Israel Medical Association Journal

Background: Germline mutations in BRCA1 and BRCA2 genes account for only 20–40% of familial breast cancer cases. The CHEK2 gene encodes a checkpoint kinase, involved in response to DNA damage, and hence is a candidate gene for breast cancer susceptibility. Indeed, the CHEK2*1100delC truncating mutation was reported in a subset of mostly North European breast cancer families. The rate of the CHEK2*1100delC variant in the Ashkenazi* Jewish population was reported to be 0.3%.

Objectives: To evaluate whether CHEK2 germline mutations contribute to a breast cancer predisposition in Ashkenazi-Jewish high risk families.

Methods: High risk Ashkenazi Jewish women, none of whom was a carrier of the predominant Jewish mutations in BRCA1/BRCA2, were genotyped for germline mutations in the CHEK2 gene by exon-specific polymerase chain reaction followed by denaturing gradient gel electrophoresis and sequencing of abnormally migrating fragments.

Results: Overall, 172 high risk women were genotyped: 75 (43.6%) with breast cancer (average age at diagnosis 49.6 ± 9.6 years, mean ± SD) and 97 asymptomatic individuals (age at counseling 48.3 ± 8.2 years). No truncating mutations were noted and four previously described missense mutations were detected (R3W 1.2%, I157T 1.2%, R180C 0.6% and S428F 5%), one silent polymorphism (E84E 20.5%) and one novel missense mutation (Y424H 1.2%). Segregation analysis of the I157T and S428F mutations (shown to affect protein function) with the cancer phenotype showed concordance for the CHK2*I157T mutation, as did two of three families with the CHK2*S428F mutation.

Conclusions: CHEK2 missense mutations may contribute to breast cancer susceptibility in Ashkenazi Jews.

A thorough medical inquiry is included in every aviation mishap investigation. While the gold standard of this investigation is a forensic pathology examination, numerous reports stress the important role of computed tomography in the postmortem evaluation of trauma victims. To characterize the findings identified by postmortem CT and compare its performance to conventional autopsy in victims of military aviation mishaps, we analyzed seven postmortem CT examinations. Musculoskeletal injuries accounted for 57.8% of traumatic findings, identified by postmortem CT. The most frequent findings were fractures of the rib (47%), skull (9.6%) and facial bones (8.6%). Abnormally located air accounted for 24% of findings, for which CT was superior (3.5% detected by autopsy, 100% by postmortem CT, P < 0.001).  The performance of autopsy in detecting injuries was superior (autopsy detected 85.8% of all injuries, postmortem CT detected 53.9%, P < 0.001), especially in the detection of superficial lesions (100% detected by autopsy, 10.5% by postmortem CT, P < 0.001) and solid organ injuries (100% by autopsy, 18.5% by postmortem CT, P < 0.001), and in the detection of musculoskeletal injuries (91.3% for autopsy, 90.3% for postmortem CT, P = not significant). Postmortem CT and autopsy have distinct performance profiles, and although the first cannot replace the latter it is a useful complementary examination.

Background: The epidemiology of bacteremic febrile neutropenia differs between locations and constitutes the basis for selection of empiric antibiotic therapy for febrile neutropenia.

Objectives: To describe the epidemiology of bacteremia among patients with neutropenia in a single center in Israel.

Methods: We conducted a prospective data collection on all patients with neutropenia (< 500/mm³) and clinically significant bacteremia or fungemia during the period 1988–2004.

Results: Among adults (462 episodes) the most common bloodstream isolate was Esherichia coli. Gram-negative bacteria predominated throughout the study period and the ratio between Gram-negative and Gram-positive bacteremia increased from 1.7 to 2.3 throughout the study period. Among children (752 episodes), the ratio between Gram-negative and Gram-positive bacteremia reversed from 1.2 to 0.7, due to increasing prevalence of coagulase-negative staphylcoccal bacteremia. Both among adults and children, the length of hospital stay prior to bacteremia had a major impact on the pathogens causing bacteremia and their antibiotic susceptibilities. The prevalence of E. coli decreased with time in hospital, while the rates of Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter spp., Acinetobacter spp., Enterococcus spp. and Candida spp. increased. Resistance to broad-spectrum empiric monotherapy in our center was observed in > 40% of Gram-negative bacteria when bacteremia was acquired after 14 days in hospital.
Conclusions: Improved infection-control measures for neutropenic cancer patients in our center are needed. Empiric antibiotic treatment should be tailored to patients’ risk for multidrug-resistant organisms. Individual hospitals should monitor infection epidemiology among cancer patients to guide empiric antibiotic treatment

Background: Most Israeli males aged 16–17 undergo a thorough medical examination prior to recruitment into the army. During the last 50 years, extensive data have been gathered enabling a study of time trends in the prevalence of common diseases in this age group.

Objectives: To examine the current prevalence of common diseases, compare the results with those of previous cohorts, and assess the influence of the massive immigration during the 1990s.         

Methods: The health examination at the recruitment centers includes a medical history, complete physical examination, and review of medical documentation provided by the family physician. If needed, additional tests and referral to specialists are ordered. The prevalence of selected diseases and severity was drawn from the computerized database of the classification board. Two cohorts, 1992–94 and 2003–04, were examined and compared with three previous cohort studies in 1957–61, 1977–78 and 1982–84. Data were stratified according to origin and country of birth.

Results: The prevalence of asthma increased dramatically during the years from 10.2 per 1000 examinees in 1957–61 to 111.6 per 1000 examinees in 2003–04. The prevalence of tuberculosis declined and then increased from 0.6 per 1000 adolescents in 1982–84 to 2.4 per 1000 adolescents in 2003–04. The prevalence of type 1 diabetes mellitus increased from 0.2 cases per 1000 examinees in 1957–61 to 0.8 cases in 1977–78 and 1982–84 and 0.9 cases per 1000 examinees in 2003–04. The prevalence of severe heart defects and severe epilepsy declined in the last 20 years (1.4 and 1.7 cases per 1000 examinees in the 1982–84 cohort to 0.4 and 0.3 cases per 1000 examinees in the 2003–4 cohort respectively). The patterns of disease prevalence were different for immigrants: tuberculosis was more common while asthma and allergic rhinitis were less prevalent.

Conclusions: The prevalence of common diseases among adolescents in Israel has changed over the last 50 years. There is a different pattern for immigrants and for those born in Israel.

Background: Debate continues in Israel as to whether to allow patients in public hospitals to choose their physician in return for an additional, out-of-pocket payment. One argument against this arrangement is that the most senior physicians will devote most of their time to private patients and not be sufficiently available to public patients with complex cases.

Objectives: To analyze the patterns of surgical seniority in Jerusalem hospitals from a number of perspectives, including the extent to which: a) opting for private care increases the likelihood of being treated by a very senior surgeon; b) public patients undergoing complex operations are being treated by very senior surgeons, c) the most senior surgeons allocate a significant portion of their time to private patients.

Methods: Demographic and clinical data were retrieved from the operating room records of three of the public hospitals in Jerusalem for all 38,840 operations performed in 2001. Of them, roughly 6000 operations (16%) were performed privately. Operations were classified as "most complex," "moderately complex" and "least complex" by averaging the independent ratings of eight medical and surgical experts. The surgeon's seniority was graded as "tenured" (tenured board-certified specialists, including department heads), "senior" (non-tenured board-certified specialists), and "residents." For each operation, we considered the seniority of the lead surgeon and of the most senior surgeon on the surgical team.

Results: The lead surgeon was of tenured rank in 99% of the most complex private cases and 74% of the most complex public cases, in 93% of the moderately complex private and 35% of the moderately complex public cases, and in 92% of the least complex private and 32% of the least complex public cases. The surgical team included a tenured physician in 97%, 66%, and 53% of the most complex, moderately complex, and least complex public operations, respectively. In both private and public cases, a board-certified (tenured or senior) specialist was a member of the surgical team for almost all of the most complex and moderately complex operations. On average, over half of the operations in which the lead surgeon was a department head were performed on public patients. Among tenured surgeons, those who spent more hours than their colleagues leading private operations also tended, on average, to spend more hours leading public operations.

Conclusions: Private patients have an advantage over public patients in terms of the seniority of the lead surgeon. However, there is also substantial involvement of very senior surgeons in the treatment of public patients, particularly in those cases that are most complex. 

Background: Sentinel lymph node mapping is the standard of care for patients with malignant melanoma and breast cancer. Recently, SLN[1] mapping was introduced to the field of gastric cancer.

Objectives: To evaluate SLN mapping in patients with gastric cancer.

Methods: In 43 patients with gastric cancer, open intraoperative subserosal dye injection in four opposing peritumoral points was used. Ten minutes following dye injection, stained LNs were located, marked and examined postoperatively from the surgical specimen.

Results: SLN mapping was performed in 43 with gastric cancer; 782 lymph nodes were harvested and evaluated. SLNs were stained in 34 of the patients (79.1%) with a mean of 2.85 SLNs per patient. The false negative rate was 20.9%, the positive predictive value 100%, the negative predictive value 78.6% and the sensitivity 86.9%.

Conclusions: SLN mapping in patients with gastric cancer is feasible and easy to perform. SLN mapping may mainly affect the extent of lymph node dissection, and to a lesser degree gastric resection. However, more data are needed.

Objectives: To establish the impact of breast MRI on women undergoing testing in our institution.

Methods: We analyzed 82 cases that underwent MRI between January 2001 and April 2003. Analysis appraised the clinical impact of MRI testing in cases where medical summaries were available.

Results: Studies were categorized into five indications: a) screening in high risk women (n=7), b) search for primary disease in the presence of disease (n=5), c) monitoring of chemotherapy (n=2), d) postoperative assessment of tumor bed (n=9), and e) diagnostic/characterization of primary or recurrent breast cancer (n=59). Results were defined as negative, positive or no impact on clinical management. MRI testing had a positive impact in 62 cases, affecting measurable change in 9 cases. Benefit was seen in screening, diagnosis and postoperative cases. In 15 cases, MRI stimulated investigations.

Conclusion: MRI is a valuable tool in breast imaging and affects management. Further trials are necessary to define clearly the role of MRI and to ascertain whether in cases where beneficial impact on management is noted, there is ultimate impact on outcome.