Cancer, Disease

CANCER, DISEASE, or Carcinoma (from Lat. cancer, Gr., an eating ulcer), the name given to a class of morbid growths or tumours which occur in man, and also in most or all vertebrate animals. The term "malignant disease" is commonly used as synonymous with "cancer." For the general pathology, etc., of tumours see Tumour.

Cancer exists in various forms, which, although differing from each other in many points, have yet certain common characters to which they owe their special significance.

1. In structure such growths are composed of nucleated cells and free nuclei together with a milky fluid called cancer juice, all contained within a more or less dense fibrous stroma or framework.

2. They have no well-defined limits, and they involve all textures in their vicinity, while they also tend to spread by the lymphatics and veins, and to cause similar growths in distant parts or organs called "secondary cancerous growths."

3. They are undergoing constant increase, and their progress is usually rapid.

4. Pain is a frequent symptom. When present it is generally of a severe and agonizing character, and together with the local effects of the disease and the resulting condition of ill health or "cachexia," hastens the fatal termination to which all cancerous growths tend.

5. When such growths are removed by the surgeon they are apt to return either at the same or at some other part.

The chief varieties of cancer are Scirrhus or hard cancer, Encephaloid or soft cancer and Epithelial cancer.

Scirrhus is remarkable for its hardness, which is due to the large amount of its fibrous, and relatively small proportion of its cell elements. It is of comparatively slow growth, but it tends to spread and to ulcerate. Its most common seat by far is the female breast, though it sometimes affects internal organs.

Encephaloid is in structure the reverse of the last, its softness depending on the preponderance of its cell over its fibrous elements. Its appearance and consistence resemble brain substance (hence its name), and it is of such rapid growth as to have given rise to its being occasionally termed acute cancer. Its most frequent seats are internal organs or the limbs. Ulceration and haemorrhage are common accompaniments of this form of cancer.

Epithelial cancer is largely composed of cells resembling the natural epithelium of the body. It occurs most frequently in those parts provided with epithelium, such as the skin and mucous membranes, or where those adjoin, as in the lips. This form of cancer does not spread so rapidly nor produce secondary growths in other organs to the same extent as the two other varieties, but it tends equally with them to involve the neighbouring lymphatic glands, and to recur after removal.

Cancer affects all parts of the body, but is much more frequent in some tissues than in others. According to recent statistics prepared by the registrar-general for England and Wales (sixty-seventh annual report) the most frequent seats are, in numerical order, as follows: - males - stomach, liver, rectum, intestines, aesophagus, tongue; females - uterus, breast, stomach, liver, intestines, rectum. Other statistics give similar, though not identical results. It may be said, broadly, that the most frequent seats are the female sexual organs and after them the digestive tract in both sexes. In children, in whom cancer is rare, the most frequent seats appear to be - under five, the kidneys and supra-renal bodies; five to ten, the brain; ten to twenty, the arm and leg bones.

Cancer tends to advance steadily to a fatal termination, but its duration varies in different cases according to the part affected and according to the variety of the disease. Soft cancer affecting important organs of the body often proves fatal in a few months, while, on the other hand, cases of hard or epithelial cancer may sometimes last for several years; but no precise limit can be assigned for any form of the disease. In some rare instances growths exhibiting all the signs of cancer may exist for a great length of time without making any progress, and may even dwindle and disappear altogether. This is called "spontaneous cure."

Cancer research

Cancer has been the subject of observation from time immemorial, and of the most elaborate investigation by innumerable workers in recent years; but the problems of its origin and character have hitherto baffled inquiry. Modern scientific study of them may be said to have begun with J. Müller's microscopic work in the structure of cancerous tissue early in the 19th century. A great impetus to this line of investigation was given by the cellular theory of R. Virchow and the pathological researches of Sir J. Paget, and general attention was directed to the microscopic examination of the cells of which cancer is composed. This led to a classification, on which much reliance was once placed, of different kinds of cancer, based on the character of the cells, and particularly to a distinction between carcinoma, in which the cells are of the epithelial type, and sarcoma, in which they are of the connective tissue type. The distinction, though still maintained, has proved barren; it never had any real significance, either clinical or pathological, and the tendency in recent research is to ignore it. The increased knowledge gained in numerous other branches of biological science has also been brought to bear on the problem of cancer and has led to a number of theories; and at the same time the apparently increasing prevalence of the disease recorded by the vital statistics of many countries has drawn more and more public attention to it. Two results have followed. One is the establishment of special endowed institutions devoted to cancer research; the other is the publication and discussion of innumerable theories and proposed methods of treatment. Popular interest has been constantly fanned by the announcement of some pretended discovery or cure, in which the public is invited to place its trust. Such announcements have no scientific value whatever. In the rare cases in which they are not pure quackery, they are always premature and based on inadequate data.

Organized cancer research stands on a different footing. It may be regarded as the revival at the end of the 19th century of what was unsuccessfully attempted at the beginning. As early as 1792, at the suggestion of Mr. John Howard, surgeon, a ward was opened at the Middlesex hospital in London for the special benefit of persons suffering from cancer. It was fitted up and endowed anonymously by Mr. Samuel Whitbread, M.P. for Bedford, and according to the terms of the benefaction at least six patients were to be continually maintained in it until relieved by art or released by death. The purpose was both philanthropic and scientific, as Mr. Howard explained in bringing forward the suggestion. Two principal objects, he said, presented themselves to his mind, "namely, the relief of persons suffering under this disease and the investigation of a complaint which, although extremely common, is both with regard to its natural history and cure but imperfectly known." This benefaction was the origin of one of the most complete institutions for the scientific study of cancer that exists to-day.

In 1804 a Society for Investigating the Nature of Cancer was formed by a number of medical men in London, Edinburgh and other towns at the instigation of John Hunter. The aim was collective investigation, and an attempt was made to carry it out by issuing forms of inquiry; but the imperfect means of communication then existing caused the scheme to be abandoned in a short time. Subsequent attempts at collective investigation also failed until recently. About 1900 a movement, which had been for some time gathering force, began to take visible shape simultaneously in different countries. The cancer ward at the Middlesex hospital had then developed into a cancer wing, and to it were added special laboratories for the investigation of cancer, which were opened on the 1st of March 1900. In this establishment the fully equipped means of clinical and laboratory research were united under one roof and manned by a staff of investigators under the direction of Dr W.S. Lazarus Barlow. In the same year the Deutsche Comité fur Krebsforschung was organized in Berlin, receiving an annual subsidy of 5000 marks (£250) from the imperial exchequer. This body devoted its energies to making a census of cancer patients in Germany on a definite date. A special ward for cancer was also set apart at the Charité hospital in Berlin, with a state endowment of 53,000 marks (£2560) per annum, and a laboratory for cancer research was attached to the first medical clinique under Professor Ernst von Leyden at the same hospital. A third institution in Germany is a special cancer department at the Royal Prussian Institute for Experimental Therapeutics at Frankfort-on-Main, which has been supported, like the Imperial Cancer Research Fund in England, by private contributions on a generous scale. The fund just mentioned was initiated in October 1901, and its operations took definite shape a year later, when Dr. E.F. Bashford was appointed general superintendent of research. The patron of the foundation was King Edward VII., and the president was the prince of Wales. It had in 1908 a capital endowment of about £120,000, subscribed by private munificence and producing an income of about £7000 a year. The central laboratory is situated in the examination building of the Royal Colleges of Physicians and Surgeons in London, and the work is conducted under the superintendence of an executive committee formed by representatives of those bodies. In the United States a cancer laboratory, which had been established in Buffalo in 1899 under Dr Roswell Park, was formally placed under the control of New York state in June 1901, and is supported by an annual grant of $15,000 (£3000). There are other provisions in the United States connected with Harvard and Cornell universities. At the former the "Caroline Brewer Croft Fund for Cancer Research" started special investigations in the surgical department of the Harvard Medical School in 1900 or the previous year, and in connexion with the Cornell University Medical School there is a small endowment called the "Huntingdon Cancer Research Fund." There appear to be institutions of a similar character in other countries, in addition to innumerable investigators at universities and other ordinary seats of scientific research.

Some attempt has been made to co-ordinate the work thus carried on in different countries. An international cancer congress was held at Heidelberg and Frankfort in 1906, and a proposal was put forward by German representatives that a permanent international conference on cancer should be established, with headquarters in Berlin. The committee of the Imperial Cancer Research Fund did not fall in with the proposal, being of opinion that more was to be gained in the existing stage of knowledge by individual intercourse and exchange of material between actual laboratory workers.

Theories of cancer

In spite of the immense concentration of effort indicated by the simultaneous establishment of so many centres of endowed research, and in spite of the light thrown upon the problem from many sides by modern biological science, our knowledge of the origin of cancer is still in such a tentative state that a detailed account of the theories put forward is not called for; it will suffice to indicate their general drift. The actual pathological process of cancer is extremely simple. Certain cells, which are apparently of a normal character and have previously performed normal functions, begin to grow and multiply in an abnormal way in some part of the body. They continue this process so persistently that they first invade and then destroy the surrounding tissues; nothing can withstand their march. They are moreover carried to other parts of the body, where they establish themselves and grow in the same way. Their activity is carried on with relentless determination, though at a varying pace, until the patient dies, unless they are bodily removed. Hence the word "malignant." The problem is - what are these cells, or why do they behave in this way? The principal answers put forward may be summarized: - (1) they are epithelial cells which grow without ceasing because the connective tissue has lost the capacity to hold their proliferative powers in check (H. Freund, following K. Thiersch and W. Waldeyer); (2) they are embryonic cells accidentally shut off (J.F. Cohnheim); (3) they are epithelial cells with a latent power of unlimited proliferation which becomes active on their being dislocated from the normal association (M.W.H. Ribbert and Borrmann); (4) they are stimulated to unlimited growth by the presence of a parasite (Plimmer, Sanfelice, Roncali and others); (5) they are fragments of reproductive tissue (G.T. Beatson); (6) they are cells which have lost their differentiated character and assumed elementary properties (von Hausemann, O. Hertwig). The very number and variety of hypotheses show that none is established. Most of them attempt to explain the growth but not the origin of the disease. The hypothesis of a parasitic origin, suggested by recent discoveries in relation to other diseases, has attracted much attention; but the observed phenomena of cancerous growths are not in keeping with those of all known parasitic diseases, and the theory is now somewhat discredited. A more recent theory that cancer is due to failure of the normal secretions of the pancreas has not met with much acceptance.

Some generalizations bearing on the problem have been drawn from the work done in the laboratories of the Imperial Cancer Research Fund. They may be summarily stated thus. Cancer has been shown to be an identical process in all vertebrates (including fishes), and to develop at a time which conforms in a striking manner to the limits imposed by the long or short compass of life in different animals. Cancerous tissue can be artificially propagated in the short-lived mouse by actual transference to another individual, but only to one of the same species. Cancerous tissue thus propagated presents all the characteristic features of the malignant growth of sporadic tumours; it infiltrates and produces extensive secondary growths. Under suitable experimental conditions the aggregate growth of a cancer is undefined, of enormous and, so far as we can judge, of limitless amount. This extraordinary growth is due to the continued proliferation of cancerous cells when transplanted. The processes by which growing cancer cells are transferred to a new individual are easily distinguishable and fundamentally different from all known processes of infection. The artificial propagation of cancer causes no specific symptoms of illness in the animal in which it proceeds. Under artificial propagation cancer maintains all the characters of the original tumours of the primary hosts. Carcinoma and sarcoma agree in possessing all the pathological and cellular features of malignant new growths.

Statistics of cancer

Simultaneously with the active pursuit of laboratory research much statistical work has been devoted to establishing the broad facts of the prevalence and incidence of cancer on a firm basis. The point of most general interest is the apparently steady increase of the disease in all countries possessing fairly trustworthy records. It will be sufficient to give the figures for England and Wales as an example.

Annual Death-rates from Cancer to a Million Living.
England and Wales.

1871-1875. 1876-1880. 1881-1885. 1886-1890. 1891-1895. 1896-1900. 1901-1904.
445 493 547 631 711 800 861

In forty years the recorded rate had risen from 403 to 861. The question how far these and similar statistics represent a real increase cannot be satisfactorily resolved, because it is impossible to ascertain how much of the apparent increase is due to more accurate diagnosis and improved registration. Some of it is certainly due to those causes, so that the recorded figures cannot be taken to represent the facts as they stand. At the same time it is certain that some increase has taken place in consequence of the increased average length of life; a larger proportion of persons now reach the ages at which cancer is most frequent. Increase due to this fact, though it is a real increase, does not indicate that the cause of cancer is more rife or more potent; it only means that the condition of the population in regard to age is more favourable to its activity. On the whole it seems probable that, when allowance has been made for this factor and for errors due to improved registration, a real increase due to other causes has taken place, though it is not so great as the recorded statistics would indicate.

The long-established conclusions concerning the incidence of the disease in regard to age and sex have been confirmed and rendered more precise by modern statistics. Cancer is a disease of old age; the incidence at the ages of sixty-five to seventy-five is ten times greater than at the ages thirty-five to forty-five. This fact is the source of frequent fallacies when different countries or districts and different periods are compared with each other, unless account is taken of the differences in age and constitution. With regard to sex females are far more liable than males; the respective death-rates per million living for England and Wales in 1904 were - males 740; females 1006. But the two rates show a tendency to approximate; the increase shown over a series of years has been considerably more rapid among males than among females. One result of more careful examination of statistics has been to discredit, though perhaps somewhat hastily, certain observations regarding the prevalence of cancer in special districts and special houses. On the other hand the fuller statistics now available concerning the relative frequency of cancer in the several organs and parts of the body, of which some account is given above, go to confirm the old observation that cancer commonly begins at the seat of some local irritation. By far the most frequent seats of disease are the uterus and breast in women and the digestive tract in both sexes, and these are all particularly subject to such irritation. With regard to the influence of heredity the trend of modern research is to minimize or deny its importance in cancer, as in phthisis, and to explain family histories by other considerations. At most heredity is only thought to confer a predisposition.

Treatment

The only "cure" for cancer remains removal by operation; but improved methods of diagnosis enable this to be done in many cases at an earlier stage of the disease than formerly; and modern methods of surgery permit not only of operation in parts of the body formerly inaccessible, but also more complete removal of the affected tissues. Numerous forms of treatment by modern therapeutic means, both internal and external, have been advocated and tried; but they are all of an experimental nature and have failed to meet with general acceptance. One of the most recent is treatment by trypsin, a pancreatic ferment. This has been suggested by Dr John Beard of Edinburgh in conformity with the theory, mentioned above, that failure of the pancreatic secretions is the cause of cancer. It has been claimed that the drug exercises a favourable influence in conjunction with operation and even without it. The experience of different observers with regard to results is contradictory; but clinical investigations conducted at Middlesex hospital in a number of cases of undoubted cancer in strict accordance with Dr Beard's directions, and summarized by Dr Walter Ball and Dr Fairfield Thomas in the Sixth Report from the Cancer Research Laboratories (Archives of Middlesex Hospital, vol. ix.) in May 1907, resulted in the conclusion "that the course of cancer, considered both as a disease and as a morbid process, is unaltered by the administration of trypsin and amylopsin." The same conclusion has been reached after similar trials at the cancer hospital. Another experimental method of treatment which has attracted much attention is application of the X-rays. The results vary in a capricious and inexplicable manner; in some cases marked benefit has followed, in others the disease has been as markedly aggravated. Until more is known both of cancer and of X-rays, their use must be considered not only experimental but risky.

(A. Sl.)