The good effects obtained with persulfides on one hand, and with selenium on the other, have led us to investigate the corresponding compound—tetraline perselenide. With its low toxicity, the compound was administered to humans in which the destruction of the tumor appeared the immediate aim. The effect upon pain was good although not immediate, the same as for the systemic level. It was at the cellular levels where these were the most manifest. Research with this agent is still in progress and for the moment the influence exerted upon the tumors seems to be very favorable. Similar good results were obtained with naphthalene perselenide and other similar preparations of aromatic hydrocarbons.

Parallel to studies with synthetic negative lipoids, synthetic positive lipoids were investigated. The problem was quite different because of the fundamental differences in biological roles of the two antagonistic groups. Among negative lipoids we singled out an effect against sterol predominance and a destructive activity through the induction of rapid cellular aging.

Photomicrograph of a liver biopsy of patient J.D

Fig. 189. Photomicrograph of a liver biopsy of patient J.D.

Among the positive lipoids, we sought agents able to correct the noxious effects induced by fatty acids. As noted previously, this led to a search in one group of experiments for substances with higher specificity for binding particular fatty acids and in other experiments for substances with broad spectrum acting against acid lipids in general. We have discussed previously the pharmacodynamic characteristics of many of these synthetic positive lipoids. Clinical results have improved with the development not only of new substances but also of new means of recognizing the pattern present and of following the changes that take place. We have mentioned the results obtained with butanol, the first of this group of synthetic lipids with positive character to be used in humans.

Butanol was unable by itself to influence the growth of tumors, although it was effective in controlling pain of an alkaline pattern. This beneficial effect upon pain was still more manifest for other aliphatic alcohols, and especially for heptanol. In high doses, however, heptanol probably acts beyond the tissue level. Besides influencing pain, it induces severe edema and changes in the evolution of the tumor. It has little influence at the systemic level upon hemorrhage, even with high doses. For tumors with offbalance of type D, a mixed treatment appeared indicated. The use of heptanol butanol, however, was not fully satisfactory although it has been employed in some cases with good clinical results.

During the progress of this research, it became increasingly important to have an accurate knowledge of the existing offbalance, and of the adequate use of the available therapeutic agents. The following observations show how the results obtained by the treatment are a function of the correct application of this concept of guided chemotherapy.

M. S.—This 52 year old woman started to lose weight in September 1953 and her abdomen became very distended several months later. An exploratory laparotomy was done in July 1954 at Brooklyn Hospital and revealed a large mass in the lower abdomen with metastases. A lymph node biopsy was performed and showed lymphosarcoma. (Fig. 190) Subsequently, she had 36 X ray treatments, followed by another course of 12 X rays, the last in December 1954. She felt relatively well until the first week in February when abdominal pains recurred. A mass in the middle abdomen, the size of a large grapefruit, could be felt.

Under treatment with sterols, the tumor first increased slightly in size so that by the middle of April, it extended, filling up the entire left side of the abdomen. At the end of the month, the pain became stronger while the abdominal mass remained unchanged. The patient was treated, according to her analyses, with 1 mgm. of hexyldiselenide daily. The tumor became much reduced in size. Pain recurred at intervals and, although only a small mass was still palpable after 1 1/2 years of treatment, the patient's general condition started to deteriorate at that point. Analyses then revealed a change in the pattern present. The treatment was changed to a mixture of higher alcohols—octanol, heptanol and polyconjugated alcohols. The tumor rapidly regressed and, at the beginning of 1957, the mass had entirely disappeared. She continued in good general condition until August 1957 when she had a coronary occlusion. At present, two years later, the patient is in good general condition and without any sign of recurrence of the tumor.

In this case, the first treatment with sterols, using urinary pH as a criterion, brought some subjective improvement but this could also be considered to be the result of the radiation. The improvement was transitory and the appearance of more symptoms, probably reflected the waning effect of radiation. The change to hexyldiselenide brought improvement but could not entirely control the condition. It was with higher alcohols that important objective as well as subjective changes were achieved. The tumor decreased rapidly. Interruption of treatment, due to the cardiac condition, did not seem to influence the favorable progress of the condition.

Photomicrograph of a lymph node of patient M.S. showing a lymphosarcoma

Fig. 190. Photomicrograph of a lymph node of patient M.S. showing a lymphosarcoma.

M. B.—Toward the end of 1950, at the age of 45, the patient began to complain of right lower quadrant and intermittent left upper quadrant pain. She discovered an abdominal mass by herself. In February 1951, an exploratory laporatomy was performed at Lenox Hill Hospital with the following findings: "Situated in the left side of the pelvis, a huge cystic structure the size of a football was found. The superior wall of this mass was attached to the mesentery of the loop of the small bowel. The anterior cyst was attached to the posterior leaf of the broad ligament and contained the left ovary. On the ovary and within the wall of the cyst were several papillomatous structures. On the right side of the pelvis was another cystic mass containing a greenish turbid fluid. This cyst contained the right tube and ovary and on its walls were several papillomatous projections. The parietal peritoneum, the liver and omentum were studded with tumor implants and several sections of bowel were matted together by the same tumoral tissue. Biopsy specimens were obtained from several areas."

The gross pathological diagnosis was papillary carcinoma of the ovary with metastases to peritoneum, liver, intestines and duodenum. The report on the frozen section was malignant. Microscopic examination confirmed the diagnosis given at the time of the operation and revealed a fibroid fatty tissue extensively infiltrated by a malignant neoplasm of epithelial origin.

The patient came under our care 11 days after her operation. The abdominal mass was palpable, rising from the pelvis to a level slightly above the umbilicus. Vaginal examination revealed large cystic masses filling both fornicis and cul de sac. The pelvic structures were partially fixed. The urinary specimen showed a pH between 7.4 and 7.8 and the surface tension was 68 to 71 dynes/centimeter. Treatment was instituted with a mixture of conjugated fatty acids, derived from cod liver oils, and a preparation of hydropersulfides as well as sodium thiosulfate. The first preparation was administered intramuscularly in a 5% oil solution in doses of from 2 to 4 cc. daily. The sulfur preparation (corresponding to 0.5% sulfur) and 10% solution of thiosulfate were administered in doses ranging up to 6 cc. daily. The treatment was continued without change for 1 year and 8 months. The abdominal mass was found somewhat smaller a month after starting treatment. A month later, a surgeon's report showed that the tumor was about 1/3 the size at the time of operation. After several months, no mass could be felt on abdominal and vaginal examination. After twenty months, the treatment was discontinued for one year. At the conclusion of this period, the patient began to relapse and a cystic mass in the cul de sac, palpable under finger examination, was found. Treatment with the same medications as before was instituted but did not change the dimension of the recurring tumor. Despite treatment, the tumor continued to grow and in April 1954, the abdomen was distended. X ray also revealed a large liver and elevation of the right diaphragm. The patient was readmitted to Lenox Hill Hospital where a small abdominal incision revealed two masses, one above the liver and another one in the lower abdomen. Fluid reac cumulated rapidly and the patient's general condition became poor. On several occasions it was necessary to tap the subdiaphragmatic cyst and lower abdomen separately as emergency procedures because of acute distress.

Because analyses now showed a low pH (around 5.2) and low surface tension (around 61 dynes/centimeters), and also because she had obviously failed to respond to conjugated fatty acids, treatment with butanol and nonsaponifiable lipids of intestine was instituted. By July the situation appeared to have been brought under control again. Fluid was no longer accumulating and leg edema, which had been pronounced, was gone. At the end of 1954, no masses could be felt. The subjective complaints disappeared slowly. In February 1955, the nonsaponifiable medications were replaced by heptanol and octanol. The patient continued to improve with this treatment. In March, the abdomen was a a little swollen. By the end of April, a mass could be found in the abdomen just above the umbilicus. At the end of May the mass had increased and the patient was hospitalized for about three weeks. A large bloody cyst was drained. A small lymph node was biopsied and microscopic examination showed the same metastatic adenocarcinoma. (Fig. 191) The patient was put on epichlorohydrin and the mass did not grow back. She has remained on epichlorohydrin and for four years has had no subjective discomfort. No mass can be felt in the abdomen and the patient is well now.

Photomicrograph of a lymph node biopsied from patient M.B. showing metastatic adenocarcinoma

Fig. 191. Photomicrograph of a lymph node biopsied from patient M.B. showing metastatic adenocarcinoma.