Emily Christison-Lagay

Cancer is increasingly understood to arise in the context of dynamically evolving genomes with continuously generated variants subject to selective pressures. Diverse mutations have been identified in papillary thyroid carcinoma (PTC), but unifying theories underlying genomic change are lacking. Applying a framework of somatic evolution, we sought to broaden understanding of the PTC genome through identification of global trends that help explain risk of tumorigenesis. Exome sequencing was performed on 53 PTC and matched adjacent non-tumor thyroid tissues (ANT). Single nucleotide substitution (SNS) signatures from each sample pair were divided into three subsets based on their presence in tumor, non-tumor thyroid, or both. Nine matched blood samples were sequenced and SNS signatures intersected with these three subsets. The intersected genomic signatures were used to define branch-points in the evolution of the tumor genome, distinguishing variants present in the tissues' common...

An increase in thyroid cancers, predominantly papillary thyroid carcinoma (PTC), has been recently reported in children. The histopathology of 28 consecutive PTCs from the northeast United States was reviewed. None of the patients (ages 6-18 years; 20 females, 8 males) had significant exposure to radiation. Nucleic acid from tumors was tested for genetic abnormalities (n = 27). Negative results were reevaluated by targeted next-generation sequencing. Seven of 27 PTCs (26%) had neurotrophic tyrosine kinase receptor (NTRK) fusion oncogenes (NTRK type 3/ets variant 6 [NTRK3/ETV6], n =5; NTRK3/unknown, n = 1; and NTRK type 1/translocated promoter region, nuclear basket protein [NTRK1/TPR], n = 1), including 5 tumors that measured >2 cm and 3 that diffusely involved the entire thyroid or lobe. All 7 tumors had lymphatic invasion, and 5 had vascular invasion. Six of 27 PTCs (22%) had ret proto-oncogene (RET) fusions (RET/PTC1, n = 5; RET/PTC3, n = 1); 2 tumors measured >2 cm and diffusely involved the thyroid, and 5 had lymphatic invasion, with vascular invasion in 2. Thirteen PTCs had the B-Raf proto-oncogene, serine/threonine kinase (BRAF) valine-to-glutamic acid mutation at position 600 (BRAF(V) (600E) ) (13 of 27 tumors; 48%), 11 measured <2 cm, and 6 had lymphatic invasion (46%), with vascular invasion in 3. Fusion oncogene tumors, compared with BRAF(V) (600E) PTCs, were associated with large size (mean, 2.2 cm vs 1.5 cm, respectively; P = .05), solid and diffuse variants (11 of 13 vs 0 of 13 tumors, respectively; P < .001), and lymphovascular invasion (12 of 13 vs 6 of 13 tumors, respectively; P = .02); BRAF(V) (600E) PTCs were predominantly the classic variant (12 of 13 vs 1 of 13 tumors). Two tumors metastasized to the lung, and both had fusion oncogenes (NTRK1/TPR, n = 1; RET/PTC1, n = 1). Fusion oncogene PTC presents with more extensive disease and aggressive pathology than BRAF(V) (600E) PTC in the pediatric population. The high prevalence of the NTRK1/NTRK3 fusion oncogene PTCs in the United States is unusual and needs further investigation. Cancer 2016. © 2016 American Cancer Society.

Historically, the rate of pathologic leadpoints in older children with intussusception is quoted as 20%-25%. Our anecdotal experience suggested a lower rate. We therefore compiled a case series to examine the actual incidence of pathologic leadpoint, and treatment success, by age. A retrospective review was performed of all patients admitted with intussusception between 1998 and 2012 and tested for differences in anatomic location, presence of pathologic leadpoint, and need for operative intervention, on the basis of age. In total, 154 cases of intussusception were diagnosed in 141 patients (136 ileo-colic), 38 of which were in children older than 3 (29 ileo-colic). Considering all anatomic locations, older children were more likely to have a pathologic leadpoint (p-value 0.01); however subgroup analysis of ileo-colic intussusception demonstrated no difference (p-value 0.38). Additionally, there was no difference in the success of pneumatic or barium enema reduction on the basis of ...

Multifocal and diffuse hepatic hemangiomas are true infantile hemangiomas, which likely exist in a continuum. We reviewed our hepatic hemangioma registry to identify prognostic indicators for mortality. Registry records entered between 1995 and 2012 were reviewed. Clinical characteristics were evaluated for prognostic significance using the multivariable Cox proportional hazards model. Survival data were analyzed using the Kaplan-Meier product-limit method. We identified 123 patients with multifocal (n=91) and diffuse (n=32) hepatic hemangiomas. Mortality was 16% (n=20); 40% (n=8) had multifocal and 60% (n=12) had diffuse lesions. A diagnosis of diffuse disease (hazard ratio: 9.9, 95% CI: 2.0-50.8, P=.002) and congestive heart failure (CHF) (hazard ratio: 3.9, 95% CI: 1.3-14.2, P=.031) were significant risk factors for mortality across the continuum; age at presentation, cardiomegaly, presence of shunts, and hypothyroidism were not statistically significant independent risk factors. Among patients with diffuse lesions, eight (67%) who died had abdominal compartment syndrome, which was also associated with mortality (P=.002). Hepatic hemangioma patients with CHF or diffuse disease are at higher risk for mortality. Patients with multifocal lesions without CHF may go undetected until lesions become diffuse. Aggressive treatment of symptomatic patients and close follow-up of asymptomatic patients may improve mortality.

Whether children with pancreatic trauma should be managed non-operatively or operatively is controversial. We reviewed outcomes of high-grade pancreatic injuries at two high-volume pediatric surgical centres comparing non-operative and operative management strategies. All pancreatic traumas presenting from January 1993 to July 2010 were reviewed. Patients with high-grade pancreatic injuries were stratified based on early operative or non-operative therapy. Baseline characteristics and outcomes were compared. Regression analyses were performed to assess complication rates, length of stay, and TPN duration while controlling for injury severity score and associated injuries. Of 77 patients with pancreatic injuries, 39 were grade 3 or higher. The mean ISS was 19.2 ± 10.8. Nineteen patients (50%) had associated injuries. Fifteen patients (38%) were managed operatively. Baseline characteristics were similar between groups other than ISS (p=0.03). Duration of hospitalization (p=0.01), days of TPN (p=0.003), and overall complications (p=0.007) were higher in non-operative patients. Controlling for both ISS and any associated injury, non-operative management was associated with more complications (OR 8.11; 95% CI 1.60-41.23) and was a significant predictor of prolonged TPN (13 days longer; p=0.024). Primary non-operative management of high-grade pancreatic injuries is associated with a significant increase in complications and TPN dependency. Early operative intervention should be pursued whenever feasible.