We saw in our last lecture that surgery had failed to check the rising mortality of cancer, and that during the year 1915, in the United States Registration Area, the death rate had augmented from 79.4 to 81.1, or an increase of 1.7 persons in every 100,000 living; this was a greater increase than the average rise in the death rate for the preceding five years which was only 1.2 points. This, moreover, occurred during a still active period of laboratory research, with wide publicity as to cancer control, by education as to the benefit of early operation, and with active and skilful surgery.
We saw that fully 50 per cent of all cases of cancer were quite inoperable when first seen by competent surgeons, while the average end result, or cure, in the cases operated on, for all kinds together, good and bad, slight and severe, did not total as much as 25 per cent; this makes but 12.5 of the entire number who applied for surgical relief. We quite naturally asked, therefore, if some form of medical treatment, including diet and hygiene, could not afford a better prospect of arresting this fearful mortality. It is especially in regard to the large number of inoperable and recurrent cases, comprising over 60 per cent of the whole, that this inquiry is particularly important. We will briefly consider these latter sad conditions.
Looked at from its broadest aspect, in connection with what I have tried to show here and on former occasions, all cancer will be inoperable, or rather, not needing operations, when the principles I have tried to develop are fully elaborated by the wide experience of others, and when they are firmly established, and correctly carried out. For when it is universally realized that it is the errors of life, determined and accentuated by advanced civilization, so-called, which lead up to and cause cancer, and when public education has been advanced along correct lines, the tendency to cancer will diminish and there will be fewer cases, either operable or inoperable. The former will melt away under correct internal and external measures, and the latter will be helped by, or slowly yield to the same, unless the malignant process has already progressed beyond the possibility of retrogressive metabolism. But, of course, it is too much to expect that such longed for results will be fully attained within a generation or two.
Inoperable cancer is truly a most distressing condition, especially after it has become so after one or more surgical operations. The hopelessness and despair of the patient when told that no operation is possible is bad enough. But when with recurrence, time and again after repeated operations, it is decided that no further relief by the knife is possible, the despondency is indeed pitiful—especially as ordinarily one can only look forward to a sure and most painful death, at a not very distant day. It is very difficult to convince many of these patients that medical treatment, including diet, can do any good, so firmly fixed is the idea that an operation is the only possible remedy; many, therefore, get weary of the restraint necessary when immediate results are not seen. And yet in my previous lectures I gave several such cases to show that much can be done medically along these lines, even in these distressing cases, and later shall hope to narrate other instances, similar to those reported in my lectures two years ago.
It is undoubtedly true that some of these cases which are inoperable when first seen could have been operated on at a much earlier period, with as much success as follows in those in which this is tried. But we have already seen in the last lecture how small a proportion of these selected cases survive a long time; for we have yet to find statistics regarding those who have been traced even as long as ten years. In my previous lectures I reported concerning two patients with undoubted cancer of the breast who had been watched for sixteen years, with no trace of the trouble remaining, and two others who had been seen each for nine years; these latter have been watched since, and have been seen recently, eleven years after beginning treatment, with the same results, all without operation. These cases had all been diagnosed as undoubted cancer by competent surgeons, some eminent, and had refused operation, which had been urged. Later I shall hope to relate other similar instances of early cancer.
Inoperable cancer, comprising at least 50 per cent of all cases applying to the surgeon, presents many features of interest and worthy of consideration. The reasons for inoperability may be grouped as follows:
1. Those occurring in regions quite inaccessible, as in the brain, esophagus, liver, pancreas, etc.
2. Those otherwise accessible, but which have advanced too far before seeking surgical relief, occurring in many locations.
3. Those in accessible regions where experience has shown that recurrence is pretty sure to take place, such as advanced cases in the oral cavity, bladder, prostate, etc.
4. Those which have recurred after repeated operations, with extensive spreading of the disease, as in many cases of the breast, uterus, etc.
5. Those with already very great metastatic involvement, in many regions, presenting a true carcinosis.
6. Those in close proximity to or involving vital organs, blood vessels, ureters, etc.
7. Those in which there are other reasons, such as advanced age, lowered vitality, great cachexia, etc.
8. Those who absolutely refuse to be treated with the knife.
There is no necessity of troubling you with details as to the character or appearance of inoperable cancer, which are dwelt on in standard works, as our study relates rather to the causes of the disease and the means of arresting its progress.
Nor need I dwell much further on this distressing aspect of cancer, for I believe that all see the necessity of seeking some other measures than operative surgery to aid in solving the question of relieving the present condition of affairs. It is for this mass of otherwise hopeless cases that any reasonable method of treatment is worthy of serious consideration, both for the measure of relief which may be secured along many lines by exactly the proper care, and especially for the possibilities of its value in regard to prophylaxis.
Unfortunately it must be acknowledged that many claims, quack and other, have been put forth in times past for remedies and measures which would control or remove, and even cure, the disease in all stages. But the failure of each in turn has very naturally discouraged many from accepting any new proposition, and the profession and laity have almost given up the hope for a real cure of cancer.
In the present instance, however, there is no attempt to present or urge any single means or measure as a cure-all for cancer. But there has been an endeavor to study the fundamental causes of the disease along biochemical lines, and to meet intelligently the errors found. We have seen cancer developing more and more as the ill effects of modern civilization have manifested themselves, and have found that its increase has kept pace coincidently with and even exceeded that shown by certain other diseases, cardiac, arterial, and renal, which are recognized as due to errors of living; and there is every reason to believe that cancer is of the same origin. In a later lecture I shall hope to show how some of these errors may be overcome, with the consequent cessation of the cancerous process and even the disappearance of the malignant lesion already formed.
Recurrent cancer represents only the continuance and further operation of the internal or systemic causes which induced the formation and development of the first lesion, and are a natural sequence therefrom. Otherwise why should there be such an almost universal tendency of the disease to redevelop either in the same or other localities? It is granted, of course, that the very complete ablation of an early tumor and its surroundings removes a focus in which disease has started, and from which is generated a hormone or poison which tends to further lower the vitality of the blood. But this does not by any means reach the basic cause, as we saw in the former lectures.
In estimating, however, the real value of an operative procedure, which has seemed to be successful for some period of time, we must also inquire if there has not been some other cause which may account for the absence of further cancerous deposits? It is more than likely, in successful cases, that the previous occurrence of the disease and the fear of recurrence have so modified the life of the patient in many respects, that the primal cause is more or less removed. It is incredible to believe that the mere removal of the portion of tissue in which the systemic disorder has localized can forever prevent a new focus from developing. As well might we expect that the removal of a gouty toe, a tubercular deposit, or a late syphilitic gumma would inhibit further manifestations of the disease.
Recurrent cancer, then, is but the result of a continuance of the operation of the same causes which produced the first local lesion, and need surprise no one, if those causes are left entirely unchecked and the system unchanged. Undoubtedly in many instances the recurrence, or increased production of the disease, is made more certain by the operation itself; it is also recognized that handling or manipulation then or at any time may also contribute to this, as may be understood from the following:
1. Cancer cells, which have a reproductive capacity, may be forced into the adjoining tissue, or find entrance into blood vessels or lymphatics severed during operation, and there continue their activity and produce new lesions.
2. By implantation, cancer cells, already started on their reproductive career, may be transferred to freshly cut surfaces, and there may develop new lesions, favored by the continued derangement of the blood current.
3. Cancer cells may have existed outside of the immediate area which was removed surgically, and so may continue to develop new lesions, being further stimulated thereto by the manipulations attending the operation.
4. We know, finally, that the occasional removal of lesions which are afterwards shown microscopically to be benign, such as adenoma, cysts, chronic mastitis, etc., will sometimes be followed by the development of true cancer, which will then pursue a malignant course.
On the occurrence, therefore, of any lump or lesion which might possibly be or become cancer, the greatest caution should be exercised to avoid all manipulation, lest a spread of the disease should render it more rebellious to treatment. For in the medical management of cancer it is naturally more difficult to cure a patient when there are large numbers of diseased cells, in one or various locations, which are already giving forth their poisonous hormone, vitiating the blood stream.
The New York Board of Health has recently inaugurated a service for the examination of specimens excised from suspected cancer, in order to establish the diagnosis microscopically before surgical operation. There could hardly be devised a more effective plan to increase the mortality from cancer and to render many more cases really inoperable than this one would surely be; for by thus cutting into cancerous tissue and opening lymphatic channels and blood vessels, with the opportunity for absorption of cancerous elements during the necessary delay, metastases would certainly be induced which would render a surgical removal or a dietary and medicinal treatment immeasurably less effective. It is to be hoped that this scheme will be immediately abandoned.
Recurrence of cancer is far more common during the first year after operation than in any other single year, but, as we shall see shortly, there is no time limit when the disease may not manifest itself anew. It is understood, of course, that recurrence depends also largely on the previous duration, extent, and malignancy of the tumor, and exact statistics are very few and imperfect in regard to these matters.
It is well known that not long ago three years was considered as the time at which, if there had been no recurrence, the cancer could be considered as cured, and very many statistics have been based on this period. But with further experience and closer observation, and with more diligent following up cases, it was found that recurrences did take place more or less frequently at subsequent periods, and now the time limit has been arbitrarily extended to five years. This is because the very large proportion of recurrences are in the first year, varying for different locations and conditions from as high as 50 to 80 per cent in different statistics.
But as the patients who have lived out the five-year limit are followed up more carefully, it is found that recurrences do happen all along the following years, so that they are recorded as occurring 6, 8, 9, 20, and 25 years after operation; I have met with many after 3 or 5 years, and even as late as 15 years after operation. The vast majority of cases, however, are not thus accurately followed out, much less reported, and thus far we have few data on which to make accurate statements as to the actual permanent cure of cancer by the knife.
Recurrent cancer, as one constantly observes it, is most deplorable, and many who have had much to do with these cases realize that the distress is often far greater than in other cases in which the disease has run a natural course, without operation and under good medical guidance. The pain attending growths in scar tissue is generally intense and commonly requires anodynes continually and increasingly; these in turn, by disturbing digestion and locking up the secretions, seem to augment the disease. Even with these patients, however, very much may be done to relieve their suffering by proper dietary and medicinal means, with suitable local medication, as I have constantly seen, so that opiates need be but little used.
Metastases form a very considerable and important element in inoperable and recurrent cancer, and we will briefly consider these. They occur mainly through three channels: 1. The lymphatic system; 2. The venous system; and 3. The arterial system. The permeation theory of Handley relates to direct extension laterally through lymphatic spaces, and belongs to the first mentioned means of extension. It is also believed that metastases may be formed in the peritoneal cavity, and likewise in the pleural cavity, by direct contact of cancer cells or pieces of malignant tissue which have gained access to those cavities and have been carried down by gravity and movement of viscera. They then become engrafted on healthy tissue and form metastases there.
While holding firmly to the belief that the original cancerous growth and other foci of disease are developed from a vicious state of the blood current, there seems to be no reason for doubting that the disease may also be extended in the manner above indicated. Although cancer material cannot be inoculated from one person to another, or from a human being to animals, nor from one species of animal to another, experience and observation show that the malignant process can be transferred from one organ or structure of the same individual to another part or structure, whether there has been a surgical operation or not.
The lymphatic system is apparently the first means for the spread of the malignant process, and all are familiar with the lymph nodes seen in the neighborhood of cancerous masses. It is supposed that these are caused by the lodgment of detached cells which have taken on the abnormal reproductive action which characterizes cancer. As with other foreign bodies, pus cocci, etc., the minute lymphatic glands seek to arrest their passage into the circulation, and it is probable that some of them are destroyed there, for the single enlarged gland will often remain for a long time as the only manifestation of metastasis. In many cases, where the original cancer has disappeared under dietary and medicinal treatment, the enlarged glands also disappear, as I have seen many times.
When the disease is unchecked, however, the glands fail in their endeavor to protect the system and continue to enlarge one after another along the line of the lymphatics, and the lymph stream then carries certain cancer elements through the thoracic duct into the venous circulation; thence they reach distant parts of the body, through the arterial system, and, being lodged in capillaries, a more or less general carcinosis results. Cancer elements can also proliferate along lymphatic tracts, and, furthermore, they may enter the venous and arterial systems directly by the invasion of a malignant growth.
All these and other points regarding the metastasis of cancer form a very interesting study, but time does not permit of further elaboration. All know that while primary carcinoma of the liver is very rare, its secondary or metastatic involvement is very common. The bones, lungs, spleen, kidney, and viscera generally are all often found to be the seat of metastases, and in general carcinosis, which has lasted some time, metastases will be found abundantly both in the lymphatics of many parts of the body and in many organs and tissues. Metastases in the lungs are not uncommon in breast cancer, as also metastasis in the bones of the thorax. In the last lecture reference was made to the frequency of metastases in the skeletal structures of the body, which probably have much to do with the pernicious anemia which carries off the patient.
An interesting study relates to the extension of the carcinomatous process in the skin; this occurs at first near, and then around, and even at a distance from the site of an operation, especially after removal of the breast. These nodules are at first small, and felt deep in or below the skin, and are not colored. They steadily increase in size, and when about that of a small pea, they become red and elevated a line or so. Later they may appear more numerous and even involve a large area, forming the so-called cancer en cuirasse, and may ulcerate. Sometimes single lesions of some size may appear here and there, even some distance from the site of the original tumor, and may not be colored. While these may represent lymphatic infarctions, it is often impossible to trace any direct connection with lymph ducts, and they more probably arise from capillary deposits of cancerous elements. I have frequently had these scattered cutaneous lesions excised, in cases under medical treatment, with a view of removing mechanically some of the foci from which the disease could be spread. The wounds have invariably healed promptly and perfectly, and no carcinomatous process has resulted.
The BLOOD IN CANCER has been studied mainly in reference to its solid constituents, and very little in regard to its plasma; whereas it is from the plasma that the blood corpuscles are formed, and this is the principal agent in the development and nutrition of tissues, normal and malignant. For it is to be remembered that the chyle is discharged directly into the venous blood current, and the venous radicles absorb much of the nutritive material directly from the abdominal organs. The plasma, therefore, carries with it constantly a varying quantity of partially assimilated material to be oxidized in the lungs, and slowly purified by the agency of the kidneys; the serum albumen and serum globulin are also active agents in the formation of tissue, malignant or other. There is great need of laboratory studies along these lines, and also on the alkalescence of the blood, which we found to have a marked diminution in cancer.
We know also comparatively little in regard to the origin and destruction of the cellular elements of the blood, and can only depend on the microscopic examination of their forms and appearances in health and in many conditions of disease. These have been abundantly studied morphologically, but mainly in the more severe forms and later stages of cancer, as detailed somewhat in my former lectures. Enough was there quoted to show the continued degeneracy of the blood after a cancerous growth had acquired some progress; there has also been observed some improvement for a while after the removal of a tumor, evidencing the deleterious effect of the hormone secreted by a cancerous mass.
The laboratory study of the blood from 22 of the cancer patients in the New York Skin and Cancer Hospital under my care, has been instructive as well as valuable along certain lines. In most of them it was made weekly, and often over long periods of time, and the results tabulated for easy comparison, in order to study closely the condition of the patient and the effect of remedies. No very startling revelations were made by these blood studies, they confirmed in the main the observations of others, though some interesting facts were learned from an analysis of the data. They referred to ten cases of cancer of the breast, four of the stomach, two of the uterus, one of the rectum, one of general abdominal carcinosis, and the rest in scattered locations.
The lowest hemoglobin index was 35, with 2,800,000 red blood cells, in a woman aged 59 with cancer of the stomach. The next lowest hemoglobin index was 45, with which the patient, aged 53, died, with inoperable cancer of the right breast; the blood count showed 3,700,000 erythrocytes, and 10,400 white blood cells, 76 per cent of which were polynuclear. During the course of observation, covering several months, the red blood cells were once 2,100,000, but under careful treatment rose to 4,110,000 not long before death. The next lowest red cell count observed was 2,200,000, with 12,000 white blood cells, and 65 hemoglobin index, in a man aged 52, with a terrible inoperative cancer of the cheek and neck, of which he died.
The highest red cell count made was 5,400,000, in a case of cancer of the uterus, in a patient aged 52, the count being 4,064,000 on entering the hospital. The highest hemoglobin index was 90 in a number of severe cases, and 100 in one case of sarcoma, to be detailed in the next lecture. In one recurrent case of cancer of the left breast, which was very distressing at first, the patient died peaceably and without pain, with a hemoglobin index of 90, and 4,900,000 red cells, and 7,400 white cells, of which 75 per cent were polynuclears, 17 per cent small lymphocytes, and 7 per cent mononuclears. Her hemoglobin had been 70 per cent on entering the hospital with 3,360,000 red cells. The highest leukocyte count observed was 18,600 in a case of inoperable cancer of the right breast, not long before death, in an unmarried female of 53; but in the course of treatment it had fallen to 6,200, about normal, from 10,520 before beginning treatment.
I will not weary you with more of these figures, which are interesting and instructive as one studies them week by week in connection with the physical condition of the patient. However much can be done for these distressing and inoperable cases of cancer, one has to acknowledge that when general carcinosis has set in we are still helpless in arresting the lethal progress of the disease, although very much can be done in prolonging life and alleviating suffering; and this does not mean with morphia or codeia which in the end does harm, and was very seldom administered to the patients referred to.
Forbes Ross, after ten years of constant microscopic clinical and surgical research, has made some interesting observations, covering many pages, on the blood of cancer patients, which have a close bearing on our subject, and to which I can only briefly allude, and I do not know if I can make it clear in the time I can give to the subject. By long study of sections of carcinomatous tissue he claims that the mononuclear leukocyte behaves in a very different manner from the polynuclear. Briefly he charges the mononuclear white corpuscles with actually producing the disease, by conjugating with certain epithelial cells, thereby giving them the reproductive capacity which enables them to push forward on their destructive career. The polynuclears seem to come up to the defense of the body, but are overcome by the poison secreted by the rapidly growing tumor cells.
The red blood cells he also finds, with other observers, nucleated more frequently in cancer than in any other form of secondary anemia, and subject to a change of composition, and deficient in lecithin and nuclein. He shows the importance of potash, which we shall later find clinically of such great value in cancer, and I cannot do better than quote some of his words: “How vitally important potassium salts are to the red corpuscles is shown by the following: One thousand parts of red corpuscles are found to contain six hundred and eighty-eight parts of water, three hundred and eight parts of organic solids, and eight parts of mineral. Of these eight parts three and one half are of potassium chlorid, two and one half are potassium phosphate, and decimal one potassium sulphate; the remaining 1.9 parts are divided between the iron, sodium, calcium, and magnesium, comprising the rest of the corpuscles. More than three quarters of the total mineral ash of the red corpuscles is, therefore, composed of potassium. This fact is an important one, and the reader is earnestly requested to bear it in mind.” Later we will again see some of the valuable clinical suggestions which arise from his researches.
From our study of inoperable and recurrent cancer, and of metastasis and the blood conditions in the disease, we see what a formidable task is before one who would attempt to lessen its morbidity and mortality. We see also how blind all have been who have so long looked to surgery to stay its progress. In my former lectures I collected and quoted statements from many surgeons of prominence in times past, and even some in quite recent times, all expressive of a belief in a constitutional origin of cancer, and many of them looking to a dietary cause. I also gave biochemical laboratory and experimental evidence showing the medical aspects of cancer. I then remarked that it seemed strange that the medical profession and the public had been so slow in accepting and acting on the accumulated evidence which I have tried to put before you in these and the former lectures.
The reason for this seems to be that the medical profession, being occupied largely with acute disease and apparently definite and speedy results, became readily discouraged with the unsatisfactory course commonly observed in cancer; as in the case of tuberculosis, until the revival of an interest in the latter in recent years, with the well known beneficial consequences. They, therefore, turned the cancer cases over to the surgeons, in the hope that they could do better.
By the brilliant advances in modern surgery along many lines, the laity also have become obsessed with the idea that it has limitless power in many directions, and have yielded to the knife in spite of the rising mortality of late years. The glamour of modern surgery and its often spectacular results have quite blinded the eyes of many to real facts.
It is not a little interesting to note that the period to which we have referred, 1910 to 1915, in which the mortality of tuberculosis has fallen so steadily while that of cancer has so steadily risen, even in greater proportion, is that in which active laboratory work has also dazzled the public and professional mind. The enormous activity with the microscope in regard to the minute structure of the diseased tissues, and the elaborate and extensive work done in animal experimentation, have turned the thoughts of many from the homely and practical studies of the human frame in its various departures from health; thus too little attention has been given to the deranged activities of its various organs, and the perverted metabolism which, has resulted from the stress and strain, with the temptations and errors accompanying the present intensity of human civilization.
Matters being as they are it is hardly to be expected that the surgeons would incline to any other treatment than by the knife, especially since good pathologists have asserted that cancer is only a local affair and have urged its early removal. Nor would one expect that the surgeon would think along medical lines and investigate metabolic conditions, when the immediate results of operation seemed often to be so satisfactory. Neither would one expect the surgeon to seek from statistics the unfavorable aspects of this line of treatment, but rather those from which he could draw encouragement in trying to overcome so dire a disease.
But slowly light is beginning to shine, and you have seen and heard enough to realize that the simple removal of the product of the cancerous process, and surrounding tissues, can never check greatly the morbidity and mortality of cancer. You know now what the real cancer problem is. It surely is not the sole continuance of a line of treatment under which the death rate has steadily risen from 63 to 81.1 persons in each 100,000 living, or 28.7 per cent since 1900, with a mortality of about 90 per cent of those once affected with the disease.
The cancer problem is by no means yet solved, but I think that you will all agree with me that we are on the right track, and I cannot do better than to close with a remark I made to you two years ago: “Scientific research must still go on in the laboratory; but clinical research and study, with laboratory work, on the human subject, which have not been hitherto sufficiently cultivated, should be pushed, so that by a mass of carefully recorded observations the truth or falsity of what has been here quoted and said may be refuted or confirmed.”