Post on 12-Dec-2016
Gut, 1976, 17, 41-47
Review of five cases of early gastric carcinomaD. I. FEVRE, P. H. R. GREEN, P. J. BARRATT, AND G. S. NAGY
From the Royal North Shore Hospital of Sydney, St Leonards, N.S. W., Australia
SUMMARY Five cases of early gastric carcinoma (EGC) were seen in 12 months. The clinical featuresdid not provide guide-lines to diagnosis, which depends on air contrast barium studies, endoscopicrecognition of early malignancy, adequate biopsies, and their interpretation. Malignancy was pre-
sent in an average of 60% of the biopsies taken. The most common type of lesion was lIc. Thesuperficial nature of the malignancy was predicted at endoscopy in four cases but was unsuspectedin one case which was considered to be advanced carcinoma until the resected specimen was
thoroughly examined microscopically. The excellent prognosis ofEGC was discussed. Only conserva-tive surgery need be performed if the superficial nature of the lesion is recognized before operation.
Early gastric cancer (EGC) can be defined as carci-noma confined to mucosa or submucosa withoutinfiltration into the muscularis propria (Murakami,1971). This condition is well recognized in Japanwhere mass screening is used to detect carcinomabecause of its high prevalence (Segi, 1969), but isseldom recognized in Australia, the UnitedKingdom, and U.S.A., judging by the sparsity ofreferences in the literature. The high five yearsurvival rate of surgically treated EGC (more than95%/0) compared with that of advanced gastriccancer (approximately 30%) (Ransom, 1953; Muto,1962) provides the stimulus for making a diagnosis atthis stage of disease.The detection of this early lesion requires team
work between expert radiologists giving good aircontrast barium studies, experienced endoscopistsaware of the condition, and histopathologistscapable of interpreting the small biopsy specimens.
This paper describes our experience of earlygastric carcinoma during a 12 month period. Duringthis period, five cases of early gastric cancer wereseen among a total of 26 cases of gastric carcinomaon whom endoscopy was performed.
Methods
RADIOLOGYAir contrast barium studies were performed in allour patients as outlined by Shirakabe (1971).
ENDOSCOPYOlympus gastroscope type GFB was used on all
Received for publication 2 October 1975
41
patients except one: Olympus JFB duodenoscopewas used in case 5. All patients had topical ligno-caine 4% applied to the pharynx together with 5 to10 mg intravenous diazepam as premedication.The classification of lesions considered to be early
gastric cancer was that used by the Japan Society forGastroenterological Endoscopy, and is shown inFig. 1.At least seven biopsies were taken from all lesions
with emphasis on edges of the depressed areas.
PATHOLOGY
Preparation and examination of biopsy materialBiopsies were placed on paper and each biopsy put
Type I Protruded
Type II SuperficialNa Elevated --
717T" SIBzl,,I" , I Z
IIb Flat _T_T ______"I____7___
IIc Depressed
Type III Excovated.... fZ,,,,,...... =z
Fig. 1 Endoscopic classification of early gastriccarcinoma.
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D. I. Fevre, P. H. R. Green, P. J. Barratt, and G. S. Nagy
Fig 2 Fig 3Fig. 2 Case 2. Radiograph showing well-circumscribed area of elevated mucosa adjacent to the lesser curvature.
Fig. 3 Case 4. Radiograph showing superficial ulceration and induration. There is mucosal deformity with thickeningof the termination of the folds, most of which fall short of the area of induration and ulceration.
into 10% formol saline in separate numbered con-
tainers. Histological sections stained with haema-toxylin and eosin were examined.
In doubtful instances of poorly differentiatedcarcinoma a PAS/Alcian Blue stain was used to showindividual malignant cells in the lamina propria.
Preparation of resected stomachThe resected stomachs were brought to the laboratoryimmediately on removal and opened along thegreater curvature. They were then laid out flat, pin-ned, and photographed. They were fixed for at least48 hours.
Blocks were then cut through the entire areas
suspected of being involved by carcinoma. The
specimen was photographed with blocks in place andeach block was carefully numbered. Lymph nodeswere also sectioned. Sections were then cut andstained routinely.
CLASSIFICATION
MacroscopicThe gross appearances were described according tothe classification of the Japan Society for Gastro-enterological Endoscopy (Fig. 1).
MicroscopicAll lesions were adenocarcinoma and were describedaccording to the degree of differentiation. They were
Patiernt Age (yr) Sex Presentation Barium meal Endoscopy Other illness
1. A.T. 76 F Anaemia 18/12 Irregularity distal antrum Depressed area mucosa Severe aortic valve? malignancy ? Ilc early gastric cancer disease
2. E.G. 68 F Anaemia weight Gastric polyps and Small elevated lesion ? Died; ischaemic heartloss 6/12 irregular polyp Ila early gastric cancer disease. No cancer at
necropsy3. L.L. 73 F Pain weight loss Irregular area in antrum Small depressed area ? Nil
2/12 ? malignancy IIc early gastric cancer4. A.S. 73 M Pain 9/52 Gastric ulcer Depressed area of Ischaemic heart disease
mucosa-cancer5. M.B. 53 F Pain weight loss Normal Depressed area of Nil
30/12 mucosa-cancer
Table 1 Presenting symptoms and results of investigations
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Review offive cases of early gastric carcinoma
Fig. 4 Case 2. Endoscopy showing a non-ulceratedelevated mucosal lesion (type lla).
predominantly either well differentiated or poorlydifferentiated. The well-differentiated tumours hadeither a tubular or a papillary pattern. The poorlydifferentiated tumours showed malignant cellsspreading singly in the lamina propria. A variablenumber of these cells were mucus secreting andsometimes had a classical signet ring appearance.
Results
The presenting symptoms and the results of investi-gations on each patient are summarized in Table 1.
RADIOLOGY
The possibility of malignancy on barium studies wassuggested in two of the five cases (1 and 3), whileendoscopy was suggested for clarification by the
Fig. 5 Case 4. Endoscopy showing a depressed areaof mucosa (type IIc lesion).
radiologist in cases 1, 2, and 3. Case 2 showed anelevated area of gastric mucosa (Fig. 2). Case 4 wasreported initially as a gastric ulcer which, on retro-spective examination of the films, had the featuresof a malignant ulcer. A repeat barium meal afterendoscopy showed many features of malignancy(Fig. 3). Case 5 had two barium meals reported asnormal during the period of her illness; review ofthese films, however, did not show an adequatemucosal pattern of the involved region.
ENDOSCOPY
At endoscopy, all the patients were considered tohave malignant lesions. Cases 1, 2, and 3 were con-sidered to be early gastric cancer, while cases 4 and 5were considered to be malignant, early gastriccarcinoma being reported only after examination of
Patient Site Size (cm) Type Total no. biopsies No. biopsies with Histopathological typetaken carcinoma seen
1. A.T. Antrum 1 x 0-5 IIc 9 4 Well-differentiated tubularadenocarcinoma
2. E.G. Anglus lesser curve 3-5 x 2 Ila, Ilb 9 8 Well-differentiated papillaryadenocarcinoma
3. L.L. Anglus lesser curve 1-7 x 1-0 IIc 7 2 Poorly-differentiated carcinoma-mucus secreting
4. A.S. Lesser curve antrum 4 x 3 tIc, III 11 8 Poorly-differentiated mucussecreting carcinoma
5. M.B. Lesser curve antrum 9 x 7-5 l1c, III Il 6 Poorly-differentiated mucussecreting carcinoma
Table 2 Relation between number of biopsies and carcinoma
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D. L Fevre, P. H. R. Green, P. J. Barratt, and G. S. Nagy.
Fig. 6 Case 5. Resected stomach showing large IIcearly gastric cancer.
the resected specimen. Figure 4 shows the elevatedappearance (Ila type lesion) seen at endoscopy incase 2. Figure 5 shows the depressed llc type lesionof case 4.
PATHOLOGY
Biopsy materialTable 2 shows the relation between the number ofbiopsies taken and those showing carcinoma.
RESECTED STOMACHS
MacroscopicFour of the five lesions were either totally or pre-dominantly llc in type. The others were Ila and ilb(Table 2). This corresponded well with opinion onendoscopy.
Figure 6 shows the unfixed stomach from case 5in which the Ilc lesion measured 9 x 7-5 cm.
MicroscopicTwo carcinomas were well differentiated and threewere poorly differentiated. They were all confinedto the mucosa. There was no evidence of lymphaticinvolvement.
In the two largest lesions, cases 4 and 5, mostsections showed carcinoma toward the periphery ofthe depressed area (Fig. 7) but towards the centrethere were areas of mucosa in which carcinoma wasnot visible. In some places the mucosa was eroded(Fig. 8) in others it was thin but intact (Fig. 9).
* . Fig. 7 Case 4. Edgeof depressed area.Poorly differentiatedcarcinoma is presentin the upper part ofthe mucosa. H and E~~~~~~ ~~x 300.44
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Review offive cases of early gastric carcinoma
-me4, r~~~~rt~~~~~~w"¾ ~~~~~'~~~4-r't ,r,* ,~~~~~~~~~~~~~~~~~' r ~ ~
.....
tj
Discussion
CLINICAL FEATURESThree of the patients presented with abdominal pain,the nature being consistent with peptic ulceration.
Fig. 8 Case 8. Thineroded mucosa fromthe centralpart ofthe depressed area.No carcinoma ispresent. H and Ex 300.
Fig. 9 Case 8. Thinintact mucosa fromthe central part ofthe depressed area. Nocarcinoma is present.Biopsies taken fromareas shown in Fig. 8and Fig. 9 wouldhave been misleading.H and E x 300.
The other two patients had anaemia which initiatedinvestigation of their gastrointestinal tract. In con-trast, most Japanese patients are asymptomatic andare diagnosed on mass screening techniques using aircontrast barium studies or gastro-camnera studies,
45
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D. L Fevre, P. H. R. Green, P. J. Barratt, and G. S. Nagy
Fig. 10 A polypoidborderline lesion whichthe Japanese call ATP(an atypical epitheliumof the stomach). Theglands are crowded andcellular atypia ispresent but not asmarked as inadenocarcinoma.H and E x 75.
Only 40% of their patients have symptoms on pre-sentation, usually pain (Kasumi, 1975). It is difficultto know whether the symptoms are related to theirgastric lesions.The long duration of symptoms in case 5 is not
incompatible with EGC, because the lesion may bepresent for five to 10 years before invasion beyondthe mucosa occurs (Sano, 1972).
PATHOLOGYTable 2 shows that carcinoma was present in onlyabout half the biopsies taken. This is partly due todfficulty in taking biopsies but mainly to the factthat part of the depressed area is devoid of carci-noma. Histological examination clearly demon-strated that the most likely place to find carcinomain a IIc type lesion was close to the edge of thedepressed area.As far as interpretation of biopsy material is con-
cerned, carcinoma can be reported with confidenceif individual malignant cells can be seen in thelamina propria. This is found in poorly differentiatedcarcinoma and was seen in three of these patients.
If the carcinoma is well differentiated, biopsyinterpretation is much more difficult. The differentialdiagnosis includes actively regenerating epitheliumand the lesion which Japanese pathologists call ATP,which stands for an atypical epithelium (Sugano etal., 1971; Yokoyama et al., 1974), ATP is a polypoidlesion with atypical features of the glandular pattern
of the epithelium (Fig. 10). It is considered to be abenign or borderline condition.The Japanese believe that it corresponds to dys-
plasia of the uterine cervix and should be followedup by endoscopy rather than resected.The main distinguishing features in differentiating
carcinoma from degenerating epithelium or ATP areas follows. Regenerating gastric epithelium is usu-ally not sharply demarcated from the surroundingepithelium but shows a more gradual transition thancarcinoma does.
In ATP the cellular atypia is not as great as it is incancer. Also, well-differentiated cancer usually in-volves the whole layer of the mucosa, whereas ATPmay have normal glands below and normal surfaceepithelium above.When examining the resected stomach, it is pre-
ferable to take blocks from the whole specimen butobviously in many routine laboratories this is notfeasible. Alternatively, the entire area involved bycarcinoma must be examined until the pathologistis confident that the limits of the lesion have beenreached. Otherwise, it is possible that an area of sub-mucosa or intramucosal invasion will be missed.At surgery, there was no evidence of metastatic
carcinoma in our five cases and no evidence wasfound at necropsy in case 2.
PROGNOSISTbe prognosis of EGC, as stated earlier, is excellent,
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Review offive cases of early gastric carcinoma 47
but, as the disease tends to occur in older patients,other illnesses may be present and death due to thesetends to occur in the follow-up period (Kidokoro,1971).The recurrence rate of EGC appears to be about
5 % (Hayashida 4'7%, 1969; Sano 4-5y%, 1971).Important factors affecting the recurrence in EGCare the depth of cancer invasion, lymph nodemetastases, and vascular invasion. Cancer confinedto the mucosa has a very low recurrence rate, sub-mucosal cases show occasional recurrence, and it isin these that metastases to lymph nodes tend tooccur (Yamada et al., 1974; Yamada, 1975).
All our patients had extensive gastrectomies shortof total gastrectomy. However, there is evidencethat more conservative surgery is sufficient (Yamada,1975).
It can be seen that the prognosis varies inverselywith the depth of invasion-that is, the earlierthe diagnosis, the better the prognosis. It is pro-bable that early diagnosis can only be madewith early endoscopy and we suggest gastrocopy inall patients with abnormalities on barium studiesat our hospital. We also endoscope those withnormal barium studies who have persistent uppergastrointestinal symptoms.
We are grateful to Dr John Hunt, Director ofRadiology, for interpretation of the barium mealsand to Professor D. W. Piper for his encouragementand help in the preparation of this article.
References
Hayashida, T. (1969). End results of early gastric cancercollected from 22 institutions. Stomach and Intestine.Japan, 4, 1077-1085.
Kasumi, A. (1975). National Cancer Centre. Japan. (Personalcommunication.)
Kawai, K. (1971). Diagnosis of early gastric cancer. Endo-scopy, vol. 3., No. 1.
Kidokoro, T. (1971). Frequency of resection, metastases andfive-year survival rate of early gastric carcinoma in asurgical clinic. Gann Monograph on Cancer Research, 11,45-49.
Murakami, T. (1971). Pathomorphological diagnosis. GannMonograph on Cancer Research, 11, 53-55.
Muto, T. (1962). Factors influencing surficial results forgastric cancer. Nichushikaishi Japan, 47, 135-145.
Ransom, H. K. (1953). Cancer of stomach. Surgery, Gyne-cology, and Obstetrics, 96, 275-287.
Sano, R., and others (1972). Pathological evaluation of recur-rence and mortality in early gastric cancer. Stomach andIntestine, 5, Japan, 531-540.
Segi, M. (1969). Cancer Mortality for Selected Sites in 24Countries, no. 5 (1964-65), pp. 100-101. Department ofPublic Health: Tohoku University School of Medicine.Sendai, Japan.
Shirakabe, H. (1971). Double Contrast Studies of the Stomach.Bunkodo: Tokyo.
Sugano, H., Nakamura, K., and Takagi, K. (1971). Anatypical epithelium on the stomach. A clinico-pathologicalentity. Gann Monograph on Cancer Research, 11, 257-269.
Yamada, K. T. (1975). A.I.C.H.I. Cancer Centre. Nagoya.(Personal communication.)
Yamada, E., Nakazato, H., Koike, A., Suzuki, K., Kato, K.,and Kito, T. (1974). Surgical results for early gastriccancer. International Surgery, 59, 7-14.
Yokoyama, Y., Yokoyama, H., and Nagayo, T. (1974).On biopsy of excavated gastric lesions-with specialreference to differential diagnosis of atypical regenerativeand cancerous epithelia. Stomach and Intestine, vol. 9, no.1, 9-20.
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carcinoma.Review of five cases of early gastric
D I Fevre, P H Green, P J Barratt and G S Nagy
doi: 10.1136/gut.17.1.411976 17: 41-47 Gut
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