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Biomedical subjects

E D Holyoke

Publications and source records attributed to E D Holyoke.

At least 37 records · Page 2Linked to original sources

Biologic markers in cancer diagnosis and treatment.

We have reviewed several tumor markers that our advocates feel are now clinically useful, involve current assay technology, and are based on already available information. These include, in selected instances, estrogen receptors for breast cancer, thyrocalcitonin for medullary cancer of the thyroid, prostatic acid phosphatase for cancer of the prostate, alpha-fetoprotein for hepatocellular cancer, and carcinoembryonic antigen for monitoring colon cancer. We have considered the potential use of measurement of serum proteases and protein degradation products due to their activity as possible future areas of development, and we have explored measurement of tissue aryl hydrocarbon hydroxylase to identify populations at risk of cancer resulting from chemical carcinogenesis. It is clear that the study of tumor markers is already improving patient care in some specific areas and offers exciting potential for the future.

Acid Phosphatase↗

Intraarterial adriamycin in the treatment of soft tissue sarcomas.

Ten patients with extremity sarcomas adriamycin 60 mg/M2 into the artery supplying the area of tumor. There were minimal local side effects consisting of occasional local erythema or slight transitory pain. Nine of these patients had subsequent surgery, and an average 32.86% histologic tumor necrosis was recorded in the peripherally viable areas of seven patients with residual tumor, compared to a 5.71% necrosis recorded in the biopsy sections (P value less than 0.01).

Adult↗

Tumor antigens as related to pancreatic cancer.

Data are presented suggesting the presence of pancreas tumor-associated antigens. Slow progress has been made during the past few years in the identification of pancreatic tumor antigens that may be of clinical usefulness and it seems unlikely that many of the practical problems now being faced in identification and isolation of these antigens and in development of a specific, sensitive assay will be solved by conventional immunochemical approaches. The study of antigen and/or antibody purified from immune complexes in the host and the application of leukocyte adherence inhibition techniques to immunodiagnosis of pancreatic cancer are among the new approaches that may provide effective alternatives in the study of pancreatic tumor antigens.

Antigen-Antibody Complex↗

Lymph node dissection in malignant melanoma.

Regional node dissection was performed in 120 patients with malignant melanoma. Patients with clinically negative nodes had a 90% survival, whereas patients with enlarged nodes had a 15% survival. In 45 inguinal dissections, usually associated with a high morbidity, there was only a 4.5% incidence of infection and a 6.5% incidence of skin edge necrosis. For all types of node dissection, the overall incidence of wound infection was 5.8%, and that of necrosis of skin edges was 5%.

Adult↗

Liposarcomas: prognosis and management.

Fifty-one evaluable patients with liposarcomas were reviewed. Two-thirds of the patients were referred after local recurrence. One-third with primary surgery at RPMI had local recurrence rate of 31.6%. Overall, one or more local recurrences presented in 78% of patients. Pulmonary metastases, occurred in 45%, while liver metastases in 13.6%. Most common primary sites were the lower extremity, followed by the retroperitoneal area and upper extremity. Median survival is better for upper and lower extremities than other areas (P less than 0.01). The medium survival was longer in the group that received radiation after resection although the difference was not statistically significant. The high rate of local recurrences suggests the adjuvant use of radiation postoperatively when the surgical margins have not been adequate. Sixteen patients are alive and disease-free, with 10 of them having had five years or longer follow-up.

Adolescent↗

Biologic behavior and treatment of intransit metastasis of melanoma.

The therapeutic approach to intransit metastasis of melanoma has been surveyed in 52 patients admitted to this institute during the past ten years with a clinical history of intransit lesions of melanoma. Ten of these patients have been long term survivors. Two additional patients died at 23 and 28 months, respectively, after surgical removal of the lesions, and at autopsy, no evidence of recurrence was noted. All long term survivors belong to the group of 35 patients that received intensive local management, while all 17 patients given systemic chemotherapy or immunotherapy only died from progression of the disease. Every trial of system chemotherapy or system immunotherapy, aiming to control these lesions of intransit metastasis, failed. Systemic chemotherapy or systemic immunotherapy should not be used alone in the treatment of intransit metastasis. Such regional modalities as hyperthermic perfusion, local immunotherapy or excisions of wide strips of skin, subcutaneous fat and fascia around these lesions, in addition to systemic treatment, should be utilized persistently.

Antineoplastic Agents↗

Technic of resection of mesenteric tumors.

In the resection of mesenteric tumors or primary malignant lesions of the small bowel, exposure of the superior mesenteric vessels is important. This is the necessary criterion of resectability and the condition of obtaining maximal margins in the lymphatic drainage area. It also helps avoid unnecessary sacrifice of branches and tributaries to the superior mesenteric vessels from uninvolved portions of the bowel.

Humans↗

Feasibility of integration of modalities in melanomas and sarcomas.

Chemotherapy was administered in the immediate postoperative period to seventy patients (52 with melanomas and 18 with sarcomas) after a total of eighty-seven major operations, with no morbidity or mortality traceable to the chemotherapy. There was no apparent interference with wound healing or what would be considered a normal postoperative course. Fourteen of these patients (5 with melanomas and 9 with sarcomas) received a combination of radiation anc chemotherapy initiated in the postoperative period, and it was tolerated well. This combination appears to be safe, provided the field of radiation is not so large that is may add significantly to the myelosuppressive effect of chemotherapy and the dosage of concomitantly administered radiopotentiating agent(s) is reduced. Sixteen patients had Bacillus Calmette-Gúerin (BCG) immunotherapy in the immediate postoperative period without complications. This policy of a tight interweaving of modalities is safe, has the theoretic advantage of an earlier concerted attack on microscopic residual tumor, and appears particularly promising in sarcomas.

BCG Vaccine↗

Lymphocytic infiltration in murine tumors.

Histologic grading of the histiolymphocytic reaction in nodules of T241 or B16 murine tumors in 94 C57BL/6J mice was performed at various time intervals post-inoculation. The infiltrate occurring in the first four days was generally sparse and no significant difference was observed between two different dose control inocula, suggesting a weak primary localization. Comparison between control inocula, and challenge inocula in mice harboring the same tumor for 10 days, showed a somewhat denser infiltrate initially in the challenge inocula. Despite the immunogenicity of these tumors, as shown by concomitant immunity, lymphocytic infiltration was generally sparse, consistent with an hypothesis of deficient localization of immunocompetent cells at tumor sites.

Animals↗

Correlations between the leukocyte adherence inhibition microassay and in vivo tests of transplantation resistance.

The leukocyte adherence inhibition (LAI) microassay detects tumor-associated antigen(s). Extracts of colon carcinoma (MCA-38 and B16 melanoma tumors, both syngeneic to the C57BL/6J mice) are recognized only by peritoneal cells from mice bearing the corresponding tumor. To ascertain whether this in vitro antigenic recognition correlates with the ability of the host to recognize and reject a tumor in vivo, serial LAI microassays were performed synchronously with experiments designed to test the ability of mice bearing tumors to reject live secondary tumor challenges. Concomitant tumor immunity was present in the MCA-38 tumor-bearing mice on 3 occasions from 5 to 15 days from primary inoculation. In the B16 system, concomitant immunity was present on one occasion 10 days after primary inoculation. These results in turn were paralleled with the specific in vitro recognition of tumor antigens as detected by the LAI microassays. Loss of immunity in the "eclipse" phase of tumor development, as detected by concomitant tumor immunity, was paralleled by nonreactivity of the indicator cells in the LAI microassay.

Adenocarcinoma↗

Cellular and humoral factors involved in the mechanism of the micro-leukocyte adherence inhibition reaction.

To study the cellular basis for specific antigen-induced leukocyte adherence inhibition, enriched populations of B-cells, T-cells, and monocytes were prepared by a two-stage adherence separation procedure from spleen cells of normal C57BL/6J mice and mice bearing progressively growing MCA-38 tumors. The reactor cell undergoing specific antigen-induced adherence inhibition was identified as a monocyte (esterase positive, did not respond to mitogens, and did not bear Thy 1.2 antigen or surface immunoglobulin). Furthermore, an enriched population of MCA-38-sensitized B-cells could program normal monocytes to undergo specific antigen-induced adherence inhibition. In contrast, enriched populations of MCA-38-sensitized T-cells could not program normal nylon wool-adherent cells to undergo antigen-specific adherence inhibition. Programming of normal monocytes by MCA-38-sensitized B-cells occurs through a soluble mediator and not by direct cell contact. The soluble mediator appears to be immunoglobulin in nature and induced both adherence inhibition and the inhibition of adherence. Thus, in this murine tumor model, leukocyte adherence inhibition appears to be due to programming of monocytes by a secretory product of specifically sensitized B-cells.

Adenocarcinoma↗

Demonstration of the microtest version of the leukocyte adherence inhibition assay.

This paper gives a detailed description of the microtest leukocyte adherence inhibition technique, as well as the results obtained with blood specimens coded by impartial observers. Three coded blood specimens from patients with colon cancer, pancreatic cancer, and melanoma were tested against crude membrane preparations of pancreatic and colon adenocarcinoma tumors. No tissue type-specific reactivity was observed. The inability to demonstrate specific reactivity was due to extensive variability observed within each test. The extensive variability resulted from time constraints of the workshop that necessitated deviations from the normal procedure.

Adenocarcinoma↗

Tourniquet infusion chemotherapy in extremities with malignant lesions.

Tourniquet infusion chemotherapy involves the direct injection of a chemotherapeutic drug into the main artery of an extremity with prior application of an external tourniquet proximally on this extremity set at above the level of systolic pressure for ten minutes. Thus, the drug is not diluted and pushed by the blood into the venous circulation before diffusion into the tissues has occurred. This technique, applied in seven patients for a total of 40 instances, proved to be safe. Skin erythema and blisters, which are reversible, occur in the treated area. Complete clinical regression was achieved in all six patients with evaluable tumor, with high percentages of tumor necrosis. It was possible to avoid amputation in five of the seven patients treated. This technique appears superior to perfusion, but the long term permanence of regression has not yet been ascertained.

Adult↗