Cancer

CANCER, a term embracing several varieties of morbid new growth or tumour and, secondarily, the disease that results from the presence of these new growths and their mode of increase. Here, cancer will be considered as a disease ; the microscopical appearances of the different varieties are described under TUMOUR, and the course of investigations under CANCER RE SEARCH.

Though cancer affects man pre-eminently, it has been found in many other varieties of vertebrate animals, including fishes, and the cells constituting the new growths resemble in essential details the normal cells of the animal in which they arise. In every case of cancer the disease is local at first. In rodent cancer and in about a third of the cases affecting the neck of the womb it re mains so throughout, but in the great majority of cases of all sites secondary growths or metastases occur sooner or later in distant parts of the body. Locally the growth extends by multi plication of the cells of which it is composed, destroying at the same time the surrounding tissues by pressure atrophy (see ATROPHY). Usually it degenerates and breaks down because the blood-supply of the tumour is insufficient to supply the needs of the growing cells. These processes occupy varying lengths of time according to the type of growth and its situation amongst other factors. Hence the duration of the disease varies within wide limits, but reckoning from the date of onset, as alleged by the patient, it is on an average two to three years. This is not all; even with cancer of the same site (e.g., breast), the duration varies in individual cases between, perhaps, six months and as many or more years. In cancer of any part where interference with nutrition is great or important structures are exposed to pressure or ulceration the average duration of the disease and the difference between maximum and minimum are less. Such is cancer of the alimentary tract, particularly in its upper part. In other cases the type of tumour naturally runs a rapid course; such are cancer of testicle and of periosteum.

Early Symptoms.—Naturally the symptoms vary according to the part primarily affected, but it is very common for cancer to be quite painless at first, a fact which explains, in part, why patients, to their own grave detriment, are slow in seeking medi cal advice when they have discovered an abnormality. Moreover, cancer is often superposed on an antecedent condition which is itself non-cancerous; e.g., some site of chronic irritation or a non-malignant tumour. A sudden increase in volume or rate of extension suggests that the pre-cancerous condition has become cancerous, but the actual transition from innocence to malignancy cannot be fixed even by means of the microscope. Thus the earliest symptoms of cancer in a part are in reality those of the pre-cancerous condition itself. When symptoms are present that can be ascribed, indubitably, to cancer the disease has already attained to some considerable size. These facts have an important bearing on treatment (see below) and prevention and must be considered in more detail.

Pre-cancerous Conditions.—Certain conditions are so often followed by local cancer that a causal relation between them has been assumed. Such are various forms of chronic irritation of which the following are the chief. Irritation by a jagged tooth or ill-fitting denture, syphilitic leukoplakia of tongue, smoking of clay pipes (lip), eating of hot rice (oesophagus, Japan), chronic ulcers at the pylorus, gallstones (gall bladder), leukoplakia of vulva, cicatrices in the neck of the womb following childbirth, chronic mastitis (breast), chronic ulcers of skin, use of the kangri by dwellers in Kashmir (skin of lower abdomen and inner sur faces of thighs), pressure of the dhobi string in Indian washermen (skin of shoulder), betel-nut chewing (inside of cheek), bil harziosis (bladder, rectum), aniline (bladder), soot (scrotum), tar (hands and arms), paraffins (hands, arms and scrotum), X-rays and radium (hands). These sources of chronic irritation may have ceased to act several years before the cancer appears or it may supervene during their action. In either case they induce at first a warty condition of skin or other part upon which the actual cancer is imperceptibly engrafted at one or more points. In addition, certain varieties of tumour, themselves non malignant, may take on malignant characters, particularly if sub jected to chronic irritation. Such are moles and warts, especially if irritated by application of acids or caustics for their removal, fibro-adenomata of breast, villous tumours of bladder, fibro myomata of uterus.

Subject to these considerations reference may be made to the earlier signs of cancer at a few of the sites more commonly affected. In the breast, a lump is felt beneath the skin or the nipple is retracted and raised above the level of the other nipple, or a small amount of blood-tinged fluid exudes from the nipple with or without pressure, or stabbing pains are felt particularly at night. In the uterus, haemorrhage independent of menstruation, or a blood-tinged discharge, sometimes foul-smelling, though this is a later sign, pain especially in the back. In the rectum, slight haemorrhage, often ascribed to haemorrhoids or piles, discharge of mucus, perhaps some alteration in shape of faeces. In the stomach, indigestion coming on at a fairly fixed interval after food, often relieved by vomiting. In the lip, a raised sore with base of cartilaginous hardness. In tongue, cheek and floor of mouth an ulcer with hard edges and base painful if touched by salt or highly seasoned foods. In skin, a small non-healing in dolent ulcer, enlargement or ulceration of a pre-existing mole or wart. In bladder, haematuria, passage of small clots. In prostate, difficulty in micturition or defaecation. In bone, local pain, often severe, or local enlargement. Of course many of the symptoms enumerated are not diagnostic of cancer ex clusively, but their frequent occurrence in cancer indicates im mediate recourse to skilled medical advice. It will be noticed that the sites mentioned above are easily accessible. With parts more deeply situated diagnosis is often impossible apart from exploratory operation unless some symptom obtains (e.g., per sistent jaundice in cancer of the pancreas or liver obstructing the main bile ducts) and sometimes cancer is unsuspected till re vealed by an autopsy.

Later Symptoms and Course of the Disease.

If a cancer runs its natural course it will extend until it reaches some free surface. Here, as the result of slight injury or because of local degeneration, putrefactive micro-organisms invade it, degenera tion proceeds apace and a foul ulcer with thickened edges re sults. Long before this has occurred, however, in most cases cancer cells from the periphery of the mass have grown along the lymphatics to the nearest group of lymphatic glands and perhaps to further groups, or minute portions of the primary growth have been carried by the blood-stream to distant parts, particularly the liver or lungs. Wherever lodged, these transported cells multiply and form secondary growths or "metastases." These metastases undergo similar degenerative changes to those of the primary growth, but owing to their situation putrefaction does not occur readily. The total mass of metastases often greatly exceeds in size that of the primary mass. A cancer of the intestine weighing half an ounce may give rise to metastases in the liver weighing altogether 8-10 lb.

When metastasis has taken place the symptoms associated with the primary mass may be greatly overshadowed by those due to the secondary growths. In cancer of the breast the local changes cause anxiety and a varying degree of pain. When the growth has reached the skin and broken down, the ulcerated surface is foetid and from its surface are absorbed into the system poisonous products of putrefaction. These interfere with blood formation so that a progressive anaemia (see ANAEMIA) sets in and the normal balance between numbers of red cells and leucocytes and numbers of different varieties of leucocytes is disturbed. The chemical composition of the blood is changed but not after a fashion characteristic of cancer unless it be that it contains more potassium than normal. This series of changes induces a general malnutrition, wasting and ill-health summed up under the name "cachexia." But the secondary growths arising from this same cancer of breast may add their own peculiar symptoms. The enlarged glands in the armpit pressing on nerves and veins may produce in the arm very severe pain and a dropsical condition reaching to the hand so great that the affected limb is twice or more the size of that on the unaffected side. The other breast may become the seat of metastasis and the entire picture be repeated on that side also. Metastasis may occur in the thigh bone and lead to fracture, in the bodies of the vertebrae leading to severe pain from implication of nerve-roots, in the brain leading to excru ciating headache or even insanity. Indeed, there are few varieties of cancer that metastasize so widely as that affecting the breast.

Cancer of the neck of the womb (cervix uteri) rarely metas tasizes beyond the lumbar glands, but whether glands are sec ondarily involved or not (about one-third of the cases) the pic ture of the disease is essentially determined by local extension of the disease. Ulceration extends rapidly until the greater part or whole of the cervix is destroyed and a foul ulcer that bleeds very readily results. Growth followed by ulceration attacks the adjacent parts of the vagina and often involves the wall of the bladder or rectum or both. Hence fistulous openings are pro duced into these parts to the infinite discomfort of the patient. Growth extends into the broad ligaments, fixes the uterus with surrounding tissue into an immovable mass, and, involving the ureters, directly or indirectly, by way of an invaded and inflamed bladder, leads to changes in the kidneys whereby their structure and function become disorganized. (See KIDNEYS, DISEASES OF.) Cancer of the tongue or other parts of the mouth and of the pharynx lead to symptoms dependent upon their situation. Food cannot be taken with comfort and some kinds cause so much pain that they are refused entirely. The jaws, too, may become fixed to an extent that the handle of a spoon can barely be inserted be tween the teeth. One of the most trying symptoms is profuse salivation. Malnutrition, however, is not so great as might be expected owing to the rapid course run by the disease. From the constancy with which lymphatic glands in the neck are invaded, secondarily by growth and septic organisms from the mouth, ulceration is frequent into the great blood vessels in their neigh bourhood and leads to profuse, even fatal, haemorrhage. Another common and disastrous occurrence is septic pneumonia due to inhalation of putrid material from the surface of the cancerous ulcer. In cancer of the oesophagus interference with swallowing is so great that early in the disease solids cannot be taken at all and wasting is extreme. Owing to the contiguity of the trachea ulceration often takes place into it and septic pneumonia results.

Site Distribution.

The primary implication of sites differs in the two sexes. In England and Wales, roughly speaking, in males 8o% of cancer is primary in some part of the alimentary tract, in females, 8o% is primary in uterus or breast. But appar ently this distribution does not hold in all countries; in some cancer of stomach is returned as a cause of death, even in females, far more commonly than in England and Wales. How far the difference is real or dependent upon methods of registration, the standard of medical education, recourse to hospitals, etc., it is impossible to say. But it is certain that in Holland and in Italy, where death registration methods are comparable with those ob taining throughout Great Britain, cancer of cervix uteri does not predominate as it does in England and Wales. The reason for this difference, which is statistically significant, is unknown, though the Cancer Sub-Committee of the League of Nations in stituted a special enquiry thereon, and examined a number of possible explanations. It follows that, quite apart from special forms of cancer associated with local customs, e.g., kangri cancer in Kashmir, betel-nut cancer in the East generally, cancer of penis common in Hindus who do not circumcise, rare in Mohammedans who do, there is reason to believe that the site distribution of cancer is not identical throughout the world.

Viewed from the aspect of their microscopical characters (see TUMOUR) the different varieties of cancer show some well-marked site preferences. These depend upon the fact that the primary growth consists in a modification of normal cells in the part affected and subsequent multiplication of those altered cells. If the part normally contains pigment, e.g., skin or choroid of eye, the cancer cells originating therefrom contain pigment also in great or small degree ; if it originate from a member of the con nective tissue group (q.v.), e.g., bone, cartilage, fibrous tissue, the cancer cells retain in great or small degree the special char acters of those tissues. The same is true for squamous, columnar and spheroidal epithelia (q.v.). Hence by microscopical examina tion it is often possible to narrow within certain limits the primary site of a growth. A pigmented cancer (melanoma) can only have originated in skin or choroid however widespread may be the distribution of secondary growths.

Very rarely a melanoma arises in the pineal body (see BRAIN) of man which normally is devoid of pigment, but phylogenetically, the pineal is the representative of a median eye, and in the Lacertilia it contains pigment. Similarly, a hypernephroma can only have originated in adrenal tissue, a squamous cell carcinoma in squamous epithelium, a spheroidal cell carcinoma in gland tissue of spheroidal character, a columnar cell carcinoma in gland tissue lined by columnar epithelium, a sarcoma from some mem ber of the connective tissue group.

Age Distribution.

Cancer is pre-eminently a disease of adult and old age but no age is exempt. Moreover, if it be divided into its two great classes of carcinomata or epithelial cancers and sarcomata or connective tissue cancers a difference in age distribution appears. For whereas the carcinomata are rare before 3o and extremely rare before 20 and liability increases with ad vancing years (due correction being made for age distribution of the population), the sarcomata show a fairly even distribution throughout life. As a corollary, malignant disease in infancy or childhood, almost without exception, is sarcomatous and parts liable to sarcoma, e.g., bone, kidney, are those commonly affected. In adult life or middle or old age it may be carcinoma or sarcoma, but probably the former since the total number of carcinoma cases greatly exceeds the total number of sarcoma cases.

In some instances, e.g., cervix uteri, there is a fall in liability in advanced old age but this is counterbalanced by an increased lia bility at some other site, e.g., skin, so that the statement that liability to cancer increases with increasing years is generally true. This does not mean that the greatest number of cancer cases seen are aged. On the contrary the greatest number falls between the ages of 45 and 65, uterine cases on the whole being a little younger than breast, and breast cases than skin. Even within the area of the same organ differences in age distribution occur, cancer of the body of the womb, on an average, affecting older women to a greater extent than that of the neck or cervix.

Civil State.

In the case of breast and uterus certain differ ences obtain in cancer incidence, between married and unmarried women. Correction being made for their respective numbers in the population, cancer of cervix is more common in the married, cancer of breast in the unmarried. It does not appear that the number of pregnancies has much influence upon the occurrence of cervical cancer, one childbirth being as liable to be followed by cancer as several. Cancer of the breast seems to be correlated with abeyance of the normal function and the occurrence therein of chronic inflammatory changes (chronic mastitis).

Cancer Mortality.

In England and Wales the death rate from cancer per million of the population, in 1926, was 1,362 as compared with 1,336 in 1925, 1,297 in 1924 and 1,267 in 1923. These figures do not indicate an actual rise in incidence, for im portant factors in the apparent rise are more accurate diagnosis, improved certification of the causes of death, and increased longevity resulting in a greater number of people reaching the age period of cancer than formerly. Probably, too, the greater attention attracted to the disease by recent national schemes of cancer research is reflected in the rise. It is noteworthy that in Switzerland where autopsies are common and death certification has long been highly efficient, the cancer death-rate has differed little from year to year during the past quarter century. In other civilized countries the figures are substantially of the same order as in England and Wales. From collected statistics for the United States registration area it has been estimated that the cancer death-rate for the whole country in 1920 was 834; in 1921, 86o; in 1922, 868 ; in 1923, 894, and in 1924, 920 per million living.

Treatment.

In 1928 the official method of treating cancer remained wide surgical removal at the earliest possible date. When the disease is still local, efficient surgical removal may fairly be described as curative in the sense that the patient's expectation of life is as great as if he or she had not suffered from cancer. The stage of the disease in which operation is performed, how ever, fundamentally influences prognosis. Thus, in cancer of the breast, 9o% of women undergoing the complete operation while the disease is still confined to the organ may expect to be alive and well ten years later, whereas of those in whom the disease has passed beyond the breast when they first seek medical advice 9o% will be dead ten years later. The average period elapsing be tween strict localization to the breast and extension beyond its limits is no more than a few weeks or months. It is probable that essentially the same is true of cancer at other primary sites but in some dissemination is even more rapid and in others satisfac tory surgical intervention is difficult or impossible.

The above-mentioned considerations, combined with the natural reluctance of patients to undergo extensive operations, have led to continued search for other methods of dealing with the disease than surgery. Of these treatment by radium or X-rays (see RADIOTHERAPY, RADIUMTHERAPY) has established itself as in some measure effective. How far radiation is destined to replace surgery, as the mode of its action and technique of its application are better understood, it is impossible to say. Already there is statistical evidence that in cancer of the cervix uteri, on the basis of five years' survival, efficient radium treatment gives nearly as good results as efficient surgery and has the additional advantage of affording a five years' survival to some 12% of cases beyond the reach of surgery.

Treatment of Coley's mixed toxins of B. prodigiosus and Str. erysipelatis has, in his hands, been followed by good results in some cases of sarcoma. Blair Bell's treatment by intravenous injection of colloid lead is still in the experimental stage and, though highly dangerous, has given some striking results. No other method of treatment aiming at cure than the above is worthy of consideration and the majority are harmful.

The treatment of inoperable cancer is symptomatic ; the pain, ulceration, anaemia, etc., are combated to afford the patient the utmost relief and length of life. Surgical procedures of various sorts such as ovariotomy (now discarded) lymphangeioplasty, an endeavour to provide alternative paths for the lymph in the en larged arm often seen in cancer of the breast, local removal of the growth to diminish the ulcerating area have been employed but the usual methods in vogue are radiation and drugs. Radiation in most instances relieves pain, and, in some, causes a diminution in the rate of local progress, but, in others, appears to cause a wider dissemination of metastases and in septic conditions ma terially worsens the patient's condition. With regard to local treatment and drugs much may be done to ease the patient. Mild disinfectants and frequent change of dressings diminish local putrefaction, reduce foetor, and the amount of toxic material liable to absorption ; it is surprising how much benefit may accrue from keeping the cancerous ulcer clean.

In respect of drugs, the pain, with the sleeplessness it may entail, is the symptom calling most for attention. Those with the greatest experience are unanimous that opium and morphia should be reserved as a last resource for as long as possible, owing to the bad effects these drugs have upon the morale of the patients, the necessity for continuously increasing doses, the severity of the pain in the intervals between doses and the greater difficulty of nursing. For a long time a drink of warm milk, a dose of aspirin or of omnopon at night gives the needed relief, and the great majority of patients in an institute specially devoted to cancer cases never require opium or morphia from beginning to end of their illness.