Part 3

Williams has also made some most interesting studies in regard to the increase of cancer in connection with changed conditions of life, and from his analysis of statistics, he very clearly shows that the spread of the disease has closely followed urbanization, and the rapid increase in material prosperity of recent years: in England where 80 per cent. of the population are now town dwellers, this tendency to collect in cities and towns has gone farther than in any other community. He recognizes that any far-reaching, environmental change of some duration is probably potent in disturbing the stability of the constituents of living bodies, and the sudden change from poverty to riches and plenty is conducive to the development of cancer: allusion has already been made to the inverse relation of deaths from cancer and tuberculosis, the latter diminishing with improved material conditions, while the former increases as wealth and indolence increase.

He shows this by statistics from various localities, and by data from towns in different countries he makes it pretty clear that “Cancer mortality is lowest where the conditions of life are hardest, the surroundings the most squalid, the density of population greatest, where the tubercle mortality is highest, the general and infantile mortality greatest, and where sanitation is least perfect—in short, among the poor of the industrial class in our great towns: whereas among the wealthy and well-to-do, where the standard of health is at its best and life is easiest, and where all the conditions of life are just the reverse of the foregoing, there the cancer mortality is highest.”

While this is a pretty strong statement and many exceptions could undoubtedly be found, careful investigation will show it to be true in the main; for it must be remembered that even among the poorer classes gluttony, especially in regard to proteids, is not at all uncommon, and indolence, with impeded metabolism, is not at all unusual. Dr. Latham found that the mortality from cancer in England, from 1881‒1890, was more than twice as great among well-to-do men having no specific occupation, as among occupied males in general, the respective mortality ratios being 96 for the former and only 44 for the latter. Sir William Banks confirms the steady increase in cancer very strongly, which he attributes to richer and more abundant food, of which males eat more than females, and consequently cancer is increasing proportionately more among men, as all statistics show.

Switzerland is reported to have the highest death rate from cancer of any country, it having augmented from 114 per 100,000 living in 1889, to 132 in 1898. There again the cancer mortality varies greatly in the different sections or cantons: thus, in wealthy Lucerne it is 204 per 100,000 living, and only 36 in poverty stricken Valais. In the city of Geneva it is 177 per 100,000 living.

Denmark, next to Switzerland, is reputed to have the highest cancer death rate of any country in Europe, viz.: 130 per 100,000 living in 1900. But here the statistics are only from the towns, which comprise but a quarter of the whole population: the per capita wealth is said to be higher there than any other country in Europe except France.

France shows a high cancer mortality, with a constantly increasing death rate; and, next to England, France is the richest country in Europe, and wealth is much more widely diffused: the French workers own nearly 8 times, per capita, more than those in England. In Paris the cancer death rate has increased as follows, for each 100,000 living, in 1865, 84; in 1870, 91; in 1880, 94; in 1890, 108; in 1900, 120.

Italy, a comparatively poor country, shows a low cancer mortality, but even here it is increasing from 20 per 100,000 living in 1880, to 52 in 1899, and 58 in 1905. The consumption of meat is there the smallest in any European nation, namely 23 pounds per capita in 1895. In the chief towns the rate of death from cancer is high: thus for each 100,000 living, in Florence 137, Ravenna 120, Venice 103, Milan 101, and Rome 77.

Time does not permit a wider survey of the field of distribution of cancer, as presented so remarkably from official statistics by Williams, and Wolff; but in connection with the high percentages of deaths above quoted among the richer classes it may be interesting to mention some of the lowest records. Thus, in the poor country of Kerry, Ireland, it was 27 per 100,000 living, in the province of Dalmaltia 19, in the Shetland Islands 16, in Servia 8 (from 1895 to 1904), and in Ceylon in 1903 the mortality from cancer was about 6 for each 100,000 living.

The United States, unfortunately, has not kept the vital statistics of the country in years past with anything like the fullness and accuracy which has obtained in England, nor even at the present time is it possible to learn definitely the frequency and increase of cancer in every locality. But all the statistics which have been gathered show unequivocally that the disease has steadily increased in a manner which is alarming. Analyzing the recorded deaths from cancer in thirty-one cities, and the percentage of increase in four years, one writer estimates that, if the same increase is continued, by the end of the century there will be a death rate, approximately, of 1000 in every 100,000 inhabitants, or one in every hundred.

In a recent Bulletin of the Board of Health of New York City the following statements are made in regard to the mortality from cancer in 1913: “The statistics of our seven largest cities recently tabulated, show that the cancer death rate was the highest on record. For New York City the rate was 82 per 100,000 of the population, against an average of 79, for the last five years: for Boston 118 against an average of 110: for Pittsburgh 79, against an average of 70: for Baltimore 105, against an average of 94: for Chicago 86, against an average of 81: for Philadelphia 95, against an average of 88: for St. Louis 95, against an average of 85.” This average increase of almost 8 per cent. of deaths from cancer in the combined population of these seven cities, during the last five years is certainly an alarming fact, and cannot be explained on the ground of greater accuracy of diagnosis: for it is not to be presumed that there has been such great improvement along diagnostic lines during the single year 1913.

It is difficult to state the exact prevalence of cancer in the entire United States, as the “registration areas” include only about two-thirds of the total population: much can be learned, however, from the annual volumes published since 1900. According to these Mortality Statistics of the United States, the deaths from cancer and other malignant tumors per 100,000 population were as follows: in 1900, 63, in 1904, 70.2, in 1909, 73.8; and in 1912 there were 46,531 deaths from cancer, or 77 per 100,000 population, an increase in the death rate from this disease of almost 25 per cent. since 1900; while, as before stated the tuberculosis mortality had fallen a little over 25 per cent. in the same period.

As in other countries, which might also be expected from the statements already made, the disease varies in frequency in different localities and communities. Thus, cancer is stated to be much more prevalent in the northern than in the southern states, and as already stated, the negroes are much less subject to the disease than whites, especially when they are living their own natural home life; but when they come to the cities, as waiters, etc., in hotels, their cancer death rate increases. But even in New York City in 1912 the deaths from cancer in negroes was 1 in 32.2 total deaths, against 1 in 17.7 in whites; the mass of negroes here, of course, live plainly and work hard. The North American Indians also are believed to be almost exempt from cancer in their primitive savage condition, but as they have come under the influence of civilization they are more affected. It has also been noted by several observers that immigrants and their descendants present a very much higher mortality from malignant diseases than prevails in their native countries; from these and other considerations Williams suggests that abrupt change of environment may also be a factor in the causation of this disease.

We have thus seen while cancer is very widely distributed over the globe it is present in varying degrees of severity in different localities, and careful analysis shows that the disease affects different classes of persons with unlike severity. All these statistical studies and observations serve to confirm the statement made earlier that cancer is a disease of so-called civilization, and that it has increased in proportion as human beings have come under the influence of wealth, and consequent luxury and overindulgence, with bodily inactivity; all these elements lead to a disturbed metabolism, which as we shall see later, is, at least, a contributing cause to the deviation from normal of some of the cellular elements of the body. It also appears that some of these metabolic shortcomings have to do with a disturbed nitrogenous balance, which is due to the constantly increased consumption of meat. In 1909 the meat consumption in the United States had reached the high figure of 172 pounds per capita, as I learned recently from Washington, a far greater amount than in England, 130 pounds, as already stated; and with this steady increase in the use of nitrogenous food cancer has also increased by leaps and bounds in both countries.

LECTURE III METABOLISM OF CANCER

In the first lecture we saw that cancer was an alteration of the normal cells of the body, whereby they take on a malignant action and continue to do so, destroying contiguous tissues and leading to a lowered vitality, with an apparent poisoning of the system, which finally causes death. As the cells of various organs furnish different secretions, which in health contribute to proper metabolism, resulting in growth or maintenance of the tissues, so these disordered cells are believed to secrete a toxic substance, or malignant hormone, which has a prejudicial action on the body, and hæmolytic action on the blood, as has been brought out pretty clearly by Troisier and others.

We saw that as yet the definite cause had not been determined, why at some period certain cells take on the action which we call cancer, nor why they persist in their destructive course. Long continued and abundant laboratory and clinical research have about decided certain questions negatively in regard to its etiology, so that in a measure the field is cleared for the study of some of the possible basic causes of the disease in question. Thus, all are pretty well agreed that cancer is _not_ contagious or infectious, that it is _not_ caused by a micro-organism or parasite, that it is _not_ wholly due to local injury, that it does _not_ appertain to any particular occupation, that it is _not_ hereditary to any great degree, that it does _not_ especially belong to or affect any particular sex, race or class of persons, _nor_ is it confined to any location or section of the earth, and that it is _not_ wholly a disease of older age.

We saw further that there appeared to be good evidence that certain misplaced “embryonal rests” were the original starting points of diseased cell action, but as these are now known to exist in every one from birth, this offers no real explanation of the occurrence of the disease at different times in life. It is, of course, quite possible that local injury of one kind or another may be the exciting cause which determines that a cell or group of cells shall revert to its original reproductive activity, as Williams contends that the process is one of agamogenesis, dependent upon excessive and faulty nutrition. The question as to the relation of uricacidæmia, or lithæmia, to cancer has never been fully studied, and it is worth considering whether, as in gout and rheumatism, to which cancer is often associated and perhaps closely allied, the exciting cause may not be the lodgment somewhere of uratic deposit, which is further excited and fed by effete or imperfectly oxidized nitrogenous elements; for later we shall see that perverted metabolism, largely of proteid elements, is closely associated with cancer.

We noted also that some attributed cancer to independent cell action, relating to the polarity of cells, etc.; but it is inconceivable that a cell or cells can idiopathically start out on a rampant course and pursue it with increasing severity, even until death results, without, at least, some definite pre-disposing cause, even though diligent and earnest work has not as yet determined just what that cause may be. The error has been, we believe, in searching too exclusively by the microscope and by certain laboratory methods, and not sufficiently along clinical and bio-chemical lines. For it must be recognized that all the cells of the body are continually bathed in the vitalizing fluid of the blood, whence they derive their nutriment, and into which, with the lymphatics, they return the products of their vital action, by anabolism and catabolism.

By exclusion, therefore, we are reduced to seek the etiology of cancer along other lines, and about all that is left is metabolism, as influenced by advancing, so-called civilization, which relates very largely to diet and mode of life. This we will take up later, but will first examine some of the scientific findings in regard to the blood in cancer, and data relating to the various secretions and excretions of the body bearing upon metabolism in this disease.

That the blood shows great changes in advanced cancer is recognized by all, as is clinically manifested by the intense cachexia and anæmia commonly present and always strongly marked toward the end, of which the cytology has been very fully studied and presented by Türk. When then examined there is found to be a marked reduction of red cells, low hæmoglobin index, and distinct leucocytosis, with greatly diminished alkalescence.

The reported changes in the blood have also varied with the location of the malignant disease, according as it may interfere mechanically or otherwise with the function of certain organs, which fact naturally obscures the question of the true relationship of the blood to cancer. Thus, it is stated that in cancer of the liver and pancreas there is always leucocytosis and glycogen, and that “cancer appears to interfere greatly with the function of the liver as a destroyer of intestinal toxins, they pass into the general circulation, probably cause the glycogen reaction, and at least part of the leucocytosis, and very often give rise to fever.” There are also other microscopical alterations in the blood in late cancer. Thus, degenerative change in the leucocytes are common, with derangement in the normal proportion of their different forms, as also changes in the erythrocytes, with nucleated red cells and megalocytes in severest cases.

Price Jones in a study of the blood in 30 cases of cancer (9 of the breast) found the red blood cells diminished on an average of 6 per cent., the white blood cells increased 38 per cent., lymphocytes increased by 10 per cent., large mononuclear cells increased 164 per cent. and polynuclears 42 per cent. Burnham states that in the severe grades of anæmia with malignant disease, poikilocytosis is marked, and nucleated cells of both normoblastic and megaloblastic type may be present. The red corpuscles may be reduced to 2,500,000, and exceptionally to 1,000,000. Cohnreich in a very technical study of blood from cancer subjects, observed very great increase in the resisting power of the red blood cells to osmotic tension, that is, in regard to their hæmoglobin, which he believed to be of diagnostic value in doubtful cases.

Unfortunately, there have been relatively few studies of the plasma of the blood in this or other diseases; and yet the condition of this fluid must be of the utmost importance, as from it are derived the nutrient principles not only of the solid constituents of the blood, but also those of the entire system, about 8 per cent. of it being serum albumen and serum globulin. It also holds in solution the phosphates, carbonates, sulphates, and chlorides, the latter often varying greatly, and being chiefly responsible for the isotonic relation of cells and serum. In cancerous cachexia a diminution of carbonic acid, a constantly diminished alkalinity, and an increase of acid principles of the blood have been fully demonstrated, pointing in all probability to the existence of an acid intoxication. The formation of the corpuscular elements of the blood must be greatly interfered with when metastases occur in the blood making organs, the lymphatic tissue, bone, marrow, and spleen, which probably occur more frequently than is generally recognized. It seems that the toxic secretion from a cancerous mass has a distinct action upon the blood, for after complete removal there is often observed an increase of hæmoglobin, as I have witnessed, and a high leucocytosis has disappeared after the removal of schirrus of the breast, only to return again with the recurrence of the tumor. Abderhalden states that in from two to three weeks after the operative removal of cancer, certain defensive ferments can no longer be found in the serum.

Many laboratory studies have been made upon the chemistry of cancer tissue, seeking to determine the nature of the toxin produced, and its experimental effect on animals, but thus far no great results have been obtained. It has been observed, however, by Gruner that when cancer juice is injected intra-venously a marked lymphocytosis arises, which is followed by the appearance of large mast cell myelocytes in the blood. This cancer juice is supposed to be autotoxic in cancer patients, and to comprise toxic albuminoids, which being in quantities too great to be quickly neutralized poison the system, especially the blood and the hæmatopoietic organs.

In regard to the real bio-chemistry of cancer, we are still greatly in the dark. Vast numbers of studies and researches have been made to determine the real character and nature of the bio-chemical changes which occur in cancerous tissue, and the mere recounting of the reported findings and theories elaborated from them would occupy far more time than can be profitably given in these lectures. Some have claimed very positive findings which account in a measure, at least, for the pathological conditions, while others, as Beebe, state that “the chemical study of tumors is in its infancy. We have scarcely proceeded far enough to know where the medical problems are, nor have methods now available been perfected to such an extent as to enable a decisive experiment to be made.” “No phase of metabolism,” says he, “has been described in cancer which does not have a counterpart in non-cancerous conditions. This applies to such questions as the nutritive relations between the cancer cells and the normal body tissue, to the nitrogenous balance, retention, elimination of sodium chloride, excretion of acetone, the relation of ammonia excretion, and a possible acidosis.” He adds, however, “Diet doubtless forms an important part in the growth of cancer, possibly even in the origin of the disease.” It is encouraging, therefore, to find that this able and careful laboratory investigator recognizes, in a measure, the basic cause of diet, toward which all evidence points so strongly, although the definite connection may not yet have been established by laboratory methods.

In all our study in regard to the relation of diet to cancer it must be remembered that there are divers elements and agencies which combine to produce the many and various disordered conditions of the body, to which we give the names of different diseases, and that cancer is no exception to this general rule. For instance, in old-fashioned gout the patient may have consumed an excess of Port and Madeira wine for years before the system finally rebelled and acute gout resulted; and among the causes for the systemic reaction we know that frequently it is great mental strain or shock which has so disturbed metabolism that the wine was no longer tolerated. Much the same is true in regard to cancer and nitrogenous diet. And we will see later that mental disturbance and nerve strain or shock often seem to be causative elements; also that constipation, or intestinal stasis, is so common in cancer subjects that it must be looked upon as one of the contributing causes among others, to be mentioned later.

Although it is quite possible that many of the reported bio-chemical changes found in primary cancerous tissue and metastases may not be of etiological importance, it may be interesting to briefly refer to some of them as indicating the vital alteration in tissues connected with what we recognize as malignancy; even as in acute and chronic gout the affected tissues exhibit abnormal conditions in regard to uratic deposit.

Many writers, some of them dating back many years, agree that albuminous constituents predominate in cancer tissue, and, as in actively growing structures in general, sugar forming substances abound. Wolter states that cancer of the breast contains 20 per cent. more nucleo-proteids than the normal breast. Casein is also present in breast cancers, and the abundance of fatty matters, contained in the cells of such neoplasms, is well known. In regard to the proteids, Wolff, after many studies, concludes that their character is identical with that of normal tissues, and it is only the quantitative distribution of these that differentiates the tumor from the physiological tissue. Wells agrees with others that there is no very distinctive character in the bio-chemistry of malignant tumors, but by reason of their excessive chemical component, as compared with benign tumors, they naturally show a high content of nuclear proteins; they, therefore, contain a high proportion of phosphorus and iron.

Interesting observations have also been made on other characteristics of cancerous tissues, such as the great abundance of enzymes of great variety which are actively autolytic, also in regard to certain relations of cholesterin, in regard to which Ewing has recently said, “There appears to be something in the chemical or mechanical nature of the irritation of cholesterin which is peculiarly effective in producing atypical proliferation of epithelium”; this has been found to be no less than 65 per cent. greater in quantity in fatty deposits, as in the mesentery, in subjects of cancer than in healthy persons, etc., etc. It would weary you to no purpose to attempt to refer further to the bewildering mass of research studies in connection with the bio-chemistry of cancer which are found in special literature: much of it is fragmentary and some of it contradictory, but all has its value as contributory to our knowledge of the actual conditions developed in connection with cancer growth; but up to the present time it cannot be claimed that any very practical results have been thus attained which will aid us in treating the disease.