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Rabbit papillomas developing on the skin as the result of virus inoculation can be readily transferred to the inner organs of favorable hosts by implanting bits of the living tissue. The growths thus produced proliferate actively as a rule and frequently cause death. Often they are markedly invasive and destructive; and they tend to recur after excision. Bacterial infection may greatly enhance their malignancy. Accidental dissemination may occur during operation, and distribution to the peritoneal surface has been repeatedly noted. There may be no cellular reaction whatever about the invading epithelium of interior growths, but usually some new formation of connective tissue takes place, its amount varying inversely with the rate of epithelial proliferation. An immediate reason exists for the inflammatory changes and scarring found beneath long-established skin papillomas, in the trauma and secondary infection to which the projecting, necrotizing masses have been subjected. In animals dying of progressively enlarging interior growths the skin papilloma may long have been stationary in size. The growths appearing after the transfer of papillomatous tissue to the inner organs are due to the survival and multiplication of transplanted cells. However, the virus can be readily recovered from them, in the case of wild rabbits. No distinctive changes in the blood of the host have been found. The virus itself is highly specific for the epithelium of the skin, failing to act not only upon that of the other organs thus far tested but even upon embryonic skin. The papilloma frequently penetrates into the blood and lymph vessels, especially at the edge of implantation growths. The intravascular injection of fragments of it sometimes results in pulmonary nodules of characteristic morphology. These are due to survival and proliferation of the injected cells. Secondary nodules have been encountered at autopsy in a lymph gland and in the lungs, but under conditions more suggestive of operative dissemination of the growth than of true metastasis. Implantation growths of the papilloma in favorable hosts have the morphology of epidermoid tumors of greater or less malignancy. They behave as these do and elicit similar changes in the surrounding tissue. The attributes and potentialities of the papilloma will be further considered in Papers II and III.

1. The occurrence of tumors in the lung in mice is dependent to a certain extent upon the age of the individual. No tumors were found in the lungs of mice less than 8 months old. They occurred with greatest frequency in mice of about 24 months or older. Mice may live to be more than 3 years old without developing growths in the lung. These facts show that the development of tumors of the lung, if hereditary, is a variable character. An individual, genetically a tumor mouse, may live to a great age without showing a tumor if the requisite environmental stimulus (external or internal) is lacking. Sex if effective at all has a comparatively slight influence upon the incidence of lung tumors. 2. Two strains of mice were studied which exhibit differences in their rates of incidence of lung tumors that are large enough to be significant. The conflict in the evidence from different laboratories as to whether or not tumors of the lung are the commonest type found in mice, is probably to be explained on the basis of a differing hereditary tendency to such growths in differing stocks. 3. Data from a number of sources indicate that offspring from parents free from lung tumors have a lower rate of lung tumor incidence than offspring from parents one of which had a tumor. If both parents had lung tumors the rate of tumor incidence among their offspring is increased still further. 4. In crosses between mice from strains which have high and low rates of incidence of lung tumor, tumors appeared in about half of the individuals of the first generation and in about one-quarter of the second generation. If the character responsible for the development of the growths is recessive it should not be found in the first filial generation unless both parents are carrying it. There is no proof that the female parents did not carry it but since they were taken from a strain in which the incidence of the growths was but 6.7 per cent the chances seem good that they were free from it. This suggests that the character determining the incidence of pulmonary tumors may be a dominant one. A dominant character is not expected to appear among the offspring from parents neither of which has shown the character. The numerous instances which have been tabulated in this paper of mice with lung tumors among the offspring of parents free from lung tumors, must be explained on the assumption that tumor susceptibility is not only dominant but variable and that some of the parents which did not actually develop tumors were genetically tumor mice and had the capacity for developing tumors although it was not brought out. As we have already concluded on the basis of the relationship between age and tumor incidence that susceptibility to the development of lung tumors is a variable character our explanation of the occurrence of tumor mice derived from tumor-free parents is justifiable. The existence of strains of mice with rates of incidence of lung tumors that differ as widely as do the two that we have studied, the relatively high incidence of pulmonary growths among mice of tumor parentage as compared with mice from non-tumor parents, and the fact that females from a strain in which pulmonary tumors are rare when crossed with individuals from a strain in which they are frequent give a fairly high rate of incidence of the growths among the first and second filial generations,—all these facts indicate that susceptibility to the development of tumors in the lung is an inherited character.

A tumor of the kidney of the leopard frog ( Rana pipiens ) has been studied in this laboratory for the last several years. It is an epithelial tumor of glandular structure, varying in appearance from a typical infiltrating and destructive adenocarcinoma, which is the usual type, to a more orderly and circumscribed adenoma. It has all the attributes of a true neoplasm, and it is of particular interest because of the frequent occurrence within the nuclei of the tumor cells of inclusion bodies such as are caused by viruses. Earlier studies (1) appeared to show a fundamental difference in the biological characteristics of the frog carcinoma and structurally similar tumors of man and other warm-blooded animals. In the first series of 158 cases reported, metastasis was not observed in a single instance. Hence, despite the histologic appearance of malignancy, and the infiltrative and locally destructive habit of the growth, one of the cardinal signs of malignancy, the tendency to form secondary tumors, appeared to be lacking. This finding was in harmony with the statement, often encountered in the literature, that malignant neoplasms of cold-blooded animals, unlike those of mammals and birds, rarely become disseminated (2–7). Further observations, however, have shown that no such fundamental difference exists between the carcinoma of the frog and similar tumors of warm-blooded animals. In a second series, 3 instances of metastasis were encountered (8) and in the series reported in this paper, 22 additional metastatic tumors have been found widely disseminated in a number of different organs.

The complete extirpation of regional lymph node is a most important concern in the curative resection of rectal cancer to prevent further dissemination.In order to disclose preoperatively the lymphatic spread of cancer of the rectum and anal canal, the direct lymphography has been performed on 58 cases in our clinic. The procedure of lymphography was performed by Kinmonth's method which had been presented on his paper. When the injection of the contrast media (38% Lipiodol ultra fluid) is finished, a first X-ray photograph is taken in which very fine lymphatic chanells will be demonstrated, so it is called as lymphangiography. A second X-ray photograph is to be taken after 24 hours, in which all the lymph nodes in the inguinal pelvic and para aortic regions, so it is usually called as lymphadenography. Both photographs are necessary to know the aspects of the lymphatic chanells and nodes.The injected contrast media reach to the inguinal nodes which are devided into two main groups-the superficial and the profound one. All proceed further to the external iliac group. This external iliac group is forked into three chains, namely the internal, middle and external one. But these chains communicate each other.The lymphatic drainages of the rectum will be devided into three groups on the basis of the course of their efferent vessels. These are grouped as superior, middle or lateral and inferior zone. But regions visualized by lymphography are limited and possibility of the metastasis into these region is little.By my investigation metastasis into the external iliac group was about 10% and into the inguinal group was about 8%. These frequencies are almost same as other reports.The main roentgenologic findings which suspect the metastasis of cancer to the nodes on lymphography are as follows : the peripheral or central filling defect of node, dilation of lymphatic channells and existence of bypathes. These findings were made sure by Softex photograph of the removed nodes.Fortunately, the majority of cases had no invasion in the regions which visualized by lymphography. It is said that the metastasis of the rectal cancer is mainly progressed through the superior zone. But this zone is not visualized by this procedure. However the lateral and inferior zone are adequately visualized, so it is emphasized that the prognosis, the degree of invasion and operative procedure should be decided by lymphography.

Giant-cell tumors have been considered capable of producing metastases. Goforth (1) attempted to grade the microscopic picture to show the gradual transition of benign giant-cell tumor to osteogenic sarcoma. Geschickter and Copeland (2) analyzed forty-one cases of giant-cell tumor showing clinical or microscopic evidence of malignant tendencies. “In the clinical group, twenty-six cases recurring after primary curettement were studied. Recurrence in this group was found to depend not on histologic structure, but on a poor selection in the type of treatment applied in the individual case or on an incomplete operation. Advanced destruction of the bone shell, incomplete curettement, failure to use chemical or thermal cauterization or needless sacrifice of cortical bone at the operation, as well as an age over thirty-five, were found to be factors predisposing to recurrence after curettage. “In seven cases showing a microscopic resemblance to malignancy, the histologic change was usually found to be the result and not the cause of the recurrence, being dependent on intervening infection, necrosis or an accentuated healing reaction following irradiation. In two cases, actual sarcoma with giant cells was found to be erroneously placed in this group.” Bloodgood in a foreword to a paper by Geschickter and Copeland, cites one death from metastasis from a possible giant-cell tumor of the epiphysis. In this case a restudy of the sections of the original tumor led to its classification as a malignant variant of the giant-cell tumor, of which eight cases were found in the authors' series, only one of which metastasized.

In this paper is reported the first avian tumor that has proved transplantable to other individuals. It is a spindle-celled sarcoma of the hen, which thus far has been propagated into its fourth tumor generation. This was accomplished by the use of fowls of pure blood from the small, intimately related stock in which the growth occurred. Market-bought fowls of similar variety have shown themselves insusceptible, as have fowls of mixed breed, pigeons and guinea-pigs. The percentage of successful transplantations has been small, but in the individuals developing a tumor its growth has been fairly rapid. Young chickens are more susceptible than adults. The reinoculation of negative fowls has never resulted in a growth. Throughout, the sarcoma has remained true to type. It is infiltrative and destructive. Metastasis has been observed once (to the heart). Experiments to determine whether the growth may be transmitted by cell-fragments have not yet been made. Repeated bacteriological examinations have yielded negative results. In its general behavior, so far as tested, this avian tumor closely resembles the typical mammalian neoplasms that are transplantable.

Carcinoma of the prostate gland is peculiarly favorable for endocrine investigation since frequent serial observations of the activity of phosphatases in serum were found to provide objective indices of activity of the neo/~i~m when the enzymes were increased in amount above normal. In the present paper data are given for the values of serum phosphatases in carcinoma of the prostate and in normal men. We shall demonstrate that the acid phosphatase of serum is reduced in metastatic carcinoma of the prostate by decreasing the activity of androgens through castration or estrogenic injections and that this enzyme is increased by injecting androgens. We have been unable to find previous observations indicating any relationship of hormones to carcinoma of the prostate gland. An enzyme capable of hydrolyzing phosphoric esters was discovered by Grosser and Husler (4) in intestinal mucosa and kidney. Robison (16) found that this enzyme was particularly high in activity in growing bone and cartilage and that its activity was greatest at pH 9 to 9.5. This ~alkaline phosphatase," was found by Kay (9) to be increased in the serum in certain bone diseases including metastasis of neoplasms to bone and later work has shown that among these conditions is carcinoma of the prostate. Davies (3) and Bamann and Riedel (1) discovered that there occurs in the spleen and kidney of swine and cattle, in addition to the alkaline phosphatase, a phosphatase with an activity maximum at pH 4.8. An enzyme believed to be identical with this "acid phosphatase" was found by Kutscher and Wolbergs (11) to be present in very large amount in the human prostate gland. This finding of great activity of acid phosphatase in the prostate gland was confirmed and extended to include prostatic cancer by Gutman, Sproul, and Gutman (7). The serum of certain patients with disseminated prostatic carcinoma was found by Gutman and Gutman (6) and Barringer and Woodard (2) to exhibit increased acid phosphatase activity. Robinson, Gutman, and Gutman'~I5) summarized the acid phosphatase activity levels of 44 patients with carcinoma of the prostate. They concluded that a marked rise in acid phosphatase in serum is associated with the appearance or spread of roentgenologically demonstrable skeletal metastases and implies dissemination of the primary tumor and thus is of unfavorable prognostic significance. METttODS AND MATERIALS

So constant is the primary seat of mumps in the parotid or other salivary glands that the disease is remarkably free of other synonyms than parotitis or parotiditis. In practice, however, we are familiar with its metastasis from its usual seat to the testicle in the male, or to the mamma or ovary in the female. But the condition to which this paper refers is rare—so rare indeed, that most text-books make no reference to it. Hence, it is worthy of note that I have met with several cases of primary testicular mumps . My attention was first called to the subject some fifteen or more years ago by a case seen with the late Dr. F. D. Cunningham of Richmond. Other cases of primary testicular mumps occurred during that otherwise ordinary epidemic of parotitis. Verbal reports were made of some of the cases to the Richmond Academy of Medicine, but

The facts that the general subject of cancer presents even to-day one of our most serious and unsolved problems; that cancer of the prostate is a comparatively frequent and exceedingly distressful form of the disease; and the probability that by a more wide-spread application of the present available knowledge of this pathologic process the prevalent high percentage of disability and death would be considerably diminished, are advanced as sufficient reason for presenting a discussion of the subject with a contribution of data to the fund of experience. The pathogenesis of cancer of the prostate is still a debatable question; the frequency of its occurrence, the usual sites of its original focus, its mode of extension and metastasis, are phases of the subject which are reasonably supported by facts. This paper is based, first, on the examination of a series of 716 prostatic specimens removed at operation in the Mayo Clinic