Life planning: an educational approach to change.

Life-planning methods that have emerged over the past several years offer alternatives to psychotherapy for the person experiencing the crises of mid-life and mid-career. The author describes several approaches to life planning and presents details regarding the implementation of life-planning methods.

Does mca contribute to the follow-up of breast-cancer patients by ca-15-3.

Mucin-like carcinoma-associated antigen (MCA) and CA 15-3 tumor markers were randomly assayed in 234 consecutive breast cancer patients. It was found that 45 patients (19.2%) had elevated MCA levels (cut-off level >14 U/ml) and normal CA 15-3 levels (cut off level >30 U/ml). In 14 of these 45 patients (31.1%), overt metastases were detected, although five had started their follow-up with no evidence of disease. In these five patients, the median lead time was nine months. In our limited experience, it was found that measuring MCA levels in the serum in the presence of normal CA15-3 levels contributes to early detection and monitoring of recurrences in follow-up of breast cancer patients.

Amplification of the expression of major histocompatibility class-I antigens by inducers of differentiation and gamma interferon in murine and human solid tumor-cell lines.

Treatment of B16 F10-9 mouse melanoma cell line and RC-29 human renal carcinoma cell line with chemical inducers of differentiation such as sodium butyrate (SB) hexamethylene bisacetamide (HMBA) and L-histidinol significantly increased the expression of major histocompatability complex (MHC) class I antigens. This effect depends on the continued exposure of the cells to these materials. Combined treatment of the B16 F10-9 melanoma cells with recombinant murine gamma interferon and SB increased the expression of MHC class I antigens in a synergistic manner. This effect of chemical inducers of differentiation might be of importance in rendering tumor cells more sensitive to the immune defense mechanisms.

Elevated pretreatment levels of soluble CD8 and Beta-2-microglobulin as indicators of relapse in breast-cancer patients.

We measured soluble CD8 ((S)CD8) and microglobulin (beta-2M) in 128 breast cancer patients and in 200 controls by the ELISA method. Patient groups were: Group A-new patients; Group B-patients on follow-up; Group C-patients with metastases. The mean (S)CD8 and beta-2M were significantly higher in patients than in controls ((S)CD8 p<0.01, beta-2M p<0.0001). Both for (S)CD8 and beta-2M, groups A and C had high levels which differed significantly from Group B ((S)CD8 p<0.04; beta-2M p<0.0001). A significant correlation between (S)CD8 and B-2M was observed (r=0.379: p=0.0001). Twenty patients relapsed. In 14/20 (70%) an initial high (S)CD8 and in 10/20 (50%), high beta-2M was observed. High initial CD8 and beta-2M were able to identify 80% of relapsed patients. High (S)CD8 and beta-2M levels are indicative of tumor bulk and are able to identify patients at.

The expression of HLA class I antigens in germ cell testicular cancer.

The expression of HLA class I antigens in testicular germ cell tumors (TGCTs) was studied by the immunoperoxidase technique. In the normal testicle, the interstitial cells of Leydig as well as most of the germ cells were significantly stained. In typical seminoma, 75% of the tumor cells in stage I and 30% in stage II were stained. In embryonal cell carcinoma, 25% of the cases in stage I and less than 10% of those in stage II were stained. Mature teratoma was stained in most of the cases, whereas in malignant teratoma only 35% of the cases showed some staining of the tumor cells. In mixed tumors each component displayed its characteristic staining pattern. The expression of class I antigens on tumor cells is required for immune recognition and lysis of the tumor by cytotoxic T-cells. The reduced expression of class I antigens that was related to histologic characteristics and stage suggests that some testicular tumors may escape immune surveillance and become biologically more aggressive.

Early combined hormonal and chemotherapy for metastatic prostatic carcinoma.

Twenty-four patients with confirmed Stage D carcinoma of the prostate were treated with a combination of bilateral orchiectomy, estrogens (diethylstilbestrol) and chemotherapy (5-fluorouracil), and cyclophosphamide soon after diagnosis was established. Patients were followed up between forty-two to seventy-two months. Seventy-five per cent of patients reported relief of bone pain after initiation of therapy, and 83.3 per cent reported relief of their urinary symptoms. The primary tumor shrank in all patients, and initial stabilization or partial disappearance of osteoblastic lesions on bone scans was noted in 79.1 per cent of patients. The cumulative survival rates at five and six years were 63.48 and 50.78 per cent, respectively. The combined therapy was well tolerated by the patients, and complications were not severe and of a transient nature.

Serum intracellular adhesion molecule-1 (sicam-1) and soluble hla class-1 antigens in breast-cancer patients in relation to tumor burden.

sICAM-1 and beta-2 microglobulin (beta-2M) serum levels were measured in 143 breast cancer patients and 43 controls. The patients were divided into three groups. A: new patients; B: patients on long term follow-up and C: metastatic patients. In all patients the mean +/-1SD sICAM-1 and beta-2M serum levels were significantly higher than normal controls (p <0.001 and p <0.0001, respectively). Analysis of the three groups showed that for both sICAM-1 and beta-2M, Groups A and C had similar serum levels, which differed significantly from Group B. sICAM-1 of Group B was similar to controls, while beta-2M of Group B was significantly higher than controls. During the study 20 patients relapsed. Initial high levels of sICAM-1 were observed in 20% and beta-2M in 50% of patients. These data suggest that sICAM-1 and beta-2M level indicate host cell-mediated immunity against tumor.

The effect of irradiation on expression of HLA class I antigens in human brain tumors in culture.

The immunosuppressive effects of irradiation are well known; however, under certain circumstances irradiation also augments the local immune response by as yet undefined mechanisms. Because of the importance of HLA class I antigen in immune regulation and the fact that killing of tumor cells by cytotoxic T cells is HLA antigen-restricted, the authors studied HLA class I antigen expression in eight glioblastomas multiforme, four meningiomas, and four medulloblastomas. Twenty fragments of each tumor specimen were placed in short-term cultures immediately after resection. For each tumor, control Sample 1 was not irradiated. Sample 2 was irradiated on Day 1, and two groups of the remaining pieces of each tumor (specimens 3 to 10) were irradiated on two consecutive days. Escalating radiation doses were given, starting at 200 cGy/day for Sample 2 up to 1000 cGy/day for Sample 10. The total dose range was 200 to 2000 cGy. Corresponding nonirradiated tumor fragments served as controls. Four hours after irradiation, each sample was processed and stained for HLA class I antigen using the immunoperoxidase technique. The tumor cells were intensely stained in nonirradiated glioblastomas and meningiomas, whereas no staining was observed in medulloblastomas. In four of the eight glioblastomas and in all four meningiomas, irradiation augmented HLA class I antigen expression compared to controls. This effect was dose-dependent and was maximum in the 1200 cGy-treated specimens. No change was observed in the other four glioblastomas or in the medulloblastomas. The data suggest that irradiation does not decrease and may even induce HLA class I antigen expression in some brain tumors. This may be one of the mechanisms by which immunotherapy operates after irradiation. Further studies are required to elucidate optimum radiation doses and fractionation as well as optimum timing of immunotherapy.

The controversial treatment of anterior commissure carcinoma of the larynx.

There are two basic approaches to the appropriate therapy for carcinoma of the anterior commissure. The dilemma of whether to treat by primary irradiation or by conservative surgery is not yet solved. In this study, 67 patients were treated between 1967 and 1987 for anterior commissure carcinoma of the larynx. Radiation was used with 47 patients and conservation surgery with 20 patients. Initial lesion control was achieved with 72% of the patients treated by primary irradiation. Conservation surgery, when used as a primary treatment modality, achieved local control in 90% of the patients. The new techniques of reconstruction of the larynx enhance the surgeon's ability, strengthen his conviction to proceed to enlarged partial laryngectomies, and thus improve the oncologic control of the anterior commissure carcinoma as well.

The use of cyclophosphamide, methotrexate, and 5-fluorouracil in the treatment of Merkel cell carcinoma.

Five patients with advanced Merkel cell carcinoma (MCC) are described. Four patients with regional lymph node involvement and one with disseminated skin metastases were treated with systemic chemotherapy, including cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). The patients received a median of six cycles of CMF (range: 2 to 6), and chemotherapy was well tolerated. Four complete and one partial response were noted. Three patients are alive and are disease-free at 5, 12, and 37 months from the onset of CMF chemotherapy. Two patients died from disseminated metastatic disease at 3 and 24 months from the onset of chemotherapy. CMF chemotherapy appears to be an active regimen in the treatment of locally advanced MCC. Further experience with this combination is warranted.

Dynamic musculotendinous transfer to replace the anterior cruciate ligament in the dog.

Dynamic muscle-tendon substitution for acute anterior cruciate deficiency in the dog was studied using the semimembranosus muscle-tendon. Nineteen mongrel dogs each had a semimembranosus transfer in one knee; as a control, the anterior cruciate ligament and the semimembranosus were released in the opposite knee. No postoperative immobilisation was used. The anterior drawer sign was assessed before and after operation and when the dogs were killed five months later. Dogs were excluded from the study if they developed infections or contractures of the hind legs. At five months, 11 dogs were available for study. The operated knees were examined histologically and evaluated using a reproducible index of arthritis based on: the macroscopic discoloration of the articular cartilage, the cellularity of the cartilage, the microscopic appearance of the articular surface, the loss of proteoglycans, the formation of osteophytes and the degree of subchondral osteosclerosis. There was no significant difference in the anterior drawer sign or the degree of arthritic changes between knees with a semimembranous transfer and the controls. Examination showed that a muscle-tendon transfer into the tibia was equivalent to transferring the muscle into the posterior capsule--the intra-articular tendon being weak but histologically viable. The transfer did not prevent the anterior drawer sign becoming positive nor the development of osteoarthritis. A second control group, in which three dogs had an arthrotomy and semimembranosus release in both their hind legs, showed that a semimembranosus release alone did not cause osteoarthritis.

[Prognostic factors in multiple myeloma].

There have been major advances in the treatment of multiple myeloma in the past 20 years, but for the individual patient the prognosis still remains uncertain. As the length of survival varies from several months to over 10 years, definition of prognostic parameters at the time of diagnosis, and early detection of disease activity are most important. In our study, median survival was 42 months with very good quality of life. Factors not helpful in prognosis were sex, WBC and platelet counts, BUN, serum M protein type, extent of osteolytic lesions, percentage of plasma cells in bone marrow and plasma cell asynchrony. However, age, hemoglobin, calcium, uric acid, Bence-Jones proteinuria and polyclonal Ig concentrations had a certain degree of prognostic importance. Due to more sensitive and more specific laboratory methods, peripheral blood findings are lately gaining in importance. With new "salvage" protocols, the detection of additional prognostic parameters and sensitive indicators of disease activity may be most important for further improvement in the survival of patients with multiple myeloma.

[Letrozole (Femara), a new aromatase inhibitor for advanced breast cancer]. / Letrozol (Femara), novyi ingibitor aromatazy dlia lecheniia bol'nykh rasprostranennym rakom molochnoi zhelezy.

The study compares letrozole (Femara and aminoglutethimide (AG), a standard therapy for postmenopausal women with advanced breast cancer, previously treated with anti-estrogens. 555 women were randomly assigned letrozole 2.5 mg once daily (n = 185), letrozole 0.5 mg once daily (n = 192) or aminoglutethimide 250 mg twice daily with corticosteroid support (n = 178) in an open-label, multicenter trial. The primary end-point was objective response rate (ORR), with time events as secondary. ORR was analysed nine months after enrollment of the last patient, while survival was analysed 15 months after the last patients was enrolled. We report the results of these analyses plus an extended period of observation (covering a total duration of approximately 45 months) to determine the duration of response and clinical benefit. Overall objective response rates (complete + partial) of 19.5%, 16.7% and 12.4% were seen for letrozole 2.5 mg, 0.5 mg and AG respectively. Median duration of response and stable disease was longest for letrozole 2.5 mg (21 months) compared with letrozole 0.5 mg (18 months) and AG (14 months). Letrozole 2.5 mg was superior to AG in time to progression, time to treatment failure and overall survival. Treatment-related adverse events occurred in fewer patients on letrozole (33%) than on AG (46%). Letrozole 2.5 mg offers longer disease control than aminoglutethimide and letrozole 0.5 mg in the treatment of postmenopausal women with advanced breast cancer, previously treated with anti-estrogens.