2.08 Generation of Patient-Derived Xenografts from Small Volume Biopsy Samples

Posted on December 22, 2014

D. Roife1,2, Y. Kang1, R. Zhang1, L. Wang3, B. Fang3, M. Katz1, J. Gershenwald1, C. Dinney4, J. Fleming1  1University Of Texas MD Anderson Cancer Center,Surgical Oncology,Houston, TX, USA 2University Of Texas Health Science Center At Houston,General Surgery,Houston, TX, USA 3University Of Texas MD Anderson Cancer Center,Thoracic And Cardiovascular Surgery,Houston, TX, USA 4University Of Texas MD Anderson Cancer Center,Urology,Houston, TX, USA 5University Of Texas MD Anderson Cancer Center,Melanoma,Houston, TX, USA

Introduction:  Patient-derived xenografts have become a powerful tool for cancer research in recent decades. One of the most significant barriers to growing xenografts from patient tumors is the need for surgical resection of tumor tissue. Thus far, patient derived xenografts have been grown from tumor tissue obtained after surgical resection of the primary tumor, and occasionally from metastatic tumors, if surgery was medically warranted. However, many cancer patients never undergo surgery for a variety of reasons, and therefore they are never given the opportunity of having their tumor tissue grown for research purposes via xenografts. We hypothesized that xenograft tumors could be grown from smaller volumes of patient tissue, such as those obtained during diagnostic biopsies. 

Methods:  Surgical specimens were obtained after resection of primary or metastatic lesions of the following cancers: pancreatic adenocarcinoma, lung adenocarcinoma, bladder (transitional cell) carcinoma, and melanoma. At least 10 cases of each cancer were included in this study. These cases did not exclude any patient in regards to neoadjuvant treatment or clinical characteristics. To mimic clinical biopsies, small fragments of the surgical specimens were biopsied with a 22g needle and the needle contents were injected subcutaneously in immunocompromised mice. The tumor fragment from which the biopsy was taken was also implanted subcutaneously in the contralateral side of the same mouse as a control.

Results: Success rates of the traditional method of xenograft implantation ranged from 30-70%, similar to what is reported in the literature. Success rates of the experimental biopsy technique ranged from 10%-40%. Since the experimental biopsy technique demonstrated successful results, the study culminated with the first patient derived xenograft grown from a percutaneous, outpatient biopsy. A patient with metastatic pancreatic adenocarcinoma underwent percutaneous ultrasound-guided core needle biopsy of a liver lesion. We divided this core biopsy and implanted the fragments into three immunocompromised mice, all of which grew into large tumors in under two months. 

Conclusion: The lower success rate of the experimental biopsy technique was to be expected due to the smaller volume of tumor tissue implanted. However, it should be noted that these biopsy derived tumors reached comparable sizes as traditionally implanted tumor fragments in the same time frame, despite implanting significantly fewer cells. Also, metastatic tumor sites had much higher successful engraftment rates than samples taken from the primary tumor site. In conclusion, we have shown that it is possible to successfully grow patient-derived xenografts with small volumes of tumor samples that are obtainable during diagnostic biopsies, which potentially can open the xenograft technique to a wider scope of cancer patients.

 

2.10 Novel actionable genomic analysis of individual PDAC specimens in real time

Posted on December 22, 2014

J. Yu1, G. Zhou1, S. Liu1, J. Wu1, R. Sanchez1, D. Dawson1, W. Fisher2, F. C. Brunicardi1  1University Of California – Los Angeles,Surgery Department,Los Angeles, CA, USA 2Baylor College Of Medicine,Houston, TX, USA

Introduction:  Recent molecular characterizations of pancreatic ductal adenocarcinoma (PDAC) have identified hundreds of genetic alterations and aberrant gene expression in key biological processes and signaling pathways. However, PDAC global database analyses are insufficient in identifying relevant PDAC biomarkers for individual patients. Our objective was to develop a list of PDAC signature genes that could serve as potential biomarkers for individuals with PDAC using a novel combination of real time genomic analysis and published PDAC databases.  

Methods:  PDAC and normal matching pancreas specimens (n=8) were procured and processed for genomic sequencing. RNA sequencing libraries were generated using Illumina TruSeq RNA v2.0 and sequenced on an Illumina HiSeq 2500 platform. Sequencing reads were aligned to the human genome hg19 using TopHat and Bowtie. Three microarray gene expression datasets from the GEO database were collected and processed with R and Bioconductor packages. PDAC signature genes were identified by comparing whole genome transcriptome profiles from gene expression microarrays on independent cohorts and microarray platforms. Weighted Gene Co-expression Network Analysis (WGCNA) was then conducted to identify hub genes that highly correlate with PDAC. Hub genes were further validated with RNAseq and QPCR in PDAC and normal tissue control specimens.

Results: 1007 differentially expressed genes were identified with a cutoff (log2 fold-change > 0.5, FDR < 0.01) by comparing whole transcriptome of PDAC with normal matching tissues from three independent cohorts of two microarray platforms. GO-term enrichment analysis revealed that these 1007 genes were significantly enriched in ECM-receptor interaction, focal adhesion, complement and coagulation cascades, and glycolysis and gluconeogenesis pathways. With higher stringency (log2 fold-change > 2 and FDR < 0.01), 83 PDAC signature genes that distinguish PDAC from the normal pancreas were identified. To identify modules of highly co-regulated genes, co-expression gene networks using the transcriptome data of the entire 1007 gene list were constructed, revealing five modules and 12 hub genes with high connectivity and significant correlation with PDAC. Three hub genes, MBOAT2, LAMC2, and TSPAN1, were validated using QPCR of individual PDAC and normal pancreas specimens.

Conclusion: This novel actionable genomic analysis utilizes a comparison of RNAseq in real time to microarray on a large number of PDAC samples and WGCNA using a multifactorial genomic analysis and reveals a list of 83 PDAC signature genes, including MBOAT2, LAMC2 and TSPAN1. The data suggest that this actionable genomic analysis platform will help increase the understanding of signaling pathways and the identification of potential therapeutic targets in real-time for each patient with PDAC.

 

2.11 Hypoxia Inducible Factor-1α Increases Pro-Tumorigenic Macrophage Activation in Pancreatic Cancer

Posted on December 22, 2014

J. A. Yi1, K. El Kasmi1, E. E. Moore1,2, C. C. Barnett1,2  1University Of Colorado Denver,Aurora, CO, USA 2Denver Health Medical Center,Aurora, CO, USA

Introduction:

Tumor-associated macrophages (TAMs) mediate tumor progression.  Macrophage polarization is categorized as M1 (classical) or M2 (alternative) activation pathways.  M1 cells are pro-inflammatory and involved in innate immunity, while M2 cells function in wound healing and cell proliferation.  The M2 phenotype is most commonly seen among TAMs, correlates with poor patient prognosis, and is considered pro-tumorigenic.  Hypoxia inducible factor-1α (HIF1α) is a transcription factor activated in hypoxia and inflammation that modulates numerous critical functions for tumor growth and metastasis.  Increased HIF1α expression in pancreatic adenocarcinoma is a marker of advanced malignancy.  We hypothesize that pancreatic cancer modulates local macrophages towards a pro-tumorigenic M2 phenotype via a HIF1α-dependent mechanism.

 

Methods:

A murine pancreas adenocarcinoma cell line (Pan02) was modified using short-hairpin RNA targeting HIF1α via lentiviral transduction to create Pan02 SH+ cells lacking HIF1α activity.  Pan02 and Pan02 SH+ cells were then incubated until 80% confluent prior to collection of supernatant.  RAW 264.7 cells, a murine macrophage line, were exposed to Pan02 or Pan02 SH+ supernatant in culture for 24 hours.  At 24 hours, the RAW 264.7 cells were harvested for mRNA extraction.  Real-time polymerase chain reaction was used to determine macrophage phenotype based on suppressor of cytokine signaling (SOCS) 1 or 3 expression, accepted markers of M1 and M2 phenotypes respectively.  Statistical analysis was performed using one-way analysis of variance with significance determined by α<0.05.

 

Results:

 

There was a modest increase in SOCS1 expression by RAW 264.7 cells exposed to either Pan02 or Pan02 SH+.  The relative expression of SOCS1 was not significantly different between the two treatment groups (mean fold change in expression of Pan02-exposed = 1.5399 ± 0.2151, Pan02 SH+-exposed = 10.3159 ± 5.1322, p=0.1384).  SOCS3 expression was significantly greater than SOCS1 in both Pan02 and Pan02 SH+ treatment groups (p=0.0015).  Among RAW 264.7 cells exposed to Pan02 SH+ supernatant, SOCS3 expression was significantly reduced as compared to the Pan02-exposed cells (mean fold change in expression of Pan02-exposed = 152.206 ± 25.795, Pan02 SH+-exposed = 66.088 ± 10.617, p=0.0368).

 

Conclusions:

 

There was an increase in M2 versus M1 differentiation upon exposure to both Pan02 and Pan02 SH+ cell supernatant. Importantly, exposure to Pan02 supernatant significantly increased M2 differentiation compared to Pan02 SH+ supernatant, implicating HIF1α in the modulation of a pro-tumorigenic M2 macrophage activation state. This may represent a therapeutic target for treatment of pancreatic cancer.

2.12 Triptolide Mediates Post-Translational Modification of Histones in Pancreatic Cancer

Posted on December 22, 2014

K. Majumder1, R. Chugh1, S. Modi1, N. Arora1, S. Banerjee1, R. Dawra1, A. Saluja1, V. Dudeja1  1University Of Minnesota,Surgery,Minneapolis, MN, USA

Introduction:  Triptolide, a diterpene triepoxide from the Chinese plant Tripterygium wilfordii, is markedly effective against pancreatic cancer cells both in vivo and in vitro. Minnelide, a water soluble analog of triptolide, is currently in phase I clinical trials. While our data suggests that downregulation of transcription factors HSF-1 (Heat shock factor -1), Sp-1 and NFκB contribute to the effect of triptolide on cancer cells, the mechanism of action of triptolide remains elusive. There is increased understanding of epigenetics in the pathogenesis of cancer and altered histone modifications can play a role in aberrant protein expression profile in cancer cells. In general post-translational modification of histones such as methylation represses gene transcription whereas acetylation activates gene transcription. For example binding of histone-3 trimethylated at lysine-9 residue (tri-methylated H3K9) leads to repression of transcription. In the current work we have evaluated whether epigenetic modulation plays a role in triptolide’s mechanism of action.

Methods:  Pancreatic cancer cells (MIA Paca2 and S2-VP10) were treated with triptolide (0-200nM). Protein and mRNA were extracted and analyzed by western blotting, qPCR and PCR array for histone methylation/acetylation and levels of chromatin modifying enzymes. CHIP qPCR was performed to analyze binding of tri-methylated histones to the promoter region of genes regulated by HSF-1 (e.g. HSP70), Sp-1 (FGFR-1) and NFκB (TNFα). 

Results: Dose dependent increase of tri-methyl histones (H3Lys27, H3Lys9 and H3Lys4) and a concurrent decrease of acetylated histones (Acetyl histone H3Lys9 and H3Lys18) were observed on western blotting suggesting that triptolide has widespread impact on histone post-translational modification. Western blotting and qPCR showed time and dose dependent decrease in levels of both the demethylases and methyltransferases with triptolide. CHIP qPCR showed increased binding of trimethylated H3K9 but not trimethylated H3K27 to promoter of FGFR-1, HSP70 and TNFα in triptolide treated Mia Paca2 cell lines as compared to untreated cells (% Fold change in occupancy of H3K9me3 on triptolide 200nM treatment when compared to no treatment: HSP70 promoter = 321%, FGFR-1 promoter = 262% and TNFα promoter= 208%).

Conclusion: Triptolide alters histone methylation and acetylation profile suggesting an epigenetic component to its action. Corresponding to these changes there is an increased binding of tri-methylated H3K9, to the response element of the transcription factors (HSF-1, Sp-1and NFκB) which are downregulated by triptolide. This is the first report suggesting that epigenetic modulation may be the mechanism of anti-tumor action of triptolide. Dissecting this mechanism further may lead to elucidation of novel therapeutic target in pancreatic cancer.

2.13 CDK4/6 Inhibitors are Potent Suppressors of Pancreatic Carcinoma Growth

Posted on December 22, 2014

N. A. Borja1, J. Franco2, E. Knudsen2,3, J. Mansour1,3, M. Choti1,3, A. Witkiewicz2,3  1UT Southwestern,Department Of Surgery,Dallas, TX, USA 2UT Southwestern,Department Of Pathology,Dallas, TX, USA 3Simmons Cancer Center,UT Southwestern,Dallas, TX, USA

Introduction: Pancreatic ductal adenocarcinoma (PDA) carries a dismal prognosis, even in patients who undergo successful surgical interventions.  Unlike other cancers, an approach tailored to its specific genetic features has not yet been developed. Loss of the CDKN2A tumor suppressor is an exceedingly frequent occurrence in PDA. The CDKN2A gene encodes the p16ink4a protein, which is a potent inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6).  Prior studies have shown that p16ink4a is dominant to KRAS and can serve to constrain oncogenic proliferation in many contexts.  Specific CDK4/6 pharmacological inhibitors have been developed and could represent a means to restore the physiological loss of CDKN2A and treat PDA.  Here we utilized multiple models to investigate the impact of CDK4/6 inhibition on PDA.

Methods: Three specific model systems were utilized to determine the therapeutic efficacy of CDK4/6 inhibition in the treatment of PDA.  First, a panel of established PDA cell lines was employed to delineate overall features of the response to CDK4/6 inhibition, mechanisms of resistance, and define novel combination treatments. Second, in order to recapitulate the complex microenvironment of PDA, we utilized a primary tumor explant model where slices from 13 clinically resected PDA specimens were cultured on semi-solid support. These explants maintained the histologic architecture, biomarker profile, and proliferative index of the primary surgical specimen. Third, a panel of patient-derived xenografts representative of resected disease were developed and utilized to examine the response to CDK4/6 inhibition in vivo.

Results: The established cell lines had variable response to PD-0332991 (CDK4/6 inhibitor) as a single agent; however, in combination with mTOR or MEK inhibitors provided substantial efficacy across all models studied. Surprisingly,  this diversity of response was not recapitulated in tumor explants. In this context, treatment with PD-0332991 led to profound suppression of proliferation in all models, with the exception of a single resistant case harboring a loss of the RB tumor suppressor.  Similarly, patient-derived xenografts exhibited profound inhibition of Ki-67 proliferation marker and growth suppression. These data indicate that CDK4/6 inhibition is effective in suppressing the growth of PDA under diverse physiological contexts.

Conclusion: Our data demonstrates that PDA growth is profoundly inhibited by selective targeting of the CDK4/6 in primary tumor explants and patient-derived xenografts. The variable response to PD-0332991 in established cell lines likely reflects a more aggressive phenotype, and potentially the altered biology of models propagated in long term culture.  Importantly, the data suggest that CDK4/6 inhibition could be particularly effective in the control of resectable disease given the potent suppression of tumorigenic growth in both explant and patient-derived xenograft models.
 

2.14 Nafamostat mesilate enhances antitumor effect of chemotherapy for pancreatic cancer.

Posted on December 22, 2014

T. Horiuchi1,2, H. Shiba1, Y. Shirai1,2, R. Iwase1,2, K. Haruki1, Y. Fujiwara1, K. Furukawa1, T. Uwagawa1, T. Ohashi2, K. Yanaga1  1The Jikei University School Of Medicine,Department Of Surgery,Tokyo, , Japan 2The Jikei University School Of Medicine,Department Of Gene Therapy, Research Center For Medical Science,Tokyo, , Japan

Introduction: ~Pancreatic cancer has a poor prognosis among visceral cancers, with an overall 5-year survival rate of around 5%. Currently, intravenous gemcitabine is a standard therapy for patient with advanced pancreatic cancer. Recently, gemcitabine plus nab-paclitaxel therapy was reported to be superior to gemcitabine alone in patients with advanced pancreatic cancer. However, the tumor resistance to chemotherapy is common and activation of nuclear factor-kappa B (NF-κB) is a key player in attenuation of anti-tumor effect of chemotherapy in pancreatic cancer. NF-κB is a transcription factor that plays an important role in the regulation of cell apoptosis, inflammation, and oncogenesis. Therefore, targeting downregulation of NF-κB activation is an important strategy to improve the efficacy of chemotherapy and outcome of patients with pancreatic cancer. We previously reported that nafamostat mesilate, a synthetic serine protease inhibitor, inhibited NF-κB activation and induced antitumor effects for pancreatic cancer. We hypothesized that nafamostat mesilate downregulates the activity of NF-κB and improves therapeutic outcome of pancreatic cancer. The purpose of this study is to prove that addition of nafamostat mesilate to gemcitabine and nab-paclitaxel enhances their antitumor effect against pancreatic cancer.

Methods: ~We assessed NF-κB activity and cell viability of human pancreatic cancer cell lines (PANC-1, MIA PaCa-2, ASPC-1) in the following five groups:  ① those treated with gemcitabine alone, ② gemcitabine and nab-paclitaxel,
③ nafamostat mesilate alone, ④ triple combination (gemcitabine, nab-paclitaxel and nafamostat mesilate), or ⑤ vehicle as control. In combination groups, the cells were treated with gemcitabine and nab-paclitaxel at the same time. In triple combination group, the cells were incubated with nafamostat mesilate at 3 hours before chemotherapy. Activation of NF-κB was evaluated by measuring nuclear localization of p65 protein.

Results:~Cell viability was assessed by the MTT assay. Cell viability in triple combination group was lower than that in gemcitabine plus nab-paclitaxel group (PANC 1: p<0.001, MIA PaCa-2: p=0.004, ASPC-1: p<0.001). The nuclear extracts were assessed using ELISA. NF-κB activity in gemcitabine plus nab-paclitaxel group was higher than that in control group, and NF-kB activity was significantly surpressed in nafamostat mesilate group and in tiple combination group compared with control group and gemcitabine plus nab-paclitaxel group, respectively (PANC-1: p<0.001, MIAPaCa-2: p<0.001, ASPC-1: p<0.001).

Conclusion:~Nafamostat mesilate significantly inhibited NF-κB activation and enhanced anti-tumor effect of gemcitabine plus nab-paclitaxel against human pancreatic cancer.

 

2.15 Role of Sphingosine Kinase 1 of the Host in the Pancreatic Cancer Peritoneal Carcinomatosis.

Posted on December 22, 2014

H. Aoki1, A. Raza1, P. Mukhopadhyay1, K. P. Terracina1, C. C. Barnett3, S. Spiegel2, K. Takabe1,2  1Virginia Commonwealth University,Surgery,Richmond, VA, USA 2Virginia Commonwealth University,Biochemistry And Molecular Biology,Richmond, VA, USA 3University Of Colorado Denver,Surgery,Aurora, CO, USA

Introduction:  Pancreatic cancer remains one of the deadliest cancer. Despite the recent improvement of survival of the small resectable tumors, prognosis of unresectable pancreatic cancer that collectively represent over 80% of individuals remains dismal with the 5-year survival of 5% and median survival is within ten months. Prognosis of patients with peritoneal carcinomatosis (PC), dissemination of cancer cells throughout the abdominal cavity, are particularly poor with median survival of only 6 weeks. This poor overall 5-year survival rate has not significantly changed over the past 5 decades, which reflects the fact that there is no effective treatment available for this condition. Sphingosine-1-phosphate (S1P), a bioactive lipid mediator produced by sphingosine kinase 1 (SphK1), plays critical roles in many aspects of cancer progression, such as cell proliferation, migration, angiogenesis and lymphangiogenesis. We have published in Cancer Cell 2013 that S1P link inflammation and cancer in colitis-associated cancer development. Given the fact that inflammation is known to be essential for establishment and progression of PC, where cancer cells need to adhere to the peritoneum and form a nodule, we hypothesized that S1P generated by SphK1 in the host animal, including peritoneum, is necessary for progression of pancreatic cancer PC.

Methods:  Panc02 cells were obtained from ATCC. Panc02-luc cells were provided in collaboration with CCB. PC models were generated by injecting the cells intraperitonealy to C57Blk6 mice. For the orthotopic model, Panc02-luc cells were implanted in the tail of the pancreas mixed in matrigel. Survival was assessed by Kaplan-Meier method. Progression of Panc02-luc cell PC in either SphK1 wild type (WT) or knockout (KO) mice were assessed by the total tumor burden determined by bioluminescence on the indicated days.

Results: Panc02 cells developed significantly less PC by intraperitoneal injections (5 out of 11 animals with less amount of nodules). On the other hand, 96% of mice developed PC when Panc02-luc cells were injected (52 out of 54 mice with more than four-fold increased amount of nodules). The median survival of Panc02-luc PC model was 18.7 days, whereas orthotopic model was 40 days, despite the fact that 7 out of 10 orthotopically implanted animals eventually developed PC. This mimics human pancreatic cancer progression that PC has remarkably shorter survival. Panc02-luc PC in SphK1 WT mice continue to progress with significant increase in tumor burden quantified by bioluminescence, whereas PC in SphK1 KO mice did not progress.

Conclusion: Our result demonstrated that intraperitoneal injection of Panc02-luc cells in C57Blk6 mice will generate orthotopic pancreatic cancer peritoneal carcinomatosis model that mimic human disease, and SphK1 expression in the host animal, including peritoneum, is necessary for progression of pancreatic cancer PC.

 

2.16 Microbial Determinants of Clinical Outcomes in Patients Undergoing the Whipple Procedure

Posted on December 22, 2014

V. G. Aveson1, R. Brower-Sinning1, B. Firek1, B. Boone1, J. Steve1, M. Hogg1, A. Zureikat1, H. J. Zeh1, M. J. Morowitz1  1University Of Pittsburgh,Department Of Surgery,Pittsburgh, PA, USA

Introduction:
Important recent studies have detailed surprising ways in which the human microbiome contributes to human health and disease. However, contributions of the microbiome to surgical outcomes have not been studied. Here, we conducted a pilot study to investigate bacterial populations present at multiple body sites in patients undergoing pancreatico-duodenectomy (PD) for pancreatic ductal adenocarcinoma (PDA). 

Methods:
We collected intraoperative swabs of pancreatic fluid, bile, and jejunal contents (PB&J) as well as postoperative fecal samples from 12 patients undergoing PD for PDA. After isolation of bacterial DNA, 16S ribosomal RNA gene sequences were sequenced on the Illumina MiSeq platform. Analysis of sequencing results with QIIME software allowed for taxonomic identification and statistical analysis of microbial communities. For each patient, we recorded preop clinical variables (biliary stent, neoadjuvant chemotherapy, antibiotics) and postop outcomes (anastomotic leak, abscess formation, wound infection, cancer recurrence, death).

Results:
Bacterial diversity was surprisingly high in PB&J samples (mean Shannon index 3.7, 2.7, and 2.7 respectively). We detected and characterized bacterial DNA within PB&J samples from 8 of 12 patients. The most abundant taxa within PB&J samples were gram-negative pathogens from the family Enterobacteriaceae (e.g. Citrobacter and Enterobacter), oral pathogens (e.g. Fusobacterium and Aggregatibacter), and intestinal commensals (e.g. Bacteroides). Correlations between PB&J samples varied. One patient had a marked abundance of Fusobacterium in each of the PB&J samples. Interestingly, a high number of DNA sequences from an Enterobacter-like species was found in the PB&J samples from a patient that developed a postop Enterobacter wound infection. Fecal samples from the 12 PDA patients were notable for a relative lack of bacterial diversity (mean Shannon diversity index 3.1), perhaps reflecting perioperative antibiotic therapy.  Additionally, several of the fecal samples contained unusually large populations of gram-negative pathogens (e.g. Citrobacter and Enterobacter). One fecal sample contained a highly unusual dominant population of Enterococcus (relative abundance >90%). Six patients developed a pancreatic anastomotic leak or postop abscess. Due to small sample size, we did not identify associations between the microbiome and either postop complications or preop exposures.

Conclusion:
Microbial diversity in biologic samples collected from PD patients has not previously been studied. Notable findings in this study were the high diversity within bile and pancreatic duct fluid and the presence of oral pathogens known to cause extraoral infections. We are currently enrolling additional study subjects. Future analyses may allow us to identify associations between intraop microbial profiles and postop outcomes. 

2.18 Characterization of a Novel Mutation in Fibrolamellar Hepatocellular Carcinoma

Posted on December 22, 2014

K. M. Riggle1, R. S. Yeung1, H. L. Kenerson1, K. J. Riehle2  1University Of Washington,Surgery,Seattle, WA, USA 2Seattle Children’s Hospital,General And Thoracic Surgery,Seattle, WA, USA

Introduction:  Hepatocellular carcinoma (HCC) is a heterogenous disease that commonly arises in a background of cirrhosis.  Fibrolamellar HCC (FL-HCC) is a subtype of HCC occurring in children and young adults in the absence of known liver disease.  Currently, there is no effective therapy for unresectable or metastatic FL-HCC.  Recent genomic analysis identified a recurrent mutation in FL-HCC involving a deletion on chromosome 19.  The mutation results in a common chimeric transcript containing the 5’-region of a heat shock protein (DNAJB1) fused to the catalytic subunit of protein kinase A (PRKACA).  We sought to characterize this chimeric protein and its effects on PKA activity in human FL-HCC. 

Methods:  We prepared tissue lysates from four snap-frozen FL-HCC samples along with paired, non-tumor liver tissues.  PRKACA expression was determined by immunoblot analysis.  PKA activity was determined via a radioactive kinase assay in the presence of cAMP, a known activator of PKA, with and without PKI, a specific inhibitor of PKA accounting for background activity.  RNA was extracted using TRIZOL reagent, and used to create cDNA for qRT-PCR analysis of the mutant transcript.     

Results:  We confirmed that all tumor samples expressed a 46-kDa fusion gene product in addition to the wild-type 41-kDa PKA protein.  The paired normal liver samples only expressed the wild-type protein.  Further, the mutant protein was not detected in ‘classic’ HCCs nor cancer-associated fibroblasts isolated from a case of FL-HCC.  Using qPCR we found that the FL-HCC tumors expressed the chimeric transcript at levels that were 10.59±4.2 fold higher than normal liver (p = 0.016).  Basal PKA activities from freshly lysed tumors and paired livers were not significantly different, but cAMP-stimulated PKA activity was significantly higher in FL-HCC tumors when compared to normal liver.  In a dose response experiment, the PKA activity in FL-HCC was 3.62, 5.52, and 6.41 pmol/min/mg (vs. normal liver with PKA activity of 2.60, 3.14, and 4.95 pmol/min/mg) at cAMP concentrations of 0.05, 0.5, and 5 uM respectively.

Conclusion:  Our data verify the unique expression of the DNAJB1-PRKACA fusion protein in all FL-HCC samples tested, but absent in the adjacent non-tumor liver and non-FL-HCCs.   Further, the lack of mutant protein expression in fibroblasts derived from FL-HCC highlights the primary effects of the mutation on transformed hepatocytes and not the stromal component.  The expression of the mutant transcript was significantly greater than that of the native PKA indicative of higher intrinsic promoter activity of DNAJB1 compared to that of PRKACA.  Importantly, PKA activity in the FL-HCCs remains cAMP-dependent but with increased sensitivity to cAMP without evidence of enhanced basal activity.  These findings suggest that the expression of DNAJB1-PRKACA in FL-HCC leads to over-activation of PKA under conditions of cAMP production, which may contribute to tumor development.

2.19 Incidental Gallbladder Pathology in Patients Undergoing Cholecystectomy

Posted on December 22, 2014

R. A. Rodriguez1, H. Overton2, K. Morris1, I. Nir1, M. Williamson3, A. Rajput1  1University Of New Mexico,Division Of Surgical Oncology, Department Of Surgery,Albuquerque, NM, USA 2University Of New Mexico,School Of Medicine,Albuquerque, NM, USA 3University Of New Mexico,Department Of Radiology,Albuquerque, NM, USA

Introduction: The highest incidence rates of gallbladder cancer (GBC) in the continental United States are in New Mexico and amongst the minority-majority Native American and Hispanic populations. This cancer is often fatal as most patients present with advanced stages of disease. Early diagnosis remains a challenge as specific signs and symptoms are absent. Early stages of disease, which have a more favorable outcome, are often found incidentally at time of cholecystectomy. The purpose of this study was to determine the incidence of gallbladder pathology in patients undergoing cholecystectomy and to correlate any pre-operative radiographic findings with the pathology.

Methods: Healthsystem database was queried for patients who underwent cholecystectomy between 1991 and 2013. A total of 6793 patients were identified. Data extracted included: demographics, previous ultrasound report, surgical and pathologic reports. Pathologic findings including gallbladder cancer, dysplasia, metaplasia and polyps were recorded. Radiographic reports were reviewed to determine if pre-operative finding predicted final pathologic diagnosis.

Results: There were 4993 (74%) females. Female patients were more likely to present at an older age (52.5) compared to males (45.4); patients who were found to have GBC were more likely to be older (73.4). Out of a total of 17 GBCs identified, 5 (29%) patients were known to have malignancy prior to surgery and 12 (71%) were discovered to have malignancy on pathologic analysis. Pre-operative radiographic findings correlated to pathological findings in only 3 (18%) cases. GB pathology stratified by ethnic group is shown in table 1. GB pathology was more likely to be found in Hispanics and Native Americans although the incidence of pathology was not statistically significant amongst ethnicities in our data set.

Conclusion: Although rare, gallbladder pathology is incidentally found at the time of cholecystectomy.  The diagnosis of cancer, dysplasia, metaplasia and polyps was more common in Hispanics and Native Americans as compared to non-Hispanic whites. Although ultrasonography continues to be a good diagnostic method for gallstones and cholecystitis, its utility in other gallbadder pathologies remains unproven. There is a need to develop new screening and diagnostic methods for patients with gallbladder cancer.

 

2.20 Development of Theranostic Mesoporous Silica Nanoparticles for Pancreatic Cancer

Posted on December 22, 2014

D. S. Pender1, A. Khanal1, S. Hudson1, L. McNally1  1University Of Louisville,Louisville, KY, USA

Introduction: Modern methods of pancreatic cancer diagnosis and treatment are severely lacking and have failed to provide effectual treatment options for patients. The root cause of this inadequacy stems from the hypovascularized nature of pancreatic cancer, making traditional chemotherapeutics and cancer detecting contrast agents nearly obsolete. A potential solution for tumor-targeting difficulties is through the implementation of nanotechnology, specifically targeting ligand capped, theranostic nanoparticles. We hypothesize that pH-responsive chitosan-capped mesoporous silica nanoparticles (MSNs) with the targeting ligand, urokinase plasminogen activator (UPA) will serve as theranostic agents for treatment and diagnosis of pancreatic cancer.

Methods: MSNs were synthesized by employing cetyl trimethylammonium bromide (CTAB), tetraethyl orthosilicate (TEOS) and chitosan through the sol-gel method. The synthesized MSNs were characterized by transmission electron microscopy (TEM) and zeta-potential measurements. Afterwards, gemzar chemotherapeutic drug was encapsulated into these nanoparticles to observe the pH dependent release profiles in vitro. Furthermore, MSNs were tagged with UPA to increase the binding efficiency of these nanoparticles towards the pancreatic tumor cells (S2CP9 and S2VP10). The binding efficiency of both tagged and non-tagged MSNs was observed at various pHs (7.4 to 6.5) by employing fluorescence microscopy, Odyssey infrared imaging and tissue phantoms. For that, various types of dyes were used, such as, rhodamine B and indocyanine green (ICG). Finally, UPA-tagged MSNs with ICG were injected into mice infected with S2CP9 tumors cells to observe the distribution of these nanoparticles in-vivo through multispectral photoacoustic Tomography system (MSOT).

Results: TEM pictures showed that the synthesized MSN had a size around 120 nm.  Zeta-potential measurements revealed that charge density of MSN was dependent on pH.  The release experiments showed that these nanoparticles were pH-sensitive because the release of gemazar depended on the pH. Gemzar released ~2x the quantity from MSNs at pH 6.5 in comparison to pH 7.4.  Fluorescence microscopy, Odyssey infrared imaging and tissue phantoms showed that uptake of MSNs by pancreatic tumor cells depended on the pH and tagging of UPA. Lowering pH and tagging a ligand drastically increased the uptake of MSNs in pancreatic tumor cell in vitro. Specifically in tissue phantoms, UPA-ICG loaded MSNs at pH 6.5 demonstrated 20X and 7X more cell signal than without ligand or at pH 7.4, respectively.  Furthermore, UPA-ICG loaded MSNs were successfully detected in orthotopic pancreatic tumor of mice within 6 hours of imaging time by MSOT.

Conclusion: UPA tagged, pH sensitive MSNs demonstrate potential as a theranostic nanoparticle for pancreatic cancer.

 

17.20 Defining success after parathyroidectomy for secondary hyperparathyroidism: Use of KDIGO guidelines

Posted on December 22, 2014

S. C. Oltmann1, T. M. Madkhali2, H. Chen2, R. S. Sippel2, D. F. Schneider2  1University Of Texas Southwestern Medical Center,Department Of Surgery,Dallas, TX, USA 2University Of Wisconsin,Department Of Surgery,Madison, WI, USA

Introduction
Patients with end stage renal disease (ESRD) suffer from hypocalcemia and secondary hyperparathyroidism (SPHPT).  Therefore, defining recurrence or persistence after parathyroidectomy (PTX) using calcium values alone becomes problematic.  The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines provide target ranges for serum calcium (Ca: 8.4 to 10.2 mg/dL), phosphorous (Phos: 2.5 to 4.6 mg/dL) and parathyroid hormone (PTH: 130 to 600 pg/mL) levels for those patients with ESRD requiring dialysis.  The study purpose is to see if KDIGO targets, which often determine need for initial surgical intervention, are also appropriate to define disease persistence or recurrence in SHPT.
Methods
A retrospective review of a prospective endocrine surgery database was performed.  Included patients had SHPT, due to ESRD, were on dialysis and underwent PTX.  Ca, Phos and PTH were classified as below, within, or above the KDIGO targets at various pre and post-operative time points.
Results
Between 2000 and 2013, 36 patients with SHPT met inclusion criteria. Mean age was 44±SEM2.1 years. 42% were females. Subtotal PTX was performed in 89%, with 11% undergoing total PTX. Follow-up time was 54±7 months. 8 patients (22%) required additional procedures to address recurrent and/or persistent SHPT. 28 patients (76%) of were alive at last follow-up, with estimated survival at 1 year (100%), 2 years (94%), 5 years (82%) and 10 years (65%) calculated. Sensipar use at last follow-up was noted in 2 patients (5%).  At time of last follow up, 46% of patients had Phos levels, and 17% had PTH levels still above the KDIGO ranges (Table).
Factors associated with need for re-operation were assessed. Patient PTH levels within or above target at time of first post-operative visit were associated with a higher rate of reoperation(p<0.01).  At the time of last follow-up, Ca levels with respect to KDIGO ranges were not associated with higher reoperation rates (p=0.33), but higher Phos (p=0.054), PTH (p<0.001) levels were associated with increased rates of reoperation.
Conclusions
Of the various KDIGO laboratory indices for patients with ESRD on dialysis with SHPT, PTH and Phos levels above target were associated with additional surgical intervention.  However, a significant number of patients had laboratory indices above suggested ranges at last follow-up, suggesting many more patients residual or recurrent disease than have undergone reoperation, suggesting that there are many patients who may benefit from more aggressive surgical or medical management.

18.02 A Novel Case Simulator to Help Predict Completion of Plastic Surgery Core Operative Requirements

Posted on December 22, 2014

T. N. Ballard1, W. Pozehl2, T. R. Grenda1, M. S. Daskin2, J. Seagull3, A. M. Cohn2,4, S. J. Kasten1, R. M. Reddy1  1University Of Michigan,Department Of Surgery,Ann Arbor, MI, USA 2University Of Michigan,Department Of Industrial And Operations Engineering,Ann Arbor, MI, USA 3University Of Michigan Medical School,Ann Arbor, MI, USA 4University Of Michigan,Center For Healthcare Engineering And Patient Safety,Ann Arbor, MI, USA

Introduction:  On July 1, 2014, the new Accreditation Council for Graduate Medical Education (ACGME) operative minimum requirements for plastic surgery residents became effective. Under the updated guidelines, the resident “assistant” option is no longer used, and up to two residents can count a case as “surgeon” if each is present for and participates in all of the critical portions of the operation. Given that specific operative case arrival/frequency and resident distribution are not equitable, we sought to assess the applicability of a case distribution simulation model to determine the threshold case volume required to certify plastic surgery residents using the new guidelines. The treatment of occlusal injuries was utilized as an example procedure.

Methods:  A novel computer model was created to simulate annual case distribution based on annual case volume, number of trainees, and rotation length, and assess for a program’s ability to train all residents each year. The simulator varies the annual volume based on historical data provided (above and below the mean).  Single institution occlusal injury treatment data (2010-2013) were used to simulate case distribution for 10,000 “simulated” years to indicate the frequency of one or more senior residents achieving the minimum number of cases during their final two years of training. 

Results: The illustrated program currently has three residents per year, and the average number of occlusal injuries treated was 27.3 ± 6.6 over a four-year period. The ACGME requires all plastic surgery residents to treat at least eight occlusal injuries during training. If the final two years of a resident’s training are simulated, with up to two residents able to count each case and each resident having equal access to all cases, all three chiefs would meet the requirement for occlusal injury treatment 98.2% of the time. If the program expands to four residents, the likelihood of all residents meeting requirements decreases to 87.1%.The minimum number of cases per year necessary to certify three and four residents 100% of the time is 28 and 29, respectively.

Conclusion: Under the new ACGME guidelines for plastic surgery, residents log only “surgeon” cases, and up to two residents may count each case. However, the number of annual cases needed each year to fulfill requirements is greater than simply the number of residents multiplied by the number of required cases (i.e., 3×8 ≠24), due to unpredictable and inequitable case occurrence.  The simulator enables residency programs to analyze the impact of the new operative requirements on the ability to certify current residents and the effect of expanding the number of residents. The broad applicability of such a model is just being realized.

18.03 Impact of “Home Call” on Residency Training in an Otolaryngology-Head & Neck Surgery Program: A Pilot Study

Posted on December 22, 2014

L. Caulley3, J. Vaccani2,3  2Children’s Hospital Of Eastern Ontario,Ottawa, ONTARIO, Canada 3University Of Ottawa,Ottawa, Ontario, Canada

Introduction: Recent studies demonstrated that duty hour restrictions have a positive impact on the quality of life in residency training programs. However, objective data on the necessity for resident duty hour restrictions or the impact of resident duty hours on the academic portion of residency training for surgical residents in a home call setting has yet to be established in the literature.  This was a pilot study to evaluate home call in an Otolaryngology-Head and Neck Surgery residency program and its impact on resident education and well-being using subjective and objective parameters.  

Methods: All PGY 2-4 residents in the University of Ottawa Department of Otolaryngology- Head and Neck Surgery (n=7) were invited to complete an electronic log of their encounters while on night call. Residents were asked to characterize the time elapsed and nature of the call event as either urgent or non-urgent according to a guideline provided by the authors. In addition, all residents completed the Stanford Sleepiness Scale (SSS) on the day of call being investigated and the post-call day to establish a subjective proxy of resident well-being. 

Results:Thirty-six call logs were analyzed for the pilot study. Fifty percent of residents qualified for a post-call day according to the Professional Association of Residents of Ontario guidelines. Residents received an average of 6.7 calls per night (5pm -7am), of which 76% of calls were classified as non-urgent. The amount of time elapsed managing non-urgent and urgent issues was 2.36 and 2.20 times greater in residents who qualified for a post-call day as compared to those who did not qualify for a post-call day, respectively. In order to estimate the effect of call on sleepiness, accounting for pre-call sleepiness score and the fact that there were multiple measurements made on each resident, a linear mixed effects analysis of covariance model was fitted. On average, sleepiness post call was 1.5 points higher (95% CI 0.22 – 2.73, p=0.03) in residents who qualified for a post-call day. The academic activities compromised by post-call included clinic (33%), operative experience (17%), and research and study time (17%). Residents did not take a post call day despite meeting requirements based on time elapsed and fatigue in 33% of calls. 

Conclusion: This was a successful pilot study evaluating the feasibility of this research project to monitor the selected variables and outcomes during resident home call. The authors identified a disproportionately high amount of non-urgent calls that residents received over the course of their call. The experiences of these residents will provide insight into the events encountered on call in a home call setting that may impede academic performance in residency training programs. The authors are optimistic that the significant results of this study will stimulate further investigations into educational reform as it relates to residency training programs in Canada.

 

18.04 The Use of Mobile Video Technology to Improve Patient Care during Call

Posted on December 22, 2014

N. Nosrati1, W. A. Wooden1, R. L. Flores1, R. Sood1, S. S. Tholpady1  1Indiana University,Plastic Surgery,INDIANAPOLIS, IN, USA

Introduction: One of the key learning opportunities in plastic surgery residency is taking call. The residents are on their own to make the initial diagnosis and plan and to effectively communicate all the data to their attending. One component is accurately reading imaging studies. The maxillofacial computed tomography imaging is among the more complex a plastic surgery resident will encounter on call. In this study, we analyzed the resident’s ability to read and process the films.

Methods: Using the plastic surgery sign out system, images were extracted from the previous 4 months. The images used were identified by the on-call resident as the crucial CT slices to make the diagnosis and plan. The corresponding computed tomography films were identified. Using a Pantech P4100 tablet, these films were video recorded. The images and films were then grouped according to resident year. Individually, each craniofacial attending was first shown the images and asked to decide on a management plan.  They were then shown the video and asked if their management changed. Changes in plans were recorded.

Results:A total of 15 films were identified, 6 in the first year independent, 2 in the second year independent, 3 in the fourth year integrated, and 4 in the second year integrated.  Image data was missing on 37 sign outs. Attending 1 changed his plan 40% of the time, attending 2 20% of the time, and attending 3 6.7% of the time for an average change of 22.2%. All attendings independently agreed on 7 operative plans.

Conclusion: As resident level progressed, selection of crucial slices of imaging improved. However, even in the more senior years there was some discordance with image selection. While CT is not the sole factor in management of craniofacial trauma, it does play a significant role. All the study participants agreed, having a full CT available improves communication and planning. In areas where information systems do not allow for easy viewing of images, the transmission of video with a full CT provides an alternate method to evaluate and change resident plans leading to improved patient care and resident education.

If feasible, especially in earlier resident years, use of computed tomography video recordings greatly enhances patient management and resident education of craniofacial trauma.
 

18.05 The Characteristics of Effective Mentorship for Female Academic Surgeons

Posted on December 22, 2014

A. Cochran1, W. B. Elder1, L. A. Neumayer2  1University Of Utah,General Surgery,Salt Lake City, UT, USA 2University Of Arizona,Tucson, AZ, USA

Introduction:  The lack of same-sex mentors and senior female role models for female academic surgeons has been postulated as a source of isolation and cited as a limitation in career development.  Inadequate mentoring also contributes disproportionately to junior female academic surgeons considering exit from academia.  The goal of this study was to describe how successful mid-career and senior female academic surgeons describe effective professional mentorship.

Methods:  A single interviewer conducted semi-structured interviews with 11 mid-career and senior female academic surgeons.  Each interviewee was asked to discuss barriers they had experienced or observed during their academic surgical career.  Participating surgeons were purposefully selected to maximize institutional, specialty, and ethnic diversity.  Grounded theory methods were used to develop a theoretical model of the mentoring needs of female academic surgeons; the use of grounded theory allows for development of a theory grounded in the unique experiences and observations of female academic surgeons.

Results: Finding appropriate invested mentorship was described as a barrier to an academic surgical career by most interviewees (6/11); this theme was explicitly expanded during the course of their interviews through discussion of how they define mentorship and how it has impacted their career development.  The theme most commonly described was the need for more than one mentor (9/11); the various participants described this need across the trajectory of their career, across disciplines to meet both clinical and scholarly needs, and even across institutions. Most interviewees also indicated a need for a mentoring committee or team if one is to succeed in academic surgery (6/11), with one surgeon stating, “Success is not in isolation.”  Seven surgeons described the key quality of a mentor as being invested in the success of the mentee without personal gain to the mentor. Almost all interviewees described the primary work of mentoring as assisting the mentee to develop a strategy to achieve their goals (10/11).  The majority of respondents recognized that while part of the work of the mentor is to insure regular engagement and interaction occurs, the mentee has a responsibility to come prepared with specific goals and issues requiring the mentor’s assistance (7/11).

Conclusion: Effective mentorship is often cited as a key to success for women in academic surgery, although no prior studies specifically delineate the characteristics of effective mentorship.  A need for multiple mentors across time and disciplines was clearly identified from both a mentor and mentee perspective.  The idea of “mentorizing” experienced individuals by actively seeking specific input was identified as an effective strategy for mentees.  Finally, effective mentors are seen as those individuals who achieve no personal gain from their role but instead derive satisfaction from the success of others.

 

18.06 Restrictive Covenants: A Survey of Residents Understanding and a Call for Increased Education

Posted on December 22, 2014

C. M. Forleiter1, A. M. Al-Ayoubi1, R. J. Chouake1, M. Barsky1, S. Rehmani1, F. Y. Bhora1  1Mount Sinai School Of Medicine,Mount Sinai Roosevelt Hospital / Department Of Thoracic Surgery,New York, NY, USA

Introduction:  Several significant concerns have been raised regarding restrictive covenants (RCs) and their impact on the medical profession. The purpose of this research is to assess the understanding of the current residents and raise awareness about this important topic.

Methods:  An anonymous electronic survey was sent to all 432 residents at a tertiary hospital in New York City. The survey was comprised of 30 questions including demographics, a pre-test, educational material, and a post-test to assess trainees understanding of restrictive covenants, and their impact on physicians’ jobs, lives, and patients’ care. 

Results: There were a total of 115 responses (27% response rate) across all the major residency programs. Overall, 45% of residents were not even aware of restrictive covenants prior to this survey and 87% of residents have received no formal education in employment contracts in medical school or residency. After a short pre-test followed by educational material, the overall percentage correctly answered improved on every question asked on the post-test (see chart). 94% of residents were concerned about a geographic and/or time restriction should they change jobs and 90% thought having to relocate would affect them significantly, citing patient relationships, referral patterns, spouse’s career and children’s schooling as reasons. Over 80% of residents never discussed contract negotiations with an Attending mentor and 83% did not know physicians could bargain RCs out of their contracts. Most residents polled think restrictive covenants damage the physician-patient relationship (84%) and do not belong in a profession like medicine (71%). Lastly, almost all respondents will pay more attention to restrictive covenants when signing their next contracts (76%).

Conclusion: There is a considerable lack of awareness and discussion among medical trainees regarding restrictive covenants. Residents feel RCs have the potential to significantly affect the practice of physicians and limit patients’ access to their doctors. With just a little educational material, residents across all specialties polled were able to demonstrate understanding and almost all seemed concerned that RCs would negatively impact their lives, both personally and professionally. Further assessment from the larger medical community is warranted, with a heavy emphasis on education.
 

18.07 An Apprenticeship Rotation Teaches Chief Residents Non-technical Skills and ACGME Core Competencies

Posted on December 22, 2014

G. Kwakye1, X. Chen1, J. Havens1, J. Irani1, D. S. Smink1  1Brigham And Women’s Hospital,Department Of Surgery,Boston, MA, USA

Introduction:   Traditionally, surgical training utilized an apprenticeship-model but has more recently moved to a service-based model, with groups of residents working with groups of attending surgeons.  We developed an apprenticeship rotation to encourage more one-on-one interaction between residents and faculty. We hypothesized that the apprenticeship-model would be effective for teaching non-technical skills (NTS) and core competencies.

Methods: Surgery chief residents from two consecutive classes at a single institution identified a preceptor to work with over a dedicated one-month rotation.  Emphasis was placed on acquiring the 4 non-technical ACGME core competencies- Interpersonal Skills and Communication (ISC), Practice-based Learning and Improvement (PBLI), Professionalism (Prof), and Systems-based Practice (SBP). Participants were surveyed anonymously afterwards about their rotation.

Results:   100% (13/13) residents and 67% (8/12) faculty completed the survey.  84.6% of residents and 87.5% of faculty would recommend the rotation to others.  Both groups felt that technical skills (TS) and NTS improved.  However, there was a trend for faculty to find the rotation more useful at teaching NTS than TS (NTS: mean 4.63, median 5.0; TS: mean 3.63, median 4.0; p<0.06). Residents reported improvement in all 4 non-technical competencies, particularly PBLI, Prof, and ICS.  85% felt the skills obtained were relevant to their intended career or fellowship training.

Conclusion:  The apprenticeship-model is an effective means of teaching residents both TS and NTS essential for independent practice. Faculty and residents, however, differ on the area of greatest impact, with faculty reporting greater improvement in non-technical competencies. Consideration should be given to introducing this program into surgical curricula nation-wide and expansion to other residents.

18.08 Palliative Care Training in Surgical Oncology and Hepatobiliary Fellowship: National Fellows Survey

Posted on December 22, 2014

G. Larrieux1, J. T. Miura1, K. J. Brasel1, D. E. Weissman2, A. B. Nattinger3, T. C. Gamblin1, K. T. Turaga1, F. M. Johnston1  1Medical College Of Wisconsin,Surgery,Milwaukee, WI, USA 2Medical College Of Wisconsin,Palliative Care,Milwaukee, WI, USA 3Medical College Of Wisconsin,Medicine,Milwaukee, WI, USA

Introduction: Surgical Oncologists (SO) and Hepatobiliary (HPB) Surgeons frequently care for patients with advanced disease stages who are near the end of life, yet little is known about their training, comfort and readiness in the provision of palliative care.  This study sought to assess the quality, adequacy and extent of palliative care training and readiness of SO and HPB Fellows in delivering palliative care.   

Methods: A self-administered survey was distributed to all fellows enrolled in Society of Surgical Oncology (SSO) and HPB fellowships during the 2013-2014 academic years.  The survey assessed attitudes, training, experience, and readiness of fellows in caring for patients at the end of life.  Descriptive analysis was performed and Chi-square, Student’s t-test as well as Mann-Whitney U test were used to compare mean or median values as appropriate.

Results:The response rate was 47.2%. 50.9% of fellows reported exposure to a palliative care specialty service during their fellowship. 75% of our participants observed their faculty discussing the side effects of surgery compared to 54% observation of faculty’s communication regarding end of life goals with patients (p<0.01). 40% of fellows were never observed by faculty discussing symptoms management, goals of care, or hospice referral with patients and 56.7% never received feedback on their palliative skills. Fellows consistently rated their quality of teaching and managment of surgical disease at better compared to palliative and end of life topics (Figure 1).

Conclusion:Fellows rated the quality of palliative care education as poor compared to other aspects of fellowship training, implying the need and lack of palliative care teaching.  Surgical oncology and HPB fellows and ultimately patients may benefit from increased clinical and didactic palliative care training.
 

18.09 Administrative Chief Residents – How are they chosen and does it matter?

Posted on December 22, 2014

A. Weiss1, D. Tandon1, B. Chandrasekaran1, V. Tapia1, K. C. Lee1, S. Ramamoorthy1, S. L. Blair1  1University Of California – San Diego,San Diego, CA, USA

Introduction: There is no existing literature on the process of appointing administrative chief residents (ACR) in surgical programs; nor on the disparity of minority representation in this position. This study’s purpose was to examine various residency’s processes and the demographics of the residents who have held the position.

Methods: After IRB approval was obtained from UCSD, a 20 question survey was sent to all surgical program directors and residency coordinators in the United States – to survey all residents and faculty. Survey Monkey, an online survey program, was used to question and analyze the results.  A survey was developed for use in this study.  It was piloted at our institution and revised prior to release.

Results: There were 101 survey respondents, an approximate 10% response rate. 99% of these were general surgeons and 97% had ACRs at their program.  85% were residents, 56% were male, 53% were resident level 3-5 and 3% were full professors. 50% of respondents were from a program with 20-50 residents, 65% from a program with 50% female residents, 76% with 25% ethnic minorities. 71% of respondents report that there is no clear policy on the ACR position, to the best of the respondent’s knowledge 63% believe the position is appointed. In the last 5 years, half of respondents had less than 25% female ACRs and 31% had less than 50% female ACRs. Similarly, 52% had zero minority ACRs and 40% had 25% minority ACRs. 49% believed making the call schedule was the most important responsibility of the ACR; 27% believe being respected by the residents is the most important quality and 24% believe organization to be most important. 54% of respondents believe their ACR receives a stipend, but 70% report there is no training involved. 35% of respondents report that in the last 5 years 50% of their ACRs went into academic practice, and 30% report that more than 75% went into academics.
 

Conclusion: Although most surgical programs in the country train 50% female residents, most have less than 25% female ACRs over the last 5 years. This trend is similar for ethnic minority residents. ACRs in the United States are often receiving a stipend, and are more often going into academic practice. ACR is a position that most respondents feel commands respect and carries with it potential monetary and career advantages; thus programs should keep diversity in mind in appointing ACR.
 

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