These experiments led us to try an extract obtained from placenta autolysates which, in our opinion at the time, would reproduce, up to a point, some of the conditions present in these experiments. Human placentas were autolyzed by being maintained from several hours to a few days at 37° C, and an alcoholic extract was obtained. The alcohol was eliminated through distillation in vacuum. The residue proved non toxic in animals and was injected intramuscularly in some terminal cancer cases.

Impressive results were observed in the first cases. Pain was markedly diminished and, in some instances, disappeared entirely. Objective changes in the tumors could be noted. While only temporary results were seen for most of these cases, for some the results appeared to last a long time. Their number would exclude pure coincidence.

Mr. H. B., 56 years old, came under our care with a cancer involving more than half of the right part of the tongue. Multiple large submaxillar and cervical gland metastases were present, two of them being approximately 8 cm. in diameter. The mouth lesion was very painful and bled occasionally; there was moderate pain in the ganglionar metastases. A biopsy performed at a much earlier stage had shown a squamous carcinoma. Considered inoperable, the subject had not received any treatment except for pain palliation.

We administered daily intramuscular injections of 5 cc. of the placenta extract. Except for a limited local reaction at the site of injection, no disagreeable effects were seen. On the contrary, after each injection, the pain in the tongue was reduced for a few hours. It disappeared entirely after one week of treatment. During the second week of treatment, the tumor of the tongue, as well as the metastases, began to decrease in size. The local reaction at the site of the injections increased, however, to such an extent that we were obliged to stop treatment after 5 weeks. In spite of this, the lesions continued to decrease so that the tongue tumor was no longer palpable after two months. At that time, the gland metastases were reduced to approximately one and a half centimeters in diameter. The patient's general condition was much improved and he gained weight. In another month, except for a scar on the tongue, no other pathology could be found. We followed this case without treatment for another year and a half during which time there was no recurrence. After that, the patient left town and we were unable to reestablish contact with him.

Mrs. B. A., 44 years old, came under our care with a massive tumor filling the entire vagina. The condition had been diagnosed 8 months previously as carcinoma of the cervix which had invaded the parametria and was propagating toward the vagina. A biopsy made at that time indicated squamous carcinoma Grade III. As the patient was considered inoperable and refused any other treatment, only sedation was prescribed. When we examined her, the tumor was protruding from the vagina as a hard mass. Rectal examination revealed invasion of the entire recto vaginal wall. The patient received a daily injection of the placenta extract preparation for 45 days, after which she interrupted the treatment. The pain had been entirely controlled in less than a week, but no other changes had been observed.

She returned three months later, having received no treatment in the interval. Examination revealed complete disappearance of the vaginal tumor, with the cervix entirely replaced by soft scar tissue. We followed this case for two years, during which no further treatment was given and the patient showed no recurrence.

Mr. A. N., 40 years old had an extensive cancer of the cheek, with massive ulceration resulting in a large communication between oral cavity and exterior. Occasionally small hemorrhagic episodes were experienced. The patient had had several courses of radium therapy. When he came under our care, he had multiple lesions, and several biopsies performed at that time revealed active carcinoma in all lesions tested. The patient received intramuscular injections of 5 cc. of the placenta extract preparation daily for 17 days. A massive hemorrhage occurred at this point, treatment was stopped, and he went home without further medication. When the patient returned three months later, scar tissue covered all areas where the tumor had been seen previously. Clinically no trace of tumor could be found. In a few months, the patient's condition was good enough to allow his surgeon to attempt a skin graft to cover the big opening in the cheek. This was not successful. The graft from the skin of the neck unfortunately underwent necrosis.

In several other cases, similar subjective and objective changes were observed with use of the same alcoholic extract of human placenta autolysates. During this time, we attempted to substitute cow placenta, utilizing both fetal and maternal parts, which are easily separable in the cow. In a relatively small number of cases in which these products were used, we could see no differences in the influence of placenta extract according to origin. Poorer results were obtained with extracts using fresh placenta instead of the autolysate. However, certain interesting clinical results indicated that fresh placenta still has a capacity to influence what can be considered to be the normal course of cancer. The following case is an example.

Mrs. C, 54 years old, had a tumor of the rectum which was considered inoperable. Only a colostomy was performed. Pain was slight and no other treatment was instituted. Several months after the colostomy, the patient came under our care. At that time, the tumor filled the entire rectal ampulla. Treatment with the fresh cow placenta alcoholic extract was started, using intramuscular injections of 5 cc. daily. After less than a month of treatment, the tumor diminished in size, leaving a small passage for the examining finger. After another month and a half, the tumor had entirely disappeared and the rectal ampulla was wide open. Proctoscopic examination showed only normal mucosa. This case was followed for two and a half years with no evidence of recurrence. Thereafter, because of the war, we lost touch with her.

In spite of such results in a few cases however, extracts of fresh placenta were judged to be much less effective in general than extracts of placenta autolysates.

At the beginning of our research, still unaware of the dualism intervening in cancer pathogenesis, we observed a series of cases in which the placenta preparations in general produced undesirable results, such as increase in pain intensity. Furthermore, when used in higher doses over a longer period of time, it induced new pains which clearly increased with each subsequent injection. For a while, this fact made us limit the use of the product to only those patients showing favorable responses in pain, until we could find an explanation for these paradoxical results.

With the progress of our research and recognition of dualism in the pathogenesis of pain, we limited the use of the placenta extracts to patients with an acid pattern of pain. This improved the subjective and objective results, and reduced the cases in which undesirable effects occurred. In over 100 terminal patients treated with this preparation between 1935 and 1938 in different hospitals in Paris, objective improvement was observed in 20%. In a few, tumors disappeared. Acid pattern pain was relieved. In many of these cases, however, after a period in which the tumor decreased in size, or even clinically disappeared, it started to grow again and could not be influenced by further treatment. Furthermore, when the dose was increased, other pathological manifestations appeared. The following cases are examples.

Mrs. B. B., 42 years old, came under our care with severe pain resulting from a widely ulcerated cancer of the cervix involving the parametria and the vagina. 5 cc. of the cow placenta extract was administered daily and the patient remained without pain for almost three weeks, after which time the pain returned. An increase in dosage—to two injections of 5 cc. daily and then to two injections of 10 cc. daily—resulted not only in an increase in pain but also caused the appearance of an abundant watery vaginal discharge. In a few days this reached several liters a day. Despite the fact that we stopped treatment, the exudate continued to increase. At one point, it amounted to 8 liters in 24 hours. The very concentrated urine was reduced to less than 200 cc. in 24 hours. The patient died in ten days in spite of all attempts to stop the excessive secretion.

Mrs. G. L., 48 years old, had a radical mastectomy for a left breast adenocarcinoma. A rapidly growing local recurrence was seen 6 months later. The patient came under our care with an ulcerated tumor occupying the entire left half of the chest. Administration of 5 cc. of cow placenta extract for two weeks not only increased the burning sensation present but caused the appearance of an abnormally abundant watery exudate. As is often true in such cases, an infection with B. pyocyaneus was seen. A clear fluid was observed surging in drops from the ulcerated lesion. By weighing the dressing, the amount excreted was measured and found to exceed 10 kilos a day. Despite use of saline infusions, calcium preparations, vitamin C in high doses, atropine, and other measures, the patient expired in less than a week. The appearance of such complications, the frequent changes toward alkaline patterns of pain, and the increase of intensity of alkaline pattern pain, made us reduce and ultimately stop use of these placenta extracts in spite of some good results obtained.