Israel Medical Association Journal

Background: Fanconi anemia complementation group C and Bloom syndrome, rare autosomal recessive disorders marked by chromosome instability, are especially prevalent in the Ashkenazi* Jewish community. A single predominant mutation for each has been reported in Ashkenazi Jews: c.711+4A→T (IVS4 +4 A→T) in FACC[1] and BLM^Ash in Bloom syndrome. Individuals affected by both syndromes are characterized by susceptibility for developing malignancies, and we questioned whether heterozygote carriers have a similarly increased risk.

Objectives: To estimate the cancer rate among FACC and BLM^Ash carriers and their families over three previous generations in unselected Ashkenazi Jewish individuals.

Methods: We studied 42 FACC carriers, 28 BLM^Ash carriers and 43 controls. The control subjects were Ashkenazi Jews participating in our prenatal genetic screening program who tested negative for FACC and BLM^Ash. All subjects filled out a questionnaire regarding their own and a three-generation family history of cancer. The prevalence rates of cancer among relatives of FACC, BLM^Ash and controls were computed and compared using the chi-square test.

Results: In 463 relatives of FACC carriers, 45 malignancies were reported (9.7%) including 10 breast (2.2%) and 13 colon cancers (2.8%). Among 326 relatives of BLM^Ash carriers there were 30 malignancies (9.2%) including 7 breast (2.1%) and 4 colon cancers (1.2%). Controls consisted of 503 family members with 63 reported malignancies (12.5%) including 11 breast (2.2%) and 11 colon cancers (2.2%).

Conclusions: We found no significantly increased prevalence of malignancies among carriers in at least three generations compared to the controls.

Background: Non-operative management of blunt splenic trauma is the preferred option in hemodynamically stable patients.

Objectives: To identify predictors for the successful non-operative management of patients with blunt splenic trauma.

Methods: The study group comprised consecutive patients admitted with the diagnosis of blunt splenic trauma to the Department of Surgery, Hadassah-Hebrew University Medical Center in Jerusalem over a 3 year period. Prospectively recorded were hemodynamic status, computed tomography grade of splenic tear, presence and extent of extra-abdominal injury, number of red blood cell units transfused, and outcome. Hemodynamic instability and the severity of associated injuries were used to determine the need for splenectomy. Hemodynamically stable patients without an indication for laparotomy were admitted to the Intensive Care Unit and monitored.

Results: There were 64 adults (45 males, mean age 30.2 years) who met the inclusion criteria. On univariate analysis the 13 patients (20.3%) who underwent immediate splenectomy were more likely to have lower admission systolic blood pressure (P = 0.001), Glasgow Coma Scale < 8 (P = 0.02), and injury to at least three extra-abdominal regions (P = 0.06). Nine of the 52 patients (17.3%) who were successfully treated non-operatively suffered from grade ≥4 splenic tear. Multivariate analysis identified admission systolic BP[1] (odds ratio 1.04) and associated injury to less than three extra-abdominal regions (OD[2] 8.03) as predictors for the success of non-operative management, while the need for blood transfusion was a strong predictor (OR 66.67) for splenectomy.

Conclusions: Admission systolic blood pressure and limited extra-abdominal injury can be used to identify patients with blunt splenic trauma who do not require splenectomy and can be safely monitored outside an ICU[3] environment. 

Background: The prevalence of obesity among children and adolescents in the western world has increased dramatically.

Objective: To assess the efficiency of routine childhood obesity screening by primary physicians in the pediatric population in Israel and the utilization of health services by overweight children.

Methods: The electronic medical records of children aged 60–83 months registered in 39 pediatric primary care centers between January 2001 and October 2004 (n=21,799) were reviewed. Those in whom height and weight were documented during a clinic visit (index visit) were classified as overweight, at risk of overweight, and normal weight by body mass index percentiles. The number of visits to the pediatrician, laboratory tests and health care costs 12 months after the index visit were calculated.

Results: Anthropomorphic measurements were performed in 1556 of the 15,364 children (10.1%) who visited the clinic during the study period. Of these, 398 (25.6%) were overweight, 185 (11.9%) were at risk of overweight, and 973 (62.5%) were normal weight. Children in the first two groups visited the clinic slightly more often than the third group, but the differences was not statistically significant (P = 0.12), and had significantly more laboratory tests than the rest of the children visiting the clinics (P = 0.053). Health care costs were 6.6% higher for the overweight than the normal-weight children.

Conclusions: Electronic medical records are a useful tool for population-based health care assessments. Current screening for obesity in children during routine care in Israel is insufficient and additional education of community pediatricians in diagnosis and intervention is urgently needed.

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.

Background: Rehabilitation camps can improve exercise tolerance and nutrition in cystic fibrosis patients.

Objectives: To assess weight gain, pulmonary function tests and daily symptoms in European CF[1] patients attending a rehabilitation camp at the Dead Sea, Israel.

Methods: We conducted a retrospective study assessing 94 CF patients who participated in winter camps held at the Dead Sea, Israel from 1997 to 2000. The camp program included daily physiotherapy, physical activities, and a high caloric diet. We assessed weight gain, pulmonary function tests, oxyhemoglobin saturation and daily symptoms before (pre), on departure (dep), and up to 3 months after the 3 week rehabilitation camp post). All data were analyzed by ANOVA for repetitive measurements. P < 0.05 was considered significant.

Results: Lung function tests and oxyhemoglobin saturation taken before, on departure and 3 months after camp were available for 35 patients. Forced expiratory volume in the first second (% predicted, average ± SD) improved by 8.2 ± 2.3% (pre, dep, post, P < 0.05). Oxyhemoglobin saturation mildly improved (1 ± 0.3%, pre, dep, post, P < 0.05). Forced vital capacity (% predicted) increased by 3.9 ± 1.2%, but was not significant (P = 0.19). Total body weight of 89 patients improved by 1.9 ± 0.9% during the camp time (P < 0.05, t-test), and in a group of 24 patients weight continuously increased up to 5.0 ± 1.7% at 3 months after the camp (P = 0.004, ANOVA).

Conclusions: In this attrition-limited retrospective study, European CF patients improved their pulmonary function and gained weight during and up to 3 months after a 3 week rehabilitation winter camp at the Dead Sea, Israel.

Background: The diagnosis of gastrointestinal stromal tumors is based on documentation of c-KIT and platelet-derived growth factor-alpha receptors or specific c-KIT mutations. Before the diagnosis of GIST[1] was possible, all cases had been classified as sarcomas or benign tumors.

Objectives: To identify cases of GIST formerly diagnosed as abdominal or retroperitoneal mesenchymal tumors.

Methods: We reviewed the archive material on all surgical cases diagnosed as gastrointestinal related malignant mesenchymal tumors or GIST in our medical center during the last decade (1995–2004).

Results: Sixty-eight cases of retroperitoneal soft tissue sarcoma were identified. Thirty-eight were reconfirmed to be GIST, 19 were newly diagnosed as GIST (the hidden cases), 8 cases were re-diagnosed as mesenchymal tumors, and 3 cases of sarcoma remained sarcomas. Of all the GIST tumors, c-KIT-positive and PDGFRα[2]-positive tumors were more characteristic of primary gastric tumors, while c-KIT-positive and PDGFRα-negative tumors were found in the colorectal area. The c-KIT-negative and PDGFRα-positive cases were of gastric origin.

Conclusions: Any c-KIT-negative malignant mesenchymal mass located near the proximal gastrointestinal tract should also be stained for PDGFRα to differentiate between GIST and other soft tissue sarcomas. Practically, formerly diagnosed abdominal or retroperitoneal soft tissue sarcomas should be reviewed to identify patients with misdiagnosed GIST and thereby avoid future unnecessary and ineffective chemotherapy.

Background: With the development of computer technology and the high-tech electronic industry over the past 30 years, the technological age is flourishing. New technologies are continually being introduced, but questions regarding the economic viability of these technologies should be addressed.

Objectives: To identify the medical technologies that are currently in use in different rehabilitation medicine settings in Israel

Methods: The TECHNO-R 2005 survey was conducted in two phases. Beginning in 2004, the first survey used a questionnaire with open questions relating to the different technologies in clinical use, including questions on their purpose, who operates the device (technician, physiotherapist, occupational therapist, physician, etc.), and a description of the treated patients. This questionnaire was sent to 31 rehabilitation medicine facilities in Israel. Due to difficulties in comprehension of the term “technology,” a second revised standardized questionnaire with closed-ended questions specifying diverse technologies was introduced in 2005. The responder had to mark from a list of 15 different medical technologies which were in use in his or her facility, as well as their purpose, who operates the device, and a description of the treated patients.

Results: Transcutaneous electrical nerve stimulation, the TILT bed, continuous passive movement, and therapeutic ultrasound were the most widely used technologies in rehabilitation medicine facilities. Monitoring of the sitting position in the wheelchair, at the bottom of the list, was found to be the least used technology (with 15.4% occurrence). Most of the technologies are used primarily for treatment purposes and to a lesser degree for diagnosis and research.

Conclusions: Our study poses a fundamental semantic and conceptual question regarding what kind of technologies are or should be part of the standard equipment of any accredited rehabilitation medicine facility for assessment, treatment and/or research. For this purpose, additional data are needed.
 

Background: Percutaneous tracheostomy has largely replaced surgical tracheostomy in the intensive care unit setting. Although it seems logical that surgeons continue to do tracheostomies, anesthesiologists and intensive care specialists are familiar with airway control and guide wire techniques and could replace surgeons in the performance of PDT.

Objectives: To assess the safety and effectiveness of bedside PDT[1] in the ICU[2].

Methods: We conducted a retrospective chart review of 207 patients in the ICU who underwent PDT by an intensive care physician.

Results: Subcutaneous emphysema without pneumothorax occurred in one patient. Four patients underwent surgical revision following PDT. Early bleeding (during the first 48 hours following the procedure) was the indication in two patients and late bleeding, on the 10th post-PDT day, in one. In one case PDT was converted to surgical tracheostomy due to inadvertent early decannulation. There was one death directly related to the procedure, due to an unrecognized paratracheal insertion of the tracheostomy tube followed by mechanical ventilation, which led to bilateral pneumothorax, pneumomediastinum and cardio-circulatory collapse. No infectious complications were seen at the stoma site or surrounding tissues.

Conclusions: PDT by intensive care physicians appears to be safe and should be included in the curriculum of intensive care residency.

Surgical resection offers the best opportunity for cure in patients with colorectal cancer metastasis to the liver, with 5 year survival rates of up to 58% following resection. However, only a small percentage of patients are eligible for resection at the time of diagnosis and the average recurrence rate is still high. Consequently, research endeavors have focused on methods aimed to increase the number of patients eligible for surgical resection, refine the selection criteria for surgery, and improve the disease-free and overall survival time in these patients. Improvements in imaging techniques and the increasing use of FDG-PET allow more accurate preoperative staging and superior identification of patients likely to benefit from surgical resection. Advances in the use of neoadjuvant chemotherapy allows up to 38% of patients previously considered unresectable to be significantly downstaged and eligible for hepatic resection. Many reports have critically evaluated the surgical techniques applied to liver resection, the concurrent or alternative use of local ablative therapies, such as radiofrequency ablation, and the subsequent utilization of adjuvant chemotherapy in patients undergoing surgical resection for hepatic metastases.