J. Ted Gerstle

Neuroblastoma Cells Isolated from Bone Marrow Metastases Contain a Naturally Enriched Tumor-Initiating Cell

Neuroblastoma is a heterogeneous pediatric tumor thought to arise from the embryonic neural crest. Identification of the cell responsible for propagating neuroblastomas is essential to understanding this often recurrent, rapidly progressing disease. We have isolated and characterized putative tumor-initiating cells from 16 tumors and bone marrow metastases from patients in all neuroblastoma risk groups. Dissociated cells from tumors or bone marrow grew as spheres in conditions used to culture neural crest stem cells, were capable of self-renewal, and exhibited chromosomal aberrations typical of neuroblastoma. Primary spheres from all tumor risk groups differentiated under neurogenic conditions to form neurons. Tumor spheres from low-risk tumors frequently formed large neuronal networks, whereas those from high-risk tumors rarely did. As few as 10 passaged tumor sphere cells from aggressive neuroblastoma injected orthotopically into severe combined immunodeficient/Beige mice formed large neuroblastoma tumors that metastasized to liver, spleen, contralateral adrenal and kidney, and lung. Furthermore, highly tumorigenic tumor spheres were isolated from the bone marrow of patients in clinical remission, suggesting that this population of cells may predict clinical behavior and serve as a biomarker for minimal residual disease in high-risk patients. Our data indicate that high-risk neuroblastoma contains a cell with cancer stem cell properties that is enriched in tumor-initiating capacity. These cells may serve as a model system to identify the molecular determinants of neuroblastoma and to develop new therapeutic strategies for this tumor.

Correlation of sonographic findings and outcome in necrotizing enterocolitis

BackgroundThere is little in the literature regarding the use of gray-scale and Doppler sonography of the bowel in necrotizing enterocolitis (NEC) and how findings depicted by this modality might assist in predicting outcome and influence management.ObjectiveTo correlate sonographic findings with outcome in NEC.Materials and methodsThis was a retrospective analysis of clinical and abdominal ultrasonography (AUS) findings in NEC from January 2003 to December 2005. AUS findings were evaluated for portal venous gas, free gas, peritoneal fluid, bowel wall thickness, echogenicity, perfusion and intramural gas. Patients were categorized into two groups, according to their outcome.ResultsA total of 40 infants were identified who had AUS for NEC prior to any surgical intervention. Group A comprised 18 neonates treated medically and recovered fully, and group B comprised 22 neonates who required surgery or died. Free gas (six patients) and focal fluid collections (three patients) were only found in group B. Increased bowel wall echogenicity, absent bowel perfusion, portal venous gas, bowel wall thinning, bowel wall thickening, free fluid with echoes and intramural gas were seen in both groups, but more frequently in group B. Anechoic free fluid was seen more frequently in group A. Increased bowel perfusion was seen equally in both groups.ConclusionAn adverse outcome was associated with the sonographic findings of free gas, focal fluid collections or three or more of the following: increased bowel wall echogenicity, absent bowel perfusion, portal venous gas, bowel wall thinning, bowel wall thickening, free fluid with echoes and intramural gas. Sonographic findings are useful in predicting outcome and therefore might help guide management.

Risk factors, complications, and outcomes of gallstones in children: a single-center review.

Background and Objective: The increasing use of sonography has resulted in an increase in the proportion of children with gallstones who are asymptomatic at the time of diagnosis. In adults, the literature supports expectant management of clinically silent gallstones. The evidence for this management approach in children is limited to a number of small series. Our objective was to review the risk factors, complications, and outcomes of gallstones at our institution, particularly in those patients who are asymptomatic at the time of initial diagnosis. Materials and Methods: We reviewed 382 cases of gallstones in children. These patients were diagnosed with sonography. Data on age at diagnosis, presentation, sonographic findings, risk factors, complications, surgery, and follow-up were collected. A χ2 test was used to compare the complication rates between symptomatic and asymptomatic groups. Descriptive statistics were used to analyze the sample. Results: At diagnosis, 50.5% of children were asymptomatic; these patients were diagnosed at a mean age of 8.23 years. Compared with symptomatic patients, they were less likely to have a hemolytic anemia but more likely to have other risk factors, including cardiac surgery, leukemia and lymphoma, short bowel syndrome, or exposure to total parenteral nutrition or cephalosporins. These patients had a lower rate of complications than the symptomatic patients (4.6% vs 28.2% of symptomatic, P < 0.0001) and only 3.1% developed symptoms that necessitated surgery (vs 59.0% of symptomatic). Of the 58 (15.1%) diagnosed in infancy, 47 (81.0%) were asymptomatic. The infant group also had low rates of complications (8.6%) and cholecystectomy (1.7%). In cases with sonographic follow-up, resolution of gallstones was demonstrated in 16.5% of asymptomatic patients and in 34.1% of infants. Conclusions: The data suggest that clinically silent gallstones in children and infants are associated with low rates of complications and can be managed conservatively, unless complications occur. Patients with sickle cell disease, spherocytosis, and elliptocytosis had high complication rates and required surgery more often.

Critical review of controversial issues in the management of advanced pediatric liver tumors

Hepatocellular carcinoma (HCC) and hepatoblastoma (HB) are the most common primary tumors of liver in children. The management of patients with locally advanced, unresectable disease or those with extra‐hepatic distant metastases provides substantial challenges to pediatric oncologists, hepatologists, and surgeons. Herein, we critically debate the two sides of three specific controversies: (1) the role of chemotherapy in the treatment of advanced pediatric HCC; (2) the indications for liver transplantation in children with HCC, specifically, the appropriateness of using adult Milan criteria; and (3) the role of liver trasplantation in children with unresectable HB that present with metastatic disease. Pediatr Blood Cancer 2011;56:1013–1018.

Management of Ovarian Dermoid Cysts in the Pediatric and Adolescent Population

STUDY OBJECTIVE To evaluate the surgical approach used in the management of ovarian dermoid cysts in the pediatric and adolescent population. DESIGN A descriptive retrospective chart review of all cases of ovarian dermoid cyst excision between January 2001 and January 2006. SETTING The Hospital for Sick Children, Toronto, Canada. PARTICIPANTS Forty-one female children and adolescents who underwent operative management of an ovarian dermoid cyst. MAIN OUTCOME MEASURES Surgical approach (laparoscopy vs laparotomy), intraoperative cyst rupture, length of hospital stay, and postoperative complications. RESULTS The mean age was 12.5 years. All cysts were unilateral. Twenty-three patients (56%) underwent laparoscopic cystectomy, 14 (34%) underwent cystectomy via laparotomy, and 4 (10%) oophorectomies were performed via laparotomy. Cyst size was significantly larger in the laparotomy group compared to the laparoscopy group (mean diameter 14.4 cm vs 7.1 cm, respectively, P < .001). A significantly higher rate of cyst rupture was experienced during laparoscopic cystectomy (100%), compared to excision via laparotomy (27.7%, P < .001). Length of hospital stay was significantly shorter in the laparoscopy group compared to the laparotomy group (median of 0 vs 3 days, respectively, P < .001). A single case in the laparoscopy group sustained a bladder injury and developed postoperative necrotizing fasciitis resulting in a prolonged hospitalization and recovery. There were no operative or postoperative complications related to cyst content spillage, regardless of the surgical approach. CONCLUSION Laparoscopic cystectomy is a safe and effective method of managing ovarian dermoid cysts in the pediatric and adolescent patient population.

Malignant pancreatic tumors in children: a single-institution series.

BACKGROUND Pancreatic tumors in children represent a very rare entity. We reviewed the clinical and pathologic features of pediatric patients with pancreatic tumors at a single institution. METHODS We conducted a retrospective review of cases diagnosed at the Hospital for Sick Children between 1986 and 2010. RESULTS Twenty-seven patients were diagnosed during the study period: 18 with solid pseudopapillary neoplasm (SPN), 6 with pancreatic endocrine neoplasia, and 3 with other tumors. Of the 27 children, 3 had associated syndromes, in specific tuberous sclerosis, von Hippel-Lindau, and polycystic ovarian syndrome. The most common symptoms were pain and vomiting in SPN and hypoglycemia and seizures in insulinomas. Magnetic resonance imaging and computed tomographic scan were equally accurate in determining size and site of origin of the tumor, and both were better than ultrasound. All patients underwent surgery (distal pancreatectomy in 14 cases, Whipple procedure in 8, other procedures in 5), which represented the only treatment for all but 3 cases. Seventeen patients (94%) with SPN are alive (median follow-up, 32 months), 3 of whom had positive margins. Two patients died: 1 male with SPN with malignant transformation and 1 with fibrosarcoma. CONCLUSIONS We describe the largest single-institution study of pediatric pancreatic tumors. Females with SPN have an excellent outcome, even in presence of positive margins, suggesting that limited surgical resection may be appropriate for these patients.

Development and validation of a pediatric laparoscopic surgery simulator

BACKGROUND Although a validated simulator exists for adult laparoscopy, there is no pediatric counterpart. The objective of this study is to develop and validate a pediatric laparoscopic surgery (PLS) simulator. METHODS A PLS simulator was developed. Participants were stratified according to level of expertise and tested on the fundamentals of laparoscopic surgery (FLS) and PLS simulators. A subsequent group was tested exclusively on the PLS simulator. RESULTS The PLS intracorporeal suturing score was lower than its adult counterpart (P = .02). The PLS pattern-cutting score was higher than in the FLS simulator (P < .001). If the latter was eliminated from the calculation, the revised total FLS score was significantly better than the revised PLS score. When all participants were combined, total PLS scores as well as performance on 3 of 5 tasks allowed differentiation between novice, intermediate, and expert. CONCLUSIONS The PLS simulator was able to discriminate between the novice, intermediate, and expert using the total PLS score and the performance on 3 of the 5 tasks, thus providing evidence for construct validity. The other 2 tasks will require formal modification or a change in the scoring metrics to establish their independent construct validity.

Surgery in Global Health Delivery

Surgical conditions account for a significant portion of the global burden of disease and have a substantial impact on public health in low- and middle-income countries. This article reviews the significance of surgical conditions within the context of public health in these settings, and describes selected approaches to global surgery delivery in specific contexts. The discussion includes programs in global trauma care, surgical care in conflict and disaster, and anesthesia and perioperative care. Programs to develop surgical training in Botswana and pediatric surgery through international partnership are also described, with a final review of broader approaches to training for global surgical delivery. In each instance, innovative solutions, as well as lessons learned and reasons for program failure, are highlighted.

Omental Infarction in Children

OBJECTIVES To analyze the clinical presentation, radiologic features, management, and outcome in children diagnosed with omental infarction. STUDY DESIGN This was a retrospective chart review of patients diagnosed with omental infarction in a tertiary care pediatric emergency department. Images and reports of the radiologic investigations were re-examined by a staff radiologist and analyzed for sensitivity. RESULTS A diagnosis of omental infarction was made in 19 children (mean age, 9.3 +/- 3.5 years). The presentation was acute right lower quadrant pain in 47% of the children and associated gastrointestinal symptoms in 63%. The sensitivity of abdominal ultrasound (US) to detect omental infarction at our institution was 64%, and the sensitivity of abdominal computed tomography was 90%. Fourteen children were treated conservatively without complications after an accurate diagnosis of omental infarction done by imaging examination. Only 5 children underwent surgery based on clinical suspicion of appendicitis. CONCLUSIONS Early identification of omental infarction by abdominal US appears to prevent unjustified surgical procedures and reduce the length of hospital stay.

Nephron Sparing Surgery for Unilateral Wilms Tumor in Children with Predisposing Syndromes: Single Center Experience Over 10 Years

PURPOSE Unilateral Wilms tumors associated with predisposing syndromes are treated with preoperative chemotherapy followed by surgical resection. We describe our experience with nephron sparing surgery for Wilms tumor in this population at risk for metachronous lesions. MATERIALS AND METHODS We conducted a retrospective review of all children with a predisposing syndrome who underwent nephrectomy for malignancy during a 10-year period (2000 to 2010). Data collected included age, mode of detection, tumor size, treatment, pathology results, followup time and recurrence episodes. RESULTS From 2000 to 2010, 13 of 75 (19%) patients treated for Wilms tumor were diagnosed with predisposing syndrome(s). Eight patients with unilateral tumors were treated and had a mean age at diagnosis of 27 months (range 7 months to 9 years). Beckwith-Wiedemann syndrome, isolated hemihyperplasia, WAGR (Wilms tumor, Aniridia, Genitourinary abnormalities, mental Retardation) syndrome and isolated 11p13 deletion were the underlying diagnoses in 3, 2, 2 and 1 patient, respectively. All but 2 patients were diagnosed by screening ultrasound and 5 underwent preoperative chemotherapy. Median tumor size at surgery was 2.5 cm (range 1 to 13). Nephron sparing surgery was performed in 6 of 8 patients. Pathological study showed favorable histology Wilms tumor and nephrogenic rests in 6 and 2 patients, respectively. After a mean followup of 36 months (range 6 to 72) no recurrences were documented and all children had normal creatinine levels. CONCLUSIONS Nephron sparing surgery appears safe for patients with unilateral Wilms tumor associated with predisposing syndrome(s), allowing for the preservation of renal function and good oncologic outcomes for the available followup time. If more studies confirm our observation, current recommendations for the surgical treatment of Wilms tumor may need to reemphasize the value of attempting nephron sparing surgery in this patient population.