Oncology

ONCOLOGY (from Greek onkos - tumor and logos - word, doctrine), the doctrine of tumors. As a completely independent chapter of medical science, O. is still young, despite the fact that our knowledge of tumors dates back to the most ancient times. The history of O. is almost as old as the history of medicine. In ancient writings (Ebers papyrus), as well as in literary sources from India and Persia, there are mentions of neoplasms. The entire history of O. from ancient times to the present day can be divided into 4 periods. The first covers the period from ancient times to the end of the 18th century; it ends with the research of Bichat, published in 1801 in "Anatomie Generale"; in it, the division of tumor tissue into stroma and parenchyma is carried out for the first time. The second period extends from 1801 to the beginning of the use of the microscope in the study of tumor morphology. This period can be considered a transitional time, however containing within it the seeds of more rigorous scientific thinking. The third period belongs to the end of the 19th century, when an improved microscope was used for scientific research and when R. Virchow appeared on the stage of scientific biological thought with the new principles of cellular pathology proclaimed by him. Finally, the fourth period belongs to the most recent time; the greatest achievements in the field of O. have been made in this period in the field of experiment. Hippocrates belongs to many descriptions of individual forms of O., and he was the first to apply the term karkinos for painless ulcers and karkinoma for progressive malignant tumors. He based the explanation of all neoplasms on the concept of black bile proposed by him, as a result of the thickening of which cancer appears. Despite the vagueness of the concepts about the essence of this disease, Hippocrates mentions a case of neck cancer, cured by him by the method of cauterization. Subsequently, Celsus, describing some varieties of tumors, mentions among other things a cancer of the breast gland that he cured, while speaking against the removal of the large pectoral muscle. Galen, who devoted much effort to the study of tumors, continued to develop Hippocrates' views on the significance of black bile for the occurrence of tumors. Galen divided neoplasms into tumors se-cundam naturam (pregnant uterus), supra naturam (callus), praeter naturam (true tumor). Subsequently, some progressive development in the field of therapy of neoplasms is found in the works of Leonidas of Alexandria (180), who advocated the excision of tumors within completely healthy tissues. The Byzantine period (475-1500) was marked by a large number of descriptive works, among which attempts at classifications, characteristics of the external features of individual neoplasms, etc., are found. The Renaissance period was a period of further attempts in the description of individual varieties of tumors. Vesalius questioned Galen's views on the reliability of bills atra; Fabricius (1537-1619) tried to draw a line between inflammatory tumors and true neoplasms. Marcus Aurelius Sevelin described myxosarcomas, drew a line between cancers of the breast gland and benign tumors of this organ. Paracelsus (1413-1541), finally rejecting black bile as the cause of cancer, considered disorders in the amount of salts in the blood as the etiological moment of tumors. During the "lymphatic theory" period (17th and early 18th centuries), Galen's theory was finally rejected. In view of the fact that "black bile" in the form in which it was supposed was not found in the body, and lymph and blood were found everywhere in the vessels, cancer came to be considered a product of the thickening or coagulation of lymph; according to this view, the density of cancer depended on the thickness of the clotted lymph, which in malignant tumors fermented, degenerated, etc. Already le Dran spoke of cancer as a local disease and believed that if even one drop of "cancer lymph" penetrated into the lymph glands nearest to the primary focus, the entire lymphatic apparatus would be affected. A serious step forward was the work of Peyrilhe (1773), who wrote a work on the topic assigned by the Lyon Academy: "Q'est ce que le cancer?" This was the first systematic study of the entire question of the essence of neoplasms. Here the author spoke of the local origin of tumors, of cachexia arising from the poisonous effect of cancer, etc. In Germany at the end of the 18th century, tumors were viewed as consequences of chemical disorders in the body fluids, in particular as a result of an increase in the general acidity of tissues and blood. In connection with this, it was proposed to treat tumors with large doses of alkalis. Approximately at the same time in England, Hunter (1728-93), although he recognized the lymphatic theory of the origin of tumors, however, in his understanding, he was already strongly approaching the later cellular theory. According to Hunter's concepts, tumors grew from lymph secreted from the blood; at the same time, tumor tissues were nourished in exactly the same way as the body's tissues and developed in the same way as the body's own tissues. The extent to which interest in the doctrine of neoplasms had grown at this time is evidenced by the fact that in 1802 a society for the study of the nature and causes of cancer was already established in London. As for French authors, the concepts of Galen and A. Pare about cancer remained approximately the same despite the difference in time periods. In 1704 Littre in France described for the first time a fatty tumor and named it a lipoma. Since tertiary forms of syphilis were not then strictly distinguished from cancer, many authors of the French school of this period (Ambroise Pare and others) wrote about the successful treatment of cancer with mercury preparations. The second period, opening with the research of Bichat and the works of his students Laennec, Dupuytren and others, is marked by a review of all pathological anatomy and attempts to apply the newly obtained morphological data on normal tissues to tumor tissues. Of particular interest are the theoretical reasoning of Broussais, who was the first in medical literature to speak of neoplasms as a result of repeated irritation of tissues. "These ulcers," he says, "if persistently irritated and caused to bleed, inevitably undergo malignant transformation and turn into an eroding chancre." In his research, known under the title "Examen des doctrines medicales et des systemes de позо^1e" (3rd ed., Paris, 1829), Broussais says: "All inflammations and sub-inflammations can lead to cancer... If you want to prevent skirrhus of the cervix, which are especially frequent in the climacteric period, take care to calm the irritations of the uterus even before the onset of painful bleeding." Cruveilhier (1827) asserts that it is not the normal tissues of the body that transform into cancerous tissue, but that on the basis of normal tissues a pathological neoplasm occurs, "heteromorphic and parasitic." Thus we see that although by the end of the second period of the history of O. tumors were no longer viewed as thickened spoiled tissue fluid, but as true formed tissue, their essence still remained unexplained. The improvement of the microscope opened the third, scientific, mainly histological period of the doctrine of tumors. Everyone agrees that Raspail (1826) belongs to one of the most valuable reports of the beginning of this period; he showed that the further growth of animal and plant tissues occurs due to the multiplication of cells. Broca (Traite de tumeurs) considers Raspail as the founder of the entire cellular theory. J. Muller (Uber den feineren Bail und die Formen der krankhaften Ge-schwulste, 1838) applied the data obtained by Raspail to the study of tumors; he asserted that cells of benign tumors do not differ from cells of normal tissues. Thus he for the first time linked tumor cells directly with the morphological elements of normal tissues. Despite these studies by Muller, the theory of the origin of cancer from liquid blastema continued to predominate even at the beginning of Virchow's activities. Langenbeck discovered the possibility of the independent existence of cancer cells, their circulation in the blood and transfer to new places with the formation of metastases. Although Recamier long before that, studying cancer of the breast gland with destruction of the vein walls by the tumor, already spoke of "metastases" appearing as a result of such a disseminated process in a woman, however, the interpretation of this fact naturally remained untouched at that time. Bruch considered metastases not as a new cancer infection, but as the implantation of cancer cells spreading along lymphatic pathways; in his joint work with Meckel he speaks of "retrograde" metastases. The question of the histogenesis of cancer was placed on a truly scientific basis by Virchow, especially since he proclaimed the most important principle of the cellular theory "omnis cellula e cellula". Having established the unshakability of this principle, Virchow, however, fell into error, from which he almost never recanted until the end. It was he who asserted that cancer cells come from connective tissue elements. This incorrect interpretation was disputed by Remak.

The latter asserted that epithelial cells can only originate from epithelial elements. Remak substantiated this position with the specificity of the three germ layers. In 1857, Meckel, based on individual case observations, demonstrated that cancer of the cheek originates directly from the epithelial layers of the mucous membrane. Subsequently, Thiersch conclusively proved the origin of epitheliomas of the skin from the underlying epithelial layers. Like Bar, he expanded Virchow's principle with the assertion 'omnis cellula e cellula ejusdem naturae'. Waldeyer expanded the body of evidence presented by Thiersch and established the origin of cancer of the stomach, liver, kidney, etc., from the epithelium of these same organs. Although this fact was disputed by Recklinghausen and others, Waldeyer's opinion became firmly established in science, and the connective tissue theory of cancer, proposed by Virchow and for some time supported by Billroth, had to yield to Waldeyer's opinion. Although Virchow supported the importance of irritation in explaining the causes of cancer, the palm of precedence for this general idea apparently still belongs to Bruch (Virchow, Die krankhaften Geschwulste). From the rather broad concept of 'cancer,' other varieties of tumors gradually separated. For example, in 1845, Lebert described 'fibroplastic tumors' consisting of fibers and spindle-shaped cells. Virchow combined these neoplasms, which at one time seemed clinically very benign, into a special group of connective tissue tumors and called them sarcomas. He also gave a classification of sarcomas that has remained almost to the present day: fibrosarcomas, myxosarcomas, melanomas, etc. In 1877, Cohnheim presented a theory of tumor development that met with wide acceptance, based on the idea of aberrant embryonic rudiments that subsequently, under the influence of various internal and external factors, undergo progressive development with true malignant transformation. The special properties of the morphological elements of the neoplasm, their insufficient differentiation, later led Hansemann to combine all special, including embryonic, tissue characteristics of tumor cells under the concept of 'anaplasia.' As histological knowledge deepened, descriptions of new types of cells appeared, but at the same time (1908), descriptions of rarer forms of embryonically derived tumors began to appear; they were sometimes of more complex, sometimes of simpler structure (placentomas, choriomas, chondromas, embryomas, etc.). Patho-anatomical research thus undoubtedly played an outstanding role in the study of tumor diseases. They served as that unshakable foundation, that material which is still used to this day. Particularly noticeable shifts in the study of the nature of tumor growth, in the study of the biology of tumors, began when science widely turned to experimentation. One of the founders of experimental oncology is undoubtedly the Russian author Novinsky, who in 1875, in Rudnev's laboratory at the Military Medical Academy in St. Petersburg, successfully began the transplantation of tumor material onto horses and dogs. Subsequently, extensive work with tumor transplants within the same species of animals was carried out by Jensen, Bashford, and others. The so-called tumor strains created as a result of this work enabled other laboratories to conduct on a very large scale the study of new scientific problems concerning the nature of growth, heredity, infectivity, and other properties of tumors. Hundreds of thousands of experimental animals, concentrated in individual laboratories, under conditions of many years of strictly scientific observation (Jung, Bashford), made it possible to establish the laws of 'organ heredity' of neoplasms, to create generations of animals that develop cancer in almost 100%, and so on. The method of growing tissues outside the body (Carrel) also gave pathologists considerable opportunities for clarifying the nature of tumor growth. With the help of this technique (Erdmann), it became possible not only to grow tumor cells outside the body and successfully reimplant them into animals, but also to transform normal cellular elements in vitro into malignant colonies, which when transplanted into animals (chickens) succeeded in causing sarcoma formation in them. The idea of the 'indivisibility of the existence of the tumor principle' with the living cell was, however, to some degree shaken by the well-known studies of Rous with the transplantation of cell-free tumor products, as a result of which the so-called 'Rous chicken sarcoma' was obtained (see Chicken sarcomas). A major advance in the same field was embryonic transplantation, as a result of which in the experiments of Askani, Petrov, and Krotkina on rats and Vereshchinsky on guinea pigs, Tiesenhausen on birds, and many others, it was possible to obtain malignant tumors in vivo. As clinical and experimental materials accumulated, oncological thought, especially in recent years, was directed toward studying the connection between various types of irritation of living tissues and the onset of tumor growth. Observations of the carcinogenic effect of X-rays were followed by similar experiments with radium, infusorial earth, and others. Experiments with chronic irritation of animal skin with coal tar deserved completely exceptional attention. These experiments were carried out for a sufficiently long time by 1916 by Yamagiwa and Ichikawa, who succeeded in a significant percentage of experiments (mice, rats, rabbits) in first causing precancerous conditions, then true cancers by the systematic application of tar to the skin. With these exceptionally important observations, an experimental basis was laid for a whole series of clinical forms of malignant neoplasms that resulted from long-term chemical, mechanical, and other tissue irritations associated with domestic, professional, industrial, and other factors. Parallel with these experimental facts, the accumulation of clinical observations continued, forming a special category (radiologists' cancers, chimney sweeps' cancers, persons engaged in the aniline industry, etc.). A series of experimental observations and works enriched oncology with materials on the carcinogenic effect of certain types of parasites and bacteria. Although to the present time all attempts by pathologists to find a 'specific causative agent of malignant growth' have only met with temporary success, the path traveled in this direction has not remained without consequences. Besides some specific forms of bacteria (Bacillus of Smith) that lead to the systematic appearance of tumors in plants, certain bacterial forms have been isolated by various authors that gave positive results both in rats and in dogs. These observations by no means resolved the question of the specificity of the mentioned causative agents in a positive sense, which were ultimately classified under the very diverse category of 'physical, chemical, bacterial, parasitic, actinic' and other irritators, which formed the actual basis of the 'theory of irritation' in the pathogenesis of tumors. Mention should also be made of the works of Fibiger that marked an era in oncology, concerning the carcinogenic effect (in experiments on rats) of the worm Spiroptera neoplastica, and the experiments of Bullock and Curtis (1920) on the tumor-producing effect of the cysticerci of Taenia crassicolis. As this most valuable factual material accumulated, oncological thought was enriched, and especially in recent times, has been enriched by a large number of works devoted to the essence and the most subtle mechanism of the tumor process. Physicochemical phenomena related to the inherent characteristic properties of the tumor cell became the subject of the study of so-called 'chemical anaplasia' of malignant elements, which made it possible to establish significantly increased energy metabolism compared to normal tissues, increased dispersion, decreased surface tension, and so on. Physicochemical explanations of blastomatous growth, however, did not compete with the 'parasitic,' 'cellular,' and other theories of blastomatous growth. They only served to deepen oncological thought to the limits possible with our current level of knowledge. Changes in the ionic composition, changes in the permeability of tumor colloids, according to the modern view, should not be considered as causes of tumor growth, but as conditions for its occurrence, conditions created by various causes that retain their independent significance. The study of the pathogenesis and etiology of blastomatous growth in the current period of the development of oncology proceeded simultaneously with the deepening of our knowledge of the physiology of tumor tissue and its influence on the entire organism. Questions of the oxygen exchange of cancer cells became the subject of extensive research by Warburg, Posener, and others. As a result of these studies, it turned out that the main source of energy for cancer is not respiration, not oxidation, but the breakdown of carbohydrates, primarily by fermentation, and not by an oxidative process.

The increased content of hydrogen ions to a greater degree than the faster growth of a given tumor was established by Russian works of Konikov (1913) at the Moscow Cancer Institute. The increased potassium content in malignant tumors and the decreased amount of calcium in them, determined by Clowes and Friesbie, begins a series of works on qualitative and quantitative chemical analysis of tumor tissue. The study of the influence of the life activity of neoplasms on the entire organism of the carrier proceeded along the path of laboratory and clinical observations. Blood studies were conducted in the direction of studying the quantities of inorganic salts in cancer disease, changes in mineral metabolism, etc. Questions about cachexia were attempted to be connected with the finding of a specific poison of tumors, the so-called "cancer or sarcoma toxin." Despite a number of works that attempted to prove the chemical detectability of this toxin, these attempts must still be considered unsuccessful; apparently the modern point of view on this question should tend to the assumption of a number of proteolytic, hemolytic and other enzymes produced by the tumor. These enzymes, breaking down the protein particle according to a special plan, lead to a picture of self-poisoning of the organism, with symptoms of anemia when there is an enhanced breakdown of carbohydrate and protein particles. Finally, especially in recent times, works increasing in number and interest, devoted to natural and active immunity with respect to neoplasms, are attracting attention. Questions of natural immunity, developed in the light of experiment by the works of Roffo, questions of local immunity (Levin), artificial active immunity and artificial passive immunity (Weil) continue to be discussed and developed with increasing energy. They are the subject of the most recent research in America. Parallel with the development of modern oncology in the indicated directions, we see a renewed increase in interest in the patho-anatomical side of tumor processes, with attention being drawn to the study of the finest structures of the cellular elements of neoplasms. With the improvement of histological technique and optical instrumentation, patho-anatomical pictures of "tar cancers" already in use in laboratories are studied in more detail. The structure and types of nuclei and especially the qualities and quantities of chromosomes serve as the subject of works by pathologists and morphologists, establishing the relationships of these formations in tumors with similar formations in normal tissues and thus studying the "karyotype" of the tumor cell. The counting of chromosomes in the nuclei of cells of normal and tumor tissues of mice, rats, etc. is the subject of a number of works (see Tumors). Research on the finest structure of tumor elements is now being supplemented by an increasing amount of data on other morphological components of neoplasms. The discovery of the presence of nerve fibers, primitive nerve endings, etc. in tumor tissue appears to be a relatively recent achievement. The accumulation of a large amount of factual, experimental and clinical material in modern oncology finds reflection in the ever-increasing number of printed organs. To orient oneself in the growing oncological literature, special review and abstract organs, summaries, etc. are already necessary. As indicated above, oncology belongs to too young a discipline to be able to speak at present of finally formed individual oncological schools. Such are nevertheless taking shape, for example the school of Regaud in Paris, Berven in Stockholm, Petrov in Leningrad, Herzen in Moscow, etc. Centers for future oncologists are now mainly large centers for the fight against cancer diseases. Special oncological institutions should become the pedagogical base for creating a staff of oncology teachers. Only by using the base of special institutions is it possible to organize lively and visual teaching of oncology. On medical faculties, the training of students in oncology is being improved by sending them in groups to production practice in anti-cancer centers. For physicians, improvement in oncology is connected with courses for the improvement of physicians, where a special cycle should be created. This cycle is necessary for creating a staff of oncologists, for preparing oncologically educated teachers of medical faculties and for raising the qualifications of persons working in professional-medical institutions on the periphery. Discussion of the principles of treatment and improvement of therapy should be the topic of special oncological congresses (for example, the First All-Union Oncological Congress in Kharkov, July 1931), anti-cancer conferences, etc. (for example, the Leningrad Regional Anti-Cancer Conference, May 1931; the Moscow Regional Anti-Cancer Conference, April 1930).