Israel Medical Association Journal

Background: Patients with non-inflamed appendix have been reported to have had more hospitalizations and emotional disorders before and after the operation than patients with acute appendicitis.

Objectives: To compare abdominal pain characteristics, as well as demographic and psychosocial data in children with histologically confirmed appendicitis compared to non-inflamed appendices.

Methods: Charts of children with suspected appendicitis who had undergone appendectomy were retrospectively reviewed for relevant clinical and laboratory data. The patients or their parents were then contacted by phone and were asked to respond to a detailed questionnaire on abdominal symptoms as well as demographic and psychosocial data.

Results: The study group comprised 156 children: 117 with histologically confirmed appendicitis and 39 with normal appendices. Eighty-two patients (53.2%) were located and interviewed: 62 (54%) with appendicitis and 20 (51%) with normal appendices. Of the 82 children, 16 reported recurrent episodes of abdominal pain before or after surgery: 11 (17.7%) in the appendicitis group and 5 (25%) in the normal appendix group. Only six patients fulfilled the formal criteria for the diagnosis of recurrent abdominal pain: 5 (8%) from the appendicitis group and 1 (5%) from the non-inflamed appendix group (not significant). In addition, no significant statistical differences were found between the groups regarding school performance, behavior and social interaction with peers.

Conclusions: We could not demonstrate an increased incidence of recurrent abdominal pain, nor could we identify significant psychosocial morbidity in those children undergoing a non-inflamed appendectomy.

Background: Dedicated, organ-specific screening clinics have been shown to significantly reduce cancer morbidity and mortality.

Objectives: To establish a dedicated clinic for Clalit Health Service patients at high risk for hereditary gastrointestinal cancer and to provide them with clinical and genetic counseling, diagnostic screening and follow–up.

Results: During the 3 years of the clinic's activity, 634 high risk families, including 3804 at-risk relatives, were evaluated. The most common conditions were hereditary colorectal syndromes, Lynch syndrome (n=259), undefined young-onset or familial colorectal cancer (n=214), familial adenomatous polyposis (n=55), and others (n=106). They entered follow-up protocols and 52 underwent surgical procedures.

Conclusions: Consistent public and professional education is needed to increase awareness of hereditary colorectal cancer and the possibility of family screening, early diagnosis and therapy. The public health services – i.e., the four health management organizations – should provide genetic testing for these patients who, at present, are required to pay for almost all of these available but costly tests. Dedicated colorectal surgical units are needed to provide the specialized therapeutic procedures needed by patients with familial colorectal cancer. Our future plans include adding psychosocial support for these at-risk patients and their families as well as preventive lifestyle and dietary intervention. 

Background: The frequency of colorectal cancer screening tests in Israel is poor, and is much lower than in the United States. This low rate has been attributed to health system failures as well as to barriers on the part of both physicians and patients.

Objectives: To further identify particular health system failures, physician and patient-based barriers, and the effectiveness of public lectures in improving the frequency of performance of CRC[1] screening tests.

Methods: Public lectures on colorectal cancer prevention were held. A gastroenterologist presented the lectures, which were followed immediately by a questionnaire and 4 months later by a telephone call.

Results: Of the 80% of attendees who had never undergone any CRC screening test, only 18% reported family physician recommendations for such tests. Eighty-four percent reported willingness to undergo fecal occult blood testing and 52% to undergo colonoscopy; 62% replied that they should undergo some CRC screening test and 90% believed that these tests save lives. Of the women, 47% expressed preference for a female gastroenterologist. Follow-up showed that 34% proceeded to undergo some CRC screening test: 60% chose colonoscopy and 40% FOBT[2].

Conclusions: Public lectures are effective at improving compliance with the CRC screening test. Physicians should recommend these tests to appropriate individuals. Same-gender gastroenterologists should be considered for individuals uneasy about someone from the opposite gender performing the test. Assessing the various health-promotion efforts can direct us in implementing finite resources to greatest effect. Local cancer institutes and societies may be supportive in disseminating screening information in this way.

Background: The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with early onset of coronary artery disease in some populations with certain ethnic backgrounds. However, data on its effect on CAD[1] development in women are limited and conflicting.

Objectives: To investigate the effects of the MTHFR C677T mutation and ethnicity on the development and age at onset of CAD in women in Israel.

Methods: The sample included 135 Jewish women with well-documented CAD (62 Ashkenazi, 44 Oriental and 29 of other origins) in whom CAD symptoms first developed at age ≤ 65 years. DNA samples from 235 women served as the control.

Results: CAD symptoms developed later in Ashkenazi than in Oriental women or women of other origins (51.0 ± 7.0 years vs. 48.3 ± 7.5 and 46.3 ± 7.7 years, respectively, P = 0.024). Among Ashkenazi women, the T/T genotype was less common in patients in whom CAD symptoms appeared after age 50 (6.4%) than in patients with earlier CAD symptoms (25.8%, P = 0.037) and Ashkenazi control subjects (23.3%, P = 0.045). Among women from other origins, these differences were not significant. On logistic regression analysis, the T/T genotype was associated with a nearly fourfold increase in the risk of early onset (age < 50 years) of CAD (odds ratio 3.87, 95% confidence interval 1.12–13.45, adjusted for risk factors and origin) and a trend towards an influence of ethnicity (P = 0.08). Compared to Ashkenazi women, the risk of early development of CAD associated with the T/T genotype among Oriental ones was 0.46 (95%CI[2] 0.189–1.114) and in women of other origins, 5.84 (95%CI 1.76–19.34). Each additional risk factor increased the risk of earlier onset of CAD by 42% (OR[3] 1.42, 95%CI 1.06–1.89).

Conclusions: The age at onset of CAD in Israeli women is influenced by the MTHFR genotype, ethnic origin and coronary risk factors.

Background: The Beer Sheva Psoriasis Severity Score is a novel instrument for the assessment of psoriasis severity, designed for use in routine clinical conditions.

Objective: To identify the main factors of the BPSS[1].

Methods: The sample used to study the BPSS comprised 70 patients with psoriasis vulgaris treated by climatotherapy at the Dead Sea. Psoriasis severity was assessed using BPSS and PASI (Psoriasis Area and Severity Index). Factor analysis was used to identify the main factors of BPSS. Internal consistency analysis was performed. Correlation matrices were generated to compare BPSS factors.

Results: Factor analysis demonstrated that BPSS included six factors that explained 74.0% of the variance as follows: patient assessment 26.0%; physician assessment 13.2%; palms and soles involvement 11.9%; genitals, nails, and pruritus 9.0%; face involvement 7.3%; and scalp involvement 6.6%. Total scale Cronbach’s alpha was 0.76; alpha for the factors ranged between 0.39 and 0.81.

Conclusion: The major factors of BPSS were identified. BPSS may be used as a comprehensive tool for measuring psoriasis severity.

[1] BPSS = Beer Sheva Psoriasis Severity Score

Background: Reports of burn injuries in children are usually made by highly specialized burn units. Our facility admits children with burns < 20% total body surface area, while those with major burns are transferred to burn units at tertiary care facilities.

Objectives: To review our experience with thermal burns.

Methods: We conducted a retrospective review of all thermal burns admitted to our hospital during a 5 year period.

Results: Among 266 patients (69.2% boys) aged 3.5 ± 3.6 years, children < 3 years old were the most frequently injured (64.7%). Scalds (71.4%) were the most common type of burn. Partial thickness burns were sustained by 96.6% of children and TBSA[1] burned was 4.2 ± 3.6%. The mean hospital stay was 3.8 ± 4.5 days, and was significantly prolonged in girls (4.6 ± 4.8 vs. 3.5 ± 4.3 days, P = 0.01). Percent TBSA burned was correlated with patient age (r = 0.12, P = 0.04) and length of hospital stay (r = 0.6, P < 0.0001). Six patients (2.3%) (mean age 3.4 ± 2.3 years) were hospitalized in the Pediatric Intensive Care Unit due to toxin-mediated illness.

Conclusions: Children under the age of 3 years are at increased risk for burn injury, but older children sustain more extensive injuries. Prevention and awareness are needed for child safety.

Background: Iron deficiency and lead poisoning are common and are often associated. This association has been suggested previously, mainly by retrospective cross-sectional studies.

Objective: To assess the impact of short-term lead exposure at indoor firing ranges, and its relationship to iron, ferritin, lead, zinc protoporphyrin, and hemoglobin concentrations in young adults.

Methods: We conducted a clinical study in 30 young healthy soldiers serving in the Israel Defense Forces. Blood samples were drawn for lead, zinc protoporphyrin, iron, hemoglobin and ferritin prior to and after a 6 week period of intensive target practice in indoor firing ranges.

Results: After a 6 week period of exposure to lead dust, a mean blood lead level increase (P < 0.0001) and a mean iron (P < 0.0005) and mean ferritin (P < 0.0625) decrease occurred simultaneously. We found a trend for inverse correlation between pre-exposure low ferritin levels and post-exposure high blood lead levels.

Conclusions: The decrease in iron and ferritin levels after short-term lead exposure can be attributed to competition between iron and lead absorption via divalent metal transport 1, suggesting that lead poisoning can cause iron depletion and that iron depletion can aggravate lead poisoning. This synergistic effect should come readily to every physician's mind when treating patients with a potential risk for each problem separately.
 

Mesenchymal stromal cells are multipotent cells capable of tissue repair and immune modulation. They are primarily found in bone marrow, but are also present in other tissues of mesenchymal origin, such as fatty tissue, muscle, tendons, etc. MSC[1] can easily be obtained by bone marrow aspiration, showing a rapid expansion in vitro. New protocols enable cell culture without the use of animal-derived sera and artificial growth factors. Avascular necroses of the bone may have different causes. AVN[2] in autoimmune and hematological diseases show a strong association with corticosteroid treatment, which is often unavoidable in severe cases. Until recently, core decompression of the affected osseous area was the standard approach. Because of their differentiation properties, easy accessibility and proliferative capacity, autologous MSCs could potentially complement AVN treatment by adding fresh “osteogenic cells” to the healing process.

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: Colonoscopy is the gold standard procedure for screening for colorectal cancer and surveillance after polypectomy or colorectal cancer surgery, for diagnosis in symptomatic patients and patients with fecal occult blood, and for screening in the high risk population. The adherence of referring physicians to the accepted recommendations can prevent long waiting lists for colonoscopy and save lives, costs and resources.

Objectives: To evaluate the knowledge of primary care physicians and gastroenterologists in Israel about current guidelines for colonoscopy screening and surveillance.

Methods: A 10-item questionnaire on proper follow-up colonoscopy for surveillance after polypectomy and screening for colorectal cancer in various clinical and epidemiological situations was administered to 100 expert gastroenterologists and 100 primary care physicians at a professional meeting. Answers were evaluated for each group of physicians and compared using the chi-square test.

Results: The compliance rate was 45% for the gastroenterologists and 80% for the primary care physicians. The rate of correct answers to the specific items ranged from 18.7% to 93.75% for the gastroenterologists and from 6.2% to 58.5% for the primary care physicians (P < 0.001 for almost every item).

Conclusions: The knowledge of physicians regarding the screening and surveillance of colorectal cancer needs to be improved.

Background: Peritoneal carcinomatosis is an advanced form of cancer with poor prognosis that in the past was treated mainly palliatively. Today, the definitive approach to peritoneal surface malignancy involves peritonectomy, visceral resection and perioperative intra-abdominal hyperthermic chemotherapy. The anticipated results range from at least palliative to as far as intent to cure. Proper patient selection is mandatory.

Objectives: To determine whether cytoreductive surgery and intraperitoneal hyperthermic chemotherapy can extend survival, and with minor complications only, in patients with peritoneal carcinomatosis.

Methods: Twenty-two IPHP[1] procedures were performed in 17 patients with peritoneal carcinomatosis in our institution between 1998 and 2007: 6 had pseudomyxoma peritonei, 5 had colorectal carcinoma, 3 had ovarian cancer and 3 had mesotheliomas. All patients underwent cytoreductive surgery, leaving only residual metastasis < 1 cm in size. Intraperitoneal chemotherapy was administered through four large catheters (2F) using a closed system of two pumps, a heat exchanger and two filters. After the patient’s abdominal temperature reached 41°C, 30–60 mg mitomycin C was circulated intraperitoneally for 1 hour.

Results: The patients had a variety of anastomoses. None demonstrated anastomotic leak and none experienced major complications. Six patients had minor complications (pleural effusion, leukopenia, fever, prolonged paralytic ileus, sepsis), two of which may be attributed to chemotherapy toxicity (leukopenia). There was no perioperative mortality. Some patients have survived more than 5 years.

Conclusions: IPHP is a safe treatment modality for patients with peritoneal carcinomatosis. It has an acceptable complications rate and ensures a marked improvement in survival and in the quality of life in selected patients.

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: Open access gastroscopy allows physicians to refer patients for endoscopic procedures without a prior consultation.

Objectives: To compare the safety and efficacy of OAG[1] with gastroscopy performed after a gastroenterological consultation.

Methods: Patients referred for gastroscopy directly (open access) or after consultation with a gastroenterologist, by physicians in the departments of internal medicine and surgery at a major tertiary center, were compared for indications, background disease, outcome and diagnostic yield. The data were collected prospectively over a 5 month period following the introduction of OAG at the center. Physicians in both departments participated in an education program on the indications and procedure of gastroscopy. For each patient referred for OAG the attending physician completed a specially designed questionnaire that had to be signed by a senior physician. Data were managed and analyzed with Excel and SPSS software.

Results: The study sample comprised 494 patients: of whom 236 were referred for OAG and 258 after prior consultation. On multivariate analysis, hospitalization in the department of internal medicine was the only independent factor for OAG. Severe background disease and aspirin treatment had no effect on physician use of OAG, although they served as a “red light” for the gastroenterology consultants. There was no difference in the diagnostic yield of the procedures (26.4% normal findings for OAG and 28.3% for consultations) or in mortality rates. The main indications for referral to gastroscopy in the surgery department were melena, hematemesis, and "coffee grounds," and anemia and vomiting in the internal medicine department.
Conclusions: OAG is feasible and beneficial in an academic medical center setting, with no bias in appropriateness of indications or decrease in the diagnostic yield compared to the traditional approach. More attention should be directed to safety issues by the referring physicians