Lab Affiliations

All Publications

  • Distraction enterogenesis in the murine colon. Journal of pediatric surgery Portelli, K. I., Thomas, A., Wood, L. S., Diyaolu, M., Taylor, J. S., Dunn, J. C. 2021


    BACKGROUND/PURPOSE: Distraction enterogenesis with intraluminal spring technology has been successfully used to lengthen segments of murine small intestine. We hypothesized that biocompatible springs could also be used to lengthen murine large intestine.METHODS: Age and weight matched C57BL/6 mice underwent surgical insertion of nitinol spring-loaded capsules into the cecum. Segment lengths were measured at initial spring placement and at euthanasia after 7 and 14 days. Histologic adaptations were evaluated at scarification.RESULTS: Cecal segments loaded with compressed springs lengthened an average of 150%, which was significantly longer than control segments loaded with either empty capsules or uncompressed springs. Muscularis layers tended to be thicker in the compressed spring groups compared to control groups.CONCLUSIONS: Insertion of a compressed nitinol spring into the cecum results in significant colonic lengthening in a mouse model. The ability to increase cecum length serves as proof of concept that distraction enterogenesis technology may be feasibly applied to large intestinal models. The use of distraction enterogenesis technology shows promise for application to clinical models in the treatment of pediatric intestinal disease.

    View details for DOI 10.1016/j.jpedsurg.2021.10.005

    View details for PubMedID 34740442

  • Small surgeries, big smiles: using virtual reality to reduce the need for sedation or general anesthesia during minor surgical procedures. Pediatric surgery international Taylor, J. S., Chandler, J. M., Menendez, M., Diyaolu, M., Austin, J. R., Gibson, M. L., Portelli, K. I., Caruso, T. J., Rodriguez, S., Chao, S. D. 2021


    PURPOSE: Children often require anesthesia for simple diagnostic and therapeutic procedures. The aim of this study was to evaluate the feasibility of using virtual reality (VR) to reduce sedation in children undergoing minor surgical procedures.METHOD: In this prospective, non-randomized clinical trial, pediatric patients at a free-standing children's hospital undergoing hormone implant placement, removal, or exchange were recruited to use VR and local anesthesia instead of procedural sedation or general anesthesia (GA). Patients were enrolled between November 2017 and March 2020, and were compared to historic controls who underwent similar procedures without VR between April 2016 and February 2020. Primary outcome measure was successful procedure completion without sedation or GA. Secondary measures included assessments of pain, fear and anxiety, patient compliance, procedural and recovery times.RESULTS: Twenty-eight patients underwent 29 procedures with VR. Hormone implants (72%), removals (7%), or exchanges (21%) were completed without GA, sedation or IV placement. Procedure lengths and pain scores were similar between VR patients and historic controls, but recovery times were significantly shorter in VR patients (18 vs 65min, p<0.001). Participant satisfaction scores were high, with 95% recommending VR to others.CONCLUSIONS: VR is a feasible alternative to sedation or GA for select pediatric patients undergoing minor surgical procedures.

    View details for DOI 10.1007/s00383-021-04955-6

    View details for PubMedID 34269867

  • Mechanical lengthening of porcine small intestine with decreased forces. Journal of pediatric surgery Wood, L. S., Hosseini, H. S., Diyaolu, M., Thomas, A., Taylor, J. S., Dunn, J. C. 2021


    INTRODUCTION: short bowel syndrome is marked by inadequate intestinal surface area to absorb nutrients. Current treatments are focused on medical management and surgical reconfiguration of the dilated intestine. We propose the use of spring-mediated distraction enterogenesis as a novel intervention to increase intestinal length. Given our previous success lengthening intestinal segments using springs with spring constant ~7N/m that exerts 0.46N or higher, we sought to determine the minimal force needed to lengthen porcine small intestinal segments, and to explore effects on intestine over time.METHODS: Juvenile Yucatan pigs underwent laparotomy with enterotomy to introduce nitinol springs intraluminally (n=21 springs). Bowel segments (control, spring-distracted) were retrieved on post-operative day (POD) 7 and 14, and lengths measured. Thickness of cross-sectional intestinal layers were measured using H&E, and submucosal collagen fiber orientation measured using trichrome stained sections.RESULTS: all pigs survived to POD7 and 14. Spring constants of at least 2N/m exerting a minimum force of 0.10N significantly lengthened intestinal segments (p<0.0001). The stronger the spring force, the greater the induced thickness of various intestinal layers at POD7 and 14. Collagen fiber orientation was also more disordered because of stronger springs.CONCLUSION: a spring constant of approximately 2N/m exerting 0.10N and greater significantly lengthens intestinal segments and stimulates intestinal structural changes at POD7 and 14. This suggests a decreased force is capable of inducing spring-mediated distraction enterogenesis.

    View details for DOI 10.1016/j.jpedsurg.2021.03.036

    View details for PubMedID 33836847

  • Combining inhibitors of Brd4 and cyclin-dependent kinase can decrease tumor growth in neuroblastoma with MYCN amplification. Journal of pediatric surgery Wood, L., Huang, M., Zeki, J., Gong, M., Taylor, J., Shimada, H., Chiu, B. 2021: 60215


    INTRODUCTION: High-risk neuroblastoma is a deadly disease; poor prognosticators are MYCN-amplification and TERT-overexpression. We hypothesized that Gene Set Enrichment Analysis (GSEA) could identify pathways associated with MYCN-amplification and that inhibition of these pathways could decrease tumor growth.METHODS: We analyzed the Neuroblastoma-Kocak dataset (GSE45547, n=649) and identified pathways associated with MYCN-amplification. Inhibitors were selected from upregulated gene sets for in vitro cytotoxicity testing using ST16-patient-derived primary neuroblastoma cells and in vivo testing using orthotopic ST16-patient-derived xenografts (PDX) in mice. Tumor volume was measured with ultrasound and tumor sections examined after H&E staining.RESULTS: GSEA identified significantly overexpressed gene sets in MYCN-amplified tumors including MYC targets, cell cycle mitotic genes, TERT associated genes, loss of RB1 gene sets, and E2Fs targets. Several genes were potential Bromodomain-containing protein 4 (Brd4) targets, making Brd4 inhibitors - JQ1, AZD5153 - and cyclin-dependent kinase (Brd4's binding partner) inhibitors - dinaciclib - potential therapeutic agents. JQ1 and dinaciclib were synergistic in inducing cytotoxicity in vitro. Dinaciclib-AZD5153 in vivo decreased tumor size compared to control, and increased tumor lymphocyte infiltration and necrosis on histology.CONCLUSIONS: GSEA is a powerful approach to identify upregulated genes and potential therapeutic targets. Dinaciclib-AZD5153 combination therapy can be effective against MYCN-amplified and TERT-overexpressing neuroblastoma tumors.

    View details for DOI 10.1016/j.jpedsurg.2021.03.037

    View details for PubMedID 33838899

  • Laparoscopic versus ultrasound-guided visualization of transversus abdominis plane blocks. Journal of pediatric surgery Diyaolu, M., Taylor, J., Austin, J., Gibson, M., Ramamurthi, R. J., Tsui, B., Chao, S. 2021


    BACKGROUND: Ultrasound-guided (US) transversus abdominis plane (TAP) block is commonly utilized as part of a multi-modal approach for postoperative pain management. This study seeks to determine whether laparoscopic-guided TAP blocks are as effective as US-guided TAP blocks among pediatric patients.METHOD: In this prospective, randomized controlled trial, pediatric patients undergoing laparoscopic procedures were randomly assigned to one of two treatment arms: US-guided TAP block (US-arm) or laparoscopic-guided TAP block (LAP-arm). Primary outcome was PACU pain scores. Secondary outcomes included PACU opioid consumption, block completion time and block accuracy.RESULTS: Twenty-five patients were enrolled in each arm. In the LAP-arm, 59% of blocks were in the transversus abdominis plane compared to 74% of TAP blocks in the US-arm (p=0.18). Blocks were completed faster in the LAP-arm (2.1±1.9vs. 7.9±3.4min, p<0.001). The average highest PACU pain score was 3.4±3.1 for the LAP-arm and 4.3±3.8 for the US-arm (p=0.37). Overall PACU pain scores and opioid consumption were similar between the groups (1.2±1.3vs. 1.6±1.6, p=0.24; 2.2±5.8vs. 0.9±1.4MME, p=0.26).CONCLUSION: Laparoscopic TAP blocks have equivalent efficacy in post-operative pain scores, narcotic use, and tissue plane accuracy as compared to US-guided TAP blocks. They are also completed faster and may result in less operating room and general anesthetic time for the pediatric patient.

    View details for DOI 10.1016/j.jpedsurg.2021.02.025

    View details for PubMedID 33771368

  • Financial burden of pediatric firearm-related injury admissions in the United States. PloS one Taylor, J. S., Madhavan, S., Han, R. W., Chandler, J. M., Tenakoon, L., Chao, S. 2021; 16 (6): e0252821


    Pediatric firearm-related injuries pose a significant public health problem in the United States, yet the associated financial burden has not been well described. This is the first study examining national data on the cost of initial hospitalization for pediatric firearm-related injuries. In this retrospective review, the Healthcare Cost and Utilization Project Kids' Inpatient Database from the years 2003, 2006, 2009, and 2012 was used to identify all patients 18 years of age and under who were admitted with firearm-related injuries. We compared demographic and discharge-level data including injury severity score, hospital length of stay, income quartile, injury intent, and inflation-adjusted hospital costs across age groups (0-5, 6-9, 10-15, 16-18 years). There were approximately 4,753 pediatric firearm-related admissions each year, with a median hospitalization cost of $12,984 per patient. Annual initial hospitalization costs for pediatric firearm injuries were approximately $109 million during the study period. Pediatric firearm-related injuries predominately occured among older teenagers (74%, 16-18 years), males (89%), black individuals (55%), and those from the lowest income quartile (53%). We found significant cost variation based on patient race, income quartile, injury severity score, intent, hospital length of stay, disposition, and hospital region. Inflation-adjusted hospitalization costs have increased significantly over the study period (p < 0.001). Pediatric firearm-related injuries are a large financial burden to the United States healthcare system. There are significant variations in cost based on predictable factors like hospital length of stay and injury severity score; however, there are also substantial discrepancies based on hospital region, patient race, and income quartile that require further investigation.

    View details for DOI 10.1371/journal.pone.0252821

    View details for PubMedID 34161341

  • Gene Expression Signature in Human Neuroblastoma with TERT Overexpression Can Be Identified by Gene Set Enrichment Analysis and Epigenetically Targeted in an Orthotopic Mouse Xenograft Model Huang, M., Wood, L., Zeki, J. C., Diyaolu, M., Gong, M., Taylor, J. S., Shimada, H., Chiu, B. ELSEVIER SCIENCE INC. 2020: S199
  • Intestinal adaptation following spring insertion into a roux limb in mice. Journal of pediatric surgery Portelli, K. I., Park, J., Taylor, J. S., Thomas, A., Stelzner, M., Martin, M. G., Dunn, J. C. 2020


    BACKGROUND/PURPOSE: Intraluminal springs have recently been shown to lengthen segments of intestine in a process known as distraction enterogenesis. We hypothesized that biocompatible springs could be used to lengthen defunctionalized murine small intestine and would lead to identifiable intestinal adaptations at the molecular level.METHODS: Age and weight matched C57BL/6 mice underwent surgical insertion of nitinol spring-loaded capsules into a Roux limb of jejunum. Segment lengths were measured at initial spring placement and at euthanasia after 14 and 21 days. Histology and gene expression of the Roux limb were evaluated at scarification and compared to untreated control segments.RESULTS: Intestinal segments loaded with compressed springs lengthened an average of 240%, which was significantly longer than control segments loaded with either empty capsules or uncompressed springs. Muscularis thickening was greater in spring-treated mice compared to controls without springs. Crypt depth and Lgr5+ expression was greater in mice that received compressed spring treatments when compared to control groups.CONCLUSIONS: Insertion of a compressed nitinol spring into a Roux limb results in significant intestinal lengthening, smooth muscle thickening, and Lgr5+ expression in a mouse model. The ability to increase small bowel length in a defunctionalized murine model may be used to understand the mechanism of distraction enterogenesis.

    View details for DOI 10.1016/j.jpedsurg.2020.06.033

    View details for PubMedID 32709529

  • Treating children with achalasia using per -oral endoscopic myotomy (POEM): Twenty-one cases in review Wood, L. Y., Chandler, J. M., Portelli, K. E., Taylor, J. S., Kethman, W. C., Wall, J. K. W B SAUNDERS CO-ELSEVIER INC. 2020: 1006–12
  • Treating children with achalasia using per-oral endoscopic myotomy (POEM): Twenty-one cases in review. Journal of pediatric surgery Wood, L. S., Chandler, J. M., Portelli, K. E., Taylor, J. S., Kethman, W. C., Wall, J. K. 2020


    BACKGROUND: Per-oral endoscopic myotomy (POEM), a modern treatment for achalasia, has only recently emerged as an option for pediatric patients. Here we describe and characterize the success of POEM in children with achalasia.METHODS: A single-institution prospective cohort study was performed of patients <18 years old who underwent POEM from 2014 to 2019. Main outcomes were success at one year (Eckardt ≤3), procedure duration, complications, reintervention.RESULTS: The median age of patients (n = 21) was 13 years (range 2-17). Median procedure duration was 92 min (range 52-259) with case duration plateau of 87.4 min and learning rate of 15.5 cases. Intraoperative complications included capnoperitoneum requiring needle decompression and mucosotomy requiring additional clips. One patient experienced chest pain with small capnoperitoneum seen on chest radiography, and three patients had extraluminal carbon dioxide found incidentally on routine radiography. All were managed with observation. Pre- versus 1-month postprocedure Eckardt scores were significantly improved (7 ± 2 versus 1 ± 2, p < 0.0001, and median ± SD) with 100% symptomatic relief at one year. To achieve this, 13 patients required further dilation(s), one required laparoscopic Heller myotomy, and two required repeat POEM.CONCLUSIONS: POEM is a viable and safe treatment for pediatric patients with achalasia. We demonstrate improvement in symptoms and procedure proficiency with minimal intra- and postoperative complications.TYPE OF STUDY: Prospective cohort study.LEVEL OF EVIDENCE: Level II.

    View details for DOI 10.1016/j.jpedsurg.2020.02.028

    View details for PubMedID 32197825

  • Enhancing sustained-release local therapy: Single versus dual chemotherapy for the treatment of neuroblastoma. Surgery Taylor, J. S., Yavuz, B., Zeki, J., Wood, L., Ikegaki, N., Coburn, J., Harrington, K., Shimada, H., Kaplan, D. L., Chiu, B. 2020


    BACKGROUND: Neuroblastoma is the most common pediatric extracranial solid malignancy with limited effective treatment. We have shown that sustained-release, single drugs delivered locally through a silk-based biomaterial are effective in decreasing orthotopic neuroblastoma xenograft growth. We further optimized this approach and hypothesized that increasing doses of local chemotherapy or delivering 2 chemotherapeutic agents simultaneously inhibit additional tumor growth.METHODS: MYCN-amplified and non-MYCN-amplified neuroblastoma cells were treated with combinations of cisplatin, vincristine, doxorubicin, and etoposide to determine cytotoxicity and synergy. Drug-loaded silk material was created, and the amounts of drug released from the material over time were recorded. Murine orthotopic neuroblastoma xenografts were generated; tumors were implanted with single- or dual-agent chemotherapy-loaded silk. Ultrasound was used to monitor tumor growth, and tumor histology was evaluated.RESULTS: Invitro, vincristine/cisplatin combination was synergistic and significantly decreased cell viability relative to other combinations. Both drugs loaded into silk could be released effectively for over 2 weeks. Locally implanted vincristine/cisplatin silk induced increased tumor growth suppression compared with either agent alone in MYCN-amplified tumors (P < .05). The dose-dependent effect seen in MYCN-amplified tumors treated with combination therapy diminished at higher doses in non-MYCN-amplified tumors, with little benefit with doses >50 mug to 500 mug for vincristine-cisplatin, respectively. Tumor histology demonstrated tumor cell necrosis adjacent to drug-loaded silk material and presence of large cell neuroblastoma.CONCLUSION: Local delivery of sustained release chemotherapy can suppress tumor growth especially at high doses or with 2 synergistic drugs. Locally delivered dual therapy is a promising approach for future clinical testing.

    View details for DOI 10.1016/j.surg.2020.01.012

    View details for PubMedID 32122657

  • Local delivery of dinutuximab from lyophilized silk fibroin foams for treatment of an orthotopic neuroblastoma model. Cancer medicine Ornell, K. J., Taylor, J. S., Zeki, J., Ikegaki, N., Shimada, H., Coburn, J. M., Chiu, B. 2020


    Immunotherapy targeting GD2 is a primary treatment for patients with high-risk neuroblastoma. Dinutuximab is a monoclonal antibody with great clinical promise but is limited by side effects such as severe pain. Local delivery has emerged as a potential mechanism to deliver higher doses of therapeutics into the tumor bed, while limiting systemic toxicity. We aim to deliver dinutuximab locally in a lyophilized silk fibroin foam for the treatment of an orthotopic neuroblastoma mouse model. Dinutuximab-loaded silk fibroin foams were fabricated through lyophilization. In vitro release profile and bioactivity of the release through complement-dependent cytotoxicity were characterized. MYCN-amplified neuroblastoma cells (KELLY) were injected into the left gland of mice to generate an orthotopic neuroblastoma model. Once the tumor volume reached 100mm3 , dinutuximab-, human IgG-, or buffer-loaded foams were implanted into the tumor and growth was monitored using high-resolution ultrasound. Post-resection histology was performed on tumors. Dinutuximab-loaded silk fibroin foams exhibited a burst release, with slow release thereafter in vitro with maintenance of bioactivity. The dinutuximab-loaded foam significantly inhibited xenograft tumor growth compared to IgG- and buffer-loaded foams. Histological analysis revealed the presence of dinutuximab within the tumor and neutrophils and macrophages infiltrating into dinutuximab-loaded silk foam. Tumors treated with local dinutuximab had decreased MYCN expression on histology compared to control or IgG-treated tumors. Silk fibroin foams offer a mechanism for local release of dinutuximab within the neuroblastoma tumor. This local delivery achieved a significant decrease in tumor growth rate in a mouse orthotopic tumor model.

    View details for DOI 10.1002/cam4.2936

    View details for PubMedID 32096344

  • EPIGENETIC TARGETING OF TERT-ASSOCIATED GENE EXPRESSION SIGNATURE IN HUMAN NEUROBLASTOMA WITH TERT OVEREXPRESSION. Cancer research Huang, M. n., Zeki, J. n., Sumarsono, N. n., Coles, G. L., Taylor, J. S., Danzer, E. n., Bruzoni, M. n., Hazard, F. K., Lacayo, N. J., Sakamoto, K. M., Dunn, J. C., Spunt, S. L., Chiu, B. n. 2020


    Neuroblastoma is a deadly pediatric solid tumor with infrequent recurrent somatic mutations. Particularly, the pathophysiology of tumors without MYCN amplification remains poorly defined. Utilizing an unbiased approach, we performed gene set enrichment analysis of RNA-seq data from 498 neuroblastoma patients and revealed a differentially overexpressed gene signature in MYCN non-amplified neuroblastomas with telomerase reverse transcriptase (TERT) gene overexpression and coordinated activation of oncogenic signaling pathways, including E2Fs, Wnt, Myc, and the DNA repair pathway. Promoter rearrangement of the TERT gene juxtaposes the coding sequence to strong enhancer elements, leading to TERT overexpression and poor prognosis in neuroblastoma, but TERT-associated oncogenic signaling remains unclear. ChIP-seq analysis of the human CLB-GA neuroblastoma cells harboring TERT rearrangement uncovered genome-wide chromatin co-occupancy of Brd4 and H3K27Ac and robust enrichment of H3K36me3 in TERT and multiple TERT-associated genes. Brd4 and cyclin-dependent kinases (CDKs) had critical regulatory roles in the expression and chromatin activation of TERT and multiple TERT-associated genes. Epigenetically targeting Brd4 or CDKs with their respective inhibitors suppressed the expression of TERT and multiple TERT-associated genes in neuroblastoma with TERT overexpression or MYCN amplification. ChIP-seq and ChIP-qPCR provided evidence that the CDK inhibitor directly inhibited Brd4 recruitment to activate chromatin globally. Therefore, inhibiting Brd4 and CDK concurrently with AZD5153 and dinaciclib would be most effective in tumor growth suppression, which we demonstrated in neuroblastoma cell lines, primary human cells, and xenografts. In summary, we describe a unique mechanism in neuroblastoma with TERT overexpression and an epigenetically targeted novel therapeutic strategy.

    View details for DOI 10.1158/0008-5472.CAN-19-2560

    View details for PubMedID 31900258

  • Human skin-derived precursor cells xenografted in aganglionic bowel. Journal of pediatric surgery Thomas, A. L., Taylor, J. S., Dunn, J. C. 2020


    One in 5000 newborns is diagnosed with Hirschsprung disease each year in the United States. The potential of employing neural crest stem cells to restore the enteric nervous system has been investigated. Skin-derived precursor cells (SKPs) are multipotent progenitor cells that can differentiate into neurons and gliocytes in vitro and generate enteric ganglion-like structures in rodents. Here we examined the behavior of human SKPs (hSKPs) after their transplantation into a large animal model of colonic aganglionosis.Juvenile minipigs underwent a chemical denervation of the colon to establish an aganglionosis model. The hSKPs were generated from human foreskin and were cultured in neuroglial-selective medium. Cells were labeled with a fluorescent dye and were injected into the porcine aganglionic colon. After one week, transplanted hSKPs were assessed by immunofluorescence for markers of multipotency and neuroglial differentiation.In culture, hSKPs expressed nestin and S100b indicative of neuroglial precursors. After xenografting in pigs, hSKPs were identified in the myenteric and submucosal plexuses of the colons. The hSKPs expressed nestin and early neuroglial differentiation markers.Human SKPs transplanted into aganglionic colon demonstrated immunophenotypes of neuroglial progenitors, suggesting their potential use for Hirschsprung disease.

    View details for DOI 10.1016/j.jpedsurg.2020.03.006

    View details for PubMedID 32253016

  • Mesenteric neovascularization during spring-mediated intestinal lengthening. Journal of pediatric surgery Diyaolu, M. n., Thomas, A. L., Wood, L. S., Taylor, J. n., Dunn, J. C. 2020


    Short gut syndrome, a condition characterized by inadequate absorption of nutrients owing to decreased bowel length, has minimal avenues for treatment. We have proposed spring-mediated distraction enterogenesis to lengthen bowel in porcine jejunum as a treatment for short gut. We aim to evaluate the extent of mesenteric neovascularization in segments of lengthened bowel via spring-mediated enterogenesis.Female juvenile Yucatan pigs underwent laparotomy and insertion of gelatin-encapsulated compressed nitinol springs, held in place with plication sutures, into the jejunum. At surgery and sacrifice, macroscopic mesenteric blood vessels were counted between the plication sites. Histologic samples of the mesentery were obtained to evaluate microscopic vasculature.A statistically significant increase in macroscopic mesenteric blood vessels was seen after intestinal lengthening (before: 1.9 ± 0.7 vessels, after: 4.7 ± 1.2 vessels, p = 0.001). A statistical significance is also seen in the density of arterioles (control: 3.0 ± 3.0 vessels/mm, spring: 7.0 ± 9.0 vessels/mm, p = 0.01) and venules (control: 4.0 ± 3.0 vessels/mm, spring: 8.0 ± 8.0 vessels/mm, p = 0.003).Intestinal segments lengthened by intraluminal springs demonstrated total greater number of macroscopic vessels and microscopic blood vessels per length of mesentery as compared to control. This suggests local changes within the mesentery to recruit blood supply to growing intestine.N/A TYPE OF STUDY: Treatment study.

    View details for DOI 10.1016/j.jpedsurg.2020.09.042

    View details for PubMedID 33143878

  • Cutaneous Patches to Monitor Myoelectric Activity of the Gastrointestinal Tract in Postoperative Pediatric Patients PEDIATRIC GASTROENTEROLOGY HEPATOLOGY & NUTRITION Taylor, J. S., de Ruijter, V., Brewster, R., Navalgund, A., Axelrod, L., Axelrod, S., Dunn, J. Y., Wall, J. K. 2019; 22 (6): 518–26
  • Optimization of In-Continuity Spring-Mediated Intestinal Lengthening. Journal of pediatric surgery Dubrovsky, G., Taylor, J. S., Thomas, A., Shekherdimian, S., Dunn, J. C. 2019


    BACKGROUND: Spring-mediated intestinal lengthening has been studied in numerous animal models to effectively achieve up to a 3-fold increase in length. In this study we are interested in optimizing this method of spring lengthening.METHODS: Juvenile mini-Yucatan pigs underwent laparotomy for spring implantation. Springs were secured by plicating the intestine around the springs. In one set of experiments, varying degrees of plication were compared to determine the necessary narrowing needed to confine the spring. In another set of experiments, dissolvable sutures were used for the plication to allow for spontaneous spring passage postoperatively. Intestinal segments were retrieved and evaluated for lengthening and histological changes.RESULTS: Pigs tolerated their diet advancement to a regular diet postoperatively. 10% plication resulted in a 1.3-fold increase in length, while 50% plication resulted in a 2.7-fold increase in length (p<0.05). At two months postoperatively, the majority of springs had safely passed out of the intestine. All lengthened intestine showed significant growth histologically.CONCLUSIONS: A 50% reduction in lumen diameter achieves optimal spring-mediated intestinal lengthening. Springs can safely pass out of the intestine, thus avoiding a second operation for spring removal. These results may be important in developing future therapies for short bowel syndrome.LEVEL OF EVIDENCE: Level I experimental study.

    View details for DOI 10.1016/j.jpedsurg.2019.09.072

    View details for PubMedID 31676077

  • Autologous Transplantation of Skin-Derived Precursor Cells in a Porcine Model. Journal of pediatric surgery Thomas, A., Taylor, J. S., Huynh, N., Dubrovsky, G., Chadarevian, J., Chen, A., Baker, S., Dunn, J. C. 2019


    BACKGROUND: Hirschprung's disease is characterized by aganglionic bowel and often requires surgical resection. Cell-based therapies have been investigated as potential alternatives to restore functioning neurons. Skin-derived precursor cells (SKPs) differentiate into neural and glial cells in vitro and generate ganglion-like structures in rodents. In this report, we aimed to translate this approach into a large animal model of aganglionosis using autologous transplantation of SKPs.METHODS: Juvenile pigs underwent skin procurement from the shoulder and simultaneous chemical denervation of an isolated colonic segment. Skin cells were cultured in neuroglial-selective medium and labeled with fluorescent dye for later identification. The cultured SKPs were then injected into the aganglionic segments of colon, and the specimens were retrieved within seven days after transplantation. SKPs in vitro and in vivo were assessed with histologic samples for various immunofluorescent markers of multipotency and differentiation. SKPs from the time of harvest were compared to those at the time of injection using PCR.RESULTS: Prior to transplantation, 72% of SKPs stained positive for nestin and S100b, markers of neural and glial precursor cells of neural crest origin, respectively. Markers of differentiated neurons and gliocytes, TUJ1 and GFAP, were detected in 47% of cultured SKPs. After transplantation, SKPs were identified in both myenteric and submucosal plexuses of the treated colon. Nestin co-expression was detected in the SKPs within the aganglionic colon in vivo. Injected SKPs appeared to migrate and express early neuroglial differentiation markers.CONCLUSIONS: Autologous SKPs implanted into aganglionic bowel demonstrated immunophenotypes of neuroglial progenitors. Our results suggest that autologous SKPs may be potentially useful for cell-based therapy for patients with enteric nervous system disorders.TYPE OF STUDY: Basic science.

    View details for DOI 10.1016/j.jpedsurg.2019.09.075

    View details for PubMedID 31704043

  • Seven-Year Experience with Laparoscopic Pedicled Omental Flap for Cerebral Revascularization in Patients with Moyamoya Disease Wood, L. Y., Jones, R. E., Chandler, J. M., Taylor, J., Dutta, S., Steinberg, G., Bruzoni, M. ELSEVIER SCIENCE INC. 2019: E126–E127
  • Optimizing Sustained Release Local Therapy: Single vs Dual Chemotherapy for the Treatment of Neuroblastoma Taylor, J. S., Yavuz, B., Zeki, J., Ikegaki, N., Coburn, J. M., Harrington, K., Shimada, H., Kaplan, D. L., Chiu, B. ELSEVIER SCIENCE INC. 2019: S210–S211
  • 10-Year Experience of Kasai Hepatoportoenterostomy in Biliary Atresia: High-Dose Adjuvant Steroids Improve Outcomes Taylor, J., Abadilla, N., Narayan, R., Pickering, J. M., Bruzoni, M. ELSEVIER SCIENCE INC. 2019: E164
  • Growth of Small Intestinal Layers Proximal and Distal to the Intestine Undergoing Distraction Enterogenesis Wood, L. Y., Taylor, J. S., Hosseini, H. S., Dubrovsky, G., Thomas, A., Dunn, J. Y. ELSEVIER SCIENCE INC. 2019: S204
  • Biomechanical signaling and collagen fiber reorientation during distraction enterogenesis. Journal of the mechanical behavior of biomedical materials Hosseini, H. S., Wood, L. S., Taylor, J. S., Dubrovsky, G., Portelli, K. I., Thomas, A., Dunn, J. C. 2019; 101: 103425


    Distraction enterogenesis has been extensively studied as a potential treatment for short bowel syndrome, which is the most common subset of intestinal failure. Spring distraction uses an intraluminal axial mechanical force to stimulate the growth and elongation of the small intestine. The tissue close to the distracted intestinal segment may also experience signaling to grow. In this study we examined the effects of distraction enterogenesis at different post-operative days on the thickness of small intestinal layers in the intestine proximal and distal to the distracted segment, as well as how the submucosal collagen fibers were reoriented. It was observed that not only different layers of intestine wall in distracted segment showed thickening due to the applied mechanical force but also adjacent tissues in both distal and proximal directions were impacted significantly where they showed thickening as well. The orientation of collagen fibers in submucosa layer was also significantly impacted due to the mechanical force in both distracted and adjacent tissue. The effect of the applied mechanical force on the main distracted tissue and the radial growth of the adjacent tissue strongly suggest actions of paracrine signaling.

    View details for DOI 10.1016/j.jmbbm.2019.103425

    View details for PubMedID 31541857

  • Biomechanics of small intestine during distraction enterogenesis with an intraluminal spring. Journal of the mechanical behavior of biomedical materials Hosseini, H. S., Taylor, J. S., Wood, L. S., Dunn, J. C. 2019; 101: 103413


    During recent years, distraction enterogenesis has been extensively studied as a treatment for short bowel syndrome, which is the most common cause of intestinal failure. Although different strategies such as parenteral nutrition and surgical lengthening have been used to manage the difficulties that patients with SBS deal with, these treatments are associated with high complication rates. Distraction enterogenesis uses mechanical force to increase the length and stimulate growth of the small intestine. In this study we combine in vivo experiments with computational modeling to explore the biomechanics of spring dependent distraction enterogenesis. We hypothesize that the self-expanding spring provides mechanical force for elastic tissue lengthening and triggers cellular proliferation. The additional growth of the intestine suggests signaling between mechanical stress and tissue response. We developed a computational modeling platform to test the correlation of applied mechanical force and tissue growth. We further validated our computational models with experimental measurements using spring-mediated distraction enterogenesis in a porcine model. This modeling platform can incorporate patient biometrics to estimate an individual's tissue response to spring mediated distraction enterogenesis.

    View details for DOI 10.1016/j.jmbbm.2019.103413

    View details for PubMedID 31518947

  • Replicating and identifying large cell neuroblastoma using high-dose intra-tumoral chemotherapy and automated digital analysis. Journal of pediatric surgery Taylor, J. S., Sha, L., Ikegaki, N., Zeki, J., Deaton, R., Harris, J., Coburn, J., Yavuz, B., Sethi, A., Shimada, H., Kaplan, D. L., Gann, P., Chiu, B. 2019


    PURPOSE: Large cell neuroblastomas (LCN) are frequently seen in recurrent, high-risk neuroblastoma but are rare in primary tumors. LCN, characterized by large nuclei with prominent nucleoli, predict a poor prognosis. We hypothesize that LCN can be created with high-dose intra-tumoral chemotherapy and identified by a digital analysis system.METHODS: Orthotopic mouse xenografts were created using human neuroblastoma and treated with high-dose chemotherapy delivered locally via sustained-release silk platforms, inducing tumor remission. After recurrence, LCN populations were identified on H&E sections manually. Clusters of typical LCN and non-LCN cells were divided equally into training and test sets for digital analysis. Marker-controlled watershed segmentation was used to identify nuclei and characterize their features. Logistic regression was developed to distinguish LCN from non-LCN.RESULTS: Image analysis identified 15,000 nuclei and characterized 70 nuclear features. A 19-feature model provided AUC >0.90 and 100% accuracy when >30% nuclei/cluster were predicted as LCN. Overall accuracy was 87%.CONCLUSIONS: We recreated LCN using high-dose chemotherapy and developed an automated method for defining LCN histologically. Features in the model provide insight into LCN nuclear phenotypic changes that may be related to increased activity. This model could be adapted to identify LCN in human tumors and correlated with clinical outcomes.

    View details for DOI 10.1016/j.jpedsurg.2019.08.022

    View details for PubMedID 31519361

  • Firearm Legislation Stringency and Firearm-Related Fatalities among Children in the US JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Madhavan, S., Taylor, J. S., Chandler, J. M., Staudenmayer, K. L., Chao, S. D. 2019; 229 (2): 150–57
  • Silk Reservoirs for Local Delivery of Cisplatin for Neuroblastoma Treatment: In Vitro and In Vivo Evaluations JOURNAL OF PHARMACEUTICAL SCIENCES Yavuz, B., Zeki, J., Taylor, J., Harrington, K., Coburn, J. M., Ikegaki, N., Kaplan, D. L., Chiu, B. 2019; 108 (8): 2748–55
  • Down-regulation of MYCN protein by CX-5461 leads to neuroblastoma tumor growth suppression Taylor, J. S., Zeki, J., Ornell, K., Coburn, J., Shimada, H., Ikegaki, N., Chiu, B. W B SAUNDERS CO-ELSEVIER INC. 2019: 1192–97
  • Cutaneous Patches to Monitor Myoelectric Activity of the Gastrointestinal Tract in Postoperative Pediatric Patients. Pediatric gastroenterology, hepatology & nutrition Taylor, J. S., de Ruijter, V. n., Brewster, R. n., Navalgund, A. n., Axelrod, L. n., Axelrod, S. n., Dunn, J. C., Wall, J. K. 2019; 22 (6): 518–26


    Limited means exist to assess gastrointestinal activity in pediatric patients postoperatively. Recently, myoelectric gastrointestinal activity recorded by cutaneous patches has been shown in adult patients to be predictive of clinical return of gastrointestinal function postoperatively. The aim of this case series is to demonstrate the feasibility of this system in pediatric patients and to correlate myoelectric signals with return of bowel function clinically.Pediatric patients undergoing abdominal surgery were recruited to have wireless patches placed on the abdomen within two hours postoperatively. Myoelectric data were transmitted wirelessly to a mobile device with a user-interface and forwarded to a cloud server where processing algorithms identified episodes of motor activity, quantified their parameters and nominally assigned them to specific gastrointestinal organs based on their frequencies.Three patients (ages 5 months, 4 year, 16 year) were recruited for this study. Multiple patches were placed on the older subjects, while the youngest had a single patch due to space limitations. Rhythmic signals of the stomach, small intestine, and colon could be identified in all three subjects. Patients showed gradual increase in myoelectric intestinal and colonic activity leading up to the first recorded bowel movement.Measuring myoelectric intestinal activity continuously using a wireless patch system is feasible in a wide age range of pediatric patients. The increase in activity over time correlated well with the patients' return of bowel function. More studies are planned to determine if this technology can predict return of bowel function or differentiate between physiologic ileus and pathologic conditions.

    View details for DOI 10.5223/pghn.2019.22.6.518

    View details for PubMedID 31777717

    View details for PubMedCentralID PMC6856497

  • 3D Optical Imaging for Pectus Excavatum Assessment. The Annals of thoracic surgery Taylor, J. S., Madhavan, S. n., Szafer, D. n., Pei, A. n., Koppolu, R. n., Barnaby, K. n., Wall, J. K., Chao, S. D. 2019


    Corrective surgery for pectus excavatum often relies on the Haller index (HI), derived from chest radiographs or computed tomography; however, this exposes children to potentially unnecessary radiation. Our aim was to develop a novel 3D optical imaging technique to accurately measure chest wall dimensions in a clinically relevant manner.Patients with pectus excavatum were imaged using a 3D structured light scanner. Patient characteristics, including height, weight, BMI, and radiographic HIs (rHI) were recorded. We defined the optical index (OI) as the ratio of the lateral to anterior-posterior measurements obtained from the 3D optical images, and compared those to patients' rHIs. Two-thirds of the patients' images were used to develop a predictive model of the rHI, utilizing their OI and biometric data in multilinear regression modeling. The predictive model was applied to the remaining images, and the predicted HIs (pHI) were compared to the rHIs.Forty-two patients (ages 5-35) with pectus excavatum underwent optical imaging; 31 had recent chest radiographs, with rHIs ranging from 2.00-7.20. The OIs derived from the images correlated closely with rHIs (R=0.850). Our predictive model, utilizing patients' OI, height, and weight was able to accurately estimate their rHIs with a median error of 8.11% (IQR 3.5-17.4%).3D optical imaging of patients with pectus excavatum is emerging as an alternative method to assess HIs without the use of ionizing radiation. Additional studies will focus on volumetric quantification of chest wall deformities, utilizing the 3D capabilities of this technology.

    View details for DOI 10.1016/j.athoracsur.2019.04.074

    View details for PubMedID 31201783

  • Algorithm for Calculating Haller Index for Pectus Excavatum Using 3-Dimensional Optical Scanning Taylor, J. S., Szafer, D., Madhavan, S., Hasseini, S., Pei, A., Koppolu, R., Barnaby, K. D., Danzer, E., Wall, J. K., Chao, S. ELSEVIER SCIENCE INC. 2018: S192
  • Impact of societal factors and health care delivery systems on gastroschisis outcomes. Seminars in pediatric surgery Taylor, J. S., Shew, S. B. 2018; 27 (5): 316–20


    Care of infants with gastroschisis is associated with a significant burden on health care delivery systems. Mortality rates in patients with gastroschisis have significantly improved over the past few decades. However, the condition is still associated with significant short-term and potentially long-term morbidity. Significant variations in clinical outcomes and resource utilization may be explained by several factors including provider and hospital experience, level of neonatal intensive care, variations in hospital regionalization of care, and differences in healthcare delivery systems. Reviewing and assessing these hospital and healthcare system related factors are paramount in addressing variations in gastroschisis care and improving outcomes for these vulnerable infants.

    View details for PubMedID 30413263

  • A Simplified Method for Three-Dimensional Optical Imaging and Measurement of Patients with Chest Wall Deformities Szafer, D., Taylor, J. S., Pei, A., de Ruijter, V., Hosseini, H., Chao, S., Wall, J. MARY ANN LIEBERT, INC. 2019: 267–71
  • Combined application of Indocyanine green (ICG) and laser lead to targeted tumor cell destruction. Journal of pediatric surgery Taylor, J. S., Zeki, J., Ikegaki, N., Chen, L. L., Chiu, B. 2018


    PURPOSE: Precise excision of neuroblastoma is challenging, especially when tumors adhere to vital structures. Indocyanine green (ICG), an FDA-approved dye with absorption peaking at 800 nm, can absorb the near IR laser energy and release heat in the dyed tissue. We hypothesize that by injecting ICG at tumor sites followed by precise laser application, tumor cell death can be selectively targeted.METHODS: Orthotopic neuroblastoma tumors were created in the adrenal gland of immunocompromised mice. Tumor, liver, kidney, and muscle tissues were chosen for ICG injection. Intervention variables included presence of tumor capsule, continuous vs. pulsed laser treatment and total energy delivered. Control groups included laser or ICG only. Tissues were stained with hematoxylin/eosin.RESULTS: Continuous wave laser generated excessive heat, causing damage in all tissues. When using pulsed laser treatment, liver, kidney, muscle, and intact tumor tissues showed no cell death when treated with laser alone or laser plus ICG. Tumor tissue with the capsule removed, however, showed cell death on histology.CONCLUSIONS: Pulsed laser treatment combined with ICG causes targeted tumor cell death in neuroblastoma tumor without capsule. No cell death was observed when tumor capsule was present, when only laser was used, or when applied over non-tumor tissues.

    View details for PubMedID 30244940

  • Disseminated injection of vincristine-loaded silk gel improves the suppression of neuroblastoma tumor growth. Surgery Zeki, J., Taylor, J. S., Yavuz, B., Coburn, J., Ikegaki, N., Kaplan, D. L., Chiu, B. 2018


    BACKGROUND: Advanced-stage neuroblastoma patients require multiagent chemotherapy. Intratumoral implantation of vincristine-loaded silk gel uses local diffusion to decrease orthotopic neuroblastoma tumor growth in mice. We hypothesize that injecting vincristine-loaded silk gel into 8 locations within the tumor, instead of only centrally, decreases the diffusion distance and improves tumor growth suppression.METHODS: Human neuroblastoma cells, KELLY, were injected into mouse adrenal glands to create orthotopic tumors. After the tumors reached 100mm3 by ultrasound, silk gels loaded with 50 g vincristine were injected centrally or in 8 areas throughout the tumor. Drug-release profile was measured in vitro. Endpoints were tumor size >1,000 mm3 and histologic examination.RESULTS: Vincristine-loaded silk gels suppressed tumor growth up to an inflection point (458.7 ± 234.4mm3 for central, 514.3 ± 165.8 mm3 for 8-point injection) before tumor growth accelerated >200mm3 over 3 days. The time to inflection point was 6.6 days for central, 13.3 days for 8-point injection (P < .05). Using the sphere volume equation to approximate tumor volume, splitting the volume into 1/8 decreased the diffusion radius by 1/2. Histologic examination confirmed tumor necrosis adjacent to vincristine-loaded silk gel.CONCLUSION: Injecting vincristine-loaded sustained release silk gel at 8 separate locations halved the diffusion distance and doubled the time for the tumor to reach the growth inflexion point.

    View details for PubMedID 30061039

  • Dilation of Esophageal Stricture in a Pediatric Patient Using Functional Lumen Imaging Probe Technology Without the Use of Fluoroscopy. Journal of pediatric gastroenterology and nutrition Taylor, J. S., Danzer, E. n., Berquist, W. E., Wall, J. K. 2018

    View details for DOI 10.1097/MPG.0000000000001936

    View details for PubMedID 29470294

  • Endoscopic Excision of Benign Facial Masses in Children: A Review of Outcomes. Journal of laparoendoscopic & advanced surgical techniques. Part A Foster, D. n., Sinclair, T. J., Taylor, J. S., Dutta, S. n., Lorenz, H. P., Bruzoni, M. n. 2018


    Benign masses of the eyebrow and forehead are common in pediatric patients and can result in facial asymmetry, discomfort, or super-infection. Excision is classically conducted via an incision directly over the mass, which can produce sub-optimal cosmesis. Recently, an endoscopic approach using pediatric brow-lift equipment has been adopted. We reviewed our center's experience with endoscopic removal of benign facial lesions and compared these cases with an equivalent series of open cases.A retrospective chart review was conducted to identify pediatric cases of endoscopic and open removal of benign eyebrow or forehead lesions at our institution from 2009 to 2016. Clinical and cosmetic outcomes were reviewed.A total of 40 endoscopic and 25 open cases of excision of benign facial lesions in children were identified. For the patients who underwent endoscopic excision, the majority (85%) presented with a cyst located at the eyebrow. Histologic examination revealed 36 dermoid cysts (90%), 2 epidermal cysts, and 2 pilomatrixomas. Of the 36 cases with post-operative follow-up, 32 patients (89%) had an uncomplicated recovery with good cosmesis. Two patients had an eyebrow droop that resolved without intervention. One patient had localized numbness overlying the site, but no motor deficits. One patient presented with a recurrent dermoid cyst that required open resection. For the patients who underwent open excision, the majority (52%) had dermoid cysts located at the eyebrow. Of the 22 cases with follow-up, 20 of the patients had an uncomplicated recovery (90%). Comparing the rate of complications, there was no statistically significant difference between the two groups (P = 1.0).Endoscopic excision of benign forehead and eyebrow lesions in pediatric patients is feasible and yields excellent cosmetic results. When compared with open excision, complication rates are similar between both approaches and a facial scar can be avoided with an endoscopic approach.

    View details for PubMedID 29446701