Coley's Toxins Research Articles

USE OF COLEY'S MIXED TOXINS IN OPHTHALMOLOGY

In a previous issue of theArchives 1 appeared my first report on the advantages of Coley's mixed toxins as a foreign protein in ophthalmologic therapy. In that article a resume of the history of foreign protein therapy was given, and the various proteins used in ophthalmologic practice were discussed. What is the preparation known as Coley's mixed toxins? It is a vaccine made from killed cultures of Streptococcus erysipelatis and Bacillus prodigiosus. It is in extremely concentrated form, a red-colored fluid put up in rubber-capped glass vials of 1 cc. and 15 cc. capacity by Parke-Davis and Company. It keeps well in an icebox, and the expiration date printed on each vial can be ignored, as the fluid does not lose its efficiency over a period of several years. How is it administered? These mixed toxins are given intramuscularly, and the deltoid muscle is used

Osteogenic Sarcoma of the Clavicle Treated with Radiation and Fever Therapy

The results of the treatment of osteogenic sarcoma have always been disappointing regardless of the therapeutic method employed. Amputation, followed by irradiation or Coley's toxins or both, has been the method of choice by several investigators who have recorded their results in the treatment of these cases. The administration of Coley's toxins, which consist of mixed toxins of erysipelas and Bacillus prodigiosus, is usually followed by definite elevation of the patient's temperature, with the usual symptoms of foreign protein reaction. We have felt for some time that the fever might be the active agent in whatever beneficial result was obtained from the use of these toxins. If this were true, the fever could be produced and controlled much more surely and exactly by mechanical means at our disposal than by the introduction of toxins into the body. The results of the work of Warren (1) in attempting to determine the thermal death time for transplantable animal tumors would seem to present experimental evidence that high fever can have a definite deterrent effect upon tumor cells. In the case under consideration the tumor involved the clavicle, which is a difficult site for excision. It was decided, therefore, to administer both fever therapy and irradiation therapy in the hope that the fever therapy might render the tumor cells more radiosensitive. Fever therapy was administered at weekly intervals and deep x-ray therapy at intervals of two months. Case Report Male, aged 30, laborer, first seen at this hospital Jan. 17, 1934. History of mild injury to shoulder two months previously, with later some swelling which disappeared and recurred several times. Two days before examination while opening a car door, he experienced pain in the region of the right clavicle which persisted on motion. Examination revealed a mass about two and a half inches in diameter near the inner third of the right clavicle. There was no redness of the skin, but considerable tenderness. The mass was hard but not movable. The shoulder drooped and there was loss of active motion in the shoulder. X-ray examination of the right clavicle revealed a pathological fracture of the clavicle at the junction of the middle and inner thirds. The bone edges had a moth-eaten appearance with considerable decalcification. There was evidence of some periosteal bone production along the superior margin of the bone. This suggested a primary sarcoma of the clavicle. A biopsy of the tumor was then done and a diagnosis of osteogenic sarcoma was returned. The x-ray examination of the lungs was negative for evidence of metastases. The Wassermann was negative. All other examinations were negative. Therapy.—This consisted of four series of deep x-ray therapy applied through the tumor anteriorly and posteriorly, using 200 K.V. with 0.5 mm. copper and 1 mm. aluminum filtration at 50 cm. F.S.D. A full erythema dose was applied anteriorly and approximately three-fourths of that amount posteriorly.

Large malignant tumor (sarcoma) of the uterus with multiple bone metastases (femur, pelvic bones and skull): A case successfully treated by hysterectomy and Coley's toxins

Large malignant tumor (sarcoma) of the uterus with multiple bone metastases (femur, pelvic bones and skull): A case successfully treated by hysterectomy and Coley's toxins

Results of Irradiation in the Treatment of Operable Osteogenic Sarcoma of the Long Bones

UP to 1923, the results following surgical treatment of periosteal or subperiosteal sarcoma, now classified as osteogenic sarcoma, were bad, one reason for this being that the diagnosis was not often made until the disease had reached such an advanced stage that there remained little hope of saving the life of the patient by amputation or other form of treatment. In a review of the statistics of various European clinics, mostly in England and Germany, Butlin (1) found only one three-year recovery in 68 cases of periosteal sarcoma of the femur treated by hip joint or high amputation, and not a single recovery in sarcoma of the humerus. Little improvement in results was noticed until 1920. In 1922, Meyerding (2), of the Mayo Clinic, reported 15 five-year recoveries in a series of 100 cases of sarcoma of the long bones, exclusive of giant-cell tumors, treated by amputation. In many of these cases, amputation was followed by prophylactic treatment with Coley's toxins, and in a number, by irradiation of the chest. An improvement in results was noticed in the European clinics also. In May, 1923, at a Symposium on Bone Sarcoma by the Association of Surgeons of Great Britain and Ireland, held in London, Gask reported 57 cases of sarcoma of the long bones, exclusive of giant-cell tumors, that had been admitted to St. Thomas' Hospital during the period from 1901 to 1921. In 46 cases amputation was performed; 12 patients were alive three years later; 7 were well for more than five years, and one died of metastasis to the skull almost seven years after amputation. These are exceptionally good results, and yet, when Meyerding read his paper at the meeting of the American College of Surgeons in 1922, Besley, of Chicago, who took part in the discussion, stated that he had amputated the limb for sarcoma of various types in 20 cases at the Cook County Hospital, and that, as far as he had been able to learn, there had not been a single permanent recovery. He added: “I have performed my last amputation for sarcoma of the long bones.” Only a few years later one of the most distinguished professors of pathology in America told me that if he personally had ever had a sarcoma of a long bone he should have an immediate amputation performed regardless of the histologic type of the tumor. Here we have two widely divergent views regarding the best method of treating sarcoma of the long bones. In further proof of this I would cite Crile (3), whose recent study of 7,390 cases of malignancy (of which 160 were bone sarcoma) has led him to the following conclusion: “It is still uncertain whether a primary malignancy of bone should be treated by x-ray or by surgery, but two things are certain—first, if an operation is performed, it should be preceded and followed by x-ray radiation, and second, if the condition is in a limb, amputation should immediately follow radiation, provided the condition is not inoperable.”

The Treatment of Flexner-Jobling Rat Carcinomas with Bacterial Proteolytic Ferments

In this paper a report is made on the results of treatment of experimental tumors in white rats with certain bacterial proteolytic ferments. The tumors were the Flexner-Jobling carcinoma type and the proteolytic ferments employed were those of certain spore-bearing anaerobes (B. sporogenes and B. histolyticus). The purpose of the study has been to find a tissue-destroying agent of bacterial origin which would have a selective action, at least in some degree, on tumor cells and which might eventually be applied to certain types of human neoplasms. Although this result has by no means been attained as yet, our findings would seem to be of sufficient interest to warrant a report, especially in view of the fact that, as far as we are aware, this particular mode of tumor treatment has not been attempted heretofore. The nearest approach is perhaps the Coley toxin but the principles involved are entirely different; with the toxin the tumor destruction is entirely dependent on the reaction of the body, whereas with these ferments the body takes no part in the lytic action, as far as we are aware, and direct application in full strength to the tumor tissue is necessary. This investigation has been carried on, as time has permitted, for several years and is being continued along somewhat different lines.

The Use of Coley Toxins in the Treatment of Sarcoma

The Use of Coley Toxins in the Treatment of Sarcoma