2.11 FAK Inhibition Decreases Stemness and Tumorigenicity of Tumor Initiating Cells in Neuroblastoma

Posted on January 18, 2018

L. Stafman1, E. Garner1, J. Aye1, A. Williams1, J. Stewart1, K. Yoon1, K. Whelan1, E. Beierle1  1University Of Alabama at Birmingham,Birmingham, Alabama, USA

Introduction:
Neuroblastoma (NB) is the most common extracranial solid tumor of childhood and despite aggressive therapies, over 50% of patients with high risk tumors will suffer disease relapse. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase present in aggressive NB. Tumor initiating cells (TICs) are cancer cells with stem cell-like properties thought to be responsible for tumor recurrence and chemoresistance. We previously demonstrated that FAK inhibition decreased CD133 expression and tumorsphere formation, both markers of TICs, in NB patient-derived xenografts (PDXs). We hypothesized that targeting FAK would decrease stemness and tumorigenicity in NB TIC population.

Methods:
Cells from two human NB PDXs (COA3, COA6) were treated with the FAK inhibitors 1,2,4,5-benzenetetraamine tetrahydrochloride (Y15) or PF-573,228 (PF). Expression of TIC markers, Sox2, Oct4, and Nanog, were assessed by immunoblotting. Cells were separated by CD133 surface expression using microbeads to obtain TIC (CD133-enriched) and non-TIC (CD133-depleted) populations. Tumorsphere formation assays were performed. Invasion was evaluated using Transwell inserts. Cell cycle analyses were performed by flow cytometry. Student’s t-test, extreme limiting dilution analysis, and χ 2 statistics were used with mean ± standard error of the mean reported and p ≤  0.05 significant.

Results:
FAK inhibition with PF or Y15 significantly decreased expression of the TIC markers Sox, Oct4, and Nanog in NB PDXs. Additionally, treatment with PF or Y15 decreased tumorsphere formation in both TICs and non-TICs (p<0.01). Invasion was significantly decreased with FAK inhibition in both TIC (98% ± 2% decrease with 5 μ M PF, 86% ± 11% decrease with 5 μM Y15) and non-TIC (96% ± 1% decrease with 5 μM PF, 62% ± 9% decrease with 5 μM Y15) populations. FAK inhibition with both small molecules resulted in significantly decreased invasion in both the TIC and non-TIC cell populations. FAK inhibition also led to cell cycle arrest with significant increases in G1 and decreases in S phase of the cell cycle in both TICs and non-TICS (Figure).

Conclusion:
Inhibition of FAK with small molecule inhibitors decreased expression of TIC markers in human NB PDXs. NB TICs (CD133-enriched cells) were not immune to FAK inhibition and exhibited decreased tumorsphere formation, invasion, and cell cycle arrest similar to their non-TIC (CD133-depleted) counterparts. These findings suggest that FAK supports the NB TIC phenotype and targeting FAK in this cell population may be an important therapeutic strategy to decrease NB chemoresistance and relapse. 
 

2.08 Fetal Lung Transcriptome Patterns in an Ex Vivo Compression Model of Diaphragmatic Hernia

Posted on January 18, 2018

Z. D. Fox1,2, G. Jiang2, K. A. Walker2, K. Ho3, A. P. Liu3, S. M. Kunisaki1,2  1University Of Michigan Medical School,Ann Arbor, MI, USA 2Michigan Medicine,Pediatric Surgery Section, Department Of Surgery,Ann Arbor, MICHIGAN, USA 3University Of Michigan,Mechanical Engineering,Ann Arbor, MICHIGAN, USA

Introduction: The molecular mechanisms associated with potentially lethal pulmonary hypoplasia and pulmonary hypertension in congenital diaphragmatic hernia (CDH) remain poorly understood. Periostin (POSTN) has been shown to be an important stress response molecule during the saccular stage of lung development and is a critical regulator of alveolar septation in association with α-smooth muscle actin (SMA) myofibroblasts. This study employed an ex vivo model to determine whether mechanical compression affects POSTN and other pulmonary transcripts during fetal CDH lung development.

Methods: Sprague-Dawley dams were gavaged with nitrofen (100 mg) at E9.5 gestation to induce fetal CDH pulmonary hypoplasia. Whole fetal rat lungs from nitrofen-exposed and control (vehicle only) dams at E15.5 were explanted and cultured ex vivo in customized chambers under static mechanical compression (0.2 or 0.4 kPa, n=8/group) for 12 hrs to mimic physiologic compression forces that occur in CDH in vivo. Lungs were evaluated for mesenchymal (POSTN, SMA, TGF-β) and epithelial (SP-C) expression by qPCR and immunohistochemistry (IHC). Statistical comparisons normalized to lungs at 0 kPa were made by analysis of variance with significance set at p<.05.

Results: Control lungs exposed to 0.2 and 0.4 kPa showed significant increases in POSTN expression (1.79±.10; 2.12±.39, respectively; both p<.001). In contrast, compressed nitrofen-exposed lungs revealed significant decreases in POSTN expression (0.4 kPa: 0.67±0.15, p<.001). IHC confirmed  increased presence of POSTN in control lungs, but not in nitrofen-exposed lungs (Figure). TGF-β was significantly increased in nitrofen-exposed lungs (1.39±.12, p=.045) and control lungs under increased compression (0.2 kPa: 1.33±.08, p=.036). Compression alone did not alter SMA expression in control lungs, but nitrofen-exposed lungs revealed significantly increased SMA at both 0.2 and 0.4 kPa (2.04±.15; 2.22±.11; both p<.001, respectively). Control lungs exposed to 0.4 kPa showed significant increases in SP-C (1.20±.20, p<.001). Conversely, nitrofen-exposed lungs had a significant reduction in SP-C expression at 0.2 and 0.4 kPa (0.53±.04, p<.01; 0.69±.23, p<.001; respectively).

Conclusion: Collectively these data suggest that mechanical compression induces a distinct transcriptome pattern within the nitrofen CDH fetal lung characterized by downregulation of POSTN and SP-C and upregulation of TGF-β and SMA. This ex vivo compression system may serve as a novel functional platform to better understand the impact of mechanical stress on the complex genetic control of matricellular dynamics during CDH lung development.

2.09 Lipocalin-2 Increases Weight Loss, Intestinal Permeability and Mortality in a Short Bowel Model

Posted on January 18, 2018

S. M. Alaish1, D. R. Shores2, A. Zhang1, M. Wang1, H. Jia1, W. Fulton1, C. Sodhi1, D. J. Hackam1  1Johns Hopkins University School Of Medicine,Pediatric Surgery/Surgery,Baltimore, MD, USA 2Johns Hopkins University School Of Medicine,Pediatric Gastroenterology/Pediatrics,Baltimore, MD, USA

Introduction: Short bowel syndrome (SBS) causes an intestinal dysbiosis and increased intestinal permeability which can lead to sepsis and even death. As an iron-sequestering protein in the antibacterial innate immune response, Lipocalin-2 (LCN2) prevents bacterial iron uptake and controls bacterial growth. In a mouse model, we have previously shown that LCN2 mRNA and protein increase in the intestine following 75% small bowel resection.  We now hypothesize that LCN2 may serve as a potential defense mechanism in the intestine against the dysbiosis that occurs in SBS and tested this by evaluating the outcome of LCN2-/- mice exposed to a model of SBS.

Methods: Under an ACUC-approved protocol, we performed a 75% small bowel resection (SBR) on both C57BL/6J (n=6) and LCN2-/- (C57BL/6J background) (n=6) mice, which mimics the extensive resection seen in SBS patients. Sham-operated C57Bl/6J (n=6) and LCN2 -/- (n=6) mice served as controls. Mice were weighed daily. On postoperative day 6, the mice were injected with BrdU.  24 hours later, the mice were gavage fed FITC-Dextran, serum was collected, intestinal permeability was assayed, and the mice then underwent euthanasia. Intestinal tissue was collected and processed for staining.  Statistical analysis was performed using ANOVA with p<0.05 considered significant.

Results:LCN2 -/- mice exposed to SBR lost significantly more weight than shams (p<0.05) but significantly less than wild-type SBR mice (p<0.05). Similarly, intestinal permeability was increased in LCN2 -/- SBR mice as compared to shams (p<0.05) but less than wild-type SBR mice (p<0.05), while enterocyte proliferation was similar for the LCN2-/- SBR mice and the wild-type SBR mice. Strikingly, survival was significantly greater in the LCN2-/- SBR mice as compared to the wild-type SBR mice (87.5% vs. 56.1%, p<0.05), suggesting that in disagreement with our original hypothesis, the presence of LCN2 exerts pro-weight loss and pro-permeability effects that contribute to increased mortality, and which are reversed in LCN2 -/- mice.

Conclusion:Contrary to our hypothesis, LCN2 exerts surprising, deleterious effects on gut permeability and weight loss in mice, contributing to increased mortality, in a mouse model of short bowel resection.  Such effects may reflect the pro-inflammatory role of LCN2 which has been observed in other systems, and suggest that LCN2 inhibition may offer a novel therapeutic approach for gut protection in children with SBS.

 

2.06 An Organotypic Spinal Cord Slice Culture Model of Fetal Myelomeningocele Hydrogel Patch Repair

Posted on January 18, 2018

K. A. Walker1, G. Jiang1, J. Di Bernardo1, K. O’Shea3, L. D. Shea4, S. M. Kunisaki1  4University Of Michigan,Biomedical Engineering,Ann Arbor, MI, USA 1University Of Michigan (Michigan Medicine),Surgery, Pediatric Surgery Section,Ann Arbor, MI, USA 3University Of Michigan (Michigan Medicine),Cell And Developmental Biology,Ann Arbor, MI, USA

Introduction:  Fetoscopic repair is an emerging surgical option to help preserve neural function in prenatally diagnosed myelomeningocele (MMC). However, the exact in utero repair strategy that would facilitate maximal regeneration of damaged neural tissue remains unknown. Our laboratory has recently developed a hydrogel-based surgical patch to facilitate tissue coverage during fetoscopic MMC repair. The purpose of this study was to determine whether an organotypic slice culture (OSC) model of fetal MMC could be established to study the effects of patch repair on underlying spinal cord development.

Methods:  Sprague-Dawley pregnant dams were gavaged with retinoic acid (60 mg/kg) at E10 gestation to induce fetal MMC. E21 rat pup spinal cords were longitudinally sectioned (400 microns) and cultured ex vivo in the presence of fibrin hydrogels (40 mg/mL) loaded with 6×105 rat dorsal root ganglion cells (group 1, n=10). Sections exposed to acellular fibrin hydrogels were used as controls (group 2, n=10). Neurotrophin expression, cell proliferation, apoptosis, and neural phenotype were subsequently analyzed at E21+7 and E21+14 by phase microscopy, qPCR, ELISA, and immunohistochemistry (IHC). The optical density (OD) of IHC sections was quantified using ImageJ. Statistical comparisons were by the unpaired t-test with significance set at p<0.05.

Results: Fetal OSCs were successfully cultured for up to 14 days while maintaining morphological integrity and demonstrating progressive neurite extension. qPCR showed upregulation of several neurotrophic genes, including neurotrophin-4/5 (NT4/5), ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 compared to native control tissues. ELISA demonstrated an increase in NT4/5 over time whereas BDNF and CNTF decreased over time. IHC (Figure) showed no significant differences between group 1 and group 2 in terms of proliferation and apoptosis based on Ki67 and Cas3 expression, respectively. The neural progenitor marker, Nestin, was significantly increased in group 1 compared to group 2 at E21+7 (mean OD: 0.60±0.14 vs. 0.33±0.16, p<0.03), but these levels were similar at E21+14 (mean OD: 0.50±0.06 vs. 0.53±0.07, p=0.38). At both time points, there were no significant differences with respect to astrocyte (GFAP) and neuronal (beta-III tubulin, NeuN, and MAP2) differentiation with the damaged spinal cord. 

Conclusion: For the first time, this study demonstrates a novel ex vivo OSC model that can be sustained for a sufficient period of time to study the impact of patch repair on MMC neural tissue. Further work utilizing this organotypic approach to evaluate the effects of biomaterials, cells, and growth factors on MMC spinal cord development is warranted.

 

2.07 The In Vitro and In Vivo Effects of Granulocyte Colony Stimulating Factor on Metastatic Neuroblastoma

Posted on January 18, 2018

W. E. Barry1, G. Asuelime1, L. Wang2, E. S. Kim1  1Children’s Hospital Los Angeles,Pediatric Surgery,Los Angeles, CA, USA 2Children’s Hospital Los Angeles,Pathology,Los Angeles, CA, USA

Introduction: We have previously described a small subpopulation of neuroblastoma (NB) cancer stem cells (CSCs) that express the granulocyte colony stimulating factor (G-CSF) receptor. In previous studies, the ligand G-CSF leads to increased primary tumor growth and increased metastasis in mice, but the impact of G-CSF on established metastatic disease is not fully understood. Despite these concerns, G-CSF is commonly administered to children with high-risk metastatic NB.  We therefore hypothesize that G-CSF will lead to a more aggressive phenotype in vitro and decreased survival in a murine NB metastatic model of minimal residual disease (MRD).

Methods: Metastatic cell lines from the liver and bone marrow of NSG mice were derived after orthotopic implantation of the human parental NB cell lines (CHLA-255 and SH-SY5Y).  DIMSCAN cell viability, colony formation and Matrigel invasion assays were performed using these metastatic cell lines with and without the addition of G-CSF. In vivo, 1 million cells (SH-SY5Y) were injected into the renal capsule of 14 NSG mice. The primary tumor was resected on post-injection day 7 and the mice were randomly assigned to either receive treatment of G-CSF (n=7) or no treatment (n=7). Mice receiving G-CSF were given 250ug/kg/day intraperitoneal for 14 days.  Metastatic disease was assessed with bioluminescent imaging and confirmed with histopathology.  Survival was analyzed using log-rank analysis, metastasis with Fisher’s exact test, and in vitro studies with Student’s t-test. 

Results: In vitro, increasing doses of G-CSF had no significant impact on cell viability by DIMSCAN assay, nor did G-CSF increase the invasive capacity of metastatic NB cells by matrigel invasion assay. Using a colony formation assay, the addition of G-CSF was found to increase colony counts in parental neuroblastoma cells (SH-SY5Y) and bone marrow metastatic cells compared to control (p≤0.01). In vivo, the burden of metastatic disease at week 4 by bioluminescent imaging, as well as the post-necropsy burden of liver disease were increased in mice treated with G-CSF, however this did not reach statistical significance (p=0.2 for both). Overall survival was significantly decreased in the mice treated with G-CSF (Figure).

Conclusions: In vitro, G-CSF does not appear to impact cell viability or invasiveness of metastatic NB cells but may have a modest effect on anchorage-independent growth, a hallmark of carcinogenesis. In vivo, G-CSF leads to decreased survival in a metastatic neuroblastoma mouse model of minimal residual disease. Further studies are necessary to validate and fully elucidate the potential etiologies of these findings to determine the safety of its use in patients with high-risk NB.

2.05 Alum Pretreatment Improves Survival from Murine Neonatal Sepsis and Alters Levels of IL-10 and pAKT

Posted on January 18, 2018

R. B. Hawkins1, J. C. Rincon1, S. L. Raymond1, R. Ungaro1, J. L. Wynn1, L. L. Moldawer1, S. D. Larson1  1University Of Florida College Of Medicine,Department Of Surgery,Gainesville, FLORIDA, USA

Introduction: Sepsis is a leading cause of morbidity and mortality in the neonatal population. Neonates have attenuated immunity compared to adult counterparts, but this difference is poorly understood. Interleukin-10 (IL-10) has emerged as an important anti-inflammatory cytokine that is associated with impaired neutrophil function and increased mortality from neonatal sepsis. Aluminum hydroxide (alum) is often used as an adjuvant in pediatric vaccines, but its use as an immune stimulant alone has not been well described. We have previously demonstrated that alum pretreatment improves survival from polymicrobial sepsis in neonatal mice. We sought to better understand the mechanism of alum’s survival benefit through its effects on IL-10 and phosphorylated protein kinase B (pAKT).

Methods:  Wild-type neonatal mice aged 5-7 days were used for experiments. Control mice received a sham injection while alum-pretreated mice received a subcutaneous injection of 50 µg alum 24 hours prior to induction of sepsis or sacrifice. 24 hours later, some mice were sacrificed and blood samples were obtained to evaluate for baseline cytokine changes associated with alum pretreatment. Sepsis was induced using the cecal slurry method. Mice were sacrificed at 6, 18, and 24 hours after induction of sepsis and blood and spleen samples were obtained. IL-10 cytokine analysis was performed using a customized mouse cytokine magnetic bead Milliplex® panel. pAKT levels were determined from splenic tissue at 6 and 24 hours following induction of sepsis using a Western blot assay.

Results: Neonatal mice who received alum pretreatment had a significant decrease in circulating IL-10 levels compared to non-treated counterparts at baseline. After induction of sepsis, both alum-pretreated and non-treated groups had significant elevation in IL-10 levels. There was no significant difference in circulating IL-10 levels between non-treated and alum-pretreated mice at 6, 18, and 24 hours after induction of sepsis. pAKT levels were significantly elevated at 6 and 24 hours after induction of sepsis. Alum pretreatment caused significantly less elevation of pAKT at 6 and 24 hours following induction of sepsis.

Conclusion: IL-10 is an important anti-inflammatory cytokine that may contribute to a diminished innate immune response in neonates. Alum pretreatment is associated with decreased circulating IL-10 levels at baseline, which may be partially responsible for alum’s survival benefit in the cecal slurry model. The PI3K-AKT pathway is involved in modulation of circulating IL-10 levels, and our data suggest that alum pretreatment limits production of pAKT following sepsis. These data suggest a possible therapeutic role for alum or other immunomodulators to affect the PI3K-AKT and IL-10 pathways to improve survival from neonatal sepsis.
 

2.04 Hydrogen Sulfide Donor GYY4137 Protects The Intestines Following Injury via eNOS Dependent Pathways

Posted on January 18, 2018

N. A. Drucker1, A. R. Jensen1, M. J. Ferkowicz1, T. A. Markel1  1Indiana University School Of Medicine,Pediatric Surgery,Indianapolis, IN, USA

Introduction: Intestinal ischemia in adults and necrotizing enterocolitis (NEC) in premature infants are both devastating intestinal conditions with poor outcomes.  GYY4137 is a long-acting hydrogen sulfide (H2S) donor, which may be protective against intestinal injury in these conditions.  We hypothesized that administration of GYY4137 would improve mesenteric perfusion, reduce intestinal injury, and reduce the inflammatory response in intestinal I/R injury and NEC, and that these benefits would be mediated through endothelial nitric oxide-dependent pathways.

Methods:  Adult male C57Bl/6 wild type (WT) and eNOS knockout (eNOSKO) mice underwent superior mesenteric artery occlusion for 60 minutes.  Prior to abdominal closure, 50mg/kg GYY4137 or PBS vehicle was administered intraperitoneally.  In separate groups, NEC was induced in WT and eNOSKO pups via maternal separation, formula feeding, enteral lipopolysaccharide, and intermittent hypoxic and hypothermic stress.  Pups received daily intraperitoneal injections of 50mg/kg GYY4137 in 10µL vehicle.  Laser Doppler Imaging was used to assess mesenteric perfusion in the adult animals at baseline and 24 hours post-ischemia.  Pups were assessed at baseline and P9.  After euthanasia, the terminal ileum of each animal was fixed, paraffin embedded, sectioned, and stained with H&E.  Sections were blindly graded using published injury scores.  Intestinal tissue was homogenized and cytokines measured by ELISA.  Data were compared using Mann-Whitney, and p-values <0.05 were significant.

Results: After I/R injury (A) and NEC (B), GYY4137 improved perfusion in WT mice compared to vehicle, but this effect was lost in the eNOSKO animals.  Histologic injury followed a similar pattern with reduced intestinal injury in WT mice treated with GYY4137, and no significant improvement in the eNOSKO group.  Cytokine expression after GYY4137 administration was altered by the ablation of eNOS in both I/R injury (C) and NEC (D).  Significant differences were noted in IL-6, IP-10, and VEGF in the NEC pups, but only in IP-10 in the adult mice after I/R.  

Conclusion: GYY4137, a long-acting donor of H2S, has potential as a therapeutic compound for intestinal ischemia.  It improves mesenteric perfusion and intestinal injury after ischemia and NEC, and these benefits appear to be mediated through endothelial nitric oxide dependent pathways.  

 

2.02 Macrophage-promoted Invasion of Osteosarcoma Requires Receptor-interacting Protein Kinase 2 (RIPK2)

Posted on January 18, 2018

C. Maloney1,2, M. P. Kallis1,2, M. C. Edelman4, M. Symons3, B. M. Steinberg1,3, S. Z. Soffer2,3  1Feinstein Institute Of Medical Research,Elmezzi School Of Molecular Medicine,Manhasset, NY, USA 2Hofstra Northwell School Of Medicine,Surgery,Manhasset, NY, USA 3Feinstein Institute Of Medical Research,Karches Center For Oncology And Cell Biology,Manhasset, NY, USA 4Hoftstra Northwell School Of Medicine,Pathology And Laboratory Medicine,Manhasset, NY, USA

Introduction: We have previously shown that macrophages promote osteosarcoma (OS) invasion in vitro which is inhibited by gefitinib, an epidermal growth factor receptor (EGFR) inhibitor (p<0.001). In vivo, gefitinib reduces both the incidence of gross lung metastasis and the metastatic outgrowth of pulmonary micro-metastases. However, EGFR is neither present on macrophages nor on OS cells, suggesting a non-EGFR mechanism for these findings. An alternative target of gefitinib, RIP2K, is expressed in antigen-presenting cells and plays a central role in NOD-mediated innate immune responses and NF-κB activation. The role of RIPK2 in tumor-associated macrophages has not been studied. We investigated the role of RIP2K in macrophage-promoted OS invasion in vitro and the effect of gefitinib on pulmonary macrophage phenotype in vivo

Methods: In vitro, mouse OS cells (K7M2) were incubated ± conditioned media from wild type or RIPK2 knock-out mouse bone marrow-derived macrophages (BMDMs) ± the RIP2K inhibitor OD36 (5.3nM).  Invasive capacity was assessed utilizing 3D-invasion assays. In vivo, K7M2 cells were implanted into the tibia of BALB/c mice (n=6). Mice were treated with either control or gefitinib-impregnated chow beginning 1 week post-implantation. Non-tumor-bearing wild type BALB/c mice were used as controls. Four weeks post-implantation, lungs were harvested and homogenized into a single-cell suspension. The cells were washed, stained with antibodies targeting the macrophage markers CD45, CD11b and F4/80, and MHC II, which is upregulated on pro-inflammatory macrophages, and subjected to flow cytometry. Data was acquired on an LSRFortessa Flow Cytometer (BD Biosciences) and analyzed with FlowJo (FlowJo, LLC).   

 

Results: In vitro, conditioned medium from wild-type BMDMs significantly promoted OS invasion (<0.001) while conditioned medium from RIPK2 knockout macrophages did not.  Conditioned medium from macrophages pretreated with the RIPK2 inhibitor also inhibited macrophage-promoted invasion (p<0.01).  Addition of the inhibitor to tumor cells in the absence of macrophages had no effect on OS invasion (p=0.876). In vivo, macrophages in the lungs of tumor-bearing mice showed decreased MHCII expression, a pro-inflammatory anti-tumor marker, when compared to non-tumor bearing control mice.  Conversely, macrophages from gefitinib-treated tumor-bearing mice displayed an increase in MHCII expression compared to untreated tumor-bearing mice, suggesting that gefitinib suppressed or reversed the polarization of the macrophages. 

Conclusions: Macrophage-promoted invasion of osteosarcoma requires RIPK2 activity. Gefitinib promotes a pro-inflammatory phenotype in pulmonary macrophages and prevents outgrowth of pulmonary metastases in vivo.  Upfront treatment with gefitinib may limit metastatic progression of OS by modulating macrophages via RIP2K inhibition.

 

 

2.03 IL6 Is An Important Paracrine Factor Of USC Mediated Intestinal Protection Following Ischemia

Posted on January 18, 2018

B. S. Morocho1, N. A. Drucker1, J. P. Te Winkel1, M. J. Ferkowicz1, T. A. Markel1  1Indiana University School Of Medicine,Pediatric Surgery,Indianapolis, IN, USA

Introduction: Human umbilical mesenchymal stromal cells (USC) improve survival and mesenteric perfusion following intestinal ischemia.  USCs likely act via the paracrine release of specific key mediators, of which IL-6 may serve an important role. We hypothesized that IL-6 would play a key role in stem cell mediated intestinal protection following ischemia and reperfusion (IR) injury.

Methods: Eight to ten week old C57BL/6J male mice were used: 1) IR + Vehicle, 2) IR + USC, 3) IR + Negative Control siRNA treated USC and 4) IR + IL-6 siRNA treated USC. Mice were anesthetized using isoflurane and a midline laparotomy was performed. Initial perfusion of the small intestine was imaged using laser Doppler imaging. The superior mesenteric artery was then occluded for 60 minute with an atraumatic vascular clamp.  After ischemia, the clamp was removed and intestines allowed to recover.  Immediately prior to closure, mice were injected intraperitoneally with either 250 ul phosphate buffered saline vehicle, or with USC transfected with siRNA as above.  siRNA efficacy was confirmed by RT-PCR.  After 24 hours of recovery, perfusion was reassessed, mice were euthanized, and the intestines were harvested for histological analysis. Tissue blocks were H&E stained and sectioned.  Mucosal injury was assessed and graded by an established injury grading scale.  Perfusion was expressed as percentage of baseline (mean+/-SEM) and analyzed by student’s t test.  Histology was presented as injury score (median and IQR) and analyzed by Mann-Whitney.  P<0.05 was significant. 

Results: IL-6 siRNA effectively knocked down USC IL-6 production.  USCs, as well as USCs transfected with a negative siRNA control significantly increased perfusion (A) and improved mucosal injury scores (B) compared to vehicle following injury (Perfusion: Vehicle 42.49+/-9.28%, USC 78.3+/-8.83, siRNA Negative Control: 77.8+/-4.37,p<0.05; Histology: Vehicle: 3(2.75), USC: 1(0.75), siRNA Negative control: 1(1),p<0.05. USCs transfected with IL-6 siRNA yielded significantly lower mesenteric perfusion and worse mucosal injury scores compared to negative control (Perfusion: siRNA Negative control: 77.8+/-4.37, IL-6 siRNA: 28.4+/-5.84,p<0.05; Histology: siRNA Negative control:1(1), IL-6 siRNA: 3.5(2.25),p<0.05). 

Conclusion: USC mediated intestinal protection was negatively impacted by the decrease in IL-6 production from USCs. IL-6 likely acts in an anti-inflammatory manner, possibly through the membrane bound IL-6 receptor. Further studies are required to delineate the downstream effects of IL-6 during stem cell mediated intestinal protection. 

 

2.01 PROMININ-1 Hepatic Progenitor Cell Ablation Increases Hepatic Fibrosis in Bile Duct Ligation

Posted on January 18, 2018

M. R. Fenlon1,2, J. Xu1, J. Zagory1, K. Asahina2, K. Wang1  1Children’s Hospital Los Angeles,Surgery,Los Angeles, CA, USA 2University Of Southern California,Los Angeles, CA, USA

Introduction:
In Biliary Atresia (BA), post-Kasai hepatoenterostomy survival with native liver inversely correlates with extent of liver fibrosis. We previously demonstrated an expansion of Prom1+ Hepatic Progenitor Cells (HPCs) within areas of developing ductular reactions in the Rhesus Rotavirus (RRV) model of experimental BA (Mavila, Hepatology 2014). Here, the degree of Prom1+ cell expansion correlated with the extent of fibrosis. We also previous demonstrated differential regenerative capacity of Prom1+ HPCs in neonatal mice compared to adult (Zhu, Cell, 2016). Moreover, null mutation of Prom1 leads to decreased ductular reaction and periportal fibrosis in RRV-induced BA (Zagory, unpublished data). Herein, we hypothesized that selective Prom1+ cell ablation is associated with decreases ductular reaction and liver fibrosis in an adult model of cholestasis caused by bile duct ligation (BDL).

Methods:
C57BL6 mice were bred to heterozygosity for both Prom1-Cre and inducible-Diphtheria Toxin Receptor (iDTR). 8-10 week old transgenic mice underwent BDL. Two weeks prior to BDL, tamoxifen was administered to induce cre-recombination in Prom1+ HPCs, resulting in targeted expression of iDTR. 1 week prior to BDL, Diphtheria Toxin (DT) or saline was injected to induce selective ablation of Prom1+ HPCs expressing iDTR. At 5 days post-BDL, whole liver tissue was collected and analyzed for histology and gene expression.

Results:
The extent of ductular reaction following BDL ± DT, as demonstrated by biliary epithelial marker CYTOKERATIN-19 (CK19) immunofluorescence, was comparable. Compared to sham, BDL resulted in increased Sirius red staining indicating increased deposition of excess extracellular matrix, a surrogate marker for liver injury (n = 13). Sirius red staining was greater post-BDL in DT treated mice compared to saline. Quantitative PCR analysis of hepatic fibrosis markers demonstrated trends towards increased fibrosis in BDL mice after DT ablation compared to saline group: α-Smooth Muscle Actin 4.19 vs 5.73, p=0.34; Vimentin 1.77 vs 6.31, p=0.15 (median fold expression of NS BDL and DT BDL groups).

Conclusion:
Contrary to our expected result, selective ablation of Prom1-expressing HPC leads to increased fibrosis following BDL in adult mice. This may be the consequence of differential regenerative capacity of Prom1+ HPC in adults compared to neonates. Further studies are essential to elucidate the functional role of Prom1+ HPC in infants with BA.
 

18.20 A Pilot Study of Surgical Resident Familiarity with Value in Healthcare and Surgery

Posted on January 18, 2018

G. T. Fankhauser1, J. Perone1, P. Roughneen1  1University Of Texas Medical Branch,Department Of Surgery,Galveston, TX, USA

Introduction: Value in healthcare and surgery involves the pursuit of the highest quality outcome for the resources used. This differs from cost-effectiveness which emphasizes pure outcome more than quality. The distinction is subtle but important in the current healthcare paradigm where reimbursement is often tied to outcome and resources are constrained. We sought to assess surgical resident understanding of value and the focus on it during training.

Methods: We constructed an anonymous nine-question survey and distributed it to residents in all surgical specialties at a university teaching hospital. The survey queried resident familiarity with value, its distinction from cost-effectiveness, prior education on value in healthcare, and sentiments on how much focus value should receive in training and in the healthcare system at-large. Resident surgical specialty and year of residency were recorded.  

Results: 61 surveys were completed (84% response). 58% reported being unfamiliar or vaguely familiar with value in healthcare while 42% reported being fairly or extremely familiar with it. 66% reported the belief that value was the same as cost-effectiveness or unfamiliarity with the difference. 40% reported no education on value during residency with 54% reporting some education and only 6% reporting quite a bit of education. 82% of residents reported that there is not enough focus on value during training while 16% felt the amount was about right and 2% felt there was too much focus on value. In regards to the healthcare system at-large, 79% felt that there should be more focus on value and 13% felt the current focus was about right. 8% felt there should be less or no focus on value in the healthcare system at-large. By year of training, residents earlier in their training tended to have received more education on value during medical school(p=NS). Year of training did not correlate to education on value received during residency or thoughts on how much focus value should receive. There was a positive association between familiarity with value and receiving education on value during medical school(p=NS) but not during residency. Feelings toward how much focus value should receive in residency correlated with thoughts on how much focus value should receive in the healthcare system at-large(p=NS). Residents with more education on value in residency were less likely to think there is insufficient focus on value in the healthcare system at-large(p=NS). Receiving education on value and thoughts about how much focus value should receive did not correlate with surgical specialty.

Conclusion: This pilot study shows a gap in education for surgical residents on value in healthcare. Further study is needed on a national scale to assess surgical resident familiarity with value then design a curriculum accordingly. Medical schools are more recently providing education on value in healthcare but there is still a need for more education on value during surgical training.

 

18.17 Evaluating System-Based Financial Knowledge of General Surgery Residents

Posted on January 18, 2018

L. Ferro1, E. Grenn2, C. Muncie2, D. Parrish1,2, L. Boomer1  1VCU Medical Center,Surgery,Richmond, VA, USA 2University Of Mississippi Medical Center,Surgery,Jackson, MS, USA

Introduction: The General Surgery Milestone Project was instituted by the Accreditation Council for Graduate Medical Education (ACGME) in 2015 as a new way to evaluate general surgery residents in their development into independent physicians based on six core competencies. One of these competency areas focuses on “System-Based Practice.” We hypothesized that resident cost knowledge and cost comparisons of various hospital services is poor, and this lack of knowledge affects their competency in regards to some portions of system-based practice.

Methods: The billing departments of two major academic institutions were queried regarding the charges for specific hospital services (cardiology consult, computed tomography (CT) scan of abdomen/pelvis, chest radiograph (CXR), stat complete blood count (CBC), magnetic resonance imaging (MRI) of the cervical spine, magnetic resonance cholangiopancreatography (MRCP), Hepatobiliary Iminodiacetic acid (HIDA), and right upper quadrant ultrasound). In an attempt to keep things standard, the costs were evaluated for uninsured patients. Once these costs were obtained, the general surgery residents were asked in an open ended survey the costs of each of these services. The residents’ responses were grouped and analyzed as a whole.

Results: Fifty-eight general surgery residents (83%) responded to the survey. The data was first evaluated to identify how many respondents could identify the cost of the service within 25% of the actual cost. The percent of residents that were able to name the cost of the service was low throughout (1.7% to 27.5% depending on service), with <10% of respondents being within 25% of the actual cost for cardiology consult, CXR, and CT scan of the abdomen and pelvis.  When the data was evaluated to see if respondents could come within 50% of the actual cost, the results were improved (6.9% to 53.4%).

Conclusion: The results show a significant lack of knowledge of the costs of hospital services among general surgery residents. We believe that increased education in this area would benefit residents as they progress through their training and into their practices. This improvement in resident knowledge may also lead to cost-savings for both patients and hospitals.

 

18.18 Do Residents Know Duty Hour Limits? How Communicating and Interpreting Duty Hours Impacts Compliance

Posted on January 18, 2018

R. R. Love3, A. Dahlke3, L. Kreutzer3, D. B. Hewitt2,3, K. Y. Bilimoria3, J. K. Johnson3  2Thomas Jefferson University,Surgery,Philadelphia, PA, USA 3Northwestern University,Surgical Outcomes And Quality Improvement Center (SOQIC),Chicago, IL, USA

Introduction: The Accreditation Council for Graduate Medical Education (ACGME) recently revised requirements to allow programs and residents the flexibility to establish and adhere to duty hours in a manner that optimizes patient safety, resident well-being, and education.  This study used qualitative research methods to explore Program Directors (PDs), Program Coordinators, and faculty members’ understanding of duty hour regulations and how they communicate those regulations to their residents.

Methods: Semi structured interviews were conducted with a total of 98 general surgery PDs, residents, and attending surgeons from institutions enrolled in the Flexibility in Duty Hour Requirements for Surgical Trainees (FIRST) Trial. Interviewees were asked about their understanding of duty hour regulations and how that information was communicated at their institution. Interviews were recorded, transcribed verbatim, and analyzed thematically using a constant comparative approach. This study was a sub-analysis of a larger study that examined implications of duty hour policies on resident wellbeing.

Results: Several themes related to knowledge of duty hour regulations were identified in our study such as interpreting, communicating, reporting, and compliance. Respondents reported differing levels of knowledge and understanding of duty hour regulations. Communication about duty hours occurs both formally (i.e., official correspondence given to residents and faculty from PDs or Program Coordinators regarding duty hour regulations) and informally (i.e., unofficial discussions of duty hours and implicit expectations among residents or faculty). These communications were thought to have a direct impact on how residents interpret their duty hours and how they report them. Residents who were unable to correctly identify duty hour policies may be more likely to violate those policies, which has an impact on reporting and ultimately compliance to duty hour policies.

Conclusion: Inconsistent communication of duty hours from faculty, PDs, and other residents contributes to a general lack of knowledge regarding ACGME duty hours. If residents are unaware of specific duty hour regulations, then violations seem more likely. Programs should use both formal and informal communication methods to systematically reinforce the message about duty hour regulations.

18.19 Current Trends in Training in the Surgical Management of Acute Appendicitis at a Veteran Affairs Hospital.

Posted on January 18, 2018

M. Ruiz1, S. Huerta1,2  1University Of Texas Southwestern Medical Center,Surgery,Dallas, TX, USA 2VA North Texas Health Care System,Dallas, TX, USA

Introduction:  An open appendectomy used to be one of the most common cases performed by interns and physical exam dictated operative intervention.   We hypothesize that the management of acute appendicitis has drastically changed from these previous practices.    

Methods:  This a retrospective, single institution analysis at the VA North Texas Health Care system (VANTHCS) between 7/05 to 6/17 for all patients who underwent an appendectomy (n=345).  Patients who had an appendectomy for cancer, or incidentally for other reasons were excluded (n=35) as were patients with interval appendectomies (n=16) as well as patients with perforated appendicitis (n=14).  Specific analysis for complications was performed by grouping residents as junior (PGY-1 to 3) and senior (PGY-4 and 5) to determine if there were differences in outcomes.  Using postoperative complications as a dependent variable, univariate analysis was performed using Fisher’s Exact Test for categorical and Student’s T-Test for continuous variables.  Significant variables were included in a multiple logistic regression model with postoperative complications as the dependent variable. Data are expressed as means ± SD and significance was established at a p≤0.05 (two-sided).

Results: There were 280 acute appendectomies during the study period (male=90%; age=46.0±15.7 y.o.; BMI=31.2±18.3 Kg/m2).  Of these, only 8 were performed by interns, PGY-2=30, PGY-3=154, PGY-4=25, and PGY-5=63.  There were 20 minor complications (7.1%) and 30-day mortality was zero. LOS was 3.7±4.3 days. On presentation, 91% of patients had a CT scan and 92% underwent a laparoscopic appendectomy.  Conversion rate was 5%.   Comparing patients operated by senior (PGY-4 and 5) to junior (PGY-1 to -3) residents: patients were of similar age, gender, BMI, ASA, and had similar co-morbid conditions, as well as similar WBC and blood pressure on initial presentation (all p’s > 0.05).  However, OR time was longer (67.2±36.3 vs. 59.7±24.5 min) and EBL was higher (31.4±54.1 vs. 18.5±29.8 mL); both p’s <0.05. Patients also were more likely to have a gangrenous appendix if operated on by senior residents and had a higher heart rate on initial presentation (90.6±19.2 vs. 84.6±16.4; p=0.008). Complications were 10% and 6% for senior and junior residents; respectively (OR 1.1; 95% CI 1.0 to 1.1). 

Conclusion: At the VANTHCS, most patients presenting with suspected appendicitis undergo a CT-scan.  Most cases are performed laparoscopically. Only a small fraction of appendectomies are performed by interns. Senior residents undertake the most difficult laparoscopic cases and, therefore, have more complications.   

 

18.15 Surgical Intern Case Volume Growth in the First Year of Post-graduate Training.

Posted on January 18, 2018

I. A. Woelfel1, D. Strosberg1, S. Abdel-Misih1,2, A. Harzman1,3  1Ohio State University,Department Of Surgery,Columbus, OH, USA 2Ohio State University,Surgical Oncology,Columbus, OH, USA 3Ohio State University,Colon And Rectal Surgery,Columbus, OH, USA

Introduction: The combination of work hour restrictions and a continual increase in the documentation tasks required of all physicians makes clinical efficiency of utmost importance in gaining operative time during the first year of post-graduate training. However, the majority of patient-care responsibilities during the first year of post-graduate training focus on perioperative patient care. While other studies have documented clinical efficiency through discrete observation and recording of all daily activities, we wanted to analyze efficiency by one of its anticipated outcomes: time in the operating room. The aim of this study is to determine if hypothesized increased clinical efficiency throughout the first year of post-graduate training translates into increased time in the operating room.

 

Methods: We completed a retrospective review of all the logged surgical cases from current general surgery residents during their PGY 1 (intern) year at a single large academic training program from 2011-2017. All logged cases are recorded on the General Surgery Operative Log (GSOL) of the Accreditation Council for Graduate Medical Education website by surgical residents using current procedural terminology code (CPT). The cases were categorized according to the month and rotation in which they occurred. A correlation coefficient was calculated to determine the strength of the relationship between month and the operative volume.

 

Results: The ACGME case logs for 25 interns spanning the years 2011 to 2017 were examined, yielding a total 3,751 cases for analysis. We included central line placements, endoscopy, as well as ultrasounds, while excluding intensive care unit and non-operative trauma cases. The number of cases per resident peaked in June of intern year with a median of 18 (range: 3-52) cases; a total of seven more cases than the 11 (range: 1-38) per resident in July.  The average numbers of cases per resident according to month are plotted in Figure 1. (Correlation coefficient = 0.26) Additionally it was found that Surgical Oncology had the highest case volume (Median = 23; range 3-88) while the Surgical Intensive Care Unit rotation had the lowest case volumes (Median = 4; Range 1-22).

 

Conclusion: Our results show that operative experience increases slightly throughout intern year with the highest average case experience in the final month. We hypothesize that this correlates positively with increasing efficiency in non-operative tasks such as documentation and care coordination. Therefore, increased early training in those areas may allow even greater early operative exposure for surgical residents.

 

18.16 Terrorism and the Challenges of Surgical Training in a Third World Country

Posted on January 18, 2018

A. B. Saeed2, F. G. Qureshi1  1UT Southwestern Medical Center,Division Of Pediatric Surgery,Dallas, TX, USA 2Services Institute Of Medical Sciences,General Surgery,Lahore, PUNJAB, Pakistan

Introduction:
Surgical training in low income countries like Pakistan provide opportunities for an extensive patient care experience within a challenging security environment such as terrorist bombings.  Trainees are affected by the event and are also part of the response. This is the experience of senior surgical trainees in Pakistan.
 

Methods:
Services Hospital is an 1160 bed teaching hospital in Lahore, Pakistan and is a receiving center for victims of terrorism. Four surgical chief residents graduate from the program each year. Six surgical, and two orthopedic residents and one junior faculty are on call for emergencies. We evaluated the response our teaching hospital to terrorist events over the last 5 years (2011-2016).  

Results:
There have been three suicide bombings in the last three years with 687 victims; mortality on scene was 152 (22%), 372 patients were transported from the scene, quickly overwhelming our center, and hospital mortality was 76 (20%). Procedures were three chest tubes, 11 laparotomies, two neck explorations and 40 orthopedic cases.  No electronic medical record existsed and patient records were not maintained by a dedicated health information management office. All notes were documented by hand, injuries and outcomes recorded.  Although triage efforts improved over each successive event, information flow from the triage area to the operating room and to concerned family members was often inadequate. Resuscitation efforts were hampered by lack of staff, equipment, training and communication.  Long term outcome data was not available after each event and there was no psychological assessment of either patients or providers. 

Conclusion:
Terrorist events unduly impact our ability to train, learn, educate and provide clinical care. Concerns about our personal safety, our families’ safety and safe transport to the hospital during crisis remain.  As such, events continue to occur, access to dedicated trauma fellowships and courses such as Advanced Cardiovascular Life Support (ACLS), Advanced Trauma Life Support (ACLS), and Advanced Trauma Operative Management (ATOM) will improve care provided.  We will need administrative support to develop better staff and family communication tools, database management and mechanisms to ensure our safety.  Support for our trainees to identify PTSD will be critical. Partnerships with trauma centers across the globe will improve the learning environment and care to the trauma victims of terrorism.
 

18.13 An Interdisciplinary Approach to Surgical Skills Training Decreases Programmatic Costs

Posted on January 18, 2018

M. Snyder1, J. D’Angelo1, J. Bleedorn2, R. Hardie2, E. Foley1, J. A. Greenberg1  1University Of Wisconsin,Department Of Surgery,Madison, WI, USA 2University Of Wisconsin,School Of Veterinary Medicine,Madison, WI, USA

Introduction:
Surgical resident duty hour limitations have necessitated operative skill training outside of the OR. Low-cost box trainers and virtual reality systems are useful for resident training; however, they do not replace surgical skill wet-labs, which produce essential learning outcomes in a more realistic and transferable exercise. Unfortunately, materials and human resource requirements make wet-labs utilizing biologic samples cost prohibitive for many residency programs. To resolve this problem, our General Surgery Residency program collaborated with the Institution’s School of Veterinary Medicine Surgery Residency program to pilot a cost-effective, interdisciplinary, surgical skills curriculum.

Methods:
The General Surgery Residency Program Manager and Program Director initiated a collaboration with the Veterinary Surgery Residency.  PGY2 general surgery residents and veterinary surgery residents participated in monthly joint surgical skills practice sessions. A novel interdisciplinary surgical skills curriculum was implemented that incorporated skills beneficial to both sets of trainees.  A cost analysis was conducted for a monthly surgical skills curriculum servicing both programs independently and compared to the actual costs of the collaborative curriculum.   Quantitative and qualitative data were collected to assess learning outcomes and obtain information on session quality.

Results:
8 general surgery residents and 5 veterinary surgery residents have participated in 9 joint skills sessions, taught by both general surgery and veterinary surgery faculty.  Three of the planned sessions did not occur due to holidays and administrative challenges at the beginning and end of the academic year.  The cost analysis estimated total savings generated by the collaborative to be $33,500.00.  An iterative review of qualitative data suggests that skill sessions reinforce knowledge and reflexivity. Participants also indicate that the collaborative skills sessions are an enjoyable and valuable learning activity.

Conclusion:
The skills curriculum collaborative has proven to be a cost-effective and high quality interdisciplinary pedagogic tool. The partnership allows for mutually-beneficial resource sharing and allowed for the initiation of a surgical skills wet-lab that had previously been unavailable to both groups.  While empirical evidence suggests that this activity supports resident skills acquisition, future research will include systematic assessment of operative skill development.
 

18.14 Surgical Residents Wellbeing and Life Satisfaction: A description of general surgery residents’ lifestyle.

Posted on January 18, 2018

O. O. Osuchukwu1, J. Tieman1, H. McClafferty2, M. Chang1, C. Coverley1, D. Cole1, T. S. Riall1  1University Of Arizona,Department Of Surgery,Tucson, AZ, USA 2University Of Arizona,Arizona Center For Integrative Medicine,Tucson, AZ, USA

Introduction:

A negative impact on lifestyle has been cited as one of the reasons for the declining popularity of general surgery residency and poses a challenge in maintaining general surgery workforce.  While burnout amongst surgical residents has been clearly documented, few studies formally evaluate general surgery residents’ lifestyle habits. Our goal was to describe surgical residents’ lifestyle to guide interventions for improving resident wellbeing. 

Methods:
In July 2016, our General Surgery residency program started the “Energy Leadership Resiliency and Wellbeing Program.” As part of the program, residents took the validated Arizona Lifestyle Inventory. This descriptive study provides information about resident sleep, eating habits, pain, and stress relieving activities.

Results:

49 of 50 general surgery residents participated in the program (PGY1=19, PGY2=8, PGY3=7, PGY4=8, PGY5=7).  28.6% were female, 89.8% were 25-34 years old. 38.1% were married, 11.9% were unmarried but living with partners, and 50% were single. Pain was common with 23.8% reporting pain >3 days/week. 69.8% of residents eat 5 or more fruits and vegetables >3 days/week and 25.6% eat breakfast every day. Caffeine consumption was high, with 66.7% of consuming caffeine 7 days/week. One quarter (25.5 %) of residents in this program slept for 9 hours >3 days/week. Moreover, only 38.1% reported feeling rested after sleep. 44.2% of residents participated in stress reducing activities >3 days of the week; these activities were varied across residents and included time with family, church, meditation, playing video games, fishing, sports (basketball, running, swimming), listening to music, cooking and sleeping. Deep breathing exercises were used by 20.9% of residents >3 days/week. 18.6 % do vigorous activities >3 days/week and 30.2% do moderate activity >3 days/week. The minority of residents (12.2%) was very or completely satisfied with their work-life balance or their health and wellness (24.5%). 

Conclusion:
While some residents maintain healthy lifestyles, the majority does not regularly participate in moderate or vigorous exercise, do not sleep regularly or well, and experience pain regularly. In addition, General Surgery residents are not satisfied with their health behaviors or work-life balance. These data have been used to design interventions to encourage healthy behaviors including physical activity challenges, healthy behavior challenges, and a variety of group activities that can serve to improve support and reduce stress for residents.

18.11 Five-year Audit of Trainee-focused Program for Surgical Management of Peritoneal Dialysis Catheters

Posted on January 18, 2018

V. Kurbatov1, C. Ibarra1, R. Haywood1, P. S. Yoo1  1Yale University School Of Medicine,General Surgery,New Haven, CT, USA

Introduction:
Laparoscopic peritoneal dialysis catheter (PDC) insertion has been determined to be the optimal method for establishing access for peritoneal dialysis. The modality allows direct intra-abdominal visualization and extraperitoneal tunneling, making it ideal for patients with significant obesity or intraabdominal adhesions.  Using a standardized and simplified surgical technique that eschews additional procedures such as omentopexy and extensive lysis of adhesions, we have developed a resident-led consulting service for laparoscopic peritoneal dialysis catheter insertion. Using a reproducible strategy, residents are trained to safely establish PDC access, ensure adequacy of function, and recognize and manage complications of PDCs.  

Methods:
We performed a 5 year retrospective chart review of a single surgeon’s experience supervising the resident-led service, as part of the transplant surgery rotation at a quaternary academic medical center. Under the direct supervision of a single attending surgeon, trainees performed all aspects of pre-operative, operative, and post-operative care.  Demographic and clinical data were collected to evaluate technical outcomes.

Results:
89 patients underwent laparoscopic primary placement of PDC. A 94.3% technical success rate at 60 days was achieved. 1-year and 2-year catheter technical success rates were 92.4% and 91.9%, respectively. 12.5% of patients required a repositioning procedure, obesity and history of previous surgery were more common in this group. Mean time to reposition was 224 days. 11.2% of patients underwent removal of PD catheter after renal transplantation.

Conclusion:
Our experience serves as a model for fostering surgical trainee expertise with laparoscopic peritoneal dialysis catheter insertion and management without sacrificing a high level of quality. Under the close supervision of an attending surgeon, clinical outcomes are comparable or superior to reported rates. Effective training of general surgery residents in laparoscopic peritoneal dialysis catheter insertion with standardized simplified technique is a key means to ensuring laparoscopic placement continues to be standard of care for peritoneal dialysis catheter placement.
 

18.12 How Well Would Digitally Native Surgery Residents Adapt to a Hospital Ransomware Attack?

Posted on January 18, 2018

J. Zhao1, E. Kessler1, C. Cooper1, J. Brewer1, S. Schwaitzberg1, W. A. Guo1  1State University Of New York At Buffalo,Buffalo, NY, USA

Introduction:  A ransomware attack during the spring of 2017 shut down all hospital-wide health information systems at an academic-affiliated tertiary referral and adult level I trauma center for two months. We used this unique opportunity to investigate the adaptability of modern day general surgery residents when faced with an abrupt shutdown of access to electronic medical records (EMR) and internet.

Methods: All surgical residents who had rotated at the affected hospital during the cyberattack were invited to complete a survey about their experience. Participants responded to 15 Likert scale format questions regarding their attitude toward medical record documentation, order placement, communication, and information access during the downtime. Semi-structured interviews were also conducted with 10 residents with representation from all year groups and with 5 attending surgeons to explore the downtime impact on surgical education in greater detail. A grounded theory approach was used to analyze the transcriptions.

Results: A total of 18 residents responded to the survey with a response rate of 85.7%. As shown in the table, face-to-face communication significantly increased, while access to online educational resources significantly decreased during the cyber attack. The ordinal logistic regression model revealed that level of post-graduate years (PGY) was a predictor of stress in daily order placement without an order set (OR 2.55, 95% CI 1.24-5.25, p=0.005).  However, there is no significant association between the PGY level and medical record documentation. Interviews with residents and attendings revealed that surgical residents adapted better than expected to the abrupt loss of EMR access. Recurrent themes were that surgical residents worked excellently as a team, were proactive, and managed their time well at baseline; these skills came to the forefront during the downtime. Furthermore, attendings continued to view surgical residents as competent, since operative ability was gauged exclusive of the EMR.      

Conclusion: Our study demonstrated that surgical residents adapted well to an unexpected shut down of the hospital computer system due to a ransomware attack, despite the necessary increase in face-to-face communication and dearth of online educational resources. Our study refutes the common misconception that digitally-native Millennials lack the adaptability to handle a paper-based system. With the increasing level of cyber security threats in healthcare, preparedness should be included in the GME curriculum.

 

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