bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global Protein Aberration Score (GloPAS): A comprehensive risk score to predict hepatocellular carcinoma biology and estimate patients’ survival.
Authors: Kaseb Ahmed Omar , Zohner Emma , Xiao Lianchun , Wang Zeya , Hassan Manal , Abdel-Wahab Reham , Ballard Karri , Wolff Robert A. , Amin Hesham M. , Wang Wenyi , Yao James C. , Morris Jeffrey 
Published: January 2019

287 Background: Existing hepatocellular carcinoma (HCC) staging systems use a small number of empirically selected clinical/biological variables. We hypothesize that GloPAS (global protein aberration score) will capture a more global measurement of disease biology that can partition HCC into three subsets: (1) essentially normal profiles, (2) extremely aberrant profiles, and (3) slightly aberrant profiles. Methods: We collected plasma samples and clinical data prospectively from 767 HCC patients (pts) and 200 healthy controls, and quantified 317 pts using Myriad RBM CLIA-certified panel, Austin, TX. We applied a deconvolution algorithm, originally developed for determining percent normal contamination for tumor, to quantify the degree of global protein aberration for each pt relative to normal controls. We defined three distinct groups of pts with low ( < 0.3), medium (0.3-0.8), and high ( > 0.8) GloPAS and assessed GloPAS association with overall survival (OS) and other prognostic factors using log-rank tests and compared the prognostic abilities of GloPAS vs. existing systems using concordance index(C-index). We developed a single-sample GloPAS (ssGloPAS) using an algorithm that can be applied to single sample setting. Results: Although determined without using information about OS or any pt-level clinical or demographic factors (i.e. unsupervised), GloPAS showed remarkable prognostic separability (low/med/high GloPAS, with median OS 38.2mo/18.3mo/7.1mo, p < 0.0001). GloPAS prognostic ability was far above any existing HCC staging system (C-index = 0.75 vs. 0.58-0.70 p < 0.0001), demonstrating even more prognostic information than key factors as metastatic status and vascular invasion. The ssGloPAS was able to recapitulate the global signal captured by the GloPAS score with a much smaller subset of 14 proteins. Conclusions: GloPAS significantly improved prediction of OS and prognostic stratification of HCC. After further validation, ssGloPAS could be used to guide therapy decisions and stratify HCC pts in clinical trials. The novel concept underlying GloPAS methodology can be applied to other cancers to build disease-specific prognostic scores.
Somatic copy number profiling of hepatocellular carcinoma circulating tumor cells.
Authors: Court Colin MacDonald , Hou Shuang , Winograd Paul , Sadeghi Saeed , Finn Richard S. , Song Min , Kaldas Fady M , Busuttil Ronald W , Graeber Thomas , Tomlinson James S , Tseng Hsian-Rong , Agopian Vatche G 
Published: January 2019

290 Background: Copy number variations (CNVs) have shown prognostic and predictive utility in hepatocellular carcinoma (HCC) but their use from percutaneous biopsies is limited due to HCC’s significant tumor heterogeneity. We investigated the feasibility of obtaining CNV profiles from circulating tumor cells (CTCs) as a liquid biopsy for HCC. Methods: Using a microfluidic HCC-specific CTC assay, CTCs were isolated from 10 patients with HCC and low-resolution (~0.01x) whole genome sequencing performed to establish CNV profiles. Primary tumor, peritumoral liver, and germline DNA was sequenced for comparison. Results: Sequencing of 18 CTC samples (median 4 CTCs/sample) from 10 HCC patients using a low-resolution whole genome sequencing strategy (median 0.88 million reads/sample) revealed frequent copy number changes in previously reported HCC regions such as 8q amplifications and 17p deletions. Analysis of CNV profiles revealed that CTCs share a median of 80% concordance with the primary tumor and that CTCs clustered with their respective primary tumor for 9/10 samples. Sequencing of 7 different CTC samples from a single patient established the reproducibility of the assay. CTCs also demonstrated CNVs not seen in the primary tumor, some with prognostic implications. Conclusions: CNV profiling of HCC-CTCs is feasible and accurately recapitulates CNVs seen in the primary tumor. The use of CTC-derived genetic profiles as clinically relevant surrogates of HCC tumors demonstrates potential and should be explored further. [Table: see text]
Comprehensive genomic profiling to identify recurrent kinase fusions in pancreatic ductal adenocarcinoma.
Authors: Singhi Aatur D. , Greenbowe Joel R. , Chung Jon , Hendifar Andrew Eugene , Bahary Nathan , Schrock Alexa Betzig , Miller Vincent A. , Stephens Philip J. , Ross Jeffrey S. , Ali Siraj Mahamed , George Ben 
Published: January 2019

292 Background: Kinases activated by gene fusions represent an important class of oncogenes that have been detected in hematologic and solid malignancies. These fusion genes have been well-described in non-small cell lung cancer, and such patients often benefit from matched kinase inhibitors. Recent work in pancreatic ductal adenocarcinoma (PDAC) has also identified recurrent ALK and BRAF rearrangements. Further, patients harboring the former have benefited from ALK inhibitors, as previously reported. We present a survey of kinase fusion genes identified in a large, consecutive series of PDACs. Methods: In the context of clinical care, hybrid-capture based CGP was performed prospectively on 3,426 PDACs for up to 315 cancer-related genes and intronic regions of up to 28 genes that are commonly rearranged in cancer. Results: Overall, kinase fusion genes were identified in 32 (1%) patients with PDAC. The patients consisted of 8 females and 23 males, and ranged in age between 31 and 83 years (median, 58 years). PDACs harboring kinase fusions were predominantly KRAS-wildtype (97%). In fact, the prevalence of kinase fusion genes among KRAS-wildtype PDACs was 8%. Gene fusions involved BRAF (n = 22), ALK (n = 5), NTRK (n = 3) and MET (n = 2). Concurrent genomic alterations included CDKN2A/B (41%), TP53 (28%), GNAS (19%), SMAD4 (16%), MCL1 (16%), ARID1A (13%) and MYC (13%). Updated clinical history will be presented on patients, who previously benefitted from ALK inhibitors. Conclusions: Recurrent gene fusions involving BRAF, ALK, NTRK and MET occur in a subset of PDACs. Although rare, these kinase fusions potentially represent actionable targets and screening should be considered, especially in KRAS-wildtype PDACs.
Incidence and risk factor analysis of the postoperative delirium after gastrointestinal surgery: An exploratory analysis of a prospective, randomized phase II trial.
Authors: Amano Shinya , Aoyama Toru , Kamiya Mariko , Morita Junya , Maesawa Yukio , Sawazaki Sho , Numata Masakatsu , Sato Tsutomu , Oshima Takashi , Rino Yasushi , Yukawa Norio , Masuda Munetaka 
Published: January 2019

30 Background: The postoperative complications, delirium are a particularly common morbidity after gastrointestinal surgery. Postoperative delirium makes patient management much more difficult, increases costs, and causes severe discomfort to the patient. The aim of this study was to evaluate the incidence of the postoperative delirium and a predictor for postoperative delirium using phase II clinical trial data. Methods: We analyzed the cases that were enrolled to randomized clinical trials of the efficacy and safety of TJ-54 (Yokukansan; a traditional Japanese medicine [Kampo]) for the prevention and/or treatment of postoperative delirium in a randomized phase II trial of patients receiving surgery for gastrointestinal and lung malignancies (UMIN000005423). The American Psychiatric Association’s the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) was used to assess. A uni- and multivariate logistic regression analyses was performed to identify risk factors for morbidity. Results: Between October 2009 and July 2011, a total of 186 patients were registered to the Yokukansan trial. Among them, 167 patients received surgery for gastrointestinal malignancy and were eligible for the present study. The incidence of postoperative delirium was 9.0% (15 patients) and postoperative delirium was the most common postoperative complication in the study. Risk factors for postoperative delirium were analyzed by uni- and multi-variate analyses using clinical factors determined before the enrollment of the study. Among these, high patients’ age ( > 80 years) and low MMSE score ( < 27) were identified as significant independent risk factor for postoperative delirium (Odds ratio: 3.90, 95% CI; 1.25-12.16, p = 0.013 and Odds ratio: 0.24, 95% CI; 0.08-0.73, p = 0.013). Conclusions: The major of the findings were that high patients’ age (≥ 80 years) and low MMSE score ( < 27) were significant independent risk factors for predicting postoperative delirium. Careful attention for postoperative delirium is required in patients with high patients’ age and MMSE score when surgeons perform surgery for gastrointestinal malignancies. Clinical trial information: 000005423.
Clinical significance of high expression of a specific solute carrier transporter in HCC.
Authors: Gifu Patricia , Brun Sonia , Wang Guanxiong , Bassissi Firas , Caron de Fromentel Claude , Merle Philippe , Halfon Philippe 
Published: January 2019

303 Background: Hepatocellular carcinoma (HCC) is the third cause of cancer-related death. GNS561 (Genoscience Pharma, France) is a small molecule inducing apoptosis by lysosome inhibition and caspase activation. GNS561 has high hepatotropism and anti-tumorigenic capacity on tumor bulk and cancer stem cells. Its main target is a specific solute carrier transporter (SLCt). We describe here the clinical relevance of the overexpression of SLCt in HCC patients. Methods: The expression of SLCt was investigated by iQRT-PCR in surgically resected HCC tumors (T) and the matched non-tumor (NT) liver tissues (n=180) as well as healthy livers (HL) devoid of chronic or acute disease (n=10). Pearson's chi-squared test was employed for significant correlation tests while univariate and multivariate survival analysis were performed by Cox proportional hazard ratio (HR) method. Results: SLCt was overexpressed in 40.5% of T and 30.3% of NT as compared to HL. High SLCt in T was associated with microvascular emboli (p=0.034) and expression of the cancer stem cell markers Sox2 (p=0.025) and CD133 (p=0.034). High SLCt in NT correlated with cirrhosis (p=0.009) and presence of satellite nodules (p<0.001). Univariate analysis showed association between high SLCt in T and shortened overall survival (OS) (HR=1.08, p=0.020), lower progression-free survival (PFS) (HR=1.76, p=0.006) as well as early recurrence-free survival (ERFS) (within 2 years post-surgery) (HR=1.88, p=0.008). In multivariate analysis, high SLCt tended to be an independent factor for OS, and this was strongly significant for PFS and ERFS. High SLCt in NT, is quite a poor outcome factor on late recurrence-free survival (HR=2.33, p=0.056) together with cirrhosis in univariate analysis, but remained dependent of cirrhosis in multivariate analysis. Late recurrence is linked to the intrinsic tumorigenic status of the liver. Conclusions: Overexpression of the SLCt in HCC tumors is associated to stemness features and appears as a poor outcome factor impacting on early recurrence. Further, SLCt in NT is associated with development of de-novo HCC. Validation cohorts and prospective assessments are needed to define high SLCt as a potential biomarker of HCC stemness and patient outcome.
Characteristics of circulating tumor cells in newly diagnosed metastatic pancreatic adenocarcinoma.
Authors: Starr Jason Scott , Parekh Hiral D. , Varillas Jose I. , Ivey Alison Marguerite , Barnes Isis , McEwan Margaret A. , Allegra Carmen Joseph , Trevino Jose Gilberto , Cioffi Jessica , Hughes Steven J. , Mramba Lazarus , Zhang Jinling , Fan Z. Hugh , George Thomas J. 
Published: January 2019

304 Background: Circulating tumor cells (CTCs) represent real time dissemination of solid tumors. Historically, CTC enumeration has been challenging to perform successfully in pancreatic cancer (PCa). Using a previously published microfluidic device designed to increase cell capture, we analyzed CTC characteristics in a cohort of newly diagnosed patients with metastatic PCa. Methods: After provision of informed consent, blood samples (7-10mL) were collected within 1 month of treatment initiation. Specimens were processed within 6 hours of collection. A UF developed microfluidic device was used to capture and identify EpCam+ CTCs. Isolated cells were verified as CTCs consistent with FDA-approved definitions (cytokeratin+, DAPI+, CD45-). Statistical analysis was performed using Scheffe’s method along with analysis of variance to test interactions between the clinical demographics and groups. The study was approved by the UF IRB. Results: A cohort of 27 patients had CTC determination at treatment onset with multi-agent chemotherapy for metastatic PCa. Cohort characteristics included: median age 65 (range 29-76), 63% male, 92% white, 85% with intact primary pancreatic tumor, pancreatic tumor location: head (n = 12), body (n = 5), tail (n = 6), number of sites of metastasis: 1 (n = 18), 2 (n = 7), 3 (n = 2), and median albumin 3.9 g/dl. Median CTC for the entire cohort was 7/mL of blood (range 2-12). CTCs were detected and quantified in all patients analyzed. In those with intact primary tumors, there were no significant differences in CTCs based on age (≥65), sex, albumin (≥3.5 g/dl), or number of metastatic organ sites (1, 2, or 3). However, primary tumor location in the head vs. tail was different (mean 7.7 vs. 4.3/mL; p = 0.02; CI -5.78 – [-] 0.41). Conclusions: This analysis demonstrates the feasibility of measuring CTCs in patients with metastatic PCa. CTC amount does not appear impacted by systemic tumor burden or demographic differences. However, anatomic differences in primary tumor location may be important in CTC studies. Further analysis of a larger and more diverse patient data set is planned.
Prognostic implication of soluble programmed death-ligand 1 (sPDL1) and its dynamic changes during FOLFIRINOX chemotherapy in unresectable pancreatic cancer.
Authors: Park Hyunkyung , Bang Ju-Hee , Nam Ah-Rong , Park Ji Eun , Kim Mei Hua , Bang Yung-Jue , Oh Do-Youn 
Published: January 2019

306 Background: Programmed death-ligand 1 (PD-L1) expressed on a tumor or in a tumor microenvironment has an important role in the tumor escaping from the immune system. The soluble form of PD-L1 (sPD-L1) has been suggested to have an immunosuppressive activity. In pancreatic cancer, the acquisition of a sufficient amount of tumor tissue is an obstacle. In this study, we measured the serum levels of sPD-L1 and evaluated its prognostic implications in unresectable pancreatic cancer. Methods: We prospectively enrolled 60 pancreatic cancer patients who were treated with FOLFIRINOX as the first-line palliative chemotherapy. We collected blood samples at the time of diagnosis, first response assessment and disease progression. Serum sPD-L1 was measured using an enzyme-linked immunosorbent assay. Results: The median sPD-L1 was 1.7ng/mL (range, 0.4-5.7ng/mL). The median overall survival (OS) and progression free survival (PFS) were 10.3 months (95% CI: 8.5-12.11) and 6.5 months (95% CI: 4.9-8.1), respectively. Patients with low levels of sPD-L1 at diagnosis ( < 4.6 ng/mL) showed a better OS than the patients with a high sPDL1 (OS: 12.6 vs. 8.0 months HR 2.796, P = 0.015). In the multivariable analysis, sPD-L1 and the neutrophil-to-lymphocyte ratio were independent prognostic factors for OS. During chemotherapy, more patients achieved CR(complete response)/PR (partial response) as the best response when sPD-L1 was decreased at the first response assessment. (CR+PR rate; sPDL1 decreased group vs. sPD-L1 increased group: 14/29 (48.3%) vs. 5/24 (20.8%), P = 0.038). For patients who achieved CR/PR as the best response, sPD-L1 was significantly increased at disease progression compared with the first response assessment (mean 3.5 vs. 1.9 ng/mL, P = 0.025). Conclusions: sPD-L1 at diagnosis confers a prognostic value for OS in pancreatic cancer patients treated with chemotherapy. The dynamics changes of sPD-L1 during chemotherapy correlates with disease progression
Prospective analysis of somatic and germline genetic alterations in patients with ampullary carcinomas.
Authors: Wong Winston , O'Reilly Eileen Mary , Varghese Anna M. , Yu Kenneth H. , Iacobuzio-Donahue Christine A , Shia Jinru , Klimstra David , Allen Peter J. , Lowery Maeve Aine 
Published: January 2019

308 Background: Ampullary carcinoma (AC) is a rare gastrointestinal cancer. Germline alterations (GA) in BRCA2 have been identified in patients with AC. Also, potentially targetable somatic alterations (SA) in other genes including ERBB2, and ELF3 have been identified in AC. MSKCC has implemented an opt-in strategy for germline (GT) and somatic genetic testing (ST) for patients with AC. Methods: Patients (pts) with pathologically confirmed AC were consented prospectively for ST using MSK-IMPACT (410 genes). A subset of pts was also consented for GT using MSK-IMPACT (76 genes) under an IRB approved protocol. Clinicopathologic features, treatment history and survival data were collected and analyzed. Results: N = 36 AC pts consented to ST from 9/2016 to 4/2017 of which 19/36 (52.7%) were male. Median age at diagnosis was 63 years, range 35-81. Pathology: 6/36 (16.7%) intestinal subtype, 19/36 (52.7%) pancreaticobiliary subtype, 4/36 (11.1%) mixed type, and 7/36 (19.4%) undifferentiated/other subtypes.29/36 (80.5%) pts had a family history of cancer. SA in KRAS 11/36 (30.5%), MDM2 (AMP) 6/36 (16.7%), ERBB2 3/36 (8.3%), PIK3cA 3/36 (8.3%), and ELF3 2/36 (5%) were seen in the highest frequency. 15/36 (41.6%) pts also consented for GT. Subgroup analysis revealed 4/15 (26.6%) pts with GA. Table 1 summarizes this subgroup. Conclusions: SA/GA in multiple genes including BRCA2, ERBB2/ELF3, and NTRK were observed. Also, novel GA in ATM (13%) and SA in MDM2 (AMP) (16.7%) were identified. Correlations of pathologic subtypes to clinical history, outcomes and mutations will be reported at the meeting. Further investigation of SA/GA in this disease is warranted given potential therapeutic and family screening implications. [Table: see text]
Perioperative inflammatory marker as a predictive factor for prolonged postoperative ileus after gastrectomy for gastric cancer.
Authors: Park Hyojin , Kim Yoon Su 
Published: January 2019

31 Background: Inflammatory markers such as the C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have recently been proposed as prognostic markers for post-operative complications and poor prognosis in solid tumors especially in colon cancer. However, there are few related reports in gastric cancer patients. Therefore, the aim of this study is to assess how perioperative inflammatory markers influence the prolonged postoperative ileus (PPOI) following gastric cancer surgery. Methods: Between 2013 and 2016, 435 patients were diagnosed with gastric cancer and underwent surgery in Gangnam Severance hospital. Patients were divided into prolonged postoperative ileus (PPOI) and control groups. Uncomplicated postoperative ileus (POI) is generally identified as an inevitable process after surgery, which typically resolves within 3 days. Ileus that persists for more than 3 days following surgery is termed PPOI. Results: The total PPOI rate was 33.8%. In univariate analysis, PPOI group was significantly associated with male sex, old age, open operative technique, preoperative gastric outlet obstruction and combined colon resection. PPOI group also was significantly associated with elevated perioperative inflammatory marker (pre- and post-operative CRP, NLR, and PLR). In multivariate analysis, open operative technique and elevated perioperative inflammatory markers (CRP, NLR and PLR) were identified as significant predictors of PPOI. In addition, postoperative length of hospital stay delayed in PPOI group compared with the control group (11.58 ± 9.48 vs.7.98 ± 5.44, respectively; P < 0.001). Conclusions: In this study, PPOI group was significantly associated with elevated perioperative inflammatory marker. Patients with PPOI also are more likely to have an increased postoperative hospital stay. Therefore, the perioperative inflammatory markers may be used as clinically relevant predictive markers for PPOI following gastric cancer surgery
Change in liver function as measured by change of Child Pugh Score to predict survival in patients with advanced hepatocellular carcinoma (HCC) during the treatment course.
Authors: Prins Petra , Sharma Titiksha , Kim Kyung S , Bhardwaj Prarthna V , Collins Noah , Lu Emily , Bowie Anna , Fegler Marcella , Lee Kathrine , Yang Andrew , He Aiwu Ruth 
Published: January 2019

310 Background: HCC is the sixth most common cancer and the second leading cause of cancer-related death worldwide. Most HCCs develop in severely damaged liver. Methods: The effect of multiple treatment options on liver function (LF) and disease outcome of patients (pts) with HCC (n = 380) were examined retrospectively. Pt LF (Child Pugh score [CPS]) was assessed at time of diagnosis (dx) and then after treatment. Kaplan Meier with log rank and Chi square test was used for comparisons. Results: Our cohort of 380 pts had the following demographics: 74% were male and 26% female; 42% were African American, 26% Caucasian, 13% Asian, and 8% undetermined. The mean age at dx was 62.7 yrs; 17% and 61% of pts were between 40-55 and 56-70 yrs, respectively. Only 2% were below 40 yrs, and 19.6% were above 70 yrs of age. About half of pts smoked (55%) or drank (54%). Regarding viral infection, 17% had Hep B, 52% Hep C, 3% both, and 26% neither. Risky behavior correlated with age of dx: pts aged 56-70 yrs of age had the highest of both (p < 0.05). Cirrhosis and vascular invasion were seen in 66% and 40% of pts, respectively. Stage I/II HCC was seen in 38% and stage III/IV in 68% of pts. Median OS was significantly higher for stage I/II pts (p < 0.001). Pts who had no change or improvement in LF had longer median OS vs. pts who had declining LF (p < 0.001). Considering all treatment scenarios including local and systemic therapy, LF improved in 13%, did not change in 41%, and worsened in 46% of pts. LF decline in pts receiving various treatments was as follows: 53%, sorafenib (SFB); 39%, TACE; 53% radiation; 58% TACE/Y-90/SFB; and 32%, immunotherapy independent of prior treatment. However the degree in LF decline, as dictated by a ΔCPS of > 4, 3 to 4, or 1 to 2 points, did not by itself correlate with significant changes in median OS. Conclusions: The outcome of pts with HCC depends on disease stage and LF. Most pts experience LF decline during treatment. The degree of LF decline is independent of median OS, but maintaining LF is significantly beneficial for OS. Balancing survival benefit with liver toxicities is critical to the successful treatment of pts with advanced HCC.