73.18 Is the Amputation Rate Higher for Individuals Over 70 Years Old?

Posted on December 22, 2014

C. Rivera1, N. J. Gargiulo1  1North Shore University And Long Island Jewish Medical Center,Vascular Surgery,Manhasset, NY, USA

Introduction:   As average life expectancy has risen, a patients age has become an important factor in the management and outcome of many pathological processes.  This study was done to determine if age plays a role in presentation, management and outcome of peripheral arterial disease i.e. critical limb ischemia (CLI).

Methods:  
This is a prospective review of all patients that presented to our institution with CLI from January 1, 2007 to December 31, 2007. CLI was defined as ischemic rest pain, non-healing ulceration or gangrene (Rutherford Class 4 and 5). All patients underwent conventional arteriography and if possible an endovascular, open or hybrid procedure for limb salvage. Data was analyzed to determine any significant differences in presentation and outcomes in the group of patients under seventy years of age compared to those over seventy years of age. Data points included in the analysis were: Rutherford class, TransAtlantic InterSociety Consensus II (TASC II) classification, types of intervention (open, endovascular or hybrid), in hospital mortality, one-year amputation free survival and rate on re-intervention.

Results:  One hundred and forty eight patients presented with CLI over this one year period. Of these, 82 (55%) were under seventy years old and 66 (45%) were older. The two groups had similar demographics. Patients in the older group were more likely to present with Rutherford class 5 lesions. Both groups had similar rates of TASC II D iliac disease, however older patients had a higher prevalence of TASC II D femoropopliteal disease (56% vs. 37%) and a higher prevalence of TASC II D infrapopliteal disease (66% vs. 52%). Patients in the older group were more likely to be treated with open procedure and had higher postoperative mortality (6.45% vs. 1.21%). One year amputation rate was significantly higher in the older population (15% vs. 6%).  Average primary patency rates in both groups were about 24 months. Rate of re-interventions was similar in both groups (17% vs. 15%).

Conclusion:  Patients over seventy years of age are more likely to present with more severe TASC II D femoropopliteal and infrapopliteal disease. This may be attributed to higher one year amputation rates in this group. Postoperative mortality is also higher in older population. Primary patency and re-intervention rates do not depend on patients’ age. 

 

71.08 Is Routine Patching Necessary Following Carotid Endarterctomy?

Posted on December 22, 2014

C. Rivera1, N. J. Gargiulo1  1North Shore University And Long Island Jewish Medical Center,Manhasset, NY, USA

Introduction:   Routine patching and periodic postoperative duplex have been widely advocated to achieve optimal results after carotid endarterectomy (CEA). The present 21 year single surgeon experience evaluates the long term outcome of CEA with selective patching and without routine postoperative duplex evaluation.
 

Methods:   An IRB approved retrospective review of all CEAs performed by a single surgeon over a 21 year (1984-2005) period. Preoperative imaging studies, operative reports, physical findings, and co-morbid conditions as well as pre- and postoperative medications were evaluated. Patients having undergone follow-up duplexes are the basis for this review. Restenosis was defined as angiographic criteria suggesting an 80% or more diameter reduction requiring re-intervention.
 

Results: Over a 21 year period, 384 CEAs were performed using a selective patch technique depending on gender, internal carotid artery diameter, cardiovascular risk factors, and preoperative arteriogram. Eighty (20.8%) patients had duplexes performed at this institution as part of their regular follow-up. The remaining 304 patients had clinical follow-up on a yearly basis. Ten of eighty (12.5%) had prosthetic or vein patch closure and seventy of eighty (87.5%) underwent primary closure. The mean follow-up was 49.5 months with a range of 1 to 237 months. Restenosis in the patch group was zero of ten (0%). Sixty-six of seventy (94.2%) patients of the primary closure group did not show any evidence of restenosis. Four patients (5.8%) had arteriographically proven greater then 90% stenosis and required repeat CEA. The remaining 304 patients without routine postoperative duplex remained neurologically asymptomatic (mean follow-up 10.3 years, range 2.5 to 17 years).
 

Conclusion:  In this experience, there is no statistically significant difference in restenosis in the primary closure and selective patch group following CEA. Additionally, the absence of routine postoperative duplex failed to change the clinical outcome in a majority of patients. Although this data set is a small, single center, single surgeon, retrospective review, it does not support the generally well accepted view of routine patching following CEA.

 

 

67.18 Iatrogenic Esophageal Perforation in Neonates

Posted on December 22, 2014

A. J. Hesketh1,2, C. A. Behr1,3, S. Z. Soffer1,3, A. R. Hong1,3, R. D. Glick1,3  1Cohen Children’s Medical Center,Division Of Pediatric Surgery,New Hyde Park, NY, USA 2Elmezzi Graduate School Of Molecular Medicine,Manhasset, NY, USA 3Hofstra North Shore-LIJ School Of Medicine,Hempstead, NY, USA

Introduction: Esophageal perforation is a rare complication of enteric instrumentation in children, most commonly following endoscopy for stricture dilation or foreign body extraction. In preterm and low birth weight infants, enteric tube placement for suction or feeding poses a particular hazard to the delicate esophagus. Esophageal perforation in neonates due to oro/nasogastric tube insertion may be misdiagnosed as esophageal atresia or may go undiagnosed altogether. Historically, management of this life-threatening iatrogenic disease was operative, until case reports published over the last several decades described successful non-operative management. In the present study, we review neonatal esophageal perforations at our own institution in an effort to evaluate management techniques, risk factors and outcomes.

 

Methods: Our institution’s clinical database was queried for the ICD-9 code for esophageal perforation. Seventeen patients were identified, and 9 were excluded because they were older than one year. The charts of the remaining 8 patients were retrospectively reviewed for the following information: age and sex, demographics, comorbidities, cause and type of perforation, diagnostic modalities, management decisions, complications and outcomes. All study components were conducted in accordance with institutional review board policies.

 

Results: All 8 patients had esophageal perforations resulting from traumatic esophageal intubations. Six of the 8 patients were preterm, with a mean gestational age of 27.2 ± 4 weeks and birth weight of 862 ± 690 grams. The average age at diagnosis was 7 ± 6.6 days with 5 patients diagnosed within the first week of life. In all 8 patients, chest x-ray was the initial radiologic modality utilized and a non-operative approach was instituted as the initial management plan. Six patients ultimately required surgical intervention, 5 for pneumothoraces (tube thoracostomy) and one for a large thoraco-abdominal air leak (peritoneal drain insertion). Three patients died due to sequelae of prematurity (grade IV IVH and subsequent withdrawal of care, fungemia from NEC, and sepsis from chorioamnionitis). Treatment strategies included removal of the offending tube, non per os and antibiotics. One patient was diagnosed as having esophageal atresia prior to transfer to our institution; esophagoscopy in the operating room prior to operative repair of the presumed esophageal atresia established the correct diagnosis of an esophageal perforation.

 

Conclusion: Preterm, extremely low birth weight neonates are at significant risk for traumatic esophageal perforation during nasogastric or orogastric intubation. Non-operative management may be a safe initial management of esophageal perforation in the neonatal setting, but surgical interventions are often eventually indicated. Although recent early recognition and awareness of this iatrogenic disease has improved, missed and incorrect diagnoses still occur.

60.13 Feasibility of Arteriovenous Fistula Creation After Previous Radial Artery Harvesting for Aortocoronary Bypass

Posted on December 22, 2014

C. Rivera1, N. J. Gargiulo1  1North Shore University And Long Island Jewish Medical Center,Manhasset, NY, USA

Introduction:   Arteriovenous fistula (AVF) formation remains the procedure of choice in patients requring hemodialysis. The feasibility of AVF creation in the setting of prior radial artery harvesting after aortocoronary bypass remains unknown. This investigation elucidates which patients might be candidates for AVF creation despite prior radial artery harvesting.

Methods:   A retrospective review was performed on 2,100 patients undergoing hemodialysis access procedures from 2003 to 2010. Of these patients, 11 (0.5%) were identified as having prior radial artery harvesting for aortocoronary bypass. Pre/Post-operative vein mapping, arterial duplex, digital plethysmography, selective angiography, and sestamibi scanning was performed to evaluate the ulnary artery and palmar arch. Patients with evidence suggesting an intact ulnar artery circulation then underwent AVF creation.

Results:  All 11 patients had an adequate preoperative work up.  Seven (64%) of the 11 patients had digital plethysmography suggesting an intact ulnar artery/palmar arch and underwent successful AVF creation.  Three (27%) of the patients had a variety of findings precluding successful AVF creation.  One (9%) patient with normal preoperative plethysmography developed a steal syndrome requiring revision of the arteriovenous fistula.

Conclusion:  Successful AVF creation is feasible in patients with prior radial artery harvesting for aortocoronary bypass. The use of preoperative digital plethysmography, selective ulnar artery/palmar arch arteriography and sestamibi scanning to evaluate forearm muscle perfusion may be used as adjuncts to guide a successful intervention.

 

59.14 Receptor-interacting Protein Kinase 3 Deficiency Delays Cutaneous Wound Healing

Posted on December 22, 2014

A. J. Godwin1, W. Yang1,2, A. Sharma2, J. Nicastro1, G. F. Coppa1, P. Wang1,2  1Hofstra North Shore-LIJ School Of Medicine,Surgery,Manhasset, NY, USA 2The Feinstein Institute For Medical Research,Manhasset, NY, USA

Introduction:  Acute cutaneous wounds from trauma can become chronic non-healing wounds, resulting in a significant morbidity and mortality to the patients. Wound healing consists of a complex, dynamic process which involves three overlapping processes, namely; inflammation, proliferation and tissue remodeling. A better understanding of wound healing process at the molecular levels is needed for the development of novel therapeutic strategies. Receptor-interacting protein kinase 3 (RIPK3) has been identified to involve in controlling programmed necrosis in response to TNF-α during inflammation. We then hypothesized that RIPK3 regulated the progress of cutaneous wound healing.

Methods:  Full-thickness 2.0-cm diameter circular wounds were created on the dorsum of male wild-type (WT) and RIPK3-knockout (KO) mice on C57BL/6 background. Wound area was measured daily until day 14 post-wound and the pixel of the traced area was analyzed by NIH ImageJ. Skin tissues were collected from the wound sites at various days for histological evaluation and gene expression analysis by qPCR. Mouse embryonic fibroblasts (MEFs) were isolated from WT and RIPK3-KO mice for a transwell migration assay.

Results: The wound healing rate in RIPK3-KO mice was slower than the WT mice over the 14-day course; especially, at day 7, the wound size in RIPK3-KO mice was 53% larger than WT mice (n=7/group, P < 0.05). H&E and Masson-Trichrome staining indicated that RIPK3-KO wounds had a worse quality of wound closure and less collagen deposition in comparison with WT wounds. The number of Gr-1-positive cells for indicating neutrophils infiltrating in RIPK3-KO wounds was much less than WT wounds at day 1. The expression of growth factors (VEGF and TGF-β) and proinflammatory cytokines (TNF-α and IL-1β) were less and delayed in RIPK3-KO wounds, compared to WT wounds (Table). Furthermore, the numbers of migrated MEFs from RIPK3-KO mice toward PDGF and TGF-β, as chemoattractants, were 62% and 73%, respectively, lower than those of MEFs from WT mice. 

Conclusion: RIPK3-KO mice exhibit impairment of wound healing in association with reduced and delayed production of growth factors and proinflammatory cytokines. The chemotactic activity of RIPK3-deficient fibroblasts to growth factors is suppressed. Thus, RIPK3 is an important molecule required for normal progression of wound closure.

 

58.19 Inhibition of Metastasis With Celecoxib in Ewing Sarcoma is Not Dependent on Beta-catenin Signaling

Posted on December 22, 2014

C. Behr1,2,3, A. Hesketh1,2, B. Steinberg1, M. Symons1, S. Soffer1,2,3  1The Feinstein Institute For Medical Research,Manhasset, NY, USA 2Cohen Children’s Medical Center,Division Of Pediatric Surgery,New Hyde Park, NY, USA 3Hofstra North Shore – LIJ School Of Medicine,Hempstead, NY, USA

Introduction:  
Ewing Sarcoma (ES) is an aggressive childhood solid tumor in which 30% of cases are metastatic at presentation, and subsequently carry a poor prognosis. We have previously shown that treatment with the COX-2 inhibitor celecoxib significantly reduces invasion and metastasis of ES cells in a COX-2 independent fashion, suggesting that an off-target of celecoxib is likely responsible for this effect. Celecoxib is known to downregulate beta-catenin independently of COX-2, and beta-catenin upregulation is considered a poor prognostic sign in a host of metastatic and aggressive human cancers. Thus we hypothesized that celecoxib’s antimetastatic effect in ES acts via modulation of the beta-catenin signaling pathway.

Methods:
Human ES cells (SK-NEP1) were transfected with siRNA oligomers targeting beta-catenin. Non-targeting siRNAs were used as controls. Knockdown was verified using western blotting. A portion of the samples were also treated with celecoxib. An in vitro invasion assay was performed using standard Boyden chambers by layering a suspension of ES cells within basement membrane extract. After 72 hours, cells were fixed in the wells and stained with crystal violet. The number of invading cells was assessed using light microscopy. Non-transfected SK-NEP1 cells were additionally treated with celecoxib, and beta-catenin levels and activity were assessed using western blotting, qPCR, and immunocytochemistry.

Results:
Reduction of beta-catenin by at least 75% with two different beta-catenin siRNA oligomers did not reduce the ability of the cells to invade compared to their siRNA negative controls (mean of 161 and 176 cells invaded respectively for each siRNA oligomer versus 153 for the non-targeting siRNA control). As expected from our previous experiments, treatment with celecoxib resulted in decreased invasion and this effect was not dependent on the presence of beta-catenin in the cells. Furthermore, western blotting and qPCR failed to demonstrate any difference in beta-catenin protein and RNA levels within the cells after celecoxib treatment, and immunocytochemistry showed no change in the gross amount of beta-catenin nor in its cellular location compared to untreated tumor cells. 

Conclusion:
Celecoxib’s inhibition of Ewing Sarcoma invasion is independent of beta-catenin signaling. Decreasing beta-catenin levels in SK-NEP1 cells does not affect their ability to invade, ruling out beta-catenin as a potential mediator of celecoxib’s anti-metastatic properties. Another COX-2 independent target is likely responsible for celecoxib’s anti-metastatic effect.
 

58.17 The Macrophage Inhibitor CNI-1493 Prevents Ewing’s Sarcoma Tumor Cell Extravasation

Posted on December 22, 2014

A. J. Hesketh1,2,3, C. A. Behr1,2,4, M. Edelman1,4, R. D. Glick1,4, Y. J. Al-Abed2,3, M. J. Symons2,3, B. M. Steinberg2,3,4, S. Z. Soffer1,2,4  1Cohen Children’s Medical Center,Division Of Pediatric Surgery,New Hyde Park, NY, USA 2Feinstein Institute For Medical Research,Manhasset, NY, USA 3Elmezzi Graduate School Of Molecular Medicine,Manhasset, NY, USA 4Hofstra North Shore-LIJ School Of Medicine,Hempstead, NY, USA

Introduction: Metastatic Ewing’s Sarcoma (ES) carries a poor prognosis. Recent evidence demonstrates that tumor-associated macrophages in ES are associated with more advanced disease. While some macrophage phenotypes (M1) exhibit anti-tumor activity, distinct phenotypes (M2) may contribute to malignant progression and metastasis. Preliminary in vitro and animal model studies demonstrate that the macrophage inhibitor CNI-1493 prevents ES tumor cell invasion and lung metastases. We hypothesized that CNI-1493 inhibits M2 macrophage-stimulated ES tumor cell extravasation into the lung parenchyma, a key step in the establishment of viable metastatic foci.

 

Methods: To simulate the architecture of the lung extravasation process, in vitro extravasation assays were constructed using basement membrane-coated cell culture inserts featuring an opaque polyethylene membrane containing 8μm pores. A monolayer of primary human pulmonary microvascular endothelial cells (HPMECs) was plated on the surface of the basement membrane and impermeability was verified with Evans blue. Primary macrophages isolated from human blood were polarized to express the M2 phenotype by treatment with M-CSF followed by activation with IL-4. Fluorescently tagged human ES cells (SK-NEP) were grown in monoculture or in co-culture with M2 macrophages in the upper chamber of the cell culture insert. Alternatively, M2 macrophages were plated on the undersurface of the cell culture insert with SK-NEP cells in the upper chamber. After 48 hours, tumor cells that had invaded through the endothelial monolayer, basement membrane and culture insert into the lower chamber were quantified using fluorescence microscopy.

 

Results: Tumor cell extravasation was increased 3.4-fold in the presence of M2 macrophages (p<0.05) with no significant difference between SK-NEP/M2 co-cultures and cultures separated by the assay insert (Table 1).  CNI-1493 significantly decreased the quantity of invading tumor cells stimulated by M2 macrophages (p<0.01), and the degree of this inhibition was similar whether an HPMEC monolayer was present or not (54% and 58% reduction, respectively).

 

Conclusion: M2 macrophages promote tumor cell extravasation in vitro. This interaction is independent of direct tumor cell contact, suggesting soluble mediators. CNI-1493 decreases M2-induced tumor cell extravasation independent of the presence of an endothelium, indicating a direct effect on macrophages expressing pro-metastatic phenotypes. CNI-1493 may be useful as a novel adjunct in the treatment or prevention of metastatic ES.

43.01 Sirt1 Stimulation Preserves Mitochondria and Enhances Autophagy in Hepatocytes after Hypoxic Injury

Posted on December 22, 2014

A. Khader1,2, W. Yang1,2, J. M. Prince1, J. Nicastro1, G. F. Coppa1, P. Wang1,2  1Hofstra North Shore-LIJ School Of Medicine,Surgery,Manhasset, NEW YORK, USA 2Elmezzi Graduate School Of Molecular Medicine,Manhasset, NEW YORK, USA

Introduction: Liver ischemia-reperfusion (I/R) often occurs in trauma, transplantation and prolonged shock state, where it lacks specific treatment. We have recently demonstrated that pharmacologic sirtuin 1 (Sirt1) activation, with SRT1720, is protective in a murine model of liver I/R. However, the detailed mechanism of which is not yet characterized. Sirt1 is an energy-sensing enzyme with multiple roles, including the regulation of energy metabolism, mitochondrial function and autophagy. We therefore hypothesized that SRT1720 protects hepatocytes from hypoxia-induced injury through the activation of mitochondrial biogenesis and the autophagy salvage pathway.

Methods:  Rat hepatocyte epithelial H4IIE cells were subjected to 6 h of hypoxia using 5% Oxyrase, followed by reoxygenation in the presence or absence of SRT1720 (500 nM) for 4 or 24 h. Cell survival was determined by cell counts and ATP assay. Cells were stained with MitoTracker green and red FM for measuring mitochondrial mass (mtMass) and membrane potential (MMP), respectively, by flow cytometry. Acridine orange stain was used to assess the formation of autophagic vesicles under fluorescent microscopy. Protein levels were determined by Western blot. 

Results: We observed a 27.6% and 21.7% reduction in cell numbers and ATP levels, respectively, at 4 h of reoxygenation (H/R), while SRT1720-treated cells were comparable to the normoxia control. At 4 h of H/R, the mtMass and MMP per cell, as measured by mean fluorescent intensity (MFI), were decreased by 44.6% and 27.6%, respectively, compared to the normoxia control. In contrast, treatment with SRT1720 enhanced both parameters by 3.4- and 5.5-fold, respectively, compared to untreated cells at 4 h of H/R. This enhancement of mtMass and MMP by SRT1720 persisted to 24 h of reoxygenation. Treatment with SRT1720 increased the expression of PGC1α, the master regulator of mitochondrial biogenesis, by 11.0% and 36.7% at 4 h and 24 h of H/R, respectively. In addition, there was a significant enhancement in autophagy in the SRT1720 treated cells as demonstrated by an increase in LC3aII/LC3aI protein ratio to 3.3 compared to 1.7 in the untreated cells at 4 h of H/R. Further, there was an observable increase in autophagic vesicles (bright contrast) at 24 h of reoxygenation which was remarkably increased by SRT1720, as shown by the increase in vesicle numbers and intensity of acridine orange precipitation (Figure).

Conclusion: Pharmacologic activation of Sirt1 improves the survival of hepatocytes under hypoxic stress, which is associated with maintenance of mitochondrial mass and integrity as well as an increase in autophagic activity. Thus, stimulation of mitochondrial function may provide a new protective strategy against liver I/R injury. 

32.02 Clinicopathologic Features and Time Interval Analysis of Contralateral Breast Cancers

Posted on December 22, 2014

E. L. Liederbach1, R. Piro1, R. Watkin1, K. Hughes1, C. Wang2, C. Pesce1, D. J. Winchester1, K. Yao1  1Northshore University Health System,Surgery,Evanston, IL, USA 2Northshore University Health System,Center For Biomedical Research Informatics,Evanston, IL, USA

Introduction: Multiple studies have shown that contralateral prophylactic mastectomy improves survival, but follow-up for most of these studies are five years or less and provide little data on tumor characteristics of the contralateral breast cancer (CBC). We hypothesized that most CBCs develop after five years and that these CBCs have favorable tumor characteristics.

Methods: This is a single institution retrospective review of 323 patients who were diagnosed with CBCs from 1990 to 2014. CBCs were diagnosed at least one year after the primary cancer diagnosis. BRCA mutation carriers were not excluded. Utilizing chi-square tests and one-way ANOVA tests, we examined the time interval and pathological features between the primary and contralateral cancer.

Results: The average time interval between the primary and CBC was 7.15 years (median: 6.2, range: 1.01-23.0), with 60.4% of patients having a time interval of >5 years. Older patients ≥70 yo developed a CBC sooner than patients <70 yo (5.0 and 7.6 years respectively, p<.001). A majority of stage III patients (69.2%) developed a CBC within 5 years compared to 51.9% of stage 0, 39.3% of stage I, and 36.6% of stage II patients (p=.039). On average, patients with ILC developed their CBC in 9.2 years compared to 7.1 years for IDC patients, 6.6 years for mixed histology patients, and 5.9 years for DCIS patients (p=.016).  Factors that had no influence on the time interval between CBCs were race, body mass index, menopausal status, use of hormone replacement therapy, family history of breast/ovarian cancer, estrogen receptor (ER) status, BRCA status, tumor grade, and presence of lymphatic vascular invasion. In comparison to the first primary breast cancer, a higher proportion of CBCs were stage I (51.0% vs. 36.2%), T1 tumors (72.1% vs. 59.1%), node negative (67.5% vs. 62.2%), and ER(+) tumors (68.7% vs. 51.7%).  Of the 252 patients with available tumor size information for both breast cancers, 54 (21.4%) patients developed a CBC that was >1cm larger than their original primary, and only 25 (9.9%) patients developed a CBC that was >2cm larger than their original primary. There were 201 (62.2%) patients with node negative disease for their first breast cancer, and only 28 (13.9%) of these patients developed a node positive CBC. Of the 300 patients with stage information, 85 (28.3%) patients had a higher stage CBC compared to their first primary. Of the 67 patients with an ER(-) primary, 44 (62.7%) developed an ER(+) CBC. 

Conclusion: A majority of CBCs develop >5 years after the diagnosis of the first primary breast cancer. CBCs have more favorable tumor characteristics than the primary tumor because they tend to be smaller, less aggressive, and lower in stage compared to the primary breast cancer. Patient age, stage, and tumor histology significantly influence the time interval from primary to CBCs. It is unlikely that CBC would affect survival at five years of follow-up given this data.
 

30.04 Trends in Radiation Therapy for Elderly Women with Early Stage Breast Cancer: A Report from the NCDB

Posted on December 22, 2014

O. Kantor1, E. Leiderbach2, C. Wang3, D. J. Winchester2, C. E. Pesce2, K. Yao2  1University Of Chicago,Department Of Surgery,Chicago, IL, USA 2NorthShore University Health System,Department Of Surgery,Evanston, IL, USA 3Northshore University Health Systems,Center For Biomedical Research Informatics,Evanstol, IL, USA

Introduction:
Several randomized controlled trials in 2004 have examined the efficacy of radiation in elderly women with early stage breast cancer without demonstrating a survival benefit to radiation. Omission of radiation for this cohort has been incorporated into National Comprehensive Cancer Network guidelines for patients meeting criteria. We examined trends in radiation utilization for elderly patients since publication of these trials.

Methods:
Using the National Cancer Data Base (NCDB), radiation therapy utilization was determined for patients with early stage, estrogen receptor positive (ER+), clinically node negative invasive cancer treated with breast conserving surgery and hormone therapy from 2004 to 2011. Chi square tests and logistic regression models were used for analysis.

Results:
Adjuvant radiation therapy after breast conserving surgery decreased from 83.8% to 76.0% among those ≥70yo with ER+ tumors ≤2cm. For patients who did not receive hormonal therapy, radiation utilization significantly decreased from 60.7% to 52.4% over the study period.  Among those patients who did not undergo radiation therapy, the rate of hormone therapy significantly increased from 36.9% to 52.7%. There is variation in the use of radiation according to patient and tumor factors; 95.3% of 60-69 year olds, 81.6% of 70-79 year olds, and only 59.1% of 80-90 year olds received radiation therapy in 2011. 83.2% of grade 3 tumors received radiation in 2011, compared to 73.3% of grade 1 tumors. Patients without lymph node staging were much less likely to receive radiation therapy compared to those that did (45.7% versus 77.8%).

The rate of external beam radiation has significantly decreased from 69.9% to 46.2%, while alternate forms of radiation have increased twofold from 14.2% to 29.8% (Figure 1). Brachytherapy has increased from 5% in 2004 to 11.7% in 2011. Independent predictors of receiving alternate forms of radiation include being treated at a community cancer center (OR 1.43, CI: 1.32-1.54), living >50 miles from the hospital (OR 1.50, CI:1.28-1.76), and living in the Mid-Atlantic (OR 2.42, CI: 2.16-2.71) or South Atlantic (OR 2.14, CI: 1.91-2.39) regions. Caucasian women, those with private insurance, grade 1 tumors, T1a tumors, and PR positive tumors were also more likely to receive alternate forms of radiation.

Conclusion:
Time trends in the NCDB reflect a gradual acceptance of evidence from randomized clinical trials supporting the omission of radiation therapy for women 70 and older with ER+ early stage breast cancer.  However, the majority still receive radiation, influenced by tumor size and grade, and many are receiving alternate forms of radiation, particularly brachytherapy.
 

19.02 Inhibition of Ubiqutin-Activating Enzyme Protects Organ Injury from Intestinal Ischemia-Reperfusion

Posted on December 22, 2014

W. Yang1, S. Matsuo2, A. J. Chaung1, P. Wang1  1Hofstra North Shore-LIJ School Of Medicine,Surgery,Mnahasset, NY, USA 2Tokyo Women’s Medical University,Surgery,Tokyo, , Japan

Introduction:  Intestinal ischemia-reperfusion (I/R) occurs in various clinical settings, such as transplantation, acute mesenteric arterial occlusion, trauma and shock. I/R injury causes severe systemic inflammation, leading to multiple organ dysfunction associated with high rates of morbidity and mortality. Ubiquitin proteasome pathway has been indicated in the regulation of inflammation, particularly through NF-κB signaling pathway. PYR-41 is a small molecule compound that selectively inhibits ubiquitin-activating enzyme E1. We hypothesized that administration of PYR-41 attenuated organ injury after intestinal I/R.

Methods:  Male C57BL/6 mice (20-25 g) were subjected to intestinal ischemia by clamping the superior mesenteric artery for 45 min, followed by reperfusion. At the beginning of reperfusion, PYR-41 (5 mg/kg BW) or 20% DMSO (vehicle) in normal saline was administered intravenously (n=5/group). After 4 h, blood and tissues were collected for various measurements. Apoptotic cells in tissue sections were detected by TUNEL assay. Cytokines were measured by ELISA. Ubiquitination and protein levels were determined by Western blotting. Gene expression was assessed by qPCR.

Results:PYR-41 significantly reduced LDH, AST and IL-6 serum levels from 752.8 to 155.3 IU/L, 76.7 to 47.0 IU/L and 10.4 to 5.1 ng/ml, respectively, compared to the vehicle group (P < 0.05). The integrity of microscopic structures of the small intestine and lungs was much more preserved in the PYR-41-treated group than in the vehicle group (Figure). PYR-41 decreased the number of TUNEL-positive cells in the small intestine and lungs from 144 to 32 and 120 to 38 cells/field, respectively, which were associated with a reduction of cleaved caspase-3 levels in both organs. The IL-6 and IL-1β levels were decreased from 166.8 to 64.8 and 65.8 to 37.7 pg/mg protein in the intestine as well as from 53.2 to 38.3 and 132.6 to 70.7 pg/mg protein in the lungs, respectively, with PYR-41 treatment. Myeloperoxidase activity in the intestine and lungs is reduced by 69% and 38%, respectively, with PYR-41 treatment. PYR-41 also inhibited the expression of KC and MIP-2 mRNA in the intestine as well as lungs. In addition, PYR-41 inhibited the degradation of IκB in the intestine and the ubiquitination in the lungs after intestinal I/R.      

Conclusion: Treatment with PYR-41 effectively attenuates intestinal and pulmonary injuries through inhibiting NF-κB activation to reduce local and systemic inflammation after intestinal I/R. Thus, ubiquitination may be a potential therapeutic target for treating patients suffering from intestinal I/R.

 

10.02 Identification of risk factors for cervical spine injury from pediatric trauma registry

Posted on December 22, 2014

A. S. Chaudhry1, S. Bloom1, J. McGinn1, C. Fasanya1, J. Schulz1, M. Price1  1North Shore University And Long Island Jewish Medical Center,Staten Island University Hospital/ Surgery,Manhasset, NY, USA

Cervical spine injuries (CSI) are rare in children. A vast majority is related to blunt trauma, occurring in less than 1% of those evaluated. So far, there is no established standardized protocol in the pediatric population to clear the cervical spine. Exposing children to harmful radiations due to excessive CT scan runs a risk of malignancy, that is 25% higher in the exposed group. The Canadian C-Spine rule and National Emergency X-Radiography Utilization Study (NEXUS) criteria for adults are more than 99% sensitive for identifying cervical spine injuries in adults.  The purpose of this study is to evaluate certain risk stratification strategies for identification of cervical spine injury (CSI) in pediatric trauma patients. 

Methods

With IRB approval we retrospectively reviewed the records of Pediatric Trauma Registries from two state designated level 1 pediatric trauma centers for 11 years (January 2002 and June 2013),inclusive. Patients age 1 month to 17 years who had a CT of the C-spine and evaluated for Cervical Spine Injury (CSI). We identified variables associated with increasing incidence of CSI in the literature and evaluated all patients as per these variables. The Age, Gender, Injury severity score (ISS), Glasgow coma score (GCS), LOC (Loss of consciousness), neck tenderness, significant injuries, and mechanism of injuries were examined for differences based on the presence or absence of cervical spine Injuries (CSI).

Results

A total of 220 cases were reviewed 46 (21%) were positive for CSI and 174(79%) were negative for CSI. Patients with a positive CSI were male (p=0.0261) had ISS > 25 (p=0.00076) and presented with neck tenderness (p=0.0001). The most common mechanism of injury was motor vehicle crashes (39%). LOC unexpectadly was not associated with having CSI (p=0.0003). Upper CSI (C1-C4) were more prevalent inyounger age group (0-8yrs) i.e (82.35%), while lower CSI (C5-C8) were more common in older children (9-16yrs) i.e (44.83%). However this result was not statistically significant (p=0.0617). There was statistically no significant association between CSI and Age, GCS, other significant injuries, or mechanism of injury.

 

Conclusion:

In our study significant CSI is related to male gender, higher ISS and neck tenderness. Patients with significant ISS and those with neck tenderness require diagnostic imaging appropriate for patients who have a higher likelihood of CSI. We propose a protocol for cervical spine injury clearance in children based on this data. Those patients who do not need the above criteria may be saved from undergoing excessive CT scans, in an effort to lower children radiation exposuretion:

 

10.12 Radiologic Interpretation of Nutrition at Base of Spine (RIBS) – Reliability and Reproducibility

Posted on December 22, 2014

I. Shnaydman1, J. McLatchy1, R. Barrera1  1North Shore University And Long Island Jewish Medical Center,Manhasset, NY, USA

Introduction:

Critically ill patients suffer from nutritional deficiency, resulting in poor wound healing, prolonged ventilator dependence and poor outcomes. There is currently no objective method to accurately assess nutritional status and determine effectiveness of nutritional support. Albumin, Prealbumin and Transferrin have been used as nutritional markers, but are unreliable in the critically ill patient due to being acute phase reactants. Radiologic Interpretation at Base of Spine, RIBS, was created to objectively assess nutrition and correlate to postoperative outcomes. The purpose of this study is to evaluate the reproducibility, reliability and clinical potential of the RIBS application.

Methods:

The RIBS application, developed by one of the authors, allows users to determine the ratio of visceral fat to muscle tissue. The easy to use program guides users through a few steps involving uploading a scan of the sacral area obtained from a routine CTAP and selecting the boundaries of fat and muscle adjacent to the spine. The application calculates this ratio of fat to muscle to determine a RIBS score. The application is cross-platform compatible and may be used on desktop computers and handheld devices.

Twenty surgical residents were given a brief introduction, and then ran the application on the same series of images. Half of the subjects used a portable device and half used a desktop computer. Results were compared to determine average time to completion, intra and inter-user reliability and reproducibility.

Clinical use of the RIBS application was assessed using a case study that followed the hospital course of a critically ill patient over the course of a year.  RIBS scores were compared to albumin, prealbumin and BMI.

Results:

Preliminary results demonstrate the reliability and reproducibility of the RIBS application. Test subjects found the program practical with an average completion time of 8 and 12 seconds on desktop and mobile devices respectively.

The case study showed that RIBS scores can provide clinical  insight into the nutritional status of a patient.  The RIBS scores correlated positively with BMI, Albumin and Prealbumin.

Conclusion:

In critically ill patients, appropriate nutritional support is often based on caloric need with adjustments made for specific illnesses. During an inflammatory process such as sepsis, it is important to use an objective marker for nutrition to both assess a patient’s prognosis as well as to trend their response to nutritional support. The data suggests that RIBS could be used to accurately and easily assess nutritional status.  Further research is underway to determine the efficacy of RIBS as a nutritional marker and correlate it to outcome measures.