bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significance of Inter aorto-caval lymph nodes in gall bladder cancer management.
Authors: Singh Kishore , Srivastava Anurita , Srivastava Siddharth , Aggarwal Aditi , Goel Varshu , Rathi Arun Kumar , Saluja Sundeep , Sakhuja Pooja 
Published: May 2020

e16607 Background: Gallbladder cancer (GBC) is one of the three leading cancer among women of North and North-east India. The age standardized rate (ASR) for GBC in women of North and north-east India are 11.8/100,000 population and 17.1/100,000 population respectively It is one of the most fatal cancer, characterized by early spread, both local as well as distant. Radical resection is associated with the highest control rates. Presence of inter-aorto-caval lymph nodes (IAC) during preoperative workup is designated as metastatic disease in GBC and radical surgery is deferred. This study attempts to confirm the validity of such an approach. Methods: Between January 2017 and December 2018, 178 patients of GBC were registered at our hospital. Of these, 108 patients with radiologically resectable disease were evaluated preoperatively with endoscopic ultrasound (EUS) to look for IAC lymph nodes lying below the level of the renal vein. Patients with IAC involvement were taken up for chemotherapy while the others underwent upfront surgery. Results: Mean age at presentation was 51.1 (±10.9) years with a female predominance (N = 77, 71.2%). Presenting symptoms were either pain (N = 91, 84.2%) or jaundice (N = 42, 38.8%) in majority cases. Patients with jaundice presented earlier with mean of 53.27 days (Range2-240 days) while those with pain presented at a mean of 71.5 days (1-360 days) prior to diagnosis. Pathologically positive IAC cases (n = 12) of resectable GBC received systemic therapy upfront rather than immediate radical surgery. Rest of the patients underwent surgical resection followed by adjuvant treatment as indicated. Mean follow up was 179 days with a mortality of 62%(n = 67). No significant difference was seen in the stage distribution in IAC positive versus negative group. Median survival with Kaplan Meier method of IAC positive patients was 239 days versus 190 days in IAC negative patients. Conclusions: IAC lymph node may not necessarily portend poor prognosis. It needs to be validated in large sample size.
Efficacy and safety of anlotinib combined with transarterial chemoembolization versus transarterial chemoembolization alone in patients with unresectable hepatocellular carcinoma: A retrospective study.
Authors: Guo Wenbo , Chen Song 
Published: May 2020

e16611 Background: HCC is one of the most common cancer among all the malignant tumor, while the efficacy of TACE alone for unresectable HCC patients still remains unsatisfactory. With the development of targeted drug, more and more targeted drugs are applying to the treatment of HCC. Objective: The aim of the stidy is to investigate the efficacy and safety of transarterial chemoembolization (TACE) combined with Anlotinib versus TACE alone in patients with unresectable HCC. Methods: This single-center retrospective study involved 82 patients with unresectable HCC who underwent TACE alone (TA group; n=46) or TACE combined with Anlotinib (TC group; n=36) between Jan 2018 and Jan 2019. The primary outcomes were progression-free survival (PFS) and overall survival (OS), while the secondary outcomes included the objective response rate (ORR), the disease control rate (DCR) and main complications. Results: The TC group showed relatively higher PFS than the TA group (7.35months vs. 5.54 months, p=0.035). The 3-month survival rate was not statistically different between the two groups (97.2% vs. 93.5%, p=0.627), while both the 6-month survival rate and 1-year survival rate were significantly higher in the TC group than in the TA group (83.3% vs. 56.5%, p=0.016; 66.7% vs. 19.6%, p<0.01). ORR in the TA group was significantly higher than in the TC group (77.8% vs. 32.6%, p<0.01), while the two groups showed no statistical difference in DCR (94.4% vs. 82.6%, p=0.17). No treatment-related mortality or grade 4 adverse event was observed, but grade 3 adverse events occurred in two patients in the TC group (one suffered with erythra, and another suffered with hand-foot-skin reaction). Both of them disappeared after prompt treatment. Conclusions: TACE combined with Anlotinib is safe and may improve outcomes for unresectable HCC patients comparing with TACE alone. It still needs more further randomized controlled trials to clarify the potential role of Anlotinib in hepatocellular carcinoma. Key words: Hepatocellular carcinoma; Anlotinib; Transarterial chemoembolization
Impact of tumor histology and socioeconomic factors on survival of patients suffering from malignant vascular tumors of liver and hepatocellular carcinomas: A SEER database analysis.
Authors: Shreenivas Aditya Varnam , Guru Murthy Guru Subramanian , George Ben , Thomas James P. , Chakrabarti Sakti , Kamgar Mandana , Ritch Paul S. 
Published: May 2020

e16612 Background: Primary malignant vascular tumors of the liver are rare, aggressive and poorly understood subtypes of liver cancers. In this analysis, we aim to determine the impact of tumor histology and other socio economic factors on survival of these tumors and hepatocellular carcinomas. Methods: Patients with malignant histopathological diagnoses of hepatocellular carcinoma not otherwise specified (HCC NOS), hepatocellular carcinoma with spindle cell (HCC SP), fibrolamellar (HCC F), clear cell (HCC CL), scirrhous (HCC SC) and pleomorphic variants ( HCC PL), combined hepatocellular carcinoma and cholangiocarcinoma (Mixed), hepatic angiosarcoma (AS), hemangioendothelioma (HE), its epithelioid variant (EHE) and hemangiopericytoma (HP) were identified using the SEER (version 2018) database. Overall survival was studied with Kaplan–Meier with the log rank method. Multivariable analysis was performed to assess the impact of race, ethnicity, marital and insurance status on survival of these patients. Results: We analyzed de-identified data of 104502 patients from the year 1973 to 2016 with hepatocellular carcinomas and malignant vascular tumors of liver (including 101851 patients with HCCNOS, 70 with HCC SP, 378 with HCC F, 104 with HCC SC, 593 with HCC CL, 23 with HCC PL, 950 with Mixed, 367 with AS, 36 with HE, 120 with EHE and 10 with HP ) respectively. Median overall survival (OS) of HCC NOS was calculated to be 7 months. Among hepatocellular carcinoma patients HCC F had the longest median OS of 29 months and HCC SP had the shortest median OS of 3months (P < 0.001). Additionally, among patients with malignant vascular tumors, AS had the shortest median OS (1 month) while patients with EHE had the longest median OS of 81 months (P < 0.001). Overall, married and insured patients had a better overall survival than unmarried and uninsured patients (P < 0.04). Conclusions: Malignant vascular tumors of liver are rare in comparison to hepatocellular carcinomas. Spindle cell variant of HCC and liver angiosarcomas carry the worst prognosis and fibrolamellar variant of HCC, hemangioendothelioma (HE) and its epithelioid variant (EHE) have the best prognosis. Insurance and marital status has a positive impact on overall survival of liver cancer patients.
Effect of an lncRNA-associated ceRNA regulatory network in MVI-positive hepatocellular carcinoma on their sensitivity to sorafenib.
Authors: Luo Zhiwen , Bi Xinyu 
Published: May 2020

e16615 Background: Microvascular invasion (MVI) is a histological feature of hepatocellular carcinoma (HCC) related to aggressiveness. But different sensitivity to first line targeted drug, sorafenib, in MVI+ HCC has been observed. Long noncoding RNAs (lncRNAs) can act as microRNA (miRNA) sponges to regulate protein-coding gene expression; so lncRNAs are considered as a major part of competitive endogenous RNA (ceRNA) network and have attracted growing attention. We explored the regulatory mechanisms and functional roles of lncRNAs as ceRNAs in MVI+ HCC, and ceRNA network’s potential impact on prognosis and sensitivity to sorafenib in MVI+ HCC patient. Methods: We studied the expression profiles, prognostic value of lncRNA, miRNA, and mRNA from MVI+ HCC patients, established a prognosis-related network of dysregulated ceRNAs and analyzed its role in sensitivity to sorafenib and radiomics features by bioinformatics methods. Results: A ceRNA network including 13 lncRNAs, 3 miRNAs, and 2 mRNAs specific to MVI+ HCC was established. 6 lncRNAs ( ARHGEF7-AS1, ATP2B2-IT1, LINC00330, MUC2, TLR8-AS1 and ZNF385D-AS1), 2 miRNAs ( hsa-mir-206 and hsa-mir-373) and two mRNAs ( PAX3, SIK1) were prognostic biomarkers for MVI+ HCC. PAX3 was an unfavorable prognostic gene (HR = 1.9, 95%CI 1.01 ~ 3.60), while SIK1 favored the prognosis (HR = 0.4, 95%CI 0.19 ~ 0.85). PAX3 as a stratification in recurrence predicting model was used to identify MVI+ HCC with high or low recurrence risk. Datamining into the dataset of phase 3 STORM trial showed no difference in the influence of PAX3 level on the outcome between sorafenib HCC group and placebo HCC group. However, deep datamining into GDSC dataset revealed our high PAX3 group in MVI+ HCC related to resistance to sorafenib ( P = 0.0039). Radiomics features were extracted from CT of MVI+ HCC, and texture analysis in MVI+ HCCs is ongoing. Conclusions: The proposed ceRNA network may help elucidate the regulatory mechanism by which lncRNAs function as ceRNAs and contribute to the pathogenesis of MVI in HCC. Importantly, the candidate lncRNAs, miRNAs, and mRNAs involved in the ceRNA network have shown to be potential therapeutic targets and prognostic biomarkers for MVI+ HCC. PAX3 might play a vital role in the mechanism of sorafenib resistance in MVI+ HCC, exclusively, this aggressive HCC subtype. The ongoing experiments on radiomics might add potent supports to identify sorafenib sensitive MVI+ HCC.
A risk scoring system to predict overall survival for patients with liver cancer.
Authors: Xin Haibei , Zhang Guanxiong , Zhou Wei , Chen Huan , Liang Dandan , Zhang Henghui , Li Nan 
Published: May 2020

e16635 Background: Surgical resection is a common curative treatment for patients with primary hepatocellular carcinoma (HCC), and conventional strategies of assessing clinical and pathologic risk factors have been adopted to predict clinic outcomes in patients after curative surgery. We hypothesized that an ensemble learning approach which incorporates multidimensional features would enable effective prediction of patient survival. Methods: We analyzed data from 222 stage II-III HCC patients who underwent surgical resection at Eastern Hepatobiliary Surgery Hospital (Shanghai, China). Baseline information for each patient includes clinical and pathologic risk factors, laboratory tests and in situ immunological profiles. Using machine learning, we developed CoxPH, GBS, CGBS, FSVM and NSVM models for patient overall survival (OS). Models were trained on 155 cases with 48 features. Thirteen-fold cross-validation (CV) was used to measure performance with area under the ROC curve (AUC) and C-Index (CI). The ensemble model was used to predict patient OS and validated on the subsequent 67 cases. Results: For all models tested, immune features, including the fraction of CD68+ and CD8+ cells in tumor, and CD8+ cells in stroma, play a crucial role in predicting patient OS. Using the ensemble CoxPH model (with superior value of AUC and CI), a risk scoring system for patient OS was developed. The scoring system could stratify patients into high-risk or low-risk groups, revealing different prognosis (validation cohort: HR, 6.5, 95% CI, 2.4-18, P = 3.4e-05). The CoxPH model was also predictive of the time to-recurrence (p < 0.0001). In validation set, the scoring system predicted half-year mortality of patients with AUC of 0.9, and 1-year mortality of patients with AUC of 0.897. The scoring system could also predict half-year recurrence and 1-year recurrence with AUC more than 0.83. Conclusions: The machine learning-based risk scoring system offers a novel strategy for incorporating multidimensional risk factors to predict clinic outcome and may help medical practitioners to optimize clinical follow-up or therapeutic interventions. [Table: see text]
Hepatocellular carcinoma with ARID1A mutation is associated with higher TMB and poor survival.
Authors: Peng Yaorong , Gao Bowen , Zhou Zhenyu , Chen Tingting , Xie Wenzhuan , Huang Mengli , Li Wenbin 
Published: May 2020

e16667 Background: Hepatocellular carcinoma (HCC) is a heterogeneous disease that lacks molecular predictors of response to available treatments. AT-rich interactive domain 1A (ARID1A), a SWI/SNF chromatin remodeling gene, is commonly mutated in human cancers and hypothesized to be a tumor suppressor gene. In recent years, immune checkpoint blockade immunotherapies (ICIs) are promising therapies for multiple cancers including HCC, and tumor mutation burden (TMB) was an important biomarker to predict the efficacy of ICIs. Besides, previous research reported that ARID1A deficiency was associated with mismatch repair (MMR) in cancer, and may cooperated with ICIs. Methods: Whole exome sequencing data of 10336 pan-cancer patients including 353 HCC patients was obtained from the Cancer Genome Altas (TCGA). Next generation sequencing (NGS) data of 15849 pan-cancer patients including 1926 HCC patients from Chinese clinical dataset were analyzed to explore the correlation between ARID1A gene mutation and TMB. TMB was defined as total number of somatic non-synonymous mutations in coding region. Prognostic data of 136 HCC patients were obtained from the MSK-IMPACT Clinical Sequencing Cohort (MSKCC). Results: In total, 8.62% (891/10336) of pan-cancer patients in TCGA harboring ARID1A mutation and 8.47% (3188/37628) in Chinese cohort, while mutant percentage of HCC was 9.35% (33/353) in TCGA, 9.03% (174/1926) in Chinese cohort, the alternation frequency of ARID1A in two cohorts was no significant difference (P = 0.3334). The medium TMB level of ARID1A mutant group was higher than wild-type group with significant difference both in Chinese pan-cancer and HCC (medium TMB level, P < 0.0001). Results of 18 kinds of ARID1A mutated tumors patients in TCGA cohort indicated that ARID1A mutation was an independent risk factor in liver cancer affecting overall survival (OS, HR 2.43, 95% IC 1.07-5.54, P = 0.0286). Besides, Kaplan-Meier analysis was performed on HCC patients in MSKCC cohort, ARID1A statue resulted in significantly shorter OS (median, 12.2 vs 21.43 months; HR 2.5; P = 0.0092). Conclusions: The results indicated that ARID1A gene mutation was a poor prognostic factor in hepatocellular carcinoma, and these mutational states were associated with higher TMB level, which might be a potential positive biomarker of immunotherapy.
Cabozantinib in advanced hepatocellular carcinoma: Efficacy and safety data from an international multicenter real-world cohort.
Authors: Finkelmeier Fabian , Scheiner Bernhard , Leyh Catherine , Best Jan , Fründt Thorben Wilhelm , Czauderna Carolin , Beutel Alica , Bettinger Dominik , Weiß Johannes , Meischl Tobias , Kuetting Fabian , Waldschmidt Dirk Thomas , Schultheiß Michael , Ettrich Thomas Jens , Weinmann Arndt , Wege Henning , Venerito Marino , Lange Christian , Pinter Matthias , Waidmann Oliver 
Published: May 2020

e16668 Background: The multikinase inhibitor cabozantinib has been approved by the European Medicines Agency in November 2018 for hepatocellular carcinoma (HCC) prior treated with sorafenib. We report, to our knowledge, for the first time safety and efficacy data of an international, multicenter, real-world cohort of patients with advanced HCC treated with cabozantinib. Methods: Patients with HCC who were treated with cabozantinib were retrospectively identified across 10 centers in Austria and Germany. Patients´ characteristics, side effects, duration of treatment and survival data were analyzed until January 17, 2020. Results: 74 patients were identified of whom 65 patients were male (88%) and 9 were female (12%). The median age at the start of cabozantinib treatment was 66 years. The most common underlying liver diseases included hepatitis C in 15 (20%), hepatitis B in 6 (8%), alcohol in 17 (23%) and NAFLD/NASH in 20 (27%) patients, respectively. 64 patients (86%) had BCLC stage C and 43 patients (58%) were Child Pugh A. Cabozantinib was used as systemic second- and third-line treatment in 37 (50%), and 25 (34%) patients, respectively. In the remaining patients cabozantinib was used in further lines. The median starting dose was 40 mg (20-60 mg). In 26 patients (35%) a dose reduction due to side effects was performed. Following best responses under cabozantinib were documented: partial response in 4 (5%), stable disease in 22 (30%), and progressive disease in 24 (32%) patients, respectively. 24 patients (32%) had not yet been evaluable. The median duration of cabozantinib treatment was 4.4 months. 35 patients (47%) had died at day of data analysis. The median overall survival from start of cabozantinib treatment was 7.7 months. Most common adverse events were fatigue and diarrhea. Conclusions: Cabozantinib treatment was effective, safe and feasible in patients with advanced HCC. Patients in the real life setting had more advanced liver disease – only 58% of patients were Child A. Duration of treatment was similar to the phase 3 trial (CELESTIAL). However, overall survival was shorter, probably due to more advanced liver disease.
CFL1 to promote proliferation and invasiveness and to regulate NF-κB-mediated inflammatory factors in hepatocellular carcinoma.
Authors: Zhang Chunyan , Dai Qian , Ma Xiaolu , Yang Wenjing , Lv Lihua , Zhu Jie , Zhou Yan , Pan Baishen , Wang Beili , Yang Xinrong , Guo Wei 
Published: May 2020

e16669 Background: Cofilin1 (CFL1) is an actin-binding protein that plays an essential role in cytoskeleton regulation. However, its function in hepatocellular carcinoma (HCC) is largely unknown. The aim of study was to investigate the role of CFL1 in HCC. Methods: We used qRT-PCR and western blot assays to detect CFL1 expression. The role of CFL1 in regulating HCC cell growth and invasion were assessed by forced expression and downregulation. A tissue microarray study containing 189 HCC cases was conducted to evaluate the clinical relevance and prognostic significance of CFL1. Results: The expression level of CFL1 in high metastasis cell lines was significantly higher than that in low metastasis lines ( P < 0.05). Knockdown of CFL1 reduced the proliferation and invasion activities of Huh7 and MHHC97H cells ( P < 0.05). Western blot revealed that the cytoplasmic level of the p65 subunit of NF-κB was significantly elevated along with reduced nuclear levels and NF-κB-targeted genes MMP9, BCL2, EZH2, COX2 and VCAM1 levels significantly inhibited n HCC cells silenced for CFL1. Immunohistochemistry in a primary tissue array revealed that CFL1 expression correlated with Tumor encapsulation and microvascular invasion ( P < 0.05). High CFL1 expression patients had significantly higher recurrence and deaths rates (recurrence: 72.9% vs. 42.9%, death: 20.8% vs. 51.1%) than low CFL1 expression patients ( P < 0.001). Conclusions: CFL1 regulate the proliferation and dissemination of HCC and TNF-α induced NF-κB nuclear translocation. CFL1 may serve as a prognostic marker in HCC and might be a promising therapeutic target for suppressing metastasis.
Clinical utility of comprehensive genomic profiling and targeted therapy in biliary tract cancers: A real-world experience.
Authors: Shahid Mahum , Abdallah Mohamed A. , Ellithi Moataz , Abdullah Hafez Mohammad , Nelson Morgan , Solomon Benjamin Maurice , Bleeker Jonathan 
Published: May 2020

e16671 Background: Biliary tract cancers (BTC) are a highly aggressive group of malignancies with high mortality and poor prognosis. Chemotherapy is the mainstay of treatment for advanced disease. The role of molecular targeted therapy and immunotherapy using comprehensive genomic profiling (CGP) is evolving. We investigated the role of CGP directed therapy in patients with BTC. Methods: A multi-center retrospective study of CGP done on 35 patients with BTC at Sanford USD Medical Center and Avera McKennan Hospital, Sioux Falls, SD, between 2014 and 2019. 27 patients had cholangiocarcinoma (fifteen intrahepatic, two extrahepatic and ten unclassified), two had gallbladder carcinoma and six had ampullary carcinoma. Results: 22 of 35 BTC (63%) had potentially actionable genetic alterations(GA). Nine of these 22 (41%) received molecular therapy based on CGP. Four patients had microsatellite instability (MSI-H) and two of them received immunotherapy (Table). CDKN2A/B was the most common mutation (23%) followed by PIK3CA (13%), ARID1A (13%) and Tp53(13%). By the end of the follow up period, median overall survival (OS) was 569 days(19 months) for those who received targeted therapy compared to 315 days(10.5 months) for those who did not. (P = 0.051). Conclusions: In this multi-center cohort, 63% of patients had at least one targetable GA. Furthermore, CGP guided treatment decisions in 41% of patients. CGP has the potential to provide clinically meaningful treatment options for patients with BTC. New studies are warranted to further investigate this promising prospect for BTC management. [Table: see text]
Real-world use of second-line treatments in patients with advanced hepatocellular carcinoma (HCC) of varying liver dysfunction: Analysis at a Hispanic-majority cancer center.
Authors: Xia Jeffrey , Arora Sukeshi Patel 
Published: May 2020

e16676 Background: Hispanics have a higher incidence of HCC but are underrepresented in clinical trials leading to approvals of new therapies for HCC. Further, there is a lack of prospective trials comparing second-line treatments for HCC. Therefore, we reviewed the treatment patterns and tolerability of second-line treatments for HCC at our Hispanic-majority NCI-designated cancer center. Methods: Retrospective analysis of patients with advanced HCC, diagnosed at Mays Cancer Center at UT Health San Antonio from 1/2015-3/2019, who received second-line therapies, including, tyrosine kinase inhibitors (TKIs; Ie, cabozantinib, regorafenib) and immunotherapy (IO; ie, nivolumab), clinical trials, hospice/best supportive care (BSC). Child Pugh cirrhosis and adverse events were be compared. Results: Median age 59 (n = 58), Hispanics n = 43 (74%), Cause of cirrhosis: HCV 42 (74%), HBV 1, EtOH 33, NAFLD/NASH 13. BMI overweight/obese 33 (57%). Child-Pugh: A 9 (16%), B 30 (52%), C 16 (28%) (Table). BCLC B 6 (10%), C 47 (81%). CLIP: 1-2 (16%), 3 (38%), 4+ (41%). Second-line treatments: TKI (4, 7%), IO (24, 41%), Clinical trials (3, 5%), BSC (24, 41%). Toxicities (Table). Dose interruptions or reductions: All 18 (31%), TKIs 3 (75%), IOs (58%), trials (33%). Conclusions: In our Hispanic-majority cohort, 41% of patients with HCC were not candidates for second-line treatments (BSC). Of those who received second-line treatments, most received IOs, including patients with Child-Pugh B and C cirrhosis, with 58% requiring dose interruptions. Only 5% enrolled on clinical trials. Real-world patients are significantly different than clinical trial populations, and we need more prospective real-world analyses of these treatments to better understand efficacy, tolerability and quality of life. [Table: see text]