High-dose-rate brachytherapy in the treatment of carcinoma of the prostate.

BACKGROUND: Although radical prostatectomy for localized disease is considered as a standard of care, external-beam radiotherapy and brachytherapy are equally effective. We report on the technique and preliminary results of high-dose-rate (HDR) brachytherapy using a temporary iridium-192 implant technique. METHODS: The authors reviewed the literature on the techniques, treatment protocols, and results of HDR brachytherapy in the treatment of carcinoma of the prostate, and they report their own protocols, technique, and results. RESULTS: The combination of HDR brachytherapy and external irradiation has been well tolerated by all 200 patients in our series, with less than 3% grade 3 late complications and with 95% PSA relapse-free survival with a median follow-up of 24 months. CONCLUSIONS: HDR brachytherapy may be the most conformal type of irradiation in the treatment of carcinoma of the prostate regardless of tumor size, anatomical distortion, and organ mobility.

Diagnostic evaluation of type I latex allergy.

BACKGROUND: Latex hypersensitivity affects a significant number of health care workers. No universally accepted method for the diagnosis of latex allergy is currently available in the United States. OBJECTIVE: Determine the accuracy of clinical assessment in predicting type I latex allergy, and compare the ability of various latex skin test preparations and in vitro assays in confirming the diagnosis of latex allergy. METHODS: Subjects were classified into "history positive," "history ambiguous," or "history negative" based on reports of clinical symptoms. Skin prick tests were performed with ammoniated latex and glove extracts. Sera were analyzed for latex-specific IgE using the Pharmacia CAP and DPC AlaSTAT assays. RESULTS: A total of 207 subjects had histories taken, skin testing, and blood drawn. Out of 49 type I latex-allergy "history positive," 42 (86%) were skin test positive, and 24 (49%) were serum positive. Fifty-nine subjects were latex allergy "history ambiguous." In this group, skin testing showed 19 (32%) positives, and latex-specific IgE were detected in 10 (17%). Out of 99 latex "history negative," 9 (9%) were skin test positive, and 11 (11%) were positive for latex-specific IgE. Out of the 61 subjects with IgE symptoms following latex exposure who were skin test positive, a positive in vitro assay was found in 32 (52%). CONCLUSIONS: Skin testing is more likely to confirm a positive latex allergy history. Use of raw ammoniated and glove skin testing preparation sources combined adds to the diagnostic sensitivity. AlaSTAT and CAP correlate well with each other and have good negative predictive value, but lack the sensitivity of skin testing. Use of AlaSTAT and CAP assays combined raises the diagnostic sensitivity as compared to using one in vitro test alone.

Circulating anti-tumor and autoantibodies in breast carcinoma: relationship to stage and prognosis.

Serum antibodies to breast tumor antigen(s) and circulating autoantibodies were tested in 175 patients with various stages of carcinoma of the breast, followed for a mean period of 51 months. Antibodies to surface membrane and to cytoplasmic antigens of autologous and allogeneic tumor cells were measured. Peripheral lymphocyte count and skin reaction to six recall antigens were also tested. Patients with metastatic disease had significantly lower prevalence of antibodies to autologous tumor cells and lower total lymphocyte count than patients with early breast cancer. Patients with locally advanced disease (greater than or equal to 4 positive axillary nodes) had the highest frequency of anti-tumor antibodies, the second highest lymphocyte count, but with the lowest prevalance of autoantibodies. Presence or absence of anti-tumor or autoantibody did not correlate with results of skin tests or other standard blood tests. Among patients with locally advanced or metastatic breast cancer, those who had a positive skin test or whose lymphocyte count was 1500 to 2500 per cu mm had significantly better 5-year absolute survival rates (p = 0.04, p = 0.002, respectively). This study suggests that in patients with locally advanced or metastatic breast cancers, skin test reactivity and optimal peripheral lymphocyte count may be useful prognostic indicators. In contrast, neither the presence of anti-tumor antibodies to membrane or cytoplasmic antigens, nor the presence of autoantibodies, correlates with prognosis in patients with early or late breast cancers.

Combined external and interstitial irradiation in the treatment of stage III breast cancer.

One hundred six patients with locally advanced carcinoma of the breast underwent definitive radiation therapy for loco-regional control following incisional and/or needle biopsy. Doses of external and interstitial irradiation were 5000 rad (50 Gy) in 5 to 6 weeks, and 3000 to 4000 rad (30-40 Gy) in 60 to 80 hours, respectively. Forty-eight of 106 patients (45%) also received adjuvant systemic chemotherapy. Loco-regional control was observed in 93 of the 106 patients (88%), with five-year disease-free survival of 47%. Distant metastases developed in 59 of the 106 patients (56%). Good to satisfactory cosmetic results were obtained in the majority of these patients; morbidity was at an acceptable level. Locally advanced breast cancer can be treated adequately and satisfactorily without mastectomy by a combination of external and interstitial irradiation.

Primary irradiation in the management of early and locally advanced carcinoma of the breast.

Between September 1, 1974, and July 31, 1979, we have treated 142 patients with a diagnosis of carcinoma of the breast by a combination of megavoltage external irradiation and interstitial iridium-192 implant. Sixty-four patients had T1 and T2 lesions and 78 patients had T3 and T4 lesions of the breast. Since June 1977, pre- and perimenopausal patients with T1 and T2 lesions have undergone axillary node dissection in addition to excisional biopsies of the breasts. All patients received external irradiation to the breast and regional lymph nodes and an interstitial implant boost to the primary site and residual axillary nodes. Most of the patients with positive axillary nodes, and those with locally advanced disease, received systemic chemotherapy. Sixty-two of 64 patients (97%) with T1 and T2 lesions and 72 of 78 (92%) patients w ith T3 and T4 lesions achieved ultimate loco-regional control. The minimum follow-up period was 48 months.

An experimental histopathologic study of surgical glove powders.

Tissue reactions to surgical glove powders, ie, talc (magnesium silicate) and Keoflo (low cross-linked cornstarch) were studied histologically from day 1 to 16 weeks. These materials were tested as a contaminant on the surface of surgical suture or in a pellet form implanted in abdominal muscle of rat. Use of Keoflo resulted in an intense acute inflammatory response, with a progressive decrease in the amount of starch with time after implant. By the fourth week, most of the starch had disappeared with minimal tissue damage and scar formation. Rats implanted with talc showed an initial mild to moderate acute inflammation followed by chronic inflammatory response and granuloma formation by the third day. From the fourth week on, granulomas showed talc crystals within the giant cells surrounded by histiocytes, lymphocytes, some collagen, and fibroblasts. This study indicates that talc molecules are not absorbed, whereas low cross-linked cornstarch is an absorbable substance; therefore the latter is a safe material for use as surgical glove powder.

Elevated levels of smooth muscle autoantibodies in patients with acromegaly.

Screening of sera from patients with central nervous system (CNS) tumors for serum antibodies to tumor and normal tissue antigens revealed that the sera from a significant percentage of patients with pituitary adenoma demonstrated reactivity for smooth muscle antibodies (SMA) at a serum titer (1/25) at which other CNS tumors are devoid of this reaction. The sera were assessed by an indirect immunofluorescent antibody assay on fresh cryostat sections of rat kidney, liver, diaphragm, and stomach tissue. Absorption of SMA-positive sera with extracts containing smooth muscle tissue abolished the reaction. The overall incidence of SMA among patients harboring pituitary tumors was 30% (12/40). Assessment of the functional types of the tumor revealed a distinct predilection for such findings among patients with clinical acromegaly. Among patients with hypersecretion of growth hormone (CA) 90% (9/10) have SMA (both IgG and IgM type) whereas SMA was positive in only 10% (3/30) of corresponding group of patients with pituitary tumors resulting in hypercortisolemia or those that did not result in a hyperfunctional endocrine state.

Melanoma. Associated antigens in benign melanocytic disorders.

Three instances of depigmentation occurring in children with congenital large nevocytic nevi are reported. Serologic studies for tumour-associated antigens to melanoma were performed by indirect immunofluorescence and complement fixation on these patients and others with benign melanocytic disorders. Positive reactivity in several children was observed. The small numbers studied and lack of uniformity of other testing methods leave open the question of relevance of such reactivity to malignant conversion or protection in congenital nevi.

The utilization of native glioma antigens in the assessment of cellular and humoral immune responses in malignant glioma patients.

Cellular and humoral components of the immune response have been studied preoperatively, concurrently, and serially in patients with malignant glial neoplasms. In order to assess titres of circulating antibodies to tumour cell constituents an indirect immunofluorescent technique was applied to single cell suspensions and snap frozen cell smears. In an allogeneic system, 49% of 47 test and 7% of 124 control sera gave a positive response to cytoplasmic components. The leucocyte adherence inhibition assay was applied to study 39 test and 64 control patients. Significant non-adherence of leukocytes was observed in 77% of test cases. Control parameters indicated specificity of the response. Simultaneous assessment in 28 test patients yielded a positive response for one or both assays in 89% of cases..

Combination of external and interstitial irradiation in the primary management of breast carcinoma.

The authors treated 83 patients with carcinoma of the breast using a combination of external and interstitial irradiation at Los Angeles County--University of Southern California Medical Center and Southern California Cancer Center between February 1, 1974, and May 31, 1977. All 30 patients who had T1 and T2 lesions, and who were followed for a minimum period of 24 months (24-50 months) are clinically still free of disease. Thirty-nine of 53 patients with T3 and T4 lesions, who were followed for a minimum of 30 months (30-56 months) are still alive with local control. Details of treatment techniques, dosimetry, results and complications are presented.

Ductular carcinoma of the breast: serum antibodies to tumor-associated antigens.

Serum antibodies to tumor-associated antigens of breast carcinoma have been studied by indirect immunofluorescence in 109 patients with breast carcinoma and 125 controls, including age/sex matched normal individuals, patients with nonmalignant disease, and patients with malignant disease other than breast cancer. We report here that sera of a large proportion of patients with ductular carcinoma of the breast have antibodies to cell surface and/or intracellular antigens of autologous tumor cells and include evidence that the antigens are absent from a considerable range of normal and other types of malignant tissues. In addition to testing of control sera, specificity of the reacting antibodies was investigated further by testing of sera with normal breast tissue and the absorption of sera from breast cancer patients with various normal tissues and cancer cells. The significance of the findings in breast cancer is discussed.

Definition of cellular immune responses to brain antigens in human head trauma.

Cellular immune responses to brain antigens in patients with head injury were studied by applying the leukocyte adherence inhibition (LAI) assay. The investigation was conducted in three phases. 1) In the initial phase, evaluation of a series of 22 test and 25 control cases obtained at random during a 2- to 6-week time frame following a traumatic event indicated significant non-adherence of leukocytes (NAL) in 77% of the test group and 20% of the control group in the presence of brain antigen. 2) In a second phase, larger test population was divided into four groups of different posttraumatic intervals. This study measured NAL in the presence of normal heart of normal brain antigen. Assays revealed an initial significant NAL in the presence of both antigens; however, after the first week following injury the majority of cases manifested significant NAL only with brain antigen. These values of NAL persisted over a 6- to 8-week period. 3) As a final phase of investigation, analysis of a sequential series of assays in 12 patients over a 90-day period indicated significant NAL in the presence of brain antigen within the first week of injury, this was followed by a drop in NAL in most of the cases. Studies at 7 to 60 days posttrauma demonstrated significant NAL with brain antigen alone, with a subsequent drop by 90 days. These observations are interpreted to represent sensitization of leukocyte subgroups to brain proteins that are immunologically recognized following the traumatic event.

Specific cellular immune responses in patients with malignant gliomas.

The leukocyte adherence inhibition assay was used to measure cell-mediated immunity in 26 patients with malignant glial neoplasms and 41 control subjects. A significant inhibition of leukocyte adherence was observed in 21 of 26 (80%) glioma patients in the presence of a 3 M KCl extract of glioma tissue, as compared to that of normal brain extract. Among the control group, no significant difference in the percentage of nonadherent leukocytes was noted in the presence of either antigen. To study the specificity of the reaction, a 3 M KCl extract of meningioma, pituitary tumor, carcinomas of breast, and lung, melanoma, brain, and heart tissues were used as nonspecific antigens. Such studies revealed significantly lower values of nonadherent leukocytes. These data indicate that patients with malignant glial neoplasms manifest a cellular immune response to glioma-associated antigens which can be measured by the tube leukocyte adherence inhibition assay and that leukocyte adherence inhibition assay may render additional useful information in diagnostic and prognostic evaluation of malignant glial neoplasms.

Preoperative cell-mediated immune status of patients with malignant glial tumors.

The leukocyte adherence inhibition assay (LAI) was used to measure cell-mediated immunity in 26 patients with malignant glial neoplasms and in 41 control subjects. A significant inhibition of leukocyte adherence was observed in 21 out of 26 (80%) patients with malignant astrocytic gliomas in the presence of a 3M KC1 extract of glioma tissue compared to that of normal brain extract. Among the control group, no significant difference in the percentage of nonadherent leukocytes (NAL) was noted in the presence of either antigen. To study the specificity of the reaction, 3M KC1 extracts of meningioma, pituitary tumor, carcinoma of breast, carcinomas of lung, melanoma, brain, and heart tissues were employed as non-specific antigens. Such studies revealed significantly lower values of NAL. These data indicate that patients with malignant glial neoplasms manifest a cellularimmune response to glioma-associated antigens that can be measured by the tube LAI assay and that LAI assay may render additional useful information in the diagnostic and prognostic evaluation of malignant glial neoplasms.

Serological reactivity in cancer patients to human and mouse fetal liver cells.

The occurrence of antibodies to human and mouse fetal liver cells has been quantitated in the sera from patients with carcinoma of breast, colon, and lung and with malignant melanoma. Also, we have demonstrated cross-reacting murine antibodies in the sera from multiparous, antifetal, and pregnant mice, which bind to mouse fetal liver cells and/or several types of human tumor cells. A comparative evaluation of these antibodies with two immunological techniques has demonstrated a greater number of positive sera from cancer patients assayed by isotopic antiglobulin (25 of 27, or 92%) than by membrane immunofluorescence (12 of 17, or 71%). In the non-cancer control group, positive reactions were found in 11 and 31% by the two techniques, respectively. The specificity of such serologically reactivity has been demonstrated by adsorption with fetal liver cells. These detected antibodies are not restricted to a particular type of human neoplasm, but rather to the presence of cancer. Because of their relative capacity of discrimination between benign and malignant conditions and because the assay for their detection is relatively simple, these techniques may provide alternative methods for diagnosis or monitoring of cancer patients.