William W. Shingleton

Specific Active Immunotherapy for Melanoma

The most effective immunization historically has been active immunization against a specific disease process. We report here the results of specific active immunization of 719 patients with invasive melanoma. The patients were sequentially immunized with approximately 2.5 × 107 x-irradiated, neuraminidase treated melanoma cells and BCG was used for its adjuvant effect. The sites of primary tumor location included trunk (42%), extremity (35%), head and neck (15%), unknown (3%), eye (2%) and mucocutaneous (1%). Two hundred thirty-six Clarks Level III patients with Stage I disease experienced an 88% survival ar four years while 47 Stage II patients had an observed survival of 82% during this same lime period. Very similar statistics were observed for 124 State I Clarks Level IV patients and 70 Stage II patients. Nineteen and 26 Clarks Level V patients with Stage I and Stage II disease realized a 100% and 55% observed survival at four years respectively. Fifty-two patients with either an unknown primary and metastatic disease prior to immunotherapy or mucous membrane primaries with metastatic disease prior to immunization were observed to have a 65% survival at four years while invasive ocular primary patients without metastatie disease prior to immunotherapy had a 70% four year survival in the 19 patients evaluable. The largest number of patients fall in the first two years of follow-up, therefore, the degree of confidence concerning the survival statistics for years 3 and 4 is broad at this point in time. Further follow-up with careful evaluation will be required before definition statements can be made and comparisons can be elicited. The overall survival statistics do, however, encourage continued evaluation of specific active immunotherapy for patients with invasive melanoma with both Stage I and Stage II disease.

The Evaluation of Pancreatic Function by Use of I131 Labeled Fat

Summary A study using an I 131 labeled fat meal has been carried out on 30 patients with proven pancreatic disease. Measurements were made of the per cent of blood radioactivity at four, five, and six hours following the test meal, and on a subsequent 48-hour collection of feces. The test yielded information of diagnostic value in 10 of 12 patients found to have chronic relapsing pancreatitis, in 17 of 18 patients with pancreatic carcinoma. In the absence of small bowel disease, pyloric obstruction, or gastric surgery, an impairment of fat absorption using this technique is strongly suggestive of pancreatic disease. The method can further be used as a laboratory aid in evaluating substitution therapy in patients with pancreatic insufficiency.

I131 blood levels correlated with gastric emptying determined radiographically. I. Protein test meal.

Conclusions 1. A characteristic and reproducible curve of radioisotope blood levels was obtained in normal humans and normal dogs following an I131 labeled protein test meal. 2. Radiographic determination of gastric emptying is necessary for the proper interpretation of data. 3. Delayed gastric emptying significantly altered the radioisotope blood levels. 4. Fainting and change in position may alter radioisotope blood levels.

Use of I131 Labeled Oleic Acid in Study of Gastrointestinal Function.

Summary and Conclusion 1. Constant and reproducible curves of blood radioactivity levels are found in normal humans and dogs after an oleic acid test. 2. Following pancreatectomy and induced pancreatitis in dogs, the curves obtained with oleic acid test were within normal range while those obtained with triolein were depressed.

Management of recurrent melanoma of the extremity

Two forms of therapy employed for treatment of patients with recurrent melanoma limited to the extremity, and carried out during different intervals of time, are presented. Perfusion of the involved extremity with phenylalanine mustard has resulted in a 5‐year survival rate of 28% in 43 patients. A second group of 25 patients has been treated by a four‐stage immunotherapy program consisting of sensitization with intradermal BCG, followed in 6 weeks by intra‐tumor injection of BCG. A third stage involved the activation of the patients lymphocytes, after removal by a blood cell separator, incubated in vitro with irradiated neuraminidase‐treated melanoma cells and reintroduced into the patient either by subcutaneous or intratumor injection. The fourth stage of immunotherapy involves injection of an inoculum of irradiated neuraminidase‐treated autochothonous tumor cells plus BCG injected intratumorally or subcutaneously. Sixteen of 24 patients receiving immunotherapy treatment program have experienced arrest of their disease lasting from 5 to 42 months.

Intralesional BCG, intravenous immune lymphocytes, and immunization with neuraminidase-treated tumor cells to manage melanoma; A clinical assessment.

An attempt was made to produce tumor immunity in 193 patients who had melanoma, 160 of whom had metastases and 33 of whom did not. Four stages of treatment are outlined. The patients whose disease was confined to the skin, subcutaneous tissues, and lymph nodes seemed to benefit most. The treatment was of no benefit to patients whose disease had progressed to the visceral, skeletal, or central nervous systems.

Absorption in Dogs Following Exclusion of Bile and Pancreatic Juice Using I131 Labeled Fat

Summary Using a fat test meal containing a radioactive labeled fat, a study has been carried out in dogs to assess the rate and total amount of radioactive labeled fat entering the blood in normal dogs and in dogs with exclusion of bile and pancreatic juice during a 6-hour period after administration of the meal. These studies indicate that bile plays a minor role and pancreatic juice a major role in fat digestion and absorption. This study suggests the use of a similar test for clinical use in evaluating pancreatic function in suspected pancreatic disease.

Breast carcinoma: An overview

Breast cancer incidence in the United States is increasing, and the role of the gynecologist is becoming increasingly important in early detection of this common tumor of women. This article presents basic information on the anatomy and physiology of the female breast and their relationship to benign and malignant conditions commonly seen in clinical practice. An overview of detection screening, diagnosis, and treatment of breast carcinoma is also provided.

ADOPTIVE TRANSFER AND SPECIFIC ACTIVE IMMUNIZATION OF PATIENTS WITH MALIGNANT MELANOMA

Numerous investigators have reported on documented changes of the antigenic profile expressed on mammalian cells that have undergone malignant transformation. The presence of tumor-associated antigen( s) on a wide variety of spontaneously occurring neoplastic disorders in man has been detected by use of several different experimental methods. Immunologic surveillance and response to these antigens have been assessed by utilizing both in vitro and in vivo techniques. Colony inhibition, cell-mediated cytolysis, complementdependent cytotoxicity, lymphocyte-dependent antibody, serum-blocking and “-unblocking” factors, lymphoblastogenesis, and delayed cutaneous hypersensitivity have all been studied exhaustively in an effort to more clearly define what role, if any, the host immune response plays in the natural history of malignant diseases. The ability of a patient to develop a delayed cutaneous hypersensitivity response has been reported to predict a more favorable prognosis than for patients who fail to demonstrate this capability.’ Attempts to convey a degree of immunity to patients with cancer have been reported with some success. The very early usage of nonspecific techniques that utilized bacterial toxins,’ followed more recently by hyperimmunizations with Bacillus Calmette-Gutrin (BCG) ,3 Corynebacterium parvurn,‘ and vaccinia have been beneficial to a minority of patients. Specific immunologic techniques, including transfer factor,5 immune RNA,B adoptive transfer of immune lymphocytes,3 infusion of hyperimmune globulin, and active vaccination with both altered and unaltered tumor cells 7 have not undergone sufficient investigation to permit valid data analysis. During the past several years, we have studied immunologic responsiveness in patients with melanoma by utilizing most of the aforementioned techniques. Our efforts have been aimed toward documenting cellular and humoral immune responses prior to, and sequentially with, immunologic manipulation in an effort to correlate what, if any, change is observed with the clinical course.

Ethical considerations in the treatment of breast cancer

There is a growing awareness by the medical profession and the public of the increasing complexity of medical ethics. Advances in medical technology have raised new ethical problems. The scope of medical ethics needs to be broadened to provide guidance for new problems encountered by physicians in the rapidly developing science of medicine. Major bioethical principles have been suggested‐beneficience, nonmaleficence, justice, equity, veracity, and autonomy. These are all issues debated in the general field of ethics. Society can gain greatest benefit by having these issues debated and discussed by physicians, philosophers, theologians, lawyers, and laymen.