signs of threatening perforation. These, he thinks, are “dyscrotic.” Lebert is remarkably silent about these forms of peritonitis. Köhler holds this form of peritonitis to be due to acute cachectic changes in the organism produced by rapidly growing medullary carcinomata or caused by changes in the blood (anemia). I found peritonitis without perforation in 2 of my cases. One of these was a cylindric carcinoma in the pyloric end, with a soft node as large as a nut on the serous surface of the stomach. A slight amount of purulent material could be pressed into the peritoneal cavity from a couple of small openings in this nodule, although the openings were not in direct communication with the stomach cavity. This instance must be considered analogous with those observed by Dittrich in which perforation was imminent. My second case was the carcinoma on the lesser curvature mentioned above (Case IV), in which peritonitis seemed to be caused by the large metastatic nodules in the hepatic glands.

Ascites is frequent. It was present in 10 of my cases. In 5 instances the amount exceeded 1000 c.c. In 6 the ascites was due to multiple carcinomatous growths in the peritoneum. Fluid in the peritoneal cavity was present 4 times without malignant growths in the peritoneum. The retroperitoneal glands were carcinomatous in 2 of these, 1 had malignant thrombosis of the portal vein, and there was no local cause for the ascites in the tenth.

Hemorrhage into the peritoneal cavity is not common. It comes from highly vascular tumors in which the serosa is destroyed. It may at times become serious enough to cause death, as in the following case:

CASE VI.-Medullary carcinoma. Small, soft, ulcerated tumor in the pyloric end, close to lesser curvature. A walnut-sized soft vascular tumor (fungus hematoides) between the serosa and the muscularis in the pyloric end of the stomach. This has broken through the peritoneal coat and caused a considerable amount of hemorrhage into the peritoneal cavity. Large soft tumors in the liver. Smaller nodules in the omentum; carcinomatous degeneration of the lymph-glands of the lesser currature.

Niels Johansen, forty-four years old, laborer. Autopsy April 20, 1872, twenty-four hours after death. A small amount of fluid was detected in the peritoneal cavity a few weeks prior to death. This increased greatly during his last days. In the peritoneal cavity two quarts of liquid blood, which contains red and white cells in normal proportions and is free from other formed elements.

The stomach is of normal size and shape; the pyloric end is not constricted to any marked degree, although a round, flat, ulcerated tumor of soft consistence and yellowishgray color is situated on the anterior surface near the lesser curvature, and about 2 cm. from the pylorus. This tumor is 2 cm. in diameter and 11⁄2 cm. in height. It originates in the wall, and rises perpendicularly up from the mucosa. The ulcerated surface is covered with irregular shreds and villi, between which are small, pale-red coagula. On the serosa opposite this tumor is a group of yellowish-gray nodules, varying in size from a pinhead to that of a hempseed. There is a soft, dark-red, walnut-sized tumor on the posterior wall of the stomach. The surface of this is roughened here and there, but otherwise covered with peritoneum. The cut surface simulates a coagulum. The tumor is situated in the connective tissue between the serosa and the muscularis. It is loosely adherent to the normal muscularis. The mucosa is unchanged. The liver is changed into a nodular mass. On its surface are numerous soft, semispheric tumors, of a yellowish-gray color, and varying

in size up to that of goose-eggs. Some of these fluctuate. The liver tissue makes up but a small part of the liver mass, which is 31 cm. wide, 28 cm. vertically, 11 cm. anteroposteriorly, and weighs about 6 kilos. Near the gall-bladder is a nodule as large as a goose-egg, having a rough surface, covered with petechia. This is loosely adherent to the transverse colon.

Icterus occurs at times. It is due either to compression of the gallpassages by carcinomatous lymph-nodes, or to carcinoma of the passages themselves. In one of my cases carcinomatous glands at the hilum of the liver compressed the ducts, and in another case a part of the gallbladder, the cystic duct, and the ductus choledochus were changed into a whitish-gray mass, 2 to 4 mm. thick, by carcinomatous infiltration, the lumen being entirely obliterated, making the passage, of bile impossible.

Granular and fatty degeneration of the myocardium is not unusual in persons suffering from carcinoma. E. Vagner* observed that about one-sixth of ulcerating carcinomata of any part of the body lead to fatty changes in the heart. I found fatty degeneration of the heart in 9 of my cases. In 2 the carcinoma of the stomach was uncomplicated by any other disease, but of the 7 others, 1 had adhesive pericarditis, 2 had icterus, 1 peritonitis, 1 a large abscess between esophagus and the trachea, 1 suffered from lobar pneumonia, and the seventh had parenchymatous nephritis. I cite these complications because they alone might produce granular degeneration. This precaution has not been taken by Vagner in the two cases of carcinoma of the uterus where fatty changes were present in the heart, for both of these had diffuse peritonitis. Just how great a percentage of his cases showing fatty degeneration of the heart were complicated by diseases other than carcinoma is hard to estimate, but the carcinoma probably has a less severe influence on the heart than he has indicated. Still, my two cases of uncomplicated malignant growth of the stomach clearly indicate that carcinoma can produce fatty changes in the heart.

Marantic thrombosis of the large veins is not a rare complication of carcinoma. Dittrich found thrombi in the veins of the lower extremities in nine cases, and of the transverse sinus twice. One of my cases had thrombosis of both crural veins, 2 had thrombi in the crural vein and in the inferior vena cava, and 1 of the portal vein.

Lobar pneumonia, which Dittrich looks upon as a secondary disease, occurs frequently. Thus it was found in 5 of my cases. In 2 instances it was bilateral. I fail to see any etiologic relation between these two diseases, although the frequency of secondary pneumonia does indicate that such exist, since one-sixth of my cases had pneumonia; but other observers fail to find such a high percentage. Thus Dittrich found only 5 instances of secondary pneumonia, i. e., 1 in every 31 cases, and Lebert saw only 1 in 57.

Secondary croupous processes in the large intestines may readily be conceived as having a connection with carcinoma of the stomach, since gangrenous decomposition products might cause this by their passage through the bowel. Dittrich was the first to call attention to this * Die Fettmetamorphose d. Herzfleisches, Leipsic, 1864, p. 113.

sequel, of which he found 16 instances. It is doubtful, however, if the cause of croupous colitis is to be found in the carcinoma, because neither Lebert nor I found a single instance of this type.

Simple catarrhal enteritis is not rare. Lebert emphasized the fact that the large intestine is more frequently involved than the small. Dittrich gives 9 cases of acute catarrhal colitis and 4 of ulcerative folliculitis. The intestines were rarely involved in my cases. I only saw 1 instance of acute catarrh of the small intestines. Follicular ulcers were present both in the large and small intestines in one of my cases, but in this particular case there was an acute spreading tuberculosis of the lung, hence the ulcerative condition of the bowel might easily be connected with that.

The purely accidental complications are of little interest, with the exception of chronic tuberculosis of the lungs. It is well known that carcinoma and tuberculosis rarely occur together, and, according to the old notion, one of these bars the others. Cruveilhier did occasionally find them in the same person, but he thought they never originated during the same period. Martins,* who collected a number of cases of this nature, came to the conclusion that the two diseases occur together, although very rarely. Thus only 1 out of 150 cases of carcinoma seems to be associated with tuberculosis, and yet both may start at the same time. In Martin's cases of this kind the large majority of the carcinomata-9 in 13-were located in the stomach. I found the two diseases present together in 1 of my cases; here the tuberculosis was much more recent than the carcinoma, and had started when the carcinoma was at the zenith of its growth.

Other complications present in my cases were pachymeningitis interna, twice, in a woman seventy years old, who had scirrhous carcinoma of the pylorus, and in a woman fifty-one years of age, who had a medullary carcinoma of the pylorus. Dittrich considers this form of meningitis a consecutive disease, and holds it to occur frequently. But a direct connection is hard to find. Pachymeningitis is not rare in older persons, and it may be that the fact that both these diseases occur in older people is the only real connection between them. Nephritis occurred twice, fatty liver twice, scirrhosis of the liver, bronchitis, hypostatic pneumonia, polypus uteri, oöphoritis, abscess between esophagus and trachea, and a decubital ulcer, each once.

ORIGIN AND DEVELOPMENT OF CARCINOMA OF THE STOMACH

(4) Point of Origin.-It is hard to decide whether the carcinoma originates in the mucosa, submucosa, muscularis, or serosa, since the early stages of primary carcinoma in this organ can be seen only in patients dead from other diseases, and then the disease is usually overlooked. In order to decide this question it is necessary to have a large series of carcinomata at a very early stage, when only one layer is involved. Accurate descriptions of carcinoma in this stage are not found, largely beDie Combinationsverhältnisse des Krebses und Tuberculose, Erlangen, 1853.

cause the malignant cells early infiltrate the other layers. As far as volume goes, the largest tumor mass is nearly always in the submucosa, regardless of whether the tumor is seen early or one is looking at the edge of a carcinomatous ulcer. The mucosa covering the tumor is often not thickened, or but slightly so. It is rarely more than 2 mm. in thickness, even when a tumor mass from 6 to 15 mm. is present in the submucosa. However, this difference in volume does not indicate that the tumor started in the submucosa, any more than the fact that the carcinomata ("cancroids") of the skin always are largest in the subcutaneous connective tissue indicates that they originate there. An erroneous conclusion of this type is in all likelihood the basis of the older views as to the origin of carcinoma of the stomach.

(a) The Connective Tissue.-(1) The Submucous. All the older writers (Roux, Louis, Cruveilhier, and Prus*) consider the submucous connective tissue to be the most frequent point of origin of the cancer. Rokitansky states that scirrhous and alveolar carcinoma always originate here, while other forms, as the medullary carcinomata, may begin in the mucosa. Förster‡ holds that the connective tissue of the mucosa and the submucosa oftenest is the beginning of cancer, whereas the subserous tissue is rarely primarily involved. Dittrich, § too, grants the submucosa the highest frequency, but states there are unquestionable instances in which cancer has originated in the serosa and the subperitoneal connective tissue.

2. The Subserous Connective Tissue.-Contrary to Prus|| and others, Dittrich believes this may be the starting-point. Dittrich, however, cites but one case against which there can be no objection. He found a scirrhous tumor, 4 mm. thick, involving the peritoneum and the serosa, in which the muscularis was 2 mm. thick and penetrated by white strings, whereas the submucosa and the mucosa were only a trifle firmer than usual. But it is certainly far-fetched when Dittrich gives a case of cancer in which, in addition to scirrhous infiltration of the serosa, a medullary carcinoma occurred in the submucosa and the mucosa as an instance of cancer primary in the outer coats of the stomach. It happens that secondary growths of a firmer nature do occur when a soft cancer is present in the layers internal to the muscularis. He himself realizes the difficulty of deciding where the malignant cells were first formed by granting that the point of origin may be hard to decide on when the tumor of the serosa is larger than the mass in the submucosa. It is hard to see just what has made him think the subserous connective tissue should be the starting-point of the cancer in such cases. I have never seen a case in which the malignancy might have started outside the muscular layers. (b) Muscularis.-Older writers, Andral and Louis,** thought they found the muscularis to be the point of origin of cancer in a few cases, but

* Prus: Loc. cit., p. 48.

† Lehrbuch der pathol. Anat., 1861, vol. iii, pp. 172, 175.

Handbuch der pathol. Anat., 1863, vol. ii, p. 74.

§ Prag. Vierteljahresschr., 1848, vol. i, p. 3.

|| Loc. cit., p. 51.

** Prus: Loc. cit.,

p. 49.

Dittrich takes firm issue with them by stating flatly that primary cancer never occurs in the muscularis. Up to the present time none has disputed his assertion. The muscularis is, therefore, not the point of origin, but is always involved secondarily, and by extension of the malignant cells into it from the submucosa. It was observed early that the muscular layer was thicker than normal and penetrated by trabeculæ under the tumor. In such cases it becomes necessary to distinguish between a thickening due to hypertrophy and hyperplasia of the muscular fibers and that due to new-growths in the connective tissue between them. These changes always, or nearly always, occur together, and it is often very hard to decide just what part each of them plays in the thickening of the muscular layer. Regarding the muscular fibers, Rokitansky* states that they hypertrophy at the beginning of malignancy and may reach a monstrous size. In cross-section the muscularis may appear as a transparent, reddish, pale substance. The hypertrophy is followed by a gradual atrophy of the muscle-fibers and a new formation of interstitial connective tissue. I have never seen a true hypertrophy of the muscle-fibers. In a case showing a very early stage of development of carcinoma I found, to be sure, the muscularis thickened, but the interstitial tissue was also increased. The tumor was a round, cylindric carcinoma, 3 cm. wide and 8 cm. high. In this case the muscularis was 2 to 3 mm. thick beneath the tumor, while in other parts it measured only 1 mm. The individual muscle-fibers were not perceptibly hypertrophied. The interstitial connective tissue appeared as white septa between the muscular bundles. Microscopically, these consisted of adult connective tissue without granulation cells or carcinomatous tissue. The white septa between the muscular bundles increase in thickness with the further development of the cancer, and can then be seen to consist of malignant tissue. In times past there was some dispute as to the significance of these septa, although Müller† early observed that they contained cancerous cells both in carcinoma and alveolar cancer. Later on Burch‡ claimed that the septa were signs of hypertrophy, and that Müller's belief, later shared by Rokitansky, was wrong. The exact condition can be determined only by the microscope in each individual case. It may be said to be the rule that the tissue of the septa corresponds with that of the submucosa underneath it, whether this is the seat of simple hypertrophy or of a malignant infiltration. Cancerous tissue always occurred in the interstitial tissue in the completely developed carcinomatous tumors that I investigated. In the early case already referred to, the septa consisted wholly of connective tissue. It appears, therefore, that a hyperplasia of the interstitial connective tissue, and perhaps of the muscularis as well, takes place prior to the invasion of the muscularis by cancer-cells. Then, as the malignant tumor develops, further, cancercells infiltrate the interstitial tissue, and the musculature is gradually destroyed as the malignant cells increase.

Loc. cit., pp. 172 and 173.

Krankhaften Geschwülste, Berlin, 1810, p. 10. "Ueber Magenkrebs und Hypertrofi der Magenhaute," Zeitschr. f. rationalle Medicin, 1849, vol. viii, p. 2.