[Protective effect of the aerosol immunization of mice with the polycomponent vaccine Immunovac VP-4 after the challenge of the animals with Klebsiella pneumoniae virulent strain].

Used four schemes of the administration of the preparation with different time of the exposition of the animals in an aerosol chamber were tested with their subsequent intraperitoneal challenge with K. pneumoniae virulent strain K16. Irrespective of the number of immunization courses, the administration of the preparation made at intervals of 1 day, or daily, did not ensure any protective effect, but only led to an insignificant increase in their survival time in comparison with nonimmunized animals. After intervals between immunizations were increased to 3 days the protective effect of aerosol immumization was obtained (the survival rate was 65-80 % and considerably differed from that of the controls). The protective effect of aerosol immunization thus obtained was comparable with the effectiveness immunization made in a single subcutaneous injection. Aerosol immunization resulted in low antibody titers to the antigens contained in the vaccine, while after a single subcutaneous injection high antibody titers to Klebsiella and Proteus antigens were detected. The antigen-stimulated blast transformation of spleen lymphocytes in mice subjected to aerosol immunizations in 5 exposures was high. After subcutaneous immunization significant changes in such characteristics were detected on day 15. The data thus obtained were indicative of good prospects in the development Immunovac VP-4 as the medicinal form intended for use in aerosols.

[Bacterial chemotaxis to naphthalene]. / Izuchenie khemotaksisa bakterii k naftalinu.

The chemotaxis of two pseudomonads, P. putida AZ (Naph+) and P. putida AZ (Naph-), differing in the ability to metabolize naphthalene was studied by the known capillary method of Adler and the densitometric method devised in our laboratory. The migration of P. putida AZ (Naph+) cells toward increasing levels of naphthalene was accompanied by the formation of a migrating front of converted naphthalene. P. putida AZ (Naph-) cells, too, exhibited positive chemotaxis to naphthalene, but they did not form the front of converted naphthalene. The analysis of experimental data in terms of a kinetic model of bacterial chemotaxis showed that the densitometric method is a potential tool for studying bacterial chemotaxis to hydrophobic organic substances.

CMF (cyclophosphamide, methotrexate, 5-fluorouracil) versus cnf (cyclophosphamide, mitoxantrone, 5-fluorouracil) as adjuvant chemotherapy for stage II lymph-node positive breast cancer: a phase III randomized multicenter study.

A multicenter phase III randomized study compared the efficacies of two adjuvant polychemotherapeutic regimens in 145 patients with stage II node-positive breast cancer. The standard chemotherapy combination, CMF (cyclophosphamide, methotrexate, 5-fluorouracil), was administered to 77 women. The experimental protocol, CNF (cyclophosphamide, mitoxantrone, 5-FU), in which mitoxantrone (Novantrone) replaced methotrexate, was given to 68 patients. Follow-up of the 145 patients by six participating hospitals showed no statistically significant difference (p = 0.6) between the two treatment regimens during a median follow-up of 4.5 years in terms of overall survival. There was, however, a significant advantage (p = 0.04) in the disease-free survival for those receiving mitoxantrone (mean survival 4.4 years for CNF versus 2.7 years for CMF). Toxic side effects associated with CNF (particularly alopecia and myelotoxicity) were relatively more frequent but acceptable and did not lead to dose reduction. In light of its association with improved disease-free survival in this study, larger studies should be undertaken on the role of mitoxantrone as adjuvant treatment in stage II breast cancer.

[Breast conservation: safe for early breast cancer].

Between 1981-1993 581 women with primary breast cancer were treated by breast conservation. Their mean age was 56 +/- 12 years and 63% were postmenopausal and 37% pre- or perimenopausal. The median follow-up time was 56 months. 45% had pathological Stage I disease, 49% Stage II, 2.5% Stage III and 3.5% clinical Stage I-II disease. 54% of lesions were excised with good margins, 10% with close margins (< 0.5 cm), 9% with microscopic residual, 3% with macroscopic residual, and in 24% margins were not reported. Adjuvant therapy, consisting of combination chemotherapy and/or hormones, was given to 69%. Radiotherapy, usually 50 Gy tangential photon irradiation to the whole breast, was given to 564 (97%); an electron or photon "boost" to the tumor with a median dose of 17.5 Gy was given to 378 (65%). Most of those with positive nodes received 50 Gy to the lymphatic drainage system. 1 year after radiotherapy cosmetic results were rated as "good" or "excellent" in 80%, "moderate" in 17% and "poor" in 3%. The 5-year actuarial survival was 97% in Stage I and 88% in Stage II. 37 patients (6.5%) developed breast recurrence; 11 of these (2%) had simultaneous distant metastases. 5 (< 1%) developed axillary or supraclavicular lymph node metastases, and 81 (14%) developed distant metastases. Most local recurrences were in those younger than 40, and in those with primary tumors > 1.75 cm. The satisfactory level of local control achieved is attributed to the high doses of radiation (up to 75 Gy) administered to those with high risk lesions.

How daughters of women with breast cancer cope with the threat of the illness.

Coping strategies and attitudes toward medical treatment of 45 daughters of women who had had breast cancer were compared with strategies (sense of coherence) and attitudes on a health opinion survey of 51 women with no such family history who were referred to a breast health clinic in northern Israel. The daughters of women with breast cancer ranked lower on sense of coherence than the women with no such history. They also were more actively involved in the medical setting and requested more medical information than women whose mothers did not have breast cancer. The age of the daughter at the time her mother's cancer was diagnosed predicted her level of coherence and attitudes toward treatment.

[Taxol (paclitaxel) as second-line therapy in breast and ovarian cancer].

Results of chemotherapy with taxol (paclitaxel) in 55 patients with recurrent breast and ovarian cancer were reviewed. Taxol was given as a 3-hour infusion, every 3 weeks, on an outpatient basis. There was complete or partial response in 8 patients (23%) with breast cancer and 10 (50%) with ovarian cancer. Performance status and previous response to adriamycin were important prognostic factors. Toxicity was manageable. Treatment had to be stopped for hypersensitivity reactions in only 2 patients. Taxol given in an ambulatory clinic is safe and effective.

[Experience with conservative therapy in primary breast cancer: experiences Northern Israel Oncology Center, 1981-1990].

Between 1981 and 1990, 346 patients with primary breast cancer were treated using breast conservation. Mean age was 55 +/- 13 years and median follow-up 53 months. 36.5% were in pathological Stage I, 55% in Stage II, and 4% in Stage III, while 4.5% were in clinical Stages I-II. 60% of the lesions were excised with good margins, 12% with close margins (0.5 cm), 2.5% with macroscopic residuals, 7.5% with microscopic residuals and 18% with margins that could not be determined. Level II lymph node dissection was performed in 334 patients (97%). Adjuvant therapy (combination of chemotherapy and/ or hormones) was given to 223 (64%). Radiotherapy, usually 50-55 Gy tangential photon irradiation to the whole breast, was given to 335 (97%); electron or photon "boost" to the tumor bed was given to 234 (70%); most patients received 20 Gy. Most node-positive patients received 50 Gy to the lymphatic drainage system. A year after completion of radiotherapy cosmetic results were rated as good in 195/212 (92%), moderate in 17/212 (8%), but in none as poor. 5-year actuarial survival was 90% for Stage I and 81% for Stage II disease. 24 (7%) developed breast recurrence, 8 of whom (2%) also had distant metastases; 5 (1.5%) developed supraclavicular lymph node metastases and 59 (17%) distant metastases. Predictors of poor survival or local recurrence were: age under 40 years, premenopausal status, multifocality, and blood/lymph vessel infiltration by tumor cells. The satisfactory level of local control achieved is attributed to the high doses of radiation administered in high-risk lesions (up to 70 Gy total tumor dose).

Screening for ovarian cancer in women with breast cancer with transvaginal sonography and color flow imaging.

The aim of the present study was to determine the efficacy of transvaginal color flow imaging as a screening tool for ovarian cancer. Six hundred patients with previous breast carcinoma were screened for ovarian cancer. Screening was performed using transvaginal sonography with color flow imaging. Serum CA 125 levels were measured in patients with abnormal sonographic findings. Eighty-three percent of the ovaries were detected in the premenopausal patients by ultrasonographic scanning and only 26% of the ovaries were detected in the postmenopausal patients. Intraovarian blood vessels were detected in 11% of the premenopausal women. The PI was less than 1 in 80% of these ovaries, but, on repeated examinations, the values of PI increased in all the blood vessels to greater than 1. Intraovarian blood vessels were detected in 1.8% of the normal ovaries observed in the postmenopausal women, but PI was always greater than 1. Eleven women with complex ovarian cysts (not simple) and one woman with enlarged ovaries underwent explorative laparotomy. In three women, primary malignant ovarian tumors were diagnosed and in one woman metastatic ovarian cancer was diagnosed. The specificity of sonography in detecting malignant ovarian tumors was 97.5% and the positive predictive value was 25%. The specificity of color flow imaging in detecting primary malignant ovarian tumors was 99.8% and the positive predictive value was 60%. In selected groups of women, screening for ovarian cancer with transvaginal color flow imaging may be justified.

Mitoxantrone as second-line single agent in metastatic breast cancer.

Mitoxantrone (MIX), a member of the anthraquinone chemical class, was found to be a potential anticancer agent. It has a similar spectrum of activity as Adriamycin in experimental and human tumors. Thirty-five female patients with metastatic breast cancer, refractory to previous chemotherapy, were treated between 1986 and 1987 with MIX (14 mg/m2 i.v. every 3 weeks); patients with diffuse bone metastases or heavily pretreated patients received 10-12 mg/m2 MIX. All patients were evaluable for response and toxicity. Two patients achieved complete response and 4 partial response, giving an overall response rate of 17%. Median time of response was 5.5 months. The drug was well tolerated. Objective response was obtained mostly in patients with a performance status (Karnofsky scale) of more than 70%, and in those who received more than 12 mg/m2 MIX per course. One patient developed cardiomyopathy, another an acute myocardial infarction, and 3 patients had pathological changes on echocardiography or multigated nuclear angiography. Hematological and gastrointestinal toxicity was tolerable. We found MIX to be a potentially effective second-line treatment with mild toxicity in patients with metastatic breast cancer.

Malignant melanoma occurring during pregnancy: a report of the Northern Israel Oncology Center (1968-1988).

Medical records of seven patients treated within a 20 year period for malignant melanoma during pregnancy were reviewed. No significant detrimental prognostic effects could be attributed to pregnancy. The current literature on melanoma and pregnancy is discussed. Based on this, pregnancy seems not to be contraindicated in melanoma patients.

Malignant pericardial tamponade.

We studied the clinical course and management of 27 patients with malignant pericardial tamponade seen in a single Medical Center over a 10 year period. Patients treated with repeat pericardial tap as their only mode of therapy had a high rate of recurrent tamponade (6 of 13 subjects) whereas most patients treated with drainage (either surgical or percutaneous) had sustained control of their pericardial effusion (achieved in 10/13 subjects). Intra-pericardial instillation of tetracycline or cyclophosphamide did not clearly improve the good results obtained with drainage alone. Extensive pericardiectomy was required in 2 patients only. Irrespective of the mode of therapy, survival was poor in patients with carcinoma of lung (N = 10) with a median survival of 30 days only vs. 135 days for patients with breast carcinoma (N = 10). Patients with malignant pericardial tamponade are best treated with immediate drainage. Percutaneous and sub-xiphoid surgical drainage are equally effective. Despite invasion of the pericardium by carcinoma, patients with a good oncologic prognosis may enjoy an appreciable survival with adequate quality of life following relief of tamponade.

[Treatment of stage I malignant melanoma].

In 259 patients with malignant melanoma of the skin referred here during 1973-1984, the median follow-up was 46 months. Of 182 with stage I disease, 97 (53.2%) were women and 85 men. Of these, 90.1% were Jews of European extraction and 8.2% were Jews of Asian-African extraction, while only 1.8% were non-Jews. 171 (94%) of the patients were treated by wide excision, with or without skin graft, as primary treatment, while 11 had limited local excision. In 16.4% the primary tumor was located on the upper limbs, in 34.6% the lower limbs, in 27.5% the trunk and in 19.2% the head and neck. 5-year survival was 70%. The 5-year actuarial survival was significantly influenced by: age (those under 50 had better survival, 79.5% vs 58.4%, p less than 0.05); by site of the primary lesion (88.5% for those of the upper limbs vs 59.4% for those of the lower limbs), p less than 0.01]; by depth of invasion as seen microscopically (81.2% for Clark I-II vs 52.8% for Clark IV-V, p less than 0.02); and by site of recurrence (43.4% if local vs 0 for distant, p less than 0.02).

Cardiac tamponade in medical patients: treatment and prognosis in the echocardiographic era.

Experience was reviewed in the management of pericardial tamponade in 36 patients with emphasis on factors governing short and long-term survival. Malignant pericardial effusion was the most common etiology and accounted for pericardial tamponade in 14 of the 36 patients (39%). Of the 36 patients, three received medical therapy alone, 18 were treated by one or more needle pericardiocentesis, pericardial drains were inserted in six patients, and thoracotomy was performed in nine. Needle pericardiocentesis was attempted as the initial therapy in all but two patients and was initially successful in relieving tamponade in 30 patients. Twenty-four patients died during a follow-up of from 1 day to 6 years. Delay in diagnosing tamponade was frequent and accounted for three deaths. Two more patients died from recurrent tamponade following initial relief. Eighteen patients died primarily from complications related to their basic illness, though recurrent pericardial effusion was a contributory factor in five. One patient died following pericardiectomy. The remaining 12 patients are well and free of pericardial disease. Short-term survival in pericardial tamponade is mostly dependent upon early diagnosis and relief of tamponade. Long-term survival depends upon the prognosis of the primary illness, irrespective of the mode of treatment used.

Factors affecting delay in diagnosis of breast cancer: relationship of delay to stage of disease.

In a study of 523 patients with breast cancer, delay in diagnosis was examined in relation to stage of disease, age and ethnic origin. Localized disease was found in 44% of the patients, regional disease in 40%, and metastatic disease in 9%. Stage was unknown in 7%. The incidence of breast cancer was significantly higher in Occidental Jews (of European origin) than in Oriental Jews (of Asian or North African origin) or in Arabs. The median and mean age were significantly higher in the Occidental Jewish group. Older patients (greater than 70) had more advanced disease and longer delay. Diagnosis was delayed (greater than 6 weeks) in 43% of the patients. Diagnosis was attributable to the patient in 69% of cases and to the physician in 30%. There was no delay in diagnosis for most of the patients with localized disease, whereas there was for most of those at an advanced stage. When there was a delay, it was longer in those with advanced disease. Delay due to physician responsibility was longer than the delay due to patient responsibility. Although the percentage of patients with delayed diagnosis was similar in the three ethnic groups studied, the stage of disease was significantly more advanced in Oriental Jews and Arabs than in Occidental Jews. The possible explanations for these findings are discussed. The importance of patient education aimed at breast self-examination and the role of the physician in preventing delay in diagnosis are stressed.

Mitomycin, doxorubicin, and vinblastine as second-line chemotherapy in patients with advanced breast cancer.

Thirty-seven patients with disseminated breast cancer refractory to previous therapy were treated with a combination of mitomycin, doxorubicin, and vinblastine (MAV). One complete and eight partial responses were achieved, with an overall response rate of 24.3%. The median duration of response was 5+ months. The MAV regimen had generally moderate but acceptable toxicity. This study indicates that the MAV combination is no better than doxorubicin given as a single agent.

Multimodal approach (surgery, chemotherapy, and radiotherapy) in the treatment of advanced ovarian carcinoma.

Forty-five patients with advanced ovarian carcinoma without prior chemotherapy were treated with cisplatin-Adriamycin (doxorubicin) combination, 50 mg/m2 intravenously, for 11 cycles. Second-look operation (SLO) was performed in patients without evidence of disease at the end of chemotherapy. Abdominopelvic irradiation was administered to those found to have microscopic or minimal disease (tumor less than 2 cm) at SLO. Forty patients were evaluable. Chemotherapy induced complete response in 56.7% and partial response in 16.7%. In 25% of the reoperated patients, no tumor was found; 30% had microscopic disease; 25% had minimal disease; and 20% had larger tumors. Two-year survival rate was 45%. The residual tumor left at initial operation, the histologic grade, and the response to chemotherapy influenced survival. Toxicity was moderate. There were three treatment-related deaths (one due to sepsis, one due to cardiotoxicity, and one at SLO, respectively). Radiotherapy was poorly tolerated after chemotherapy. The median duration of follow-up was 21.5 months. Further follow-up is needed to study the long-term benefits of this multimodal approach.

Postirradiation soft tissue sarcoma occurring in breast cancer patients: report of seven cases and results of combination chemotherapy.

Seven cases of soft tissue sarcoma developing after primary or postoperative radiotherapy for breast carcinoma are reported. The sarcomas occurred within the irradiated volume, after a latent period of 4-26 years. These cases conform well to established criteria for the diagnosis of radiation-induced sarcoma. Chemotherapy, consisting of the four-drug combination CYVADIC (cyclophosphamide, vincristine, adriamycin, DTIC) was employed in six of the seven patients. Only two of them achieved partial remission, lasting only 2 and 3 months, respectively. The effectiveness of adriamycin-containing chemotherapy regimens in soft tissue sarcomas as well as the remote hazard of radiation-related sarcoma in primary or postoperative breast irradiation are discussed.