Publications by authors named "Dai H Chung"

111 Publications

Effect of Quarantine and Reopening Measures on Pediatric Trauma Admissions During the 2019 SARS-CoV2 Virus Pandemic.

J Am Coll Surg 2022 04;234(4):685-690

From the Department of Pediatric Surgery, Children's Medical Center Dallas, Dallas, TX.

Background: Several studies have reported decreased trauma admissions and increased physical abuse in children resulting from stay-at-home measures. However, these studies have focused on a limited period after the implementation of lockdown policies. The purpose of this study was to examine the effect of quarantine and reopening initiatives on admissions for varying types of injuries in pediatric patients.

Study Design: Registry data for an urban Level I pediatric trauma center were evaluated from April 1, 2018, to March 30, 2021. A timeline of local shutdown and reopening measures was established and used to partition the data into 6-month intervals. Data about demographics and injury characteristics were compared with similar intervals in 2018 and 2019 using appropriate statistical methodology for categorical, parametric, and nonparametric data.

Results: A total of 3,110 patients met criteria for inclusion. A total of 1,106 patients were admitted the year after the closure of schools and nonessential businesses. Decreases in overall admissions and evaluations for suspected child abuse noted early in the pandemic were not sustained during shutdown or reopening periods. However, we observed a 77% increase in all-terrain vehicle injuries, along with a 59% reduction in sports injuries (chi-square [8, N = 3,110] = 49.7; p < 0.001). Significant shifts in demographic and payor status were also noted.

Conclusions: This is the first study to comprehensively examine the effects of quarantine and reopening policies on admission patterns for a pediatric trauma center in a metropolitan area. Total admissions and child abuse evaluations were not impacted. If shutdown measures are re-instituted, preventative efforts should be directed towards ATV use and recreational activities.
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http://dx.doi.org/10.1097/XCS.0000000000000130DOI Listing
April 2022

Impact of Cryoablation on Pectus Excavatum Repair in Pediatric Patients.

J Am Coll Surg 2022 04;234(4):484-492

From the Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX.

Background: Minimally invasive repair of pectus excavatum (MIRPE) involves placement of a transthoracic, retrosternal support bar under thoracoscopic guidance. Despite its minimally invasive technical approach, postoperative pain is a significant morbidity that often results in increased length of stay. Multi-modal pain control strategies have been used in the past with limited success. Recently, the use of intraoperative intercostal nerve cryoablation (CA) has been added. In the present study, we aim to evaluate the effects of CA on postoperative pain control, opioid requirements, and perioperative outcomes.

Study Design: A single-center, retrospective chart review of all patients (less than 18 years old) who underwent MIRPE from 2009 to 2020 was performed. CA was started in June 2018. Data collection included demographics, preoperative characteristics, intraoperative findings, and postoperative outcomes. We hypothesized that CA would be associated with improved pain scores, lower doses of total inpatient opioid requirement, and shorter length of stay (LOS).

Results: One hundred sixty-one patients met inclusion criteria: 75 underwent intraoperative CA and 86 underwent MIRPE without CA (NCA group). CA significantly decreased median LOS from 4 days in NCA to 2 days; the use of CA was the only significant predictor of LOS on linear regression. CA was also associated with decreased total PCA, intravenous opioid, and oral opioid dosages. There was no difference in inpatient pain scores and a slight increase in mean procedure time. However, CA was associated with significantly decreased postoperative complications.

Conclusions: The use of cryoablation during MIRPE significantly decreases LOS, perioperative opioid requirements, and postoperative complications, with a minimal increase in operative time. Cryoablation is an effective pain control modality in the surgical management of chest wall deformities in children.
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http://dx.doi.org/10.1097/XCS.0000000000000103DOI Listing
April 2022

Induction of serine hydroxymethyltransferase 2 promotes tumorigenesis and metastasis in neuroblastoma.

Oncotarget 2022 6;13:32-45. Epub 2022 Jan 6.

Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75234, USA.

High-risk neuroblastoma (NB) remains an extremely difficult subgroup to cure and is associated with amplification. Serine hydroxymethyltransferase 2 (SHMT2) regulates serine metabolism in a myc-dependent manner; it is upregulated in several cancers and is associated with tumor aggressiveness. Akt-2, an important regulator of via the PI3K/Akt pathway, induces metastatic potential in NB. The association between SHMT2 and PI3K/Akt in hepatocyte regeneration has been well established but its mechanistic interaction in cancer has yet to be clearly elucidated. Herein, we evaluated the exact role of SHMT2 on the PI3K/Akt pathway, in addition to NB tumorigenesis and metastatic potential . gene expression and overall survival (OS) were assessed. Two human NB cell lines were examined. SHMT2 silencing and overexpression were performed. The downstream effects were analyzed with immunoblotting, RT-qPCR and functional assays were performed. We found gene expression is associated with decreased OS and amplification. SHMT2 protein and mRNA expression are increased in -amplified cells. SHMT2 expression has a direct interaction with Akt-2 and . Induction of increased cellular proliferation, colony formation and cellular migration and expression was increased in metastatic NB cells. We conclude that SHMT2 regulates N-Myc via phosphorylation of Akt-2 and plays an important role in NB tumorigenesis by contributing to cell growth, migration, colony formation and metastasis .
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http://dx.doi.org/10.18632/oncotarget.28168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8735882PMC
January 2022

Reactivation of silenced α-N-catenin induces retinoic acid sensitivity in neuroblastoma cells.

Surgery 2021 11 3;170(5):1546-1553. Epub 2021 Jun 3.

Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address:

Background: High-risk neuroblastoma remains the most difficult pediatric solid tumor to treat and is associated with chemotherapy and radiation resistance that may be secondary to epigenetic modifications. We have previously found that α-N-catenin, a cell-adhesion protein encoded by the gene CTNNA2, plays a tumor suppressor role in neuroblastoma by inhibiting the NF-κB signaling pathway. A subset of neuroblastoma tumors that lack α-N-catenin are resistant to all-trans retinoic acid. However, the mechanism of CTNNA2 silencing in neuroblastoma remains unknown. Herein, we sought to determine the mechanism of α-N-catenin silencing in neuroblastoma.

Methods: Two human neuroblastoma cell lines, SK-N-AS and BE(2)-C, were stably transfected with a plasmid expressing CTNNA2. Both cell lines were treated with the histone deacetylase inhibitor Trichostatin A alone and in combination with retinoic acid. Cell survival and colony formation were measured. Cellular differentiation and expression of cell survival signaling pathways were analyzed. Immunoblotting and reverse transcription quantitative polymerase chain reaction were used to examine protein and messenger RNA expression.

Results: Retinoic acid treatment induced cellular differentiation and inhibited cellular proliferation in BE(2)-C cells but did not induce differentiation in SK-N-AS cells. Re-expression of α-N-catenin enhanced the sensitivity to retinoic acid-induced cell growth arrest and downregulated key cell survival pathways in both cell lines. Trichostatin A treatment induced CTNNA2 expression in SK-N-AS cells, and combination treatment with Trichostatin A induced retinoic acid sensitivity in retinoic acid-resistant cells.

Conclusion: Re-expression of α-N-catenin in retinoic acid-resistant cells induced sensitivity to retinoic acid treatment and is controlled epigenetically via histone deacetylase. α-N-catenin is a potential biomarker for retinoic acid sensitivity and combination treatment with Trichostatin A and retinoic acid may improve survival among children with high-risk, retinoic acid-resistant neuroblastoma.
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http://dx.doi.org/10.1016/j.surg.2021.04.039DOI Listing
November 2021

Pediatric Subcutaneous Abscess: Still a Clinical Exam-Based Diagnosis and Treatment.

Children (Basel) 2021 May 14;8(5). Epub 2021 May 14.

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Subcutaneous abscesses occur frequently in the pediatric population, yet there is great variability in the approach to diagnosis and management, partly due to opposing recommendations in the current literature and the lack of a standardized protocol for diagnosis and management among pediatric medical centers. This has led to inconsistencies by the providers, as well as the hospital clinical pathways, with regards to the appropriate management of subcutaneous abscesses. We hypothesize that the current variability in diagnostic work-up and management contributes to the wide use of unnecessary imaging and therapeutics without altering the overall outcomes. We performed a retrospective chart review that compared 200 encounters for patients < 18 years of age with a diagnosis of subcutaneous abscess at a single large tertiary pediatric institution. Our results showed that only 13.6% of wound cultures obtained led to a change in the antibiotic regimen and that blood cultures were positive in only 2.1% of cases. There was no difference in the incision and drainage performed based on ultrasound findings in the presence of fluctuance on physical exam. Patients presenting with fever were more likely to be admitted to the hospital for further care than those without fever. Our results showed no difference in outcome after incision and drainage for abscesses packed with gauze versus those left to drain via a vessel loop drain. There was no difference in recurrence in patients discharged with oral antibiotics versus without oral antibiotic treatment. Our data indicate that many of the diagnostic studies used for the management of a subcutaneous abscess have little to no effect on the outcome. Subcutaneous abscesses are a common pediatric complaint, and this study could help healthcare providers utilize more effective and efficient management strategies for skin and soft tissue infections.
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http://dx.doi.org/10.3390/children8050392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153592PMC
May 2021

Predictive Factors and Outcomes for Successful Thoracoscopic Lung Resection in Pediatric Patients.

J Am Coll Surg 2021 04 29;232(4):551-558. Epub 2021 Jan 29.

Department of Surgery, Division of Pediatric Surgery, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address:

Background: Less than 50% of children with congenital lung lesions are treated thoracoscopically. There are variable data regarding the benefits and limited information on factors contributing to successful thoracoscopic lobectomies in pediatric patients. We sought to identify predictive factors leading to safe and efficient thoracoscopic lung resection.

Study Design: We performed a single-center, retrospective chart review of patients (age <18 y) who underwent lung resection between June 2009 and July 2020. Pulmonary wedge resection was excluded. Data collected included demographics, perioperative findings, such as symptoms or infection, and postoperative outcomes. Univariate, multivariate, and sensitivity analyses were performed.

Results: Ninety-six patients were identified. Sixty-nine patients (72%) underwent initial thoracoscopy, with 15 (22%) converting to open thoracotomy (CTO). Forty-one (43%) patients had preoperative symptoms and 15 (15.6%) had an active infection. Among symptomatic patients, 18 (43.9%) underwent thoracotomy and 23 (56%) were attempted thoracoscopically, 13 (31%) of whom were completed thoracoscopically. On univariate analysis, age >1 year, infection, preoperative symptoms, and intraoperative adhesions were associated with CTO. Older age (odds ratio [OR] = 1.041) and estimated blood loss (EBL) (OR = 2.398) were significant prognostic factors of CTO on logistic regression. Thoracoscopy was significantly associated with decreased length of stay, opioid use, chest tube duration, blood loss and need for blood transfusion. There was no difference in operative time, 30-day readmission, or mortality.

Conclusions: Thoracoscopy has become a standard approach for pediatric lung resection. Our findings indicate that age < 1 year and the absence of active respiratory infection and preoperative symptoms may be predictive of successful completion of the thoracoscopic approach. Thoracoscopy offers significant advantages over the traditional open thoracotomy with regard to blood loss and opioid requirements, LOS, and chest tube duration.
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http://dx.doi.org/10.1016/j.jamcollsurg.2020.12.013DOI Listing
April 2021

Children Are Not Little Adults When Prescribing Opioids.

JAMA Surg 2021 01;156(1):91

Pediatric Surgery, University of Texas Southwestern Medical Center, Dallas.

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http://dx.doi.org/10.1001/jamasurg.2020.5150DOI Listing
January 2021

Preclinical evaluation of the anti-tumor activity of pralatrexate in high-risk neuroblastoma cells.

Oncotarget 2020 Aug 11;11(32):3069-3077. Epub 2020 Aug 11.

Department of Surgery, Division of Pediatric Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.

Introduction: Pralatrexate is a folate analogue inhibitor of dihydrofolate reductase exhibiting high affinity for reduced folate carrier-1 with antineoplastic and immunosuppressive activities, similar to methotrexate. Despite advances in multi-modality treatment strategies, the survival rates for children with high-risk neuroblastoma have failed to improve. Therefore, the intense research continues in order to identify the ideal novel agent or combination of chemotherapy drugs to treat high-risk neuroblastoma.

Materials And Methods: Four human neuroblastoma cell lines were used to determine IC values of select chemotherapy agents. Antiproliferative effects of pralatrexate were assessed by adherent and non-adherent colony formation assays. Cell cycle arrest and apoptosis were measured by flow cytometry and immunoblotting. PDX tissue culture was used to assess efficacy.

Results: Treatment with pralatrexate in all four neuroblastoma cell lines blocked cell growth in 2D and 3D culture conditions in a time-dependent manner. The potency of pralatrexate was ten-fold stronger than methotrexate, as measured by IC. Pralatrexate-induced apoptosis was confirmed by caspase-3 activation and PARP cleavage. and mRNA expressions were decreased with pralatrexate in -amplified neuroblastoma cells.

Conclusions: Pralatrexate demonstrated effective inhibition of cell growth and viability. The higher potency of pralatrexate compared to methotrexate, a drug with high levels of toxicity, suggests pralatrexate may be a safer alternative to methotrexate as an effective chemotherapeutic agent in the treatment of patients with high-risk neuroblastoma.
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http://dx.doi.org/10.18632/oncotarget.27697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429182PMC
August 2020

Overexpression of microRNA-145 inhibits tumorigenesis through autophagy in chemotherapy and radiation resistant neuroblastoma cells.

Oncoscience 2020 Jan 1;7(1-2):1-9. Epub 2020 Feb 1.

UT Southwestern Medical Center, Department of Surgery, Dallas, TX, USA.

MicroRNA-145 (miR-145) plays a suppressive role in the process of tumorigenesis and an important role in induction of autophagy. However, the exact role of miR-145 in therapeutically resistant neuroblastoma cells remain elusive. Herein, we sought to evaluate the effects of miR-145 overexpression in chemo‑ and radiation-resistant neuroblastoma cells. We hypothesized that miR-145 affects the aggressiveness of resistant cells by enhancing autophagy. We established Cisplatin-resistant (CDDP-R), Vincristine-resistant (Vin-R), and radiation-resistant (Rad-R) neuroblastoma cells and found that miR-145 expression was significantly decreased in the resistant cells compared to the parental cells. Exogenously expression of miR-145 inhibited oncogenic properties such as proliferation, clonogenicity, anchorage-independent growth, cell migration, and tubule formation in the resistant cells. In addition, we also found that an autophagy protein marker, LC3, was only minimally expressed in the resistant cells. In particular, when miR-145 was overexpressed in the resistant cells, LC3 I and II were expressed and an increased punctate fluorescence of LC3 protein was found indicating the induction of autophagy. Taken together, our data suggests that miR-145 inhibits tumorigenesis and aggressiveness via modulation of autophagy in neuroblastoma.
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http://dx.doi.org/10.18632/oncoscience.496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105155PMC
January 2020

WDR5 is a conserved regulator of protein synthesis gene expression.

Nucleic Acids Res 2020 04;48(6):2924-2941

Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37240, USA.

WDR5 is a highly-conserved nuclear protein that performs multiple scaffolding functions in the context of chromatin. WDR5 is also a promising target for pharmacological inhibition in cancer, with small molecule inhibitors of an arginine-binding pocket of WDR5 (the 'WIN' site) showing efficacy against a range of cancer cell lines in vitro. Efforts to understand WDR5, or establish the mechanism of action of WIN site inhibitors, however, are stymied by its many functions in the nucleus, and a lack of knowledge of the conserved gene networks-if any-that are under its control. Here, we have performed comparative genomic analyses to identify the conserved sites of WDR5 binding to chromatin, and the conserved genes regulated by WDR5, across a diverse panel of cancer cell lines. We show that a specific cohort of protein synthesis genes (PSGs) are invariantly bound by WDR5, demonstrate that the WIN site anchors WDR5 to chromatin at these sites, and establish that PSGs are bona fide, acute, and persistent targets of WIN site blockade. Together, these data reveal that WDR5 plays a predominant transcriptional role in biomass accumulation and provide further evidence that WIN site inhibitors act to repress gene networks linked to protein synthesis homeostasis.
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http://dx.doi.org/10.1093/nar/gkaa051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102967PMC
April 2020

Dual-Targeting AKT2 and ERK in cancer stem-like cells in neuroblastoma.

Oncotarget 2019 Sep 24;10(54):5645-5659. Epub 2019 Sep 24.

Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.

Neuroblastoma remains one of the most difficult pediatric solid tumors to treat. In particular, the refractory and relapsing neuroblastomas are highly heterogeneous with diverse molecular profiles. We previously demonstrated that AKT2 plays critical roles in the regulation of neuroblastoma tumorigenesis. Here we hypothesize that targeting AKT2 could block the signal transduction pathways enhanced in chemo- and/or radiation-resistant neuroblastoma cancer stem-like cells. We found cell proliferation and survival signaling pathways AKT2/mTOR and MAPK were enhanced in cisplatin (CDDP)- and radiation-resistant neuroblastoma cells. Blocking these two pathways with specific inhibitors, CCT128930 (AKT2 inhibitor) and PD98059 (MEK inhibitor) decreased cell proliferation, angiogenesis, and cell migration in these resistant cells. We further demonstrated that the resistant cells had a higher sphere-forming capacity with increased expression of stem cell markers CD133, SOX2, ALDH, Nestin, Oct4, and Nanog. Importantly, the tumorsphere formation, which is a surrogate assay for self-renewal, was sensitive to the inhibitors of AKT2 and MAPK. Taken together, our findings suggest that CDDP- and radiation-resistant cancer stem-like neuroblastoma cells might serve as a useful tool to improve the understanding of molecular mechanisms of therapeutic resistance. This may aid in the development of more effective novel treatment strategies and better clinical outcomes in patients with neuroblastoma.
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http://dx.doi.org/10.18632/oncotarget.27210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771463PMC
September 2019

Identification of α-N-catenin as a novel tumor suppressor in neuroblastoma.

Oncotarget 2019 Aug 20;10(49):5028-5040. Epub 2019 Aug 20.

Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.

The lost expression of α-catenin has been found in cancers, and reinstalling α-catenin inhibits tumor growth. Here we hypothesized that the α-N-catenin, a homologous member of α-catenin and neural-specific expressed, functions as a novel tumor suppressor in neural crest-derived tumor, neuroblastoma. We correlated CTNNA2 (encodes α-N-catenin) expression to neuroblastoma disease relapse-free survival probability using publicly accessible human neuroblastoma datasets in R2 platform. The result showed that it negatively correlated to relapse-free survival probability significantly in patients with neuroblastoma with non-MYCN amplified tumor. Conversely, overexpressing CTNNA2 suppressed the neuroblastoma cell proliferation as measuring by the clonogenesis, inhibited anchorage-independent growth with soft agar colony formation assay. Forced expression of CTNNA2 decreased cell migration and invasion. Further, overexpression of CTNNA2 reduced the secretion of angiogenic factor IL-8 and HUVEC tubule formation. Our results show, for the first time, that α-N-catenin is a tumor suppressor in neuroblastoma cells. These findings were further corroborated with tumor xenograft study, in which α-N-catenin inhibited tumor growth and reduced tumor blood vessel formation. Interestingly, this is only observed in SK-N-AS xenografts lacking MYCN expression, and not in BE(2)-C xenografts with MYCN amplification. Mechanistically, α-N-catenin attenuated NF-κB responsive genes by inhibiting NF-κB transcriptional activity. In conclusion, these data demonstrate that α-N-catenin is a tumor suppressor in non-MYCN-amplified neuroblastomas and it inhibits NF-κB signaling pathway to suppress tumor growth in human neuroblastomas. Therefore, restoring the expression of α-N-catenin can be a novel therapeutic approach for neuroblastoma patients who have the deletion of CTNNA2 and lack of MYCN amplification.
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http://dx.doi.org/10.18632/oncotarget.27096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707940PMC
August 2019

Association between image-defined risk factors and neuroblastoma outcomes.

J Pediatr Surg 2019 Jun 1;54(6):1184-1191. Epub 2019 Mar 1.

Surgical Outcomes Center for Kids, Vanderbilt University Medical Center, Nashville, TN; Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN.

Background: The current neuroblastoma (NBL) staging system employs image-defined risk factors (IDRFs) to assess numerous anatomic features, but the impact of IDRFs on surgical and oncologic outcomes is unclear.

Methods: The Vanderbilt Cancer Registry identified children treated for NBL from 2002 to 2017. Tumor volume (TV) and IDRFs were measured radiographically at diagnosis and before resection. Perioperative and oncologic outcomes were evaluated.

Results: At diagnosis of 106 NBL, 61% were IDRF positive. MYCN-amplified and undifferentiated NBL had more IDRFs than nonamplified and more differentiated tumors (p = 0.001 and p = 0.01). Of 86 NBLs resected, 43% were IDRF positive, which associated with higher stage, risk, and TV (each p < 0.001). The presence of IDRF at resection was also associated with increased blood loss (p < 0.001), longer operating times (p < 0.001), greater incidence of intraoperative complications (p = 0.03), more frequent ICU admissions postoperatively (p < 0.001), and longer hospital stays (p < 0.001). IDRF negative and positive tumors did not have significantly different rates of gross total resection (p = 0.2). Five-year relapse-free and overall survival was similar for IDRF negative and positive NBL (p = 0.9 and p = 0.8).

Conclusions: IDRFs at diagnosis were associated with larger, less differentiated, advanced stage, and higher risk NBL and at resection with increased operative difficulty and perioperative morbidity. However, the frequency of gross total resection and patient survival after resection were not associated with the presence of IDRFs.

Type Of Study: Retrospective cohort study.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1016/j.jpedsurg.2019.02.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628713PMC
June 2019

Neuroblastoma: Tumor Biology and Its Implications for Staging and Treatment.

Children (Basel) 2019 Jan 17;6(1). Epub 2019 Jan 17.

Department of Surgery, Children's Medical Center Dallas, UT Southwestern Medical Center, Dallas, TX 75235, USA.

Neuroblastoma, the most common extracranial solid tumor of childhood, has widely variable outcomes dependent on the specific biology of the tumor. In this review, current biologic principles that are used to stratify risk and guide treatment algorithms are discussed. The role for surgical resection in neuroblastoma is also reviewed, including the indications and timing of surgery within the greater treatment plan.
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http://dx.doi.org/10.3390/children6010012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352222PMC
January 2019

Characterization of pediatric golf cart injuries to guide injury prevention efforts.

Am J Emerg Med 2018 Jun 2;36(6):1049-1052. Epub 2018 Mar 2.

Vanderbilt University Medical Center, Department of Pediatric Surgery, 2200 Children's Way, Nashville, TN 37232, USA. Electronic address:

Background: Golf cart injuries represent an increasing source of morbidity and mortality in the United States. Characterization of the circumstances of these injuries can inform injury prevention efforts.

Methods: This study retrospectively reviews a prospective trauma registry at a level-one pediatric trauma center for golf cart-related injuries in patients under 18years of age admitted to the hospital between 2008 and 2016.

Results: The 40 identified crashes were associated with 82 hospital days, 17 ICU days, and more than $1 million in hospital charges over the study period. The median hospital stay was 1.5days, and the median hospital charge was $20,489. Severe injuries with an Injury Severity Score of >15 were identified in 25% of patients, and moderate injuries with scores between nine and 15 were identified in an additional 30%. The most common injures were head and neck (60%) and external injuries to the body surface (52.5%). Only a single child was wearing a seatbelt, and the vast majority was not using any safety equipment. Children as young as nine years old were driving golf carts, and child drivers were associated with the cart overturning (p=0.007).

Conclusions: Golf cart crashes were a source of substantial morbidity at a level-one trauma center. Increased safety measures, such as higher hip restraints, seatbelts, and front-wheel breaks could substantially increase the safety of golf carts. Increased regulation of driving age as well as driver education may also reduce these injuries.
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http://dx.doi.org/10.1016/j.ajem.2018.03.002DOI Listing
June 2018

Inhibition of Sirtuin 6 Induces Neuroblastoma Differentiation.

Anticancer Res 2018 02;38(2):647-654

Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN, U.S.A.

Background/aim: Sirtuins (SIRTs) play crucial roles in various signaling pathways that modulate differentiation and proliferation. We sought to elucidate the role of SIRTs in differentiation and proliferation of human neuroblastoma (NB).

Materials And Methods: NB cells were treated with nicotinamide (NAM), a non-specific SIRT inhibitor, SIRT-targeted short hairpin RNAs, and retinoic acid to assess cell growth and differentiation.

Results: SIRTs are involved in proliferation and differentiation using NAM in BE(2)-C cells. Specifically, SIRT6 knockdown in BE(2)-C cells reduced cell proliferation, induced neurite extension, corresponding with induction of p21 expression and G cell-cycle arrest. These effects were rescued by forced re-overexpression of SIRT6. SIRT6 expression was reduced in differentiated human NB sections, and RA-induced differentiation in BE(2)-C cells.

Conclusion: SIRTs have important oncogenic properties in NB beyond its established functions in aging and genome stability. SIRT6 may represent a novel target for developing future therapeutics for the treatment of aggressive NBs.
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http://dx.doi.org/10.21873/anticanres.12268DOI Listing
February 2018

Evolution of a level I pediatric trauma center: Changes in injury mechanisms and improved outcomes.

Surgery 2018 05 17;163(5):1173-1177. Epub 2018 Jan 17.

Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.

Background: Trauma is the leading cause of mortality among children, underscoring the need for specialized child-centered care. The impact on presenting mechanisms of injury and outcomes during the evolution of independent pediatric trauma centers is unknown. The aim of this study was to evaluate the impact of our single center transition from an adult to American College of Surgeons-verified pediatric trauma center.

Methods: A retrospective analysis was performed of 1,190 children who presented as level I trauma activations between 2005 and 2016. Patients were divided into 3 chronological treatment eras: adult trauma center, early pediatric trauma center, and late pediatric trauma center after American College of Surgeons verification review. Comparisons were made using Pearson χ, Wilcoxon rank sum, and Kruskal-Wallis tests.

Results: The predominant mechanism of injury was motor vehicle crash, with increases noted in assault/abuse (2% adult trauma center, 11% late pediatric trauma center). A decrease in intensive care admissions was identified during late pediatric trauma center compared with early pediatric trauma center and adult trauma center (51% vs 62.4% vs 67%, P < .001), with concomitant increases in admissions to the floor and immediate operative interventions, but overall mortality was unchanged.

Conclusion: Transition to a verified pediatric trauma center maintains the safety expected of the American College of Surgeons certification, but with notable changes identified in mechanism of injury and improvements in resource utilization.
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http://dx.doi.org/10.1016/j.surg.2017.10.070DOI Listing
May 2018

cFLIP critically modulates apoptotic resistance in epithelial-to-mesenchymal transition.

Oncotarget 2017 Nov 25;8(60):101072-101086. Epub 2017 Jul 25.

Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville TN, 37232, USA.

Epithelial cancers (carcinomas) comprise the top four causes of cancer-related deaths in the United States. While overall survival has been steadily improving, therapy-resistant disease continues to present a major therapeutic challenge. Carcinomas often exploit the normal developmental program, epithelial-to-mesenchymal transition (EMT), to gain a mesenchymal phenotype associated with increased invasiveness and resistance to apoptosis. We have previously shown that an isoxazole-based small molecule, ML327, partially reverses TGF-β-induced EMT in an immortalized mouse mammary epithelial cell line. Herein, we demonstrate that ML327 reverses much of the EMT gene expression program in cultured carcinoma cell lines. The reversal of EMT sensitizes these cancer cells to the apoptosis-inducing ligand TRAIL. This sensitization is independent of E-cadherin expression and rather relies on the downregulation of a major anti-apoptotic protein, cFLIP. Loss of cFLIP is sufficient to overcome resistance to TRAIL and exogenous overexpression of cFLIP restores resistance to TRAIL-induced apoptosis despite EMT reversal with ML327. In summary, we have utilized an isoxazole-based small molecule that partially reverses EMT in carcinoma cells to demonstrate that cFLIP critically regulates the apoptosis resistance phenotype associated with EMT.
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http://dx.doi.org/10.18632/oncotarget.19557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731856PMC
November 2017

Isoxazole compound ML327 blocks MYC expression and tumor formation in neuroblastoma.

Oncotarget 2017 Oct 20;8(53):91040-91051. Epub 2017 Jul 20.

Section of Surgical Sciences, Department of Surgery, at Vanderbilt University Medical Center, TN 37232, Nashville, USA.

Neuroblastomas are the most common extracranial solid tumors in children and arise from the embryonic neural crest. -amplification is a feature of ∼30% of neuroblastoma tumors and portends a poor prognosis. Neural crest precursors undergo epithelial-to-mesenchymal transition (EMT) to gain migratory potential and populate the sympathoadrenal axis. Neuroblastomas are posited to arise due to a blockade of neural crest differentiation. We have recently reported effects of a novel MET inducing compound ML327 (-(3-(2-hydroxynicotinamido) propyl)-5-phenylisoxazole-3-carboxamide) in colon cancer cells. Herein, we hypothesized that forced epithelial differentiation using ML327 would promote neuroblastoma differentiation. In this study, we demonstrate that ML327 in neuroblastoma cells induces a gene signature consistent with both epithelial and neuronal differentiation features with adaptation of an elongated phenotype. These features accompany induction of cell death and G1 cell cycle arrest with blockage of anchorage-independent growth and neurosphere formation. Furthermore, pretreatment with ML327 results in persistent defects in proliferative potential and tumor-initiating capacity, validating the pro-differentiating effects of our compound. Intriguingly, we have identified destabilization of MYC signaling as an early and consistent feature of ML327 treatment that is observed in both -amplified and -single copy neuroblastoma cell lines. Moreover, ML327 blocked mRNA levels and tumor progression in established -amplified xenografts. As such, ML327 may have potential efficacy, alone or in conjunction with existing therapeutic strategies against neuroblastoma. Future identification of the specific intracellular target of ML327 may inform future drug discovery efforts and enhance our understanding of MYC regulation.
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http://dx.doi.org/10.18632/oncotarget.19406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710904PMC
October 2017

Elevated TIMP-1 expression is associated with a prometastatic phenotype, disease relapse, and poor survival in neuroblastoma.

Oncotarget 2017 Oct 28;8(47):82609-82620. Epub 2017 Jul 28.

Section of Surgical Sciences, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Approximately two-thirds of patients with neuroblastoma are found to have metastatic disease at time of diagnosis with frequent skeletal, lymph node, central nervous system, and liver involvement. Using a serial splenic injection model, we have isolated an aggressive subclone (BE(2)-C/LM2) from -amplified neuroblastomas that demonstrate an enhanced propensity to develop metastatic liver lesions. BE(2)-C/LM2 subclone cells demonstrate increased adherent, soft agar colony and tumorsphere growth . Components of the tumor microenvironment regulate cancer progression, via networks of cytokines and growth factors. Cytokine array analysis identified increased TIMP-1 in the plasma of mice injected with BE(2)-C/LM2 subclone cells, leading us to hypothesize that TIMP-1 may play a role in our observed prometastatic phenotype. Immunoblotting and ELISA demonstrated enhanced endogenous TIMP-1 expression in our isolated neuroblastoma subclone. Silencing endogenous TIMP-1 successfully blocked proliferation, soft agar colony formation and tumorsphere formation by BE(2)-C/LM2 cells. Stable RNA interference of endogenous TIMP-1 failed to reverse the prometastatic phenotype of our BE(2)-C/LM2 subclone in our liver metastasis model, suggesting that endogenous TIMP-1 levels may not be an essential component of this behavior. Notably, tissue microarray analysis and Kaplan-Meier by gene expression demonstrates that elevated TIMP-1 expression is correlated with increased disease relapse and mortality in patients with neuroblastoma. Taken together, our study identifies TIMP-1 as a novel soluble factor that is associated with a prometastatic phenotype in our model and adverse outcomes in patients with neuroblastoma.
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http://dx.doi.org/10.18632/oncotarget.19664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669914PMC
October 2017

A multiyear assessment of a hospital-school program to promote teen motor vehicle safety.

J Trauma Acute Care Surg 2017 11;83(5S Suppl 2):S190-S196

From the Pediatric Surgery/Trauma (P.U.), Monroe Carell Jr. Children's Hospital at Vanderbilt; Pediatric Emergency Medicine (C.M.E.); Department of Pediatric Surgery (D.H.C.), Vanderbilt University Medical Center; Pediatric Surgery/Trauma (E.B.R.), and Pediatric Emergency Medicine (L.W.-H., N.S.), Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee.

Background: Motor vehicle crashes are the leading cause of death among teen drivers. The main goal of this program was to reduce texting while driving among high school teens through a unique peer-generated anti-texting campaign.

Methods: The program consisted of two phases. In phase 1, student leaders participated in a half-day, hospital-based experiential program that emphasized safe teen driving. In phase 2, these students conceptualized and implemented an anti-texting while driving campaign during the school year. The program enrolled 32 schools with 137 student participants in phase 1. This study uses a prospective quasi-experimental pre-post design. A presurvey and a follow-up online survey were used. Response rate was 81%. In phase 2, two rounds of observations of drivers were made near the participating schools at the beginning and end of the phase 2 campaign. The results were analyzed using proportion tests.

Results: There was a strong belief (6.49 on a seven-point scale) that texting while driving could result in a crash. About 58% had texted while driving in the previous 7 days in the pre-survey. This proportion decreased significantly to 44% in the follow-up (p < 0.05). Knowledge of Tennessee Graduated Driver Licensing laws and feeling of empowerment to take action with a teen driver who was texting improved significantly (p < 0.05). In phase 2, 12,309 drivers (adults and teens) were observed in the first round, and 13,153 were observed in the second round of observations. Significant reduction in the proportion of drivers texting while driving (from 13% to 9%; p < 0.0001) was observed.

Conclusion: Results of driver observations support the effectiveness of this program in meeting the key objective of reducing texting while driving. The program also influenced teenagers' willingness to take positive steps when faced with a driver who was texting. Future efforts should aim to influence social and peer norms.

Level Of Evidence: Therapeutic study, level IV.
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http://dx.doi.org/10.1097/TA.0000000000001521DOI Listing
November 2017

ML327 induces apoptosis and sensitizes Ewing sarcoma cells to TNF-related apoptosis-inducing ligand.

Biochem Biophys Res Commun 2017 09 14;491(2):463-468. Epub 2017 Jul 14.

Section of Surgical Sciences, Department of Surgery, United States; Department of Cancer Biology, United States; Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, United States. Electronic address:

Ewing sarcomas are rare mesenchymal-derived bone and soft tissue tumors in children. Afflicted children with distant metastases have poor survival despite aggressive therapeutics. Epithelial-to-mesenchymal transition in epithelial carcinomas is associated with loss of E-cadherin and resistance to apoptosis. ML327 is a novel small molecule that we have previously shown to reverse epithelial-to-mesenchymal transition features in both epithelial and neural crest-derived cancers. Herein, we sought to evaluate the effects of ML327 on mesenchymal-derived Ewing sarcoma cells, hypothesizing that ML327 initiates growth arrest and sensitizes to TNF-related apoptosis-inducing ligand. ML327 induced protein expression changes, increased E-cadherin and decreased vimentin, consistent with partial induction of mesenchymal-to-epithelial transition in multiple Ewing Sarcoma cell lines (SK-N-MC, TC71, and ES-5838). Induction of epithelial features was associated with apoptosis, as demonstrated by PARP and Caspase 3 cleavage by immunoblotting. Cell cycle analysis validated these findings by marked induction of the subG cell population. In vitro combination treatment with TRAIL demonstrated additive induction of apoptotic markers. Taken together, these findings establish a rationale for further in vivo trials of ML327 in cells of mesenchymal origin both alone and in combination with TRAIL.
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http://dx.doi.org/10.1016/j.bbrc.2017.07.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564678PMC
September 2017

A multiyear assessment of a hospital-school program to promote teen motor vehicle safety.

J Trauma Acute Care Surg 2017 08;83(2):289-295

From the Pediatric Surgery/Trauma (P.U.), Monroe Carell Jr. Children's Hospital at Vanderbilt; Pediatric Emergency Medicine (C.M.E.); Department of Pediatric Surgery (D.H.C.), Vanderbilt University Medical Center; Pediatric Surgery/Trauma (E.B.R.), and Pediatric Emergency Medicine (L.W.-H., N.S.), Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee.

Background: Motor vehicle crashes are the leading cause of death among teen drivers. The main goal of this program was to reduce texting while driving among high school teens through a unique peer-generated anti-texting campaign.

Methods: The program consisted of two phases. In phase 1, student leaders participated in a half-day, hospital-based experiential program that emphasized safe teen driving. In phase 2, these students conceptualized and implemented an anti-texting while driving campaign during the school year. The program enrolled 32 schools with 137 student participants in phase 1.This study uses a prospective quasi-experimental pre-post design. A presurvey and a follow-up online survey were used. Response rate was 81%. In phase 2, two rounds of observations of drivers were made near the participating schools at the beginning and end of the phase 2 campaign. The results were analyzed using proportion tests.

Results: There was a strong belief (6.49 on a seven-point scale) that texting while driving could result in a crash. About 58% had texted while driving in the previous 7 days in the pre-survey. This proportion decreased significantly to 44% in the follow-up (p < 0.05). Knowledge of Tennessee Graduated Driver Licensing laws and feeling of empowerment to take action with a teen driver who was texting improved significantly (p < 0.05). In phase 2, 12,309 drivers (adults and teens) were observed in the first round, and 13,153 were observed in the second round of observations. Significant reduction in the proportion of drivers texting while driving (from 13% to 9%; p < 0.0001) was observed.

Conclusion: Results of driver observations support the effectiveness of this program in meeting the key objective of reducing texting while driving. The program also influenced teenagers' willingness to take positive steps when faced with a driver who was texting. Future efforts should aim to influence social and peer norms.

Level Of Evidence: Therapeutic study, level III.
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http://dx.doi.org/10.1097/TA.0000000000001521DOI Listing
August 2017

Mutations in BMPR2 are not present in patients with pulmonary hypertension associated with congenital diaphragmatic hernia.

J Pediatr Surg 2017 Nov 26;52(11):1747-1750. Epub 2017 Jan 26.

Department of Pediatrics, Division of Molecular Genetics, Columbia University Medical Center, 1150 St. Nicholas Avenue, Room 620, New York, NY 10032, USA.

Background: Congenital diaphragmatic hernia (CDH) is a prevalent major congenital anomaly with significant morbidity and mortality. Thirty to 40% mortality in CDH is largely attributed to pulmonary hypoplasia and pulmonary hypertension (PH). We hypothesized that the underlying genetic risk factors for hereditary PH are shared with CDH associated PH.

Methods: Participants were recruited as part of the Diaphragmatic Hernia Research & Exploration; Advancing Molecular Science (DHREAMS) study, a prospective cohort of neonates with a diaphragmatic defect enrolled from 2005 to 2012. PH affected patients with available DNA for sequencing had one of the following: moderate or severe PH on echocardiography at 3months of age; moderate of severe PH at 1month of age with death occurring prior to the 3month echocardiogram; or on PH medications at 1month of age. We sequenced the coding regions of the hereditary PH genes bone morphogenetic protein receptor type II (BMPR2), caveolin 1 (CAV1) and potassium channel subfamily K, member 3 (KCNK3) to screen for mutations.

Results: There were 29 CDH patients with PH including 16 males and 13 females. Sequencing of BMPR2, CAV1, and KCNK3 coding regions did not identify any pathogenic variants in these genes.

Type Of Study: Prognosis study LEVEL OF EVIDENCE: Level IV.
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http://dx.doi.org/10.1016/j.jpedsurg.2017.01.007DOI Listing
November 2017

FX11 inhibits aerobic glycolysis and growth of neuroblastoma cells.

Surgery 2017 03 2;161(3):747-752. Epub 2016 Dec 2.

Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN; Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN. Electronic address:

Background: The MYC family of proteins promotes neuroblastoma tumorigenesis at least in part through the induction of aerobic glycolysis by promoting the transcription of key glycolytic enzymes, such as LDHA. FX11 is a selective inhibitor of LDHA that has demonstrated preclinical efficacy in adult cancers. Herein, we hypothesized that FX11 would inhibit aerobic glycolysis and block growth of neuroblastoma cells.

Methods: We surveyed 3 MYCN-single copy and 5 MYCN-amplified neuroblastoma cell lines to correlate C-MYC/N-MYC protein levels with LDHA expression. Cell viability was measured with FX11 using a tetrazolium-based assay. Cell cycle analysis using propidium iodide with flow cytometry was performed to evaluate for growth arrest. Immunoblotting demonstrated PARP and Caspase 3 cleavage as evidence of apoptosis.

Results: LDHA is frequently expressed in both MYCN--amplified and MYCN-single copy cell lines. N-MYC and C-MYC protein levels did not correlate with LDHA protein expression. FX11 inhibits aerobic glycolysis and growth in three MYCN-amplified and one MYCN-single copy neuroblastoma cell lines. FX11 induces modest G1 cell cycle arrest with selective induction of apoptosis.

Conclusion: Small molecule LDHA inhibition is capable of blocking aerobic glycolysis and growth of neuroblastoma cell lines in vitro and merits further in vivo evaluation of its preclinical efficacy in neuroblastomas.
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http://dx.doi.org/10.1016/j.surg.2016.09.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369647PMC
March 2017

Activation of GRP/GRP-R signaling contributes to castration-resistant prostate cancer progression.

Oncotarget 2016 Sep;7(38):61955-61969

Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, USA.

Numerous studies indicate that androgen receptor splice variants (ARVs) play a critical role in the development of castration-resistant prostate cancer (CRPC), including the resistance to the new generation of inhibitors of androgen receptor (AR) action. Previously, we demonstrated that activation of NF-κB signaling increases ARVs expression in prostate cancer (PC) cells, thereby promoting progression to CRPC. However, it is unclear how NF-κB signaling is activated in CRPC. In this study, we report that long-term treatment with anti-androgens increases a neuroendocrine (NE) hormone - gastrin-releasing peptide (GRP) and its receptor (GRP-R) expression in PC cells. In addition, activation of GRP/GRP-R signaling increases ARVs expression through activating NF-κB signaling. This results in an androgen-dependent tumor progressing to a castrate resistant tumor. The knock-down of AR-V7 restores sensitivity to antiandrogens of PC cells over-expressing the GRP/GRP-R signaling pathway. These findings strongly indicate that the axis of Androgen-Deprivation Therapy (ADT) induces GRP/GRP-R activity, activation NF-κB and increased levels of AR-V7 expression resulting in progression to CRPC. Both prostate adenocarcinoma and small cell NE prostate cancer express GRP-R. Since the GRP-R is clinically targetable by analogue-based approach, this provides a novel therapeutic approach to treat advanced CRPC.
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http://dx.doi.org/10.18632/oncotarget.11326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308703PMC
September 2016

Induced differentiation inhibits sphere formation in neuroblastoma.

Biochem Biophys Res Commun 2016 08 11;477(2):255-9. Epub 2016 Jun 11.

Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA. Electronic address:

Neuroblastoma arises from the neural crest, the precursor cells of the sympathoadrenal axis, and differentiation status is a key prognostic factor used for clinical risk group stratification and treatment strategies. Neuroblastoma tumor-initiating cells have been successfully isolated from patient tumor samples and bone marrow using sphere culture, which is well established to promote growth of neural crest stem cells. However, accurate quantification of sphere-forming frequency of commonly used neuroblastoma cell lines has not been reported. Here, we show that MYCN-amplified neuroblastoma cell lines form spheres more frequently than non-MYCN-amplified cell lines. We also show that sphere formation is directly sensitive to cellular differentiation status. 13-cis-retinoic acid is a clinically used differentiating agent that induces a neuronal phenotype in neuroblastoma cells. Induced differentiation nearly completely blocked sphere formation. Furthermore, sphere formation was specifically FGF-responsive and did not respond to increasing doses of EGF. Taken together, these data suggest that sphere formation is an accurate method of quantifying the stemness phenotype in neuroblastoma.
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http://dx.doi.org/10.1016/j.bbrc.2016.06.053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333757PMC
August 2016

Erratum to: Non-fecalith-induced appendicitis: etiology, imaging, and pathology.

Emerg Radiol 2016 Jun;23(3):313-314

Department of Surgery-General Surgery, The University of Texas Medical Branch, Galveston, TX, USA.

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http://dx.doi.org/10.1007/s10140-016-1388-zDOI Listing
June 2016

Understanding the Operative Experience of the Practicing Pediatric Surgeon: Implications for Training and Maintaining Competency.

JAMA Surg 2016 08;151(8):735-41

Department of Surgery, University of Michigan Health System, Ann Arbor.

Importance: The number of practicing pediatric surgeons has increased rapidly in the past 4 decades, without a significant increase in the incidence of rare diseases specific to the field. Maintenance of competency in the index procedures for these rare diseases is essential to the future of the profession.

Objective: To describe the demographic characteristics and operative experiences of practicing pediatric surgeons using Pediatric Surgery Board recertification case log data.

Design, Setting, And Participants: We performed a retrospective review of 5 years of pediatric surgery certification renewal applications submitted to the Pediatric Surgery Board between 2009 and 2013. A surgeon's location was defined by population as urban, large rural, small rural, or isolated. Case log data were examined to determine case volume by category and type of procedures. Surgeons were categorized according to recertification at 10, 20, or 30 years.

Main Outcome And Measure: Number of index cases during the preceding year.

Results: Of 308 recertifying pediatric surgeons, 249 (80.8%) were men, and 143 (46.4%) were 46 to 55 years of age. Most of the pediatric surgeons (304 of 308 [98.7%]) practiced in urban areas (ie, with a population >50 000 people). All recertifying applicants were clinically active. An appendectomy was the most commonly performed procedure (with a mean [SD] number of 49.3 [35.0] procedures per year), nonoperative trauma management came in second (with 20.0 [33.0] procedures per year), and inguinal hernia repair for children younger than 6 months of age came in third (with 14.7 [13.8] procedures per year). In 6 of 10 "rare" pediatric surgery cases, the mean number of procedures was less than 2. Of 308 surgeons, 193 (62.7%) had performed a neuroblastoma resection, 170 (55.2%) a kidney tumor resection, and 123 (39.9%) an operation to treat biliary atresia or choledochal cyst in the preceding year. Laparoscopy was more frequently performed in the 10-year recertification group for Nissen fundoplication, appendectomy, splenectomy, gastrostomy/jejunostomy, orchidopexy, and cholecystectomy (P < .05) but not lung resection (P = .70). It was more frequently used by surgeons recertifying in the 10-year group (used in 11 375 of 14 456 procedures [78.7%]) than by surgeons recertifying in the 20-year (used in 6214 of 8712 procedures [71.3%]) or 30-year group (used in 2022 of 3805 procedures [53.1%]).

Conclusions And Relevance: Practicing pediatric surgeons receive limited exposure to index cases after training. With regard to maintaining competency in an era in which health care outcomes have become increasingly important, these results are concerning.
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http://dx.doi.org/10.1001/jamasurg.2016.0261DOI Listing
August 2016

Laparoscopic Nissen fundoplication in infants with hypoplastic left heart syndrome.

J Pediatr Surg 2016 Jan 23;51(1):76-80. Epub 2015 Oct 23.

Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address:

Background/purpose: Patients with hypoplastic left heart syndrome (HLHS) experience a higher risk for complications from gastroesophageal reflux, prompting frequent need for fundoplication. Patients between stage I and II palliation ("interstage") are at particularly high operative risk because of the parallel nature of their pulmonary and systemic blood flow. Laparoscopic approach for fundoplication is common for pediatric patients. However, its safety in interstage HLHS is relatively unknown. We examined the perioperative physiologic burden of a laparoscopic fundoplication in HLHS patients.

Methods: All patients who underwent open or laparoscopic fundoplication during the interstage period at our institution since 2006 were reviewed. Perioperative physiologic data, echocardiographic findings, survival, and complications were collected from the anesthetic record and patient chart.

Results: Nineteen patients with HLHS had laparoscopic fundoplication, 13 (68%) during the interstage period, compared to 64 performed by the open approach. Ten (77%) of 13 interstage patients had perioperative hemodynamic instability. Incidence of instability between open and laparoscopic groups was not different. One laparoscopic patient required ECMO support for shunt thrombosis.

Conclusions: Despite a high incidence of hemodynamic instability, overall outcomes are consistent with those reported in the literature for this high-risk patient population. Laparoscopic approach for fundoplication during the interstage period appears to be a relatively safe option for these patients.
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http://dx.doi.org/10.1016/j.jpedsurg.2015.10.013DOI Listing
January 2016
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