Israel Medical Association Journal

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.

Sex steroid hormones (estrogens, progestagens and androgens) have been associated with healthy and neoplastic pancreatic biology, although the precise significance of the findings has not been well established. Receptors for the three different types of SSH are expressed in normal and tumoral pancreatic tissue with varying profiles related to cell origin (exocrine or endocrine), to type of neoplasm. and probably even to tumoral behavior. The activity of specific enzymes involved in the synthesis and transformation of SSH are increased in some neoplastic pancreatic tissues, which may influence the circulating concentrations of these hormones, such as the low serum testosterone: dihydrotestosterone ratio described in male patients with pancreatic carcinoma. Different patterns of age and gender-related incidence and growth of neoplasms have been identified. Experimental studies have shown that pancreatic carcinogenesis is promoted or inhibited by SSH. At present, the data supporting hormonal manipula­tion for the treatment of these tumors are non-conclusive. Normal and tumoral pancreatic tissues may be regarded as a target for SSH and an additional site of biosynthesis. The influence of these hormones on physiological activities is not well known but should be further explored. The study of SSH in pancreatic neoplasms will provide clues about its origin, development, tumoral behavior, prognosis and more specific hormonal therapy. We review here the evidence favoring the role of SSH and their possible clinical implications in pancreatic function.

Background: The free-to-total prostate-specificantigen ratio is the best marker for optimizing prostate cancer detection. The main problem with studies of percent free PSA is the variability of reported cutoff values.

Objectives: To evaluate the influence of prostate size on the ratio of free to total PSA.

Methods: The study group included 58 patients (mean age 66.4 years) with clinically localized prostate cancer treated surgically at our institution. Total PSA and free PSA levels were measured by a solid phase enzyme immunoassay test (Hoffman-La Roche, Basel, Switzerland). The percent free PSA was compared with prostate size as determined from the surgical specimen.

Results: A direct relation was noted between prostate size and the percent free PSA value (r=0.49, P=0.0001). Mean percentage free PSA was 9%0.004 in men with normal-sized gland while in men with large prostate (60 g) the average percent free PSA was 15.90.09 (P=0.001).

Conclusions: In patients with prostate cancer the percent free PSA level is influenced by the gland size. The larger the prostate the higher the proportion of the free PSA. Such information may have influence on the recommendation for prostate biopsy in screening programs for early detection of prostate cancer.

Background: First-degree relatives of colorectal cancer patients are the largest groups of individuals at increased risk for colorectal cancer.

Objective: To assess the knowledge, attitudes and behavior to disease prevention and colorectal cancer screening among first-degree relatives of colon cancer patients.

Methods: A descriptive, point-prevalence epidemiological study was conducted among 215 first-degree relatives of survivors of colorectal cancer in the southern (Negev) region of Israel. Variables included perceived health status, knowledge about cancer screening, compliance rates with colorectal cancer screening, and interest in participation in early detection programs in the future.

Results: The mean age of the respondents was 47.9111.2 years, and 54% were males. Only 58 (27%) remembered having been encouraged to undergo an early detection test. In the previous year only 15% underwent fecal occult blood tests, while 9% had a barium enema and 14% an endoscopic examination of the colon by sigmoidoscopy or colonoscopy. A total of 49% of the asymptomatic respondents were unaware of recommendations for screening, and only 38.3% expressed any interest in participating in early detection programs in the future. Only 19% of respondents over the age of 50 and 8% of respondents over age 60 were interested in participating compared with 49% under the age of 50 (P0.0001).

Conclusion: A minority of first-degree relatives of colorectal cancer patients reported having been counseled to undergo screening, although most had seen their family physician in the previous 3 years. Primary care physicians should be more active in informing at-risk patients and encouraging them to undergo periodic screening.

There is increasing evidence to suggest that aspirin and other non-steroidal anti-inflammatory drugs reduce the risk of colorectal cancer. This observation is supported by animal studies that show fewer tumors per animal and fewer animals with tumors after administration of several different NSAIDs. Intervention data in familial adenomatous polyposis have established that the effect is exerted on the process of human colonic adenoma formation. Supportive evidence in sporadic colorectal neoplasia, derived from 22 of 24 studies (both case-control and cohort), found a reduced risk in men and women for cancers of the colon and the rectum and for both aspirin and the other NSAIDs. Earlier detection of lesions as a result of drug-induced bleeding does not seem to account for these findings. Although the molecular mechanism responsible for the chemopreventive action of this class of drugs is not yet completely understood, the protection may affect several pathways including both cell cycle arrest and induction of apoptosis.

In the third millennium the question is not if but how. Based on the consistency of epidemiological, clinical and experimental data, the association between regular long-term aspirin or NSAIDs intake and a decreased death rate from colorectal cancer is sound and there is no need for further placebo trials. At the same time, despite this consistency there is no clear data on the dose, duration or frequency of use for cancer-preventive activity.