Ran Steinberg

Colorectal carcinoma in childhood: a retrospective multicenter study.

Objectives:Colorectal carcinoma, a common adult malignancy, has an estimated childhood incidence of 0.3 to 1.5/million in Western countries and 0.2/million in Israel. Diagnosis is difficult because adult screening measures are unfeasible in children. The tumor is frequently associated with predisposing genetic factors, aggressive biological behavior, and poor prognosis. The aim of this multicenter study was to document the clinical profile, treatment and prognosis of colorectal carcinoma in children in Israel. Patients and Methods:The clinical, laboratory, therapeutic, and prognostic parameters of all 7 children from 4 medical centers in Israel who were diagnosed with colorectal carcinoma over a 25-y period were reviewed. Results:Patients presented with rectal bleeding (4 of 7), abdominal pain (2 of 7), and abdominal distension (2 of 7). Average time to diagnosis was 6 months. Six patients underwent surgery (1 refused), and 5 received chemotherapy. Histopathological studies showed poorly differentiated mucinous adenocarcinoma, signet-ring type, in 4 cases, moderately differentiated adenocarcinoma in 2, and well-differentiated carcinoma in 1. Three patients died of the disease, 2 shortly after diagnosis. One patient with recurrent metastatic disease was lost to follow-up. Conclusion:Colorectal carcinoma in children is characterized by aggressive tumor behavior and delayed diagnosis, resulting in a worse prognosis than in adults. Heightened physician awareness of the possibility of this disease in children, with special attention to adolescents with predisposing factors and rectal bleeding, could help to improve outcome.

Reduced levels of miR‐34a in neuroblastoma are not caused by mutations in the TP53 binding site

Neuroblastoma (NB) is the most common extracranial solid tumor in children below the age of 5 years. miR‐34a, located in chromosome band 1p36, has been recently implicated as a tumor suppressor gene in NB. In addition, it has been shown that miR‐34a is activated by TP53 by binding to a TP53 binding site upstream to the mature miR‐34a. We studied NB tumors from 57 patients for miR‐34a expression levels, 1p status, mutations in the TP53 coding region and mutations of the TP53 binding site. Reduced expression levels of miR‐34a were identified in tumors harboring 1p36.3 Loss (P = 0.028). No mutations were identified in the coding region of TP53, or in the TP53 binding site. Thus, mutations in the binding site are not an additional mechanism for the inactivation of miR‐34a in NB. Other regulatory mechanisms controlling miR‐34a expression and its relationship to TP53 should be further explored.

The efficacy and safety of valganciclovir vs. oral ganciclovir in the prevention of symptomatic CMV infection in children after solid organ transplantation

Lapidus‐Krol E, Shapiro R, Amir J, Davidovits M, Steinberg R, Mor E, Avitzur Y. The efficacy and safety of valganciclovir vs. oral ganciclovir in the prevention of symptomatic CMV infection in children after solid organ transplantation.
Pediatr Transplantation 2010: 14:753–760.

Xanthogranulomatous pyelonephritis mimicking malignant disease : is preservation of the kidney possible ?

Xanthogranulomatous pyelonephritis (XGP) is an uncommon form of pyelonephritis rarely seen in children. It is characterized by destruction of the renal parenchyma and invasion of adjacent tissues, mimicking renal tumors. Preoperative diagnosis is very difficult. Two children with XGP are presented. One underwent nephrectomy and the other drainage of a renal abscess with kidney preservation. Although surgery is considered the only effective treatment, a high index of suspicion and renal biopsy may prevent radical nephrectomy.

High Frequency of Loss of Heterozygosity for 1p35–p36 (D1S247) in Wilms Tumor

We analyzed the loss of heterozygosity (LOH) for 1p in 18 Wilms tumors using a panel of 11 polymorphic markers. Loss of heterozygosity was identified in 56% of the tumors. The smallest region of overlap was defined for marker D1S247, underlying the 1p35-1p36.1 locus. This is the highest LOH frequency for 1p, or for the well-defined 11p13 and 11p15.5 loci. Based on the fact that tumors of all stages, with both favorable and unfavorable histology, exhibited LOH, we suggest that the 1p35-1p36.1 locus is involved in the etiology of Wilms tumor.

Nitric oxide for post-liver-transplantation hypoxemia in pediatric hepatopulmonary syndrome: Case report and review

Schiller O, Avitzur Y, Kadmon G, Nahum E, Steinberg RM, Nachmias V, Schonfeld T. Nitric oxide for post‐liver‐transplantation hypoxemia in pediatric hepatopulmonary syndrome: Case report and review.
Pediatr Transplantation 2011: 15: E130–E134.

2p24 Gain Region Harboring MYCN Gene Compared with MYCN Amplified and Nonamplified Neuroblastoma: Biological and Clinical Characteristics

Although the role of MYCN amplification in neuroblastoma is well established, the biological and clinical characteristics of the 2p gain region harboring the MYCN gene remain unclear. The aim of this study was to compare the biological and clinical characteristics of these tumors with MYCN amplified and nonamplified neuroblastoma and to determine their impact on disease outcome. Samples from 177 patients were analyzed by fluorescence in situ hybridization, including MYCN, 1p, 17q, and 11q regions; 2p gain was identified in 25 patients, MYCN amplification in 31, and no amplification in 121 patients. Patients with 2p gain had a significantly worse 5-year event-free survival rate than patients with no MYCN amplified (P < 0.001), and an intermediate 5-year overall survival rate difference existed between the MYCN amplified tumors (P = 0.025) and nonamplified (P = 0.003) groups. All of the 2p gain samples were associated with segmental and/or numerical alterations in the other tested regions. The presence of segmental alterations with or without MYCN amplification was recently found to be the strongest predictor of relapse in a multivariate analysis. The results of the present study suggest that the determination of MYCN gene copy number relative to chromosome 2, when evaluating MYCN status at diagnosis, may help to reveal the underlying genetic pattern of these tumors and better understand their clinical behavior.

Compliance with surgical antibiotic prophylaxis guidelines in pediatric surgery.

INTRODUCTION Surgical antibiotic prophylaxis (AP) guidelines balance the need to prevent infection with the risks of adverse drug effects. Our aim was to assess compliance with AP guidelines. METHODS A retrospective study was performed in a pediatric medical center. Included were patients aged 0 to 18 years that underwent clean-contaminated surgery during a 1-year period (2008-2009) and required AP. Compliance with four AP bundle guidelines was evaluated. Risk factors for noncompliance were identified using univariate and multivariate analyses. RESULTS AP was given to 239 of 247 (96.8%) of patients. Complete compliance with AP guidelines was achieved in 16 of 247 (6.5%) patients. Compliance with guidelines for appropriate antibiotic, drug dose, correct timing, and treatment duration were found in 97.1, 52.2, 31.9, and 35.9% of patients, respectively. Multivariable analysis showed that inappropriate timing was associated with age ≥ 4 years (p = 0.002), urgent surgery (p = 0.0018), surgical department AP administration (p = 0.0001), and night-time surgery (p = 0.015). Incorrect AP dose was associated with presence of comorbidities (p = 0.006). No risk factor was related to incorrect AP duration. CONCLUSIONS We have found a low rate of full compliance with AP guidelines. AP should only be given in the operating room. Increased awareness to AP guidelines is needed.

Colonic stricture secondary to torsion of an ovarian cyst

Intestinal obstruction in the newborn is a potentially life-threatening complication. The most common causes are meconium plug, meconium ileus, intestinal atresia, intestinal malrotation, and Hirschprungs disease. We present an unusual case of intestinal obstruction caused by torsion of an ovarian cyst. The left fimbria and ovary swirled around the sigmoid colon, causing colonic stricture.

BK virus infection and its effect on renal function in pediatric liver-transplant recipients: a cross-sectional, longitudinal, prospective study.

Background. Chronic renal failure (CRF) is a well-documented complication of liver transplantation. BK virus (BKV) is a common cause of CRF in renal-transplant recipients and has been sporadically associated with renal failure after nonrenal solid-organ transplantation. The aims of the study were to determine the prevalence of BK viruria and viremia in pediatric liver-transplant recipients, assess the natural course of BKV infection over time, and examine the association between BKV positivity and renal function. Methods. A prospective, cross-sectional study of 59 pediatric liver-transplant recipients. Blood and urine samples were collected at enrollment for creatinine level and BKV polymerase chain reaction test. BKV-positive patients underwent repeated testing and follow-up. The medical files were reviewed for clinical data. Results. Median age at enrollment was 11.5 years, and median time from transplantation was 61 months. One child (1.7%) had viremia, and nine children (15.3%) had viruria (median: 610 copies/mL). All cases of viruria/viremia resolved spontaneously, nine of them within 10 months. There were no significant differences in demographic or clinical variables between the BKV-positive and BKV-negative children. None of the BKV-positive patients had evidence of renal dysfunction. Conclusions. Pediatric liver-transplant recipients have a low prevalence of BK viruria/viremia. BKV infection is associated with low viral loads and resolves spontaneously within a relatively short period, without residua. BKV is not associated with CRF postliver transplantation. BKV testing should not be part of the routine follow-up of children after liver transplantation.