can be obtained by instrumental palpation, which can estimate elasticity of the wall. Possible revival of peristalsis during fibergastroscopy in a patient with exacerbation of peptic ulcer, which is described in the literature, is, in our opinion, unimportant for the differential diagnosis. There is another incorrect belief that in cancer, even at its early stage, the motor function is absent. Peristalsis in blastomatous affections is absent only when the muscular coat is involved. This means that motor dysfunction may not be associated with the early stage of cancer, because it is characteristic only of deep invasion. The so-called therapeutic test acquires certain significance in such situations. It consists in a 2- to 3-week course of intensive anti-inflammatory therapy with subsequent radiological and endoscopic examinations. If the condition stems from an ulcer, the dynamics will be distinctly positive: edema and hyperemia of the mucous membrane will subside, peristalsis will be restored, etc. The pyloric function is restored in some cases as a result of the formerly existing functional spasm, which was mistaken for stenosis. Radiological examination is reasonable and effective in such situations. Although the presence of fluid and mucus, and in some cases food masses, interferes with the examination, skillful use of the classical method and double contrast help to verify the characteristic signs of blastoma-tous affection, on the basis of which one can conduct a differential diagnosis [55].

Data on the pathogenesis of gastric cancer that have accumulated to date indicate a close connection between malignant affection and chronic gastritis - one of the most common varieties of gastric pathology. Chronic inflammation of the mucous membrane often becomes the background against which a malignant tumor originates and develops. Atrophic gastritis is especially dangerous in this respect, and it is emphasized as being a risk factor in current gastro-oncology. This explains to a certain

□ Fig. 113. Patient G., age 41. Diagnosis: antral gastritis. Endo-photograph: the antral part is strongly disfigured and narrowed due to rough transverse folds, which do not straighten completely after insufflation of air. The mucous membrane is pale pink, smooth, and glassy.

degree the difficulties we face while differentiating between symptoms preceding cancer and signs that characterize tumor infiltration. It should be remembered that, in their early stages, neither gastric cancer nor chronic gastritis have pathognomonic signs. In advanced cancers, which are characterized by disintegration of tumor, metastases, and invasion of the neighboring anatomical structures, there appear subjective signs and changes that are detectable by instrumental examinations and leave no doubt as to the true nature of the pathology.

Based on such situations, clinicians concluded that it is possible to differentiate clinically between gastritis and gastric cancer. This, in turn, explains why the patient is directed to an endoscopist without a preliminary traditional X-ray examination of the stomach. Experience shows that this approach lengthens the diagnostic search significantly. By giving the patient an X-ray examination with subsequent endoscopy we have considerably shortened the time for establishing the diagnosis. Situations sometimes occur - especially in patients with diffuse intramuscular inflammatory processes, characterized by pronounced fibrous proliferation, leu-ko- and lymphocytic infiltration of the stomach wall, and thickening of its muscular coat - which cause rigidity of the wall, narrow and disfigure the antral part of the stomach, and cause disorders in peristalsis. Endoscopic examination alone is not enough to establish an accurate diagnosis, even if this is chronic gastritis, the most common pathology.

The symptoms described were the basis for the concept of »rigid antral gastritis«. Contrarily, we think it more reasonable to use the term »diffuse interstitial gastritis«, which demonstrates the connections between meta- and anaplastic processes in the stomach wall. Moreover, rigidity proper sometimes becomes a subjective factor in conclusions made by an endoscopist. Difficulties arising during the examination of such patients may be ruled out by the skilled performance of endoscopy. At the same time, the final conclusion as to the nature of the disease can only be reached by morphological examination of bioptates (□ Fig. 113). Sometimes repeated endoscopy is required after a course of anti-inflammatory therapy, because a single examination cannot always diagnose these pathologies.

Difficulties in verifying the character of the pathology arise in Ménétrier's disease. Differential diagnosis and exclusion of a possible tumor require fi-

bergastroscopy and biopsy. In order to verify the diagnosis morphologically, bioptates must contain tissues taken from the submucous coat, because the process often begins in the epithelium of the glandular floor of the mucous membrane (□ Fig. 114).

Menetrier's disease manifests endoscopically as hyperemia and edema of the mucous membrane and severe thickening of the folds, which are sometimes covered with polypoid growths. It is important to study the functional symptoms for a differential diagnosis. Stretching of the folds and distinct reduction of their caliber (which are detectable by endoscopy) leave practically no doubt as to the inflammatory nature of hyperplasia of the mucous membrane. The benign character of changes is also confirmed by the preservation of a certain elasticity of the walls, which is detectable by X-ray examination at the phase of double contrast, as well as by instrumental palpation during endoscopy. Disfiguring and narrowing of the stomach lumen in the gigantic-fold type of endophytic cancer do not disappear even during inflation of the stomach with air; wall rigidity also remains stable at the double-contrast phase during the X-ray examination. Locations of erosion and sub-mucous bleeding in the involved zone are also important for the differential diagnosis. In Menetrier's disease, erosions are usually few and are located on the fold apices, but in in-filtrative cancer these changes are multiple and more often located between the folds.

□ Fig. 114. Patient L., age 56. Diagnosis: Ménétrier's disease. Endophotograph: very thick and closely spaced sinuous folds in the stomach body on the greater curvature, which do not straighten after stomach inflation with air. The mucous membrane is hyperemic and edematous; occasional sites with fibrin deposits

□ Fig. 115. Patient V., age 62. Diagnosis: infiltrative cancer concurrent with atrophy of the gastric mucosa. Endophotograph: against the background of marked vascular injection in the submucous coat, seen is a dull portion of the mucous membrane lacking vascular pattern, with punctate submucous hemorrhages and rough surface. Histologically, adenocarcinoma.

□ Fig. 115. Patient V., age 62. Diagnosis: infiltrative cancer concurrent with atrophy of the gastric mucosa. Endophotograph: against the background of marked vascular injection in the submucous coat, seen is a dull portion of the mucous membrane lacking vascular pattern, with punctate submucous hemorrhages and rough surface. Histologically, adenocarcinoma.

□ Fig. 116. Female patient O., age 43. Diagnosis: superficial gastritis. Endophotograph: the mucous membrane of the stomach is pink, smooth, and glassy, with foci of hyperemia.

It should be noted that in some cases, endoscopic signs of the tumor are difficult to distinguish from visual signs of atrophic and superficial forms of gastritis (□ Fig. 115), but thorough and purposeful examination and interpretation of the revealed chang es can give grounds to suspect cancer even in cases where the differential diagnosis is difficult. Thus, in the endoscopic picture resembling atrophic gastritis (smooth relief of the mucous membrane, its whitish shade, absence of folds), the tumor character is evidenced by the focal nature of affection, by the color contrast between the »frosted« infiltrated wall and surrounding scarlet intact tissues, and by the absence of a vascular pattern in the tumor zone.

Endoscopic signs that are common to both superficial gastritis and diffuse cancer include smooth relief in the involved zone, its uniform elevation, hy-peremia, edema, and easy vulnerability on physical contact. The differential diagnosis in such cases is based mostly on inflammatory changes in the mucous membrane which are less pronounced in gastritis than in cancer, but this parameter is so relative and subjective that, in our opinion, it cannot be regarded as convincing (□ Fig. 116). In addition, the limited nature of affection, the local character of the changes, their homogeneity, and the rigidity of tissues are the distinguishing signs of tumor in such cases (□ Fig. 117). A correct diagnosis can be established in most cases with a preliminary traditional roentgenological examination. Moreover, the complex approach, including radiological diagnosis and endoscopy, with subsequent histological examination of the tissue specimens obtrained, guarantees a correct diagnosis.

Thus, establishing the diagnosis of gastric cancer, especially in its early stages, requires rational use of all modern methods of examination (radiological, endoscopic, morphological). The initial and very important stage includes the use of the traditional X-ray examination based on the study of stomach contours and also on information obtained by double-contrast radiology. Using the complex of methods of radiological diagnosis (ultrasonography, CT, MRI) in difficult diagnostic cases requiring verification broadens the possibilities for correct assessment of the radiologically revealed changes and helps to carry out purposeful and adequate endos-copy with the taking of tissue specimens for histological examination. With due account to the specific character of the spread of infiltrative cancers, which presents the greatest difficulties for their identification, much effort should be directed at increasing the efficacy of endoscopic diagnosis, by conduct-

□ Fig. 117. Patient D., age 60. Diagnosis: gastric cancer. Endo-photograph: the lumen of the stomach is hyperemic and narrowed due to circular intramural infiltration. Histologically, signet-ring cell carcinoma.

ing multiple target biopsies and also by improving methods for taking tissue specimens from deeper parts of the mucous and submucous coats. New potentials for timely detection of minor endophytic gastric cancer, which is usually characterized by meager and atypical clinical signs (or to be more accurate, by their absence) may be realized by conducting control X-ray examinations of persons belonging to the so-called risk groups (e.g., patients with chronic inflammatory diseases of the stomach).

The problem of diagnosing diffuse cancer is the problem of diagnosing gastric cancer on the whole, because infiltrative tumors account for the discouraging statistics of advanced cancer in modern gas-tro-oncology. The problem of early diagnosis and adequate treatment can only be solved with due consideration of all available signs in radiological and endoscopic studies of tumor infiltration. The new technologies of radiological diagnosis, such as ultra-sonography, computed tomography, and magnetic-resonance imaging, provide additional help in particular situations.

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