Circulatory changes in tumors offer an interesting group of clinical symptoms. The observation has often been made, especially in ulcerated new growths, that treatment is associated with swelling, peripheral hyperemia, and an altered character of the discharge. In spite of the fact that there is no reasonable relationship between this congeries of symptoms and the actual cure of the tumor, they generally receive considerable emphasis and are cited as an indication of the specific local action of the agent employed. It is also true, however, that the growth may continue to advance in spite of their presence. It is of some importance to inquire into the mechanism which produces these circulatory changes and into their clinical interpretation. It is a well known fact that many drugs, when introduced into the body either by the mouth or through the skin, are excreted not only by the normal channels of elimination, such as the kidney or the intestine, but also from such ulcerated surfaces as may be present on the body. This is easily shown to be true, for example, of certain of the anilin dyes, which, when introduced by way of the veins, produce an intense discoloration of the dressings over ulcers. It is likewise true of certain of the metals, such as arsenic. In order to understand the series of events previously enumerated it is therefore only necessary to assume that the therapeutic agent is excreted from the ulcerated surface of tumors. If an irritant, it will tend to produce hyperemia of the margins of the ulcer, and an increase of the secretions. If an astringent, however, it may produce just the opposite of these effects. Such a result, however striking, is purely accidental, and has no necessary bearing on the growth or destruction of the tumor itself. It constitutes a symptom on which no reliance should be placed.
Excluding from consideration all of these secondary factors, we may conclude that the observation of the size of the tumor itself is the sole criterion on which we can place reliance in judging of the effect of therapeutic measures. This implies, in the first place, that a tumor must be accessible to fairly accurate measurement. Tumors of the uterus, for example, and intra-abdominal growths will only exceptionally fall into this class. In the second place, indirect evidence of a decrease in the size of tumors, such as is afforded by the increased permeability of obstructed passages, as in the case of tumors of the esophagus, pylorus or intestine, must be accepted only with great reserve. Remissions in the obstructive symptoms characteristic of such tumors are a frequent feature of the normal evolution of the clinical history of such growths. The relief of obstruction, however, may be due either to necrosis of the obstructing portions of the tumor, while the remainder continues to grow progressively, or to a relief of the accompanying muscular spasm. Finally, evidence of decrease afforded by the roentgenogram is not sufficiently exact in most cases to afford ground for so important a conclusion as that at present in question.
Not only must there be unquestionable evidence, however, of the diminution in size of the tumor, but this diminution must be of a kind not ordinarily attributable to the natural evolution of the tumor.... It is safe to say that multiple tumors offer enormous difficulties in the matter of interpreting therapeutic results. At present we have in the wards of the hospital a patient with multiple metastatic carcinomas of the skin. For several months we have at intervals made accurate measurements of certain of these tumors and have found that some have undergone retrogression, others have entirely disappeared, while still others have continued to grow steadily. In the case which afforded the ascitic fluid used in Hodenpyl’s experiments, many of the lymphatic metastases underwent complete retrogression, while the metastatic process in the liver, as was demonstrated at necropsy, increased progressively, and ultimately almost destroyed that organ. Thus, in multiple carcinosis, the retrogression of individual nodules is no indication that therapeutic intervention has produced an improvement.
I shall not delay to emphasize those variations in the size of solid tumors which accompany hemorrhage and its absorption, edematous swelling, necrosis in the depths, and other familiar factors which clinically simulate, or induce, the softening and the reduction that are so often attributed to therapeutic interference. But it is important to draw attention to a similar feature in that type of superficial epithelioma known as rodent ulcer. These new growths not infrequently advance at one point of the periphery, while they recede at another, and thus cicatrization and contracture may simulate a partial recovery. This effect is due in part to alterations not in the growth itself, but in the accompanying ulcerative process. The secretions from the growths, especially if confined under dressings, may have eroded and destroyed the surrounding skin, and it is tempting to interpret a recession of the associated ulcerative disease as an indication of a favorable effect on the new growth. It is unquestionably this aspect of rodent ulcers which plays so generously into the hands of the numerous venders of nostrums for this disease.
In brief, the demonstrable reduction in size of a tumor, of a kind not to be attributed to the natural processes of evolution of that tumor or of its associated lesions, is the one essential feature of effective therapeutic intervention.
When the various methods of treatment which have been discussed in this paper are judged by the standard advocated above, it is apparent that none of them can lay claim to therapeutic effectiveness. The modifications of the disease attributed to them are modifications which occur spontaneously in a very large proportion of cases as a result of the natural evolution of the disease process. This is a fact which cannot be too strongly emphasized. Owing unfortunately to the hopeless character of cancer, men are not prone to study with care all the lesser changes which the disease and the patient present under ordinary conditions; but when a “cure” is under investigation, the patient and his medical attendant note every apparent improvement with painstaking attention and enthusiasm. As a result, some evidence of improvement in treatment is entered on the books.—(From The Journal A. M. A., April 17, 1915.)
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