Israel Medical Association Journal

Background: Tissue expansion is a well-recognized technique for reconstructing a wide variety of skin and soft tissue defects. Its application in the pediatric population has enabled the plastic surgeon to achieve functional and aesthetic goals that were previously unobtainable.

Objectives: To review the use of tissue expansion in the pediatric population, with particular emphasis on indication, operative technique, regional considerations and how to avoid complications.

Methods: We retrospectively reviewed data on 103 expanded flap reconstructions performed in 41 pediatric patients during the period 2003–2006. Tissue expanders were placed on a subcutaneous plane above the fascia and inflated weekly. The expanded skin was used as a transposition flap or a full thickness skin graft for the reconstruction of the involved area. Forty-three tissue expanders were inserted to the head and neck in 21 patients, 45 were inserted to the trunk in 13 patients and 15 were inserted to the groin and lower extremity in 8 patients. Twenty-eight patients had one round of tissue expansion, while 13 patients had two to six rounds. A plastic surgeon, medical student and a lawyer reviewed the patients' photographs and evaluated their aesthetic outcome:

Results: Eighty-six percent of the head and neck reconstructions and 40% of the trunk and extremity reconstructions were graded as having excellent aesthetic outcome, and 11% of the head and neck reconstructions and 37% of the trunk and extremity reconstructions were graded with good aesthetic outcome. The remaining patients were graded with moderate outcome. None of our patients was graded as poor aesthetic outcome. Complications included infection in 6 patients (6%), extrusion in 3 (3%), hematoma in 2 (2%), flap ischemia in one patient (1%), and expander perforation after percutaneous stabbing in one patient (1%).

Conclusions: Tissue expansion is an efficient and valuable technique for reconstruction of large skin lesions and scars.

Background: Anti-ribosomal-P antibodies have been associated with central nervous manifestations of systemic lupus erythematosus. However, inconsistencies in their prevalence and clinical correlations have become an obstacle to their use as a diagnostic marker of the disease. This lack of consistency might stem from several factors, such as the lag period between clinical manifestations and the time blood was drawn, or the different methods used for antibodies detection.

Objectives: To evaluate three different enzyme-linked immunosorbent assay tests for the detection of anti-Rib-P Abs[1] in patients with SLE[2] and normal controls.

Methods: Sera from 50 SLE outpatients and 50 healthy subjects were tested with three ELISA[3] kits: Kit-1, which uses synthetic peptide comprising the 22 C-terminal amino-acids; Kit-2, which uses native human ribosomal proteins (P0, P1, P2); and Kit-3, which is coated with affinity-purified human ribosomal proteins. ELISA studies were performed according to the manufacturers' instructions.

Results: The prevalence of anti-Rib-P Abs in SLE patients and controls was 30% vs. 0%, 17% vs. 21%, and 30% vs. 14% in kits 1-3 respectively. Anti-Rib-P Abs detected by Kit-1 correlated with the SLEDAI score (SLE Disease Activity Index). No correlation between prior CNS[4] manifestations and anti-Rib-P Abs was observed.

Conclusions: A significant difference was documented between the ELISA kits used for the detection of anti-Rib-P Abs. A correlation was found between these antibodies (evaluated by Kit-1) and concurrent SLEDAI scores, in contrast to the lack of correlation with previous CNS manifestations. This supports the notion of "active serology" that is evaluated at the same time manifestations are present, as well as the need for standardization of laboratory assays in the future that enable a better assessment of anti-Rib-P Abs presence and clinical correlation. 

Background: Uveal melanoma is the most common primary intraocular tumor in adults. In the last two decades the Hadassah-Hebrew University ocular oncology clinic has become a referral center for uveal melanoma patients.

Objectives: To describe the characteristics of uveal melanoma patients in Israel, their treatment modalities and outcomes during the years 1988–2007.

Methods: Data were collected from the files of uveal melanoma patients in the departments of ophthalmology and oncology in our facility. Statistical analysis was performed using JMP statistical software.

Results: Data were available for 558 patients. The annual incidence of uveal melanoma in the last 5 years was 47.2 ± 7.1 new cases per year (mean ± standard error). There were 309 women (55.4%). The age at diagnosis was 60.8 ± 16.5 years (range 5–95). Overall, 6.6%, 16.8% and 86.9% involved the iris, ciliary-body and choroid, respectively. Tumors were classified as small, medium and large (9.0%, 64.5% and 17.9%, respectively) according to the COMS grouping criteria. The most common primary treatment was brachytherapy (74%), followed by enucleation (17.9%). Local recurrence was noted in 11.1% of patients, while metastases developed in 13.3%. The 5, 10 and 15 year melanoma-related mortality rate was 11.4%, 17.0% and 23.3%, respectively. Of the overall study population 9.3% died of metastatic uveal melanoma.

Conclusions: Uveal melanoma patients in Israel have tumors with characteristics similar to those in other countries. Brachytherapy is the predominant treatment, the local recurrence rate is low, and survival is comparable to that reported in the medical literature.

Background: The role of endoscopic ultrasound in evaluating the response of esophageal cancer to neoadjuvant chemotherapy is controversial.

Objectives: To evaluate the accuracy of EUS[1] in restaging patients who underwent NAC[2].

Methods: The disease stage of patients with esophageal cancer was established by means of the TNM classification system. The initial staging was determined by chest and abdominal computed tomography and EUS. Patients who needed NAC underwent a preoperative regimen consisting of cisplatin and fluouracil. Upon completion of the chemotherapy, patients were restaged and then underwent esophagectomy. The results of the EUS staging were compared with the results of the surgical pathology staging. This comparison was done in two groups of patients: the study group (all patients who received NAC) and the control group (all patients who underwent primary esophagectomy without NAC).

Results: NAC was conducted in 20 patients with initial stage IIB and III carcinoma of the esophagus (study group). Post-chemotherapy EUS accurately predicted the surgical pathology stage in 6 patients (30%). Pathological down-staging was noted in 8 patients (40%). However, the EUS was able to observe it in only 2 patients (25%). The accuracy of EUS in determining the T status alone was 80%. The accuracy for N status alone was 35%. In 65% of examinations the EUS either overestimated (35%) or underestimated (30%) the N status. Thirteen patients with initial stage I-IIA underwent primary esophagectomy after the initial staging (control group). EUS accurately predicted the surgical pathology disease stage in 11 patients (85%).

Conclusions: EUS is an accurate modality for initial staging of esophageal carcinoma. However, it is not a reliable tool for restaging esophageal cancer after NAC and it cannot predict response to chemotherapy.

Background: High levels of plasma homocysteine constitute a risk for cardiovascular disease. Physical activity, known to reduce CVD[1] risk, has been related to levels of Hcy[2]. Recently, higher Hcy was shown to be associated with lower cardiovascular fitness in women but not in men.

Objectives: To further explore the relationship between cardiorespiratory fitness and plasma total homocysteine levels in a large cohort of adult males and females.

Methods: This cross-sectional study included 2576 fitness and Hcy examinations in adults (62% males) aged 30–59 years, randomly drawn from a population undergoing a periodic health examination in the Sheba Medical Center's Executive Screening Survey. Blood tests were collected for tHcy[3] and a sub-maximal exercise test was performed to estimate cardiorespiratory fitness. Information on CVD/CVD risk factors (coronary heart disease, cerebrovascular accident, diabetes, hypertension or dyslipidemia) was self-reported.

Results: Mean tHcy plasma levels were 14.4 ± 7.7 and 10.2 ± 3.0 µmol/ml, and mean maximal oxygen uptake 36.5 ± 11.7 and 29 2 ± 9.5 ml/kg/min for males and females, respectively. A multiple regression analysis, adjusting for age, body mass index and CVD/CVD risk factors, showed no association between cardiorespiratory fitness and level of tHcy in males (P = 0.09) or in females (P = 0.62).

Conclusions: In this sample no relationship was found between level of cardiorespiratory fitness and plasma tHcy in men or women. The inconsistency of findings and the small number of studies warrant further research of the association between cardiorespiratory fitness and tHcy, an association that may have clinical implications for the modifications of cardiovascular risk factors.

Background: Gastrointestinal stromal tumors are the most common mesenchymal neoplasms of the human gastrointestinal tract.

Objectives: To review our accumulated experience using surgery to treat gastrointestinal stromal tumors.

Methods: We reviewed all patient charts and histological diagnoses of leiomyomas, leiomyosarcomas, leiomyoblastomas and schwannomas. Only tumors that displayed c-kit (CD117) immunopositivity were defined as GISTs[1].

Results: The study group comprised 40 female and 53 male patients (age 26–89 years); 40.9% of the tumors were classified as malignant, 39.8% as benign, and 19.4% as of uncertain malignancy. Fifty-six GISTs were located in the stomach (60.2%), 29 in the small bowel (31.2%), 4 in the duodenum (4.3%), 2 in the colon (2.1%) and 2 in the rectum (2.1%). Incidental GISTs were found in 23.7% of our patients. Mean overall survival time for malignant gastric GISTs was 102.6 months (95% confidence interval 74.2–131.1) as compared to 61.4 months mean overall survival for malignant small bowel GISTs (95% CI[2] 35.7–87) (P = 0.262). The mean disease-free survival period for patients with malignant gastric GISTs was 97.5 months (95% CI 69.7–125.2) as compared to only 49.6 months (95% CI 27.4–71.7) for patients with small bowel malignant GISTs (P = 0.041).

Conclusions: We found a high percentage of incidental GISTs. Gastric GISTs are more common than small bowel GISTs. Patients with malignant gastric GISTs have a significantly better prognosis than patients with malignant small bowel GISTs. A statistically significant correlation was found between age and malignant potential of the GIST.

Background: Dyslipidemia remains underdiagnosed and undertreated in patients with coronary artery disease. The Computer-based Clinical Decision Support System provides an opportunity to close these gaps.

Objectives: To study the impact of computerized intervention on secondary prevention of CAD[1].

Methods: The CDSS[2] was programmed to automatically detect patients with CAD and to evaluate the availability of an updated lipoprotein profile and treatment with lipid-lowering drugs. The program produced automatic computer-generated monitoring and treatment recommendations. Adjusted primary clinics were randomly assigned to intervention (n=56) or standard care arms (n=56). Reminders were mailed to the primary medical teams in the intervention arm every 4 months updating them with current lipid levels and recommendations for further treatment. Compliance and lipid levels were monitored. The study group comprised all patients with CAD who were alive at least 3 months after hospitalization.

Results: Follow-up was available for 7448 patients with CAD (median 19.8 months, range 6–36 months). Overall, 51.7% of patients were adequately screened, and 55.7% of patients were compliant with treatment recommended to lower lipid level. A significant decrease in low density lipoprotein levels was observed in both arms, but was more pronounced in the intervention arm: 121.9 ± 34.2 vs. 124.3 ± 34.6 mg/dl (P < 0.02). A significantly lower rate of cardiac rehospitalizations was documented in patients who were adequately treated with lipid-lowering drugs, 37% vs. 40.9% (P < 0.001).

Conclusions: This initial assessment of our data represent a real-world snapshot where physicians and CAD patients often do not adhere to clinical guidelines, presenting a major obstacle to implementing effective secondary prevention. Our automatic computerized reminders system substantially facilitates adherence to guidelines and supports wide-range implementation.

Background: The Israel National Poison Information Center, Rambam Health Care Campus, provides telephone consultations on clinical toxicology as well as drug and teratogen information around the clock. The Center participates in research, teaching and regulatory activities, and also provides laboratory services.

Objectives: To analyze data on the epidemiology of poisonings and poison exposures in Israel.

Methods: We conducted computerized queries and a descriptive analysis of the medical records database of the IPIC[1] during 2007.

Results: Overall, 26,738 poison exposure cases were recorded, a 118.5% increase compared to 1995. Children under 6 years old were involved in 45% of cases; 73% of the calls were made by the public and 25.5% by physicians; 74.4% of exposures were unintentional and 9.2% intentional. Chemicals were involved in 37.9% of cases, pharmaceuticals in 44.2%, bites and stings in 4.3% and poisonous plants in 1.2%. Substances most frequently involved were analgesics, cleaning products and antimicrobials. Clinical severity was moderate/major in 3.5%. Substances most frequently involved in moderate/major exposures were insecticides, drugs of abuse and corrosives. Eight fatalities were recorded – three unintentional exposures (all chemicals) and five intentional (chemicals, medications, drugs of abuse).

Conclusions: The rates of poison exposures and poisonings in Israel have increased significantly, contributing substantially to morbidity and mortality. The IPIC database is a valuable national resource for collecting and monitoring cases of poison exposure and can be used as a real-time surveillance system. It is recommended that reporting to the IPIC become mandatory and that its activities be adequately supported by national resources.

Background: Manganism is a central nervous system disorder caused by toxic exposure to manganese. Manganism has been related to occupational exposures, liver diseases, prolonged parenteral nutrition, and abuse of illicit drugs. Initially manifested by a reversible neuropsychiatric syndrome (locura manganica), the main symptoms and signs of manganism are emotional lability, compulsive behavior and visual hallucinations. Locura manganica is followed by an irreversible extrapyramidal syndrome, the onset of which occurs years after chronic exposure.

Objectives: To characterize the regional distribution of Mn[1] in the rat brain after subchronic exposure to Mn. This animal model holds special clinical relevance, reflecting the earlier clinical stages of manganism before chronic exposure to Mn exerts its irreversible effects.

Methods: Sprague-Dawley rats were intravenously injected with MnCl₂ weekly, for a total of 14 weeks – approximately 1/10 of the lifetime of the rat. T1-weighted magnetic resonance imaging was used to detect the distribution of Mn deposition in brain tissues, as evidenced by areas of T1-weighted hyperintense signals.

Results: A consistent region-specific pattern of T1-weighted hyperintensities was observed in the brains of Mn-treated rats. Cortical hyperintensities were prominent in the hippocampus and dentate gyrus. Hyperintensities were also observed in the olfactory bulbs, pituitary gland, optic nerves and chiasma, pons, midbrain tegmentum, habenula, lentiform and caudate nuclei, thalamus, chorioid plexus and cerebellar hemispheres.

Conclusions: Prominent Mn depositions, evidenced by T1-weighted hyperintensities in the hippocampus after subacute exposure to Mn, are compatible with the clinical picture of manganism during its early stages; and may explain its pathophysiology.