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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The results of various in vitro analyses indicate there is an active immune response against antigens associated with human malignancies. This immune response apparently can be augmented by nonspecific immunologic stimulates such as BCG. These agents are effective for destroying tumor when injected locally into intracutaneous disease but are not as effective for subcutaneous disease. Preliminary clinical trials indicated that immune stimulants are effective when administered systemically. The effect is only minimal for diseminated disease, but the therapeutic benefit is clearly augmented for patients with a minimal residual tumor burden, such as those patients with metastases to regional lymph nodes. Thus immunotherapy is a systemically active mode of therapy. Its toxicity is minimal, and it appears to be effective in a wide spectrum of the disease. However, immunotherapy is not effective for a large residual tumor burden; consequently it must be used in combination with other modes of treatment such as irradiation therapy or chemotherapy. Early experiences with BCG immunotherapy for malignant melanoma and C. parvum for oat cell carcinoma are encouraging. It is remarkable that a nonspecific immunologic stimulant does, in fact, have this effect. Immunotherapy experiments in animals suggest that in order to achieve maximal benefit. BCG must have close contact with tumor cells or must be combined with a tumor-associated antigen. If these principles are true for man, it would seem that improvements for nonspecific immunotherapy in human neoplasms would be further augmented if a tumor-related antigen could be extracted from human tumours and combined with a nonspecific immunologic stimulant.
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PMID:Immunotherapy of malignancies: current status. 17 34

One hundred and seven patients with carcinoma of the lung underwent immunologic testing, and 62 of these patients were randomized to an immunotherapy protocol comparing the effects of Pasteur strain BCG, either alone or combined with allogeneic tumor cells, to the effects of no immunotherapy. Patients with residual disease left at the time of surgery or with metastatic disease at the time of diagnosis showed no increase in survival as a result of this form of immunotherapy. An insufficient number of patients with less advanced disease, in whom we would expect the most beneficial effect, have been entered in this study. In general, we were unable to document substantial effects of immunotherapy on the immunologic parameters tested. Only in recall antigen skin testing was there a statistically significant increase in reactivity in the immunotherapy groups. Tests of general immune status appeared to have a predictive value in monitoring lung cancer patients. Anergic patients had a poorer prognosis than did patients who demonstrated skin test reactivity. Patients with normal percentages of lymphocytes (T cells) forming rosettes with sheep erythrocytes at 29 degrees C were generally normal in other tests of immune competence. In serial studies of rosette formation, all patients who developed recurrent disease had a pattern of depressed or falling rosette values, and these abnormalities occurred an average of 3.1 months prior to clinical detection of recurrence. Patients with large-cell anaplastic carcinoma were found to have a significantly higher incidence of depressed rosette levels than the other histologic types. Both large and small-cell anaplastic patients had significantly depressed lymphocyte proliferation by mitogens and allogeneic cells. Although lung cancer patients have been described as immunologically depressed, they are capable of recognizing tumor-associated antigens. When tested in leukocyte migration inhibition assays with tumor-associated antigens, the majority of the patients in our study were found to be reactive. The use of a 3 M KCl extract of pleural effusion cells from a patient with pulmonary adenocarcinoma has given good reactivity and specificity in lung cancer patients of all histologic types. In addition, these patients have been shown to respond in a mixed lymphocyte/tumor interaction to tumor-associated antigens (Dean, 1976b).
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PMID:Immunological monitoring and immunotherapy in carcinoma of the lung. 18 17

In inbred guinea pigs, administration of Mycobacterium bovis strain BCG by scarification at a site distant from an excised skin tumor, but in the regional lymph node drainage, was evaluated for its immunotherapeutic effect on the development of lymph node metastases. Scarification was performed after surgical excision of intradermally transplanted syngeneic (line-10) hepatocarcinoma at a time when microscopic foci of tumor cells were present in regional lymph nodes. Various strains of BCG were evaluated for their immunotherapeutic potential: fresh-frozen Phipps, Pasteur, and Tice; and lyophilized Pasteur, Tice, and Connaught. Scarification commenced 3 days after surgical removal of the tumor and continued once a week for 5 weeks. Only lymph nodes from fresh-frozen Phipps- and Pasteur-scarified animals were significantly smaller than those in the control groups. Differences in lymph node weight correlated histologically with less detectable metastases. This cytostatic effect was short lived; eventually, the metastatic tumor growth was not significantly different from that of control animals. No significant differences were observed in mean survival time: All animals died as a result of metastases 3 months after tumor inoculation. These results demonstrated that limited scarification with BCG of certain strains temporarily inhibits the growth and proliferation of metastases in regional lymph nodes after removal of the primary tumor.
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PMID:Evaluation of BCG administered by scarification for immunotherapy of metastatic hepatocarcinoma in the guinea pig. 18 11

From 1950 through 1975, 671 patients with malignant major salivary gland neoplasms were referred to M. D. Anderson Hospital and Tumor Institute. Thirty-six patients with advanced local or metastatic disease subsequently underwent 62 evaluable trials with a variety of chemotherapeutic agents, either alone or in combination. Six patients achieved a partial response, with a median duration of 3 months. Ten additional patients had stable disease for 2 or more months. Anthracyclines appeared to be the most effective agents in this study, with three partial responses of six evaluable trials. The longest partial response (10 months) occurred in a patient receiving combination chemotherapy plus BCG immunotherapy. Pulmonary metastases were most commonly responsive to chemotherapy. The median intervals from diagnosis to death or to last follow-up and from initiation of chemotherapy to death or to last follow-up were 30 months and 6 months, respectively. Further therapeutic trials are necessary before response rates to single chemotherapeutic agents or combinations can be accurately assessed. In view of the poor prognosis of patients with recurrent disease, postoperative adjuvant studies with chemoimmunotherapy in patients with a high risk of recurrence are planned.
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PMID:Chemotherapy of malignant major salivary gland neoplasms: a 25-year review of M. D. Anderson Hospital experience. 19 35

A freeze dried preparation of BCG with a low ratio of living to dead organisms (LV) was compared to a frozen liquid preparation with high viability (HV) for its ability to eradicate established dermal tumors and microscopic lymph node metastases in guinea pigs. The cure rate achieved by the intralesional injection of LV-BCG did not differ significantly from that of HV-bcg when similar numbers of viable organisms were injected.
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PMID:Immunotherapy of a guinea pig hepatoma with living BCG: a frozen liquid and a lyophilized preparation are equally active. 20 59

BCG (TICE) was safely administered to 15 patients with metastatic cancer to the lungs in weekly doses of up to 3 X 107 organisms by the aerosol route. The aerosol route of administration is associated in approximately 33% of the doses with a toxicity syndrome of malaise, fever, and chills beginning 4 to 8 hours after treatment and ending within 24-36 hours. This syndrome is experienced by all patients and symptoms gradually subside with continuation of therapy. No hepatic or pulmonary toxicity was documented during the 221 treatment doses.
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PMID:Aerosol BCG treatment of carcinoma metastatic to the lung: a phase I study. 23 87

A complete response to BCG is described in a case of recurrent melanoma. In a woman aged 38 years, intracutaneous metastatic deposits confined to the limb of origin had occurred after excision of a malignant melanoma from the ankle, and elective groin dissection had shown two lymph nodes infiltrated with melanoma. BCG vaccine was applied to the buttock, initially by scarification and later by a multiple puncture gun. All metastases slowly regressed, and biopsy of a metastatic site at six months showed no tumour cells. The patient remains free of detectable disease 36 months after the commencement of therapy. It is inferred that BCG may facilitate remission of melanoma, perhaps by reason of antigenic cross-reactivity between BCG and surface components of human melanoma cells.
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PMID:Complete remission of metastatic malignant melanoma following immunotherapy with Bacillus Calmette-Guerin (BCG): report of a case. 26 5

BCG administered by the multiple-puncture technique has been used in a prospective, randomized study of the adjuvant treatment of patients with osteogenic sarcoma. Pulmonary granulomas were found in the lungs of four of five patients receiving BCG, that underwent thoracotomy for the diagnosis of pulmonary nodules within three weeks of the last BCG injection. Except for a single, foreign-body granuloma no pulmonary granulomas were seen in seven randomized patients who did not receive BCG. In addition, two patients receiving BCG had evidence of granulomas in bone marrow and in a mediastinal lymph node. BCG administered by the multiple-puncture technique is capable of causing granulomas at sites distant from that of the BCG application. BCG can cause pulmonary granulomas and these granulomas may be confused with pulmonary metastatic disease.
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PMID:Pulmonary granulomas induced by BCG. 27 92

Endolymphatic isotope therapy had such promising early clinical results that the M.R.C. (Medical Research Council) U.K. set up a clinical trial in 1966. This was to compare the effect of endolymphatic isotope therapy with the results of standard methods in the treatment of lower limb malignant melanoma. The interim report had three groups for analysis: Standard Methods (S); Endolymphatic Satisfactory (ES); and Endolymphatic Unsatisfactory (EU). This third group was a subdivision, as a significant number of patients did not have the correct endolymphatic treatment. The five-year survival figures expressed as actuarial percentages were ES=78.8%; S=82.3%; and EU=57.3%. Lymph node recurrence showed a significant difference: ES=2.3%; EU=12%; and S=19%. The conclusions were that endolymphatic isotope therapy was justified in specialized centres where good results could be obtained. Further animal experiments using the VX2 tumour in rabbits indicated that BCG given intracutaneously or intravenously had no therapeutic effect, whereas when applied by intralymphatic injection BCG was successful in treating lymph node metastases. Nineteen patients with poor-prognosis malignant melanoma have received endolymphatic BCG. The clinical results are recorded in this paper and are sufficiently encouraging to warrant its continued use.
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PMID:Endolymphatic isotope and BCG in the management of malignant melanoma. 27 47

Inbred Sewall Wright strain 2 male guinea pigs with established intradermal tumors and microscopic lymph node metastases were treated either by local excision, cryosurgery, or intralesional injection of BCG. Cryosurgery and local excision were effective in eliminating growth of the primary tumor but failed to prevent growth of lymph node metastases. In contrast, intralesional injection of BCG caused regression of primary tumors and prevented growth of lymph node metastases.
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PMID:Failure of cryosurgical treatment of experimental intradermal tumors to eradicate microscopic lymph node metastases in guinea pigs. 28 20


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