Background
Technetium‐99 (99mTc) lymphoscintigraphy with blue dye injection is an accepted method for sentinel lymph node (SLN) mapping, but blue dye has known adverse effects, and injection of 99mTc ...may increase time under anesthesia for pediatric patients. Indocyanine green (ICG) may serve as an adjunct to assist with visibility and identification of SLNs. We hypothesized that sensitivity of ICG was similar to blue dye in SLN biopsies.
Methods
Thirty patients (36 procedures with 96 total specimens) underwent preoperative intradermal injection of 99mTc, followed by intradermal injection of isosulfan blue and ICG. Test characteristics of blue dye, ICG, and 99mTc included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
Results
ICG had a sensitivity of 87% and PPV of 83% for detection of 99mTc‐hot lymph nodes; blue dye had a sensitivity of 44% and PPV of 97%. For detection of pathologically confirmed lymph nodes, ICG had a sensitivity of 84% and a positive predictive value (PPV) of 91%. 99mTc had a sensitivity of 82% and a PPV of 94%. ICG had no significant difference in odds of being positive in pathology‐confirmed lymph nodes compared to 99mTc (odds ratio OR, 0.818; 95% confidence interval CI, 0.3–2.172; p = .823) and had higher odds than isosulfan blue (OR, 0.025, 95% CI, 0.001–0.148; p < .001).
Conclusion
This study established the efficacy of ICG as an adjunct to SLNB in the pediatric and young adult population. ICG was safe, more efficacious than blue dye, and may obviate the need for lymphoscintigraphy in selected patients resulting in reduced time under anesthesia.
This trial in the pediatric and young adult oncology population studied patients undergoing sentinel lymph node biopsy with the use of gold‐standard technetium‐99, isosulfan blue, and indocyanine green. Indocyanine green was found to be safe, more efficacious than blue dye, and noninferior to technetium‐99, potentially obviating the need for nuclear scanning in select patient populations, resulting in reduced time under anesthesia.
The Bethesda System for Reporting Thyroid Cytopathology was formalized in 2007 to stratify cytologic specimens based on their risk of malignancy. Several studies have reported significant variations ...between their institutional rate of malignancy compared to the Bethesda System for Reporting Thyroid Cytopathology. The objective of this study was to determine the national rate of malignancy for Bethesda III, Bethesda IV, and Bethesda V thyroid nodules.
From 2016 to 2019, patients with preoperative thyroid cytopathology and pathology results in National Surgical Quality Improvement database were included. The rate of malignancy was compared to the median the Bethesda System for Reporting Thyroid Cytopathology 2017, and risk factors associated with malignancy were identified for Bethesda III, Bethesda IV, and Bethesda V specimens.
In total, 13,121 patients with preoperative cytopathology and postresection pathology were identified. The national rate of malignancy was significantly higher than the Bethesda System for Reporting Thyroid Cytopathology 2017 for Bethesda III (36.2% vs 12.0%, P < .01), Bethesda IV (36.7% vs 25.0%, P < .01), and Bethesda V (91.1% vs 52.5%, P < .01) specimens. Male sex was significantly associated with malignancy in Bethesda III, Bethesda IV, and Bethesda V nodules (Bethesda III, odds ratio: 1.20, 1.01–1.42; Bethesda IV, odds ratio: 1.47, 1.27–1.71; Bethesda V, odds ratio: 1.28, 1.03–1.58). Younger age was associated with malignancy in Bethesda III patients under 55 (odds ratio: 1.23, 1.06–1.42), Bethesda IV patients under 42 (odds ratio: 1.23, 1.06–1.43), and Bethesda V patients aged less than 47 (odds ratio: 1.38, 1.15–1.67).
This is the largest cohort study to describe the national rate of malignancy for Bethesda III, IV, and V specimens in the United States. These results reveal the national rate of malignancy is higher than the implied rate of malignancy reported to patients based on the Bethesda System for Reporting Thyroid Cytopathology. We recommend counseling patients regarding this increased rate of malignancy to set appropriate expectations after surgical intervention.
Total colonic aganglionosis (TCA) is a rare variant of Hirschsprung disease (HD) where the colon and portion of distal ileum lack ganglion cells. Most pediatric use either a straight ileoanal ...(Swenson or Yancey-Soave) or a short Duhamel pull-through for TCA. There are no large studies comparing these techniques. We aimed to compare short-and medium-term outcomes between these approaches.
A retrospective review was performed among children with TCA from 2001 to 2019 undergoing a primary Duhamel or Swenson pull-through across three large children's hospitals. Patients undergoing redo and patients with greater than 30 % small bowel aganglionosis were excluded. We gathered data on demographics, operative approach, and outcomes at one, two, and three years. Continuous variables were analyzed with t-tests and categorical variables with Chi square or Fisher's tests.
There were 54 patients, with 26 (48 %) undergoing Duhamel and 28 (52 %) undergoing Swenson pull-through. There were no differences in sex, age, medical comorbidities, or operative details, including age at pull-through, laparoscopic vs open, length of involved small bowel, and operative time. Length of stay and post-operative complications were not different. Three years after pull-through, patients undergoing Duhamel had fewer stools per day (1-3 stools 69.6 % vs 14.3 %, p = 0.003) and were less likely to be prescribed fiber supplementation (4.2 % vs 43.8 %, p = 0.003). There were no differences in irrigations, botulinum toxin administration, loperamide, or HD admissions.
Both Duhamel and straight pull-throughs are safe for treatment of TCA, with acceptable short- and medium-term outcomes. Further studies on patient-reported outcomes are necessary to examine long-term differences.
III.
Lead (Pb) exposure is associated with a wide range of neurological deficits. Environmental exposures may impact epigenetic changes, such as DNA methylation, and can affect neurodevelopmental outcomes ...over the life-course. Mating mice were obtained from a genetically invariant C57BL/6J background agouti viable yellow
strain. Virgin dams
/
were randomly assigned 0 ppm (control), 2.1 ppm (low), or 32 ppm (high) Pb-acetate water two weeks prior to mating with male mice (
/
), and this continued through weaning. At age 10 months, cortex neuronal nuclei were separated with NeuN⁺ antibodies in male mice to investigate neuron-specific genome-wide promoter DNA methylation using the Roche NimbleGen Mouse 3x720K CpG Island Promoter Array in nine pooled samples (three per dose). Several probes reached p-value < 10
, all of which were hypomethylated: 12 for high Pb (minimum false discovery rate (FDR) = 0.16, largest intensity ratio difference = -2.1) and 7 for low Pb (minimum FDR = 0.56, largest intensity ratio difference = -2.2). Consistent with previous results in bulk tissue, we observed a weak association between early-life exposure to Pb and DNA hypomethylation, with some affected genes related to neurodevelopment or cognitive function. Although these analyses were limited to males, data indicate that non-dividing cells such as neurons can be carriers of long-term epigenetic changes induced in development.
Accurate identification of child physical abuse is crucial during the evaluation of injured children. Retinal hemorrhages (RH) are used for diagnosis, but clear criteria for screening with direct ...fundoscopic exam are lacking. We sought to identify key factors associated with RH to guide evaluations.
Electronic medical records for patients <1 year of age presenting to a Level I Pediatric Trauma Center with unwitnessed head injury from January 2015 to December 2018 were retrospectively reviewed. Multivariable logistic regression was used to identify factors associated with RH.
Two hundred and seventy-six patients were included; 63% underwent direct fundoscopic examination, of which 23% were positive and 77% were negative for RH. Unscreened patients tended to be older and have isolated skull fractures. Multivariable regression analysis revealed that abnormal GCS and subdural hemorrhage were positively associated with a diagnosis of retinal hemorrhage, while isolated skull fracture was negatively associated.
Children under 1 year of age with subdural hemorrhage have a greater risk of associated RH and should undergo routine screening with direct fundoscopic examination. Conversely, those with isolated skull fractures may not require an ophthalmology consultation. Standardized screening protocols may help reduce the risk of missing child physical abuse.
III (Diagnostic Test).
Hepatoblastoma is the most common malignant liver tumor of childhood, with liver transplant and extended resection used as surgical treatments for locally advanced tumors. Although each approach has ...well-described post-operative complications, quality-of-life outcomes have not been described following the two interventions. Long-term pediatric survivors of hepatoblastoma who underwent conventional liver resection or liver transplantation at a single institution from January 2000-December 2013 were recruited to complete quality-of-life surveys. Survey responses for the Pediatric Quality of Life Generic Core 4.0 (PedsQL, n = 30 patient and n = 31 parent surveys) and Pediatric Quality of Life Cancer Module 3.0 (PedsQL-Cancer, n = 29 patient and n = 31 parent surveys) were collected from patients and parents. The mean total patient-reported PedsQL score was 73.7, and the parent-reported score was 73.9. There were no significant differences in scores on the PedsQL between patients who underwent resection compared to those who underwent transplantation (
> 0.05 for all comparisons). On the PedsQL-Cancer module, procedural anxiety scores were significantly lower for patients who underwent resection as compared to transplant (M = 33.47 points less, CI -60.41, -6.53,
-value 0.017). This cross-sectional study demonstrates that quality of life outcomes are overall similar among patients receiving transplants and resections. Patients who received a resection reported worse procedural anxiety.
This paper aims to evaluate the pediatric surgery training pipeline vis-à-vis the pediatric surgery match and operative experience of pediatric surgery fellows.
Pediatric surgery remains a ...competitive surgical subspecialty. However, there is concern that operative experience for pediatric surgery fellows is changing. This paper examines the selectivity of the pediatric surgery match, along with the operative experience of pediatric surgery fellows to characterize the state of pediatric surgery training.
The pediatric surgery fellowship match was analyzed from the National Resident Matching Program data from 2010 to 2019. Selectivity among fellowships was compared using analysis of variance with Dunnett test. Operative log data for pediatric fellows was analyzed using the Accreditation Council for Graduate Medical Education case logs from 2009 to 2019. Linear regression analysis was used to evaluate trends in operative volume over time.
Pediatric surgery had the highest proportion of unmatched applicants (47.2% ± 5.3%) and lowest proportion of unfilled positions (1.4% ± 1.6%) when compared to other National Resident Matching Program surgical fellowships. Accreditation Council for Graduate Medical Education case log analysis revealed a statistically significant decrease in cases for graduating fellows (-5.3 cases/year, P < 0.05). Total index cases decreased (-4.7 cases/year, P < 0.01, R 2 = 0.83) such that graduates in 2019 completed 59 fewer index operations than graduates in 2009.
Although pediatric surgery fellowship remains highly selective there has been a decline in the operative experience for graduating fellows. This highlights the need for evaluation of training paradigms and operative exposure in pediatric surgery to ensure the training of competent pediatric surgeons.
UGT1A1 (UDP glucuronosyltransferase family 1 member A1) is the primary enzyme required for bilirubin conjugation, which is essential for preventing hyperbilirubinemia. Animal models lack key human ...organic anion transporting polypeptides with distinct epigenetic control over bilirubin metabolism, necessitating a human model to interrogate the regulatory mechanism behind UGT1A1 function. Here, we use induced pluripotent stem cells to develop human liver organoids that can emulate conjugation failure phenotype. Bilirubin conjugation assays, chromatin immunoprecipitation, and transcriptome analysis elucidated the role of glucocorticoid antagonism in UGT1A1 activation. This antagonism prevents the binding of transcriptional repressor MECP2 at the expense of NRF2 with associated off-target effects. Therefore, we introduced functional GULO (L-gulonolactone oxidase) in human organoids to augment intracellular ascorbate for NRF2 reactivation. This engineered organoid conjugated more bilirubin and protected against hyperbilirubinemia when transplanted in immunosuppressed Crigler-Najjar syndrome rat model. Collectively, we demonstrate that our organoid system serves as a manipulatable model for interrogating hyperbilirubinemia and potential therapeutic development.
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•HLOs are amenable for studying mediated bilirubin conjugation•HLOs inform the glucocorticoid-mediated epigenetic regulation of UGT1A1•Synthetic introduction of murine GULO in HLOs more efficiently conjugates bilirubin•Engineered HLO transplantation alleviates the symptoms of Crigler-Najjar syndrome model
This paper describes the development of pluripotent stem cell-derived human liver organoid (HLO) models to study UGT1A1 gene regulation and function. We engineered active GULO (murine gulonolactone oxidase) expressing HLO to augment therapeutic potential, thus alleviating symptoms in Crigler-Najjar syndrome model rats upon transplantation.
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