bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatocellular carcinoma with tumor thrombus in portal vein branch: Transarterial chemoembolization combined with Iodine125 brachytherapy versus transarterial chemoembolization combined with sorafenib.
Authors: Huang Jingjun , Huang Wensou , Cai Mingyue , Guo Yongjian , Zhou Jingwen , Zhu Kangshun 
Published: May 2019

e15646 Background: Patients with hepatocellular carcinoma (HCC) accompanied with portal vein tumor thrombus (PVTT) have a poor prognosis. Although transarterial chemoembolization (TACE) plus sorafenib (TACE-S) could lead to an improved survival than TACE alone in HCC patients with first- or second-branch PVTT (branch PVTT), the survival was very limited. We compared the safety and efficacy of TACE plus Iodine125 brachytherapy (TACE-I) with TACE-S in patients with unresectable HCC and branch PVTT. Methods: The medical records of consecutive patients with HCC and branch PVTT who underwent TACE-I (TACE-I group) or TACE-S (TACE-S group) from January 2015 to December 2017 were retrospectively evaluated. Iodine125 seeds were implanted into the PVTT under CT guidance 3-5 days after the initial TACE. The matched peripheral dose of Iodine125 brachytherapy was set to be 120-140 Gy. Sorafenib was administered 400 mg twice daily. Outcomes of patients who underwent TACE-I, including adverse events, treatment responses, time to progression (TTP), and overall survival (OS), were compared with those of patients who underwent TACE-S. Results: One hundred and twenty patients were included in the analysis; 62 patients underwent TACE-I and 58 underwent TACE-S. The overall incidence of adverse events was significantly lower in TACE-I group than in TACE-S group (58.1% vs. 93.1%, P < .001), and incidence of grade 3 or higher adverse events also was significantly lower in TACE-I group than in TACE-S group (3.2% vs. 27.6%, P < .001). PVTT OR rates at 12 weeks (58.1% vs. 13.8%, P < .001) and at 24 weeks after the treatment (68.9 % vs. 10.9%, P < .001) in TACE-I group were higher than those in TACE-S group. TACE-I led to significantly longer TTP (median, 11.2 months vs. 6.2 months, P < .001) and OS (median, 20.9 months vs. 14.0 months, P < .001) than TACE-S. In uni- and multivariable analyses, TACE-I treatment, PVTT extent, tumor size ≥10 cm, PVTT OR at 12 weeks, and intrahepatic tumor OR at 12 weeks were independent prognostic factors for OS. Conclusions: TACE-I had less side effects and may improve OS than TACE-S for HCC patients with branch PVTT.
Effect of cholangitis on pre-operative evaluation of regional lymphadenopathy by CT in pancreato-biliary malignancies.
Authors: Chandra Abhijit , Gupta Vivek , Kumar Saket , Joshi Pradeep , Gupta Vishal , Gorla Pavan Kumar , Agarwal Akshay Anand 
Published: May 2019

e15651 Background: Regional lymph nodes metastasis is a poor prognostic factor in pancreato-biliary malignancies. CT findings like lymph node size > 10mm, irregular shape, heterogenous enhancement, conglomeration and infiltration can suggest metastatic involvement. Cholangitis can induce reactive changes in regional lymph nodes. This study aimed to find if episodes of cholangitis interfere with the pre-operative CT evaluation of regional lymphadenopathy in pancreato-biliary malignancies. Methods: Regional lymph nodes metastasis is a poor prognostic factor in pancreato-biliary malignancies. CT findings like lymph node size > 10mm, irregular shape, heterogenous enhancement, conglomeration and infiltration can suggest metastatic involvement. Cholangitis can induce reactive changes in regional lymph nodes. This study aimed to find if episodes of cholangitis interfere with the pre-operative CT evaluation of regional lymphadenopathy in pancreato-biliary malignancies. Results: A total of 41 patients of gallbladder cancer and 20 patients of periampullary cancer were included. A total of 206 lymph node stations were sampled. In gallbladder cancer group, CT finding of lymph node size > 10mm, ill-defined borders and conglomeration; while intra-operative findings were node size > 10mm, hard consistency and necrosis on cut-section significantly predicted metastatic lymphadenopathy on univariate analysis. In multivariate analysis, size > 10mm measured intra-operatively was the only significant predictor of metastatic lymphadenopathy.21.9% patients (9/41) had history of cholangitis pre-operatively. In this subgroup, none of the CT characteristic or intra-operative nodal feature significantly predicted malignant involvement. In periampullary cancer, nodal necrosis on intra-operative cut-section was a significant predictor of malignant involvement in univariate, but not in multivariate analysis. Subgroup analysis of patients with history of cholangitis (10/20) did not reveal any significant pre-operative or intra-operative lymph nodal feature predicting malignant involvement. Conclusions: In patients with gallbladder or periampullary cancer with history of cholangitis, the typical CT characteristics or the intra-operative characteristics of regional lymph nodes cannot be relied on to predict metastatic lymph node involvement. Thus, cholangitis affects the clinical staging of these malignancies.
Expression and heterodimerization of Type A and B Cholecystokinin Receptors in Gallbladder cancer.
Authors: Chandra Abhijit , Nigam Jaya , Goel Madhumati , Parmar Devendra , Satyam Leena Khare 
Published: May 2019

e15655 Background: Gallbladder cancer is the most common malignancy of the biliary tract and endemic in Northern India. The prognosis of gallbladder cancer remains dismal despite any treatment because of late presentation and aggressive tumor biology. Cholecystokinin (CCK) is present in abundance in gallbladder tissue and mediates function through two structurally related receptors, the type A (CCKAR) and B (CCKBR) receptors. Previously, heterodimerization of CCKAR and CCKBR receptor has been demonstrated in vitro, and was shown to bind natural agonists normally but exhibited agonist stimulated cellular signaling, promoting cell growth. In this study we examined the expression level of CCKAR and CCKBR in resected gallbladder tissue samples and also attempted to determine the dimerization status of CCKAR and CCKBR receptors in gallbladder cancer comparing them to cholelithiasis and normal gallbladder tissue. Methods: Tissue samples from resected normal gallbladder (n = 10), cholelithiasis (n = 25) and gallbladder cancer (n = 25)) were evaluated for the expression of CCKAR and CCKBR by immunohistochemistry. Determination of CCKAR and CCKBR expression was also done by western blot in representative samples from each of these tissue types while their dimerization status was evaluated by immunoprecipitation. Results: By Immunohistochemistry technique, positive CCKAR expression was observed in 80% gallbladder cancer, 84% cholelithiasis, 90% normal gallbladder, P = 0.76. However significantly higher expression of CCKBR was noted in gallbladder cancer (60%) as compared to cholelithiasis (25%) and normal gallbladder (20%), P = 0.013. We also observed progressively increasing level of expression of CCKAR and CCKBR in gallbladder cancer as compared to cholelithiasis and normal gallbladder by western blot. In addition, we also observed a higher level of heterodimer formation in gallbladder cancer compared to cholelithiasis and normal gallbladder using immunoprecipitation technique. Conclusions: Our results provide the first evidence of increasing trend of heterodimerization of CCKAR and CCKBR in gallbladder cancer which has potential clinical and therapeutic significance.
Characterization of tumor mutation burden, PD-L1 and hepatitis B virus in Chinese hepatocellular carcinoma patients.
Authors: Xu Junjie , Liang Xiao , Liu Lingxiang , Mou Haibo , Wan Zhe , Jiang Shi , Yang Zhe , Zeng Daobing , Chen Xiaoqian , Shi Junping , Yao Ming , Chen Zhonghai , Wang Kai 
Published: May 2019

e15666 Background: Hepatocellular carcinoma (HCC) has a high mortality rate and is the fourth most common cancer in China. Immunotherapy of immune checkpoint inhibitors (ICI) is a promising novel treatment strategy, but the response rate is generally low and it is not clear which patients will benefit from ICI immunotherapy. Methods: Deep sequencing targeting 450 cancer genes was done on FFPE and matched blood samples from 601 Chinese HCC patients (pts). Genomic alterations including single nucleotide variations, short and long insertions/deletions, copy number variations (CNV), gene rearrangements and fusions were analyzed. Tumor mutation burden (TMB) was measured by an algorithm developed in-house, PD-L1 expression was done by immunohistochemistry staining and Hepatitis B Virus (HBV) by target capture. Results: Patients, median age 55 years old, had TMB values in a range of 0.7 to 69.6 Muts/Mb. The 1st Quartile, median and 3rd Quartile TMB values were 3.8, 5.4 and 7.8 Muts/Mb, respectively. Comparing 155 pts with TMB-H (≥3rd Quartile) to 181 TMB-L (≤1st Quartile) pts, the mutant frequencies of TERT (49% vs 38%, p= 0.044), CTNNB1 (32% vs 11%, p< 0.001), LRP1B (14% vs 5%, p= 0.004) and ARID1A (12% vs 5%, p= 0.014) were higher. The mutant frequency of TP53 was lower (57% vs 68%, p= 0.035). TMB-L had younger pts (median age 50y vs 60y, p< 0.001) and CNV (382 vs 232, p< 0.001). PD-L1 expression was detected seen in 222 pts, including 152 pts of Dako 28-8 Ab and 70 pts of Dako 22C3 Ab with no preference. The PD-L1 positive rate (TPS ≥1%) was 7% and 34% in 28-8 group and 22-C3 group, respectively. Eleven pts were both TMB-H and PD-L1 positive. HBV probe signal was detected in 285 pts, 262 of which were positive (≥10 reads). TMB, PD-L1 expression and HBV were not found to be significantly correlated. Conclusions: In our study, 37% of Chinese HCC pts with PD-L1 positive or TMB-H may benefit from immunotherapy. TMB-H HCC pts were older, had more common TERT, CTNNB1, LRP1B and ARID1A mutations, and fewer TP53 mutations and CNV. In our current cohort, TMB and PD-L1, TMB and HBV, and PD-L1 expression and HBV were not correlated significantly.
Imaging biomarker phenotyping system (iBiopsy) to accelerate hepatocellular carcinoma (HCC) drug development.
Authors: Liu Yan , Ramos Corinne , Baudot Pierre , Brag Johan , Lucidarme Olivier 
Published: May 2019

e15671 Background: Current drug therapies in HCC remain limited because of substantial genomic, cellular and molecular heterogeneity of the liver tumor microenvironment (TME). This heterogeneity has implications for tumor development, immune response and cellular invasion and is compounded by multiple molecular pathways related to the various HCC etiologies. In this context, it is challenging to find biomarkers that are predictive of therapeutic response or outcome. A systems biology approach leveraging the iBiopsy phenotyping platform to automatically detect HCC and TME subtypes using non-invasive medical imaging could help identify specific disease pathways and accelerate HCC drug development. Methods: In this retrospective study, 50 patients with primary HCC were used to extract voxel level image signatures from the segmented livers on CT scans. The automatic classification of liver signatures was obtained by Log Linear Local density peak clustering computed using Wasserstein’s optimal transport distance between Gray Level Co-occurrence matrices of local luminance tiles of the Liver. Through this hypothesis-free clustering, phenotypes representative of tumor and tumor environment were identified and further correlated with clinical data. Results: Nine classes of statistically significantly distant clusters were identified on the 50 patients. Preliminary correlation analysis on individual patient showed that up to 3 clusters were specific to the tumor and characterized phenotype heterogeneity within the tumor. Notably, specific clusters at the tumor front-line and surrounding adjacent non-tumoral tissue were also identified. Conclusions: Preliminary results show that a multiplicity of phenotypes representative of a complex heterogeneous lesion and tissue microenvironment that might have prognostic and predictive value can be identified. This support the use of a non-invasive phenotypic approach for the subtyping of HCC that can be used for the identification of a multiplicity of important biological pathways that can be specifically targeted to treat HCC.
HIV associated hepatocellular cancer (HCC) in an inner-city minority population.
Authors: Mukthinuthalapati V V Pavan Kedar , Putta Aakash , Farooq Muhammad Zain , Batra Kunnal , Rubinstein Paul G. , Gupta Shweta 
Published: May 2019

e15680 Background: The Highly Active Anti-Retroviral Therapy (HAART) era has seen a rise in the incidence of non-AIDs defining cancers. This study was undertaken to study the characteristics associated with HIV+ HCC in an inner-city minority population. Methods: Patients with diagnosis of HCC since January 2011 until December 2018 were identified from our hospital’s electronic medical database using ICD-9/ICD-10 codes. Charts were retrospectively screened to confirm diagnosis of HCC and identify HIV+ patients. HIV+ HCC were compared to HIV- cohort from 2011 to 2016. Statistical analysis was done using the chi-square and t-test. Results: A total of 14 HIV+ HCCs were identified and compared to 239 HIV- HCC (Table 1). All HIV+ HCC were men (100%) with 86% African Americans (AA) (p < 0.05). HIV+ HCC were more likely to be HCV+, HBV+ and less likely to have history of alcoholism. Seventy-nine percent HIV+ HCC were Child-Pugh A at diagnosis compared to 35% in HIV- HCC. The median years between diagnosis of HIV and HCC was 18. All 14 HIV+ HCC (100%) were on HAART at the time of HCC diagnosis with viral load (available for 12) undetectable in 10 (83%) and < 100 copies/mL in 2 (17%). The average CD4 count at HCC diagnosis was 258 cells/µL with 10 (71%) having CD4 counts > 200 cells/µL. HCC was multifocal in 71% HIV+ compared to 49% of HIV- patients. AFP levels were < 20 ng/mL for 50% of the HIV+ HCC patients. There were 43% BCLC B and no BCLC D patients in HIV+ HCC compared to 17% and 24% in HIV- (p < 0.05 for both). 67% HIV+ BCLC Stage C patients died within 20 weeks of HCC diagnosis. Conclusions: HIV+ HCC is predominantly AA, exclusively male disease in our inner-city population. Compared to other studies showing HIV+ HCC to be younger than the HIV- patients, our HIV+ patients were similar in age to the HIV- cohort. HIV+ HCC is more multifocal with early mortality despite early BCLC stage.. Studies are needed to investigate if frequent HCC screening may be needed in HIV+ patients with HCV/HBV co-infection.[Table: see text]
Trends from NSQIP 2015 to 2017 in neoadjuvant therapy use before pancreatic adenocarcinoma resection.
Authors: Gologorsky Rebecca C , Ely Sora , Dominguez Dana , Huyser Michelle , Chang CK 
Published: May 2019

e15685 Background: Morbidity and mortality associated with surgical resection of pancreatic adenocarcinoma remains high, and prognosis is poor even after R0 resection. Preoperative chemoradiation, previously only indicated to downstage borderline-resectable disease, has been increasingly used even in cases that appear resectable at time of diagnosis. Response to therapy can be prognostic and guide clinical decision-making. We investigated significant trends over time in neoadjuvant treatment of patients within the National Surgical Quality Improvement Project (NSQIP) database treated surgically for pancreatic adenocarcinoma. Methods: We queried NSQIP data for patients who underwent pancreaticoduodenectomy or subtotal pancreatectomy for pancreatic adenocarcinoma in 2015-2017. We examined differences by year in neoadjuvant treatment use with Chi-square test. Results: There were 8626 patients included. Use of neoadjuvant treatment (chemotherapy or chemoradiotherapy) increased over the study period, and complication by pancreatic fistula and delayed gastric emptying decreased qualitatively over the same time (12% to 9%; 14% to 12%). This increase in use of neoadjuvant chemotherapy was significant among patients with T1, T2, and T3 tumors (Table 1). However, despite NCCN/ASCO guidelines recommending neoadjuvant for all patients with T4 tumors, only about a quarter of these patients received it, and this proportion did not change over time. Conclusions: Preoperative chemotherapy is particularly important in ≥T3 disease because of low rates (50%) of adjuvant therapy, likely secondary to postoperative morbidity. The NSQIP data reflects the trend toward increasing neoadjuvant therapy in lower-T stage disease, but not among patients with T4 disease. This may be because NSQIP data largely reflects community hospital populations, and this practice was first adopted by academic institutions. Based on our findings, it is important that medical oncology be involved early in the multidisciplinary care of patients with pancreatic adenocarcinoma.[Table: see text]
The effect of race on adherence to NCCN Guidelines for patients with biliary tract cancers (BTC) after surgery.
Authors: Alahmadi Asrar , Cioffi Gino , Opneja Aman , Patil Nirav , Bajor David Lawrence , Saltzman Joel N. , Barnholtz-Sloan Jill , Lee Richard T. 
Published: May 2019

e15686 Background: BTC has a limited prognosis even for localized cancers (15-30% 5-year survival) emphasizing the importance of multidisciplinary management. NCCN guidelines recommend adjuvant chemotherapy (CT) +/- radiotherapy (RT) for high risk disease. We analyzed adherence to NCCN guidelines among patients following surgery for BTC and the influence of race. Methods: Subjects were identified from the National Cancer Database (NCDB) for BTC patients who underwent surgery and found to have metastatic lymph nodes (LN+) or positive surgical margins (M+) from 2004 to 2015. We defined adherence to NCCN guidelines as receiving surgery+ CT +/- RT and non-adherence to the guidelines as surgery +/- RT. Descriptive studies and multivariate logistic regression analysis was performed. Results: A total of 3,792 patients were identified with approximately half being female (55.4%) and between the ages of 50-69 (52.8%). Most were White (76.3%) followed by Black (10.6%), Hispanic (8.5%), and Asian (5.3%). The BTC included extrahepatic cholangiocarcinoma (CCA) (48.6%), gallbladder cancer (43.5%), and intrahepatic CCA (7.9%). Most patients had an R0 resection (71.9%) but also had LN+ disease (88.0%). There were no significant differences between racial groups in disease presentation (histological grade, tumor stage) and surgical outcomes (LN+, M+, hospital readmission, and 90 day post-surgery mortality). Hispanic patients as compared to White patients were less likely to be insured (85.7% vs 96.3%, p < 0.001) and less likely to be treated at an academic facility (42.1% vs 52.1%, p = 0.008). Overall 29.7% of patient did not adhere to NCCN guidelines with Hispanics having the highest proportion of non-adherence as compared to Whites, (36.1% vs 28.7%, p = 0.029). On multivariate analysis, Hispanic race (HR = 1.51, 95% CI: 1.15-1.99) remained significant for receiving treatment non-adherent to NCCN guidelines. Conclusions: This study indicates that Hispanics are significantly more likely to receive non-adherent care in comparison to White patients in accordance with NCCN guidelines. More research is needed to confirm and understand the observed disparities and guide targeted interventions.
Evaluation of Ki67 and other predictors of survival in metastatic neuroendocrine tumor (NET) to the liver treated with Y90 radioembolization.
Authors: Cronan Julie , White Bernadette , Ermentrout Robert Mitchell , Bercu Zachary Louis , Shaib Walid Labib , Newsome Janice , Kokabi Nima 
Published: May 2019

e15687 Background: Ki67 index is a predictor of survival in patients with metastatic neuroendocrine tumor (NET). The purpose of this study is to evaluate Ki67 index and other potential predictors of overall survival (OS) in patients with NET metastases to the liver treated with Y90 radioembolization. Methods: In an institutional review board-approved retrospective study, consecutive patients with NET metastases to the liver who were treated with Y90 radioembolization from 2013-2018 at a single institution were evaluated. Patients with documented Ki67 index were stratified according to 2017 World Health Organization (WHO) grading based on Ki67 index (G1: < 3%, G2: 3-20%, G3: > 20%). Age, gender, and objective tumor response on post Y90 imaging were also evaluated as potential predictors of survival after Y90. Objective tumor response was evaluated at 1 and/or 3 months post Y90 with multiphase MRI utilizing Response Evaluation Criteria for Solid Tumors (RECIST). Overall survival (OS) from time of Y90 was analyzed using Kaplan-Meier estimation. Predictors of survival were evaluated using log-rank test with p < 0.05 as the statistically significant level. SPSS software v. 25 (IBM Corporation, Armonk, NY) was used for all statistical analysis. Results: A total of 77 patients were identified; 36 (47%) had a documented Ki67 index from either their primary tumor, liver metastasis, or both. Primary tumor site included pancreatic (n = 10), small bowel (n = 7), pulmonary (n = 5), gastric (n = 3), large bowel (n = 3), and renal (n = 1). A primary site was not identified in several patients (n = 7).G1 tumors comprised 31% (n = 11) of patients, while G2 and G3 tumors made up 50% (n = 18) and 19% (n = 7) of the cohort, respectively. Median overall survival (OS) of the entire cohort was 51.1 months. Median OS in patients was 63.0 months in G1 tumors, 51.1 months in G2 tumors, and 3.1 months in G3 tumors (p < 0.001). Objective response on initial MRI follow-up after Y90 radioembolization also predicted prolonged OS (51.2 months versus 17.9 months, p < 0.001). Age at time of diagnosis and gender were not predictors of survival after Y90 radioembolization. Conclusions: WHO grading based on KI67 index and objective tumor response appear to be predictors of prolonged survival in patients with metastatic NET to the liver treated with Y90 radioembolization.