Israel Medical Association Journal

Background: Recent years have brought significant progress to the development of hormonal therapies for the treatment of breast cancer. Several new agents have been approved for the treatment of breast cancer in the metastatic setting, among which is the new non-steroidal aromatase inhibitor, anastrozole, introduced for clinical use in Israel in March 1997.

Objectives: To evaluate the response rate and survival duration of patients treated with anastrozole for metastatic breast cancer, who had previously received at least one line of hormonal therapy.

Methods: Anastrozole was administered to 37 patients with metastatic breast cancer. The median age was 64 years. Estrogen receptor was positive in 20 patients, negative in 10 and unknown in 7. All patients were previously treated with tamoxifen in the adjuvant setting or as first-line hormonal therapy for metastatic disease. Anastrozole was given orally, 1 mg/day. Response was evaluated 2 months after the initiation of treatment and reevaluated every 2 months. Therapy was given until disease progression. Ten ER[1]-negative patients were excluded from the final analysis.

Results: Twenty-seven patients were eligible for response and toxicity analysis. The median follow-up was 20 months. One patient (3.7%) achieved complete response and remains free of disease 28 months after start of therapy. No partial responses were seen. Twenty patients (74%) had stable disease. Two year actuarial survival was 57%. Median survival was 26.5 months after starting therapy and median progression free survival was 11 months. The toxicity was mild: one patient (3.7%) complained of weight gain and one patient (3.7%) had mild fatigue.

Conclusion: Although the response rate was low, hormonal therapy with anastrozole seems to be beneficial in terms of disease stabilization, freedom from progression, and overall survival without serious toxicity.  

Background: The importance of health promotion and disease prevention in health policy and clinical practice is widely accepted in many countries. However, a large number of medical schools do not dedicate a significant part of their curriculum to these aspects. In Israel, there are no reports on the training of the future physician towards his or her role as health promoter in general, or in the areas of cardiovascular and cancer diseases specifically.

Objectives: To examine the preparation of Israel medical students for the role of health promoter in cancer and cardiovascular diseases.

Methods: The study was carried out over 2 years in two of the four medical schools in Israel: the Sackler Faculty of Medicine at Tel Aviv University and the Faculty of Health Sciences at Ben Gurion University in Beer Sheva. The students (n=172, 70% response rate) were surveyed during 1999-2000 by means of a questionnaire, which included assessment of their training towards the role of health promoter, their clinical experiences and exposure to patients at different stages of illnesses at various medical sites, and the specific skills and relevant knowledge they acquired.

Results: Most of the students’ learning experiences occurred in hospitals with patients at the treatment stage and little time was dedicated to prevention, especially in the community. They demonstrated better knowledge, skills and satisfaction with their learning experiences in CVD than in cancer; and reported having insufficient exposure to several common cancer diseases and lacking examining skills for early detection of cancer. The students in Beer Sheva had significantly more interaction with patients at different stages of CVD and acquired more examination skills than the Tel Aviv students.

Conclusions: A change in the curriculum is urgently needed: namely training medical students in community settings and preparing them to promote the well-being of their patients, including prevention. Attention should be given to launching new learning modes in the pre-clinical and clinical curriculum. We propose that: a) pre-clinical courses include prevention techniques in CVD and cancer, problems of cancer patients, and some examining skills; and b) the clinical phase should integrate oncology concepts and total cancer and CVD care into existing clerkships in the hospitals and in the community.
 

Background: Breast cancer is the most common malignancy among women in Israel and throughout the world. Israeli women aged 50–75 years are advised to undergo a mammographic screening examination every 2 years. However, the lack of a structured referral system is reflected in the low utilization rate of mammography.

Objectives: To describe an innovative program in which family physicians in an urban clinic developed a model framework for referrals, coordinated with radiologists and surgeons, aimed at increasing compliance among women referred for mammography.

Methods: A community-based study was conducted, outside of the regular reception hours, in a neighborhood practice with a population of 527 women aged 50–75. A referral system under the supervision of family physicians was designed, and the women received appointments for mammography at specified days and hours. The results of the examination were sent to the physician who used dedicated time to continue the diagnostic and/or therapeutic process, as appropriate. At the physician’s instructions a research assistant contacted the women who did not keep their appointments and scheduled a second appointment.

Results: In 1993, the year prior to the study, when women referred themselves for mammography, the utilization rate was 9%. During the study year the utilization rate was 77%. Women born in Europe or America had higher compliance rates than women born in Asia or Africa (81% vs. 72%, respectively). Married women were more compliant than unmarried women (81% vs. 70%, respectively). No correlation was found between compliance and age, family history of cancer in general, or breast cancer in particular. Six new cases of breast cancer were detected.

Conclusions: The initiative of family physicians increased the utilization of mammography among women under their care. Family physicians allocated time outside of their regular reception hours for the program. A relatively large number of new malignancies were found, but this impression should be confirmed or negated by a large-scale study using the same methods.
 

Background: Fibroadema, one of the most common benign breast lesions, has a characteristic age-specific incidence and is associated with other pathological entities in 50% of cases. The clinical or imaging diagnosis of fibroadenoma may be erroneous, and in some cases is found to be invasive cancer. The clustering of such entities, their correlation with age, and the risk of synchronous breast malignancy are uncertain.

Objective: To explore the possibility of any sigficant clustering of fibroadenoma-associated benign breast disease and to assess the possible risk of concomitant breast cancer.

Method: We analyzed the pathological results of 147 women undergoing excisional biopsies for fibroadenoma diagnosed pre-operatively either by clinical examination and imaging (n=117) or by radiology alone (n=30). The inter-relationships among all entities associated with fibroadenoma were studies by hierarchial cluster analysis. The correlation of the various pathologies with the risk of invasive breast cancer in relation to the patient’s age was also evaluated.

Results: Fibroadema-associated pathologies were found in 48% of the cases: sclerosing adenosis (23%), duct ectasia (17/7%), apocrine metaplasia (15.6%), florid fibrocystic disease (12.9%), duct papillomatosis (11.6%), infiltrating duct carcinoma (5.4%), duct carcinoma in situ (3.4%), and 1 case of lobular carcinoma in situ (0.6%). An orderly internal hierarchy and three significant clusters emerged: a) epithelial apocrine metaplasia, duct ectasia and sclerosing adenosis (similarity coefficients 16.0, 11.0 and 8.0 respectively); b) papillomatosis, florid fibrocystic disease and calcifications (similarity coefficients of 6.0, 4.0 and 2.0 respectively); and c) infiltrating duct carcinoma in situ (similarity coefficients of 1.8 and 1.6 respectively). Seven of the eight patients with breast cancer were older than 40 years.

Conclusions: In about half of the cases fibroadema was associated with other pathological entities clustered in an orderly hierarchy. The rarity of synchronous breast cancer in the younger age group and its more common association with fibroadema in the older age groups dictate a different approach to each. The finding of fibroadema in women older than 40 indicates the need for surgical excision.
 

Background: Breast cancer is one of the most prevalent malignancies in women, yet one of the most treatable. Early detection is essential to obtain the desired remission and longevity. Numerous studies have shown that periodic screen­ing for breast cancer can reduce mortality by 20-30%.

Objective: To assess the rates, compliance, character­istics as well as barriers in women regarding mammography screening.

Methods: The study group comprised a random sample of 702 women aged 50 or older from 5914 eligible women in two teaching clinics in southern Israel. Phone interviews using structured questionnaires were conducted.

Results: The mean age of the study population was 61 years. The vast majority of the women were not born in Israel. Sixty-three percent of the women had undergone a mammo­graphy screening, 48% in the past 2 years. Monthly self-breast examinations were performed by 12% of the women in the last 2 years. Significant factors associated with undergoing mammography were: more than 7 years since immigration, married, a higher education level, adequate knowledge about breast cancer and mammography, presence of past or current cancer, and cancer in relatives. The main reasons for not being screened was no referral (54%) and a lack of knowledge about breast cancer and mammography (19%) - conditions easily remedied by physician counseling.

Conclusion: The study suggests that promotional efforts should be concentrated on new immigrants and on less educated and unmarried women.

Background: Cryosurgery is a minimally invasive treat­ment option for prostate cancer.

Objectives: To report on the first series of cryosurgical ablation for prostate cancer performed in Israel.

Methods: Cryosurgical ablation of the prostate was undertaken in 2 patients aged 53-72 diagnosed with adenocarcinoma of the prostate. The procedures were performed percutaneously and were monitored by real-time trans-rectal ultrasound. The CRYOHIT machine applying Argon gas was used with standard or ultra-thin cryoprobes. The average follow-up was 12.8 months postsurgery (range 1- 24 months).

Results: No rectal or urethral injuries occurred and all patients were discharged from hospital within 24-48 hours. The duration of suprapubic drainage was 14 days in 10 patients and prolonged in 2. Early complications included penoscrotal edema in four patients, perineal hematoma in three, hemorrhoids in two and epidydimitis in one. Long-term complications included extensive prostatic sloughing in one patient and a perineal fistula in another, both of whom required prolonged suprapubic drainage. Minimal stress incontinence was noted in two patients for the first 8 weeks after surgery. None of the patients has yet regained spontaneous potency. A prostate-specific antigen nadir of less than 0.5 ng/ml was achieved in eight patients and an undetectable PSA level below 0.1 ng/ml in five patients.

Conclusion: Cryoablation for prostate cancer is safe and feasible, and the preliminary results are encouraging. Further study is needed to elucidate the efficacy of the procedure.

Between the 1960s and 1980s, the main focus of biological research was nucleic acids and the translation of the coded information into proteins. Protein degradation was a neglected area and regarded by many as a scavenger, non-specific and end process. While it was known that proteins are turning over, the large extent and high specificity of the process - where distinct proteins have half-lives that range from a few minutes to several days - have not been appreciated. The discovery of the lysosome by Dr. Christian de Duve did not change this view significantly, as this organelle is involved mostly in the degradation of extra- and not intracellular proteins, and it was clear that lysosomal proteases, similar to those of the gastrointestinal tract, cannot be substrate specific. The discovery of the complex cascade of the ubiquitin pathway has changed this view dramatically. It is now clear that degradation of cellular proteins is a highly complex, temporally controlled, and tightly regulated process that plays major roles in a broad array of basic pathways during cell life and death. With the multitude of substrates targeted and processes involved, it is not surprising that aberrations in the pathway have been recently implicated in the pathogenesis of many diseases, certain malignancies and neurodegeneration among them. Degradation of a protein via the ubiquitin pathway involves two successive steps: a) conjugation of multiple ubiquitin moieties to the substrate, and b) degradation of the tagged protein by the downstream 263 proteasome complex with release of free and re-utilizable ubiquitin. Despite intensive research, the unknown still exceeds what we currently know on intracellular protein degradation and major key problems remain unsolved. Among these are the modes of specific and timed recognition of the myriad substrates of the system and the nature of the mechanisms that underlie aberrations in the system and pathogenesis of diseases.

Background: Recent genetic susceptibility findings in Jews of Eastern European descent, commonly called Ashke­nazi Jews, have led to concerns that they may be stigmatized as being more cancer prone than other groups.

Objective: To examine the hypothesis that site-specific or all-cancer incidence and mortality rates are higher than expected in Ashkenazi Jews worldwide when compared with referent populations.

Methods: A MEDLINE search was performed using keywords "Jews", "cancer", "incidence" and "mortality" to identify studies directly relevant to the primary study question.

Results: Little evidence suggested that all-cancer inci­dence or mortality is higher in Ashkenazi Jews than in North American non-Hispanic whites. Ashkenazi Jewish men appear to have relatively low cancer rates, which may be due to lower tobacco use. Colorectal cancer was shown to disproportio­nately overburden Ashkenazi Jews, who may also be at increased risk for ovarian, pancreatic and stomach cancer, and non-Hodgkin’s lymphoma. Little evidence was found support­ing an elevated risk of breast cancer in Ashkenazi Jewish women. Rates of lung, cervical, penile and prostate cancers appear low in this population. Rate disparities were generally attributed to lifestyle differences, particularly diet and tobacco use, rather than to genetic predisposition.

Conclusions: Ashkenazi Jews do not appear to have a higher total cancer burden than comparable North American populations. Any cancer rate differentials in this group are more likely to be related to lifestyle and dietary factors than to genetics. However, colorectal cancer rates in Ashkenazi Jews may be the highest of any ethnic group in the world and cancer controllers should consider this when developing future screening, diagnostic and policy strategies.