The Childhood Adenotonsillectomy Trial (CHAT): rationale, design, and challenges of a randomized controlled trial evaluating a standard surgical procedure in a pediatric population

Each year, over 500,000 adenotonsillectomies (AT), mostly for the treatment of pediatric obstructive sleep apnea (OSA) are performed in the US in children under 15 years of age. No definitive study, however, has been yet conducted that has rigorously evaluated the effectiveness of AT for not only improving sleep disordered breathing, but also for improving clinically relevant outcomes, such as neurocognitive function, behavior, and quality of life. The Childhood Adenotonsillectomy Trial (CHAT) was designed to assess neuropsychological and health outcomes in children randomized to receive early AT (eAT) as compared to Watchful Waiting with Supportive Care (WWSC). Important secondary goals of the study are to evaluate outcomes in subgroups defined by obesity and race. This paper addresses key elements in the design and implementation of a controlled trial for a widely used "standard practice" surgical intervention in a pediatric population, that include establishment of standardized data collection procedures across sites for a wide variety of data types, establishment of equipoise, and approaches for minimizing unblinding of selected key personnel. The study framework that was established should provide a useful template for other pediatric controlled studies or other studies that evaluate surgical interventions.     

Association of ApoE genetic variants with obstructive sleep apnea in children

BACKGROUND AND PURPOSE: Although several studies have reported an association between obstructive sleep apnea (OSA) and the chromosomal region containing the Apolipoprotein E (ApoE) gene, findings about the exact location in the ApoE gene have been inconsistent. The objective of our study was thus to determine the allele, genotype, and haplotype frequencies at several single nucleotide polymorphisms (SNPs) in the region of ApoE and test their association with OSA status in children. PATIENTS AND METHODS: Caucasian children, ranging in age from 2 to 21 years, with polysomnographic evidence of OSA (>1 obstructive apnea or obstructive hypopnea episodes per hour of sleep) were recruited in the case group. Our race- and gender-matched control group was recruited from a population-based cohort of children enrolled in the Princeton School District Study. RESULTS: Comparison of allele and genotype frequencies between cases (n=92) and controls (n=92) revealed significant differences for SNPs rs405509 and rs7412. Multivariate logistic regression analysis with age and body mass index (BMI) as covariates revealed a significant association between OSA status and SNPs rs157580, rs405509, rs769455 and rs7412. The sliding window haplotype trend regression test revealed that SNP rs405509 was included in all haplotypes that are significantly associated with OSA status. CONCLUSIONS: We conclude that polymorphisms involving more than one locus in the ApoE gene and its regulatory region are associated with OSA in children. Further studies replicating these findings in different populations are needed as are studies involving fine mapping of this region.     

Chondroid cystic malformation of the lung with trisomy 8 mosaicism: a new cystic lung malformation

Neonatal cystic disorders of the lungs are a heterogeneous malformative group including giant lobar hyperinflation, congenital pulmonary airway malformations, intralobar pulmonary sequestration, and bronchogenic cyst. Here, we describe a giant cystic pulmonary malformation in a 5-year-old girl, morphologically characterized by a highly disorganized proliferation of numerous cartilage islands, abundant mesenchymal tissue with abundant adipose differentiation, and epithelium-lined cysts. Cytogenetic analysis revealed an isolated trisomy 8, as the sole karyotype anomaly, a finding further confirmed by a whole-genome single nucleotide polymorphism array genotyping. The trisomy 8 was observed by fluorescent in situ hybridization within the malformation, and also in adjacent pulmonary parenchyma. A search of the literature revealed only 2 cases having similarities with the present case, but bearing different names. We believe that this lesion differs from congenital pulmonary airway malformations and from adult-type pulmonary hamartomas. We propose for this malformative mass the name "chondroid cystic malformation of the lung."     

Laparoscopic donor nephrectomy: single-center experience in Egypt with 400 consecutive cases

INTRODUCTION: In this study, we present our experience with laparoscopic donor nephrectomy and evaluate the outcomes of donors and recipients. PATIENTS AND METHODS: Between March 2003 and August 2006, 400 laparoscopic donor nephrectomies were performed in our institution. Donors were evaluated for renal vasculature using computed tomography angiography. We used the left kidney in 329 donors and the right kidney in 71. Donor surgeries were done transperitoneally using three trocars on the left side and four trocars on the right side. Kidneys were extracted manually through a 7-cm Pfanenstiel incision. RESULTS: All cases were completed laparoscopically. Mean operative time was 117 +/- 34 minutes. Mean blood loss was 56 +/- 28 mL. None of the donors required a blood transfusion. Mean warm ischemia time was 2.6 +/- 0.4 minutes. The mean renal artery length was 3.1 +/- 0.4 cm; the mean renal vein length was 2.4 +/- 1.2 cm. Mean hospital stay was 2.1 days. No donor required readmission. Kidneys were transplanted successfully and the mean recipient creatinine on discharge was 1.2 +/- 0.6 mg/dL. One patient had a renal artery thrombosis on postoperative day 2. Another patient with double renal arteries had thrombosis of the smaller artery just after surgery. Acute tubular necrosis was seen in 17 patients, four of whom required dialysis. Kidney function recovered thereafter in all acute tubular necrosis cases. CONCLUSION: Laparoscopic surgery is a minimally invasive approach for living donor nephrectomy with good functional outcomes. The donor benefits from lesser morbidity without compromising the anatomic or physiological outcome of the nephrectomized kidney.     

Robotic uretero-ureterostomy of the retrocaval ureter without excision of the retrocaval segment

Robotic reconstruction of the retrocaval ureter is gaining momentum as the method of choice for surgically treating this rare condition. Maintaining the retrocaval ureteric segment further facilitates the procedure. We report a case of a 23-year-old man who underwent intraperitoneal robotic resection anastomosis and repositioning of the retrocaval ureter. We also discuss the advantages of this technique.     

Chronic gastritis in children

BACKGROUND: Active gastritis, atrophic gastritis (AG) and intestinal metaplasia are lesions associated with Helicobacter pylori (H. pylori) infection in adults. AIM: To assess the prevalence of chronic gastritis, its histological characteristics and clinical features in children. METHODS: 345 children (M/F: 151/194, mean age: 8.6 +/- 3.7 years; range: 1-18 years) were enrolled, referred for upper gastrointestinal endoscopy (UGI endo) with clinical manifestations of gastritis, i.e., recurrent abdominal pain (n = 232, 67.2%), upper gastrointestinal bleeding (n = 59, 17.1%) and miscellaneous (n = 53, 15.3%). Four perendoscopic gastric biopsy specimens (antrum: 2, fundus: 2) were taken. Biopsies were assessed and graded according to the updated Sydney system. H. pylori infection was considered if 2 out 3 tests were positive (culture, histology and rapid urease test), whereas 3 concordant negative results identified H. pylori negative children. RESULTS: H. pylori infection and chronic gastritis were detected in 215/345 (62.3%) (M/F: 104/117, sex ratio M/F = 0.89) and 221/345 (64.05%) children, respectively. Recurrent abdominal pain (n = 149, 67.4%) was the main clinical features of chronic gastritis followed by vomiting (n = 43, 19.5%) and upper gastrointestinal bleeding (n = 41, 18.6%). Any clinical features were however found to be specific. UGI endo showed; nodular gastritis (n = 90, 40.72%), congestive gastritis (n = 84, 38%), gastric ulcer (n = 9), bulbar ulcer (n = 5) and normal (n = 47, 21.2%). Chronic gastritis was active in 115 cases (52%) and was significantly associated with nodular gastritis (p < 0.05). Thirty two chronic gastritis (14.4%) exhibited AG (M/F: 16/16, mean age: 9.4 +/- 3.4 years) and 30/32 (93.7%) were H. pylori positive. AG was significantly associated with H. pylori infection (p < 0.0001) and nodular gastritis (p < 0.005). Active, follicular and AG were significantly associated with H. pylori infection (p < 0.00001). Three patients exhibited intestinal metaplasia. CONCLUSION: Chronic gastritis is frequent in children. Any clinical features were found to be specific. It significantly associated H. pylori infection and nodular gastritis. Atrophic gastritis was found in 14.5% of children.     

Circulating histocompatibility antigen (HLA) gene products may help differentiate benign from malignant indeterminate pulmonary lesions

Background

This study explores the potential diagnostic utility of soluble Human Leukocyte Antigen (sHLA) molecules differentially released by lung adenocarcinoma and benign lung lesions.