In what way the muscular bundles are destroyed has not been definitely explained up to the present time. Dittrich* states that it is difficult in the later stages of cancer to decide whether the muscular bundles are forced aside by the malignant cells or are destroyed by being infiltrated by cells. Rokitansky believes that they undergo atrophy due to proliferation of the connective tissue between them, and Förster agrees with him in this. On the whole, however, writers so far have paid but scant attention to this point. For this reason I shall discuss it in some detail, and describe the condition I have found present in all types of carcinoma studied by me. This excludes alveolar cancer, since there was no opportunity to observe this form in my cases.

At first the carcinomatous cells extend from the submucosa down between the larger muscular bundles. Granulation tissue is often found in the connective-tissue framework in the neighborhood of the cancer mass. The malignant tissue is then seen to form white bundles and partitions around the grayish, transparent muscle substance. In these cases the cancerous tissues are completely developed, containing both alveoli and stroma. From the interstitial tissue of the larger bundles the malignant cells next extend between the smaller muscular bundles. Finally, the cancer-cells penetrate between the individual muscle-fibers, and these are then destroyed by fatty degeneration. This condition is illustrated in Fig. 1 of Plate I, which represents a section of the musculature of the lower part of the esophagus. It came from a case of ulcerated scirrhous carcinoma of the cardia in which the muscular layer was thickened due to infiltrated cancerous masses. In the center of the picture at 1 appears a bundle of smooth muscle-fibers cut longitudinally, and between them are seen groups of cancer-cells which are without stroma and lie naked against the muscle-fibers. In some of these (at 5) are found oblong groups of fat-granules. On either side of these longitudinal layers are swollen muscle-bundles cut crosswise (at 3), and between the individual fibers of these occur groups of malignant cells which have forced the fibers apart and separated them into irregular groups. I was unable to find any evidence of the muscle-fibers taking an active part in this process. There was no pronounced division of nuclei or any transition of muscle-fibers into cancer-cells. The formation of fat-granules which, as far as I can determine, begins near the nuclei of the fibers, indicates the destruction of the musculature by fatty degeneration.

(c) The Mucosa.-The mucosa was rarely considered as the point of origin of cancer by older writers. Thus Prust had not personally seen a single instance of this kind, but cites a case observed by Andral in support of the theory that the mucosa may be the site of primary cancer, while the other layers are unchanged. But the case to which he refers was not malignant, as is plain from the description given by Andral, who also considered it as a case of chronic catarrh of the stomach in a person with tuberculosis of the lungs with ulcers in the ileum. Rokitansky thinks that certain forms of medullary carcinoma may occur as diffuse infiltra*Loc. cit., p. 9. † Loc. cit., p. 49.

Clinique medicale, vol. iv, p. 397.

tion of the mucosa, but that this layer is far less frequently the primary site of cancer than is the connective tissue of the submucosa. At the present time, however, the mucosa has become the center of interest, and it is now looked upon as the point of origin of carcinoma in an entirely different proportion of cases than earlier. It was first observed that certain types of cancer-the cylinder-celled carcinomata-originated here (Reinhardt, Förster, Virchow, etc.) Later on, Cornil called attention to the fact that medullary carcinomata also originated in the mucosa, and finally Waldeyer has recently advanced the view that all ' types of cancer of the stomach have their starting-point in the mucosa.

(B) Development.-Without attempting to give a developmental history of cancer, I wish to bring out the salient features of the various theories held today. I shall limit myself to carcinomata, since the sarcomata are very rare in the stomach. The characteristic thing about carcinomata is the fact that each growth consists of two elementary substances, viz., the connective tissue and the carcinomatous cells. The connective tissue forms the supporting framework carrying vessels and forming the walls of cavities of varied form, shape, and arrangement, the alveoli containing the other elementary substance the cells. This fundamental structure is found in scirrhous carcinoma, cancroids, and colloid cancer, which are the different types occurring in the stomach. The real query then becomes, where do the alveolar cells originate? They are the central point in the development of cancer, and since Joh. Müller's time the attention of observers has been focused on them.

(a) Development from Connective-tissue Cells.-The old notion that these cells originate from amorphous ones as exudates from the blood and lymph-vessels was overthrown by Virchow, who advanced the theory that they originated from the mother-cells of the connective tissue. Since Virchow is the originator as well as the main representative of this theory, at present held by a number of our best histologists (Förster, Rindfleisch, and others), I wish to recall his ideas concerning the origin and development of cancer.

Virchow* divides the development of cancer into five stages: (1) The irritative stage forms the beginning and is characterized by changed nutritive conditions in the connective tissue produced by the cancer poison (he does not give the character of this poison), whereby the connectivetissue cells undergo an active proliferation similar to that of ordinary inflammation, giving rise to masses of non-differentiated cells-granulation cells. (2) The next is called, after these cells, the granulation stage. At this stage the tumor cannot be recognized from ordinary inflammatory tissue. The non-differentiated cells are like those of a young tubercle. There is this inherent difference, however, that only the malignant cells are capable of further development. This difference is shown by recurrence of the malignant tumor in the apparently healthy tissue surrounding a removed cancer. It is the connective tissue that has the most pronounced ability to form granulation tissue, hence cancer most frequently develops from connective tissue. (3) In the third stage-the * Onkologie, 1863, p. 77.

stage of differentiation-changes characteristic of malignancy, by which the specific structure of carcinoma is produced, occur, and first in the granulation tissue. The undifferentiated cells now develop along two distinct lines. One part of them is changed into connective tissue and vessels, forming the tumor stroma; the others assume the form and appearance of epithelial cells, either cylindric, squamous, or transitional, and these epithelial cells fill the spaces formed by the stroma and make up the alveolar contents. (4) The fourth stage is the flowering stage, and, (5) the fifth the stage of retrogression, have nothing to do with the development, and hence are left out.

(b) Development from Preëxisting Epithelial Cells.-As early as 1847 Virchow* pointed out the similarity of carcinomatous cells and epithelium without, however, thinking about a genetic relation between them. In 1854 Remak† demonstrated the development of the epithelioma of the skin from the secreting cells of the sebaceous and sudoriparous glands. He held that the cancer mass was of similar structure to these glands, and suggested the name adenoma for them, because the cancer growths develop similarly to the glands in the embryo. He, therefore, pointed out an entirely new mode of development for cancer-cells, namely, origin from preexisting epithelial cells in the glands of the skin. Such a view was entirely contrary to the belief then held that the malignant cells developed from amorphous "blastomer." For a long time Remak's observations stood alone and did not prevent Virchow's theory of origin from ordinary connective tissue from being generally accepted. Meanwhile the epitheliomata (Hannover), or squamous cancroids, as they were called by Alibert, became separated from the other types, and as far as these tumors were concerned, Remak's theory as to their origin was definitely proved by Thiersch,§ who added that cells of the rete malpighii, as well as the gland-cells, might become the origin of cancercells.

As far as cancer of the stomach goes, it was of greater interest that the real origin of cylinder-celled cancroids became known (Reinhardt, Bidder,** and Virchow††), because these tumors were first found in the stomach. So far as these tumors go, it was known from the very beginning that the gastric glands played a part in their development. Waldeyer‡‡ made it sufficiently plain that the relation between the stomach glands and these cancers was the same as that between the glands of the skin and the epitheliomata. Cornil§§ had, to be sure, come close to the truth when he observed the enlargement of the glands and the *Virchow's Archiv, 1847, vol. i, p. 94.

†“Ein Beitrag zur Entwickelungsgeschichte der krebshaften Geschwülste,” Deutsche Klinik, 1854, p. 170.

Das Epitheliom, Leipsic, 1852.

§ Der Epithelialkrebs nämentlich der Haut, Leipsic, 1865.

|| Annalen d. Charité, 1851, vol. ii, p. 1.

** Müller's Archiv, 1852, p. 178.

†† Gazette Med. de Paris, 1855, p. 211.

"Die Entwickelung der Carcinome," Virchow's Archiv, 1868, vol. xli, p. 470.

§§ "Contribution a l'histoire du developpement histologique des tumeurs epitheliales,” Journal de l'anat. et de physiol., 1865, vol. ii, p. 266.

development of branches on the side of the fundi, and also the disappearance of the membrana propria, but instead of considering these bare cell-masses the content of the alveoli, he thought epithelial cells were formed in the stroma.

When it had been proved that the cells of the cancroids, both squamous and cylinder-celled, originated either from gland-cells or other epithelial cells, it was yet left to show whether the other forms of carcinoma have a similar starting-point, and Waldeyer* showed that there is no difference between cancroids and other carcinomata, and now holds that the cells of the carcinomata in general spring from preëxisting epithelium either in the skin, the mucous membrane, or in the glands.

When there is no difference in structure, it seems reasonable that there should be a common mode of development of all varieties of the same type of tumor.

According to German writers, more especially to Virchow,† the difference between "carcinoma" and "cancroid" consisted in that the cancroids had large alveoli visible to the naked eye, which were filled with epithelial cells; between the alveoli occurred a stroma made from the connective tissue of the involved organ, and not from the new-formed tissue. The "carcinomata," on the other hand, had small alveoli the cells of which originated from granulation tissue, part of which developed into cells and part into stroma. Such a conception as to the character of these two forms of tumors had the weakness that it was based both on form and on development, and it was impossible, in an individual case, to decide whether the stroma had developed from the new-growth or from preexisting connective tissue. French histologists never recognized this difference. In Robin's "Tumeurs heteradeniques" the alveoli contained at times squamous and at other times round- or angular cells, hence they include both the squamous cancroids and the carcinomata. Cornil§ shows that the difference between cancroids and carcinomata described by the Germans does not exist, but he fails to arrange them into a single group, consequently he only adds to the already existing confusion by suggesting new forms with strange names. Waldeyer was the first to have courage enough to annul the theoretic difference which had caused so much confusion in the description of tumors. At the same time as he was tearing down this theoretic distinction he sought to show that both varieties have the same origin, namely, from preexisting epithelial cells.

Accepting the theory that carcinoma springs from epithelium, its development, according to Waldeyer, must occur as follows: In an organ containing epithelial cells, for example, glands, or the mucosa of

* Virchow's Archiv, 1872, vol. lv, p. 67.

"Ueber Cancroide und Papillargeschwülste, "Virchow's gesammelte Abhandlungen, 1862, p. 1018.

"Memoire sur le tissu heteradenique," Gaz. hebd. 1856.

"Memoire sur les tumeurs epitheliales du col de l'uterus," Jour. de l'anat. et de las

physiologie, 1864, vol. i, p. 472.

the alimentary tract, the acini develop irregularly. The gland-cells proliferate first, filling the acini, then dilating them, and finally grow as cellbuds out in the surrounding tissue. These protruding cell-masses are designated carcinomatous bodies by Waldeyer. At first they appear as buds on the sides of the acini, but soon they can be distinguished from these by the fact that they are not limited by a basement-membrane and form solid masses of cells. The carcinomatous masses, growing still further out in the surrounding tissue, continually branch in all directions, forming an anastomosing network of cells, which in cross-section form the alveolar contents. The connective tissue surrounding the cancercell is at first simply the stroma of the original gland. Soon granulation cells appear. These may come either from the proliferation of the existing connective-tissue cells or from the blood. Waldeyer calls this process "periacinöse oder intralobuläre Wucherung," and he considers this granulation tissue simply a by-product, playing a subordinate part in the development of the carcinoma, contrary to Virchow who holds the granulation tissue to be a single stage in the development of the tumor. The stroma of the carcinoma is, therefore, composed partly of preëxisting connective tissue and partly of periacinous granulation tissue. The numerous writers on cancer adhere to one or the other of these two theories.

In my work on Carcinoma of the Stomach I have paid particular attention to the development by means of a thorough study of the mucosa at the edge of the tumor. I shall give my observations more in detail in connection with the individual cases, but in general I have found Waldeyer's theory to hold good in many of my cases. However, I have been unable to find it true, as he has, in every case. At this point I wish to present Waldeyer's ideas of the development, and explain it by a case which is interesting in this connection.

Prior to Waldeyer, the connection between the gastric glands and carcinoma was recognized but once by Cornil,* to which I have already referred. Waldeyer found that the degenerated gland-cells at first broke through the muscularis mucosa and then rapidly invaded the readily movable, loose submucous connective tissue. At this point the real cancer nodules are formed. They occur at first as small isolated knobs, which suggest their analogy to the gastric glands, and later these grow together, forming diffuse masses. He has proved, furthermore, that both the gastric glands and the mucous glands at the pylorus may be the starting-points of cancer. It was only rarely that a larger portion of the gastric glands underwent carcinomatous degeneration-nearly always a small group of glands, 10 to 20 individual fundi, or even less, became malignant. As soon as these penetrated the muscularis mucosa a rapid development took place, leading to the formation of a large node, connected with the glands above by a small pedicle. This pedicle is not always in the very center of the tumor, but often lies to one side, so that a series of sections is often needed to find it. The gastric glands surrounding the malignant cells are often dilated in their lower ends. They * Robin's Journal, 1865, p. 476.