bluuebunny/crossref_metadata_2025_split huggingface dataset:
Field deployable platform for prognostic hepatic cancer screening.
Authors: Shea Jill E. , Granger Jennifer H , Porter Mark D , Scaife Courtney L. 
Published: March 2017

267 Background: Hepatocellular carcinoma (HCC) incidence rates are increasing in many parts of the world particularly in low- and middle-income countries (LMICs). Although treatable if identified in the early stages in many LMICs patients are identified later in disease. A low cost point of care system that could identify patients at a higher risk of having HCC could be used as a screening tool to identify patients at an earlier stage. We are currently developing a low cost point of care hand held platform that can simultaneously evaluate the blood levels of common HCC markers. We present our preliminary findings on the limit of detection (LOD) of our system. Methods: Our device combines the rapid but qualitative results of a vertical flow assay with the quantitative capabilities of surface enhanced Raman scattering spectroscopy. Our final product will be able to simultaneously measure the blood levels of the five most proven markers of HCC: alphafetoprotein (AFP), lens-culinaris agglutinin binding alphafetoprotein (AFP-L3), des-gamma-carboxy prothrombin (DCP), core antibodies to hepatitis B virus (HBV), and core antibodies to hepatitis C virus (HCV). In this pilot study we initially evaluated the LOD of our system by evaluating known concentrations of AFP in human serum samples. We then evaluated serum levels of AFP in HCC patient samples (n = 5) with our device and compared with values obtained using a standard ELISA. Results: The LOD of our system for the detection of AFP in spiked serum samples was 1 ng/mL. Our quantitative lateral flow assay measured AFP within 10% of the values of obtained by standard ELISA, with serum values ranging from 10-900 ng/mL. The quantitative vertical flow assay was able to provide results within 5 minutes at a cost of approximately $2/sample. Conclusions: Our inexpensive, portable and rapid test was able to measure serum levels of AFP at values comparable to standard clinical methods. Importantly, one blood marker would be insufficient to identify high risk patients, so further research will be required to expand the number of markers within the panel. The end goal will be to evaluate the ability of our point of care system to screen high risk population in LMICs, thereby identifying at risk patients earlier in disease progression.
Ethnicity and hepatocellular carcinoma risk factors in New Mexico: A retrospective analysis over a 12-year period.
Authors: Win Khine Zar , Osman Diaa , Du Ruofei , Patt Yehuda Z. 
Published: March 2017

269 Background: Common hepatocellular carcinoma (HCC) risk factors, such as hepatitis C virus (HCV) and hepatitis B virus infections, heavy exposure to alcohol and non-alcoholic steatohepatitis (NASH), vary in relation to gender, ethnicity, and geographic regions. New Mexico (NM) has the highest adjusted risk ratio of 1.27 for HCC when compared with other US geographic regions. The population of Hispanic Whites (HW), non-Hispanic Whites (NHW) and American Indians (AI) in NM provides a unique opportunity to study the prevalence of the known HCC risk factors among different ethnicities. Methods: We identified about 550 patients who were diagnosed and/or received treatment for HCC at the University of New Mexico (UNM) Hospital and the UNM Cancer Center from 2003 to 2015, using ICD 9/10 codes. Following approval by institutional review board, a retrospective chart review was conducted to correlate the known HCC risk factors and ethnicity of patients. This is a preliminary report of the findings in a randomly selected 226 of the 550 patients, and we expect to complete the analysis by the time of the GI ASCO symposium. A logistic regression with pairwise comparison was conducted to determine the distribution of the HCC risk factors among different ethnicities. Results: Among NHW, HCV is the most prevalent risk factor for HCC. AI have lower proportion of HCV infection, compared to NHW (35% vs 74%; P= 0.0008). However, DM and NASH were more frequently observed among AI than NHW, 54% vs 27% and 27% vs 9% ( P= 0.025 and 0.038) respectively. Table 1: Proportion of HCV, diabetes, NASH among AI, NHW and HW and pairwise comparison between ethnic groups. Conclusions: Among AI, the major risk factors for HCC seem diabetes mellitus and NASH. However, among NHW, chronic HCV infection is the most prevalent risk factor for HCC.[Table: see text]
Cholangiocarcinomas: A study of patient and disease characteristics and the potential use of tumor molecular profiling.
Authors: Prins Petra , Riskin Jeff , Charipova Karina , Dea Michelle , Furlong Ben , He Aiwu Ruth 
Published: March 2017

270 Background: There are approximately 12,000 new cases of cholangiocarcinoma in the US annually and, as for most GI cancers, the incidence is rising each year. Unfortunately treatment options are limited and surgery is only a possible curative option if the disease is diagnosed at an early stage (5 yr. survival, 20-30 %). Molecular profiling may play a crucial role in the discovery of new (early) biomarkers and treatment options for cholangiocarcinoma. Methods: Clinical records 104 cholangiocarcinoma patients (pts) at the Lombardi Comprehensive Cancer Center were reviewed. Only pts that had received surgical therapy were eligible for study. Variables collected included pt demographics, initial disease stage, tumor differentiation, and clinical (pre-existing) conditions. Tumor recurrence and pt survival from time of surgery was evaluated. Molecular profiling data was analyzed when present. Results: In our cohort we identified 41 pts with cholangiocarcinoma who underwent surgery at LCCC. Clinical data was as follows: 20 males and 21 females. Average BMI at diagnosis was 25.8 kg/m2. Twelve pts had extrahepatic cancer, 20 intrahepatic, 5 gallbladder, 3 Hilar and 1 combined hepatocellular and bile duct cancer. Most tumors were stage T2 or T3 (61%), and were moderately (71%) to poorly differentiated (22%). Vascular or perineural invasion was identified in 46% of cases. Thirty-four percent and 37% had diabetes and hyperlipidemia, respectively. Tumor recurrence had occurred in 13 cases (32%), and median time to recurrence was 8.5 months (m). Median OS from surgery was 10.5 m (to date, 4 pts > 36 m). Molecular profiles were obtained in 5 cases. Most frequently observed genetic mutations were related to tumor suppression (PTEN, 4 cases) and DNA synthesis, repair, and regulation (TOP2A [3x], TOPO1 [2x], TP53 [2x]). Conclusions: Five-year survival rates for cholangiocarcinomas are low. To improve outcomes, improved early detection methods and better treatment options are urgently needed. Increasing the frequency of molecular profiling can result in new prognostic biomarkers as well as the potential for new treatment ideas.
Agreement validation between axial imaging modalities and endoscopic ultrasonography in staging resectability of pancreatic cancer.
Authors: Pham Nghia , Pappas Sam G. , Enchia Ebenezer , Gliniewicz Adam , Small William , Gupta Neil , Dudiak Christine M. , Mahmoud Faaiza , Ahuja Aakash , Aquisto Thomas , Gooneratne Nihal , Nanda Tejvir , Ozga Timothy , Martin Brendan , Thomas Tarita 
Published: March 2017

273 Background: Vascular involvement is a key determinant of resectability and treatment sequencing in pancreatic cancer (PC). Current staging requires multidetector CT (MDCT) and endoscopic ultrasonography (EUS), but there are still occasions when vascular involvement cannot be fully assessed. Current NCCN guidelines recommend using magnetic resonance imaging (MRI) for clarifying these ambiguities. The primary aim of our study is to access the accuracy of CT, MRI, and EUS in staging resectabilty of PC. The secondary aim is to assess internal consistency in the evaluation of vascular involvement among different staging modalities. Methods: We retrospectively reviewed 40 medical records of patients who were treated at LUMC for PC from 2006 to present. We evaluated 8 MDCT scans and 8 MRI scans in addition to their EUS reports. Seven board certified radiologists analyzed the 16 imaging studies using a standardized template. Unweighted Kappa statistic and observed agreement analysis was calculated to assess inter-observer agreement on vessel involvement between the imaging studies compared to the EUS reports. We sought to examine degree of concordance for involvement of the superior mesenteric artery (SMA), superior mesenteric vein (SMV), and main portal vein (MPV) with the pancreatic tumor. Results: Low Kappa and observed agreement in respect to vascular involvement between MDCT and EUS was found for SMV (K = 0.33, 62.5%), SMA (K = -0.2, 62.5%), and MPV (K = 0.38, 75%), indicating low concordance. Low Kappa and observed agreement in respect to vascular involvement between MRI and EUS was found for SMV (K = 0.09, 37.5%), SMA (K = 0.14, 62.5%), and MPV (K = 0.47, 75%). Low Kappa and observed agreement in respect to vascular involvement between MRI and MDCT in comparison to EUS was found for SMV (K = 0.11, 50%), SMA (K = 0.20, 75%), and MPV (K = 0.14, 62.5%). Conclusions: Concordance was shown within each imaging modality when analyzed by radiologists. Due to high discordance across different staging modalities, however, MRI and CT scans complement each other in determining degree of vascular involvement. We believe both imaging modalities should be used in staging borderline resectable PC.
Opportunities for improving outcomes in pancreatic cancer patients: Characterizing the unresected “resectable” population.
Authors: Kish Jonathan , Feinberg Bruce A. , Maida Tracy , Biggs Craig , Mujumdar Urvi , Chopra Dhruv , Laney Jalyna R. , Kennedy Eugene 
Published: March 2017

274 Background: Resection is the only curative intent therapeutic option for pancreatic adenocarcinoma (PA). Recent studies suggest adjuvant chemo can significantly improve overall survival (OS). Patients who may be eligible for, but do not receive, a resection (“resectable”) may represent an opportunity to improve pancreatic cancer outcomes. This research sought to characterize this population using real-world data. Methods: Individuals with pancreatic cancer (ICD-9=157.x, excluding 157.4) diagnosed between 03/2012-06/2015 were selected from the Inovalon More2 claims database. Resection was defined as the presence of any of the following codes on any claim following diagnosis: CPT=48140, 48146, 48150, 48152-5. A diagnosis of metastatic disease was said to occur if any of the following ICD-9 CM codes were present on a claim: 196.0-196.3, 196.5-196.6, 197.0-197.8, and 198.0-198.8. Patients were deemed “resectable” if there was no claim for surgical resection and if their claim for metastatic disease was post-initiation of chemotherapy. Results: Of 7,159 patients identified with PA, 85.8% (n=6,145) were unresected, 40.8% (n=2,924) had received chemotherapy which included 54.4% (n=552) of resected patients and 38.6% (n=2,372) of non-resected patients. Of unresected patients receiving chemotherapy, 27.4% had no record of a metastatic diagnosis, 51.9% had a metastatic diagnosis prior to the start of chemotherapy (mean time metastatic diagnosis = 0.4 months) and 20.7% had a metastatic diagnosis after the initiation of chemotherapy (mean time metastatic diagnosis = 4.8 months). Overall, 18.5% (n=1139) of non-resected patients were classified as unresected “resectable”. Conclusions: The vast majority (85.8%) of pancreatic cancer patients did not undergo a surgical resection. We estimate as many as 18.5% of non-resected patients may be unresected “resectable” given 4.8 months between diagnosis, chemotherapy start and documentation of metastases. As surgical resection is the only curative intent therapeutic option, and prolongs survival even in those not cured, identifying patients who may be eligible for resection is critical to improving pancreatic cancer outcomes.
Impact of major vascular resection on short- and long-term outcomes in patients with intrahepatic cholangiocarcinoma.
Authors: Reames Bradley , Pawlik Timothy M. , Ejaz Aslam , Marques Hugo , Aldrighetti Luca , Maithel Shishir Kumar , Bauer Todd W. , Shen Feng , Poultsides George A. , Marsh J. Wallis , Popescu Irinel , Sandroussi Charbel , Clark T 
Published: March 2017

275 Background: Major vascular (IVC or portal vein) resection for Intrahepatic Cholangiocarcinoma (ICC) has traditionally been considered a relative contraindication to resection. We sought to define perioperative outcomes and survival of ICC patients undergoing liver surgery with major vascular resection using a multi-institutional database. Methods: 1,087 ICC patients who underwent liver resection between 1990-2016 were identified from 13 participating institutions. Multivariable logistic and cox regressions were used to determine the impact of major vascular resection on perioperative outcomes and long-term overall survival. Results: Of 1,087 patients who underwent resection, 128(11.8%) also underwent major vascular resection [21(16.4%)IVC resections, 98(76.6%)PV resections, 9(7.0%)combined resections]. One hundred eighty-seven(17.2%) patients received neoadjuvant therapy. Most patients underwent a major hepatectomy involving ≥ 3 liver segments(n = 664,61.1%). On final pathology, the majority of patients had T1(40.4%) or T2(35.5%) tumors; 194(17.8%) had lymph node metastasis. Patients undergoing major vascular resection had more advanced T3/T4 tumors [44(34.4%) vs. 137(14.3%) without resection;P < 0.001]. Of note, major vascular resection was not associated with the risk of any complication (OR .680,95%CI 0.32-1.45) or major complication (OR 0.69,95%CI 0.35-1.33); post-operative mortality was also comparable between groups (OR 1.06, 95%CI 0.32-3.48). In addition, median recurrence-free (14.0 months vs.14.7 months, HR.737,95%CI .49-1.10) and overall (33.4 months vs.40.2 months, HR .709,95%CI.36-1.40) survival were similar among patients who did and did not undergo major vascular resection, respectively(both P > 0.05). Conclusions: Among patients with ICC, major vascular resection was not associated with increased peri-operative morbidity or mortality at major centers. Long-term outcomes following resection of ICC requiring vascular resection were also comparable to outcomes following resection of tumors without vascular involvement. Concurrent major vascular resection should be considered in appropriately selected ICC patients.
The impact of extrahepatic disease among patients undergoing liver-directed therapy for neuroendocrine liver metastasis: A multi-institutional analysis.
Authors: Ejaz Aslam , Pawlik Timothy M. , Reames Bradley , Maithel Shishir Kumar , Poultsides George A. , Bauer Todd W. , Fields Ryan C. , Weiss Matthew J. , Marques Hugo , Aldrighetti Luca 
Published: March 2017

277 Background: Management of neuroendocrine liver metastasis (NELM) in the presence of synchronous extrahepatic disease (EHD) is controversial. We sought to examine the outcomes of patients undergoing liver-directed therapy for NELM in the presence of EHD using a large multicenter international cohort of patients. Methods: 612 patients who underwent liver-directed therapy were identified from 8 participating institutions. Postoperative outcomes, as well as overall (OS) and progression-free survival (PFS) were compared between patients with (N = 70, 11.4%) and without (N = 542, 88.6%) EHD. Results: Median age of the cohort was 57 years (IQR: 48, 65) with a slight majority of patients being male (N = 326, 53.3%). The majority of primary tumors were located in the pancreas (N = 254, 41.8%) followed by the small bowel (N = 188, 30.9%). At the time of liver-directed surgery, patients underwent surgery alone (N = 471, 77.0%), ablation alone (N = 15, 2.5%), or a combined approach (N = 126, 20.6%). Most patients underwent a non-anatomic wedge resection (N = 404, 66.0%). Patients with EHD had more aggressive high-grade tumors (EHD: 44.4% vs. no EHD: 16.1%; P < 0.001). EHD was most commonly located in the peritoneum (N = 29, 41.4%) and lung (N = 19, 27.1%). Among the 70 patients with EHD, 20.0% (N = 14) underwent concurrent resection for the EHD. After a median follow-up of 51 months, 174 (28.4%) patients died with a median OS of 140.4 months among the entire cohort. Patients with EHD had a shorter median OS versus patients who did not have EHD (EHD: 87 months vs. no EHD: not reached; P = 0.002). Similarly, PFS was shorter among patients with EHD compared with patients without EHD (EHD: 46.8 months vs. no EHD: 68.6 months; P = 0.005). In the cox regression model, the presence of EHD was independently associated with an increased risk of death (HR: 2.56, 95%CI 1.16-5.62; P = 0.02). Conclusions: Patients with NELM and EHD had more aggressive tumors, which conferred over a 2-fold increased risk of death compared with patients who did not have EHD. Surgical treatment of NELM among patients with EHD should be individualized.
Molecular biomarkers as predictors of patient survival in pancreatic adenocarcinoma (PDA): An analysis of the Know Your Tumor initiative (KYT).
Authors: Bender R Joseph , Halverson David , Mason Kimberly , Luo Linlin , Brody Jonathan Robert , Rahib Lola , Matrisian Lynn McCormick , Hendifar Andrew Eugene , Hoos William Arthur , Mikhail Sameh , Chung Vincent M. , Picozzi Vincent J. , Ramos Corinne , Heartwell Craig , Varieur Katelyn , Aberra Metasebia , Petricoin Emanuel , Madhavan Subha , Pishvaian Michael J. 
Published: March 2017

278 Background: Recent studies have expanded our knowledge of the genomic landscape of PDA. While critical and in some cases, potentially actionable alterations are being identified, limited outcomes data have thus far made it difficult to validate the relevance of these observations. Methods: The Pancreatic Cancer Action Network (PanCAN) and Perthera have facilitated commercial tumor molecular profiling for over 400 PDA pts since 2014 through KYT, and have developed a database of molecular and clinical information useful for data mining of biomarker-survival correlations. The survival significance of biomarkers was assessed using standard statistical methodology including Kaplan-Meier analysis and Cox proportional hazard models. Results: Linked molecular and outcomes data were available for 360 pts, of which 173 had treatment (tx) information available. Pathogenic mutations from targeted NGS, protein expression from IHC, and protein phosphorylation from RPPA were screened for correlations with overall survival (OS) and progression-free survival (PFS) independent of tx received. As shown in the table, mutations in 3 genes were associated with a better OS; while mutations in 8 genes were associated with poorer OS. Only two mutations were correlated with PFS in 1st or 2nd-line tx ( BRCA2 and KDM6A, worse PFS). Positive expression of 7 proteins, including TS, TOP1, and RRM1, were associated with reduced OS but were not correlated with PFS. High levels of phospho-ribosomal protein S6 were associated with both poor OS (HR=10.3, p=0.001) and poor PFS (HR=9.6, p=0.006). Conclusions: Multiple biomarkers had significant correlations with OS in PDA, while fewer were correlated with PFS. Growth of this registry database will further validate tx-specific predictive biomarkers for use in pts with multi-omic profiling data. [Table: see text]
Influence of cytotoxic tumor-infiltrating T lymphocytes on outcome in resectable pancreatic cancer: Results from the CONKO 001 trial.
Authors: Striefler Jana Kaethe , Sinn Marianne , Jöhrens Korinna , Pelzer Uwe , Blaeker Hendrik , Jühling Anja , Sinn Bruno Valentin , Oettle Helmut , Wislocka Lilianna , Bischoff Sven , Denkert Carsten , Riess Hanno , Lohneis Philipp 
Published: March 2017

281 Background: The role of T lymphocytes, frequently found in the tumor microenvironment, on development and behavior of several solid tumors is well recognized. Studies on breast cancer and colon carcinoma showed the prognostic and predictive impact of tumor infiltrating T lymphocytes (TILs) while there are no similar studies on pancreatic cancer (PC) until now. Methods: We evaluated the prognostic effect of CD8 and CD103 positive TILs in a cohort of PC patients in the CONKO-001 study treated with adjuvant Gemcitabine or observed only. In 165 formalin-fixed paraffin-embedded (FFPE) tissue samples suitable for tissue microarray construction, CD 8 und CD 103 positive TILs were identified by immunohistochemical staining and counted manually; a ratio of intraepithelial to total CD 103 positive TILs was calculated. Results: The mean number of CD8 positive TILs was 69, a high number ( > 42 TILs) of CD8 positive lymphocytes was significantly associated with longer disease-free (DFS) and overall survival (OS) in the overall study population (high vs low median DFS 12.8 vs 7.4 months; p = 0.007, median OS 26.7 vs 18.1 months; p = 0.018). Furthermore, a ratio of intraepithelial to total CD103 positive lymphocytes < 0.3 was associated with significantly improved DFS and OS in the overall study population (high vs low median DFS 6.5 vs 11.8 months; p = 0.031, median OS 16.6 vs 24.7 months; p = 0.009). Conclusions: Our results suggest that the presence of TILs is important for prognosis in resected PC. We showed for the first time a prognostic effect of CD 8 and CD 103 expressing lymphocytes in PC. Therefore, we suggest further analysis of lymphocyte populations in this dismal entity.
Impact of age on genomic alterations associated with pancreatic ductal adenocarcinoma (PDAC).
Authors: George Ben , Bailey Mark , Schrock Alexa Betzig , Thorpe Lauren , Gay Laurie M. , Ritch Paul S. , Thomas James P. , Erickson Beth , Tsai Susan , Christians Kathleen K. , Evans Douglas B. , Stephens Philip J. , Miller Vincent A. , Ross Jeffrey S. , Singhi Aatur D. , Ali Siraj Mahamed 
Published: March 2017

282 Background: Large scale, retrospective, sequencing projects have identified well-defined subtypes of PDAC, but therapeutic paradigms remain unchanged. We hypothesized that genomic alterations associated with PDAC in young adults (YA, age < 50) are distinctly different from that of older adults (OA, age > 50) to identify an enrichment of targetable alterations. Methods: DNA was extracted from formalin fixed paraffin embedded (FFPE) PDAC clinical specimens and comprehensive genomic profiling (CGP) was performed on hybrid-capture, adaptor ligation based libraries to a mean coverage depth of > 600 for up to 315 genes plus 47 introns from 19 genes frequently rearranged in cancer. Results: CGP was performed on 1533 FFPE PDAC specimens, 566 (36.9%) were from the primary tumor, 967 (63.1%) from metastatic sites. Median age at diagnosis was 63 years (yrs), 180 (11.7%) were YA. KRAS mutations were identified in 78.7 of YA and 87.7% of OA. The differentially altered genes between the two groups were KRAS (p = 0.004), TP53 (p = 0.04), BRCA2 (p = 0.02), AKT2 (p = 0.03), MAP2K4 (P = 0.003) and DNMT3A (p = 0.0002). The median tumor mutational burden (TMB) for the entire study set was 2.7 (YA – 2.5, OA –2.7). BRAF kinase domain deletion was observed in 1 patient (OA). ALK fusions were present in 2 patients (1 YA & 1 OA) and these patients had durable responses to specific ALK inhibitors. Conclusions: The majority of the genomic alterations identified were not significantly different on the basis of age. However, identification of subpopulations, such as ALK kinase fusions and BRAF kinase domain deletions that can translate into sustained clinical benefit from matched targeted therapy is promising. This underscores the importance of CGP in PDAC to investigate other targetable genomic alterations.