“Considerations about superficial and ‘Early’ gastric carcinoma”に答えて

CONSIDERATIONS ABOUT SUPERFICIAL AND “EARLY” GASTRIC CARCINOMA

　左記のような原稿が春日井委員を通じて編集委員会にもたらされた．相談の結果，これは早期胃癌という言葉を私どもが用いている限りつきまとう閥題であるので，この際，手紙に対する返事のような形で私どもの考えを表明しようということになった．ことに日本で用い始めた医学用語が外国に輸出されることは比較的稀なことなので，それなりに十分な配慮というか，それが生まれてきたいきさつ，ないしは背景をある程度詳しく述べておくことが必要であるように思われる．

　私どもも現在，すなわち1969年の時点に立ってこの種の胃癌を学問的に正しく命名せよといわれれば，あるいはsuperficial carcinoma，もしくはlimited carcinomaという言葉を選んだかもしれないと思う．しかし予後のよい胃癌，切れば100％に治る胃癌を早期胃癌という旗印の下に求めて，長い間暗中模索し，その後，次第に手懸りを得て，ある種の症例をグループ化し，その概念をまとめあげて，それにもっともよく適合する定義として「癌のひろがりが粘膜層または粘膜下層までで限局しているもの」という組織学的な約束を作り上げるに至ったさい，それでは最初に掲げた旗印の表現が少し非論理的になったからといって，そう簡単に変更できるものではない．いいかえれば，私どもも始めからすべてを知っていたのではなく，治る癌をと追い求める長い間の努力によって次第に現行の概念へと近づいたのである．そして私どもは，その結果生じた論理と名称の食い違いを多少残念だとは思うけれども，学問ことに医学の進歩というものには，ことに臨床や公衆の健康に関係する知識の進歩には，多少の食い違いが生ずることは止むを得ないのではないかと考えている．私どもが日頃用いている言葉の中にもそれに類する沢山の医学用語を多数見出すことができるからである．

Question

　The recognition of gastric carcinoma in a still curable phase must be our goal in dealing with this malignant tumor. As McNeer and Pack (1) said, “the words “early” and “curable” as applied to cancer are not of necessity synonymous, although it is only human to equate both terms with the small size of the cancer and with symptomatology of short duration”. However, it is all too common to find that the 5-year survivors have usually a long history, suggesting that they had an “old” cancer in a chronogical sense but, more important, slow-growing or of low biological aggressiveness.

　The word “early” has a chronological meaning, and when applied to cancer would have to mean a tumor of recent onset. However, it is reasonable to assume that most of human epithelial tumors have periods, each one measurable in several years, of non-vinvasive stages. This has been especially well documentecl in the cases of the uterine cervix and urinary bladder.

　In the case of the urinary bladder, it has been shown that a latent period, from the initial exposure to the carcinogenic agent, of normal carcinogenic findings, and of unpredictable duration, often as long as 10 to 15 years, precedes the stage of cellular abnormalities. This second period of pre-malignant changes also has a long duration, until the stage of in situ (non-invasive intraepithelial) carcinoma is reached. The data in the urinary bladder studies (2-5) support the idea that from 2 to 7 years elapse from the first initial diagnosis of in situ carcinoma until the development of invasive carcinoma of the bladder.

　In the uterine cervix, the long duration of the in situ stage has been established by Boyes et al (6) and Koss et al (7): such lesions can take 13 to 20 years to progress to the invasive stages.

　The studies of Schade (8) on in sizu and superficial gastric carcinoma support the view that similarly long periods of time are involved in the development and growth of gastric carcinoma.

　When a carcinoma breaks the basement membrane of the epithelium of its origin, and becomes invasive, it does not spreads locally or metastasizes immediately: there are reasons to suspect that it stays micro-invasive for some time. There are several reports of superficial carcinomas of the stomach, bronchi, uterine cervix and urinary bladder that did not “grow” for long periods of time. But, there is little we can do in predicting how long it will remain so, or if such a case has not already metastasizecl when first seen. Having break (sic) the barrier (?) of the basement membrane, the now invasive tumors, differ very much in growth capacity and speed in metastasizing. Factors to be determined appear to have more importance than the pure histologic features. From this “unpredictable” behavior, the theory of biologic predeterminism of malignant tumors has its inception.

　We usually recognize cancer in its last stage, after metastatic spread. At this point, very little can be offered to the patient in addition to palliative procedures. The vast majority of gastric carcinomas are seen in this stage, and the only country that is reversing the trend is Japan. Some authors (9, 10) have been impressed by the fact that a long history usually has a good prognostic value and use this argument against the concept of “early” diagnosis in the chronological sense. MacDonald (9), coined the expression “biologic precleterminism” to explain this “contradictory” behavior of cancer. To him, the prognosis of a case is decided much earlier than we can diagnose, and is determined probably by genetic principles. Attractive as it is, this theory has been very clifiicult to prove, and in our opinion, has been refuted by the Japanese experience, at least 1 the case of gastric carcinoma.

　The mucosal and submucosal carcinomas ocasionally have lymph node involvement, especially of the peri-gastric groups: this shows that even minute and superficial foci of gastrlc carcinoma can disseminate. However, the clinical behavior of this type of “metastasis” has not been fully studied, and apparently they do not necessarily have the same signficance of the similar counterparts in advanced frankly invasive carcinoma.

　With the remarkable progress made in the diagnostic methods, especially endoscopy, radiology, and the use of mass surveys, the Japanese clinicians are making in increasing number of cases the diagnosis of gastric cancer in its curable phase. Right now, about 25% of the gastric (11) carcinomas operated in Japan will be cruutitvely excised because the cancer is limited to the mucosa or submucosa. However, we feel that a change in terminology is needed. The Japan Gastroenterological Endoscopy Society defined such tumors as Early Carcinoma. Based upon the fact we do not know how old these carcinomas are, on the above outlined natural history of epithelial tumors, and on the fact their definition is based upon morphological features, I suggest that this type of gastric carcinoma should be called Superficial Gastric Carcinoma. This name has been used in the past with the exactly same morphological meaning (12, 13). This term has been considered more applicable than “Superficial spreading Carcinoma” of Stout because it is not certain that all these tumors have spread superficially, at the time and in the place they were observed (13). The equivalent to the English word has been used by German pathologists describing these lesions: “oberfiiichlicher Schleimhautkrebs des Magens” by Konjestzny (14), that can be literally translated by “Superficial Mucosal Carcinoma of the Stomach”.

　This morphological name, Superficial Gastric Carcinoma, would make the Japanese contribution more easily understood and accepted in the English literature, and would avoid the great controversy about “early” cancer and “early” diagnosis of cancer.

　As said in the beginning, the words “early” and “curable” when applied to cancer are taken as synonymous, especially in the lay language. As mass media communication is probably important in the organization and success of mass surveys, the name “early” may have psychological advantage over “superficial”, that not usually means curable in the lay language. Remains to the Japanese clinicians to weight (sic) this probable advantage against the above outlined arguments.

REFERENCES

1) McNEER, G., and PACK, G. T. (Edit.) Neoplasms of the Stomach. J. B. Lippincott Co., Philaclel phia, 1967.

2) MELAINIED, KOSS, L. G., RICCI, A., and VV. F.; Cytohistological Observations on Developing Carcinoma of Urinary Bladder in Man. Cancer 13: 67-74, 1960.

3) MELAMED, M. R., VOUTSA, N. G., and GRABSTALD, H.: Natural History and Clinical Behavior of in situ Carcinoma of Human Urinary Bladder. Cancer 17: 1533-1545, 1964.

4) KOSS, L. G,, MELAMED, M. R., RICCI, A., MELICK, W. F., and KELLY, R. E.: Carcinogenesis in the Human Urinary Bladder. Observations after Exposure to Para-aminodiphenil. New England J. Med. 272: 767-770, 1965.

5) MELAMED, M. R., GRABSTALD, H., and WHITMORE, W. F.: Carcinoma in situ of Bladder: Clinico-Pathologic Study of Case with a Suggested Approach to Detection. J. Urol. 96: 466-471, 1966.

6) BOYES, D. A., FIDLER, H. K., and LOCK, D. R.: Significance of in silu Carcinoma of Uterine Cervix. Brit. M. J. 1: 203-205, 1962.

7) KOSS, L. G.: The Cytological Diagnosis of Cancer. Geriatrics 19: 745-759, 1964.

8) SCHADE, R. O. K.: The Development and Growth of Gastric Cancer. Also an Attempt at the Definition of Gastric Carcinoma in situ. In RECENT ADVANCES IN GASTROENTEROLOGY. The Proceedings of the 3rd World Congress of Gastroenterology, Tokyo, 1966. Vol I: pgs 255-259.

9) MACDONALD, I.: Biologic Predeterminism in Gastric Carcinoma as the Limiting Factor of Curability. Surg., Gynec. Obst. 98: 148-152, 1954.

10) MAIMON, S. N., PALMER, W. L., and KIRSNER, Prognosis in Gastric Cancer. A Study of Five-Year Survivors. Amer. J. Med. 5: 230-236, 1948.

11) YAMAGATA, S., MASUDA, H., and ISHIOKA, K.: Epidemiology and Symptomatology of Early Cancer of the Stomach. in RECENT ADVANCES IN GASTROENTEROLOGY. The Proceedings of the 3rd World Congress of Gastroenterology, Tokyo, 1966. Vol.1: pgs 487-489.

12) HEBBEL, R.: Superficial Carcinoma of the Stomach. Bull. Univ. Minn. Hospital 22: 59-67, 1950.

13) FRIESEN, G., DOCKERTY, M. B., and ReMINE, W. H.: Superficial Carcinoma of the Stomach. Surgery 51: 300-312, 1962.

14) KONTJESTZNY, G. E.: Der oberfiiichlicher Schleimhautkrebs des Magens. (Ein weiterer Beitrag zur Kenntnis des Magenkrebses im Beginn). Chirurg 12: 192, 1940.

Reply

　The above contribution was recently sent to the editorial committee of this nagazine by way of one of its staff members, Dr. Kasugai. After discussing among us regarding the purport of this paper, we decided that as a moot point would invariably arise as long as we use the word “early” gastric cancer, our definition as well as our present concept should be made clear once for all in the form of an answer to the above contribution.

　This we assumed especially pertinent to the problem as a medical term first begun to be used in Japan has rarely been “exported” to foreign countries before We considered, therefore, satisfactory explanation must be given how the matter stood when we first began to adopt the word “early” in the initial stage of the study of our early gastric cancer.

　Were we asked now in 1969 to designate this category of gastric cancer precisely from the scientific standpoint, certainly we might favor either “superficial” carcinoma or “limited” carcinoma for its designation. However, in the past or in the beginning of its study, “early” gastric cancer was the watch word under which we Japanese researchers have long toiled, groping as it were in darkness for gastric cancer with good prognosis, or cancer with one hundred per cent curability if resectecl. Then some clues were found in certain varieties of gastric cancer in the long steps of the research. We triecl to pick up such cases out of many suspicious ones to form the common conception or to give the definition of early gastric carcinoma. At last their histological features were examined and it was settled finally to define the “early gastric cancer” as a cancer whose extent is confined within the mucosa or at most within the submucosal layer. And now when the prospects have become bright for the management of gastric cancer, we do not intend to alter the designation we initially chose simply because it has become a little inconsistent. In other words, it is not that we knew all about “early” gastric cancer from the outset but that the results of our long endeavors in search of curable cancer have gradually led us to approach the present-day conception of “early” gastric carcinoma. Discrepancy, regrettably found between the term and the current usage of the word, can not be helped, we think, for such incongruity is abundantly found elsewhere in technical terms as inevitable adjuncts to the progress of science, especially of medical science, the more so in the knowledge related to clinical medicine and to people's welfare.

　We shall further itemize concerning the history of the origin, as applied to gastric cancer, of the word “early” as well as its background now being placed in Japan.

　1. The term “early” cancer as it is now used in Japan is employed in common with the Japan Lung Cancer Society. The word “superficial” can not be applied to cancer of the lung. The members of the Japan Lung Cancer Society are composed mostly of specialists in the surgery of lung tuberculosis, to whom the slogan “early detection and early management of lung tuberculosis” had once been an expression synonymous with the highest mission they had to accomplish. It was quite natural for them to prefer “early lung cancer” in the sense of curable cancer. Their proposition to standardize the expression “early cancer” was therefore readily accepted by our group, whose researches were carried out not only for the sake of medical interest, but also, and that is far more important, because of their sincere wish to save lives of people from gastric cancer that shows a high incidence and mortality in this country.

　2. The advent of gastrocamera, invented in this country, further facilitated our study of gastric cancer, as pliable gastroscope employed up to that time had not been popular here on account of its unfitness for the physical constitution of the Japanese people. Propagation of gastrocamera enabled us to diagnose With relative ease such a cancer as was considered to be early gastric cancer, or cancer in a stage of high curability. At the outset early cancer meant to us only such a cancer as was curable by resection. We did not know what kind of gastric cancer should be called early or advanced one.

　3. Accumulation of a great number of cancer cases having good prognosis, after they had been lively discussed among us, led our group to the conclusion that for the definition of early gastric cancer that has a closest connection with its curability, priority must be given to the depth of cancer infiltration into the gastric wall rather than to its gross extent. We owe this conclusion in a great measure to the report of a Japanese surgeon who bore out that the most important single factor that runs parallel with the prognosis of surgically resected gastric cancer cases is the depth of cancer invasion. If not, the radiologists, the gastroscopists and the surgeons could not have coincided with one another in one definition.

　4. Various designations for curable cancer were debated among our group, including the word “superficial,” but it was finally rejected, prompted by the name “superficial spreading carcinoma” given by Stout, whom the present contributor also quoted in his paper. Stout's report, already then well known among us, nevertheless did not satisfy us in one respect, that is, in the adjective “spreading”. As it was inconceivable that all types of gastric cancer, developing from one single place in the mucosa, should spread horizontally along its surface, many of us were of opinion that the expression “superfical carcinoma” had better not be employed lest it might be indiscriminately used in common with Stout's “superficial spreading carcinoma.” The word “superficial” remained instead limitedly to one of three types (type Ⅱ) of early gastric cancer, viz., the superficial type, neither excavated nor protruded. In this respect, it would be impossible for people of Englishspeaking nations to elicit further convincing explanation concerning different shades of meaning from us Japanese whose mother tongue is quite different from theirs. This is especially true because most of workers in this field have never been abroad for study, either in the States or in Europe. One example shall be shown here of difficulties in discriminating the nicer shades of meaning in English. It was hard for us to understand Why Stout did not designate “superficially spreading type” instead of “superficial spreading type” as he did. Had he used “superficially” in his designation, we would certainly have adopted “superficial” carcinoma as applied to early gastric cancer, fully convinced that superficially spreading carcinoma was of a different entity from superficial carcinoma.

　5. For the same reason as of the contributor, there is in Japan a professional circle that refuses to accept “early gastric cancer” as an orthodox medical term. It is called the Research Society for Gastric Cancer, to which also I personally belong, where a name “hyozaigan” (literally it means superficially existing carcinoma) is officially employed. However, the term “early gastric cancer” can be used in this Society as an alias of superficially existing carcinoma. It had been agreed among all concerned that both are identical in their meaning; there, early cancer means superficially existing carcinoma and nothing else. This agreement was (lone out of respect for those many pioneers in this field who devoted themselves to the advancement of the diagnosis of early gastric cancer and its diagnostic technics, all joining the banner of early gastric cancer.

　We hope the contributor is now convinced of the reason for the conventional use of the term “early” gastric cancer. A history, though of a short span, there has been from the time of the beginning of the study for the curable carcinoma through the designation of early gastric cancer up to the present when a certain incongruity has already come about between its name and its import. Its history is even now flowing like a current. When in future scientific logicality is weighed against the conventional usage of the word “early” the former may prevail and “hyozaigan” or “hyosogan” (superficially existing carcinoma or superficial carcinoma) may replace “early” cancer. It is again not impossible that more weight may be given to conventionality (or popularization of medicine) so that “early cancer,” being employed as a kind of alias (EGC is now being used as a simpler form of early gastric cancer), may bring about no inconvenience to all concerned as its import is elsewhere already established. In that case, “early” gastric cancer may survive. After all time will solve the question at issue. For the time being, at any rate, we have no intension of altering the name of “early gastric cancer.”