bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of epithelial-mesenchymal transition with an immunosuppressive tumor microenvironment with elevated levels of PD-L1 in esophageal carcinoma.
Authors: Oki Eiji , Saeki Hiroshi , Tsutsumi Satoshi , Nakashima Yuichiro , Nakanishi Ryota , Sugiyama Masahiko , Kurashige Junji , Ando Koji , Oda Yoshinao , Maehara Yoshihiko 
Published: September 2018

e15585 Background: Programmed death-ligand 1 (PD-L1) plays a crucial role in the host immune system in cancer progression and is has become a new target for cancer therapy. PD-L1 gene promoter region contains a binding site of ZEB1, a transcription factor related to epithelial-mesenchymal transition (EMT). The purpose of this study is to clarify relationships between PD-L1, EMT and its clinical importance in esophageal squamous cell carcinoma (ESCC). Methods: We conducted preclinical studies using cell lines and clinical specimens. ZEB1, PD-L1 expression in TE8 cell line, demonstrating EMT phenotype, was determined following ZEB1 knockdown by siZEB1. TE5, 6 and 11 cell lines with non-EMT phenotype were also used for studies of TGF-β1-dependent EMT induction and ZEB1, PD-L1 expression. PD-L1 and ZEB1 expression at the tumor invasive front was examined in resected specimens from 90 patients with ESCC who underwent surgery without preoperative therapy by immunohistochemistry and their expression and clinicopathological factors were compared. Results: A correlation was observed between PD-L1 and ZEB1 expression. In TE8 cells which express EMT character , siZEB1 suppressed PD-L1 and promoted E-cadherin mRNA and protein expression. In TE5, 6 and 11 cell lines which are not EMT phenotype, TGF-β1 induced EMT and surface expression of PD-L1. In cases of high PD-L1 expression at invasive front, greater depth of tumor invasion, EMT, less CD8 expression were significantly observed. High PD-L1 expression was also associated with worse overall and relapse-free survival. Conclusions: PD-L1 expression at the invasive front was related to ZEB1 expression, EMT and poor prognosis in ESCC. We suggest that cooperative mechanism between tumor immune avoidance and EMT contributes to tumor malignancy. Whether or not ZEB1-PD-L1 signal pathway could be a target in treatment for ESCC requires further investigations.
Comparison of demographic variables related to 30-day readmission in cancers with similar risk factors: Analysis of 290,270 hospitalizations.
Authors: Sivsammye Suceil , Kailasam Karthik 
Published: September 2018

e15596 Background: There has been increasing focus on reducing hospital readmissions which are an ongoing economic challenge. This study was targeted at cancer of the esophagus (CE), stomach (CS), and pancreas (CP) which share similar risk factors to identify if these patient subsets also share risk for hospital readmission. Methods: Data was extracted from Nationwide Inpatient Sample database, which approximates 20% of U.S. community hospitals. Patients with a diagnosis CE, CS, and CP were identified by Clinical Classification Software code 11, 12, and 17, respectively. Demographic parameters associated with high readmission rates were collected for patients readmitted within 30 days over 2009-2013. Chi-square test was used to asses differences between variables. Results: We identified a total of 290,270 hospitalizations over the 5-year period of which 26.2% were readmitted within 30 days. The total number of readmissions were comparable for CS (28.0%), CP (27.89%), and CE (26.81%). Patients 45 to 64 years (28.58%, p < 0.001), Medicaid insurances (33.4%, p < 0.001), and metropolitan areas (26.8%, p < 0.001) were associated with higher 30-day readmission rates amongst all three cancers. Males had higher readmission rates in CS (25.64%, p < 0.001) and CP (28.6%, p < 0.001) compared to females in CE (28.0%, p < 0.001). Lowest median income for zip code patients were readmitted more often in CS (26.2%, p < 0.001) vs. third median income in CP (27.78, p < 0.001) and fourth (highest) median income in CE (28.38 %, p < 0.001). The most common identified causes of readmission in all three cancers were complications of surgical procedures or medical care (8.51% ± 2.03%), and septicemia (6.5% ± 1.95%). Conclusions: Our analysis shows that some variables for readmission are similar however more studies are needed to further elucidate whether this is primarily due to analogous treatment techniques. If so interventions to limit readmissions related to these treatments should be taken. Differences in readmissions rate amongst income classes could be related to the ease of accessing the most endorsed treatments for each individual cancer, however further studies are needed to clarify this discrepancy.
Antitumor efficacy of CDK 4/6 dual inhibitor, abemaciclib, in an esophageal adenocarcinoma model.
Authors: Omstead Ashten N , Matsui Daisuke , Kosovec Juliann E , Martin Samantha A , Kelly Ronan Joseph , Zaidi Ali Hussainy , Jobe Blair Anderson 
Published: September 2018

e15598 Background: Esophageal adenocarcinoma (EAC) is a leading cause of cancer death, and current treatment options are extremely limited. Cell cycle regulators CDK6 and its homolog, CDK4, are known to be up-regulated in EAC and are associated with poor prognosis. At the molecular level, CDK4 and 6 bind to cyclin D1 and activates E2F transcription factor via phosphorylation of pRb. Up-regulation of this pathway leads to deregulation of the G1 checkpoint, resulting in increased cellular proliferation. Previously, studies have shown progressive up-regulation of CDK6 in pre-neoplastic lesions from Barrett’s esophagus to low-grade and high-grade dysplasia, thus establishing a rational for testing of a CDK4/6 dual inhibitor, Abemaciclib, in an established EAC model. Methods: Esophagojejunostomy was performed on Sprague-Dawley rats to induce gastroduodenojejunal reflux resulting in a sequence of histologic and molecular events that lead to the development esophageal adenocarcinoma. At 36 weeks post operatively, rats were randomized to receive Abemaciclib at 26 mg/kg or placebo (acetate buffer), intraperitoneally once daily for 4 weeks. Drug efficacy was evaluated with magnetic resonance imaging (MRI), endoscopic biopsy, histology, and CDK4/6 pathway expression by RT-PCR. Results: Twelve of 15 (80.0%) treated animals and all of 18 (100%) control animals reached study end-point. All of the treatment group mortality consisted of rats afflicted with moderate peritonitis, diarrhea and weight loss. Mean MRI tumor volume decreased by 93.55% in treatment animals and increased by 108.33% in control animals (P = 0.003). Treatment with Abemaciclib demonstrated tumor volume increase in 0% (control = 66.7%) (P = 0.0003), decrease in 75% (control = 0%) (P = 0.00001), and stable volume in 25% (control = 33.3%) (P = 0.63). EAC prevalence in treatment animals decreased by 50%; whereas, prevalence in control animals increased by 5.6% (P = 0.003). mRNA expression, pre- and post-treatment, demonstrated significant downregulation of CDK4, CDK6, RB1, pRB1 and Cyclin-D. Conclusions: Abemaciclib exhibits potent in vivo antitumor efficacy in a de novo EAC model, providing the rationale for clinical testing.
Current trends in the interventional treatment of hepatocellular carcinoma: A cross-sectional survey of transarterial embolization techniques.
Authors: Craig Paul , Young Shamar , Lunos Scott , Golzarian Jafar 
Published: September 2018

e15627 Background: Since two randomized controlled trials demonstrated the superiority of Transarterial chemoembolization (TACE) to supportive care, it has been a mainstay of treatment for unresectable hepatocellular carcinoma (HCC). The technical aspects of the TACE procedure, including drug type, embolic agent, bead type and size, procedural endpoint and follow up are heterogeneous throughout the literature, making meaningful comparisons less impactful. The goal of this study was to determine the common technical practices in the interventional therapy of HCC over several geographical areas. Methods: An anonymous 18 question online survey was distributed via email to practicing members of the Cardiovascular and Interventional Radiology Society of Europe (CIRSE), Chinese Society of Interventional Radiology (CSIR), Japanese Society of Interventional Radiology (JSIR), Korean Society of Interventional Radiology (KSIR), and the Society of Interventional Radiology (SIR). An estimated 15,700 surveys were distributed and 1160 responses obtained from 62 countries for a total response rate of 7.4%. Results: Excluding bead size, responses were statistically different by region (p < 0.05). Doxorubicin was more commonly used among SIR, CIRSE, and KSIR members than JSIR and CSIR members (p < 0.05). A fixed dose of cytotoxin was favored by SIR and CIRSE members, while dosing dependent on tumor-size was used by KSIR, JSIR, and CSIR members (p < 0.05). Drug eluting bead-TACE (DEB-TACE) was most popular in SIR and CIRSE, while classical TACE (cTACE) was most popular in Japan, Korea, and China (p < 0.05). For DEB-TACE procedures, the favored bead size was 100 μm – 300 μm for all groups. Procedural endpoint, type of embolic agent, and use of additives and antibiotics varied among groups (p < 0.05). CT was the most commonly used modality for follow up amongst all respondents, but MR was used more by SIR members than all other groups (p < 0.05). Conclusions: This study demonstrated that there is clear evidence that the TACE technique differs by region. Understanding and reporting the current practice trends is an important step to optimize and standardize future randomized controlled trials.
A pilot study on cisplatin-based transarterial chemoembolization combined with systemic cisplatin plus gemcitabine for advanced or metastatic intrahepatic cholangiocellular carcinoma.
Authors: Ogasawara Sadahisa , Ooka Yoshihiko , Suzuki Eiichiro , Sugiyama Harutoshi , Tawada Akinobu , Sakai Yuji , Chiba Tetsuhiro , Kanai Fumihiko , Tsuyuguchi Toshio , Yokosuka Osamu 
Published: September 2018

e15629 Background: Systemic cisplatin plus gemcitabine (CisGem) is the standard treatment for patients with advanced or metastatic intrahepatic cholangiocellular carcinoma (ICC). Transarterial chemoembolization (TACE) is a treatment procedure for patients with liver cancer. This prospective study was to evaluate the safety and efficacy of cisplatin-based TACE combined with systemic CisGem in patients with ICC. Methods: Eligibility criteria were histologically or cytologically confirmed, unresectable, recurrent or metastatic mass-forming type ICC; Eastern Cooperative Oncology Group performance status 0–2; and an adequate major organ function. Patients may have had prior treatment, including surgery, but no prior CisGem therapy. Cisplatin (25 mg/m2) plus gemcitabine (1000 mg/m2) were intravenously administered on days 1 and 8 of a 21-day cycle for 12 cycles. Three sessions of TACE were scheduled—before first, fifth, and ninth cycle of CisGem. A suspension of CDDP-powder 35 mg/m2 and lipiodol was injected through tumor-feeding branch of intrahepatic lesions, and embolization of the feeding arteries was performed using gelatin sponge (UMIN000004776). Results: Of 14 patients enrolled between December 2010 and December 2013, 7 (50%) completed treatment schedule, whereas 4 (29%) and 3 (21%) discontinued due to disease progression and adverse events (one patients each due to allergic reaction, platelet count reduction, and hepatic infection), respectively. The most common severe adverse events were elevated aspartate aminotransferase (86%) and alanine aminotransferase (71%) levels; reduced neutrophil (36%), platelet (36%), and white blood cell (28%) counts; and hepatic infection (21%). Eleven patients (79%) were evaluated for objective response (RECIST version 1.1): 9 were observed to have a partial response and 2 had a stable disease. The 6-month progression-free survival rate was 64%, and median overall survival was 25.8 months. Conclusions: Cisplatin-based TACE combined with CisGem is a feasible treatment option; however, a randomized clinical trial for comparison with CisGem is required in future. Clinical trial information: UMIN000004776.
Efficacy and safety of anti-VEGF therapy in metastatic unresectable hepatocellular carcinoma: A meta-analysis.
Authors: Chintalacheruvu Lakshmi Manogna , Buddam Avanija , Kanmanthareddy Arun , Ganti Apar Kishor 
Published: September 2018

e15632 Background:Conventional chemotherapy has limited role in metastatic unresectable hepatocellular carcinoma (HCC). Sorafenib is currently approved for metastatic unresectable HCC. We wanted to assess the efficacy and safety of other tyrosine kinase inhibitors (TKI) targeting vascular endothelial growth factor (VEGF) receptor such as brivanib, linifanib and regorafenib in metastatic HCC. Methods: We have searched electronic databases Pubmed, Google scholar to identify published trials using brivanib, linifanib and regorafenib in HCC. The outcomes evaluated were overall survival, time to disease progression (TTDP) and adverse effects. Hazard ratios (HR) with their respective 95% confidence intervals (CI) were then computed using the appropriate model for categorical variables. We used STATA 13.0 and Comprehensive Meta Analysis 2.0 software for all analyses. Results: We included seven randomized control studies. A combined analysis of these seven randomised control trials showed improved overall survival (OS) in VEGF-TKI group when compared to placebo HR - 0.79; (95% CI 0.62-1.00). However, there was no significant survival benefit of the newer VEGF receptor inhibitors when compared to sorafenib (HR - 1.05; 95% CI 0.95-1.17). The time to disease progression (TTDP) was significantly better in VEGF-TKI group as compared to placebo (HR - 0.61; 95% CI 0.39-0.97). However, there was no significant difference in TTDP between VEGF-TKI group and Sorafenib (HR - 0.88; 95% CI 0.66-1.16). Adverse effects were noted to be higher in VEGF-TKI group when compared to placebo (HR- 1.07; 95% CI 1.01-1.13). Conclusions: Treatment with TKI targeting VEGF receptor is associated with a significant improvement in OS and TTDP with tolerable side effect profile. Inhibiting the VEGF receptor pathway could lead to improved outcomes in HCC.
Preoperative hemoglobin-to-red cell distribution width ratio as a novel prognostic parameter in hepatocellular carcinoma after curative resection.
Authors: Lin Ze-xiao , Ruan Dan-yun , Li Yang , Wu Dong-hao , Wang Tian-tian , Lin Jin-Xiang , Wu Xiang-yuan 
Published: September 2018

e15634 Background: Cumulative evidence has demonstrated that interaction between tumor and the inflammatory microenvironment plays a critical role in the development and progression of hepatocellular carcinoma (HCC). This study aims to investigate the prognostic value of hemoglobin to red cell distribution width (RDW) ratio (HRR), as a novel and simple biomarker reflecting both the host inflammatory response and nutrition status, in patients with HCC undergoing curative hepatectomy. Methods: We retrospectively analyzed 373 HCC patients treated with hepatic resection between January 2004 and December 2012. Preoperative complete blood counts were used to calculate HRR. The best cut-off for survival analysis was determined by receiver operating characteristics (ROC) curve analysis. Univariate and multivariate analyses were applied to assess HRR and other clinicopathological variables. Results: The optimal cutoff value of HRR was 1.06 with an area under the curve (AUC) of 0.591 (95% CI, 0.540-0.642, p = 0.0072). A low preoperative HRR level ( < 1.06) was significantly correlated with hypoalbuminemia, female sex, the presence of portal hypertension and elevated level of total bilirubin. After a median follow-up of 48.5 months (range, 2-148.2 months), patients with a low HRR had significantly worse 5-year overall survival (OS) (69.2% vs 83.9%, p = 0.002). However, no significant difference was observed between low and high HRR groups with respect to recurrence free survival. The HRR (p = 0.009), histological differentiation (p = 0.003), Barcelona Clinic Liver Cancer stage (p = 0.003), serum alkaline phosphatase level (p = 0.008) and serum alanine aminotransferase level (p = 0.041) were identified to be independent prognostic factors of OS by multivariate analysis. This cox model was validated by bootstrap resampling, confirming low HRR as an independent predictor of shorter OS after adjustment (p = 0.01). Conclusions: Our study demonstrates for the first time that preoperative HRR can serve as an independent prognostic maker in HCC patients after radical surgery. Incorporation of HRR into other indices may provide better prognostic stratification.
Transarterial chemoembolization with or without microwave ablation in the treatment of intermediate (BCLC B) hepatocellular carcinoma.
Authors: Shi Feng , Lian Shanshan , Wu Peihong , Shen Lujun 
Published: September 2018

e15635 Background: Transarterial chemoembolization (TACE) is currently the first-line treatment for patients with intermediate (BCLC stage B) hepatocellular carcinoma (HCC). However, the prognosis of patients with intermediate HCC remains unsatisfactory, because TACE was limited by its lack of ability to achieve complete tumor necrosis. In this study, we retrospectively compare the outcome of TACE with or without microwave ablation (MWA) in the treatment of intermediate HCC. Methods: Included in this study were 140 patients with intermediate stage HCC who underwent initial TACE and were potentially amendable for MWA (the sum of the size of the largest tumor in centimeters and the number of tumors should be no more than nine; and a total tumor diameter ≤11 cm) between January 2005 and February 2015. 75 patients were treated with following MWA (TACE-MWA), and the remaining 65 patients were treated with TACE alone. Cumulative overall survival (OS) and progression-free survival (PFS) rates were compared. Results: The respective 1-, 3-, and 5-year OS rates were 80%, 30%, and 20% in the TACE group; and 96%, 69%, and 48% in the TACE-MWA group (Fig. 2). The OS was statistically significantly better in the TACE-MWA group compared with the TACE group (P < 0.001). The respective 1-, 3-, and 5-year PFS rates were 53%, 13%, and 0% in the TACE group; and 59%, 27%, and 17% in the TACE-MWA group (Fig. 3B). PFS rates between the two groups did not differ significantly (P = 0.069). Conclusions: MWA following initial TACE prolongs OS and PFS of patients with potentially amendable intermediate HCC.
Dynamically trace the prognosis of patients with hepatocellular carcinoma through constructing survival paths with time-series data.
Authors: Shen Lujun , Li Wang , Chen Chen , Shi Feng , Wu Peihong 
Published: September 2018

e15636 Background: Hepatocellular carcinoma (HCC) is featured by high risk of local recurrence and intrahepatic metastasis, and always requires repeated treatment. A novel prognostic system maximally utilizes time-series data and facilitates dynamic prognosis prediction is warranted. Methods: 1341 BCLC stage B HCC patients received treatment at Sun Yat-sen University Cancer Center from Jan, 2007 to Dec, 2012 were enrolled (979 pts for derivation, 362 pts for validation). Time-series data on serum tumor markers, biochemical and hematological index, medical imaging and associated changes (CT and/or MRI) were collected. Every 3 months represented an individual time point and a total of 9 time points were defined (Table 1); data in each time interval were allocated to associated time point. To construct the survival path, the derivation cohort was sequentially divided into subgroups by one selected feature in each time point; the feature selection criteria were: 1. independent prognostic factor in Cox model; 2. most impactful based on the change of -2Log likelihood after elimination from the model. The survival path of HCC patients was further visualized and its predictive value at each time point was compared with BCLC staging system. Results: Based on the time-series data of derivation cohort, we divided the population into 13 different paths with distinct response of treatment. The survival path system showed superior prognostic value than BCLC staging system at all time points except for the no.2 time point (Table). The validation cohort showed consistent finding. Conclusions: The methodology of survival path was valuable in dynamically tracing the prognosis of HCC patients and could further facilitate treatment planning. The visualization of data by survival path could be a new tool in processing the big data of cancer in the future. [Table: see text]
Cost and morbidity of surgical management of resectable gallbladder cancer (GBC): Results from the National Inpatient Sample database.
Authors: Fountzilas Christos , Mahalingam Devalingam , Michalek Joel , Arora Sukeshi Patel 
Published: September 2018

e15663 Background: GBC is the most common biliary tract cancer. Based on a retrospective, single-institution data, extended cholecystectomy (EXT) has been recommended over simple cholecystectomy (CHOL) in tumors T2 and above. Retrospective data indicate increased morbidity/mortality with removal of more than 3 segments of the liver compared to CHOL and the effect on long-term survival is unclear. Therefore, we sought to identify short-term outcomes of hospitalization, such as cost and morbidity, for surgical treatment of GBC. Methods: The National Inpatient Sample/Healthcare Cost and Utilization Project (NIS/HCUP) for years 2010, 2011, 2012 and 2013 was surveyed for GBC hospitalizations. Hospitalizations for non-surgical management of GBC were excluded. Results: We identified 5,612 cases; mean age in EXT was 66.8 years vs. 72.4 in CHOL (p<0.001). Patients insured through Medicare were less likely to have EXT (OR: 1.5, 95% CI 1.125-2.064; p=0.007). No difference based on race (OR: 1.14, 95% CI 0.854-1.519; p=0.38). Surgical/Medical morbidity is presented in Table 1. In-hospital mortality was 3.3 vs. 4.1% for EXT and CHOL, respectively (p=0.55). Mean length of stay was higher in the EXT group (9.8 vs. 8.3 days, p=0.03), cost ($32,782 vs. 22,667.3, p=0.003) and total charges ($111,714.7 vs. 81,432.9, p<0.001). Conclusions: EXT for resectable GBC is associated with higher cost of care, probably related to higher risk for surgical site infection and stump leak. Until more evidence for overall survival benefit from EXT in this rare tumor emerges, referral of patients to high-volume centers with the hepatobiliary surgery expertise is recommended. [Table: see text]