bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weak correlation of overall survival and time to progression in advanced hepatocellular carcinoma.
Authors: Huang Liping , De Sanctis Yoriko , Shan Minghua , Bruix Jordi , Llovet Josep , Cheng Ann-Lii , Meinhardt Gerold , Nakajima Keiko 
Published: March 2017

233 Background: Time to progression (TTP) is a potential surrogate endpoint in oncology clinical trials. The correlation of TTP and overall survival (OS) in advanced hepatocellular carcinoma (HCC) has been studied by meta-analyses (Terashima et al, Hepatol Res 2016;46:650); however, these analyses may be biased by trial selection and heterogeneity. We assessed the correlation between TTP and OS using simulated trials based on patient level data from 2 large sorafenib trials in patients (pts) with unresectable HCC (uHCC). Methods: To assess the correlation between OS and TTP, a bootstrap approach was applied to simulate 10,000 trials based on data from the randomized, phase III sorafenib trials in uHCC pts (SHARP [n = 602] and Asia-Pacific [AP; n = 226]). Individual data correlation between OS and TTP was conducted for 828 pts included in SHARP and AP. Pearson correlation was calculated between estimated median OS (mOS) and estimated median TTP (mTTP) for sorafenib and placebo (PLA) arms separately. Pearson correlation of log rank test statistics and hazard ratios were calculated to compare sorafenib and PLA for OS and TTP. Results: Simulated mOS and mTTP trial data were similar to that reported in SHARP and AP (Table). In SHARP, the correlation between mOS and mTTP was 0.270 for sorafenib and 0.218 for PLA, and in AP, 0.333 for sorafenib and 0.251 for PLA. The correlation of log rank test statistics comparing sorafenib and PLA was 0.387 in SHARP and 0.540 in AP. Conclusions: The simulated mOS/mTTP data was representative of pt population data in SHARP and AP. Our analysis showed a weak correlation between OS and TTP. This finding challenges TTP as a surrogate endpoint in HCC and should be considered when interpreting TTP results for the evaluation of treatment effect in uHCC. These data reinforce that the pattern of progression is potentially more relevant to OS than tumor progression as suggested by Reig et al ( Hepatol 2013;58:2023). Clinical trial information: NCT00105443; NCT00492752. [Table: see text]
Research on predictive value of five current staging systems in advanced hepatocellular carcinoma patients who received loco-regional therapies.
Authors: Chen Zhan-Hong , Wei Li , Hong Ying-Fen , Lin Jin-Xiang , Li Xing , Wu Xiang-yuan 
Published: March 2017

237 Background: Many HCC patients are diagnosed at advanced stage and loco-regional therapies improve their prognosis. Transarterial chemotherapy with or without concomitant embolization(TACE) and percutaneous ethanol injection(PEJ) are two common loco-regional therapies.Overall survival(OS) of these patients varies differently. It is very important to identify who benefits most from loco-regional therapies. We research on five current staging systems’ predictive value. Methods: Our research analyzed 220 advanced HCC patients. They received TACE or PEJ and did not receive radical surgery, chemotherapy or target therapy. At first diagnosis all patients were classified according to CLIP (Cancer of the Liver Italian Program), Advanced Liver Cancer Prognostic System (ALCPS), Japan Integrated Scoring (JIS) system, Barcelona Clinic Liver Cancer Classification (BCLC) and model for end-stage liver diseases (MELD) score. 6 month OS, 1-year OS, 2-year OS and OS were the end points. Results: The median survival is 23.8 months. When predicting 6 month OS, AUC of CLIP, ALCPS, JIS, BCLC and MELD is 0.847, 0.724, 0.710, 0.521 and 0.509,respectively;When predicting 1-year OS, AUC of CLIP, ALCPS, JIS, BCLC and MELD is 0.872, 0.689, 0.693, 0.503 and 0.552,respectively; When predicting 2-year OS, AUC of CLIP, ALCPS, JIS, BCLC and MELD is 0.855, 0.683, 0.669, 0.503 and 0.553,respectively;AUC of CLIP is significantly higher than other four staging systems in predicting 6 month OS, 1-year OS, 2-year OS(P < 0.05), while AUC difference between ALCPS and JIS does not have statistical significance in predicting 6 month OS, 1-year OS, 2-year OS(P > 0.05). When predicting OS, likelihood ratio test shows χ2 of CLIP, ALCPS, and JIS is 90.2,13.1 and 16.5 respectively. AIC of CLIP, ALCPS and JIS is 1338, 1415 and 1411 respectively. CLIP has the highest χ2 value and the lowest AIC value. As for discriminatory ability, homogeneity and monotonicity, CLIP performs best. Conclusions: The best staging system in predicting 6 month OS, 1-year OS, 2-year OS and OS for advanced HCC patients who received loco-reginal therapies is CLIP.
Early obesity and risk of cholangiocarcinoma in the United States.
Authors: Shalaby Akram , Javle Milind M. , Shroff Rachna T. , Abousamra Ahmed OS , Abdel-Wahab Reham , Rallapalli Vijayashri , Li Donghui , Hassan Manal 
Published: March 2017

239 Background: In the United States, the incidence of intrahepatic cholangiocarcinoma (ICC) has been increasing over the last few decades. Despite the public health problem of obesity and the increasing incidence of ICC, the relationship between early adulthood obesity and ICC has never been examined in the American population. Methods: At the University of Texas MD Anderson Cancer Center we conducted a case-control study aimed at examining relationship between ICC and history of obesity after controlling for the potential confounding of several risk factors. Cases were patients with pathologically confirmed diagnosis of ICC. Controls were healthy subjects recruited from spouses of patients at MD Anderson who had cancers other than liver or gastrointestinal. Each case was frequency matched to 4 controls by age (± 5 years), sex, and race. Case patients and controls were interviewed for risk factors of liver cancer. A self-reported weight and body size pictogram at ages 20, 30, 40, 50, 60 was obtained from each participant. In 2016 we recruited 63 newly diagnosed patients with ICC who were compared to 252 healthy controls. Obesity was defined as body mass index (BMI) ≥ 30.0. Results: There was a significant 3 fold increase in ICC risk for obese individuals compared to those with normal weight. The estimated odds ratio (OR), 95%; confidence interval (CI) was 3.3 (1.3-9.1); P = .02. Obesity at the mid-20s, mid-30s, and mid- 40s was significantly associated with ICC risk; the estimated OR (95% CI) was 7.3 (2.8-19.7), 7 (2.4-20.9), and 4.8 (2-11.4), respectively. In addition, viral hepatitis, heavy alcohol use ( > 40 ml ethanol/day), and family history of cancer were significantly associated with ICC. Underlying radiological, pathological, or clinical evidence of steatosis, fibrosis, and cirrhosis was significantly observed in 25% ICC patients with early obesity. Conclusions: We concluded that early adulthood obesity is a significant risk factor for ICC in USA where underlying fatty liver diseases can be a significant factor for ICC progression. Integration of obesity with other ICC risk factors into a risk model may lead to identify high-risk individuals. Future collaboration with other US institutions is highly warranted to highlight the mechanism of obesity-induced ICC.
Application of ALBI and PALBI score as prognostic variables in hepatocellular carcinoma patients treated with transarterial-chemoembolization.
Authors: Aravind Preetha , Thillai Kiruthikah , Suddle Abid , Heaton Nigel , Karani John , Kane Pauline , Peddu Praveen , Lewis Dylan , Sarker Debashis , Ross Paul J. 
Published: March 2017

241 Background: Albumin-Bilirubin Score(ALBI) is simple prognostic tool to stratify HCC patients on liver function. It is proposed as more accurate predicting score of hepatic dysfunction compared with Child-Pugh (CP) grading. Platelet-Albumin-Bilirubin Score (PALBI) incorporating platelet count may offer further prognostic sensitivity. We sought to correlate ALBI, PALBI and CP grade with overall survival in HCC patients who underwent transarterial-chemoembolization (TACE). Methods: 431 HCC patients who received TACE between 2006 and 2012 at a Liver Centre, UK was included. Serum albumin, bilirubin and platelet were used to calculate ALBI and PALBI scores. Patients were classified into three groups using previously described formulas. Survival outcomes (Median OS) were measured using Kaplan-Meier method. Results: Median age of study population was 62 years. Patients classified by ALBI score, Group 1 was 208 patients (48%), 2 was 196 (45.4%) and 3 was 27 (6.3%). Median OS for Group 1 was 26.1 months (m) (95% CI 19.5-32.6), 2 was 18.6m (95% CI 14.9-21.5) and 3 was 11.7m (95% CI 6.1-17.3) (p < 0.001). PALBI Group 1 was 179 (41.5%), 2 was 150 (34.8%) and 3 was102 (23.7%). PALBI group 1 had median OS 25.5m (95% CI 17.9-33.1), 2 had 22.3m (95% CI 18.3-26.3), 3 had 10m (95% CI 5.9-14.3) (p < 0.001). Majority were class CP-A. (A = 365, B = 63, C = 2). CP-A patients were re-stratified on ALBI and PALBI status. ALBI Group 1 (N = 204) OS 26.0m (95% CI 19.5-32.6), 2 (N = 151) OS 19.1m (95% CI 14.7-23.5), 3 (N = 7) OS 7.6m (95% CI2.27-12.9) (p = 0.04). Survival of CP-A patients by PALBI was significantly different - Group1 (N = 175) OS 28.8m (95%CI 20.79-36.74), 2 (N = 140) OS 22.6m (95%CI 18.89-26.25) and 3 (N = 50) OS 8.9m (95%CI 6.25-11.5) (p < 0.001). Conclusions: Significant comparable survival difference was seen in ALBI and PALBI groups. CP-A patients with group 3 ALBI or PALBI had significantly poorer survival than groups 1 and 2 suggesting increased sensitivity determining hepatic dysfunction compared with CP status. Our results suggest ALBI and PALBI scores likely more accurate stratifying method for mild liver disease and guide treatment. Further prospective studies using both scores are warranted.
Health insurance and pancreatic cancer.
Authors: Schlegel Cameron , Du Liping , Shyr Yu , Whiteside Martin , Parikh Alexander A. 
Published: March 2017

247 Background: Health insurance disparities affect the treatment and outcomes of many cancers and include differences in screening, surgical therapy and receipt of adjuvant therapy. The purpose of this study is to better identify the effect of health insurance on surgical therapy and overall survival (OS) in pancreatic adenocarcinoma (PDAC). Methods: 4564 patients diagnosed with PDAC between 2004 and 2013 from the Tennessee Cancer Registry were stratified into 5 groups: Private, Medicare, Military, Medicaid, and uninsured. Univariate analysis and multivariable (MV) logistic regression models were used to test the association of insurance with receipt of surgical therapy, adjuvant therapy, OS and cost. Results: Uninsured and Medicaid patients were more often black and presented with later stage disease. In patients with stage 1 and 2 disease, R0 resection rates, lymph node positivity and overall cost were similar across insurance groups. By MV analysis, Medicare and Military insurance patients were more likely to be resected (OR 2.52 and 3.30 respectively) with a trend for private insurance (OR 2.19) compared to the uninsured and Medicaid. There was no difference in the use of adjuvant chemotherapy (ACT). By Cox-proportional hazards regression, OS in resected patients amongst different insurance groups and race were similar (Table). Factors associated with decreased OS survival included increasing age, stage, lymph node status, and grade while the use of ACT, but not chemoradiation (ACRT), was associated with improved OS. Conclusions: Uninsured and Medicaid patients with PDAC present with later stage disease and are less likely to undergo resection. The use of adjuvant chemotherapy, OS and cost, however, are similar among insurance types. These results are in contrast to other cancers, suggesting that disparities in health insurance may play a smaller role in more aggressive cancers without effective screening. [Table: see text]
Role of HSF1 expression for tumor microenvironment in intrahepatic cholangiocarcinoma.
Authors: Saito Yu , Morine Yuji , Takasu Chie , Iwahashi Shuichi , Higashijima Jun , Ikemoto Tetsuya , Imura Satoru , Shimada Mitsuo 
Published: March 2017

249 Background: Heat shock factor 1 (HSF1) is a master regulator of heat shock response. HSF1 is recently identified to play a multifaceted role in cancer progression. However, the clinical significance and biological effect of HSF1 in intrahepatic cholangiocarcinoma (IHCC) remain unknown. The aim of this study was to investigate the relationship between HSF1 expression and clinicopathological factors in IHCC patients after hepatic resection, and its possible mechanism for malignant behavior. Methods: Forty-nine patients with IHCC who undergo hepatic resection were enrolled in this study. HSF1 expressions in tumor tissue were determined by immunohistochemistry. Patients were divided into two groups, the HSF1 high and low expression group. Clinicopathological factors including prognosis were compared between the high group (n = 20) and low expression groups (n = 29) in tumor tissues. Furthermore, the correlation between HSF1 with Fbxw7 or Ki-67 expressions was also examined. Results: HSF1 expression in tumor tissues was significantly higher than that in normal tissues. HSF1 expression was not significantly correlated with any clinicopathological characteristics, including age, sex, tumor markers, maximum tumor size, tumor number, and tumor staging curability . The overall survival rate in the HSF1 high expression group was significantly worse than that in the HSF1 low expression group ( p= 0.018). On multivariate analysis, HSF1 high expression was detected as the independent prognostic factor. There was a significant inverse correlation between HSF1 and Fbxw7 expression ( p= 0.008). Ki67 labeling index was significantly higher in the high than in the low HSF1 expression group ( p= 0.030). Conclusions: HSF1 high expression in tumor tissues may be prognostic biomarker in IHCC. Targeting the Fbxw7/HSF1 axis might be a critical therapeutic strategy in IHCC.
Quantitative CT imaging features for hepatocellular carcinoma (HCC) with b-catenin (CTNNB1) gene mutation.
Authors: Khalaf Ahmed M. , Fuentes David T. , Ahmed Kareem , Abdel-Wahab Reham , Hassan Manal , Kaseb Ahmed Omar , Hazle John D. , Elsayes Khaled M. 
Published: March 2017

253 Background: To determine whether CT imaging features can provide quantitative biomarkers to differentiate HCC with pathologic B-catenin gene mutation and those without mutation. Methods: Quantitative imaging features were extracted from a database of manually labeled liver with enhancing and non-enhancing tumor tissue,which were established using multiphasic CT images from 17 patients. CT studies were done before each patient underwent surgical removal of the HCC, which were subjected to pathologic analysis to evaluate B-catenin mutation.The mean period between the CT studies and the pathologic analyses was 18 days. According to the pathology results, the patients were divided into two groups: HCC with CTNNB1 mutation and HCC without. Image feature extraction included image gradients, co-occurrence matrix, and pixel neighborhood statistics of the first, second, and third moments. Pairwise analyses of the imaging features were performed on the mutated and non-mutated HCC images and the background liver tissue of both groups. Independent samples t-test and Mann Whitney U test were performed to quantitatively compare between the means of the imaging features extracted from the tumor tissues of both groups and those extracted from the background liver tissue of both groups. Results: Imaging feature analysis of the pairwise difference between the mutated and non-mutated HCC scans for multiple pixel-neighborhood image features are statistically significant.The top stratifying image features include the skewness (p = 0.02), energy (p = .03), and entropy (p = .03) during the venous and arterial phase. Conclusions: This preliminary study demonstrates the feasibility of quantitative imaging feature extraction from CE-CT imaging to differentiate between HCC with proven B-catenin gene mutation and those without mutation. Non-invasive methods of identifying HCC with B-catenin mutations may be clinically beneficial since B-catenin is an important potential target in novel cancer therapies, and identifying B-catenin mutations may also help provide information regarding prognosis.Verifying the quantitative features in larger patient populations is needed to confirm the results of this study.
Tumor stage and primary treatment selection among a large cohort patients with hepatocellular carcinoma.
Authors: You Xue-Mei , Zhong Jian-Hong , Peng Ning-Fu , Ma Liang , Li Le-Qun 
Published: March 2017

256 Background: This study reviewed the distribution of each tumor stage and each type of primary treatment modality among patients with primary hepatocellular carcinoma (HCC) treated at a tertiary tumor hospital between January 2003 and October 2013. Methods: Baseline data of patients with primary HCC treated between January 2003 and October 2013 were retrospectively collected. Tumor stage was determined according to the Barcelona Clinic Liver Cancer (BCLC) staging system and Hong Kong Clinic Liver Cancer (HKLC) staging system. Results: A total of 6241 patients with primary HCC were included in the analysis. In accordance with the BCLC, 28.9% of patients were in stage 0/A, 16.2% in stage B, 53.6% in stage C, and 1.3% in stage D. According to the HKLC stage system, 8.4% patients were in stage I, 1.5% in stage IIa, 29.0% in stage IIb, 10.0% in stage IIIa, 33.6% in stage IIIb, 3.4% in stage IVa, 2.5% in stage IVb, 0.2% in stage Va, and 11.4% in stage Vb. Treatment modalities applied to this patient group were as follows: 33.3% of patients underwent hepatic resection, 36.7% underwent transarterial chemoembolization (TACE), 2.2% underwent radiotherapy, 0.9% underwent local ablated therapy, 8.8% underwent systemic chemotherapy, 4.2% underwent traditional herbal medicine therapy, 0.1% underwent targeted drug therapy, and 13.8% received no treatment. Hepatic resection was the most frequent therapy for patients with BCLC 0/A/B disease, and TACE was the first-line therapy for patients with BCLC C disease. In the HKLC stage, the main treatments for HKLC I to IIIb disease is hepatic resection and TACE. Systemic chemotherapy was the first-line therapy for patients with HKLC IVa/IVb disease. Most HKLC Va/Vb patients received traditional Chinese medicine (TCM) treatment. Conclusions: Prevalence of stage BCLC B and C disease was high among our HCC patients. In HKLC stage, HKLC I to IIIb disease was high among our HCC patients. Hepatic resection and TACE are first-line therapies.
Comparision of adefovir and lamivudine for patients with hepatitis B virus-related hepatocellular carcinoma after hepatic resection.
Authors: Xiang Xiao , Zhong Jian-Hong , Ke Yang , You Xue-Mei , Peng Ning-Fu , Ma Liang , Li Le-Qun 
Published: March 2017

257 Background: Lamivudine (LAM) and adefovir dipivoxil (ADV) are widely used in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), but few studies have directly compared their therapeutic efficacy and treatment cost. This study aims to compare LAM with ADV head-to-head in these patients. Methods: We retrospectively analyzed 201 patients with HBV-related HCC who underwent radical resection and subsequently received LAM (n = 155) or ADV (n = 46). The two groups were compared in terms of HBV-DNA levels, liver function, antiviral resistance, recurrence-free and overall survival, as well as antiviral medication costs. Results: Despite significant improvement in HBV-DNA and ALT level in the LAM group after 1 year of antiviral therapy, these parameters did not differ significantly between the two groups over the following 2 years. Incidence of antiviral resistance after 1, 2 and 3 years of antiviral treatment was significantly higher in the LAM group (19.5%, 45.7%, 56.4%) than in the ADV group (0%, 3.3%, 14.5%; P < 0.001). Overall survival at 1, 2, 3 years after resection was similar for the LAM group (84.5%, 69.3%, 64.6%) and the ADV group (84.1%, 77.8%, 63.4%; P = 0.905). Recurrence-free survival at the three follow-up points was also similar for the LAM group (71.7%, 58.3%, 43.9%) and the ADV group (81.1%, 66.1%, 53.0%; P = 0.452). Cox regression analysis confirmed that both nucleos(t)ide analogues were associated with similar overall and recurrence-free survival. However, the average medication costs after 1, 2, 3 years of antiviral treatment were significantly higher in the LAM group (€3.0, €4.8, €5.6 per person per day) than in the ADV group (€2.2, €2.4, €3.1 per person per day; all P < 0.05). Conclusions: ADV and LAM are associated with similar survival benefit in patients with HBV-related HCC after radical resection, but ADV is more cost-effective.
Impact of preoperative sarcopenia and accelerated muscle loss on survival after resection of pancreatic cancer.
Authors: Lee Kyungjin , Choi Moon Hyung , Yoon Seung Bae , Lee In Seok , Lim Chul-Hyun , Kim Jin Soo , Cho Yu Kyung , Park Jae Myung , Lee Bo-In , Cho Young-Seok , Choi Myung-Gyu 
Published: March 2017

258 Background: Sarcopenia and accelerated muscle loss leading to cachexia is commonly observed in patients with pancreatic cancer. This study aimed to assess the influence of sarcopenia and accelerated skeletal muscle on survival in pancreatic cancer patients who underwent surgery. Methods: We analyzed the data of patients who were diagnosed with pancreatic adenocarcinoma who underwent surgery from 2008 to 2015. Skeletal muscle areas and changes were analyzed from two sets of computed tomography images at L3 vertebral levels obtained before and after resection of cancer. Sarcopenia was determined by the sex-specific cut-offs by an international consensus on the definition of cancer cachexia. Results: Among 175 patients, 83(47.4%) had preoperative sarcopenia and median survival were significantly shorter than patients without sarcopenia (423 vs. 694 days, p = 0.001). In addition, 50 (28.6%) patients with accelerated muscle loss after surgery ( > 15%/90 days) showed poorer survival compared with the patients without accelerated muscle loss (423 vs. 637 days, p = 0.017). Sarcopenia (hazard ratio [HR], 1.96: 95% confidence interval [CI], 1.24-3.10) and accelerated muscle loss (HR, 1.73: 95% CI, 1.10-2.72) were identified as independent predictors of survival on multivariate analyses. Combining these two factors, patients who had both preoperative sarcopenia and accelerated muscle loss showed the poorest survival after surgery compared with the other groups (p < 0.001). Conclusions: Preoperative sarcopenia and accelerated muscle loss identified by CT scans have negative impact on survival after resection of pancreatic cancer. Early detection and intensive nutritional support were essential for cachexic patients with pancreatic cancer.