Israel Medical Association Journal

Background: Primary liver masses in children may require intervention because of symptoms or concern about malignant transformation.

Objectives: To review the management and outcomes of benign liver masses in children. Methods: We conducted a retrospective chart review of children with liver masses referred to our institution during the period 1997–2009.

Results: Benign liver masses were identified in 53 children. Sixteen of these children (30%) had hemangioma/infantile hepatic hemangioendothelioma (IHH) and 15 (28%) had focal nodular hyperplasia. The remainder had 6 cysts, 4 hamartomas, 3 nodular regenerative hyperplasia, 2 adenomas, 2 vascular malformations, and one each of polyarteritis nodosa, granuloma, hepatic hematoma, lymphangioma, and infarction. Median age at presentation was 6 years, and 30 (57%) were female. Masses were initially noticed on imaging studies performed for unrelated symptoms in 33 children (62%), laboratory abnormalities consistent with liver disease in 11 (21%), and palpable abdominal masses in 9 (17%). Diagnosis was made based on characteristic radiographic findings in 31 (58%), but histopathological examination was required for the remaining 22 (42%). Of the 53 children, 27 (51%) were under observation while 17 (32%) had masses resected. Medications targeting masses were used in 9 (17%) and liver transplantation was performed in 4 (8%). The only death (2%) occurred in a child with multifocal IHH unresponsive to medical management and prior to liver transplant availability.

Conclusions: IHH and focal nodular hyperplasia were the most common lesions. The majority of benign lesions were found incidentally and diagnosed radiologically. Expectant management was sufficient in most children after diagnosis, although surgical intervention including liver transplant was occasionally necessary.
 

Background: Meningiomas are frequently detected incidentally. Their natural history has not yet been established because it is difficult to predict the growth pattern. Therefore, the management, after the radiological diagnosis, is still controversial.

Objectives: To evaluate the clinical outcome and growth rate of conservatively treated meningiomas at our tertiary center, identify prognostic factors of tumor growth, and suggest guidelines based on the available data and our experience.

Methods: We reviewed the clinical records of 56 patients with 63 untreated meningiomas. Most were diagnosed incidentally. Clinical features and imaging findings at diagnosis and during follow-up were compared between growing and non-growing tumors. Potential patient- and tumor-related predictive factors for growth were analyzed.

Results: The study group included 46 women (52 meningiomas) and 10 men (11 meningiomas) aged 39–83 years. Mean tumor size was 18 ± 11 mm (range 3–70 mm) at diagnosis and 22 ± 11 mm (range 8–70 mm) at last follow-up; mean follow-up time was 65 ± 34 months (range 15–152 months). During follow-up 24 tumors (38%) grew at a rate of 4 mm per year; none became symptomatic. Only two prognostic factors were statistically significantly associated with low growth rate: older age and tumor calcifications.

Conclusions: Given our finding of a low growth incidence of meningiomas in the elderly, we support conservative management in patients aged 70 years or older. Calcifications into the meningioma are also indicative of slow growth, suggesting a conservative strategy. Surgery is recommended in younger patients in whom tumor growth occurs more often and a longer follow-up is necessary.
 

Background: ST-elevation myocardial infarction is caused by occlusive coronary thrombosis where antecedent plaque disruption occurs. When treating STEMI[1] the main goal is to achieve prompt reperfusion of the infarction area. Several studies have demonstrated the efficacy of an aspiration device before percutaneous coronary intervention in patients with acute myocardial infarction.

Objectives: To determine the added value of thrombus aspiration prior to primary PCI[2] by comparing AMI[3] patients with totally occluded infarct-related artery treated with routine primary PCI to those treated with extraction device prior to primary PCI.

Methods: The study group comprised 122 consecutive patients with AMI and a totally occluded infarct artery (TIMI flow 0) who underwent primary PCI. The patients were divided into two groups: 68 who underwent primary PCI only (control group) and 54 who underwent primary thrombus extraction with an extraction device before PCI (extraction group). Baseline clinical and lesion characteristics were similar in both groups. Final TIMI grade flow and myocardial blush as well as 1 year mortality, target lesion revascularization, recurrent myocardial infarction, unstable angina and stroke were compared between the two groups.

Results: Primary angiographic results were better for the extraction group versus the control group: final grade 3 TIMI flow was 100% vs. 95.6% (P = 0.03) and final grade 3 myocardial blush grade 50% vs. 41.18% (although P was not significant). Long-term follow-up total MACE[4] showed a non-significant positive trend in the extraction group (12.96% vs. 24.71%, P = 0.26).

Conclusions: The use of extraction devices for intracoronary thrombectomy during primary PCI in patients with totally occluded infarct artery significantly improved epicardial reperfusion in the infarct-related vessel and showed a trend for more favorable long-term outcome.

Background: Data regarding the validity of self-reported weight and height in adolescents are conflicting.

Objectives: To evaluate the validity of self-reported weight and height among 13–14 year old schoolchildren. 

Methods: We conducted a cross-sectional study of 517 schoolchildren aged 13–14 years and compared self-reported and measured weight and height by gender, population group, parental education and crowdedness.

Results: Females under-reported their weight on average by 0.79 ± 5.46 kg (P = 0.03), resulting in underestimation of the body mass index with borderline significance (mean difference 0.28 ± 2.26 kg/m², P = 0.06). Males over-reported their height on average by 0.75 ± 5.81 cm (P = 0.03). Children from less crowded homes (≤ 1 person per room) overestimated their height more than children from more crowded homes, resulting in a significant underestimation of BMI[1] (mean difference between reported BMI and measured values was 0.30 ± 2.36 kg/m², P = 0.04). Measured BMI was a significant predictor of the difference between self-reported and measured BMI, adjusted for gender, population group, parents' education, and crowdedness (β = -0.3, P < 0.0001). As a result of this reporting bias, only 54.9% of children with overweight and obesity (BMI ≥ 85th percentile) were classified correctly, while 6.3% of children were wrongly classified as overweight and obese. The largest difference in BMI was observed in obese females (4.40 ± 4.34) followed by overweight females (2.18 ± 1.95) and underweight females (-1.38 ± 1.75). Similar findings were observed for males, where the largest difference was found among obese males (2.83 ± 3.44).

Conclusions: Studies based on self-reported weight and height in adolescents may be biased. Attempts should be made to correct this bias, based on the available data for each population.

Background: Patients with multiple (< 100) colorectal adenomatous polyps are at increased risk for colorectal cancer. Genetic evaluation of those patients who test negative for APC gene mutation is both a clinical and economic burden but is critical for counseling and surveillance. In Israel, this is confounded by the fact that national health insurance does not fully cover genetic evaluation of APC gene exon 16.

Objectives: To perform a comprehensive genetic evaluation of APC gene mutation-negative polyposis patients with the aim of developing a future evaluation protocol.

Methods: Genetic analyses were performed in 29 APC gene mutation-negative Jewish individuals with 5 to ≥ 40 colonic adenomas who did not fulfill Amsterdam (clinical) criteria for Lynch syndrome. Analyses included completion of APC gene exon 16 sequencing, analysis for APC gene copy number variations (deletions or duplications), MUTYH gene sequencing, and microsatellite instability in CRC[1] patients fulfilling “Bethesda” (laboratory investigation) criteria for Lynch syndrome.

Results: Completion of APC gene exon 16 sequencing revealed one patient with the E1317Q polymorphism. All were normal by APC multiplex ligation-dependent probe amplification analysis. Pathogenic MUTYH mutations were found in three patients, all of North African origin; two additional patients had variants of unknown significance. One of six patients with Bethesda-positive criteria was MSI²-High with immunohistology consistent with MLH1 mutation.

Conclusions: Based on this small but well-characterized cohort with multiple colorectal adenomas, Lynch syndrome needs to be excluded if there are compatible criteria; otherwise MUTYH sequencing is probably the first step in evaluating APC-negative patients, especially for Jews of North African descent. Completing APC exon 16 sequencing and copy number variations analysis should probably be the last evaluations.

Background: Clinical and epidemiologic features of coronary heart disease may not be explained solely by established risk factors. The role of infectious pathogens in the development and rupture of atherosclerotic plaques remains elusive but an association between Chlamydia pneumoniae, Mycoplasma pneumoniae and CHD[1] has been previously reported

Objectives: To determine whether there is an association between mycoplasmal infections and CHD.

Methods: We conducted a prospective cohort analysis of 150 consecutive hospitalized patients with CHD (85 with acute coronary syndrome and 65 admitted for unrelated reasons) and 98 healthy blood donors. Antibody titers for Mycoplasma pneumoniae, M. fermentans, M. hominis and Ureaplasma urealyticum were measured with the agglutination test or specific enzyme-linked immunosorbent assay in all three groups of patients.

Results: Analysis of the antibody titers did not reveal any significant difference in the presence of mycoplasmal antibodies between the patients with ACS[2], patients with known stable CHD hospitalized for non-CHD reasons, and healthy blood donors.

Conclusions: Determination of specific antibodies did not reveal a significant association among different types of mycoplasmal infection and CHD.





[1] CHD = coronary heart disease

[2] ACS = acute coronary syndrome

Background: Pathologic breast conditions are rare in childhood and adolescence. The spectrum of breast disease in the pediatric age group is different from that in adults, and most lesions are benign

Objectives: To describe the causes and characteristics of breast asymmetry in adolescents with normal endocrine profiles and sexual development.

Methods: The files of patients with a diagnosis of breast asymmetry referred to a tertiary pediatric center from 1990 to 2007 were reviewed for history and findings on physical examination with or without imaging, treatment and outcome.

Results: Eleven patients aged 12.5 to 18 years were identified. The cause of the breast asymmetry was traced to unpreventable medical factors in eight patients (physiologic, Poland anomaly, scleroderma), preventable/iatrogenic factors in two patients (chest tissue biopsy, thoracic drain), and possible combined medical-iatrogenic factors in one patient (scoliosis treated by a body brace). All patients were referred for breast reconstruction after full breast development.

Conclusions: Severe breast asymmetry in adolescence may be due to congenital factors, diseases involving the breast tissue, or to the effects of medical treatment, and may have severe adverse psychological and social implications. To prevent iatrogenic breast asymmetry, physicians should be made aware of the sensitivity of the breast tissue and should avoid unnecessary tests/procedures that involve the chest wall. In most cases a precise medical history and physical examination can differentiate between physiologic and non-physiologic causes.

Background: Epidemiological data show significant associations of vitamin D deficiency and autoimmune diseases. Vitamin D may prevent autoimmunity by stimulating naturally occurring regulatory T cells.

Objectives: To elucidate whether vitamin D supplementation increases Tregs[1] frequency (%Tregs) of circulating CD4+ T cells.

Methods: We performed an uncontrolled vitamin D supplementation trial among 50 apparently healthy subjects including supplementation of 140,000 IU at baseline and after 4 weeks (visit 1). The final follow-up visit was performed 8 weeks after the baseline examination (visit 2). Blood was drawn at each study visit to determine 25-hydroxyvitamin D levels and %Tregs. Tregs were characterized as CD4+CD25++ T cells with expression of the transcription factor forkhead box P3 and low or absent expression of CD127.

Results: Forty-six study participants (65% females, mean age ± SD 31 ± 8 years) completed the trial. 25(OH)D[2] levels increased from 23.9 ± 12.9 ng/ml at baseline to 45.9 ± 14.0 ng/ml at visit 1 and 58.0 ± 15.1 ng/ml at visit 2. %Tregs at baseline were 4.8 ± 1.4. Compared to baseline levels we noticed a significant increase of %Tregs at study visit 1 (5.9 ± 1.7, P < 0.001) and 2 (5.6 ± 1.6, P < 0.001).

Conclusions: Vitamin D supplementation was associated with significantly increased %Tregs in apparently healthy individuals. This immunomodulatory effect of vitamin D might underlie the associations of vitamin D deficiency and autoimmune diseases. Hence, our finding provides a rationale for further studies to investigate vitamin D effects on autoimmunological processes.