Warren H. Cole

Spontaneous regression of cancer: the metabolic triumph of the host?

Although the existence of “spontaneous” regression of cancer remains a doubtful phenomenon to many physicians, it appears that as the years go by, more are willing to concede that the phenomenon truly exists. The explanation for the increase in credence probably is that many more cases have been reported with unquestioned diagnosis (supported by adequate biopsy confirmation) and with undisputable evidence that no significant therapy had been performed. At any rate, this author is firmly convinced that the phenomenon exists. Boyd,’ who has probably devoted as much or more attention to the condition as anyone, remarks that to shut your eyes and refuse to believe in spontaneous regression of cancer is as absurd as the attitude of Pasteur and Lister’s critics, who refused to see the evidence so plainly demonstrated to them. Also one of the world’s greatest clinicians (Sir William Osler2) believed sufficiently in spontaneous regression to publish a paper that described the regression of metastases in two patients with carcinoma of the breast. The first patient had a radical mastectomy by Dr. W. Halstead in October 1897. The axillary nodes were involved; histological confirmation was obtained. Evidence of metastases developed a yeaT later, with pain in the back and down the legs, a lump in the other breast, and a mass in the sternal area. She began to improve shortly thereafter until, when seen two years later by Osler, she was completely well and the sternal mass had disappeared. The second patient developed evidence of spinal cord or nerve involvement 18 months after mastectomy, with complete paralysis of the lower extremities. Shortly afterward she began to improve; she regained use of her extremities but retained some stiffness of the back that required the use of a cane. I wish to emphasize that the term “spontaneous” is a misnomer, because there is obviously a cause of the regression, but it is not known, thus justifying the term idiopathic or biological. Evidence is accumulating to indicate that the causes of regression may be as numerous as the causes of cancer, and as the years go by the causative factors appear to be increasing. It is difficult or impossible to estimate how commonly spontaneous regression occurs, but Bashford3 has been quoted as saying that it occurs about once in 100,000 cases of cancer. Boyers4 has estimated that it occurs approximately once in 80,000 cases. If the truth were known, the present author believes it occurs much more frequently than that. The basis for this statement is that during recent years it has become more difficult to find patients with cancer who have not been treated. Yet, this decrease in the percentage of untreated cancer patients does not appear to have decreased the incidence of regression. The number of acceptable cases found by Everson and myself5 has increased during the last 15 years of our study (see TABLE 1 ), but, as stated in the legend, this is no index of frequency. It is quite possible that many of the patients we have treated successfully might have developed a period of regression at one time or other if no therapy had been given; it is impossible to determine how often this might have occurred in these cases treated by us.

Inhibiting and enhancing effect of various chemical agents on rat's resistance to inoculated Walker 256 tumor cells

Summary In our experiments, histamine did not play a major role in increasing the number of tumor takes in rats inoculated with an approximately 50% take level of Walker 256 cells. Conversely, antihistamines were found to cause a marked enhancement of takes, confirming the fact that tumor substances contain antihistaminics which are important in the enhancement of Walker 256 tumor in rats. Vitamin B 12 may have a role in enhancement of takes in this experimental system. Reserpine, the serotonin antagonist, had significant effect in decreasing tumor takes.

The development of cholecystography: the first fifty years.

Visualization of the gallbladder by x-ray was first achieved in 1923 by the intravenous introduction into the body of a halogenated compound which was excreted by the liver into the bile ducts and gallbladder [1--4]. This was the first time that visualization of an organ had been accomplished by introducing a substance into the body and obtaining a roentgenogram after the substance had been metabolized and localized primarily in one organ. Previously, visualization of an organ had been achieved only by introducing a substance opaque to the x-ray directly into the lumen and obtaining a roentgenogram to outline its inner wall. By 1925 visualization of the gallbladder had also been accomplished by the oral administration of halogenated compounds [5,6]. The drugs employed for intravenous and oral cholecystography had been synthesized specifically for that purpose based on earlier experimental work of other investigators. The following account describes in detail the experimental background of cholecystography, its origin, and its development and use during the ensuing fifty years.

Cortical extract in the treatment of shock

Abstract In an effort to determine the efficacy of cortical extract in the prophylaxis and the treatment of shock, the extract was given to animals subjected to shocking procedures and to human beings having major operations of a magnitude apt to produce shock. In animals, shock was produced by hemorrhage and by massage of the intestine with the animal under ether anesthesia. In experimental shock produced by hemorrhage cortical extract exerted a definite but slight tendency to decrease the severity of shock, particularly when the extract was given with fluids (glucose and electrolytes). Fluids alone, i.e., without cortical extract, did not significantly prevent the fall in blood pressure although the actual survival time following hemorrhage was increased. When cortical extract was given an hour or two before institution of intestinal massage (to produce shock), the average drop in systolic blood pressure after forty minutes of massage was only 19.5 mm., contrasted with 35.3 mm. in animals not receiving extract prophylactically. Moreover, when hemorrhage of a constant rate was instituted ninety minutes after intestinal massage was begun, there was a survival time of thirty-six and five-tenths minutes in animals receiving cortical extract, contrasted with a survival time of only twenty-one minutes in animals not receiving cortical extract. When glucose and electrolytes were given in addition to extract, the effect was still more prominent, there being no drop in blood pressure after forty minutes of massage and an average of only 7.5 mm. after fifty-five minutes of massage. In other words, the beneficial effect of cortical extract and fluids (glucose and electrolytes) in prevention of shock was comparable to that which might be expected from plasma. When extract was given after shock had already been produced in animals very little beneficial effect could be demonstrated; there was little or no rise in blood pressure although further drop was slightly delayed. Falling drop determinations showed an increase in specific gravity of blood in shock, and a decrease after hemorrhage as reported by others. Cortical extract showed a definite but slight tendency to counteract the increase in specific gravity produced by shock. In human beings the use of cortical extract in the presence of shock was limited to a few cases due to the relative infrequency of shock, but in every instance the effect appeared to be beneficial. In order to determine whether or not cortical extract would exert a favorable influence in prevention of shock, the average pulse rate and blood pressure was computed in a series of fifteen patients receiving cortical extract prophylactically, and upon whom major operations of unusual duration and severity were performed. From the hospital records an equal number of operations (in which no cortical extract was given), with equal number of types and duration, were obtained and the average pulse rate and blood pressure likewise determined. In the patients receiving cortical extract prophylactically, the pulse rate averaged eight beats per minute slower, and the systolic blood pressure 12 mm. higher than in the patients not receiving extract. This suggests that the cortical extract tends to minimize the changes which might be interpreted as being changes preliminary to the development of shock. Observations on animals as well as patients showed that the extract was much more effective when given prophylactically, than when given after shock was already produced.

Acute pancreatitis: With special reference to pathogenesis and the diagnostic value of the blood amylase test

Abstract Although much confusion still exists as to the classification of acute pancreatitis, an attempt should be made to identify the type of disease, particularly since the treatment and prognosis are apt to be different in the various types. All cases of acute pancreatitis may be divided roughly into an acute edematous (interstitial) type, and an acute hemorrhagic or necrotic type. It is possible that the acute edematous type is caused primarily by obstruction, whereas the main factor in the production of the hemorrhagic or necrotic type is the development of tryptic digestion within the gland. The clinical manifestations of the two groups may be very similar indeed, except that the acute edematous type is invariably the milder and is never associated with shock. It should be remembered that an acute pancreatitis, particularly of the edematous type, may readily be overlooked unless the pancreas is palpated. Areas of fat necrosis may likewise be overlooked unless special care is taken to search for them, particularly since they are occasionally located only along the surface of the pancreas. The value of the blood amylase test as a diagnostic aid has been discussed. From the experiences of the author and others who are using this test, it appears that a rise in the blood amylase level is rather consistently encountered, particularly in the acute edematous type early in the disease. It is significantly true that the rise in the blood amylase may persist no longer than two or three days. The level may then fall to normal, or more commonly in the authors experience, below normal. Obviously, if the patient is not seen during the first two or three days of the attack, the blood amylase test may be of no diagnostic value. This fact must be remembered lest the test receive undue condemnation. However, the author has noted the persistence of a high blood amylase in several cases for many days after the onset of the attack. The treatment of the acute edematous type appears definitely to be conservative. After the acute phase of the disease has receded, attention should then be directed toward operative correction of the cholecystic disease which is so frequently present in acute pancreatitis. There is difference of opinion as to the treatment of acute hemorrhagic or acute necrotic pancreatitis. Many surgeons advise immediate operation. Others advise conservative treatment and operation on the biliary tract later, as indicated. The author is inclined to favor strongly the latter method of treatment.

Immunologic Treatment of Tumors.

Summary We produced antibodies by injecting cancer cells obtained from Walker 256 tumor into rabbits; after several injections of the cell antigen, the rabbits were exsanguinated, and the serum fractionated. Antibodies to normal tissue were adsorbed out by exposure to normal tissue. Injection of the globulin fraction prevented “takes” of Walker 256 cells in slightly over half of rats inoculated with 10,000 cells. The globulin antibody solution produced a decrease in size by about one quarter when given to rats with tumors 2 to 3 cm in diameter, but the tumor masses did not disappear. The method was tried in 2 patients with decrease in size of the tumor but not disappearance.

Prophylactic measures in the spread of carcinoma of the colon and rectum.

ANY mSCUSStON of prophylactic measures in the prevention of spread of carcinoma should be preceded by a brief statement of the mechanisms of spread of the disease. There are four major mechanisms concerned in this spread. They may be summarized as follows: 1. by lymphatics, 2. by contiguity through tissue planes, 3. by implantation, and 4. by vascular channels. Efforts to prevent spread must be directed towards these various mechanisms of dissemination. The first two have been discussed in detail in the medical literature,a, is, 39 Samson Hanley was the pioneer in the study of spread by lymphatics. The medical profession has been aware of the spread by implantation and venous emboli, but in our opinion too little attention has been paid to these mechanisms by the surgeon.

Medical and Surgical Management of Duodenal Ulcer

The panelists discuss general principles of medical management of duodenal ulcer, criteria of intractability, the role of stress, the status of gastric analysis, the chances of successful medical management, and the relative merits of various surgical technics.

FACTORS IN THE DISSEMINATION OF CANCER

As an introduction to the symposium on “What’s New in Cancer Therapy,” a discussion of the dissemination of cancer is especially pertinent. The four mechanisms for the spread of cancer are: 1) by contiguity, 2) the lymphatic system, 3) the vascular system, and 4) implantation. Implantabion may be either spontaneous or iatrogenic. Surgeons are well acquainted with the spontaneous type, seen so often when operating on patients with cancer of the digestive tract; in these cases the innumerable miliary metastases on the peritoneum prevent cure even though the local lesion may be resectable. Iatrogenic implantation is caused by the surgeon, an example being the development of tumor in the wound after an operation for cancer (Figs. 1 and 2). Space and time will not permit discussion of all the phases of the dissemination of cancer, so our remarks will be confined to implantation and vascular spread.

Cancer of the gastrointestinal tract.

SummaryThere has been in the past quarter-century a definite, though perhaps not spectacular, improvement in the outlook for the patient with gastrointestinal tract cancer. Cancer of the esophagus, particularly of the lower third, is no longer universally fatal. Cancer of the stomach, colon, and rectum also have an improved outlook.It is an unpleasant fact, however, that even with cancer of the colon (where the results are best) almost 75 per cent of the patients succumb.One of the most encouraging facts of recent years is the renewed interest in the natural history of the disease process. Operations are extended or modified for pathologically valid reasons and not merely because patients will tolerate them.Finally, the entire field of the prophylactic approach to the treatment of cancer is receiving renewed interest. Herein lies one of the greatest potentialities for the immediate future.