bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized single blind controlled trial of beads versus doxorubicin-eluting beads for arterial embolization of hepatocellular carcinoma (HCC).
Authors: Brown Karen T. , Gonen Mithat , Do Kinh Gian , Covey Anne M. , Getrajdman George I. , Zhao Binsheng , Sofocleous Constantinos T. , Johnson Kristian , Beattie Christopher , DeMatteo Ronald P. , Solomon Stephen Barnett , Schwartz Lawrence H. , Abou-Alfa Ghassan K. 
Published: February 2017

143 Background: HAE using particles is a method of treatment for HCC. The added role of doxorubicin has never been fully understood biologically. To date, no study has demonstrated any difference in outcome using HAE versus trans-arterial chemoembolization (TACE). Methods: Patients (pts) with unresectable Okuda stage I or II HCC with adequate liver function were randomized to BB or LC loaded with 150 mg of doxorubicin. Pts were evaluated by multiphasic CT 2-3 weeks post-treatment. Progression by RECIST and/or evidence of ≤5% necrosis was considered treatment failure. Otherwise pts were followed with CT every 3 months until progression or death. Pts with either recurrent tumor or new tumor outside the treated area could be re-treated. The primary objective was response rate (RR) by RECIST. With 50 pts in each arm response rates can be estimated to within +/- 14%. Secondary objectives included assessing safety and tolerability, time to progression (TTP), progression free survival (PFS), and overall survival (OS). Quantification of tumor necrosis (TN) using CT volumetric data was correlated with outcome. Analyses were intention-to-treat. Results: Between December of 2007 and March of 2012, 101 pts were randomized, 51 to BB and 50 to LC. Demographics in the two groups were comparable: median age was 67, 77% were male and 81% were Okuda I. Median number of embolizations was 2 in both arms. There was no difference in adverse events, the most common being post-embolization syndrome of pain, fever, nausea, or vomiting (84% in both groups). There was no difference in RR: BB 11% vs LC 9% (p=0.58). Median TTP was not reached. 12 month TTP was 49 versus 56% (p=0.84), median PFS was 7 versus 9 (p=0.6), and OS 14 versus 16 months (p=0.7) for BB and LC respectively. Change in TN/tumor volume post treatment did not predict OS in either group (p=0.28). Conclusions: No difference in response was noted between pts treated with BB versus LC. Given the comparable safety profile, TTP, PFS and OS, HAE should be considered a reasonable and cost-effective therapeutic option and may be preferable to LC. Clinical trial information: NCT00539643.
Prognostic features and outcomes in primary liver sarcoma.
Authors: Guye Mary L. , Streja Leanne , Chen Steven L. , Uyeno Lori A. , Kim Joseph , Singh Gagandeep 
Published: February 2017

150 Background: Primary liver sarcoma (PLS) is a rare and aggressive hepatic malignancy. Due to the low incidence of PLS, prognostic factors have not been well characterized. The purpose of our study was to evaluate survival outcomes in primary hepatic sarcomas and determine which factors predict survival. Methods: The Surveillance Epidemiology and End Results registry was used to identify patients with PLS from 1988-2009. Patients were evaluated by standard clinical and pathological indices including: age, gender, race, tumor size, tumor grade, histology, and extent of disease. Treatment related factors included surgery and radiation. Overall survival was assessed by Kaplan-Meier method. Univariate and stepwise multivariate Cox proportional hazards analyses were performed to identify prognostic factors. Results: 541 patients with PLS were identified. The mean age was 52 and most patients were male (55%) and white (75%). The most common histology type was blood vessel tumors (50.1%) followed by soft tissue neoplasms (17.7%) and complex mixed-stromal neoplasms (14.6%). Only 33% of patients underwent surgery and most (93%) did not receive radiation. When assessing outcomes, we observed median overall survival (OS) and cancer specific survival (CSS) of 6 months for the entire cohort. When stratified by treatment type, those who received surgery + radiation had the best survival (MS=97mos, p<.001) compared to those who received either radiation alone (MS=5mos) or no treatment (MS=2mos). Stepwise multivariate analysis showed that age, male gender, tumor size, advanced stage, and no surgery were independent predictors of worse survival, all p-values < .005. Conclusions: Primary liver sarcoma is an aggressive hepatic malignancy with low median OS of 6 months. Patients treated with surgery + radiation had the best outcome with a median survival of 97 months. Independent predictors for decreased survival included age, gender, tumor size, advanced stage, and no surgery.
The liver function assessment: The indocyanine green retention in correlation with the cholescintigraphic measurement—Retrospective validation study in 107 patients with liver malignancies.
Authors: Tomasek Jiri , Kiss Igor , Prasek Jiri , Dusek Ladislav , Tucek Stepan , Valek Vlastimil , Vyzula Rostislav , Kala Zdenek , Zimova Iveta , Podhorec Jan , Halamkova Jana , Krakorova Dagmar Adamkova 
Published: February 2017

155 Background: The transarterial chemoembolization (TACE) and the radiofrequency ablation (RFA) are the keystones of interventional therapy of primary and secondary liver malignancies in oncology. A compromised liver function may be a relative contraindication to these therapies. Child-Pugh liver scoring system is widely used to exclude patients with low liver function. The indocyanine green (ICG) retention rate at 15 min. (ICGR15) is a frequently used liver function test in liver surgery, however it is not widely available. The quantification of dynamic cholescintigraphy and the calculation of hepatic extraction fraction (HEF) describes specifically a functional efficiency of the liver parenchyma. Methods: We retrospectively studied 107 patients with primary or secondary liver malignancies who underwent TACE or RFA between February 2005 and February 2012. ICG test and dynamic cholescintigraphy and Child-Pugh score were assessed before the procedure. The comparison of relative frequencies of categories was performed by binomial test (independent testing) or by McNemar’s test (paired design). The association in occurrence of different categories was tested by the help of Fisher’s exact test. Results: The comparison of categorized outcomes of ICGR15 and HEF examination revealed high degree of agreement between these techniques (p = 0.773). The statistically significant similarity in the outcome of both methods was also proved by the analysis of contingency tables. 81% of tested samples obtained the same scoring by both approaches. Clinically important discrepancies between these methods were rare and were not observed in the two extreme categories, i.e. normal and very low liver function. Conclusions: The ICGR15 correlates well with the HEF in liver function assessment. Thus either method can be used in patients who are to undergo liver directed therapies when the assessment by Child-Pugh score is not sufficient enough.
Usefulness of circulating tumor cell detection in pancreatic adenocarcinoma diagnosis.
Authors: Basile Paul , iwanicki-Caron Isabelle , Toure Emmanuel , Antonietti Michel , Lecleire Stephane , Di Fiore Aude , oden-Gangloff Alice , Blanchard France , Lemoine Francoise , Di Fiore Frédéric , Sabourin Jean-Christophe , Michel Pierre 
Published: February 2017

157 Background: For pancreatic tumor, guidelines recommend pancreatic cytology examination by EUS-FNA as the first diagnostic procedure in unresectable patients. Detecting CTCs in blood could play the role of a “liquid biopsy”. The usefulness of CTC detection in the clinical management of these patients has not been established yet. Here, we aimed to prospectively evaluate the accuracy of a diagnostic method based on CTC detection. Methods: All patients referred from January 2011 to March 2012 for EUS-FNA procedure in a context of pancreatic solid tumor diagnosis were prospectively enrolled after their consent. Prior EUS-FNA procedure a sample of peripheral blood was collected. CTCs were analyzed using the ScreenCell method. Cells were considered as tumoral if they met these morphological criteria: nuclear diameter >14 µ, anisocytosis, anisocaryosis, nuclear membrane irregularities, large nucleolus, clots of tumoral cells with platelets and fibrin. All analysis was performed by a pathologist blinded to the EUS-FNA results. The diagnosis of pancreatic adenocarcinoma was defined either by pathological evidence based on FNA or surgical specimen, or by clinical outcome with metastatic evolution and CA19.9 serum level rather than 10 fold normal value. Results: A total of 40 patients were included. A pancreatic adenocarcinoma was confirmed in 27/40 patients (68.3%). In 21 of the 27 patients, pathological proof of adenocarcinoma was obtained by EUS-FNA. For the diagnosis of adenocarcinoma, sensitivity and specificity of EUS-FNA were 77.8% and 100% respectively. The diagnostic accuracy of FNA was 85%. CTC detection was positive in 15 patients. Sensitivity and specificity were 55.5% (CI95% [40.1%; 70.9%]) and 100% (CI95% [75%; 100%]) respectively. The diagnostic accuracy of CTC was 70%. Metastatic statuses, lymph node involvement, vascular invasion, size of tumor and CA19.9 serum level were not statistically associated with CTC detection. Conclusions: We suggest that CTC detection be applied as first-line procedure before EUS-FNA in the strategy of pancreatic tumor diagnosis. With the implementation of this blood test on a routine basis, approximately one half of these patients could avoid invasive EUS-FNA procedure.
Prediction of prognosis in patients treated with everolimus for extrapancreatic neuroendocrine tumors by a single nucleotide polymorphism in PHLPP2.
Authors: Bellister Seth Albert , Zhou Yunfei , Sceusi Eric , Ellis Lee M. , Yao James C. 
Published: February 2017

163 Background: Rapamycin analogs (rapalogs) have improved outcomes in patients with neuroendocrine tumors (NETs). Few factors affecting response to rapalogs have been characterized. PHLPP2 is a phosphatase that inhibits PI3K-Akt-mTOR signaling. We hypothesized that an inactivating single nucleotide polymorphism (SNP) in PHLPP2 may affect outcomes in NETs treated with the rapalog everolimus. Methods: Blood was collected from 32 patients enrolled in a Phase 2 single arm trial of single agent everolimus in patients with NETs. DNA was extracted and RT-PCR products were sequenced to detect the L1016S SNP in PHLPP2. Outcomes analyses determined the role of the SNP in predicting progression-free survival (PFS), overall survival (OS), and response rates (RR) in patients with NETs treated with everolimus. Response rate (RR) assessed by RECIST criteria was evaluated as a binomial endpoint. A subset analysis was conducted to evaluate the NET site-specific role of the SNP. Results: Overall median PFS was 15.2 months (95% Confidence Interval (CI)=11.5 -18.7). The PHLPP2 SNP did not predict for a significant difference in PFS (Median PFS; wild type vs. SNP 16.8 (95% CI=14-20) vs. 11.3 (95% CI=4-19) mos., respectively, Hazard Ratio (HR)=1.2 (95% CI=0.5-3.1)), p=0.154). In a subset analysis, patients with extra-pancreatic NETs treated with everolimus with wild type PHLPP2 demonstrated increased PFS compared to patients with the SNP (Median PFS = 16.8 (95% CI=7-26) vs. 7.7 (95% CI=6-9) mos., HR=10.8 (95% CI=2-67), p=0.002). OS and RR were unaffected by the presence of the SNP in all analyses. Conclusions: In this preliminary study, the L1016S SNP in PHLPP2 may be prognostic for poorer PFS in patients with extrapancreatic NETs treated with everolimus. This study is hypothesis generating and requires validation in larger retrospective and randomized, placebo controlled studies in patients with NETs treated with everolimus.
Neuroendocrine tumors (NETs) of unknown primary: Is early surgical exploration and aggressive debulking justifiable?
Authors: Wang Yi-Zarn , Rau Jeffery , Diebold Anne E. , Opoku-Boateng Adwoa , Boudreaux J Philip , Woltering Eugene 
Published: February 2017

166 Background: Neuroendocrine Tumors (NETs) are rare tumors that often present with vague symptoms. Identification and localization of the primary NET can be challenging and up to 10% of patients are classified as having an unknown primary. These patients have been thought to have a poor prognosis compared to those patients with a known primary. Treatments for patients with unknown primaries are directed towards symptom control and/or cytoreduction of metastatic disease. We hypothesized that early surgical exploration and discovery of a previously unknown primary will increase long-term survival. Methods: The charts for all 342 surgical patients, seen in our clinic between 1/2009-9/2012 were retrospectively reviewed to determine which patients had a pre-operative diagnosis of a “NET with unknown primary”. Twenty-six patients were identified. For these patients, the rate of successful surgical exploration in which a primary site was identified were recorded. Clinical outcomes for these “unknown primary” patients were compared to historical survival data for patients with unknown primaries that did not undergo a surgical exploration in search of a primary. Results: Twenty-six (26/354, 7%) NET patients with a pre-operative diagnosis of an unknown primary were explored and cytoreduced. The primary tumor site was identified in all 26 patients (100%). The primary sites identified for these patients were 23 ileal (88.4%) and 3 pancreatic (11.6%). All twenty-six patients were still alive as of 9/2012 therefore, a survival curve could not be generated. Conclusions: Unknown primary NETs are not associated with a poor prognosis should timely surgical exploration and debulking result in an identification of the primary and a maximum cytoreduction. Early surgical exploration with aggressive debulking is indicated for the treatment of these patients.
Outcomes following stereotactic body radiotherapy for patients with Child-Pugh B/C hepatocellular carcinoma.
Authors: Culleton Shaelyn , Jiang Haiyan , Kim Joon-Hyung J. , Brierley James D. , Brade Anthony M. , Ringash Jolie , Dawson Laura A. 
Published: February 2017

167 Background: Assessment of outcomes in patients with hepatocellular carcinoma (HCC) and Child-Pugh B or C liver function treated with stereotactic body radiotherapy (SBRT). Methods: From 2004 – July 2012, 39 patients with HCC and Child-Pugh B/C liver function were treated with SBRT. Inclusion criteria included Child-Pugh B/C, treatment with SBRT, 5 to 15 fractions, and radical or palliative intent. Univariate analyses (UVA) were performed to assess relationships of patient demographics, liver function tests and treatment characteristics on overall survival (OS) and time to progression (TTP). Results: The majority of the 39 patients had Child-Pugh B7 liver function (69%), performance status ECOG 0-1 (82%), radiological evidence of tumor vascular thrombosis (62%) and hepatitis C as underlying liver disease (49%). 10 patients treated as bridge-to-transplant. The median dose was 3300 cGy in 6 fractions (range: 2000-4500 cGy in 5-15 fractions), individualized based on spared liver volume and underlying liver function. The median survival for all patients was 9.9 months (95% CI: 3.4-18.4). UVA demonstrated significantly reduced survival with Child-Pugh score > B7, baseline AFP > 1049 ng/mL (upper quartile) and gross tumor volume > 93 cm3. The median survival of patients treated with SBRT as a bridge-to-transplant versus the non-bridge-to–transplant patients was 30.7 months (95% CI: 0.6-not reached) versus 7.9 months (95% CI: 3.4-15.1; p=0.008). No HCC tumors treated with SBRT demonstrated local progression during the follow-up time. The median TTP for all patients was 18.8 months (95% CI: 6.2-not reached). Model for end stage liver disease (MELD) score > 12 was the only factor associated with reduced TTP on UVA. 31% of patients had a decline in Child-Pugh score by 2 or more points at 3 months. No acute treatment related toxicities of grade 3 or higher were reported. Conclusions: SBRT may be considered as a treatment option for HCC with impaired liver function. Survival is best in patients who are treated as a bridge-to-transplant, have smaller tumors, are Child-Pugh class B7, and have lower AFP levels. Randomized trials of radiation therapy in HCC patients with impaired liver function are warranted.
Unique histopathologic features of brain metastases from hepatocellular carcinoma.
Authors: Shao Yu Yun , Hsieh Min-Shu , Huang Chung-Yi , Lu Li-Chun , Hsu Chih-Hung , Cheng Ann-Lii 
Published: February 2017

169 Background: In the era of anti-angiogenic therapy as treatment for advanced hepatocellular carcinoma (HCC), the incidence and importance of brain metastases are increasing. We aimed to study their histopathologic features. Methods: We searched for all patients who were diagnosed to have HCC with brain metastasis from 1999 to 2010 at National Taiwan University Hospital, Taipei, Taiwan. Patients who had HCC with lung metastasis were also included for comparison. Patients with available tissues of both primary and metastatic tumors were enrolled in this study. Tumor slides from paired primary and metastatic HCCs were stained by H and E, and immunohistochemically stained for CK7, p53, Ki67, vimentin, Hes1, and c-Met. The expressions of CK7, p53, and vimentin were graded according to percentages of positive staining, but those of Hes1 and c-Met were recorded as an H score, which was defined as intensity (0, 1, 2, or 3) × percentages of positive staining. Results: A total of 14 patients had available tumor tissues of both primary and metastatic brain tumors. Another 21 patients had tumor tissues of both primary and metastatic lung tumors. The metastatic brain tumors, comparing to the metastatic lung tumors, had significantly more bizarre dilated vessels (86% vs. 14%, p < 0.001), hyaline globules (50% vs. 5%, p = 0.003), higher Hes1 H scores (mean, 245 vs. 131, p = 0.001), and lower c-Met H scores (mean, 15.4 vs. 38.1, p = 0.046). Tumor necrosis also tended to be more common among metastatic brain tumors (93% vs. 62%, p = 0.056). On the contrary, the above differences were not identified between the primary tumors which later developed brain metastasis and those which later developed lung metastasis. When disease progressed from primary liver to brain metastasis, mitosis counts (p = 0.034) and bizarre dilated vessels (p = 0.020) significantly increased, and necrosis (p = 0.059) tended to be more common. Conclusions: Metastatic brain tumors from HCC had unique histopathologic features compared to primary liver tumors or lung metastases. The increased Hes1 expression and decreased c-Met expression in HCC brain metastasis should be further explored. (This study was supported by the grant of NSC101-2314-B-002 -141, 100CAP1020-2 & NTUH.101-N1965.)
Suppression of human HCC cell growth in vitro by siRNA silencing of forkhead box M1 expression.
Authors: Park Keon Uk , Kim Ji Hong , Kim Hye-Jin , Lee Yun-Han 
Published: February 2017

173 Background: Development of targeted therapy for hepatocellular carcinoma (HCC) remains a major challenge. The transcription factor forkhead box M1 (FOXM1) is a member of the forkhead family, and it induces the expression of genes involved in the execution of mitosis. Liver regeneration studies that used the albumin promoter/enhancer cre recombinase (Alb-Cre) transgene to mediate hepatocyte-specific deletion of the mouse Foxm1 LoxP/LoxP targeted allele (Foxm1fl/fl) demonstrated that Foxm1 is required for hepatocyte DNA replication and mitosis. Methods: We explored the possibility of FoxM1 being a potential therapeutic target for HCC.To inactivate target gene expression, Huh7 and HepG2 cells were treated with the various doses of three different siRNAs (FoxM1-1, FoxM1-2 and FoxM1-3). The change of FoxM1 expression in mRNA level was then determined by quantitative real-time PCR. Cell growth was analyzed by MTT assay, and apoptosis was estimated by ELISA for the detection of denatured ssDNA only formed during apoptotic progression. Results: Among the three tested siRNA molecules, the FoxM1-1siRNA was the most effective in inhibiting HCC cell growth. Both Huh7 and HepG2 cells transfected with 15nM of FoxM1-1siRNA showed more than 60% growth inhibition by 4 days. Inhibition of cell growth was due to increased rate of apoptotic cell death which was about 2-fold higher than in untreated control cells. Upregulation of apoptosis directly correlated with down-regulation of FoxM1 mRNA level. Furthermore, siRNA-mediated silencing of FoxM1 expression in HCC cells retarded cell cycle progression. Conclusions: These results indicate that FoxM1 plays a pivotal role in HCC pathogenesis and maybe an attractive molecular target for systemic HCC therapy.
Role of biliary CEACAM6 as a biomarker for cholangiocarcinoma.
Authors: Rose John B. , Correa-Gallego Camilo , Nelson James , Alseidi Adnan , Helton Scott , Allen Peter J. , D'Angelica Michael , DeMatteo Ronald P. , Fong Yuman , Kingham T. Peter , Kowdley Kris , Jarnagin William R. , Rocha Flavio G. 
Published: February 2017

177 Background: Distinguishing bile duct carcinoma from other diagnoses is often difficult using endoscopic or percutaneous techniques. The cell surface protein CEACAM6 is over-expressed in many gastrointestinal cancers and may be selectively elevated in biliary adenocarcinoma. The aim of the present study is to determine if CEACAM6 can be detected in the bile of patients with biliary cancer and can serve as a diagnostic biomarker for cholangiocarcinoma. Methods: Bile duct and gallbladder bile from patients with benign biliary disease and cholangiocarcinoma (hilar, intrahepatic and distal) was collected at the time of index operation. The concentration of CEACAM6 was quantified by sandwich enzyme-linked immunosorbent assay (ELISA) and correlated to pathologic diagnosis. Diagnostic capability of CEACAM6 was evaluated by Wilcoxon rank-sum, logistic regression, and receiver operating characterisitic (ROC) curve analysis. Results: Bile from 73 patients was analyzed: 40 with benign disease and 33 with cholangiocarcinoma. Patients in the benign cohort were younger, predominantly female, and had lower mean biliary CEACAM6 levels than patients in the malignant cohort (102 ng/ml vs. 239 ng/ml; p=0.0006). Logistic regression analysis determined CEACAM6 to be a positive predictor of extrahepatic but not intrahepatic cholangiocarcinoma (p=0.0015). ROC curve with a CEACAM6 level >22.1 ng/ml was associated with 85% sensitivity, 73% specificity, and a likelihood ratio of 3.15 (AUC 0.82) for extrahepatic cholangiocarcinoma. Conclusions: CEACAM6 levels in bile can predict patients with extrahepatic cholangiocarcinoma with acceptable accuracy. Further investigation is warranted in a larger cohort of patients prior to clinical application.