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Radiation therapy, a mainstay of treatment for head and neck cancer, is not always curative due to the development of treatment resistance; additionally, multi-institutional trials have questioned the efficacy of concurrent radiation with cetuximab, the epidermal growth factor receptor (EGFR) inhibitor. We unraveled a mechanism for radiation resistance; that is, radiation induces EGFR, which phosphorylates TRIP13 (thyroid hormone receptor interactor 13) on tyrosine 56. Phosphorylated (phospho-)TRIP13 promotes non-homologous end joining (NHEJ) repair to induce radiation resistance. NHEJ is the main repair pathway for radiation-induced DNA damage. Tumors expressing high TRIP13 do not respond to radiation but are sensitive to cetuximab or cetuximab combined with radiation. Suppression of phosphorylation of TRIP13 at Y56 abrogates these effects. These findings show that EGFR-mediated phosphorylation of TRIP13 at Y56 is a vital mechanism of radiation resistance. Notably, TRIP13-pY56 could be used to predict the response to radiation or cetuximab and could be explored as an actionable target.

Radiation is a significant treatment for patients with head and neck cancer. Despite advances to improve treatment, many tumors acquire radiation resistance resulting in poor survival. Radiation kills cancer cells by inducing DNA double-strand breaks. Therefore, radiation resistance is enhanced by efficient repair of damaged DNA. Head and neck cancers overexpress EGFR and have a high frequency of p53 mutations, both of which enhance DNA repair. This review discusses the clinical criteria for radiation resistance in patients with head and neck cancer and summarizes how cancer cells evade radiation-mediated apoptosis by p53- and epidermal growth factor receptor (EGFR)-mediated DNA repair. In addition, we explore the role of cancer stem cells in promoting radiation resistance, and how the abscopal effect provides rationale for combination strategies with immunotherapy.

Glioblastoma (GBM) is an aggressive brain malignancy with a dismal prognosis. With emerging evidence to disprove brain-immune privilege, there has been much interest in examining immunotherapy strategies to treat central nervous system (CNS) cancers. Unfortunately, the limited success of clinical studies investigating immunotherapy regimens, has led to questions about the suitability of immunotherapy for these cancers. Inadequate inherent populations of tumor infiltrating lymphocytes (TILs) and limited trafficking of systemic, circulating T cells into the CNS likely contribute to the poor response to immunotherapy. This paucity of TILs is in concert with the finding of epigenetic silencing of genes that promote immune cell movement (chemotaxis) to the tumor. In this study we evaluated the ability of GSK126, a blood-brain barrier (BBB) permeable small molecule inhibitor of EZH2, to reverse GBM immune evasion by epigenetic suppression of T cell chemotaxis. We also evaluated the in vivo efficacy of this drug in combination with anti-PD-1 treatment on tumor growth, survival and T cell infiltration in syngeneic mouse models. GSK126 reversed H3K27me3 in murine and human GBM cell lines. When combined with anti-PD-1 treatment, a significant increase in activated T cell infiltration into the tumor was observed. This resulted in decreased tumor growth and enhanced survival both in sub-cutaneous and intracranial tumors of immunocompetent, syngeneic murine models of GBM. Additionally, a significant increase in CXCR3+ T cells was also seen in the draining lymph nodes, suggesting their readiness to migrate to the tumor. Closer examination of the mechanism of action of GSK126 revealed its ability to promote the expression of IFN-γ driven chemokines CXCL9 and CXCL10 from the tumor cells, that work to traffic T cells without directly affecting T maturation and/or proliferation. The loss of survival benefit either with single agent or combination in immunocompromised SCID mice, suggest that the therapeutic efficacy of GSK126 in GBM is primarily driven by lymphocytes. Taken together, our data suggests that in glioblastoma, epigenetic modulation using GSK126 could improve current immunotherapy strategies by reversing the epigenetic changes that enable immune cell evasion leading to enhanced immune cell trafficking to the tumor.

Background Hypertrophy of visceral adipose tissue (VAT) is a hallmark of Crohn disease (CD). The VAT produces a wide range of adipokines, biologically active factors that contribute to metabolic disorders in addition to CD pathogenesis. The study aim was to concomitantly evaluate serum adipokine profiles and VAT volumes as predictors of disease outcomes and treatment course in newly diagnosed pediatric patients with CD. Methods Pediatric patients ages 6 to 20 years were enrolled, and their clinical data and anthropometric measurements were obtained. Adipokine levels were measured at 0, 6, and 12 months after CD diagnosis and baseline in control patients (CP). The VAT volumes were measured by magnetic resonance imaging or computed tomography imaging within 3 months of diagnosis. Results One hundred four patients undergoing colonoscopy were prospectively enrolled: 36 diagnosed with CD and 68 CP. The serum adipokine resistin and plasminogen activator inhibitor (PAI)-1 levels were significantly higher in patients with CD at diagnosis than in CP. The VAT volume was similar between CD and CP. Baseline resistin levels at the time of diagnosis in patients with CD who were escalated to biologics was significantly higher than in those not treated using biologic therapy by 12 months (29.8 ng/mL vs 13.8 ng/mL; P = 0.004). A resistin level of ≥29.8 ng/mL at the time of diagnosis predicted escalation to biologic therapy in the first year after diagnosis with a specificity of 95% (sensitivity = 53%; area under the curve = 0.82; P = 0.015 for model with log-scale). There was a significantly greater reduction in resistin (P = 0.002) and PAI-1 (P = 0.010) at the 12-month follow-up in patients on biologics compared with patients who were not treated using biologics. Conclusions Serum resistin levels at diagnosis of pediatric CD predict the escalation to biologic therapy at 12 months, independent of VAT volumes. Resistin and PAI-1 levels significantly improved in patients with CD after treatment using biologics compared with those not on biologics. These results suggest the utility of resistin as a predictive biomarker in pediatric CD.

Autoimmune enteropathy is an extremely rare condition characterized by an abnormal intestinal immune response which typically manifests within the first 6 months of life as severe, intractable diarrhea that does not respond to dietary modification. Affected individuals frequently present with other signs of autoimmunity. The diagnosis is made based on a characteristic combination of clinical symptoms, laboratory studies, and histological features on small bowel biopsy. Autoimmune enteropathy is associated with a number of other conditions and syndromes, most notably immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome and autoimmune polyglandular syndrome type 1 (APS-1). Diagnosis and treatment is challenging, and further research is needed to better understand the pathogenesis, disease progression, and long-term outcomes of these conditions.

Introduction: Our hospital implemented universal pre-operative COVID-19 screening in April 2020 to reduce risk of transmission to caregivers as well to avert a potential anesthetic risk in COVID positive patients. The aim of this project was to determine the prevalence of asymptomatic COVID- 19 infection among pediatric patients undergoing ambulatory procedures and surgeries, overall and for Pediatric Gastroenterology (GI) cases specifically. Methods: A retrospective chart review identified pediatric patients (≤21 years) who underwent ambulatory pre-operative COVID-19 testing between April 1, 2020-March 31, 2021. Demographic and health-related data was collected to identify asymptomatic COVID-19 positive patients scheduled for GI procedures and other ambulatory surgeries. We compared the proportion of patients who tested positive by age group, co-morbid condition, and surgical specialty. We also compared pediatric case rates to Ohio case rates. The study was IRB approved. Results: 4,663 asymptomatic pediatric patients underwent pre-operative COVID-19 testing by PCR and 81 patients were identified as positive (1.73%). In COVID-19 positive patients, 56% were male and 44% were female. Mean age was 12 years and patients 13-18 years were the age group with the highest fraction of positive tests (35%). 11% of patients screened were undergoing a GI-related procedure with a positivity rate of 1.3%. The peak in asymptomatic positives across all procedures occurred in November 2020 (30%), which preceded the peak in COVID-19 cases in Ohio by several weeks. Most prevalent co-morbid condition was asthma (15%) and 8% had inflammatory bowel disease. 5 patients were undergoing chemotherapy and none were on biologic therapy. 94% of cases were deferred. 25% of cases that proceeded required post-operative admission. Conclusion: Asymptomatic COVID-19 positive patients were identified before 1.73% of pediatric ambulatory procedures and before 1.3% of GI procedures. These case rates were higher than the concurrent adult case rate at our institution. The higher rate of asymptomatic COVID-19 infection in pre-operative pediatric ambulatory patients may reflect the milder disease in this age group. The peak in pediatric asymptomatic case positivity seemed to predict the subsequent peak case rate in the state of Ohio by a few weeks. As the pandemic continues with a large percentage of pediatric patients unvaccinated, pre-operative COVID-19 testing has important implications for pediatric GI and other ambulatory procedures..

Background Standard therapy for chordoma consists of surgical resection followed by high-dose irradiation. Protein phosphatase 2A (PP2A) is a ubiquitously expressed serine/threonine phosphatase involved in signal transduction, cell cycle progression, cell differentiation, and DNA repair. LB100 is a small-molecule inhibitor of PP2A designed to sensitize cancer cells to DNA damage from irradiation and chemotherapy. A recently completed phase I trial of LB100 in solid tumors demonstrated its safety. Here, we show the therapeutic potential of LB100 in chordoma. Methods Three patient-derived chordoma cell lines were used: U-CH1, JHC7, and UM-Chor1. Cell proliferation was determined with LB100 alone and in combination with irradiation. Cell cycle progression was assessed by flow cytometry. Quantitative γ-H2AX immunofluorescence and immunoblot evaluated the effect of LB100 on radiation-induced DNA damage. Ultrastructural evidence for nuclear damage was investigated using Raman imaging and transmission electron microscopy. A xenograft model was established to determine potential clinical utility of adding LB100 to irradiation. Results PP2A inhibition in concert with irradiation demonstrated in vitro growth inhibition. The combination of LB100 and radiation also induced accumulation at the G2/M phase of the cell cycle, the stage most sensitive to radiation-induced damage. LB100 enhanced radiation-induced DNA double-strand breaks. Animals implanted with chordoma cells and treated with the combination of LB100 and radiation demonstrated tumor growth delay. Conclusions Combining LB100 and radiation enhanced DNA damage-induced cell death and delayed tumor growth in an animal model of chordoma. PP2A inhibition by LB100 treatment may improve the effectiveness of radiation therapy for chordoma.

Colonoscopy with polypectomy is frequently performed in pediatric patients based on symptoms, with the majority of polyps identified being benign juvenile pedunculated polyps with a vascular stalk. This is in distinction to adults where polypectomy is often performed as part of a colon cancer screening and prevention strategy and a higher fraction of polyps are sessile and or dysplastic. In adults, polypectomy techniques emphasize a need for deeper resection to ensure complete resection of adenomas or potential carcinoma in situ. Adenomatous polyps can occur in the pediatric age group and may be associated with an underlying polyposis, hereditary or chronic inflammatory conditions. Polypectomy techniques include use of cold biopsy forceps for very small polyps, cold snare polypectomy for small sessile polyps and hot snare polypectomy for the majority of polyps in the pediatric age group. Adjuvant techniques include epinephrine volume reduction, saline-assisted polypectomy and hemostatic techniques including injection, clip application and loop application to prevent or treat post-polypectomy bleeding. Electrosurgical principles guide the settings and type of current utilized during hot snare polypectomy. Polypectomy utilizing thermal techniques is associated with a higher risk of complications compared with diagnostic colonoscopy.

Crohn’s Disease is a relapsing and remitting disease involving chronic intestinal inflammation that is often characterized by hypertrophy of visceral adipose tissue (VAT). While an increased ratio of VAT to subcutaneous fat (SQF) has previously been identified as a predictor of worse outcomes in Crohn’s Disease, bowel-proximal fat regions have also been hypothesized to play a role in inflammatory response. However, there has been no detailed study of VAT and SQF regions on MRI to determine their potential utility in assessing Crohn’s Disease severity or guiding therapy. In this paper we present a fully-automated algorithm to segment and quantitatively characterize VAT and SQF via routinely acquired diagnostic bowel MRIs. Our automated segmentation scheme for VAT and SQF regions involved a combination of morphological processing and connected component analysis, and demonstrated DICE overlap scores of 0.86±0.05 and 0.91±0.04 respectively, when compared against expert annotations. Additionally, VAT regions proximal to the bowel wall (on diagnostic bowel MRIs) demonstrated a statistically significantly, higher expression of four unique radiomic features in pediatric patients with moderately active Crohn’s Disease. These features were also able to accurately cluster patients who required aggressive biologic therapy within a year of diagnosis from those who did not, with 87.5% accuracy. Our findings indicate that quantitative radiomic characterization of visceral fat regions on bowel MRIs may be highly relevant for guiding therapeutic interventions in Crohn’s Disease.

Figure S1. T cell stimulated with αCD3/αCD28 microbeads proliferate in the presence of dexamethasone.Healthy donor T cells were cultured for four days with the indicated ratio of αCD3/αCD28 microbeads:total T cells in the presence of vehicle or dexamethasone. A, Representative flow cytometry plots of CellTrace violet dilution. Plots were derived from gated CD4 (top row) or CD8 (bottom row) T cells. B-D, Proliferation analyses of CD4 T cells (top) and CD8 T cells (bottom) performed on the samples shown in (A). Precursor Frequency (B), Expansion Index (C), and Proliferation Index (D) are shown. Samples were plated in duplicate and analyzed with an unpaired students T test. Data are representative of three independent experiments. (PDF 3563 kb)

Figure S3. T cell differentiation subsets formed during in vitro stimulation with ÎąCD3/CD80 stimulation. Negatively-selected healthy donor T cells were cultured with 5Â Îźg/mL ÎąCD3 and the indicated concentration of CD80. T cell differentiation subsets were quantified following four days of culture. A, Flow plot of gating strategy to identify the indicated T cell differentiation subsets. B, Flow plots of CD4 (top) and CD8 (bottom) T cells cultured under the indicated conditions. (PDF 3995 kb)

Figure S7. Quantification of Treg and checkpoint molecules in tumor-bearing mice. GL261 ffluc-mCherry tumor-bearing mice were randomized into the indicated cohorts based on bioluminescence values from tumor. Vehicle or dexamethasone treatment was initiated on day 7, and isotype or CTLA-4 blocking antibody were administered on days 13, 16, and 19 following tumor implantation. Mice were euthanized on day 23 and tissues were harvested for flow cytometry analysis. A, Treg cell number from tumor-bearing brain hemisphere (left; n = 8) or the cervical tumor-draining lymph nodes (right; n = 10). B, The percentage of CD4 (top two plots) or CD8 (bottom two plots) T cells expressing the indicated checkpoint molecules. Co-expression of molecules was quantified using a Boolean gating strategy. Data were analyzed using a unpaired students T test. (PDF 1891 kb)

Figure S2. A, Negatively-selected healthy donor T cells were cultured with the indicated microbeads and vehicle or dexamethasone. The percent of apoptotic CD4 (top) and CD8 (bottom) T cells was assessed by Annexin V/PI. Data are representative of four independent experiments. B, Lysates from healthy donor T cells incubated with the indicated microbeads and vehicle or dexamethasone were probed for the indicated proteins. GAPDH was used as a loading control. (PDF 693 kb)

Figure S6 CTLA-4 blockade does not rescue dexamethasone pre-treated mice. A, Schema of survival experiment. Albino C57Bl/6 mice received intracranial implantation of GL261 ffluc-mCherry glioma cells. Dexamethasone was initiated one day prior to tumor implantation (dex (D-1)) or one week following tumor implantation (dex (D7)). CLTA-4 blockade or isotype antibody were injected on days 13, 16, and 19 following tumor implantation. Mice were randomized on day 6 following tumor implantation into groups of equivalent tumor luminescence. B, Kaplan Meier survival curves of mice receiving the indicated treatments. nâ =â 8 to 9 mice per cohort. Data are representative of two independent experiments. (PDF 1525 kb)

Figure S4. Increased co-stimulation ameliorates the inhibitory effects of dexamethasone. Negatively-selected healthy donor T cells were cultured with 5 μg/mL αCD3 and increasing concentrations of CD80 in the presence of vehicle or dexamethasone. A-B. CD8 T cells cultured with vehicle (A) or dexamethasone (B). Flow cytometry plots showing proliferation of cells cultured with the indicated concentration of CD80 (left) and total numbers of naïve (TN), central memory (TCM), effector memory (TEM), and terminal effector (TTE) T cells following four days of culture (right) are shown. Differentiation subsets were assessed by CD45RO and CCR7 staining. Each condition was plated in duplicate, and data are representative of three independent experiments. Data were analyzed with an unpaired, two-tailed T Test. (PDF 2573 kb)

Gastrointestinal polyps are commonly encountered during childhood and are one of the most common causes of rectal bleeding in this age group. Most polyps are benign and located in the colon, with the most frequent type being juvenile polyps. However, in older pediatric patients, if multiple polyps are present, in patients who have a positive family history, or if polyps are located outside of the colon, either adenomatous polyps or polyps associated with genetic abnormalities are more common.Imaging techniques such as ultrasound and computed tomographic colonoscopy have recently been utilized to identify simple juvenile colonic polyps in children with rectal bleeding in whom there is a high index of suspicion. Colonoscopy with polypectomy is still required for histologic evaluation and resection of the polyp. There have been significant advances in genetic testing and management of hereditary gastrointestinal cancer syndromes with onset in childhood or adolescence that may ultimately reduce long-term morbidity and mortality. In addition to enhanced gastrointestinal and extraintestinal malignancy screening for affected individuals, specific gene mutations within a given condition such as adenomatous polyposis coli may predict clinical course and timing of specific interventions such as colectomy. In other conditions such as phosphatase and tensin homolog hamartoma tumor syndrome, phenotype may not be predicted by genotype.Pediatricians, pediatric gastroenterologists, and adult gastroenterologists caring for children should understand how to differentiate benign polyps in the pediatric age group from those associated with a higher risk of complications including recurrence risk and risk of development of intestinal or extraintestinal malignancy. Recent advances in genetic testing, as well as development of consensus guidelines, are key in the identification, screening, and follow-up of children and adolescents with polyposis syndromes.

Background & Aims: Up to 30% of patients with Crohn's disease (CD) require surgery within the first 5 years from diagnosis. We investigated the recent risk of bowel surgery in an inception cohort of pediatric patients with CD and whether early use of biologics (tumor necrosis factor antagonists) alters later disease course. Methods: We collected data from the Pediatric Inflammatory Bowel Disease Collaborative Research Group registry on 1442 children (age, ó16 y) diagnosed with CD from January 2002 through December 2014. Data were collected at diagnosis, 30 days following diagnosis, and then quarterly and during hospitalizations for up to 12 years. Our primary aim was to determine the 10-year risk for surgery in children with CD. Our secondary aim was to determine whether early use of biologics (

Children inevitably swallow foreign material accidentally or intentionally. Each type of ingestion carries their own set of risks and complications, short and long term, some requiring immediate attention while others close monitoring. Alkalotic household cleaning products and lithium button batteries are increasingly common and damage the esophagus quickly. While many toys with rare-earth metals are banned, they are already present in many households and can cause necrosis of bowel that is between the magnets. This article reviews the incidence and assessment along with current literature to provide guidelines for management of pediatric patients with suspected caustic or foreign body ingestion.

Foreign body ingestions are common in pediatric patients and represent a challenge for the pediatric endoscopist. The most common objects ingested by children in the United States are coins, although toys and batteries account for a significant fraction of ingestions. The timing of and requirement for endoscopy is based on the type of foreign body ingested, its location, and the presence or absence of symptoms. In some cases, ingested foreign bodies require urgent removal even in asymptomatic patients. This is the case, for example, with esophageal batteries. In smaller pediatric patients, the size of the foreign body is an important factor in determining the timing and requirement for endoscopy, and the management may differ as compared with adults. Areas of anatomic narrowing or disease may be an underlying reason why a foreign body becomes lodged, and endoscopists are cautioned against blindly advancing a foreign body or meat impaction distally. Various techniques and endoscopic equipment are used to remove ingested foreign bodies in children, including specialized forceps, baskets, snares, nets, and friction fit adapters, and these are discussed.

Budesonide (BUD) is being used in pediatric Crohn disease (CD) because it is believed to have the potential to reduce corticosteroid-related toxicity; however, few data are available describing its use. The aim of the present study was to describe BUD use in an inception cohort of pediatric patients with CD.Data were derived from the prospective Pediatric IBD Collaborative Research Group Registry established in 2002 in North America. Use of BUD in children with CD was examined.BUD was used in 119 of 932 (13%) of children with newly diagnosed CD, with 56 of 119 (47%) starting BUD ≤ 30 days of diagnosis (26/56 with ileum and/or ascending colon [IAC] disease). BUD was used as monotherapy (9%), in combination with 5-aminosalicylates (77%), or in combination with immunomodulators (43%). Forty-three percent (24/56) went on to receive conventional corticosteroid at some point following their first BUD course. For the 63 of 119 (53%) who started BUD beyond the diagnosis period, 51 of 63 (81%) also received prednisone, with BUD used as a means of weaning from prednisone in 17 of 63 (27%). Patients with IAC disease who received BUD ≤ 30 days of diagnosis were just as likely to have received conventional corticosteroids by 1 year as were those who did not receive BUD ≤ 30 days of diagnosis. Two-thirds (77/119) of patients received BUD for ≤ 6 months.BUD is being used among pediatric patients newly diagnosed as having CD, although the majority does not have disease limited to the IAC. BUD monotherapy was rare, and further data are required to better define the role of BUD in the treatment of pediatric CD.

Despite little supporting data, thiopurine use is common in pediatric ulcerative colitis (UC). Our aim was to determine outcome following thiopurine use in a multicenter inception cohort of children diagnosed with UC.Data were obtained from a prospective observational study of newly diagnosed children16 years of age. Data are recorded at diagnosis, 30 days, and quarterly. Patients are managed by physician dictates not protocol. Disease activity is classified by physician global assessment. The primary outcome was corticosteroid (CS)-free inactive UC at 1 year following thiopurine initiation without the need for rescue therapy (infliximab, calcineurin inhibitors, or colectomy).Of 1,490 patients in our registry, 394 have UC (mean age at diagnosis 11.3±3.7 years); 197 (50%) received thiopurine (49% ≤3 months from diagnosis). Also, 84% were receiving CSs and 60% 5-aminosalicylates at thiopurine start. Of the 197 patients, there was insufficient follow-up (41), previous or concomitant use of infliximab (16), or calcineurin inhibitor (7), leaving 133 patients evaluable at 1 year. Of these, 65 (49%) had CS-free inactive UC without rescue therapy. CS-free inactive disease at 1 year after initiating thiopurine was not affected by starting thiopurine ≤3 months vs.3 months from diagnosis, gender, age, or concomitant treatment with 5-aminosalicylates. Kaplan-Meier analysis showed that the likelihood of remaining free of rescue therapy in the thiopurine-treated patients was 73% at 1 year.Approximately 50% of children with UC starting thiopurine without previous or concomitant biologic or calcineurin inhibitor therapy have CS-free inactive disease 1 year later without the need for rescue therapy.

Little is known regarding the natural history of autoimmune hepatitis in children. The aims of this longitudinal cohort study were to determine the long-term prognosis of children with autoimmune hepatitis and to determine the effect of cirrhosis at presentation on survival.Thirty-three children with autoimmune hepatitis who were seen at our institution over a 25-year period were studied retrospectively.The median age of diagnosis was 12.9 years (2.7-18.1) with a female predominance of 3:1. Liver biopsies showed cirrhosis in 18 (55%) patients at time of diagnosis. Patients with cirrhosis at baseline had a similar 10-year survival 85% (70-100%) to those without cirrhosis 75% (49-100%) (p=0.97). The overall survival was significantly lower than the expected in the age- and gender-matched U.S. population (log-rank test; p0.001). In Cox regression models, weight loss (p=0.037), baseline elevated bilirubin (p=0.028), prolonged International Normalized Ratio (INR) (p=0.013), and positive LKM-1 antibodies (p=0.007) were associated with shorter survival.AIH in children is associated with a significant shorter survival rate than the expected in the general population. Cirrhosis on initial liver biopsy does not seem to impact long-term survival in children with AIH.

Background: Checkpoint inhibitor blockade, designed to activate antitumor immune cells, is gaining enthusiasm as a potential treatment modality for patients with brain tumors. However, adjuvant therapies aimed at killing tumor (i.e., chemotherapy) or reducing tumor-related edema (i.e., corticosteroids) are often cytotoxic to lymphocytes. Yet, whether tumor-specific T cells are harmed during corticosteroid treatment is not known. Methods: The effects of dexamethasone on healthy donor T cells was tested in vitro for T cell proliferation, cell cycle analysis, glucose uptake, transcriptional changes, and protein expression. The effects of dexamethasone and CTLA-4 antibody blockade were tested in vivo using the GL261 murine glioblastoma model. Results: Here we show that dexamethasone blocks proliferation of naïve human T cells but not memory T cells. We find that dexamethasone inhibits early stages of T cell proliferation by impairing CD28-mediated cell cycle entry. Dexamethasone induced a fourfold increase in surface CTLA-4 during T cell stimulation, and neutralizing CTLA-4 with ipilimumab overcame the dexamethasone-induced blockade of cell cycle entry in vitro. Further, CTLA-4 blockade in combination with dexamethasone provided a survival benefit in vivo to mice bearing orthotopic GL261 brain tumors. Intriguingly, early dexamethasone treatment afforded the greatest survival advantage Conclusions: These findings shed light on the T cell-specific effects of dexamethasone and suggest that antigen-experienced T cells are resistant to anti-proliferative effects of corticosteroids. These findings have important implications for patients receiving immune therapy who may benefit from the anti-inflammatory properties of dexamethasone. Citation Format: Amber J. Giles, Marsha-Kay N.M. Hutchinson, Heather Sonnemann, Caitlin M. Reid, Jinkyu Jung, Wei Zhang, Hua Song, Rolanda Bailey, Dionne Davis, Deric M. Park, Mario Roederer, Mark R. Gilbert. Ipilimumab protects T cells from the antiproliferative effects of dexamethasone [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr A11.

PURPOSE OF REVIEW: The purpose of this review is to outline the current epidemiology, mechanism of injury, clinical manifestations, management and long-term complications of caustic ingestions in pediatric patients. RECENT FINDINGS: Recent data suggest that more than 200,000 exposures to household or industrial cleaning products occur annually in the United States. It is difficult to determine what fraction of these exposures represents caustic ingestions. Caustic ingestions occur most commonly in children less than age 6 years. Because of the accidental nature of the ingestions, the case fatality rate for pediatric patients is significantly less than that of adolescents and adults. Despite laws to limit the concentration of household cleaning products, farm and industrial products and products stored in nonoriginal containers represent a significant source of caustic agents. Endoscopy remains the preferred method of staging injury. In children the absence of symptoms does not predict lack of relevant injury. However, the presence of three or more symptoms is associated with a high likelihood of significant injury. Long-term complications in pediatric patients may be severe and include esophageal cancer. SUMMARY: Caustic ingestions remain a significant cause of pediatric morbidity in the United States and abroad. Endoscopy is the primary method of staging injury following a caustic ingestion. Extent of injury at initial evaluation remains the best predictor of morbidity and mortality in pediatric patients following an accidental caustic ingestion. Language: en

Objectives: Capsule retention is a potential complication of capsule endoscopy (CE). The aims of our study were to determine the incidence of capsule retention in pediatric patients undergoing CE and to identify potential risk factors for capsule retention. Materials and Methods: We performed an institutional review board-approved retrospective chart review of pediatric patients undergoing CE studies at a single center. Data collected included patient age, sex, prior diagnosis of inflammatory bowel disease (IBD), CE indication, prior small bowel series results, study result, and complications. Results: Two hundred seven CE procedures were performed in pediatric patients during the study period. Capsule retention occurred in 3 (1.4%) of the 207 studies. All 3 patients had known Crohn disease (CD). The risk of capsule retention in pediatric patients with known IBD was 5.2% (3/58). The risk of capsule retention for patients with suspected IBD and all other indications was 0%. If small bowel disease was identified on upper gastrointestinal series in patients with known CD, then the risk of capsule retention was 37.5% (3/8). Only 7 patients with known IBD had a body mass index (BMI) below the 5th percentile. Of these 7 patients, 3 (43%) had capsule retention. Conclusions: Red flags for potential CE retention identified in our study include known IBD (5.2% retention risk), previous small bowel follow-through demonstrating small bowel CD (37.5% retention risk), and BMI