Clinical responses with active specific intralymphatic immunotherapy for cancer--a phase I-II trial.

We evaluated the method of active specific intralymphatic immunization to treat cancer in 32 patients with various tumor types as part of a broad-based phase I-II evaluation and describe the results of 3 sequential series. In series 1, the patients (n = 13) received 2 or more injections of autologous, cryopreserved, irradiated tumor cells directly into the lymphatic system through the cannulation of a dorsal pedal lymphatic channel. In series 2, the patients (n = 7) received low-dose cyclophosphamide, 300 mg per m2, 3 days before the autologous cell vaccine was administered. Series 3 (12 patients) was similar to series 2 except that the tumor cells were treated with cholesteryl hemisuccinate immediately before irradiation. Patients received from 2 to 6 injections of cells, depending on availability, at 2-week intervals. In all, 91 treatments are evaluated in this study. Clinical responses occurred in 7 of the 32 patients and were seen in all 3 series with about the same frequency. These responses occurred in cases of melanoma, lung cancer, colon cancer, and sarcoma. Regressions occurred in both visceral and subcutaneous sites. There was little toxicity, the chief side effect being local discomfort or inflammation. This experience indicates that active specific intralymphatic immunotherapy is safe, produces antitumor effects, and requires more investigation to increase the frequency and duration of observable tumor regression.

Buserelin treatment of advanced prostatic carcinoma. Long-term follow-up of antitumor responses and improved quality of life.

The safety and efficacy of buserelin, a luteinizing hormone-releasing hormone (LH-RH) agonist, was tested in 33 evaluable patients with Stages C or D adenocarcinoma of the prostate. With a minimum follow-up duration of 10 months, there was one complete response and 22 partial responses (69%) by National Prostatic Cancer Project criteria, with a median duration greater than 18 months. Six patients (18%) had stable disease, median duration greater than 25 months, and only 12 patients have progressed. Performance status improved in 67%, patient-scored pain improved in 75%, and quality of life improved in 58%. Symptoms occurring during treatment consisted of hot flashes, loss of libido, and impotence. Buserelin produces a high frequency of durable objective and subjective responses in patients with advanced prostatic carcinoma.

Verapamil reversal of clinical doxorubicin resistance in human cancer. A Wilshire Oncology Medical Group pilot phase I-II study.

A pilot study of the use of verapamil and adriamycin in patients with advanced malignancy was conducted to determine if the two drugs could be safely combined and to explore whether antitumor responses were frequent. The dosage of adriamycin was 50 mg/M2 every 3 weeks. Eight doses of verapamil were given orally every 6 hours, with adriamycin being administered after the fourth dose. In five patients 240 mg of verapamil taken every 6 hours produced unacceptable nausea, vomiting, hypotension, and arrhythmia. In eight patients, 120 mg of verapamil taken every 6 hours was tolerated moderately well. In four adriamycin-resistant patients, the combination of adriamycin and verapamil produced one partial response and two minor regressions. Further studies using this combination are warranted.

Buserelin as primary therapy in advanced prostatic carcinoma.

The effectiveness of buserelin, a luteinizing hormone-releasing hormone agonist, was tested in 28 patients with Stages C or D adenocarcinoma of the prostate. Of 24 evaluable patients, there were 13 partial responses (54%) by National Prostatic Cancer Project criteria, median duration greater than 6 months. Nine patients had stable disease (38%), median duration greater than 5 months, and only two patients progressed. Performance status improved in 38%, patient-scored pain improved in 46%, and quality of life improved in 57%. Symptoms occurring during treatment consisted of hot flashes, loss of libido, and impotence. A flare of symptoms was observed in only one patient, despite a transient 25% increase in testosterone in 36% of patients. Buserelin is an effective treatment for inducing frequent and meaningful remissions in advanced prostatic cancer.

Management of patients with metastatic adenocarcinoma of unknown origin: a Southwest Oncology Group study.

The Southwest Oncology Group evaluated 51 patients with a histologic diagnosis of metastatic adenocarcinoma and an occult primary tumor. Even though all patients received an extensive diagnostic evaluation, only six (12%) primary sites were found. Thirty-six patients whose primary tumor sites remained occult were randomized to receive either 5-FU or combination chemotherapy (5-FU, doxorubicin, and cyclophosphamide [FAC]). There were no responses in either group. The median survival with 5-FU was 105 days and with FAC was 95 days. Toxicity with FAC was more common and more severe.

Factors affecting the size of platelet aggregates in blood.

Factors affecting the size distribution of platelet aggregates formed in whole blood were measured using an electronic particle counter. Lysis of red cells after dilution of blood for analysis allows detection of smaller aggregates without altering aggregate measurement. Differences in platelet response to increasing concentrations of ADP are detected by an increase in the mean size of platelet aggregates while the total volume of aggregates varies linearly with the volume of available platelets (r = .99). The mean aggregate size varies directly with the total volume of aggregates formed (r = .99). Mean aggregate size is inversely related to the packed red cell volume. As the reactivity of platelets is reduced by incubation with aggregation inhibitors at increasing concentrations, the mean size of aggregates becomes smaller, followed by a decrease in the total volume of aggregates. The total volume and mean size of aggregates formed after incubation with collagen and epinephrine, but not ADP, increases with time after venepuncture.

Metastatic neuroblastoma in bone marrow aspirate smears.

The authors observed rosette formation and partially fibrillar, blue-grey, extracellular material in Wright-Giemsa-stained bone marrow aspirate smears in five preparations from three cases of neuroblastoma metastatic to bone marrow. These features are little publicized in the literature and textbooks. These findings in neuroblastoma metastatic to bone marrow should prove helpful in differentiating that entity from acute leukemia and from other metastatic small-cell neoplasms in bone marrow.

Histopathogenesis of skin and subcutaneous injury induced by adriamycin.

Extravasation of Adriamycin from an intravenous needle or catheter can produce a progressive skin necrosis and deep painful ulceration. The pathological changes which result in this ulceration were studied in a rabbit model. The earliest changes include vascular obliteration and necrobiosis of collagen. At no point were inflammatory cells found to play a primary role.

A simplified [3H] serotonin release assay for the detection of platelet antibodies.

The [3H] platelet serotonin release assay is a sensitive means for detecting antiplatelet antibodies. We have found that by using prelabeled frozen platelets which have been treated with the cryoprotective agent dimethyl sulfoxide (DMSO) the performance of this assay can be facilitated without interfering with its sensitivity. There was 100% correlation between the standard [3H] platelet serotonin release assay using fresh platelets and the modified assay using prelabeled, frozen, cryopreserved platelets when sera from 12 patients with known antiplatelet antibodies were tested. When normal serum samples (n = 111) were tested against ten platelet donors, a false-positive rate of 3.9% was observed. This modification provides a simple means for quickly screening large numbers of potential platelet donors at one time.

Adenocarcinoma of unknown origin. A rational approach to a diagnostic puzzle.

Determination of the tissue of origin of disseminated adenocarcinoma is often difficult. Careful clinical evaluation of the patient in light of known characteristics of certain primary tumors, followed by appropriate screening tests, may yield decisive information. If not, a decision for or against more specific tests must be made.

Cardiopulmonary bypass surgery. Platelet aggregation during induction of anesthesia and following heparinization of patients.

Measurements of platelet count and platelet aggregation in response to adenosine diphosphate and epinephrine were made before and after administration of preanesthetic medications and at intervals during induction of anesthesia, before and after thoractomy, and before and after systemic heparinization in patients undergoing cardiopulmonary bypass operations. Substantial decreases in circulating platelet count occurred only after induction of anesthesia and following thoracotomy. There was no notable change in the percent of platelets involved in aggregation over the period studied, but the reactivity of platelets was increased after induction of anesthesia and after thoracotomy.

False-positive Sternberg-Reed cells present in pericardial effusion. Report of a case.

Recent reviews have emphasized the value of cytodiagnosis in the evaluation of malignant effusions from patients with lymphoproliferative disorders. We present a case in which the presence of Sternberg-Reed-like cells in pericardial fluid was related to prior radiotherapy and not to recurrent Hodgkin's disease.

Radionuclide scans in staging of carcinoma of the lung.

Radionuclide scans are relatively accurate, non-invasive, diagnostic tools when used in patients with carcinoma of the lung with clinically suspected metastases. Their role as a screening or staging procedure in patients without signs or symptoms of metastases is less clear. Brain scans in asymptomatic patients have a low yield. Liver scans done in the absence of hepatomegaly or elevated liver function tests show a high per cent of false-negative and negative results. Bone scans appear to be of considerable value in patients with or without clinical evidence of metastases, in spite of limitations imposed by frequent false-positive results.

An evaluation of several blood transfusion filters.

Several blood transfusion filters designed to remove microemboli were evaluated for filtration and flow characteristics, as well as for hemolysis and for release of particulate debris from the filter. The Dacron wool filter, a depth filter, was superior at removing microemboli measured with an electronic particle size analyzer. A 25 micrometer pore mesh filter was least effective at removing microemboli from stored blood, but demonstrated the most favorable flow rates and induced no apparent red blood cell destruction during filtration. In general, filter efficiency and filter induced hemolysis correlated inversely with flow rate. No filter tested released significant quantities of particulate debris when compared with unfiltered isotonic saline.

Oral fluorouracil therapy of hepatoma.

Oral fluorouracil was administered weekly to 12 consecutive patients with unresectable hepatoma. Six patients showed an objective response with a significant increase in survival duration compared to nonresponders and to untreated patients. The clinical features of these cases are discussed, along with details of therapy, and possible reasons for the encouraging results noted with this treatment regimen.

Cardiopulmonary bypass. Microembolization and platelet aggregation.

Particulate microemboli and in vitro platelet aggregation were studied in blood of patients during cardiac operations with an electronic particle size analyzer. A small gradient of microemboli developed on passage of blood through a bubble oxygenator but not through a membrane oxygenator. However, with both types of oxygenators, there was a sustained increase in the volume of microemboli in cardiotomy return blood which was much greater than in aterial blood. After cardiopulmonary bypass with both oxygenators, there was a comparable reduction in the volume of circulating platelets which exceeded that of the hemoglobin concentration, indicating platelet loss exceeded that that expected from hemodilution alone. However, the total volume and mean size of platelet aggregates induced in blood of patients after membrane oxygenation was significantly greater than similar measurements after bubble oxygenation. This study shows that membrane oxygenation reduces particulate microembolization and preserves platelet function in patients undergoing cardiac operations when compared to bubble oxygenation.