Tumors

TUMORS. Contents: I. Distribution of T. in the animal world . . .44 6 II. Statistics..................44 7 III. Structural and functional characteristics .... 449 IV. Pathogenesis and etiology............469 V. Classification and nomenclature.......478 VI. Diagnosis and treatment............480 VII. Fight against T...................481 Tumors and, neoplasms (neoplasma), are commonly called prolonged tissue growths of atypical structure that do not fit into the general plan of structure and metabolism of the organism. The field of medicine that studies the entire complex of processes related to tumor growth is called oncology (see). With the current state of knowledge about T., giving a definition that exhausts the essence of this process appears difficult. Schwalbe in 1911 even expressed himself as to its impossibility. Therefore, existing definitions, which have different formulations by various authors, consist of a characterization of the most essential features of the tumor process. For this reason, the formulation given at the beginning requires detailing that establishes the structural and physiological features of T., distinguishing it from a number of related pathological processes and from normal body tissue. In addition, this definition of T. requires distinguishing them from certain other formations that have some external resemblance to blastomatous growth. These include so-called choristomas (see), hamartomas (see), then so-called blastoids, which include adult teratomas, dermoid cyst of the ovary, fibroma of the kidney, etc., which represent developmental and growth defects of tissue, often having a large volume, but unlike true blastomas, do not show prolonged growth, and finally multiple or accessory organs (accessory spleens, nodules of the pancreas, etc.). In practice, differentiation of true blastomas from so-called infectious granulomas (tuberculosis, syphilis, etc.) and other types of productive inflammation is sometimes not easy. Decisive is the certain cyclical development of granulomas and other types of productive inflammation, their etiological connection with a specific causative agent, which can mostly be established, as well as the fact that infectious granulomas are mostly only one pathological-anatomical detail, although sometimes a dominant one, in the diverse picture of the corresponding pathological process. Tumors also have nothing in common with tissue swellings of inflammatory origin, which are the result of exudation and infiltration, as well as inflammatory tissue growth ("inflammatory tumors" of clinicians). I. Distribution of tumors in the animal world. In the review material by Teutschlander, Roussy and Wolff, there are indications of the widespread distribution of T. among animals; they occur in almost all vertebrates, both warm-blooded and cold-blooded, carnivorous and herbivorous, wild and domestic. In addition, Roussy and Wolff point to the presence of myxomas and sarcomas in invertebrates (mollusks). At the same time, it is necessary to emphasize that animal T. are in no way identical to human T., that they often represent only analogous formations. This is important to keep in mind when transferring the results of experimental study of animal T. to humans. In cold-blooded animals, T. occur less frequently than in warm-blooded ones. Sarcomas and carcinomas of the ovaries and kidneys in frogs, fibromas and carcinomas of the testes in salamanders, malignant struma in turtles, carcinomas of the ovaries in snakes, carcinomas of the skin in lizards have been described. Fish are particularly rich in T.; in them occur rhabdomyomas, melanomas, lipomas and papillomas of the skin, further spindle cell sarcomas, osteo-chondromas, sarcomas of the liver, etc. In America, endemics and epidemics of carcinoma of the thyroid gland have been described in trout, devastating entire ponds. In the larvae of the fruit fly Drosophila, melanotic T. have been described. In birds, the most diverse T. are encountered: fibromas, myxomas, chondromas, osteomas, sarcomas, various types of cancer, embryomas, lymphomas and leukemic growths. According to the data of Ernesti, tumors in birds occur as often as in dogs, usually proceed malignantly, and give metastases. Sarcomas often arise multiple; one of them (Rous sarcoma) is of particular interest to researchers, serving as material for transplantation and numerous studies: (see Chicken sarcomas). Spontaneous T. of mice and rats are of great importance in experimental oncology, being objects of transplants. In them occur cancers and sarcomas. Slye and others found among 28,000* mice that died of natural causes 123. carcinomas of various organs (more often of the skin, mouth, mammary gland). In guinea pigs, T. occur rarely; spindle cell sarcoma (Lubarsch), chorion-epithelioma of the ovary (Roussy), hypernephroma (Roskin), adenocarcinoma of the mammary gland (Migunov) have been described. In cats, cancer of the mammary gland often occurs; in rabbits, cancer of the mammary and pancreas glands, kidneys and uterus and transplantable sarcoma, endothelioma (Migunov) have been observed. In dogs, various T. have been described—sarcoma and cancer of various organs, cancer of the liver in case of its cirrhosis, malignant struma of the thyroid gland. In horses, cancer of the lung and respiratory tract, cancer of the sexual organs and glands, cancer of the kidneys/urinary bladder, stomach, skin, melanomas of the skin occur. T. have also been described in elephants. According to Teutschlander, cancer occurs more often in old animals than in young ones, more often in females than in males. In plants, tumor-like formations—galls, clubroot, root-knot of beet—have also been described, which were attempted to be connected with the problem of neoplasms in humans (Jensen). However, further research by Smith and Townsend showed that these T. are caused by a special bacterium (B. tumefaciens) and represent a productive form of inflammation specific to plants. II. Statistics of tumors. In humans, T. of all tissues and organs occur. Statistics of benign T. are subject to no accounting, and all statistical materials concern malignant T. In this, in the overwhelming majority, cancer predominates over other types of malignant T.; thus, according to the data of Hamburg statistics, for 100 deaths from cancer there are 4.7 sarcomas. T. occur in all latitudes and among all peoples. The once prevailing and erroneously established scientific opinion that T. occur only in civilized countries has not been justified. For all exotic countries, this statement systematically falls away as a medical network is established in them. Thus, for example, Clunet in 1912, studying the spread of cancer in Africa, claimed that in Morocco this T. almost does not occur. At present, Colombani speaks of the extraordinary frequency of cancer in Morocco and considers this country almost the favorite place for cancer diseases on the entire globe. The geographical latitude of the country's location also does not predetermine the frequency of tumor forms. At the extreme north and at the equator, T. apparently occur no less and no more often than in middle latitudes, although individual forms and localization of T. may vary depending on local conditions, development and character of industry, national customs, etc. According to the calculations of Hoffman, we have the following data on mortality from malignant T. in various places on earth, calculated per 100,000 inhabitants: in Europe—76.6, in Oceania—73.0, in America—65.7, in Asia—54.0. All these figures are given with a large degree of approximation, but they confirm the fact of the susceptibility of all humanity to T. The existing statistical data on the spread of malignant T. in humans must be treated with considerable caution. In particular, the result of unskillful use of statistics is the spread of the erroneous view of a sharp increase in mortality in recent years from malignant neoplasms. Such an impression can indeed be formed with a superficial study of some statistics. In reality, the increase in malignant T. is in large part not factual but apparent, depending on improved diagnosis, on decreased mortality and other causes. The relative increase in mortality from malignant T. can be explained by the decrease in mortality from tuberculosis and other diseases. In addition, the change in the age composition and especially the age composition of the urban population make relative mortality coefficients over a significant period of time statistically incomparable with each other. The decrease in birth rates in cities, on the one hand, immigration of able-bodied and emigration of disabled population, on the other, have sharply changed the average age-sex composition of the population of large cities; therefore, only age-specific mortality coefficients can give a correct picture of mortality from cancer. In statistical data, the material from autopsies has special value, excluding the possibility of a significant percentage of errors related to ante-mortem diagnosis and based on the use only of death certificates.

But even according to autopsy statistics, a systematic sharp increase in mortality from malignant T. has not been proven; at the same time, statistics based on medical certificates show such an increase. According to data from Lyubars (1924), who takes into account a certain percentage of erroneous antemortem diagnoses, mortality from malignant neoplasms for people over 20 years reaches 10%. The statistics of Berblinger (Berblinger, city of Kiel) give 14-17% mortality for people over 20 years. According to data from Berencsy and Wolff based on 20,000 autopsies, malignant T. were found in 11.6%. Furthermore, the denial of an increase in malignant T. is found in the data of Peller (Peller; 1925) on mortality in large European cities, of Bilz in the mortality statistics of Jena, and in the large American statistics (Prinzing; 1926). Of all forms of T., a significant increase in cancer of the respiratory tract (bronchi and lungs) can be considered indisputable, confirmed by numerous data from both our and foreign oncological statistics. (Possible explanations for this growth are given below.) For the USSR, exact statistical data are absent. According to approximate calculations (Kholdin) in the RSFSR, 90-95 thousand people die annually from malignant tumors. At the same time, high mortality coefficients are noted for Moscow and Leningrad, which probably depends on more thorough examination and more accurate diagnosis. For the Ukrainian SSR (Merkov), mortality rates from malignant T. per 100,000 urban population of Ukraine are as follows: Table 1. 1923 G.......65 1924 »......67 1925 »......64 1926 G.......65 1927 »......70 1928 >......69 From all malignant neoplasms in 1926-27, 72.9 people per 100,000 men and 82.7 people per 100,000 women died. In 4 large cities of Ukraine (Kharkov, Kiev, Odessa, Dnepropetrovsk), mortality per 100,000 people is as follows: Table 2. Mortality from cancer from all malignant T. 1923 1924 1925 1926 1927 1928 1929 tumors Among the causes of mortality for the entire population of Ukraine, malignant T. rank 4th, moving by age to 3rd place for 30-35 years, 2nd place for 50-60 years, and to 1st place for women aged 50-54 years. Approximately according to Merkov's statistics for 31,500,000 population of Ukraine, 31,500 people die annually from malignant T. The highest mortality according to this statistics falls on the age group 60-69 years, with the average age for men being 59.3 years and for women 57.9 years. According to combined data from Moscow morgues for 1923-27 (Davydovsky), out of 37,899 autopsies, 8.84% died from T.; if stillborns are excluded, this percentage increases to 9.98%. It is important to keep in mind in principle that morgue statistics, since it covers only a certain part of the deceased, is not a completely accurate reflection of oncological mortality; in particular, it depends on the degree of hospitalization of tumor patients; on the other hand, this same statistics, conducted on a large material when covering the main mass of the deceased by sections, is undoubtedly closer to the truth than statistics based on medical certificates of death. III. Structural and functional characteristics. General structure of T. Atypism. The special place that T. occupy among processes associated with an increase in tissue mass is due to the following moments: 1) the special structure of T., 2) the character and peculiarities of growth, 3) special forms of relative connection with the carrier of T. The external form of T. represents extraordinary diversity depending on the type of T., peculiarities of its structure, and relationship with surrounding tissues. From a histological side, T. is determined by the atypism of its structure, which has different expression and different degree in T. of different types and different course. Every T., consisting of connective tissue stroma and parenchyma determining its character (in epithelial T.-flat, glandular epithelium, in muscular-muscle fibers and bundles, etc.), has an organoid structure, expressed more or less clearly. The division of all T. into histoid (see Histoid) and organoid, based on the presence or absence of stroma and preserved since Virchow's time, has lost its absolute significance, since in any T. a vascular stroma and specific parenchyma for this T. are morphologically established; therefore, this division in its modern understanding refers only to the greater or lesser development of stroma. In some T., the amount of stroma is negligible and limited only to vascular tubes (sarcomas), in others it is so great that it quantitatively significantly exceeds the specific parenchyma of T., which gave some authors reason to interpret such forms of T. (e.g. scirrhous) as undergoing self-healing through scarring (Borst). However, there are a number of indications of the absence of a direct dependence of the clinical course of T. and its tendency to metastasize on the amount of stroma. The stroma consists mostly of fibrous connective tissue, in which vessels pass. Elastic tissue is not always uniformly represented in the stroma. Before the development of T., it mostly atrophies. In other cases, on the contrary, an increase in elastic fibers is observed, forming either in the parenchyma of T. (mixed tumors of salivary glands, so-called elastoid sarcoma-Fischer) or around it around vessels and glandular tubes (scirrhous of the mammary gland). To the present day, the question of the origin of stroma is controversial: whether it is an organic part of T. itself or represents a product of the local connective tissue of the organ. Most researchers adhere to the latter point of view, proving it by such processes as, for example, osteoplastic carcinomas, i.e., the formation of stroma from bone tissue in metastases of cancer to bone. The opposition of stroma to the parenchyma of T., resulting from this view, contradicts the general concept of their organic unity. In a proliferating T., infiltrating healthy surrounding tissues of an organ, one can assume the inclusion of the stroma of the latter into the stroma of T. In a formed T., the proliferations of stroma and parenchyma are interdependent processes determining the unity of the organoid structure of T. Confirmation of this view is the known constancy of the relationship between stroma and parenchyma in the primary focus and in the metastasis (e.g. scirrhous retains in the metastasis the peculiarities of connective tissue development), the mixed structure type of many glandular T. (fibroadenoma), etc. Now it can be considered almost indisputably established that in many epithelial T., stroma as well as blood vessels are formed from elements of the parenchyma of T. itself (Borst, Marchand, Herzog). The uneven distribution of stroma and parenchyma is one of the frequent, superficial forms of atypism of T. tissue. This form of atypism is especially clearly manifested in glandular T., in some places of which glandular elements are crowded in a small amount of stroma alongside large spaces of the latter devoid of parenchyma. The question of the blood supply to T., important for studying the peculiarities of its growth, has been studied repeatedly. The significance of the vascular system for the development of T. is emphasized by the experiments of Sittenfield, who showed that in an anemic rat limb, 18% of T. transplants took, while in a limb with venous hyperemia-96%. The atypism of the structure of T. is also reflected in the development of the vascular system. According to Goldman, the latter never reaches the degree of development as in a normal organ; the division into arteries and veins is especially often absent. Sometimes in T., blood sinuses lined with endothelium are formed, considered by Koritsky as formed by T. itself from its elements. Schmorl points to the possibility of replacement by T. cells of 'coastal cells', i.e., endothelium of vessels (phenomena of Vertretung). Dibbelt, based on his numerous studies, notes that the degree of differentiation and development of the vascular system fully corresponds to the degree of differentiation of the T. it supplies. A number of oncologists, including Ribbert, tend to attribute all phenomena of degeneration in T., up to necrosis, to the weak development of the vascular system. From the further exposition, the primitive mechanistic nature of such a view will be clear, since circulatory disorders play a secondary role in all processes of metabolic disorders in T. compared to factors inherent in the properties of the tumor cell itself. Lymphatic vessels are as a rule poorly developed in tumors, especially in malignant tumors (Monogenov). The question of the development of nerves in T. is given great importance by many. Observations available until recently deny any presence of nerves in T. except preformed ones (Goldman, Jung). The latest data of Itchikawa and Uwatoko, who found proliferation of nerve fibers in malignant and benign T., are doubtful even to the authors themselves. It is necessary to emphasize that differentiated tumors (muscular, glandular) do not react functionally to nerve irritation. It is nevertheless necessary to point out that the development of a tumor is associated with the peculiarities of innervation of the organ in which it develops.

Experiments have established that the disruption of animal and vegetative innervation by cutting the p. auricularis and sympathetic nerve affects the development of tar cancer in the rabbit's ear; according to the data of Ichikawa and Kotzareff, confirmed by a number of other researchers, the disruption of the trophic connection by cutting the animal nerve inhibits tumor development; the importance of sympathetic innervation is also noted, possibly through the regulation of blood supply. In the parenchyma of Tumors, manifestations of structural atypism have different characters in different Tumors. Common to all Tumors is a disruption in the relationship and mutual arrangement of their cellular elements. In a normal organ, there is an organization of cellular elements into complex associations forming the so-called histosystems. Heidenhain rightly emphasizes that every organ is not a simple aggregate of cells, but the latter are united into systems of ascending orders. In most benign Tumors, such associations of cells into histiosystems of lower orders are quite distinguishable: in fatty Tumors, lobules are formed; in glandular ones, glandular tubules; in muscular, connective tissue ones, bundles of fibers, etc. But the limitation, and for malignant Tumors often the complete absence of formation into associations of higher order, is an essential sign of atypism. (For example, in glandular Tumors, individual tubules are not united into glandular lobules; if such is formed, it does not have a common excretory duct, or the latter is not included in the general system of excretory ducts of the gland. Glandular Tumors are mostly formed not from secreting elements, but from poorly differentiated epithelium of the excretory ducts. In muscular Tumors, the mutual arrangement of bundles and fibers is such that a muscle not adapted for a specific function is formed, but a random conglomerate of muscular elements.) Thus, histologically a picture is obtained that has only a distant resemblance to the structure of the organ and is therefore designated as an organoid structure. Tumors that have preserved morphological similarity with the structure of the corresponding organ are called homologous or homotypic; those that have lost this similarity-heterologous or heterotypic. Further manifestations of atypism of Tumors in its more superficial forms consist in the polymorphism of the elements making up its composition. This polymorphism concerns either cellular complexes (for example, polymorphism of fat lobules in lipoma, glandular tubules in adenoma, colloid follicles in adenomas of the thyroid gland) or, as is almost always the case, the individual cellular elements constituting the Tumor. The shape and size of the latter often present great variety; particular importance is attached to the disruption of the relationship between the size of the nucleus and the size of the protoplasm (Kernplasmarelation of German authors). For example, there are indications by Heiberg of an increase in the size of the nuclei of cancer cells compared to their size in the original normal tissue. This atypism penetrates deeply into the individual structural elements of the cell (see below). The growth of Tumors presents specific features for it, distinguishing it from other manifestations of growth in the organism. The general rule is considered to be its duration and uninterruptedness, the absence of a certain cyclicity and completeness, as is the case in processes of regenerative tissue neoplasia. The establishment of such a rule is based on the contrast between the development processes of Tumor tissue and the development of embryonic tissue. In the latter, the result of its development is the formation of complete structural elements of the corresponding organ, while in Tumors this development of their elements does not reach such a degree of differentiation, being limited to allegedly continuously lower stages of development. However, according to some data, which formed the basis of the transformation theory of Tumors (see below), Tumors also have a certain cyclicity of growth and development of their elements. The growth of Tumors sometimes occurs extremely slowly, especially in benign Tumors, although there are also malignant Tumors for which rapid growth is generally typical, with extremely slow growth. For example, Hansemann described a cancer of the stomach of 40 years' and a hypernephroma of 30 years' duration. A frequent phenomenon, especially in benign Tumors, are fluctuations in growth with long intervals of its complete arrest. Cases of spontaneous regression are also described in the literature. Regression of uterine myomas after the loss of ovarian function is known; complete regression with self-healing of malignant Tumors is also known, although such cases are described as rare casuistry. With respect to surrounding tissues, two forms of growth of Tumors are known: expansive growth and infiltrating growth. The first is generally characteristic of benign Tumors; in it, the tumor compresses the tissues of the organ, grows outside them, being isolated from them by a capsule. Infiltrating growth with ingrowth into surrounding tissues and their destruction is usually a property of malignant Tumors, being one of the essential, though not absolute, criteria of malignancy. It is believed that the destruction of tissues is produced by the toxic action of the elements of the Tumor, but the role of this factor as the sole cause is disputed by some authors. Fischer-Wasels explains the degree of infiltrating growth by the greater or lesser connection of individual elements of the Tumor with each other and their greater or lesser ability to move through the tissue. This parallelism between the forms of growth and malignancy and benignity has only rare exceptions; for example, benign angiomas of the skin sometimes grow into the subcutaneous tissue, muscles, bones; malignant Tumors with infiltrating growth in the primary focus sometimes show expansive growth in metastases. According to most modern views, the growth of Tumors occurs from a tumor rudiment. The latter is most often single, although sometimes Tumors can begin immediately as multiple. Subsequently, the growth of Tumors may not be uniform, but concentrated around so-called 'proliferation centers', described in both benign and malignant Tumors. The growth of Tumors, as is accepted by most authors, occurs by the multiplication of its own elements. 'Growth from itself' (this definition of Ribbert is often used and gives rise to incorrect interpretations) should be understood as follows: in the formation of the rudiment of the Tumor, its subsequent growth goes only by the multiplication of its elements. This viewpoint denies the possibility of the so-called 'appositional' growth and development of Tumors, i.e., the increase in tissue mass by the transformation of cells of the surrounding normal tissue into tumor cells. However, the existence of the latter method of development of Tumors is proved by a number of authors: for example, Hauser proved the presence of appositional growth in cancer of the intestine; Verse on serial sections also established the transition from normal epithelium to tumor epithelium in polyps and cancer of the stomach and intestines; the same data were obtained for other forms of Tumors by Goldzieher, Rosenthal, Herzog and others. According to Menetrier, the formation of cancer itself is preceded by visible benign, but limited tissue proliferations, for example, for squamous epithelium-warts, papillomas; for glandular-adenomatous proliferations. The formation of the rudiment of Tumors by appositional growth is also not denied by Fischer and others. The assumption of wide transitions of the surrounding tissue into tumor tissue lies at the basis of the transformation theory of tumors by G. Koritsky. Func. interrelationships of Tumors and the organism. Particularly essential among the biological properties of Tumors are those that are united in the oncological literature under the term 'autonomy', falsely reflecting special forms of subordination existing between Tumors and their carrier. These properties are considered as the exit of metabolic processes of Tumors and products of functions of their specific elements (colloid, mucus, bile, hormones) beyond the limits of correlational relations existing between all tissues of the organism, included in the general unified plan of its metabolism. This exclusion of Tumors from the general plan of metabolism is illustrated by the preservation and continued accumulation of fat in a lipoma with general exhaustion and disappearance of fat from all other areas of the body; by the absence of obesity of Tumor cells in phosphorus poisoning along with degenerative obesity of various organs. The specific function of glandular elements of Tumors (mucus, bile, hormones) according to these views also goes beyond the limits of correlational relations. In this connection, according to atypism of structure and chemical character, and also the very method of formation by the Tumor of substances, they often essentially differ from the products of the corresponding organ (colloid in Tumors of the thyroid gland often has a different composition than colloid of the gland itself); the formation of substances is often the result not of physiological functional processes of cells, but of their degeneration (colloid, mucoid degeneration, etc.). However, it should be noted that these substances, especially products of Tumors of endocrine glands, entering the general circulation, can cause serious shifts in the general state of the organism (adenoma of the pituitary gland-acromegaly;)

Tumors of the thyroid gland—disease of Basedow; teratomas, tumors of the adrenal gland, tumors of the pineal gland—premature sexual maturation, etc.). In this circumstance, one should see the inclusion of tumors in the general metabolism of the organism. The latter is especially vividly illustrated by the replacement of the function of a normal organ by a tumor, as was the case in the case of thyroid adenocarcinoma described by Eiselsberg, where the phenomena of myxedema that developed after repeated operations ceased with the development of recurrences and metastases. The concept of the 'autonomy' of tumors arose due to the apparent independence of the growth and functions of tumors from the general state of the organism. The a priori falsity of such a view is proven by a number of facts establishing the actual interdependence of the processes of tumors and the entire organism, proceeding according to the principle of the general and the local. Such facts include the following: 1. The influence of constitution on the development of tumors. This can include inherited predisposition to tumors with certain corrections arising from the chromosomal transmission of hereditary traits. There are known cases in human pathology of various familial tumors, both benign and malignant. This factor is especially prominent in animals, where, as Slye showed, it is possible by artificial breeding to cause a cumulation of constitutional factors that increase spontaneous cancer morbidity. The same author points to the manifestation of Mendelian heredity in the occurrence of spontaneous cancers in mice. The importance of constitution is also evident in transplantation and attempts to obtain experimental tar cancer; some families of mice and rats give 100% transplantability, others from 0% to 20%. There are indisputable indications of species susceptibility to disease with one or another form of tumor in animals (mice-cancer, rats-sarcoma, chickens-sarcoma, etc.). The importance of species and race is evident in experiments with tar cancer: it is not obtained in guinea pigs and rats, but is obtained in rabbits and mice; furthermore, cancer caused by infection with Spiroptera neoplastica occurs in gray rats 10 times more often than in white mice. 2. The influence of endocrine glands on the course of tumors. There are numerous indications, coming from both human and experimental oncology, regarding the dependence of the course and transplantability of cancer (in animals) on various endocrine factors (sexual, pancreatic, adrenal glands). Numerous recent experimental works have been devoted to this question, with results that do not yet allow establishing any regularity of individual forms of such dependence. There are numerous indications of the inhibitory effect of the sex glands on the development of tumors. Pregnancy also sometimes inhibits or causes the reverse development of existing tumors, and in other cases accelerates the course of tumors. It is possible that the indicated dependence is not achieved by the direct action of the hormone of the corresponding gland on the tumor, but through a change in metabolism, but this does not change the essence of the matter, establishing the dependence of tumors on the general processes of the organism. The above-mentioned influence of the secretory products of tumors of endocrine glands on the entire organism also establishes such interdependence. 3. The influence of dietary regimen on the course of tumors. The influence of the quantity and qualitative composition of food on the course and development of tumors is the subject of numerous clinical and experimental investigations, forming the basis of rational dietary therapy of tumors. Of great interest are the observations of many authors establishing that under a starvation regimen, tumor cells suffer to the same extent as the cells of the body. Mareschi and Apolant discovered that mice that had starved for several days before tumor transplantation survived longer than those that were normally fed. After removal of sarcoma, well-fed animals gave 83% recurrences, poorly fed ones—41%. The influence of one-sided nutrition was studied with particular care, in which the dependence of the transplantability of experimental tumors and their development on the quality of food was established (feeding with meat inhibits the growth of sarcoma in rats, while food rich in blood and yeast stimulates it; feeding with lard inhibited the growth of malignant chondroma, feeding with oats stimulated it). The importance of vitamins was investigated many times, and it was noted that vitamins have some positive significance for the transplantability of a cancerous graft, but they have no effect on its further development. Carbohydrates are of particular interest in connection with the peculiarities of carbohydrate metabolism in tumor cells (see below), and there is a tendency to attribute to a carbohydrate-free diet an inhibitory effect on the development of tumors. The importance of one or another salts was also studied in a number of works, and a number of authors allegedly establish the stimulation of tumor growth by large introduction of potassium and magnesium, and inhibition by the introduction of calcium and sodium. Numerous experiments were also conducted with other forms of one-sided nutrition (especially with feeding with lipoids); the data obtained are of considerable interest both for studying the peculiarities of tumor growth and for practical application in the clinic. 4. The influence of the spleen, blood, and mesenchyme on the development of tumors. In clinical practice, the fact of the absence of cancer metastases in the spleen has long been known. It was found that splenectomy increases susceptibility to cancer transplants, while immunization with the spleen reduces it. It turned out that the spleen inhibits the growth of transplants of normal tissues as well (thyroid gland, adrenal glands). Then in numerous observations, the positive value of the lymphocytic reaction of blood in weakening the tumor process was established. Similarly, a connection is established between the development of a transplant and the state of the mesenchyme, manifested in the fact that any impairment of the functions of mesenchymal elements is a favorable factor for the growth of tumors (Bogomolets, Blumenthal, etc.). 5. Experimental tumors caused by various local irritations (X-rays, tar cancer) also confirm the dependence of the development of these tumors on the general state of the organism. It is known that with local irradiation without simultaneous irradiation of the entire animal, no blastomatous process develops. Smearing with tar causes not only atypical tissue growth at the site of smearing, but also a number of changes in other organs, especially in the liver, where a number of serious changes in its parenchymal elements are noted. The existence of so-called 'sensitive periods' of tumor occurrence is of great importance, between which the organism remains refractory to any influences provoking it. From this point of view, attempts to 'carcinomatize' cells in tissue cultures outside of a general connection with the organism must be considered as not having a serious basis. 6. Tumor cachexia is a fact of reverse relationship, i.e., the influence of tumors on the organism. There is a tendency to attribute to tumor cachexia a specific character, supposedly depending on the excretion of specific substances by tumors. It is necessary, however, to point out that cachexia is not a characteristic feature of all tumors, since it occurs only in their malignant form. But even here it is far from always present, being absent, for example, in bleeding tumors accompanied by pronounced anemia: such anemias themselves, as is known, sometimes predispose to a certain degree of obesity. Unlike cachexia caused by other diseases, many authors wanted to attribute cancer cachexia to the action of a specific 'cancer poison'. However, all attempts to discover such a chemical method in the blood and by serological reactions upon critical examination turned out to be negative. Close observations showed that the mechanism of the development of cachexia consists of many moments, of which poisoning by non-specific breakdown products of tumors is essential; in numerous cases of cancer of the breast with multiple metastases, cachexia occurs only after the ulceration of the tumor. In addition, the indisputable importance is either the production of pathological enzymes by the tumor or the hyperproduction of enzymes inherent in the organism, which were mentioned above (tumors of the thyroid gland, pituitary gland, the destructive effect on the tissues of the organism of digestive enzymes produced by stomach cancer, according to Borst). The general condition of the organism worsens due to frequent secondary infection of the tumor, which, according to Heymann's data, is of great importance for the outcome of operations. Besides, it is necessary to take into account the increased load on the organism as a whole and its individual organs, caused by the mass of the tumor and the increased metabolism caused by it. In this case, in the pathogenesis of cachexia, the so-called dioxidative carbonuria (see below) may have special significance, which is also a vivid illustration of the interdependence of tumor metabolism and the entire organism. Metastases and recurrences. An essential feature of tumors is their ability, when their particles are carried by the blood or lymph to other distant organs, to give rise to the development of daughter foci called metastases. Depending on the routes of spread, two groups of metastases are distinguished: hematogenous and lymphatic.

Tumor masses that grow into vascular lumens shed tumor cells or groups of cells from their surface, which are carried either by the bloodstream to all organs of the small, large, and portal circles, or by the lymph flow to the nearest lymph glands. The small size of tumor cells, and also presumably their amoeboid movements, facilitate their displacement. The spread of metastases in the lymphatic system occurs either in the direction of lymph flow (so-called 'orthograde metastases') or against the flow of lymph ('retrograde metastases'). An example of the latter is the so-called Krukenberg's tumor of the ovary, which is a metastasis from stomach cancer. Sometimes the spread of metastases occurs along the peri- and endoneural lymphatic spaces of peripheral nerves. In this way, isolated necrotic meningitis (Ernst, Marchand and others) can arise. The first lymphatic metastases develop in the regional lymph glands, following which the next stages of the lymphatic system become affected, usually in a regular sequence. In addition to this, there are also so-called 'auto-inoculation' metastases, resulting from the implantation of cancer cells onto a surface in contact with the tumor, for example, the mucous membrane. Thus, for example, in cancer of the lower lip, the upper lip can serve as a site for the implantation of cancer elements in contact with it. Furthermore, for certain types of tumors, metastases to specific groups of lymph glands or to specific organs are considered classic and regularly recurring; in the formation of such metastases, not only mechanical conditions but also the properties of the surrounding environment play a role. Examples of such metastases are metastases of prostate and thyroid tumors into the skeletal system, metastases of melanoma into the liver, of lung cancer into the brain and adrenal glands, of chorion-epithelioma into the brain and lungs, etc. The explanation for this regularity should not be sought in the conditions of mechanical transfer of these metastases by the bloodstream or lymph to the specified organs, but in the conditions of the environment favorable for the development of the tumor in that organ. The latter also explains the frequently encountered fact when a metastasis significantly exceeds the primary tumor in size and has greater importance for the symptoms it causes. The very fact of tumor cells being carried into an organ does not yet mean that a metastasis will necessarily develop there. In the mechanism of this development, the following phases can be indicated: 1) entry of tumor cells into the circulation, 2) their fixation in a new location, 3) multiplication in that organ under favorable environmental conditions. It must be emphasized that the first phase does not necessarily lead to the second, nor the second to the third. The viability of tumor cells entering the circulation has been proven histologically; however, the overwhelming majority of them die in the blood and in the organs to which they are carried. The picture of the necrobiosis of tumor cells carried into the lung has been established by the research of Goldman, Schmidt and others. In this respect, the spleen is of great interest, where the development of cancer metastases almost never occurs due to the death of the cells carried there. Sometimes the filling of blood vessels with tumor elements can lead to their thrombosis with complete obstruction. The formation of metastases is also promoted by a number of external irritations. Thus, for example, a biopsy performed for histological examination of the tumor and carried out without observing the required rules can lead to metastasis of the tumor; it is noted that the development of metastases is sometimes facilitated by massages of the tumor, radiotherapy, pregnancy and some other factors. In terms of time of appearance, some metastases develop almost simultaneously with the detection of the primary focus, while others develop many, sometimes tens of years after the removal of the latter (for example, melanoma, some cancers of the breast, chorion-epithelioma). In structure, metastases usually coincide with the structure of the primary tumor, although sometimes they can differ significantly. In this case, the degree of morphological anaplasia in most cases increases in metastatic tumors. Furthermore, it is necessary to note the significant variations found in the structure of metastases. Even Virchow noted that the organ in which a metastasis develops leaves its imprint on the structure of the latter; nevertheless, this does not provide grounds for speaking of the presence of 'organ mimicry' of the metastasis, as some authors do. Apparently, more common are cases where a tumor metastasis in a certain organ itself carries some features of the primary organ of the tumor. Metastases usually develop only in malignant tumors, although metastases (extremely rare) have also been described in benign tumors (lipoma, chondroma, cavernous angioma, goiter of the thyroid gland, etc.). Usually, the quantity and character of metastasis spread differ in cancer and sarcoma. The spread of metastases through the bloodstream is found predominantly, although not necessarily, in sarcomas, while through the lymphatic system in cancer. Metastasis sometimes takes on such extensive proportions that a picture of dissemination of the tumor throughout the body with the formation of multiple metastases results. Such cases must be distinguished from primarily multiple and systemic tumors (for example, gliomatosis of the brain).-Recurrences of the tumor at the site of the primary focus after surgical removal are called recurrences. They are explained by the fact that not all of the tumor was removed during the operation, but microscopic parts of it remained in the tissue; part of the recurrences can be attributed to so-called implantation recurrences, depending on the infection of the surgical wound with viable tumor cells that separated during the removal of the tumor and were subsequently implanted in the wound. The time of appearance of local recurrences is extremely varied; they can follow immediately after surgical intervention or appear many years after it. Biological features of the tumor cell. Anaplasia. The properties outlined above, which place tumors in a special position among other processes of normal and pathological tissue growth in modern concepts, have led a number of researchers to consider tumors as formations foreign to the body, being in relation to it a true parasite. Some authors even claim that the tumor is a colony of cells foreign to the body that entered it from the outside world. Therefore, elucidating the pathogenesis of the tumor requires as the first task the establishment of the true genetic relationship between the tumor and the body. The overwhelming majority of modern oncologists have no doubt that the tumor cell is a cell of the organism itself. The following facts speak for this: 1. The structure of the tumor and its individual elements. A number of tumors show such a great similarity in the structure of individual elements to the structure of the original normal tissue that their genetic connection becomes indisputable. Tumor cells contain the same structural elements as normal body cells. In them, in addition to the basic elements of the cell, the Golgi apparatus, mitochondria, Altmann's granules, the cell center with centrioles and others have been found; in tumors of nervous tissue, neurofibrils have been found, in muscular tissue, the development of a fibrillar apparatus and cross-striations. It must be pointed out that according to the general atypism of structure, these elements can differ significantly from the normal corresponding body cells in structure, number, and arrangement. 2. The connection between the origin of the tumor and disturbances and defects in embryonic development (choristomas, hamartomas, etc.). 3. The function of the tumor, which often, although in a perverted form, repeats the function of the original tissue (keratinization, production of bile, colloid, etc.). 4. Species specificity of tumor cells in transplants-sarcoma of a rabbit, transplanted for example to a rabbit, retains the specific precipitin reaction of the rabbit. 5. Immunity reactions, which are generally not specific for tumors, turn out to be the stronger the closer the tissue used for immunization is in structure to the tumor. In this connection, Uhlenhuth and Seifert indicate that the greatest immunity is achieved with a specific tumor of the same species. Against the view of the foreignness of the tumor in relation to its carrier, Virchow rebelled, pointing out that the tumor originates from body cells but is removed from its laws in the process of its growth and development. Thus established genetic relationship of the tumor cell with the body cells in the study of its pathogenesis requires a comparative study of their biological properties. Of these, for the tumor cell, the main ones are considered to be the reduction or loss of the ability to morphological and physiological differentiation. At the same time, it should be emphasized that morphological and functional differentiation are not necessarily parallel. The totality of all characteristics underlying the loss of differentiation, distinguishing the tumor cell from the normal one, Hansemann designated by the term 'anaplasia'. In this connection, Hansemann considered that such cells lose their mutual connection and the tumor, at higher stages of anaplasia, acquires the character of a true parasite with a complete loss of 'altruism'. The term 'loss of altruism', used to denote the relationship of the tumor to its carrier, widely appears in oncological literature, both foreign and Soviet. The above relationships between the tumor and the body indicate the complete inadmissibility of such a definition, either terminologically or in substance.

The term "anaplasia" has become entrenched in the oncological literature, although it no longer contains the meaning originally invested in it by Hansem (see Anaplasia). Manifestations of anaplasia in tumors. 1. An essential property of tumor cells is their mobility, their ability to wander through tissue similar to amebocytes. This property, by no means belonging only to tumor cells and widely distributed among normal elements of the organism, mainly concerns so-called malignant tumors, where the intensity of this mobility is parallel to the degree of malignancy. 2. The ability to phagocytosis, characteristic of many normal cells of the organism, has in cells of malignant tumors greater intensity than in benign ones. At the same time, phenomena of autophagocytosis are observed, consisting in the phagocytosis of autolytically disintegrating tumor cells by other tumor cells. 3. As for the relationship of tumor cells to external influences, according to some data, their resistance to low temperatures is noted. Tumors of mice subjected to 20-30 minute exposure to 4° temperature of liquid air did not lose their transplantability. These same temperatures proved fatal to normal skin epithelium. Tumors that had been stored for two years at -8° temperature proved transplantable (Ehrlich). Tumor cells exhibit exactly the same resistance to high temperatures; according to Caspari's data, three minutes of boiling still allows transplantation of such a tumor. An interesting fact is that according to some data, germ cells - eggs and sperm - exhibit the same resistance. This resistance is also manifested in the fact that phagocytosis of dead tumor cells occurs only after autolysis of their nuclei. It should be noted that these data refer to animal tumors, where the criterion for evaluating external influence is transplantability. Meanwhile, Virchow already noted that tumor cells, especially malignant ones, are little resistant and viable, because with rapid multiplication they die just as rapidly and in masses. Animal tumors also show little resistance to pharmacological agents that reduce their transplantability; this includes the action of spleen extract, cocaine, morphine, adrenaline, diphtheria antitoxin, cholesterol-lecithin and other substances. Spontaneous tumors also show reduced resistance to external influences, e.g., to inflammatory infiltration, heat, electric current, diathermy, etc. Cases of spontaneous healing of angiomata upon ulceration, epitheliomas under the influence of diathermy, etc., have been described. In this regard, external influences show the individuality of different types of tumors; e.g., non-keratinizing skin cancer, undifferentiated cancers of mucous membranes, many sarcomas respond well to radiotherapy, while the same influence stimulates the growth of melanomas (Laborde, Clairmont); uterine and ovarian sarcomas respond well to roentgenotherapy, while the latter is powerless in cancers of the lips, tongue, larynx, and in cancer of the breast, preventive roentgenotherapy even worsened the results of the operation. Thus, the opinions of most researchers coincide in that tumor cells of spontaneous tumors, both benign and malignant, show much less resistance than normal cells of the body; they are less durable and less capable of regeneration than cells of the analogous normal tissue of the tumor carrier. This fact (along with the possible significance of insufficient blood supply to the rapidly growing tumor) should find appropriate evaluation when judging the causes of tumor disintegration. In these phenomena of cell disintegration, some researchers see conditions for stimulating the growth of the tumor as a whole, attributing to the products of this disintegration the role of a stimulator of cell division in the surrounding tissue. Caspari, without predetermining the nature of this stimulator, introduced the concept of "necrohormones of growth" released by disintegrating tissue; Gurevich established the presence in tumors of so-called mitogenetic rays (see). 4. Morphological anaplasia of the tumor cell. Numerous attempts to find the morphological substrate of the specific feature of the tumor cell have not led to the expected results. The morphological criterion for determining the essence of the tumor cell and explaining the peculiarities of its functions proved insufficient. It is accepted that the tumor cell does not reach the morphological degree of differentiation of an adult cell of analogous tissue; under differentiation should be understood not only the development of certain structures in the cell itself, but also the inclusion of these structures in the system of a single organism. For the cell itself, the loss of differentiation finds its morphological expression in the poverty of its structure, which runs parallel to the increase in malignancy; at the same time, remnants of special function may finally disappear from the tumor cell. There are indications of a connection between this impoverishment of structure and unfavorable conditions of the external environment, associated with the rapidity of growth; in favor of such indications is the transformation upon transplantation of skin epithelium of sebaceous glands into stratified epithelium; further, in most transplanted normal tissues, especially glands, degenerative processes occur caused by disturbance of nutrition; the same thing happens in tissue cultures under unfavorable nutritional conditions. However, the transfer to the tumor cell of special significance of external factors for its structure is not justified: it would be incomprehensible in such a case the preservation of structural poverty even in those conditions when the tumor is placed in good conditions for nutrition and growth - in recurrences, metastases, transplants, tissue cultures, etc. Therefore, it must be assumed that the loss of the ability to differentiate in general and morphological in particular is the essential quality of the tumor cell itself. Assumptions about the existence of a parallelism between the degree of morphological differentiation of the cell and the degree of its malignancy exist only as a scheme, far from always realized. A number of unquestionably malignant tumors, both in clinical course and according to structural features, consist of cells of high morphological differentiation, including complex structural elements of protoplasm. Therefore, it is necessary to take into account the absence of an unquestionable cytological criterion of malignancy and benignity. An essential criterion of loss of differentiation is the above-mentioned absence of formation of high cell complexes. According to Koritsky, the peculiarities of the cancer cell consist in the loss of complexity and polarity (the latter quality consists in the distribution of various functional elements of the tumor to its poles). Fischer points out that every stage of differentiation is associated with the fixation and increase of the correlational dependence of cells in tissue complexes. Therefore, the loss of the ability to differentiation is manifested in the non-inclusion of tumor cells into complex connections, in their acquisition of the ability to wander through tissue, phagocytosis, etc. The structure of the nucleus of the tumor cell is an essential sign of morphological anaplasia. The nucleus, especially the forms of its division, has been the subject of numerous works, because in the peculiarities of division of the tumor cell some researchers want to find an explanation for the whole complex of phenomena of blastomatous growth. The size of the nucleus in various tumors has been studied repeatedly, establishing in general its greater size compared to the nuclei of cells of the maternal soil (Sokolov, McCarty, Heiberg). The development of the doctrine of chromosomal transmission has attracted special attention to the nucleus of the tumor cell. The latter as a rule multiplies by mitosis. Hansem was the first to note in malignant tumors the presence of atypical mitoses in the form of asymmetry in the distribution of chromosomes, multipolarity of mitoses, conglomeration of chromosomes, their dissolution, etc. At the same time, Hansem attributed the greatest significance to the asymmetry of mitosis, thanks to which daughter cells received an unequal number of chromosomes. Hansem believed that by such division with loss of cells of a certain number of chromosomes, undifferentiated cells should be formed. Boveri (in recent time a number of other authors have joined his point of view) hypothetically assumes that in asymmetric division some cells lose chromosomes that inhibit the exchange and growth of the cell, thanks to which these cells acquire the ability to unlimited nutrition and multiplication. Recent works (Painter, Winge and others), partly on human tumors, partly on tumors of various animals, have established great variations in the number of chromosomes dividing in tumor cells: from haploid to octoploid and polyploid giant mitoses. These researchers and a number of others attribute decisive importance in the pathogenesis and etiology of tumors to these factors, as being able to explain the origin of blastomatous growth from the point of view of the general foundations of normal and pathological heredity. It is necessary, however, to point out the facts that require caution in such an approach. Atypical mitoses can be caused by the action on normal tissue of various physical and chemical factors (heat, cold, various poisons, narcotics, various types of radiant energy, etc.). In rapidly growing normal tissue, with an increase in the number of dividing cells, the number of atypical mitoses also increases.

In benign tumors, based on data available up to the present time, atypical mitoses have not been detected. It is also worthy of note that radiant energy has a destructive effect on the nucleus of the tumor cell and at the same time causes the appearance of atypical mitoses and even atypical growth of tissue. These data suggest that irregularities in mitoses and in the number of chromosomes in tumor cells may not be the cause, but a consequence of the biological peculiarities of tumor tissue. Further study of the karyology of tumors should resolve the question of the causal significance of atypical mitoses in the pathogenesis of tumor growth. Here one can note attempts to explain the malignancy of tumors by mutual fertilization of its cells with 'karyogamic rejuvenation' of them. To this point of view also adheres Rotter, who believes that the increase in the number of chromosomes in the nuclei of malignant tumors is caused by conjugation of cells. The low degree of differentiation of the tumor cell gave rise to the strengthening in oncology of the view of it as an embryonic cell and to attempts to seek in this an explanation of its specific peculiarities. From this originates the existing division in oncology of tumors into those consisting of mature and of immature elements, with immaturity being a synonym for malignancy and maturity for benignity. To verify the actual existence of such a regularity, it is extremely important to compare the biological peculiarities of tumor and embryonic cells. The identification of these two types is based on the commonality of the phenomena of growth and morphological structure of them, as well as on certain analogies in chemical composition and metabolism. A considerable part of these properties - the absence of degenerative obesity in poisoning with phosphorus (Saxl), the solubility of both types of cells in normal serum in contrast to the insolubility of mature cells (Kraus, Ishiwara), similarity in the peculiarities of carbohydrate metabolism (Warburg), the same reaction to X-rays - by some authors is explained by the non-specific commonality of chemical properties of any rapidly growing tissue (Fischer). Against the complete identification of tumor and embryonic cells speaks a number of indications, namely: 1) different attitude to local effects; for example freezing a tumor does not prevent its transplantability, while freezing embryonic tissue kills it. 2) The paths of their further development, which constitute the basic difference between embryonic and tumor cells. According to the views prevailing in modern science, as a result of each division of a germ cell, offspring with increasing differentiation is obtained; this quality in the tumor cell is sharply limited: multiplying cells both in the organism and in tissue culture in vitro in the overwhelming majority of cases give offspring with equal differentiation. In this respect the data of Eckmann are instructive, in which undifferentiated fibers of the heart of an amphibian embryo in tissue culture differentiated into contractile muscle fibers. These facts created the concept of the pluripotency of the embryonic cell and of the limited potency of the tumor cell. It is necessary to further note that every stage of multiplication of embryonic cells in the organism is connected with the formation of histosystems, which is absent in tumor cells. Proceeding from these considerations, a number of researchers, to whom belong Ganssman, Fischer, Weigert, as well as Virchow, categorically object to the identification of embryonic and tumor cells. However, this in no way should exclude the presence of development in tumor cells. The view of the tumor cell as one that has quite completed its limited cycle of development at a certain stage and is incapable of further differentiation is shaken by numerous facts of variability of tumor cells. It is manifested in the development of sarcoma from transplanted elements of cancer of the mammary gland of mice; this was first observed by Ehrlich and Apolant in 1906, after which it was confirmed by a large number of studies. Murray and Haaland observed a keratinizing cancer of mice, which in further passages turned into an alveolar carcinoma, and then again into a keratinizing cancer; Lewin observed in a rat an adenocarcinoma which in 11 generations gave a carcinoma, a spindle-cell sarcoma, a round-cell sarcoma and a mixed tumor of all four of these forms. Phenomena similar to these exist also in human oncology. Very often already in the primary tumor focus a mixed type of tumor is found; this especially applies to glandular tumors, where in the primary focus areas of adenocarcinoma, colloid cancer, medullary cancer are mixed, which appear in metastases separately or in different combinations. Jastram observed a malignant adenoma of the uterus, the recurrence of which after five months gave a picture of glandular cancer. Cases are not rare of medullary cancer which in metastases shows the picture of adenocarcinoma. A malignant struma of the thyroid gland in metastases approaches more closely the structure of the normal thyroid gland than its primary focus. Sometimes one can observe the transition of cancer of the thyroid gland, as well as of malignant hypernephroma into sarcoma. In man these individual facts, as well as the possibility recognized by a large number of oncologists of the formation of the stroma of cancer from its epithelial cells, shake the concept of the tumor cell as one that is in a static, fixed state for its further development. 5. Chemical anaplasia of the tumor cell. The chemical composition of the tumor cell was the subject of numerous studies attempting by this way to reveal its specific peculiarities. In this respect one should note the attempts to discover the specificity of protein composition. A number of authors found that the tumor, in particular the cancer cell, contains less protein than the normal (% quantity of the normal cell), thus requiring less protein for its formation. An increase in the content of albumin in relation to globulins was found (Blumenthal, Wolff and others). In rapidly growing non-disintegrating cancers Kahn discovered a significant increase in the most hydrophilic part of the albumin fraction, which he called albumin 'A'; to this albumin Kahn attached special importance for the processes of growth and nutrition. The established increase in nucleoproteins is a consequence of the richness of tumors in nuclear substance, in consequence of which there is increased excretion of phosphoric acid in the urine and content of phosphorus in the red blood cells in cachexia. The study of protein decomposition products gave nothing characteristic for tumors. Great attention was paid to the study of the lipoid composition of the cell, especially of cholesterol and lecithin, in view of the importance of these substances forming the cell membrane in the processes of growth and multiplication. In this the content of lipoids proved to be inconstant (Kahn). Cholesterol in numerous experiments enhanced, lecithin inhibited the growth of tumors; this circumstance however also takes place in any growing tissue. Bell found that colloidal lead in the organism is bound by cells rich in lecithin, and finding such an increase in binding in tumor cells, he proposed this method for the treatment of tumors. The content of glycogen is generally higher in malignant tumors than in benign ones. The content of fatty acids and carbohydrates in tumor cells has no definite regularity; the same applies to the content of elementary chemical parts of the cell (Mg, Zn, Si, J, Cl, etc.). Ladreyt establishes a special intensity of the reaction of tumor cells to intracellular phosphorus, their richness in iron and potassium and poverty in calcium (while the elements of inflammatory tissue give the reverse ratio). The data regarding the content of potassium and calcium were confirmed by Policard and Doubrow, finding an increase of this ratio in malignant and a decrease in benign tumors. Wolff, confirming the increased content of potassium in malignant tumors, discovered an inhibiting effect of calcium on their growth. Velden, Gottlieb note the accumulation of J by cancerous tumors. Some authors attach great importance to the change in concentration of ions of organic salts on the surfaces of cells and to the subsequent changes in the state of lipoids and the disturbed permeability of cells connected with this. The concentration of hydrogen ions in tumor cells was repeatedly investigated (Woglom, Chambers, Schmidtmann), the data of which are not quite definite; by many authors only an increased alkalinity of the blood of cancer patients is noted. This alkalosis some authors regarded as a factor predisposing to the disease of cancer. According to Magrou, the disturbed permeability of the cell membrane facilitates the intensified penetration of potassium ions into the depth of the cell, the potassium detained in the cell playing the role of a radioactive substance, stimulating blastomatous growth. Perdue connects the mechanism of the origin of blastomatous growth with hyper-alkaloidal poisoning, and the malignant growth with the further increased accumulation of water by the cells.

However, in the water content of tumor cells, they repeat the properties of embryonic tissues. A large number of works are devoted to the enzyme content in tumor cells, on which great hopes were pinned in studying the pathogenesis of tumor growth due to the special significance that enzymes generally have in the problem of growth. Russi, for example, believes that tumor growth is a consequence of disturbed intracellular regulation of an enzymatic nature. However, it must be pointed out that all works in this direction have not yet yielded definite results. A significant number of studies (Leyden, Kraus, Hess and Saxl, Neuberg and others) are devoted to proteolytic enzymes, both hetero- and autolytic, but data for concrete conclusions are still lacking; an intensification of both auto- and heterolysis is noted in cancerous tumors. Likewise, the study of other tumor enzymes and the enzymatic exchange of its carrier have not justified the hopes placed on the possibility of finding in enzymes the key to understanding the blastomatous process. Abderhalden found that the juice squeezed from cancerous tumors breaks down the tripeptide alanyl-glycyl-glycine in a different direction than the juice from normal tissues. 6. Physical anaplasia of the tumor cell. In connection with the development of physicochemical theories of growth in general, a large number of works are devoted to the physicochemical peculiarities of blastomatous growth. Many of these works are of considerable interest due to the factual material they contain, but the attempts in them to reduce all phenomena of growth mechanically to some physicochemical process require a cautious approach to them. Among such works, mention should be made of the works of Kottmann, who found a significantly increased dispersion of the colloids of the tumor cell (24 times compared to the dispersion of a normal cell). It is interesting that accordingly, the dispersion of the colloids of the blood in the vessels of the tumor is also increased, which puts the latter cells in the most favorable conditions for the intensity of assimilation of nutritional materials. Wales, Strauss found that X-ray irradiation converts this highly dispersed colloidal system into a coarsely dispersed one, thereby reducing the ability of cells to multiply. Bauer sees the mechanism of blastomatous growth in the reduction of surface tension (see Anaplasia). 7. Metabolism of the tumor cell. With regard to the protein and lipid composition and exchange of tumor cells, the main data were given above with an indication of their insufficient definiteness. Special importance is attached to the study of the carbohydrate metabolism of the cell since the works of Warburg (see Anaplasia). The sharply increased production of lactic acid (up to 10-12% of the weight of the tumor itself in 1 hour), associated with enhanced sugar breakdown, is not specific to tumors, but is found, although to a lesser extent, in many other processes (muscle work, various poisonings, anemia, liver damage). Studies by Warburg and other authors, whose object was mainly animal tumors, gave less categorical results with respect to human tumors. Unlike experimental cancer in animals, the glycolytic ability of human cancer cells in the studies of Bauer and Nyiri differed little from normal tissue. Whether this is connected with the variability and greater diversity of forms of human tumors and with their decay, while animal tumors possess greater constancy of structure and course, as Rona and Deutsch believe, will be shown by further research. According to the data of Dische and Laszlo, changes in carbohydrate metabolism occur not only in the tumor but spread throughout the body. The mass breakdown of sugar with its delayed oxidation overloads the body with carbon compounds, and the enhanced excretion of these under-oxidized products by the kidneys causes a condition described by Bickel and Kauffmann as dioxidative carbonuria; some researchers attribute significant importance to this process, as well as to the enhanced formation of products of incomplete protein breakdown, in the pathogenesis of cachexia. 8. Blood chemistry and serological reactions in tumor patients. Benign tumors, as indicated above, do not cause any special changes in the blood. Various researchers are attempting to establish the nature of tumor cells, their specific peculiarities according to serological reactions and phenomena of immunity. Old indications of the existence in childhood of immunity to malignant tumors have been strongly shaken by observations showing that malignant tumors of various kinds (both cancer and sarcoma) occur at any age. This leads to the inadequacy of attempts to find in the blood or tissue of a young organism specific substances that inhibit, and in old age stimulate, tumor development. Freund and Kaminer found in the intestine of healthy people a saturated dicarboxylic acid, which, penetrating into the blood, acts carcinolytically, while in cancer patients there appears an unsaturated dicarboxylic acid, which, penetrating into cancer cells, allegedly protects them from destruction. These same authors, as well as Neuberg, found that the blood serum of healthy people acts carcinolytically, and this action allegedly decreases by 45 years, while the serum of cancer patients does not show such a carcinolytic effect. Control studies revealed the variability of this action with respect to different tumors in general and even to different forms of cancer in particular, thereby refuting the specificity of the substances mentioned. Immunization of animals against transplanted tumors revealed that in these phenomena there is a non-specific irritating effect, and not the production of immune bodies. Moreover, such immunity to transplantation does not prevent the development of tar cancer. Further studies of blood, concerning the total protein content, the rate of erythrocyte sedimentation, enzyme content, have revealed nothing specific. The significance of the old works of Brieger, who found an increase in antitrypsin in the blood of cancer patients, has been shaken by subsequent studies finding such an increase in any non-specific protein breakdown. All other attempts to detect anaphylactic antibodies, a specific antigen of cancer cells, have been negative, as have the binding and complement deviation reactions. The meostagmine reaction also turned out to be non-specific, representing the result of the binding of fatty acids by protein bodies and the change in surface tension. All other types of hemolytic reactions, the reaction for determining the lability of protein colloids, the Kan lipoid reaction and many others, upon verification, turned out to be consequences of non-specific cachexia. Tumors 9. Transplantation of tumors. The transplantability of tumors from one animal to another was first discovered by Hanau in 1889 in the sarcoma of the rat vagina and since then has been the subject of a huge number of studies. In recent years, in oncology, strains of rat cancer Flexner-Jobling, Jensen's sarcoma, Fisher's sarcoma, Ehrlich's adenocarcinoma, Rous's sarcoma have become widespread, serving as the object of study of the biological properties of tumors in laboratories throughout the world. In the USSR, there is its own mouse strain, maintained by N. Krotkina in the Leningrad Oncological Institute, as well as strains of rat cancer. However, this transplantability proved to be limited by the small number of spontaneous tumors (according to Ehrlich about 2%), so that any biological generalizations about tumors in general can be made only with great caution. No reliable facts of successful transplantation of cancer from person to person, to a monkey or to other animals have been obtained to this day. Still, in transplantability, a phenomenon specific to tumors is seen, distinguishing tumors from the other tissues of the body. As for the cultivation of tumors in vitro, in this respect no particular difference was found with cultures of normal or embryonic tissue, except for the sharply expressed ability of tumor cultures to liquefy plasma; moreover, Fischer allegedly succeeded in obtaining a sarcoma culture from a single cell, which is completely impossible for other tissues that multiply in the explant only in a cellular complex. Thus, the consideration of the basic properties of tumors as a whole and the properties of their unit-the tumor cell-leads to the following conclusions: 1) the tumor cell is a cell of the organism itself and is genetically connected with it. 2) The processes of metabolism, growth and specific functions of tumors and the organism are in mutual dependence, subject to the principle of general and local. 3) An essential feature of the tumor cell is the limited differentiation of its structure and function.

This limitation is morphologically characterized mainly by the loss of the mutual connection between cells with the cessation of the formation of higher-order histosystems. 4) The metabolism (intensified glycolysis), chemical composition, physicochemical structure, as well as the morphological structure of the nucleus and protoplasm and a number of other above-mentioned features are not specific only for the blastomatous cell. 5) At the same time, the combination of these features gives the tumor cell a qualitatively special character among other cells of the body. IV. Pathogenesis and etiology. Existing theories link the formation of T. with the following factors: 1) violation of embryonic development, 2) the introduction of parasites into tissue, 3) irritation. - Theories of disturbed embryonic development. The following facts serve as proof of the connection between the occurrence of T. and such violations. 1. T. with a simultaneous developmental defect of an organ. Examples: tumors of the sex glands in hermaphroditism, cryptorchidism, aplasia of the testicles; developmental defects of the uterus with T. of it, nephroma in a hermaphrodite, nephroma of an underdeveloped lobe of the kidney; gliomas of the lung in anencephaly; lipomas, hemangiomas, lymphangiomas in the area of spina bifida; T. from accessory organs-accessory mammary glands, nodules of the pancreas, etc. Mathias considers the formation of such developmental defects to be an atavistic repetition of the structure of organs of animals standing at lower stages of the phylogenetic ladder, and proposed for them the name 'progona,' and for tumors arising from them-'progonoblastoma.' 2. T. with embryonic structure of cells. This is one of the common forms of T.; they include T. from birthmarks, sympathogoniomas of the adrenal glands, teratomas with T. arising from their individual constituent parts, often malignant (e.g. struma and cystadenoma of the ovary, carcinoma of the testicle with cartilage anlagen, cancroids in dermoid cysts, various malignant T. from the rudiments of nervous tissue of teratomas, etc., T. of the mammary gland, corresponding to various stages of its embryonic development). 3. T. from persistent remnants of normal embryogenesis, e.g. cancers from remnants of the primary kidney, from the Gartnerian duct, from Rathke's pouch, chordomas of the base of the skull, T. from remnants of the branchial arches, etc. 4. T., developing from heterotopia (e.g. squamous cell carcinoma of the pituitary gland, adenocarcinomas of lymph glands, etc.).-All these facts formed the basis of attempts to experimentally obtain T. by inoculating an animal with embryonic tissue or particles of teratoid T. In this way, recently it has been possible to obtain tumors by Askhanazy, Carrel, Vereshchinsky, Krotkina. These experiments do not yet prove the actual occurrence of T. from embryonic cells. In most of these studies, out of hundreds of experiments, a positive result was obtained in individual cases, after an extremely long latent period from the moment of injection of embryonic tissue to the occurrence of T. (21-27 months). Simultaneous injection of arsenic or other interventions shortened this period; however, such a long period of time does not exclude the possibility of the addition of other factors of blastomatous growth. The above-mentioned methods of occurrence of T. formed the basis of the theory created by Cohnheim of the origin of T. from displacements (distopias) of embryonic rudiments. According to this theory, which occupies a prominent place in oncology, all T. arise from embryonic anomalies in the laying down of germ layers, distopias of groups of germ cells, which occur especially easily during embryogenesis in places where different germ layers transition into each other. However, Cohnheim himself saw the weak points of the theory he created in that, while providing a morphological substrate for future blastomatous growth, it does not explain the cause and mechanism of its occurrence. The formation of distopia and the occurrence of T. from it are often separated by a huge latent period of time, during which these rudiments show no signs of blastomatous growth. For Cohnheim himself, it was obvious that his distopias have the significance of a local predisposing factor for the formation of T.-'dizontogenetic pre-blastomatous process' (in the formulation of some authors), but by no means the significance of a realizing or determining factor; therefore, Cohnheim supplemented his theory with a second pathogenetic factor-'a decrease in the physiological resistance of the surrounding normal tissue,' facilitating the development of T. from the embryonic rudiment. However, this addition does not clarify the essence of the matter. Not to mention that a number of T. arise without any connection with embryonic developmental disorders, the proof of which is the experimental obtaining of T., Cohnheim's theory in its supplemented form does not reveal the essence and cause of the process in which germ cells develop into T. cells. Similarly, the theory of Ribbert, which supplements Cohnheim's theory, the essence of which is that prolonged 'subepithelial inflammations' lead to the displacement of cells from their complex connection with their 'wilding' and transformation into protists, also does not explain the cause and essence of all phenomena of blastomatous growth. Infectious theory of T. The idea of the infectious origin of blastomatous growth has long existed in pathology. It found its confirmation in 'cancer epidemics,' described both among humans and among animals. Hence the numerous attempts to discover the causative agent of the blastomatous process in a microscopic preparation. In this case, all the formations described as protozoan parasites in the end turned out to be the product of the authors' insufficient orientation in the histological features of individual elements of T. Into the category of 'cancer parasites' were included all products of cell degeneration, special types of changes in the structure of the nucleus (the so-called bird's eye) and even foreign inclusions. For the first time, parasites (roundworms, worms) were discovered in T. by Borel in 1909. In the following years, such findings in tumors of various animals were made by a large number of authors. A number of authors link the formation of benign papillomas of the bile ducts, large intestine, urinary bladder in rabbits with animal parasites. An indisputable connection with infection is possessed by the following tumor processes in humans: 1) cancers of the urinary bladder in Egyptians, caused by the eggs of Bilharzia haematobia (Goebel); 2) cancers of the liver, caused by flukes (Opisthorchis felineus); in Japan, cancers of the liver are relatively often caused by infection with Distomum hepaticum. Hence arose attempts to experimentally reproduce T. by infecting animals with various parasites. In this case, a considerable number of the described positive results, upon careful histological control, turned out to be non-specific granulomas. An indisputable connection with the blastomatous process in animals is Spiroptera neoplastica, causing cancer of the stomach in rats. The oncogenic significance of this parasite (roundworm) was discovered by the Dutch scientist Fibiger when feeding gray rats with black cockroaches, which are intermediate hosts of this worm. In this case, within 3-5¹/₂ months, the animals died from cancer of the tongue, stomach with metastases to the lungs. In the same way, although with greater difficulty, it was possible to obtain cancer of the stomach in white mice, which turned out to be transplantable. In this case, the presence of the parasite in the transplant is not necessary for transplantability; in metastases, parasites were also never found. Therefore, Fibiger believes that the occurrence of T. is associated with a chemical product of the parasite's life activity. In recent times, the works of Bullock and Curtis have been published, who obtained sarcoma of the liver in a certain percentage of rats infected with the eggs of Taenia crassicolis. This sarcoma in most cases turned out to be transplantable to other rats. Taenia crassicolis lives in the intestine of cats; from the eggs excreted by it with feces, a cysticercus (Cysticercus fasciolaris) develops in the liver of the rat, around which the sarcoma develops. In young rats, this T. can be caused more often than in old ones, metastases are found in 60% of cases. The latent period from the moment of infection to the occurrence of T. is quite long-8-16 months. Different races of rats react differently to this parasite; in some, it causes no changes. A number of researchers have described and continue to describe various bacteria found by them in T. or in their vicinity, to which they attribute specific neoplastic abilities. These include Micrococcus neoformans (Doyen); a microorganism discovered by Schumacher at the border with a cancerous T.; a Gram-positive diplococcus of Nuzum; Jung almost always finds a polymorphic microorganism in T., the 'amorphous phase' of which, according to the author, 'is the key to the question of cancer'; a number of cancer-causing agents have been 'discovered' by Americans (Scott, Steam, London, etc.). In the USSR, the representative of the infectious direction is Nievadomsky, who attributes the role of the causative agent of cancer to a parasite allegedly discovered by him in adenocarcinoma of the mouse, which he classifies as a gregarine. Blumenthal, Auer and Meyer isolated bacteria from the juice of human cancer, which, when inoculated into mice and rats, allegedly gave malignant T., but only after preliminary irritation of the injection site with infusorial earth (!).

Such an abundance of agents causing blastomatous growth raises doubts about their specific causal connection with the origin of T. It must be emphasized that none of the researchers in the aforementioned group has been able to provide any convincing evidence of a real connection between the 'agents' they discovered and the origin of T. Experiments by Rous on f sarcoma aroused great interest in oncology (see F Sarcomas). Thus, even if one disregards the numerous questionable data about the connection between the origin of T and some parasite, such a connection remains undoubted for some higher forms of parasites (Spiroptera, Bilharzia, etc.). However, even if one assumes the completely impossible from the modern point of view that the origin of all T, even those arising from embryonic rudiments, is connected with animal parasites, this still does not solve the essence of the question, what developmental process lies at the basis of the transformation of a body cell into a tumor cell. Between the moment of infection and the appearance of T there usually lies a fairly long latent period, during which this development takes place. With its completion, the role of the parasite in the formation of T ends, and the further course of the tumor is entirely determined by the specific properties of the blastomatous anaplastic cell; it has been pointed out that successful transplantation of T to another animal no longer requires the presence of the parasite. Thus, it is quite clear that infection in the pathogenesis of T can play only the role of a non-specific external irritant that gives impetus to the development of a chain of anaplastic processes. The same role can be played by other irritants, as can be seen from what follows. The Theory of Irritation. Irritation was placed by Virchow at the foundation of his 'irritation' theory of the origin of T. This theory, along with the theory of Cohnheim, belongs to the classical theories of blastomatous growth and is based on Virchow's hypothetical assumption of the presence of a specific formative irritation. In the medical literature for more than a century and a half, reports have appeared about the connection between the origin of malignant T and external prolonged irritation. The first literary indications of this belong to Percival Pott, an English surgeon, who in 1775 published his view on the origin of scrotal cancer in chimney sweeps as a result of prolonged irritation by coal tar products accumulating in the folds of the scrotum. Exactly the same indications existed in the middle of the 19th century regarding skin cancer in workers of paraffin production in Scotland. In 1875, Hartung and Hesse established that 75% of miners in cobalt mines in Schneeberg (Germany) die from lung cancer, the origin of which they connected with prolonged irritation by arsenic-cobalt compounds. In addition to these, which have become historical facts in human oncology, there are numerous other T, the origin of which is connected with prolonged professional and domestic irritation (mechanical, thermal, chemical, various types of radiant energy). In professional pathology, as statistics show, these T occupy such an insignificant place that there is no basis for speaking of 'oncogenic professions.' However, the theoretical significance of these facts in elucidating the essence of the mechanism of development of T is enormous. The causal connection between irritation and the origin of T can be illustrated by the following examples from the clinic of human T. 1. Carcinomas forming: in old scars of skin of various origins: in lupus, syphilis, injuries, especially burns; the latter form includes the so-called 'cancer kangri'-squamous cell carcinoma of the abdominal skin, developing in Tibetans as a result of repeated burns from hot pots used for warming the body. 2. The transition of various kinds of ulcers and erosions into malignant neoplasms: stomach ulcers, tuberculous ulcers of skin, intestine, Fallopian tube, erosions of the cervix uteri, etc. To this same category belong malignant T arising as a result of prolonged inflammations in various organs. Of course, such an outcome of the listed processes is in no way obligatory. 3. Some researchers consider possible and quite probable the connection between the increased frequency of cancer of the respiratory tract and transferred influenza infections; at the same time, they believe that the metaplasia of the epithelium occurring in prolonged inflammations of the respiratory tract, as well as in avitaminosis, is the source of the origin of malignant T. 4. A number of cancerous neoplasms have a connection with professional irritations (X-ray cancer, arsenical skin cancers, cancer of the bladder in workers of the aniline industry and a number of others). These data formed the basis of numerous experimental attempts to obtain T by means of prolonged irritation. In this case, attention of researchers was long ago directed to the products of coal distillation as giving a high percentage of professional tumors. The first successful experiments, which created an era in experimental oncology, belong to the Japanese scientists Yamagiva and Itchikawa, who published them in 1915. They succeeded in obtaining true skin cancer in rabbits by prolonged (for several months) smearing of the ear with coal tar. Since then, the field of experimental study of oncogenic factors has grown considerably; it has included a number of other chemical (arsenic, petroleum products, various fat-soluble coloring substances-scarlet, Sudan, caustic substances, etc.), radiant (X-rays, radium, ultraviolet rays) and mechanical irritants, with the help of which malignant neoplasms, mostly various forms of cancer, were obtained with greater or lesser success. Thus, the factor of irritation has acquired the most important significance in the problem of the etiology of the tumor process. The duration of the period during which T is formed is of great importance here. For human T this period is sometimes counted in decades, for experimental T-in months, and during this period the formation of the tumor rudiment takes place in the process of developing cellular anaplasia. Above were presented the views on the origin of the elements making up the tumor rudiment. At the same time, it was noted that in the initial phases of its development it is possible to prove its formation from elements of the surrounding tissue through a series of transitional forms. The extreme similarity of the rudiment of tar cancer with the rudiments of human skin cancer is of great importance, which confirms the single path of formation of both rudiments and possibly their single etiology. Therefore, the individual stages of development of the tumor rudiment were subjected to careful research, which established the sequence of processes occurring in the place of formation of the rudiment. It was established that the first effect of irritation is of an alterative nature (loss of hair with death of hair follicles, atrophic processes of the skin, necroses in the area of irritation and at a distance, etc.). This is followed by productive-inflammatory processes with papillary proliferation of the skin and, with continuation of irritation, increasing hypertrophy of the epithelial covering; further in the latter appear strands of atypically proliferating epithelium, which already forms the tumor rudiment. This course of the process can be established schematically for all cases of malignant T of the skin and mucous membranes arising in humans on the basis of prolonged irritation. Thus, the formation of T is preceded by prolonged, repeatedly superimposed on each other processes of inflammatory-regenerative tissue proliferation, going parallel with alterative processes and entering together with them into a single complex of chronic productive inflammation. Thus, the formation of the T rudiment occurs through the stage of regeneration. Of interest is Dillman's indication of the necessity of systematic irritation only until the appearance of a nest of atypical proliferation, after which the further role of the external irritant is removed, it ceases to be necessary for the development of tumor growth; in other words, with the completion of anaplasia, the essence of the tumor process is already contained in the tumor tissue itself and in its relationship with the environment. This connection of the origin of blastomatous growth with the regenerative process is also confirmed by histological studies of individual phases of development of many human tumors. Bloch, for example, points out that X-ray carcinoma begins at the edges of an X-ray ulcer, i.e., where intensive regeneration processes occur; in exactly the same way, stomach cancer, arising from an ulcer, shows the first rudiments at its edges. Liver cancer, developing in cirrhosis of the liver, also indicates the connection of T with regenerative processes; this is particularly emphasized by the observations of de Raadt, who in the extremely high frequency of primary liver cancer among inhabitants of the Dutch East Indies found cirrhosis of the liver in 90% of all cases. Similar reports come from a number of other authors. Often it is possible to establish the indisputable connection of cancer rudiments, sometimes arising in multiple foci, with nests of regeneration of liver parenchyma.

A similar connection in the development of adenomas was observed by Silfeerberg in the shrunken kidney; those arising in the process of regeneration can also be considered adenomas of the prostate, thyroid gland, and others. Interesting is the observation by Slay, who in the primary cancer of the mouse's bronchus could trace all stages of its development, starting from inflammatory hyperplasia through papillomatous growths to papillary adenocarcinomas. The number of such examples of the transition of a productive-inflammatory process into a blastoma can be cited endlessly; they are found in the experience of everyone working in this field. For this reason, the specific etiological significance of infection falls away, which can have its place in the blastomatous process only along with many other external factors of irritation. Thus, two processes remain that have an indisputable connection with the origin of T.: 1) disruption of embryonic development and 2) anomaly of regenerative development. In both cases, the body's cell on the path of transformation into a tumor passes through the stage of a young, 'undifferentiated' cell. The assumption of the possibility of the direct transition of a mature differentiated organ cell into a poorly differentiated 'embryonic,' tumor cell (Hertwig, Ribbert) is possible only on the assumption of regressive development and must therefore be decisively rejected. It is permissible only when recognizing in the cells that make up any organ further development, as G. Koritsky does in his transformation theory of tumors. Koritsky recognizes the function of multiplication and variability of cells as their inalienable property, expression of their dialectical essence. On this basis, he considers Virchow's theory of irritation, which treats this function as intermittent and dependent on an external cause (formative irritation), untenable. The concept of the completion of the formative process in the adult organism and the lack of continuity in the development of cell types in this period contradicts, according to Koritsky, the fact of the continuity of the so-called physiological regeneration of cells. Subjecting the views of W. His on histogenesis of tissues to criticism and based on facts contradicting the so-called law of specific productivity of tissues by Waldeyer-Tiersch-Bar, Koritsky gives a general scheme of the sequence in the development of cell types in the adult organism; in this case, a decrease in the potential for multiplication from epithelial to syncytial, fibroblastic, and movable mesenchymal cells (leuko- and hematopoietic series) is established. Asserting that histogenesis in the adult organism proceeds generally and always in the above-mentioned direction, Koritsky defines T. as the multiplication of high-potential cells in the direction of forms with lower potential. The difference between the multiplication of cells in T. and in other formative processes lies in the fact that in the latter, mutation of cells with loss of potential proceeds through stages fixed for a given animal species, whereas in T. the mutation of cells represents an intermediate, insertional form not fixed in organs; these cellular mutants, multiplying evolutionarily, create the mass of a given tumor. Thus, according to Koritsky, if cancer cells are the negation of the normal epithelium of organs, then the connective tissue stroma formed by them is the negation of negation and partial completion of the malignant process. Muscular, bony, fatty, and other syncytia give rise to sarcomas, and the autochthonous vessels of the latter complete the process. Benign connective tissue T.s, according to Koritsky, also develop from high-potential epithelial and syncytial cells and, losing energy through more acute mutation, approach normal tissues with lower potential and fixed in the ontogeny of the animal. According to Koritsky, the proper connective tissue and movable mesenchymal cells of T.s no longer develop. Koritsky's theory is a further development of similar views by Milman, Kromayer, and Krompecher (Kromayer, Krompecher). At present, the task before oncology is to establish the details of the mechanism of development of the tumor cell and the causes that cause this development. Many researchers believe that in the formation of tumors, pathogenesis and etiology completely coincide, that the cause of the transformation of a normal tissue cell into a tumor cell is the combination of local and general processes leading to anaplasia of the cell. Since in these processes the number of general and local factors of anaplasia is quite large (constitutional factors, nutrition, hormones, local physicochemical processes, etc.), such a concept recognizes the necessity of multiplicity of conditions for the formation of T.s (Anichkov). This view gives some authors (Medvedeva) the basis to assert the 'victory of conditionality over causality' in oncology. Such a point of view is in no way acceptable. As in any biological process, the mechanism of its development includes the interaction of many factors, close and distant, local and general. Undoubtedly, this multiplicity of factors also exists in the mechanism of development of tumor tissue. The latter, as already noted, passes through the stage of embryonization, and its anaplasia is the result of a special path of further development, different from the path of development of any other tissue that makes up a normal organ. This process can be considered as a mutation of a somatic cell under the influence of external factors. The speculative mutation theory of tumors created by Bauer is based on such a concept. Changes in the nucleus and especially the atypism of mitoses in the tumor cell provide the morphological substrate for such a concept; such a mutation of a cell, either occurring in the embryonic period with the formation of an embryonic rudiment of a tumor, or in subsequent periods, with corresponding changes in the chromosomal apparatus of the cell, leads to the formation of a cellular offspring with all the features of anaplastic cells. The clinic of human and animal oncology gives every reason to assert the existence of genotypical forms of T.s. Familial T.s of the same organs are known: Sippel operated on three sisters with ovarian dermoids, Hoffmann observed two brothers with gliomatosis of the brain, Leschziner observed a mother and three daughters with completely identical in structure, course, and metastasis forms of cancer of the breast. Burckardt observed twin sisters of the same age with fibroma of the breast in the same place. From animal oncology, data have already been cited by Slay on the significance of the genotypical factor in the origin of T.s in mice. It is noted that the transmission of T.s occurs according to Mendelian principles as a recessive trait. These cases give reason to assume the existence not only of somatic mutation but also of mutation of the corresponding sex chromosome, which may possibly lead to the disruption of the processes of physiological regeneration of tissue cells. However, the process of change in the chromosomal apparatus of the cell itself is a constituent part of that mechanism of development which is determined by the concept 'anaplasia' and which is connected with a number of physicochemical and other factors. The assumption of a mutation that has occurred does not remove the need to find the cause that causes this pathological development, and in no way gives grounds for combining pathogenesis with etiology in oncology; the reason for such a combination is the circumstance that the nature of the specific etiological factor of the blastomatous development of the cell remains hidden to this day. A significant number of researchers considers this factor to belong to physicochemical influences; however, although the significance of these influences in the process of growth cannot be disputed, still none of them individually is a growth factor. Thus, the problem of tumor growth and development is closely connected with the problem of general biological growth, and the study of these factors will proceed in parallel with the study of the factors of pathological growth and development. For now, the main factor in the etiology of the blastomatous process remains irritation, the revelation of the specific nature of which is the task of the future. Classification and nomenclature. The basis of the modern classification of T.s is the histological character of their structure, i.e. their similarity to the normal tissues of the organism; if such similarity is lost, it is sought in the embryonic stages of development of the corresponding tissue, thus introducing into the classification the genetic principle. This histological-cytogenetic principle repeats all the defects of the modern classification and nomenclature of normal histology, which with insufficient clarity defines the structural profile and genetic relationships of individual types of cells and tissues. Hence the preserved to this day variety of terminology, depending on the views of the researchers proposing it on the genesis of various elements of T.s. Questions of classification and nomenclature in oncology were the subject of works of special international conferences (in Paris-1910, in Brussels-1913), which did not achieve unity of views in this respect.

The pure cytogenetic principle, with a certain consistency, can be consistently applied in the classification of tumors of the nervous system, where special research methods sometimes allow, even with the embryonic structure of the tumor, to establish their actual origin. For the majority of other tumors, however, striving for the consistent application of the cytogenetic principle must lead to inevitable errors based on attempts to establish genetic unity based on external similarity. Therefore, the existing combined principle (or rather the absence of a single principle) with greater or lesser consistency reflects the actual relationship of tumor elements to the corresponding tissue of the body. Accordingly, all tumors are divided into tumors of epithelial, connective, nervous, and muscular tissue. These are the main types of tumors, among which various types are distinguished depending on the type of tissue from which they consist: connective tissue - fibromas, lipomas, chondromas, osteomas, etc.; epithelial - from squamous and cylindrical epithelium, etc. Then there is a group of tumors of mixed structure, for example, sarcomacarcinoma, lipomyoma, etc. In addition to this, a group of tumors from vascular, hematopoietic, and pigment tissue is especially singled out, although the latter can be classified with full justification as epithelial tumors. Some forms of tumors that repeat the structure of a particular organ are also singled out into a separate group: hepatoma, endometrioma, hypernephroma, meningioma, etc.; similarly, tumors originating from embryonic remnants (chordoma, nephroma, tumors from remnants of branchial arches, etc.) and consisting of underdeveloped organs of various embryonic leaflets (teratomas, embryomas) occupy a special place in the existing classification. The division of tumors into benign and malignant, important from a clinical point of view, does not have any fundamental justification. It is mostly based on a combination of anatomical-histological and clinical signs that develop in parallel in most cases. From the anatomical-histological side, a malignant tumor is characterized by rapid growth, infiltration of surrounding tissue, loss of organoid structure and complex structure, and immaturity and undifferentiation of tumor elements. From the clinical side, a malignant tumor is characterized by a tendency to recur after its removal, to metastasize, and general cachexia. However, none of these signs is mandatory only for a malignant tumor; it was pointed out above that a rapid growth rate and infiltration of surrounding tissues can also exist in a benign tumor. Similarly, a benign tumor, although extremely rarely, can give metastases and, by pressing on vital organs, cause an extremely severe general condition of the body: a benign in structure brain glioma causes death by destruction of nerve centers. On the other hand, a malignant tumor, as was indicated earlier, can grow extremely slowly, be organoid in structure, consist of fully mature and differentiated elements in structural and functional respects, and not cause general cachexia. Therefore, benignity and malignancy are concepts that are to a large extent clinical, formed from the totality of the signs mentioned above. From the histological side, the most reliable criterion of malignancy is infiltrating growth. In the nomenclature of tumors, the starting point is its basic tissue, to the name of which the ending "oma" is added: fibroma (connective tissue tumor), chondroma (cartilaginous tumor), adenoma (glandular tumor), etc. Malignant tumors are divided into two main groups: connective tissue - sarcoma (see) and epithelial - cancer (see). To the main name of the tumor, some characteristic of it is usually added, either specifying the cellular composition of the tumor (round cell sarcoma, basal cell cancer, etc.), or indicating the presence of a morphological criterion of malignancy (malignant adenoma), or emphasizing the nature and development of the stroma (fibroadenoma, fibrous cancer-carcinoma, osteoplastic carcinoma, etc.). Other proposed classifications and nomenclatures for use, built either on the histogenetic principle (Klebs, Adami), or on the mechanics of embryonic development (Albrecht), or on the maturity and immaturity of the elements included in the tumor (Petrov), etc., have not found application in oncology as unreliable in their basic criterion. VI. Diagnosis and treatment. General principles of diagnosis. The diagnosis of a tumor in general is made relatively easily with the help of ordinary methods of clinical research (inspection, palpation, percussion, X-ray examination, etc.) and according to the local and general phenomena caused by the tumor (bleeding, pressure on organs with disruption of their function and atrophy, cachexia, etc.). The significance of serological reactions, as was indicated above, is very limited. The diagnosis of malignancy is often more difficult, which is mostly decided on the basis of the totality of signs characterizing it. In doubtful cases, the question is decided by a trial biopsy of the tumor, which many consider mandatory in all cases accessible to it. Histological examination of the biopsy material is sometimes necessary to perform during the operation, the further course of which often depends on the results of this examination. For this purpose, a number of techniques have been developed that allow rapid microscopic examination of the tumor (fixation by boiling in formalin, frozen sections, staining with hematoxylin; staining of sections made by hand with a razor blade with methylene blue or toluidine blue and examination of the surface of the sections with incident light). General principles of treatment. The main methods of treating an already developed tumor are: 1) surgical (bloody and electro- and endothermic), 2) radiant energy (X-ray, radium), 3) medicinal-dietetic and chemotherapeutic. The first two methods, used by themselves or in mutual combination, to this day are the most reliable in results and the most technically developed. The application of these methods varies considerably depending on the localization of the tumor, its structure, course, etc. Some tumors require immediate radical surgery. X-ray therapy is usually used in combination with the surgical method; it sometimes precedes surgery (preventive X-ray therapy, proposed by Americans) and in this case sometimes facilitates the radical removal of the tumor. Postoperative X-ray therapy is indicated for almost all malignant tumors. In addition, X-ray therapy has independent significance for many skin tumors, as well as for all cases inaccessible to surgical intervention. For some forms of tumors, the use of radiotherapy in its various forms is also present. Medicinal and dietetic therapy and chemotherapy. Oncology is a new field being developed in parallel with the study of the biological features of the tumor cell. Its basis is attempts to create for the tumor conditions unfavorable for further multiplication or that promote its disintegration. The mentioned relationship of the blastomatous cell to colloidal lead and phosphorus in the description of chemical and physicochemical analysis of the blastomatous cell formed the basis for the treatment of tumors with preparations of the tribasic colloidal lead phosphate salt, which is supposedly bound by cancer cells. The experience of this treatment is still small, but according to some authors, it gave positive results in a number of cases. A similar principle is the basis for the treatment with preparations of iodine, bismuth, antimony, arsenic, selenium (selenium-eosin), cobalt, copper, etc. Also under study is the treatment by inhaling a gas mixture according to Fischer-Wasels (95% air + 5% CO₂). The theoretical premise of this treatment is the reduction of glycolysis in cancer cells with an increase in gas exchange caused by irritation of the respiratory center by carbon dioxide. Treatment with insulin is also based on attempts to affect carbohydrate metabolism. The results of the above types of therapy are still contradictory. Also under study is the treatment with various lipoids that can change the structure of the lipoid shell of the tumor cell and thereby affect the growth and multiplication of the tumor cell. The significance of the quantity and quality of nutritional material for the development of a tumor (see above) formed the basis for the development of a rational diet for tumor patients. Under study is the effect of avitaminotic and carbohydrate-free diets. In addition, this same group of tumor therapy includes the use of various endocrine preparations, the inhibitory effect of which on tumor growth was noted above.

Y. Rapoport. VII. The Fight Against Tumors. The high mortality rate from T. makes the fight against them one of the most important tasks of medicine. Since the current state of science has not yet brought complete clarity to the etiology of T., scientific research in this regard, as well as the search for new methods of therapy*, are the most important sectors of the front in the fight against T. The creation of special scientific oncological institutions is a necessary prerequisite for the proper organization of the fight against T. On the other hand, even with the current state of knowledge, much can be done in the fight against T., not only in terms of timely surgical treatment of them, but also in terms of prevention. Not to mention the fight against professional hazards that play a role in the etiology of malignant neoplasms (tar, aniline production, processing of arsenic ores, X-rays), prevention should pay attention to preblastomatous processes and conditions through widespread dispensarization of appropriate categories of patients with the involvement of oncology specialists in general dispensaries and outpatient clinics. In France, the anti-cancer fight began earlier than in other countries. Thus, in the 18th century, the canon Godinot bequeathed to the city of Reims 25,000 livres for a hospital for incurable cancer patients; the hospital was indeed founded in 1740. Somewhat later, similar treatment institutions gradually developed in other countries, although it was in France that the anti-cancer fight began to take on an organized character earlier than anywhere else. After the end of the world war in 1918, the Franco-Anglo-American league for the fight against cancer was created. It was recognized as socially useful in Paris on November 22, 1920, and later (1927) it was dissolved and replaced by the French league. There, in 1923, at the Ministry of Hygiene, on the initiative of the League, the "Ministerial Commission for the Anti-Cancer Fight" was established under the chairmanship of the surgeon Quenu. The subject of its concern was the establishment of anti-cancer centers, consisting of outpatient dispensaries, treatment departments (outpatient X-ray, outpatient surgery), hospital inpatient departments, and departments for educational oncological purposes and for research. Anti-cancer centers in France have their own budget and are opened in university cities. They are under the administration of public health (Assistance publique). Such centers exist in Angers, Bordeaux, Lyon, Montpellier, Nancy, Nantes, Paris, Strasbourg, Toulouse. The centers are located in city hospitals. In 1921, the Paris municipality allocated 5 million francs for the purchase of radium, and by 1922 it had already opened a cancer consultation department in the hospitals Hôtel Dieu, Tenon, Salpêtrière; at present, there are already 10 such institutions in Paris and a total of 22 oncological reception days per week. Periodic courses on the study of cancer are given at the Institut du radium. By 1926, 8,700 cancer patients had been taken under systematic care through consultations and dispensaries in Paris. By this time, the so-called Cancer Institute of Paris had also been begun. Given the grandiose plans of this institution, which requires time for its creation, the institute began its work in the laboratories of the medical faculty, with special allocations of 150,000 francs annually, in addition to private donations. No less serious are similar institutions in England, where as early as 1791, Dr. Howard (S. Howard) received 400 pounds sterling from an unknown person for the establishment of a cancer department in Middlesex Hospital and an additional 3,000 pounds for its maintenance. Thanks to further similar large donations, this department has grown, exists to this day, and the so-called "cancer charter", drawn up for this institution by Howard and Whitebread more than 100 years ago, remains fundamentally acceptable even at present. The basic principles of anti-cancer institutions, according to this charter, are: 1) care of incurable cancer patients, 2) inpatient treatment for curable cases, 3) outpatient assistance, 4) accumulation of scientific and clinical observations for scientific use, 5) testing of new but harmless therapeutic methods, 6) deepening of scientific research in the field of understanding the causes and essence of cancer disease. In Middlesex Hospital, in addition to an inpatient department with 90 beds, there is a laboratory of the Cancer Investigation Committee (headed by L. Barlow). In addition, there is the Cancer Hospital, founded in 1851 with 120 beds, directed by Leitch (A. Leitch). In London, there is the famous Imperial Cancer Research Fund, formerly directed by Bashford, and now by Murray. Further energetic progress in England in this field continues. In 1926, a banquet was organized in Leeds that raised 50,000 pounds sterling for the establishment of a research anti-cancer center in Yorkshire. The British Empire Cancer Campaign in 1924 allocated 25,260 pounds sterling to British anti-cancer institutions. The Medical Research Council is in the process of building special laboratories for the study of the etiology of cancer. In Germany, in Berlin, the Deutsches Komitee für Krebsforschung has existed since 1900. There, Leyden also established a cancer institute and laboratory for the study of cancer (headed by Blumenthal). No less famous is also the Cancer Institute in Heidelberg (Samariterhaus). In Hamburg, a laboratory has been opened, directed by Bierich, known for his research. In Holland, in 1914, an anti-cancer institute was established, called Het Nederlandsche Kankerinstituut. In Belgium, on the funds of the Red Cross, the Institut du radium de la Croix Rouge de Belgique was founded. Similar institutions exist in Switzerland, Denmark, Argentina, Italy and other countries. At present, serious attention is being paid to the anti-cancer fight in the USA. In 1926, the American Society "American Society for the control of cancer" organized an international "meeting" of surgeons, radiologists, and scientists working on the problem of cancer. The purpose of the meeting was to precisely formulate the principles on which the anti-cancer fight should develop in the future. Very serious attention is being paid to the anti-cancer fight by health authorities and in the USSR. In pre-revolutionary Russia, the initiators of the public fight against cancer should be recognized as Levshin and his student Zykov. Thanks to private donations on their call, in 1903, the Institute for the Treatment of Tumor Patients was established in Moscow. In 1911, the Yelenskaya Hospital for poor women suffering from malignant tumors was built in Petersburg. In other cities, in separate hospitals, there were only individual wards for cancer patients. In 1914, the All-Russian Society for the Fight Against Cancer in Petersburg, along with similar local societies (e.g., in Kyiv and others), convened the I All-Russian Congress on the Fight Against Cancer Diseases. At that time, the society petitioned the government for funds to establish a cancer institute, but was refused in this (in 1907). The free cancer outpatient clinic in Petersburg and the city laboratory for the free examination of material suspicious for cancer did not receive further development. Only in 1920 was the State Radiological Institute established in Petrograd, equipped with powerful installations for actinotherapy of various diseases, among which malignant tumors occupy a prominent place. In the autumn of 1926, the Leningrad Department of Health, on the initiative and with the energetic assistance of Professor N. N. Petrov, founded the Scientific-Practical Oncological Institute. This is currently the largest institution dedicated exclusively to the fight against tumor diseases, consisting of a number of departments and divisions of a practical and scientific nature. A great organizational and practical work has been done in providing medical assistance for tumor diseases in Ukraine. One of the pioneers in this field was Professor Silberberg in Odessa. As early as December 1924, a project for the establishment of an "anti-cancer center" at this society was heard and accepted at the Odessa Surgical Society. The tasks of the center included the creation of chemical and path-histological laboratories, a polyclinic, an inpatient department for diagnostic purposes, and an inpatient department for all types of surgical and radiation therapy of tumors. It was planned to create propaganda sections with a library fund, a traveling exhibition, etc. A special statistical section was planned at the cancer center. Subsequently, work in this direction in the Ukrainian SSR took on a more systematic character on a state scale, with the main center of the anti-cancer fight concentrating in Kharkov, around which 300 districts are grouped, as well as around Odessa and Kyiv. The All-Ukrainian State X-ray-Radiological Institute is in all respects a major treatment and scientific institution, largely dedicated to the cause of fighting and studying tumors. The Regional Oncological Dispensary in Kharkov, equipped and built according to a special plan, has a high throughput capacity, so that during its 5-year existence (1925-1929), 3,774 cancer patients (Merkov) passed through this institution. The fight against malign.

Tumors encompasses a range of public health and medical tasks. These include tasks related to creating the structure of the entire network of anti-cancer institutions from the central organ to the most peripheral cells. However, the 'anti-cancer centers' of individual districts, cities, etc., also have larger-scale anti-cancer centers, as we see for example in France, where there is a main Ministry Commission for the Study of Cancer and a network of subordinate institutions. According to the plan of the 'Commission', small anti-cancer centers with their own budgets, as well as subordinate institutions, are being built and supplied throughout the country. In Leningrad, under the Scientific Medical Council of the regional health department, there is an Oncological subsection that develops the implementation of anti-cancer measures. The tasks of anti-cancer centers include performing functions of: 1) educational, 2) preventive, 3) diagnostic, 4) therapeutic, and 5) custodial nature. The preventive tasks are very broad. They reduce to preventing the disease itself through general protective measures (for example, preventing premature aging of the body as a factor predisposing to the appearance of cancer) and to local preventive measures, which include for example sanitation of the oral cavity, gynecological sphere (prevention of cancer of the tongue, palate, uterus, etc.). To the preventive measures of anti-cancer struggle also belongs the treatment of precancerous diseases, for example, removal of benign tumors, timely treatment of gastric ulcers and other conditions that often lead to cancer. The most important tasks of prevention coincide with informing both doctors and organized groups of the population about the early signs of tumors. To obtain real results from these measures, much work and organizational initiative is needed, and it is absolutely essential to instill in the public consciousness the correct understanding of malignant T. as a disease that is curable in its early stages, as a non-communicable disease, but playing an extremely important role among the social factors that send thousands of able-bodied citizens to an early grave. The fight against this disease is an urgent and most important socio-political task. Oncological prevention should also include the prevention of T. passing from a curable to an incurable state. The small percentage of actually curable cancers is in most cases explained not by the insufficiency of diagnostic methods, but by the poor awareness of the population and doctors about the immeasurable importance of early consultation and insufficient knowledge of the early signs of the disease. For the practical implementation and increase of the percentage of early consultation, the tasks of oncology include: organization of special health education among the population and among doctors. To popularize among the population elementary information about the signs and dangers of cancer, both abroad and in our Union, special popular publications, leaflets, brochures, etc., are published, for example Prof. N. N. Petrov-'Cancer Reminder', 'What One Should Know About Cancer' (Bibliography of the journal 'Hygiene and Health of the Working Family', 1925, issue 1, Leningrad). The initiative in the matter of educating the population regarding the danger of cancer belongs to the German gynecologists Winter and Runge. Literary data on this question have been collected among others by Moro. Winter reported his observations on the consultation with doctors of 1062 patients with uterine cancer, and it turned out that in the first month after the appearance of symptoms of the disease, only 13% consulted a doctor, in the 2-3rd months-30%, in the 4-6th-27%, in the 7-9th-11% and in the 10-12th-2%; over 1 year-4%. As a result, 87% of these patients wasted precious time for therapy. Public and literary appearances by Winter resulted in brilliant outcomes of anti-cancer propaganda in connection with increased consultation. By the method of printing periodic popular articles, mass distribution of leaflets, organizing public lectures, posting posters and radio broadcasts about the danger of cancer, the percentage of curable patients usually increases quickly and obviously. Thus, Bloodgood noted that before 1910, among those consulting for diseases of the tongue, 3% were non-cancerous, but by 1920, due to propaganda, it was already 55% non-cancerous patients of the same group who consulted for the purpose of examination. Films, cancer departments in health museums, organization of anti-cancer weeks are milestones in the path of anti-cancer struggle among the population. No less energy is required for the education of doctors regarding the danger of cancer than for popularizing information about cancer among the population. Here improvement of clinical teaching of oncology, organization of special courses and publication of clinical guides that vividly illustrate the diagnosis of neoplasms are needed. The organization of as early as possible diagnosis is associated with the wide use of special diagnostic methods: roentgenoscopy, endoscopy, etc. For diagnostic purposes, the practice of biopsies should be expanded and central oncological diagnostic stations with pathological-anatomical cabinets should be created, where all doctors and all medical institutions could apply for competent advice and examination of taken from tumors sample pieces. Improvement of diagnosis is associated with the creation of capital and large regional tumor centers, scientific-practical oncological institutes or corresponding departments in hospitals, where combined methods of treatment of neoplasms would be applied and studied. For successful struggle, it is necessary to provide for the creation of a network of anti-cancer points directly connected with the central oncological institution of the district or region. The constant live connection of anti-cancer points with urban outpatient clinics and district hospitals can facilitate the accounting and dispensarization of tumor patients. By publishing separate brochures ('Which cancer patients should be appropriately referred to the Oncological Institute', N. N. Petrov, Leningrad, published by the Institute of Advanced Physicians, 1931), information can be popularized among doctors about the nature of patients needing special treatment in oncological institutions, in order to avoid overloading them with incurable chronic cases. The health-educational work of medical personnel within the walls of medical institutions, in clubs and workers' auditoriums can be guided by general information published about the danger of cancer in separate brochures, leaflets, etc. (see 'Materials for conversations about the danger of cancer and the fight against it', compiled by Dr. S. A. Kholdin, edited by Prof. N. N. Petrov, published by the Leningrad Regional Health Department, 1931; 'Draft appeal to doctors about anti-cancer struggle', Petrov, Vetvinov, Nikolsky, Shanin, Medical Gazette, 1930, No. 22).-The question of improving the therapy of neoplasms is connected with the creation of special tumor treatment institutions where large amounts of oncological material could be concentrated for the purpose of training medical personnel. The success of anti-cancer struggle in Western European countries is explained among other things by the vigorous activity in the field of preventive measures in the matter of the appearance and development of recurrences. The necessary systematic control over tumor patients discharged from medical institutions is best carried out by methods of dispensarization. In the works of the Conference on the Fight Against Cancer Diseases under the People's Commissariat of Health (June, 1925), there is a whole range of materials on the dispensarization of cancer patients. In these same protocols, the anti-cancer struggle (especially in the resolutions on organizational issues) is recognized as 'part of modern Soviet health care'; it is also recognized that 'the main mass struggle against malignant neoplasms is part of dispensary service'. It is also mentioned about the establishment at provincial health departments and at their treatment subdepartments of anti-cancer conferences with the participation of broad public masses. The main tasks of dispensary institutions of the anti-cancer type include systematic examination at regular intervals of cancer patients taken on record, persons with precancerous tissue conditions, persons burdened with heavy hereditary cancer, etc. For the practical implementation of these tasks, staffs of workers consisting of oncologists and nurse-investigators are established at oncological dispensaries, who observe the timely appearance of patients at anti-cancer points according to the instructions they receive from special statistical and archival departments of these dispensaries, where all patients are monitored in terms of the time of appearance. In Western European countries, these methods of anti-cancer struggle are carried out consistently, however in the USSR the anti-cancer struggle, although in the stage of organization, will apparently have a more systematic character. The participation of authority, for example in France in the person of Assistance publique, in the anti-cancer struggle is expressed in the allocation of funds and in the printing of literature for propaganda.

The French 'League Against Cancer', managed by a Council of Administration (Conseil d'Administration), includes a 'Scientific Committee' and a 'Central Ladies Committee', which is divided into a Propaganda Section and an Assistance Section. The league's main resources consist of private donations. The Scientific Committee publishes a quarterly journal 'La lutte contre le cancer', a bibliographical section in the journal 'Bulletin de l'association francaise pour l'etude du cancer', and finally a repository on T. for physicians in the journal 'La presse medicale'. To each hospital department in Paris attached to an anti-cancer center, 2-3 female investigators are assigned, who attend all outpatient consultations and register tumor patients to collect further information. In the USSR, at anti-cancer points (e.g., at the Oncological Institute, Oncological Dispensary in Leningrad), special archival departments and statistical offices have been established, where with the help of a specially developed card system, all cancer patients are registered. The handing over of special cards to patients with the date of their next visit and the addresses of the corresponding control points creates constant communication between medical institutions and patients. For patients from other cities, the question of the need for re-examination at the same oncological institution where the patient was treated is decided in writing. All postal expenses related to the anti-cancer fight must be absolutely free, as is the case, for example, in Sweden, where the world-renowned institution 'Radium Hemmet Stockholm' is in constant contact with all tumor patients who have come to its attention. At the call of this same institution, a patient from any part of Sweden is provided with free railway passage to Stockholm. The prevention of the appearance and development of recurrences includes conducting preventive X-ray irradiations for certain forms of cancer, dietary prescriptions for treated patients, and finally early diagnosis and timely treatment of already appeared recurrences. The successes of the anti-cancer fight in Western European countries serve as proof of the viability of all the principles outlined above. The fight against tumor diseases cannot be considered realistically implemented until large 'collectors for incurable cancer patients' are established, which are a burden for both oncological institutions and hospitals. The organization and maintenance of 'cancer shelters' will require the state relatively small material expenditures, since in shelters mainly general medical care is needed, the possibility of carrying out the most primitive operations (gastrostomies, etc.) with usually a short hospital stay.

a. Vereshchinsky.