Publications by authors named "Eugene S Kim"

67 Publications

Appendectomy Versus Observation for Appendicitis in Neutropenic Children With Cancer.

Pediatrics 2021 Feb;147(2)

Division of Pediatric Surgery, Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, Wisconsin;

Background: Optimal management of neutropenic appendicitis (NA) in children undergoing cancer therapy remains undefined. Management strategies include upfront appendectomy or initial nonoperative management. We aimed to characterize the effect of management strategy on complications and length of stay (LOS) and describe implications for chemotherapy delay or alteration.

Methods: Sites from the Pediatric Surgery Oncology Research Collaborative performed a retrospective review of children with NA over a 6-year period.

Results: Sixty-six children, with a median age of 11 years (range 1-17), were identified with NA while undergoing cancer treatment. The most common cancer diagnoses were leukemia (62%) and brain tumor (12%). Upfront appendectomy was performed in 41% of patients; the remainder had initial nonoperative management. Rates of abscess or perforation at diagnosis were equivalent in the groups (30% vs 24%; = .23). Of patients who had initial nonoperative management, 46% (17 of 37) underwent delayed appendectomy during the same hospitalization. Delayed appendectomy was due to failure of initial nonoperative management in 65% ( = 11) and count recovery in 35% ( = 6). Cancer therapy was delayed in 35% ( = 23). Initial nonoperative management was associated with a delay in cancer treatment (46% vs. 22%, = .05) and longer LOS (29 vs 12 days; = .01). Patients who had initial nonoperative management and delayed appendectomy had a higher rate of postoperative complications ( < .01).

Conclusions: In pediatric patients with NA from oncologic treatment, upfront appendectomy resulted in lower complication rates, reduced LOS, and fewer alterations in chemotherapy regimens compared to initial nonoperative management.
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http://dx.doi.org/10.1542/peds.2020-027797DOI Listing
February 2021

Initiation of immunotherapy with activated natural killer cells and anti-GD2 antibody dinutuximab prior to resection of primary neuroblastoma prolongs survival in mice.

J Immunother Cancer 2020 12;8(2)

Division of Pediatric Surgery, Department of Surgery, Children's Hospital Los Angeles, Los Angeles, California, USA

Background: Immunotherapy with anti-disialoganglioside dinutuximab has improved survival for children with high-risk neuroblastoma (NB) when given after induction chemotherapy and surgery. However, disease recurrence and resistance persist. Dinutuximab efficacy has not been evaluated when initiated before primary tumor removal. Using a surgical mouse model of human NB, we examined if initiating dinutuximab plus ex vivo-activated natural killer (aNK) cells before resection of the primary tumor improves survival.

Methods: In vitro, human NB cells (SMS-KCNR-Fluc, CHLA-255-Fluc) were treated with dinutuximab and/or aNK cells and cytotoxicity was measured. In vivo, NB cells (SMS-KCNR-Fluc, CHLA-255-Fluc, or COG-N-415x PDX) were injected into the kidney of NOD-scid gamma mice. Mice received eight intravenous infusions of aNK cells plus dinutuximab beginning either 12 days before or 2 days after resection of primary tumors. Tumors in control mice were treated by resection alone or with immunotherapy alone. Disease was quantified by bioluminescent imaging and survival was monitored. aNK cell infiltration into primary tumors was quantified by flow cytometry and immunohistochemistry at varying timepoints.

Results: In vitro, aNK cells and dinutuximab were more cytotoxic than either treatment alone. In vivo, treatment with aNK cells plus dinutuximab prior to resection of the primary tumor was most effective in limiting metastatic disease and prolonging survival. aNK cell infiltration into xenograft tumors was observed after 1 day and peaked at 5 days following injection.

Conclusion: Dinutuximab plus aNK cell immunotherapy initiated before resection of primary tumors decreases disease burden and prolongs survival in an experimental mouse model of NB. These findings support the clinical investigation of this treatment strategy during induction therapy in patients with high-risk NB.
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http://dx.doi.org/10.1136/jitc-2020-001560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751216PMC
December 2020

Implications of Tumor Characteristics and Treatment Modality on Local Recurrence and Functional Outcomes in Children with Chest Wall Sarcoma: A Pediatric Surgical Oncology Research Collaborative Study.

Ann Surg 2020 Nov 4. Epub 2020 Nov 4.

Division of Pediatric Surgery, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.

Objective: To determine the impact of tumor characteristics and treatment approach on (1) local recurrence, (2) scoliosis development and (3) patient-reported quality of life in children with sarcoma of the chest wall.

Summary Background Data: Children with chest wall sarcoma require multimodal therapy including chemotherapy, surgery and/or radiation. Despite aggressive therapy which places them at risk for functional impairment and scoliosis, these patients are also at significant risk for local recurrence.

Methods: A multi-institutional review of 175 children (median age 13 years) with chest wall sarcoma treated at seventeen Pediatric Surgical Oncology Research Collaborative institutions between 2008-2017 was performed. Patient-reported quality of life was assessed prospectively using PROMIS surveys.

Results: The most common diagnoses were Ewing sarcoma (67%) and osteosarcoma (9%). Surgical resection was performed in 85% and radiation in 55%. A median of 2 ribs were resected (IQR = 1-3), and number of ribs resected did not correlate with margin status (p = 0.36). Local recurrence occurred in 23% and margin status was the only predictive factor (HR 2.24, p = 0.039). With a median follow-up of 5 years, 13% developed scoliosis (median Cobb angle 26) and 5% required corrective spine surgery. Scoliosis was associated with posterior rib resection (HR 8.43; p = 0.003) and increased number of ribs resected (HR 1.78; p = 0.02). Overall, patient-reported quality of life is not impaired following chest wall tumor resection.

Conclusions: Local recurrence occurs in one-quarter of children with chest wall sarcoma and is independent of tumor type. Scoliosis occurs in 13% of patients, but patient-reported quality of life is excellent.
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http://dx.doi.org/10.1097/SLA.0000000000004579DOI Listing
November 2020

Impact of the coronavirus disease 2019 pandemic on surgical research and lessons for the future.

Surgery 2021 02 19;169(2):257-263. Epub 2020 Sep 19.

Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Background: The current coronavirus disease 2019 pandemic has had an unprecedented impact on all physicians and has resulted in dramatic changes to clinical and research operations. No study has yet looked at the impact of coronavirus disease 2019 on the surgical research community. In this study, we sought to understand the impact of the pandemic and its associated restrictions on academic surgeons.

Methods: We surveyed members of the Association for Academic Surgery and the Society of University Surgeons. Survey questions included demographics, current challenges to basic and clinical research activities, attitudes toward remote work and productivity maintenance, and the solutions implemented to maintain productivity.

Results: Of 301 respondents, 70% cited a negative impact on research productivity due to mandatory building shutdowns, minimized personnel as a result of social distancing, and suspensions of animal work and clinical trials, with senior faculty and division chiefs and chairs more likely to report a negative impact (P = .001). Only 11% of respondents are documenting their financial losses, and only 19% indicated they received appropriate guidance regarding why and how to monitor the financial impact of the pandemic. Researchers have attempted to maintain research productivity through a focus on remote work, including manuscript writing, grant writing, and data analysis. Some participants have found silver linings, including more time to dedicate to research and family as a result of fewer clinical duties.

Conclusion: Productivity strategies developed during the pandemic, including writing, remote work and meetings, and structured scheduling, are lessons that will allow the surgical research community to be resilient in the face of future disruptions.
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http://dx.doi.org/10.1016/j.surg.2020.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502013PMC
February 2021

A smartphone-based particle diffusometry platform for sub-attomolar detection of Vibrio cholerae in environmental water.

Biosens Bioelectron 2020 Nov 8;167:112497. Epub 2020 Aug 8.

Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, 47907, USA. Electronic address:

Each year, 3.4 million people die from waterborne diseases worldwide. Development of a rapid and portable platform for detecting and monitoring waterborne pathogens would significantly aid in reducing the incidence and spread of infectious diseases. By combining optical methods and smartphone technology with molecular assays, the sensitivity required to detect exceedingly low concentrations of waterborne pathogens can readily be achieved. Here, we implement smartphone-based particle diffusometry (PD) detection of loop-mediated isothermal amplification (LAMP) targeting the waterborne pathogen Vibrio cholerae (V. cholerae). By measuring the diffusion of 400 nm streptavidin-coated fluorescent nanoparticles imaged at 68X magnification on a smartphone, we can detect as few as 6 V. cholerae cells per reaction (0.66 aM) in just 35 minutes. In a double-blinded study with 132 pond water samples, we establish a 91.8% sensitivity, 95.2% specificity, and 94.3% accuracy of the smartphone-based PD platform for detection of V. cholerae. Together, these results demonstrate the utility of this smartphone-based PD platform for rapid and sensitive detection of V. cholerae at the point of use.
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http://dx.doi.org/10.1016/j.bios.2020.112497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532658PMC
November 2020

Thoracoscopy vs thoracotomy for the management of metastatic osteosarcoma: A Pediatric Surgical Oncology Research Collaborative Study.

Int J Cancer 2021 Mar 31;148(5):1164-1171. Epub 2020 Aug 31.

Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.

Complete surgical resection of pulmonary metastatic disease in patients with osteosarcoma is crucial to long-term survival. Open thoracotomy allows palpation of nodules not identified on imaging but the impact on survival is unknown. The objective of this study was to compare overall survival (OS) and pulmonary disease-free survival (DFS) in children who underwent thoracotomy vs thoracoscopic surgery for pulmonary metastasectomy. A multi-institutional collaborative group retrospectively reviewed 202 pediatric patients with osteosarcoma who underwent pulmonary metastasectomy by thoracotomy (n = 154) or thoracoscopy (n = 48). Results were analyzed by Kaplan-Meier survival estimates and multivariate Cox proportional hazard regression models. With median follow-up of 45 months, 135 (67.5%) patients had a pulmonary relapse and 95 (47%) patients were deceased. Kaplan-Meier analysis showed no significant difference in 5-year pulmonary DFS (25% vs 38%; P = .18) or OS (49% vs 42%, P = .37) between the surgical approaches of thoracotomy and thoracoscopy. In Cox regression analysis controlling for other factors impacting outcome, there was a significantly increased risk of mortality (HR 2.11; P = .027; 95% CI 1.09-4.09) but not pulmonary recurrence (HR 0.96; P = .90; 95% CI 0.52-1.79) with a thoracoscopic approach. However, in the subset analysis limited to patients with oligometastatic disease, thoracoscopy had no increased risk of mortality (HR 1.16; P = .62; 0.64-2.11). In conclusion, patients with metastatic osteosarcoma and limited pulmonary disease burden demonstrate comparable outcomes after thoracotomy and thoracoscopy for metastasectomy. While significant selection bias in these surgical cohorts limits the generalizability of the conclusions, clinical equipoise for a randomized clinical trial in patients with oligometastatic disease is supported.
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http://dx.doi.org/10.1002/ijc.33264DOI Listing
March 2021

Pancreaticoduodenectomy for the treatment of pancreatic neoplasms in children: A Pediatric Surgical Oncology Research Collaborative study.

Pediatr Blood Cancer 2020 09 13;67(9):e28425. Epub 2020 Jul 13.

Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.

Background: To better characterize short-term and long-term outcomes in children with pancreatic tumors treated with pancreaticoduodenectomy (PD).

Methods: Patients 21 years of age or younger who underwent PD at Pediatric Surgical Oncology Collaborative (PSORC) hospitals between 1990 and 2017 were identified. Demographic, clinical information, and outcomes (operative complications, long-term pancreatic function, recurrence, and survival) were collected.

Results: Sixty-five patients from 18 institutions with a median age of 13 years (4 months-22 years) and a median (IQR) follow-up of 2.8 (4.3) years were analyzed. Solid pseudopapillary tumor of the pancreas (SPN) was the most common histology. Postoperative complications included pancreatic leak in 14% (n = 9), delayed gastric emptying in 9% (n = 6), marginal ulcer in one patient, and perioperative (30-day) death due to hepatic failure in one patient. Pancreatic insufficiency was observed in 32% (n = 21) of patients, with 23%, 3%, and 6% with exocrine, or endocrine insufficiencies, or both, respectively. Children with SPN and benign neoplasms all survived. Overall, there were 14 (22%) recurrences and 11 deaths (17%). Univariate analysis revealed non-SPN malignant tumor diagnosis, preoperative vascular involvement, intraoperative transfusion requirement, pathologic vascular invasion, positive margins, and need for neoadjuvant chemotherapy as risk factors for recurrence and poor survival. Multivariate analysis only revealed pathologic vascular invasion as a risk factor for recurrence and poor survival.

Conclusion: This is the largest series of pediatric PD patients. PD is curative for SPN and benign neoplasms. Pancreatic insufficiency is the most common postoperative complication. Outcome is primarily associated with histology.
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http://dx.doi.org/10.1002/pbc.28425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674210PMC
September 2020

The Effect of Gross Total Resection on Patients with Pleuropulmonary Blastoma.

J Surg Res 2020 09 27;253:115-120. Epub 2020 Apr 27.

Division of Pediatric Surgery, Children's Hospital Los Angeles, Los Angeles, California; Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California. Electronic address:

Background: Pleuropulmonary blastoma (PPB) is the most common primary lung cancer in children. While rare, these tumors are highly aggressive. Tumor recurrence and overall survival are dependent on histologic grade and extent of surgical resection. We sought to examine our institutional experience with PPB to determine the effect of gross total resection (GTR) on recurrence and patient outcomes.

Materials And Methods: After IRB approval, a retrospective chart review from 1998 to 2018 was performed. Cases were confirmed by histology and Dehner Grade (I to III). Data collection included demographics, treatment, extent of surgical resection, and patient outcomes.

Results: Eight patients with nine procedures were identified. Histologically, three cases were type 1, 2 type 2, and four poor prognosis type 3. Three patients received neoadjuvant chemotherapy to facilitate surgical resection. The operative goal was to achieve GTR (>95%), and to this end, three partial lobectomies, five lobectomies, and one pneumonectomy were performed. All nine cases achieved GTR, of which eight had negative microscopic margins. Two patients with type III disease recurred (one locally, one distant) and died. One type 3 patient had a positive microscopic hilar margin not amenable to further resection. The patient recurred (distant) but is in remission. With respect to patient outcomes, the event-free survival was 2.3 y with an overall survival of 3.3 y.

Conclusions: From our experience, GTR of PPB is associated with minimal surgical morbidity and good overall survival. Multi-institutional studies are needed to determine if positive surgical margins affect outcomes given the morbidity of mediastinal dissection.
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http://dx.doi.org/10.1016/j.jss.2020.03.019DOI Listing
September 2020

Normalization of Serum Lipase Levels Versus Resolution of Abdominal Pain: A Comparison of Preoperative Management in Children With Biliary Pancreatitis.

J Surg Res 2020 08 9;252:133-138. Epub 2020 Apr 9.

Division of Pediatric Surgery, Department of Surgery, Children's Hospital Los Angeles, USC Keck School of Medicine, Los Angeles, California. Electronic address:

Background: Controversy exists over the timing of cholecystectomy for biliary pancreatitis in children. Some surgeons await normalization of serum lipase levels while others are guided by resolution of abdominal pain; however, there are minimal data to support either practice. We hypothesized that resolution of abdominal pain is equivalent in outcome to awaiting normalization of lipase levels in patients undergoing cholecystectomy for biliary pancreatitis.

Methods: After institutional review board (IRB) approval, the medical record was retrospectively queried for all cases of cholecystectomy for biliary pancreatitis at our institution from 2007 to 2017. Patients undergoing chemotherapy, admitted for another cause, or who had severe underlying comorbidities like ventilator dependence were excluded. Patients were stratified into two cohorts: those managed preoperatively by normalization of serum lipase levels versus resolution of abdominal pain. Demographics, serum lipase levels, postoperative complications, cost of stay, readmissions, and return to the emergency department were collected and analyzed using multivariate regression.

Results: Seventy-four patients met inclusion: 29 patients had lipase levels trended until normalization compared with 45 patients who had resolution of abdominal pain prior to cholecystectomy. Among the two cohorts there was no statistical difference in age, gender, race, ethnicity, or type of preoperative imaging used. Trended patients were found to have more serum lipase levels tested (8.5 ± 6.2 versus 3.4 ± 2.5, P < 0.0001). The trended lipase cohort was significantly more likely to require preoperative total parenteral nutrition (48% versus 11%, P = 0.007) and consequently a longer time before resuming a diet (10 ± 7.3 versus 4.6 ± 2.4 d, P < 0.0001). When comparing the two groups, we found no significant difference in the duration of surgery, postoperative complications, or readmissions. Lipase trended patients had a significantly longer length of stay compared with nontrended patients (11.5 ± 8.1 versus 4.2 ± 2.3 d, P < 0.0001) and had a higher total cost of stay ($38,094 ± 25,910 versus $20,205 ± 5918, P = 0.0007).

Conclusions: Our data suggest that in children with biliary pancreatitis, proceeding with cholecystectomy after resolution of abdominal pain is equivalent in outcomes to trending serum lipase levels but is more cost-effective with a decreased length of stay and decreased need for preoperative total parenteral nutrition.
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http://dx.doi.org/10.1016/j.jss.2020.03.012DOI Listing
August 2020

Invited commentary for "Outpatient thyroidectomy in the pediatric population".

Am J Surg 2020 06 29;219(6):888-889. Epub 2020 Mar 29.

Division of Pediatric Surgery, Department of Surgery, University of Tennessee Health Sciences Center, Children's Foundation Research Institute, Le Bonheur Children's Hospital, Memphis, TN, USA.

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http://dx.doi.org/10.1016/j.amjsurg.2020.03.029DOI Listing
June 2020

Pneumonectomy for Pediatric Tumors-a Pediatric Surgical Oncology Research Collaborative Study.

Ann Surg 2020 Mar 20. Epub 2020 Mar 20.

Division of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

Objective: To describe utilization and long-term outcomes of pneumonectomy in children and adolescents with cancer.

Summary Background Data: Pneumonectomy in adults is associated with significant morbidity and mortality. Little is known about the indications and outcomes of pneumonectomy for pediatric tumors.

Methods: The Pediatric Surgical Oncology Research Collaborative (PSORC) identified pediatric patients <21 years of age who underwent pneumonectomy from 1990 to 2017 for primary or metastatic tumors at 12 institutions. Clinical information was collected; outcomes included operative complications, long-term function, recurrence, and survival. Univariate log rank, and multivariable Cox analyses determined factors associated with survival.

Results: Thirty-eight patients (mean 12 ± 6 yrs) were identified; median (IQR) follow-up was 19 (5-38) months. Twenty-six patients (68%) underwent pneumonectomy for primary tumors and 12 (32%) for metastases. The most frequent histologies were osteosarcoma (n = 6), inflammatory myofibroblastic tumors (IMT; n = 6), and pleuropulmonary blastoma (n = 5). Median postoperative ventilator days were 0 (0-1), intensive care 2 (1-3), and hospital 8 (5-16). Early postoperative complications occurred in 10 patients including 1 death. Of 25 (66%) patients alive at 1 year, 15 reported return to preoperative pulmonary status. All IMT patients survived while all osteosarcoma patients died during follow-up. On multivariable analysis, metastatic indications were associated with nonsurvival (HR = 3.37, P = 0.045) CONCLUSION:: This is the largest review of children who underwent pneumonectomy for cancer. There is decreased procedure-related morbidity and mortality than reported for adults. Survival is worse with preoperative metastatic disease, especially osteosarcoma.
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http://dx.doi.org/10.1097/SLA.0000000000003795DOI Listing
March 2020

The Clinical Management and Outcomes of Pelvic Neuroblastic Tumors.

J Surg Res 2020 05 7;249:8-12. Epub 2020 Jan 7.

Division of Pediatric Surgery, Department of Surgery, Children's Hospital Los Angeles, Los Angeles, California; Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California. Electronic address:

Background: Pelvic neuroblastomas are rare and often present in children as massive tumors whose surgical resection can be associated with significant morbidity, given sacral nerve root involvement and close proximity to pelvic vascular structures. We sought to examine the characteristics of patients with pelvic neuroblastoma and the effect of extent of surgical resection on survival and surgical outcomes.

Materials And Methods: After institutional review board approval, a retrospective chart review was performed at Children's Hospital Los Angeles from 2000 to 2018. Collected data included tumor location, size, image-defined risk factors histology, stage and risk classification, amplification of the oncogene MYCN or N-myc, use of preoperative chemotherapy, and extent of surgical resection. Outcome variables included postoperative complications and survival.

Results: Ten patients with primary pelvic neuroblastoma tumors were identified. The median age at diagnosis was 4.2 y (3 mo to 11 y). Four patients presented with a localized pelvic tumor (stage I or stage II) and underwent upfront tumor resection. Six patients presented with advanced disease (stage III or stage IV) and underwent neoadjuvant chemotherapy, followed by partial resection (30%-90% debulked). One patient experienced a complication: lower extremity hypotonia after tumor resection. One patient died from extensive metastatic disease for which no resection was attempted. The mean postoperative follow-up was 3.9 y with 90% overall survival.

Conclusions: Our data show that patients who undergo gross total resection for localized pelvic neuroblastoma or neoadjuvant chemotherapy, followed by partial resection for advanced disease have excellent survival. We recommend that small localized pelvic neuroblastoma undergo gross total resection and large unresectable tumors undergo neoadjuvant chemotherapy, followed by partial debulking resection to avoid neurovascular morbidity.
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http://dx.doi.org/10.1016/j.jss.2019.12.009DOI Listing
May 2020

Non-Operative Management is More Cost-Effective than Immediate Operation in Perforated Appendicitis Patients with Seven or More Days of Symptoms.

J Surg Res 2019 08 22;240:70-79. Epub 2019 Mar 22.

Division of Pediatric Surgery, Children's Hospital Los Angeles, Los Angeles, California; Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California. Electronic address:

Background: Management of perforated appendicitis in children remains controversial. Nonoperative (NO) and immediate operative (IO) strategies are used with varying outcomes. We hypothesized that IO intervention for patients with perforated appendicitis would be more cost-effective than NO management.

Methods: A retrospective chart review of all patients with appendicitis from 2012 to 2015 was performed. Patients with perforated appendicitis were defined by evidence of perforation on imaging. We excluded patients who presented with sepsis, organ failure, and ventriculoperitoneal shunts. NO management was determined by surgeon preference. Univariate and multivariate analyses were performed.

Results: IO was performed on 145 patients with perforated appendicitis, whereas 83 were treated with NO management. Compared to IO patients, NO patients incurred higher overall costs, greater length of stay, more readmissions, complications, peripherally inserted central venous catheter lines, interventional radiology drains, and unplanned clinic and emergency department visits (P < 0.0001 for all). Multivariate analysis adjusting for age, days of symptoms, admission C-reactive protein and white blood cell count revealed that NO management was independently associated with increased costs (OR 1.35, 1.12-1.62, 95% CI). Cost curves demonstrated that total cost for IO surpasses that of NO management when patients present with greater than 6.3 d of symptoms (P = 0.01).

Conclusions: Our data suggest that IO is more cost-effective than NO management for patients with perforated appendicitis who present with less than 6.3 d of symptoms, after which point, NO management is more cost-effective.

Level Of Evidence: IV.
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http://dx.doi.org/10.1016/j.jss.2019.02.033DOI Listing
August 2019

A 10-Month-Old Infant Presenting With Signs of Precocious Puberty Secondary to a Sclerosing Stromal Tumor of the Ovary in the Absence of Hormonal Elevation.

Pediatr Dev Pathol 2019 Jul-Aug;22(4):375-379. Epub 2018 Dec 21.

1 Division of Pediatric Surgery, Children's Hospital Los Angeles, Los Angeles, California.

Precocious puberty in an infant is an alarming and infrequent finding, making the differential diagnosis difficult for practitioners. Precocious puberty secondary to a sclerosing stromal tumor (SST) of the ovary is rare. We present a case of a child that began precocious puberty at 3 months of age including development of breast buds, pubic hair, growth spurt, and menarche 5 days prior to presenting to pediatric endocrinology at 10 months. She underwent right salpingo-oophorectomy which demonstrated a soft tissue mass occupying almost the entire ovary with a tan-pink fleshy cut surface. Histological examination confirmed a variant of SST. This case represents an extremely young onset of precocious puberty secondary to a variant of SST without hormonal elevation.
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http://dx.doi.org/10.1177/1093526618819605DOI Listing
January 2020

Activated Natural Killer Cells in Combination with Anti-GD2 Antibody Dinutuximab Improve Survival of Mice after Surgical Resection of Primary Neuroblastoma.

Clin Cancer Res 2019 01 19;25(1):325-333. Epub 2018 Sep 19.

Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California.

Purpose: Immunotherapy of neuroblastoma that remains after myeloablative chemotherapy with anti-GD2 antibody dinutuximab has increased the two-year event-free and overall survival of high-risk neuroblastoma patients; however, 40% of patients develop recurrent disease during or after this treatment. To determine the potential of such antibody-based immunotherapy earlier in treatment, a mouse model was developed in which surgical resection of the primary tumor was followed by therapy of residual disease with dinutuximab combined with -activated human natural killer (aNK) cells.

Experimental Design: The effect of combining dinutuximab with human aNK cells was determined with cellular cytotoxicity and Matrigel invasion assays. The efficacy of dinutuximab and aNK cells against neuroblastoma was assessed following resection of primary tumors formed by two cell lines or a patient-derived xenograft (PDX) in immunodeficient NOD-scid gamma mice.

Results: , the combination of aNK cells and dinutuximab caused cytotoxicity and decreased invasiveness of three human neuroblastoma cell lines. Treatment of mice with dinutuximab combined with aNK cells after surgical resection of primary intrarenal tumors formed by two cell lines or a PDX decreased tumor cells in liver and bone marrow as evaluated by histopathology and bioluminescence imaging. Survival of mice after resection of these tumors was most significantly increased by treatment with dinutuximab combined with aNK cells compared with that of untreated mice.

Conclusions: The combination of dinutuximab and adoptively transferred human aNK cells following surgical resection of primary neuroblastomas significantly improves survival of immunodeficient mice.
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http://dx.doi.org/10.1158/1078-0432.CCR-18-1317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320320PMC
January 2019

Is less more? Laparoscopic versus open Ladd's procedure in children with malrotation.

J Surg Res 2018 09 11;229:351-356. Epub 2018 May 11.

Division of Pediatric Surgery, Children's Hospital Los Angeles, Los Angeles, California; Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California. Electronic address:

Background: With the advent of minimally invasive techniques, laparoscopic Ladd's procedure is increasingly used to treat children with malrotation, yet evidence regarding its safety and efficacy is lacking. We hypothesize that operative and postoperative outcomes with the open technique are superior to the laparoscopic Ladd's procedure.

Methods: We conducted a 5-y retrospective chart review of all patients who underwent Ladd's procedure at our institution from 2010-2015. Exclusion of patients included those with concomitant conditions, such as poor gut perfusion, significant reflux, tracheoesophageal fistula, failure to thrive requiring concomitant gastrostomy, and biliary atresia. Kruskal-Wallis and Mann-Whitney tests were used where appropriate.

Results: Between 2010 and 2015, of 130 patients who underwent Ladd's procedure, 77 met inclusion criteria. Sixty-two patients underwent initial open surgery, 15 patients underwent laparoscopy, seven of which were converted to open. Patients undergoing open surgery were younger compared to the laparoscopic groups. Thirty-three of the 77 malrotation patients (43%) presented with volvulus, 27 underwent open surgery, four had laparoscopic converted to open procedures, and two patients underwent laparoscopic Ladd's without incident. Laparoscopy resulted in increased operative time and clinic visits. Patients undergoing laparoscopic to open surgery had longer operative times, time to resume diet, and length of hospital stay. No difference was noted in complications among the groups.

Conclusions: Although minimally invasive approaches are becoming increasingly used, no evidence supports laparoscopic superiority over open Ladd's procedure. We found that open surgery was associated with shorter operating times and fewer clinic visits. Furthermore, laparotomy remains the favored procedure for patients presenting with volvulus.
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http://dx.doi.org/10.1016/j.jss.2018.04.016DOI Listing
September 2018

Congenital Perirectal Dermoid Cyst: A Rare Cause of Complex, Recurrent Pediatric Fistula-in-ano.

Front Pediatr 2018 16;6:143. Epub 2018 May 16.

Division of Pediatric Surgery, Children's Hospital Los Angeles, Los Angeles, CA, United States.

Perianal abscess and fistula-in-ano are well-described in the pediatric population. They are most common in infants less than 1 year of age and often resolve with oral antibiotics; occasionally they require drainage or fistulotomy. The etiology is commonly associated with cryptoglandular obstruction and subsequent infection, however alternative diagnoses should be considered in cases of recurrent abscesses and fistulae that are refractory to standard treatments. In this report, we present the case of an 8-year-old boy with a complex, recurrent fistula-in-ano that resulted from a rare congenital perirectal dermoid cyst.
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http://dx.doi.org/10.3389/fped.2018.00143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964207PMC
May 2018

p53 Nongenotoxic Activation and mTORC1 Inhibition Lead to Effective Combination for Neuroblastoma Therapy.

Clin Cancer Res 2017 Nov 18;23(21):6629-6639. Epub 2017 Aug 18.

Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas.

mTORC1 inhibitors are promising agents for neuroblastoma therapy; however, they have shown limited clinical activity as monotherapy, thus rational drug combinations need to be explored to improve efficacy. Importantly, neuroblastoma maintains both an active p53 and an aberrant mTOR signaling. Using an orthotopic xenograft model and modulating p53 levels, we investigated the antitumor effects of the mTORC1 inhibitor temsirolimus in neuroblastoma expressing normal, decreased, or mutant p53, both as single agent and in combination with first- and second-generation MDM2 inhibitors to reactivate p53. Nongenotoxic p53 activation suppresses mTOR activity. Moreover, p53 reactivation via RG7388, a second-generation MDM2 inhibitor, strongly enhances the antitumor activity of temsirolimus. Single-agent temsirolimus does not elicit apoptosis, and tumors rapidly regrow after treatment suspension. In contrast, our combination therapy triggers a potent apoptotic response in wild-type p53 xenografts and efficiently blocks tumor regrowth after treatment completion. We also found that this combination uniquely led to p53-dependent suppression of survivin whose ectopic expression is sufficient to rescue the apoptosis induced by our combination. Our study supports a novel highly effective strategy that combines RG7388 and temsirolimus in wild-type p53 neuroblastoma, which warrants testing in early-phase clinical trials. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-0668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959272PMC
November 2017

TGFβR1 Blockade with Galunisertib (LY2157299) Enhances Anti-Neuroblastoma Activity of the Anti-GD2 Antibody Dinutuximab (ch14.18) with Natural Killer Cells.

Clin Cancer Res 2017 Feb 10;23(3):804-813. Epub 2016 Oct 10.

Children's Hospital Los Angeles and the Saban Research Institute, Los Angeles, California.

Purpose: Immunotherapy of high-risk neuroblastoma using the anti-GD2 antibody dinutuximab induces antibody-dependent cell-mediated cytotoxicity (ADCC). Galunisertib, an inhibitor of TGFβR1, was examined for its ability to enhance the efficacy of dinutuximab in combination with human ex vivo activated NK (aNK) cells against neuroblastoma.

Experimental Design: TGFB1 and TGFBR1 mRNA expression was determined for 249 primary neuroblastoma tumors by microarray analysis. The ability of galunisertib to inhibit SMAD activity induced by neuroblastoma patient blood and bone marrow plasmas in neuroblastoma cells was tested. The impact of galunisertib on TGFβ1-induced inhibition of aNK cytotoxicity and ADCC in vitro and on anti-neuroblastoma activity in NOD-scid gamma (NSG) mice was determined.

Results: Neuroblastomas express TGFB1 and TGFBR1 mRNA. Galunisertib suppressed SMAD activation in neuroblastoma cells induced by exogenous TGFβ1 or by patient blood and bone marrow plasma, and suppressed SMAD2 phosphorylation in human neuroblastoma cells growing in NSG mice. In NK cells treated in vitro with exogenous TGFβ1, galunisertib suppressed SMAD2 phosphorylation and restored the expression of DNAM-1, NKp30, and NKG2D cytotoxicity receptors and the TRAIL death ligand, the release of perforin and granzyme A, and the direct cytotoxicity and ADCC of aNK cells against neuroblastoma cells. Addition of galunisertib to adoptive cell therapy with aNK cells plus dinutuximab reduced tumor growth and increased survival of mice injected with two neuroblastoma cell lines or a patient-derived xenograft.

Conclusions: Galunisertib suppresses activation of SMAD2 in neuroblastomas and aNK cells, restores NK cytotoxic mechanisms, and increases the efficacy of dinutuximab with aNK cells against neuroblastoma tumors. Clin Cancer Res; 23(3); 804-13. ©2016 AACRSee related commentary by Zenarruzabeitia et al., p. 615.
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http://dx.doi.org/10.1158/1078-0432.CCR-16-1743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5361893PMC
February 2017

The clinical management and outcomes of cervical neuroblastic tumors.

J Surg Res 2016 07 23;204(1):109-13. Epub 2016 Apr 23.

Division of Pediatric Surgery, Department of Surgery, Children's Hospital Los Angeles, Los Angeles, California. Electronic address:

Background: Although patients with peripheral neuroblastoma (NB; pelvic and thoracic) typically have better outcomes and less aggressive disease compared with patients with abdominal disease, little has been published with regard to the management and outcomes of patients with cervical NB. Herein, we sought to determine the characteristics of cervical neuroblastic tumors and the effect of extent of resection on survival and outcomes.

Methods: We performed a retrospective review of 325 children with neuroblastic tumors at Children's Hospital Los Angeles over a 15-y period (January 1990-February 2015). Data collected from the medical record included location of tumor, age at diagnosis, age at resection, extent of resection, chemotherapy course, International Neuroblastoma Staging System stage, histologic International Neuroblastoma Pathology Classification, and MYCN amplification, a poor prognostic marker. Outcome variables included postoperative complications and overall survival.

Results: Twelve patients (3.6%) were found to have cervical neuroblastic tumors (nine NBs, one ganglioneuroblastoma, and two ganglioneuromas). All had favorable histology, and none (0/12) had MYCN amplification. Of the NB patients, four of nine patients underwent resection, whereas the other five underwent biopsy followed by chemotherapy or observation alone. Of the 12 total patients, six underwent gross total resection, four (67%) of which developed complications. At a median follow-up of 4.4 y, there were no recurrences or deaths.

Conclusions: Cervical neuroblastic tumors represent favorable lesions with good outcomes similar to other peripheral neuroblastic tumors. In our study, survival was excellent regardless of extent of tumor resection. Based on our data, we recommend a minimally aggressive surgical approach in managing children with cervical neuroblastic tumors.
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http://dx.doi.org/10.1016/j.jss.2016.04.030DOI Listing
July 2016

The optimal timing of surgical resection in high-risk neuroblastoma.

J Pediatr Surg 2016 Oct 7;51(10):1665-9. Epub 2016 Jun 7.

Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Division of Pediatric Surgery, Department of Surgery, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA. Electronic address:

Background: While most high-risk neuroblastoma (HRNB) patients are enrolled in cooperative group or institutional protocols, variability exists within these protocols as to when surgical resection of the primary tumor should be performed after neoadjuvant induction chemotherapy. We sought to determine if the number of chemotherapy cycles prior to surgery affects surgical or survival outcomes in HRNB patients.

Methods: We performed a retrospective review of all HRNB patients <18years of age from 2000 to 2010, at Texas Children's Hospital. Patients were stratified based on the number of neoadjuvant induction chemotherapy cycles prior to surgical resection. Pre and post- chemotherapy tumor size, MYCN status, iodine-131-metaiodobenzylguanidine (MIBG) score at diagnosis, extent of surgical resection, estimated surgical blood loss, post-operative outcomes, and event free (EFS) and overall survival (OS) were evaluated. Data were analyzed using Wilcoxon rank-sum test, Kruskal-Wallis test, Fisher's exact test, Kaplan-Meier analyses, and Cox regression analyses. P-value <0.05 was considered significant.

Results: Data from 50 patients with HRNB were analyzed. Patients were stratified by the number of cycles of chemotherapy received prior to surgery. Six patients received 2cycles of chemotherapy (12%), 20 patients received 3cycles (40%), 13 patients received 4cycles (26%), and 11 patients received 5cycles (22%) prior to surgical resection of the primary tumor. The 5-year OS was 33%, 45%, 83% and 36% in patients who received 2, 3, 4 and 5cycles of chemotherapy prior to surgery, respectively (p=0.07). Multivariate analysis revealed that patients who received 4cycles of chemotherapy had a significantly lower mortality (HR: 0.11, 95% CI: 0.01-0.87, p=0.04) compared to those with 2cycles of chemotherapy. Among the different cohorts, there were no differences with respect to MYCN status, MIBG score at diagnosis, incidence of bone marrow metastasis, extent of surgical resection, estimated blood loss, incidence of post-operative complications, or length of stay.

Conclusion: HRNB patients who receive 4cycles of chemotherapy prior to surgical resection have a superior OS than patients who receive 2. Based on the superior survival of patients who received 4cycles of chemotherapy prior to surgery, further studies are warranted to elucidate these differences.
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http://dx.doi.org/10.1016/j.jpedsurg.2016.05.021DOI Listing
October 2016

A novel minimal residual disease model of neuroblastoma in mice.

J Pediatr Surg 2016 Jun 4;51(6):991-4. Epub 2016 Mar 4.

Division of Pediatric Surgery, Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA. Electronic address:

Introduction: Patients with high-risk neuroblastoma rarely succumb to their primary tumor but rather from relapsed metastatic disease after surgery. We, therefore, sought to create an in vivo model of minimal residual disease (MRD), which clinically replicates tumor recurrence and metastasis after surgical resection.

Methods: Neuroblastoma cell lines CHLA-255, CHLA-136, and SH-SY5Y were used. After establishing orthotopic xenografts, mice were divided into control tumor group (sham operation at 14days) and tumor resection group (resection at 14days). Mice were monitored by bioluminescent imaging and sacrificed when institutional criteria for euthanasia were met.

Results: In the CHLA-255 and CHLA-136 cell lines, mice experienced significantly longer survival following tumor resection (p<0.007). There was no survival benefit seen in the SH-SY5Y cell line (p=0.29). Bioluminescent imaging demonstrated metastatic disease in 100% of all tumor resection mice and varying rates of metastasis in control mice (4 of 5 CHLA-255, 2 of 4 CHLA-136, and 7 of 7 SH-SY5Y).

Conclusion: In this study, we describe a novel neuroblastoma model of MRD in mice. This MRD model serves as an innovative means to test preclinical therapies as well as elucidate mechanisms of metastatic disease in experimental neuroblastoma.
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http://dx.doi.org/10.1016/j.jpedsurg.2016.02.066DOI Listing
June 2016

Transmembrane adaptor protein PAG1 is a novel tumor suppressor in neuroblastoma.

Oncotarget 2016 Apr;7(17):24018-26

Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Cancer Center, and Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA.

Neuroblastoma (NB) is the most common extracranial pediatric solid tumor with high mortality rates. The tyrosine kinase c-Src has been known to play an important role in differentiation of NB cells, but the mechanism of c-Src regulation has not been defined. Here, we characterize PAG1 (Cbp, Csk binding protein), a central inhibitor of c-Src and other Src family kinases, as a novel tumor suppressor in NB. Clinical cohort analysis demonstrate that low expression of PAG1 is a significant prognostic factor for high stage disease, increased relapse, and worse overall survival for children with NB. PAG1 knockdown in NB cells promotes proliferation and anchorage-independent colony formation with increased activation of AKT and ERK downstream of c-Src, while PAG1 overexpression significantly rescues these effects. In vivo, PAG1 overexpression significantly inhibits NB tumorigenicity in an orthotopic xenograft model. Our results establish PAG1 as a potent tumor suppressor in NB by inhibiting c-Src and downstream effector pathways. Thus, reactivation of PAG1 and inhibition of c-Src kinase activity represents an important novel therapeutic approach for high-risk NB.
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http://dx.doi.org/10.18632/oncotarget.8116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029681PMC
April 2016

Successful endoscopic ablation of a pyriform sinus fistula in a child: case report and literature review.

Pediatr Surg Int 2016 Jun 28;32(6):623-7. Epub 2016 Jan 28.

Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Hospital, Baylor College of Medicine, 6701 Fannin Street, Suite 1210, Houston, Texas, 77030, USA.

Recurrent thyroid infections are rare in children. When present, patients should be evaluated for anatomic anomalies such as pyriform sinus fistulae. We describe a 12-year-old girl with history of recurrent thyroid abscesses secondary to a pyriform sinus fistula and managed with concurrent endoscopic ablation and incision and drainage.
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http://dx.doi.org/10.1007/s00383-016-3868-3DOI Listing
June 2016

Novel ALK inhibitor AZD3463 inhibits neuroblastoma growth by overcoming crizotinib resistance and inducing apoptosis.

Sci Rep 2016 Jan 20;6:19423. Epub 2016 Jan 20.

Texas Children's Cancer Center, Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.

ALK receptor tyrosine kinase has been shown to be a therapeutic target in neuroblastoma. Germline ALK activating mutations are responsible for the majority of hereditary neuroblastoma and somatic ALK activating mutations are also frequently observed in sporadic cases of advanced NB. Crizotinib, a first-line therapy in the treatment of advanced non-small cell lung cancer (NSCLC) harboring ALK rearrangements, demonstrates striking efficacy against ALK-rearranged NB. However, crizotinib fails to effectively inhibit the activity of ALK when activating mutations are present within its kinase domain, as with the F1174L mutation. Here we show that a new ALK inhibitor AZD3463 effectively suppressed the proliferation of NB cell lines with wild type ALK (WT) as well as ALK activating mutations (F1174L and D1091N) by blocking the ALK-mediated PI3K/AKT/mTOR pathway and ultimately induced apoptosis and autophagy. In addition, AZD3463 enhanced the cytotoxic effects of doxorubicin on NB cells. AZD3463 also exhibited significant therapeutic efficacy on the growth of the NB tumors with WT and F1174L activating mutation ALK in orthotopic xenograft mouse models. These results indicate that AZD3463 is a promising therapeutic agent in the treatment of NB.
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http://dx.doi.org/10.1038/srep19423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4726162PMC
January 2016

G-CSF Is a Cancer Stem Cell-Specific Growth Factor-Response.

Cancer Res 2015 Sep 3;75(18):3992. Epub 2015 Sep 3.

Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.

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http://dx.doi.org/10.1158/0008-5472.CAN-15-1599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608385PMC
September 2015

G-CSF Promotes Neuroblastoma Tumorigenicity and Metastasis via STAT3-Dependent Cancer Stem Cell Activation.

Cancer Res 2015 Jun 23;75(12):2566-79. Epub 2015 Apr 23.

Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Cancer Center, Houston, Texas. Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas.

Increasing evidence suggests that inflammatory cytokines play a critical role in tumor initiation and progression. A cancer stem cell (CSC)-like subpopulation in neuroblastoma is known to be marked by expression of the G-CSF receptor (G-CSFR). Here, we report on the mechanistic contributions of the G-CSFR in neuroblastoma CSCs. Specifically, we demonstrate that the receptor ligand G-CSF selectively activates STAT3 within neuroblastoma CSC subpopulations, promoting their expansion in vitro and in vivo. Exogenous G-CSF enhances tumor growth and metastasis in human xenograft and murine neuroblastoma tumor models. In response to G-CSF, STAT3 acts in a feed-forward loop to transcriptionally activate the G-CSFR and sustain neuroblastoma CSCs. Blockade of this G-CSF-STAT3 signaling loop with either anti-G-CSF antibody or STAT3 inhibitor depleted the CSC subpopulation within tumors, driving correlated tumor growth inhibition, decreased metastasis, and increased chemosensitivity. Taken together, our results define G-CSF as a CSC-activating factor in neuroblastoma, suggest a comprehensive reevaluation of the clinical use of G-CSF in these patients to support white blood cell counts, and suggest that direct targeting of the G-CSF-STAT3 signaling represents a novel therapeutic approach for neuroblastoma.
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http://dx.doi.org/10.1158/0008-5472.CAN-14-2946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470771PMC
June 2015

Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes.

Nat Med 2015 May 13;21(5):524-9. Epub 2015 Apr 13.

1] Center for Cell and Gene Therapy, Baylor College of Medicine and Houston Methodist Hospital, Houston, Texas, USA. [2] Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA. [3] Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.

Adoptive transfer of chimeric antigen receptor (CAR)-redirected T lymphocytes (CAR-T cells) has had less striking therapeutic effects in solid tumors than in lymphoid malignancies. Although active tumor-mediated immunosuppression may have a role in limiting the efficacy of CAR-T cells, functional changes in T lymphocytes after their ex vivo manipulation may also account for the reduced ability of cultured CAR-T cells to penetrate stroma-rich solid tumors compared with lymphoid tissues. We therefore studied the capacity of human in vitro-cultured CAR-T cells to degrade components of the extracellular matrix (ECM). In contrast to freshly isolated T lymphocytes, we found that in vitro-cultured T lymphocytes lack expression of the enzyme heparanase (HPSE), which degrades heparan sulfate proteoglycans, the main components of ECM. We found that HPSE mRNA is downregulated in in vitro-expanded T cells, which may be a consequence of p53 (officially known as TP53, encoding tumor protein 53) binding to the HPSE gene promoter. We therefore engineered CAR-T cells to express HPSE and showed their improved capacity to degrade the ECM, which promoted tumor T cell infiltration and antitumor activity. The use of this strategy may enhance the activity of CAR-T cells in individuals with stroma-rich solid tumors.
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http://dx.doi.org/10.1038/nm.3833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425589PMC
May 2015

Analysis of submitted abstracts for the American Academy of Pediatrics, Section on Surgery, National Conference (AAP SoSU).

J Pediatr Surg 2015 Jun 14;50(6):1058-61. Epub 2015 Mar 14.

Pediatric Surgery Division, Department of Surgery, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, 4650 Sunset Boulevard, MS 100, Los Angeles, CA 90027, USA. Electronic address:

Purpose: In this study, we characterized the topics and type of research performed for abstracts submitted to the AAP SoSU national conferences from 2010-2013.

Methods: All abstracts submitted to the AAP SoSU Program Committee from 2010-2013 were analyzed. Abstracts were classified as basic science, clinical, domestic, international, as well as by disease processes, single, multicenter, retrospective, prospective, registry data, or other.

Results: From 2010-2013, 709 abstracts were submitted (2010 - 163, 2011 - 166, 2012 - 208, 2013 - 172), of which 349 were accepted (49% total acceptance rate (AR)). 17% represented basic science studies (74% AR), while 592 (84%) were clinical studies (44% AR). By disease state, CDH (57 abstracts, 70.2% AR), appendicitis (53 abstracts, 43% AR), and NEC (39 abstracts, 56% AR) were the most common. Most clinical abstracts (63%) were single-center retrospective reviews, 13% were large data registries, <5% were prospective studies, and only 5 abstracts were randomized controlled trials.

Conclusions: The AAP SoSU abstract submission data demonstrate a wide variety of research studies spanning the entirety of our field. Basic science studies have a higher AR than clinical studies, and the topics of CDH, appendicitis, and NEC continue to be the most popular areas of study.
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http://dx.doi.org/10.1016/j.jpedsurg.2015.03.039DOI Listing
June 2015

Focal nodular hyperplasia in children: an institutional experience with review of the literature.

J Pediatr Surg 2015 Mar 27;50(3):382-7. Epub 2014 Aug 27.

Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Hospital Liver Tumor Center, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas. Electronic address:

Background: Focal nodular hyperplasia (FNH) is uncommonly diagnosed in pediatric patients and may be difficult to distinguish from a malignancy. We present a review of all children with a tissue diagnosis of FNH at our institution, describe the diagnostic modalities, and provide recommendations for diagnosis and follow-up based on our experience and review of the literature.

Methods: A retrospective review of children <18years of age diagnosed with FNH at a single institution was performed from 2000 to 2013.

Results: Twelve patients were identified with a tissue diagnosis of FNH. Two patients required surgical resection of their lesion owing to concern for malignancy. Ten patients were managed expectantly with imaging surveillance after biopsy confirmed a diagnosis of FNH. All patients who underwent MRI had very typical findings including hypointensity on T1 weighted sequences, hyperintensity on T2, and homogenous uptake of contrast on the arterial phase. On follow-up all patients had either a stable lesion or reduction in size.

Conclusions: Focal nodular hyperplasia presents typically in children with liver disease, have undergone chemotherapy, and adolescent females. Young children, particularly <5years of age, without underlying liver disease or history of chemotherapy can pose a diagnostic dilemma. In this unique subgroup of children with FNH, MRI and/or needle biopsy should be adequate diagnostic modalities for these lesions.
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http://dx.doi.org/10.1016/j.jpedsurg.2014.06.016DOI Listing
March 2015