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Sample records for advanced hcc patients

  1. Frequency of Elevated Hepatocellular Carcinoma (HCC) Biomarkers in Patients with Advanced Hepatitis C

    PubMed Central

    Sterling, Richard K.; Wright, Elizabeth C.; Morgan, Timothy R.; Seeff, Leonard B.; Hoefs, John C.; Di Bisceglie, Adrian M.; Dienstag, Jules L.; Lok, Anna S.

    2013-01-01

    Background Prospective studies of serum HCC biomarkers in patients with advanced hepatitis C are lacking. Aims To determine frequencies and performance of elevated alpha-fetoprotein (AFP), AFP-L3, and des-gamma-carboxy prothrombin (DCP) levels as HCC biomarkers in advanced hepatitis C. Methods Patients in the HALT-C Trial were tested every 3 months for 42 months. Screening ultrasound was performed every 12 months. Levels of biomarkers were compared in patients in whom HCC did or did not develop. Results 855 patients were evaluated; HCC developed in 46. Among patients without HCC, 73.2% had AFP consistently <20, 24.5% had at least one AFP between 20-199, while 2.3% had at least one AFP value ≥200 ng/mL; 73.7% had DCP consistently <90, 11.6% had at least one DCP between 90-149, and 14.7% had at least one DCP value ≥150 mAU/mL. AFP-L3 ≥10% was present at least once in 9.0% and in 17.1% of those with AFP >20 ng/mL. Among all patients with elevated biomarkers, a diagnosis of HCC was made in 0-31.6% (depending on the biomarker and cutoff) during the subsequent 24 months. AFP ≥200 ng/mL had the highest specificity (99%), but sensitivity was ≤20%. DCP ≥40 mAU/mL had the highest sensitivity (76%), but specificity was ≤58%. Independent predictors of elevated AFP were gender (female), race (Black), more advanced disease, and HCC. Elevated DCP was associated with more advanced disease and HCC. Conclusions Mild-moderate elevations in total AFP and DCP but not AFP-L3 occur frequently in patients with chronic hepatitis C and advanced fibrosis, are related to factors other than HCC, and are poor predictors of HCC. PMID:21931376

  2. Early onset of hypertension and serum electrolyte changes as potential predictive factors of activity in advanced HCC patients treated with sorafenib: results from a retrospective analysis of the HCC-AVR group

    PubMed Central

    Gardini, Andrea Casadei; Scarpi, Emanuela; Marisi, Giorgia; Foschi, Francesco Giuseppe; Donati, Gabriele; Giampalma, Emanuela; Faloppi, Luca; Scartozzi, Mario; Silvestris, Nicola; Bisulli, Marcello; Corbelli, Jody; Gardini, Andrea; Barba, Giuliano La; Veneroni, Luigi; Tamberi, Stefano; Cascinu, Stefano; Frassineti, Giovanni Luca

    2016-01-01

    Hypertension (HTN) is frequently associated with the use of angiogenesis inhibitors targeting the vascular endothelial growth factor pathway and appears to be a generalized effect of this class of agent. We investigated the phenomenon in 61 patients with advanced hepatocellular carcinoma (HCC) receiving sorafenib. Blood pressure and plasma electrolytes were measured on days 1 and 15 of the treatment. Patients with sorafenib-induced HTN had a better outcome than those without HTN (disease control rate: 63.4% vs. 17.2% (p=0.001); progression-free survival 6.0 months (95% CI 3.2-10.1) vs. 2.5 months (95% CI 1.9-2.6) (p<0.001) and overall survival 14.6 months (95% CI9.7-19.0) vs. 3.9 months (95% CI 3.1-8.7) (p=0.003). Sodium levels were generally higher on day 15 than at baseline (+2.38, p<0.0001) in the group of responders (+4.95, p <0.0001) compared to patients who progressed (PD) (+0.28, p=0.607). In contrast, potassium was lower on day 14 (−0.30, p=0.0008) in the responder group (−0.58, p=0.003) than in those with progressive disease (−0.06, p=0.500). The early onset of hypertension is associated with improved clinical outcome in HCC patients treated with sorafenib. Our data are suggestive of an activation of the renin-angiotensin system in patients with advanced disease who developed HTN during sorafenib treatment. PMID:26893366

  3. Cyproheptadine significantly improves the overall and progression-free survival of sorafenib-treated advanced HCC patients

    PubMed Central

    Feng, Yu-Min; Feng, Chin-Wen; Lu, Chin-Li; Lee, Ming-Yang; Chen, Chi-Yi; Chen, Solomon Chih-Cheng

    2015-01-01

    Objective Sorafenib is a recommended treatment for advanced hepatocellular carcinoma. The study is to evaluate the efficacy of sorafenib plus cyproheptadine compared with sorafenib alone in patients with advanced hepatocellular carcinoma. Methods A retrospective cohort study reviewed all consecutive advanced hepatocellular carcinoma cases with Child-Pugh Class A disease starting sorafenib treatment at our hospital from August 2012 to March 2013. They were followed up until 31 December 2013. A total of 52 patients were enrolled: 32 patients in the combination (sorafenib–cyproheptadine) group and 20 patients in the control (sorafenib alone) group. The response to treatment, overall survival and progression-free survival were compared. Results The median overall survival was 11.0 months (95% confidence interval: 6.8–15.1 months) in the combination group compared with 4.8 months (95% confidence interval: 3.1–6.6 months) in the control group (crude hazard ratio = 0.45, 95% confidence interval: 0.22–0.82). The median progression-free survival time was 7.5 months (95% confidence interval: 5.1–10.0 months) in the combination group compared with 1.7 months (95% confidence interval: 1.4–2.1 months) in the control group (crude hazard ratio = 0.43, 95% confidence interval: 0.22–0.86). Kaplan–Meier survival analysis revealed that both overall survival and progression-free survival in the combination group were significantly longer than that in the control group. The multivariate model found patients in the combination group were 76% less likely to die (adjusted hazard ratio = 0.24, 95% confidence interval: 0.10–0.58) and 82% less likely to have progression (adjusted hazard ratio = 0.18, 95% confidence interval: 0.08–0.44) during the 17 months of follow-up. Conclusion Cyproheptadine may significantly improve survival outcomes of sorafenib-treated advanced hepatocellular carcinoma patients. PMID:25646358

  4. eNOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: final results of the ePHAS study.

    PubMed

    Casadei Gardini, Andrea; Marisi, Giorgia; Faloppi, Luca; Scarpi, Emanuela; Foschi, Francesco Giuseppe; Iavarone, Massimo; Lauletta, Gianfranco; Corbelli, Jody; Valgiusti, Martina; Facchetti, Floriana; Della Corte, Cristina; Neri, Luca Maria; Tamberi, Stefano; Cascinu, Stefano; Scartozzi, Mario; Amadori, Dino; Nanni, Oriana; Tenti, Elena; Ulivi, Paola; Frassineti, Giovanni Luca

    2016-05-10

    Sorafenib may reduce endothelial nitric oxide synthase (eNOS) activity by inhibiting vascular endothelial growth factor receptors (VEGF-R), leading to a decrease in nitric oxide production. In the Italian multicenter ePHAS (eNOS polymorphisms in HCC and sorafenib) study, we analyzed the role of eNOS polymorphisms in relation to clinical outcome in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Our retrospective study included a training cohort of 41 HCC patients and a validation cohort of 87 HCC patients, all undergoing sorafenib treatment. Three eNOS polymorphisms (eNOS -786T>C, eNOS VNTR 27bp 4a/b and eNOS+894G>T) were analyzed by direct sequencing or Real Time PCR in relation to progression-free survival (PFS) and overall survival (OS) (log-rank test). In univariate analysis, training cohort patients homozygous for eNOS haplotype (HT1:T-4b at eNOS-786/eNOS VNTR) had a lower median PFS (2.6 vs. 5.8 months, P < 0.0001) and OS (3.2 vs.14.6 months, P = 0.024) than those with other haplotypes. In the validation set, patients homozygous for HT1 had a lower median PFS (2.0 vs. 6.7 months, P < 0.0001) and OS (6.4 vs.18.0 months, P < 0.0001) than those with other haplotypes. Multivariate analysis confirmed this haplotype as the only independent prognostic factor. Our results suggest that haplotype HT1 in the eNOS gene may be capable of identifying a subset of HCC patients who are resistant to sorafenib. PMID:27058899

  5. eNOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: final results of the ePHAS study

    PubMed Central

    Faloppi, Luca; Scarpi, Emanuela; Foschi, Francesco Giuseppe; Iavarone, Massimo; Lauletta, Gianfranco; Corbelli, Jody; Valgiusti, Martina; Facchetti, Floriana; Corte, Cristina della; Neri, Luca Maria; Tamberi, Stefano; Cascinu, Stefano; Scartozzi, Mario; Amadori, Dino; Nanni, Oriana; Tenti, Elena

    2016-01-01

    Sorafenib may reduce endothelial nitric oxide synthase (eNOS) activity by inhibiting vascular endothelial growth factor receptors (VEGF-R), leading to a decrease in nitric oxide production. In the Italian multicenter ePHAS (eNOS polymorphisms in HCC and sorafenib) study, we analyzed the role of eNOS polymorphisms in relation to clinical outcome in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Our retrospective study included a training cohort of 41 HCC patients and a validation cohort of 87 HCC patients, all undergoing sorafenib treatment. Three eNOS polymorphisms (eNOS -786T>C, eNOS VNTR 27bp 4a/b and eNOS+894G>T) were analyzed by direct sequencing or Real Time PCR in relation to progression-free survival (PFS) and overall survival (OS) (log-rank test). In univariate analysis, training cohort patients homozygous for eNOS haplotype (HT1:T-4b at eNOS-786/eNOS VNTR) had a lower median PFS (2.6 vs. 5.8 months, P < 0.0001) and OS (3.2 vs.14.6 months, P = 0.024) than those with other haplotypes. In the validation set, patients homozygous for HT1 had a lower median PFS (2.0 vs. 6.7 months, P < 0.0001) and OS (6.4 vs.18.0 months, P < 0.0001) than those with other haplotypes. Multivariate analysis confirmed this haplotype as the only independent prognostic factor. Our results suggest that haplotype HT1 in the eNOS gene may be capable of identifying a subset of HCC patients who are resistant to sorafenib. PMID:27058899

  6. eNOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: final results of the ePHAS study.

    PubMed

    Casadei Gardini, Andrea; Marisi, Giorgia; Faloppi, Luca; Scarpi, Emanuela; Foschi, Francesco Giuseppe; Iavarone, Massimo; Lauletta, Gianfranco; Corbelli, Jody; Valgiusti, Martina; Facchetti, Floriana; Della Corte, Cristina; Neri, Luca Maria; Tamberi, Stefano; Cascinu, Stefano; Scartozzi, Mario; Amadori, Dino; Nanni, Oriana; Tenti, Elena; Ulivi, Paola; Frassineti, Giovanni Luca

    2016-05-10

    Sorafenib may reduce endothelial nitric oxide synthase (eNOS) activity by inhibiting vascular endothelial growth factor receptors (VEGF-R), leading to a decrease in nitric oxide production. In the Italian multicenter ePHAS (eNOS polymorphisms in HCC and sorafenib) study, we analyzed the role of eNOS polymorphisms in relation to clinical outcome in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Our retrospective study included a training cohort of 41 HCC patients and a validation cohort of 87 HCC patients, all undergoing sorafenib treatment. Three eNOS polymorphisms (eNOS -786T>C, eNOS VNTR 27bp 4a/b and eNOS+894G>T) were analyzed by direct sequencing or Real Time PCR in relation to progression-free survival (PFS) and overall survival (OS) (log-rank test). In univariate analysis, training cohort patients homozygous for eNOS haplotype (HT1:T-4b at eNOS-786/eNOS VNTR) had a lower median PFS (2.6 vs. 5.8 months, P < 0.0001) and OS (3.2 vs.14.6 months, P = 0.024) than those with other haplotypes. In the validation set, patients homozygous for HT1 had a lower median PFS (2.0 vs. 6.7 months, P < 0.0001) and OS (6.4 vs.18.0 months, P < 0.0001) than those with other haplotypes. Multivariate analysis confirmed this haplotype as the only independent prognostic factor. Our results suggest that haplotype HT1 in the eNOS gene may be capable of identifying a subset of HCC patients who are resistant to sorafenib.

  7. Significance of serum microRNA-21 in diagnosis of hepatocellular carcinoma (HCC): clinical analyses of patients and an HCC rat model

    PubMed Central

    Wang, Xing; Zhang, Juan; Zhou, Liang; Lu, Peng; Zheng, Zhi-Gang; Sun, Wei; Wang, Jian-Lin; Yang, Xi-Sheng; Li, Xiao-Lei; Xia, Ning; Zhang, Ning; Dou, Ke-Feng

    2015-01-01

    MicroRNAs (miRNAs) are associated with human carcinogenesis and tumor development. Moreover, serum miRNAs can reflect the level of tissue miRNAs and be potential tumor markers. Serum microRNA-21 (miR-21) is overexpressed in many human cancers including hepatocellular carcinoma (HCC). However, how serum miR-21 changes during the HCC formation and whether miR-21 plays a regulatory role in this whole process are unknown. The current study evaluated the prognostic and diagnostic potential of serum miR-21 in HCC patients. Next, we established a HCC rat model and collected the blood and liver tissues at regular time points. AFP from the serum, RNA from the serum and liver tissues were collected and quantified separately. The results revealed that tissue and serum miR-21 was upregulated significantly in the groups of cirrhosis, early and advanced HCC compared with normal and fibrosis groups. The AFP levels were increased in early and advanced HCC compared with other groups. Then, the changes of miR-21 downstream proteins (i.e., programmed cell death 4 [PDCD4] and phosphatase and tensin homolog [PTEN]) in the liver tissues were measured. PDCD4 and PTEN expression was decreased gradually after tumor induction and negatively correlated with miR-21 expression. All these results suggested that serum miR-21 was associated with the prognosis of HCC; the changes in serum miR-21 were earlier and more accurately reflected the pathogenesis of HCC than AFP; therefore, it could be used as an early diagnostic marker for HCC. Our in vivo experiments further confirmed that miR-21 plays an important role in promoting the occurrence and development of HCC by regulating PDCD4 and PTEN. PMID:25973032

  8. Problems of Long Survival Following Surgery in Patients with NonBNonC-HCC: Comparison with HBV and HCV Related-HCC

    PubMed Central

    Hiwatashi, Kiyokazu; Ueno, Shinichi; Sakoda, Masahiko; Iino, Satoshi; Minami, Koji; Yamasaki, Yoichi; Okubo, Keishi; Noda, Masahiro; Kurahara, Hiroshi; Mataki, Yuko; Maemura, Kosei; Shinchi, Hiroyuki; Natsugoe, Shoji

    2015-01-01

    Background: The number of patients with hepatocellular carcinoma (HCC) in the absence of both hepatitis B virus surface antigen (HBsAg) and hepatitis C virus antibody (HCVAb) (NBNC-HCC) has been rapidly increasing in Japan. The objective of this study was to compare the clinical and pathological characteristics between patients with the NBNC-HCC, those with HBsAg positive HCC (B-related HCC) and HCVAb positive HCC (C-related HCC). A better understanding will facilitate the development of postoperative strategies to better manage patients with NBNC-HCC. Methods: Consecutive 219 patients with primary HCC: (B-related, n=35; C-related, n = 104; NBNC, n = 80) were treated by hepatic resection or ablation. Clinicopathological characteristics including postoperative course were retrospectively compared between the three groups. Results: When comparing within stage I and II, the NBNC-HCC group had improved recurrence free survival (RFS) compared to the C-related HCC (p = 0.013) but had not been good overall survival (OS). Moreover, the NBNC-HCC group showed higher rate of death due to other cancers and cardiovascular disease (p = 0.011) compared to the C-related HCC. Multivariate analysis revealed that the only prognostic factor for RFS in the NBNC-HCC group was high serum total bilirubin. Conclusions: In the patients with the NBNC-HCC, elevated serum bilirubin could predict poor RFS after surgery. Furthermore, patients must be carefully followed-up not only for HCC but also for the occurrence of other critical diseases including multiple other cancers. PMID:25874007

  9. Quantitative proteomics and phosphoproteomics on serial tumor biopsies from a sorafenib-treated HCC patient

    PubMed Central

    Dazert, Eva; Colombi, Marco; Boldanova, Tujana; Moes, Suzette; Adametz, David; Quagliata, Luca; Roth, Volker; Terracciano, Luigi; Heim, Markus H.; Jenoe, Paul; Hall, Michael N.

    2016-01-01

    Compensatory signaling pathways in tumors confer resistance to targeted therapy, but the pathways and their mechanisms of activation remain largely unknown. We describe a procedure for quantitative proteomics and phosphoproteomics on snap-frozen biopsies of hepatocellular carcinoma (HCC) and matched nontumor liver tissue. We applied this procedure to monitor signaling pathways in serial biopsies taken from an HCC patient before and during treatment with the multikinase inhibitor sorafenib. At diagnosis, the patient had an advanced HCC. At the time of the second biopsy, abdominal imaging revealed progressive disease despite sorafenib treatment. Sorafenib was confirmed to inhibit MAPK signaling in the tumor, as measured by reduced ribosomal protein S6 kinase phosphorylation. Hierarchical clustering and enrichment analysis revealed pathways broadly implicated in tumor progression and resistance, such as epithelial-to-mesenchymal transition and cell adhesion pathways. Thus, we describe a protocol for quantitative analysis of oncogenic pathways in HCC biopsies and obtained first insights into the effect of sorafenib in vivo. This protocol will allow elucidation of mechanisms of resistance and enable precision medicine. PMID:26787912

  10. Quantitative proteomics and phosphoproteomics on serial tumor biopsies from a sorafenib-treated HCC patient.

    PubMed

    Dazert, Eva; Colombi, Marco; Boldanova, Tujana; Moes, Suzette; Adametz, David; Quagliata, Luca; Roth, Volker; Terracciano, Luigi; Heim, Markus H; Jenoe, Paul; Hall, Michael N

    2016-02-01

    Compensatory signaling pathways in tumors confer resistance to targeted therapy, but the pathways and their mechanisms of activation remain largely unknown. We describe a procedure for quantitative proteomics and phosphoproteomics on snap-frozen biopsies of hepatocellular carcinoma (HCC) and matched nontumor liver tissue. We applied this procedure to monitor signaling pathways in serial biopsies taken from an HCC patient before and during treatment with the multikinase inhibitor sorafenib. At diagnosis, the patient had an advanced HCC. At the time of the second biopsy, abdominal imaging revealed progressive disease despite sorafenib treatment. Sorafenib was confirmed to inhibit MAPK signaling in the tumor, as measured by reduced ribosomal protein S6 kinase phosphorylation. Hierarchical clustering and enrichment analysis revealed pathways broadly implicated in tumor progression and resistance, such as epithelial-to-mesenchymal transition and cell adhesion pathways. Thus, we describe a protocol for quantitative analysis of oncogenic pathways in HCC biopsies and obtained first insights into the effect of sorafenib in vivo. This protocol will allow elucidation of mechanisms of resistance and enable precision medicine. PMID:26787912

  11. Tumor Markers for Hepatocellular Carcinoma: Simple and Significant Predictors of Outcome in Patients with HCC

    PubMed Central

    Toyoda, Hidenori; Kumada, Takashi; Tada, Toshifumi; Sone, Yasuhiro; Kaneoka, Yuji; Maeda, Atsuyuki

    2015-01-01

    Background The effectiveness of tumor markers in evaluating outcomes of patients with hepatocellular carcinoma (HCC) remains to be clarified. Summary The usefulness of the HCC tumor markers, alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), and des-gamma-carboxy prothrombin (DCP) was reviewed. Elevations in these tumor markers at the time of HCC diagnosis correlate with disease progression as assessed by both imaging studies and pathologic examinations. The combination of these three tumor markers results in good predictive ability for patient survival after diagnosis. In addition, combination at the time of HCC diagnosis of these three tumor markers (as a measure of tumor progression) and serum albumin and bilirubin levels (as indicators of remnant liver function) can be used for HCC staging and further predicts prognosis in patients with HCC. Key Message The prognosis of patients with HCC can be well discriminated based solely on serum markers. Staging of HCC with serum markers is objective; if stored serum samples are available, HCC stages can be standardized across different countries and time periods. PMID:26020034

  12. PD-1+ and Foxp3+ T cell reduction correlates with survival of HCC patients after sorafenib therapy

    PubMed Central

    Kalathil, Suresh Gopi; Lugade, Amit Anand; Iyer, Renuka

    2016-01-01

    BACKGROUND. Sorafenib is an oral antiangiogenic agent administered in advanced-stage hepatocellular carcinoma (HCC). Based on preclinical and human studies, we hypothesized that, in addition to its antiangiogenic properties, sorafenib may beneficially reduce the extent of the immunosuppressive network in HCC patients. To test this hypothesis, we examined whether alterations in the immunosuppressive burden of advanced-stage HCC patients correlated with clinical outcome. METHODS. In before and after sorafenib treatment, blood samples collected from 19 patients with advanced HCC, the frequency of PD-1+ T cells, Tregs, and myeloid derived suppressor cells (MDSC) were quantified by multiparameter FACS. Cytokine levels in plasma were determined by ELISA. RESULTS. Overall survival (OS) was significantly impacted by the reduction in the absolute number of both CD4+PD-1+ T cells and CD8+PD-1+ T cells following sorafenib treatment. Significant decreases in the frequency and absolute number of Foxp3+ Tregs were also observed, and a statistically significant improvement in OS was noted in patients exhibiting a greater decrease in the number of Foxp3+ Tregs. The ratio of CD4+CD127+PD-1– T effector cells to CD4+Foxp3+PD-1+ Tregs was significantly increased following treatment with sorafenib. Increased frequency of CD4+CD127+ T effector cells in the posttreatment samples significantly correlated with OS. CONCLUSION. This study is the first to our knowledge to demonstrate the potent immunomodulatory effects of sorafenib therapy on PD-1+ T cells and Tregs and the ensuing correlation with survival. These phenotypes could serve as predictive biomarkers to identify HCC patients who are likely to benefit from sorafenib treatment. TRIAL REGISTRATION. Registration is not required for observational studies. FUNDING. This study was supported by NCI Core Grant to RPCI (NIH P30 CA016056) and discretionary funds to Y. Thanavala. PMID:27540594

  13. PD-1+ and Foxp3+ T cell reduction correlates with survival of HCC patients after sorafenib therapy

    PubMed Central

    Kalathil, Suresh Gopi; Lugade, Amit Anand; Miller, Austin; Iyer, Renuka; Thanavala, Yasmin

    2016-01-01

    BACKGROUND Sorafenib is an oral antiangiogenic agent administered in advanced-stage hepatocellular carcinoma (HCC). Based on preclinical and human studies, we hypothesized that, in addition to its antiangiogenic properties, sorafenib may beneficially reduce the extent of the immunosuppressive network in HCC patients. To test this hypothesis, we examined whether alterations in the immunosuppressive burden of advanced-stage HCC patients correlated with clinical outcome. METHODS In before and after sorafenib treatment, blood samples collected from 19 patients with advanced HCC, the frequency of PD-1+ T cells, Tregs, and myeloid derived suppressor cells (MDSC) were quantified by multiparameter FACS. Cytokine levels in plasma were determined by ELISA. RESULTS Overall survival (OS) was significantly impacted by the reduction in the absolute number of both CD4+PD-1+ T cells and CD8+PD-1+ T cells following sorafenib treatment. Significant decreases in the frequency and absolute number of Foxp3+ Tregs were also observed, and a statistically significant improvement in OS was noted in patients exhibiting a greater decrease in the number of Foxp3+ Tregs. The ratio of CD4+CD127+PD-1− T effector cells to CD4+Foxp3+PD-1+ Tregs was significantly increased following treatment with sorafenib. Increased frequency of CD4+CD127+ T effector cells in the posttreatment samples significantly correlated with OS. CONCLUSION This study is the first to our knowledge to demonstrate the potent immunomodulatory effects of sorafenib therapy on PD-1+ T cells and Tregs and the ensuing correlation with survival. These phenotypes could serve as predictive biomarkers to identify HCC patients who are likely to benefit from sorafenib treatment. TRIAL REGISTRATION Registration is not required for observational studies. FUNDING This study was supported by NCI Core Grant to RPCI (NIH P30 CA016056) and discretionary funds to Y. Thanavala. PMID:27540594

  14. Low expression of GNAI3 predicts poor prognosis in patients with HCC

    PubMed Central

    Chen, Guodong; Li, Xiaoyan; He, Gengsheng; Yu, Zijian; Luo, Jiaxing; He, Jun; Huang, Zonghai

    2015-01-01

    Purposes: This study was performed with an aim to explain the underlying role of GNAI3 on the prognosis of patients with HCC. Methods: The expression of GNAI3 at protein level was detected with the utilization of Immunohistochemistry (IHC). Chi-square test was conducted to assay the relationship between GNAI3 expression and clinical parameters of HCC patients. The correlation between expression level of GNAI3 and survival time after surgeries of HCC patients was evaluated by Kaplan-Meier method. Finally, the Cox regression was established to evaluate the relationship between GNAI3 expression and the prognosis of patients with HCC. Results: In this study, the negative rate of GNAI3 expression in HCC samples was about 76.6%, which was significantly higher than that in paired normal specimens (12.5%). Result showed that there was no correlation between GNAI3 expression and age, gender, liver cirrhosis and vein invasion (P>0.05), but tight relationship between GNAI3 expression and TNM stage and tumor size was found (P<0.05). The following Kaplan-Meier analysis result illustrated that negative expression of GNAI3 induced high mortality of HCC patients. Cox regression result revealed that GNAI3 might be a biomarker for prognosis of patients with HCC (HR: 0.218, P=0.016, 95% CI 0.063-0.750). Conclusion: Generally, results of this study demonstrated that expression of GNAI3 shared a tight relationship with the prognosis of patients with HCC. Therefore, GNAI3 could be considered as a novel index for prognosis of patients with HCC. PMID:26885096

  15. Proteomic analysis of HCV cirrhosis and HCV-induced HCC: Identifying biomarkers for monitoring HCV-cirrhotic patients awaiting liver transplantation

    PubMed Central

    Mas, Valeria R; Maluf, Daniel G; Archer, Kellie J; Yanek, Kenneth; Bornstein, Karen; Fisher, Robert A

    2009-01-01

    Background Progression from chronic Hepatitis C virus (HCV) infection to cirrhosis and hepatocellular carcinoma (HCC) results in protein changes in the peripheral blood. We evaluated global protein expression in plasma samples of HCV-cirrhotic and HCV-cirrhotic-HCC patients. Patients and Methods Plasma samples from 25 HCV-cirrhotic-HCC and 10 HCV-cirrhotic patients were quantitatively evaluated for protein expression. Tryptic peptides were analyzed using Thermo linear ion-trap mass specttometer (LTQ) coupled with a Surveyoy HPLC system (Thermo). SEQUEST and X!Tandem database search algorithms were used for peptide sequence identification. Protein relative quantification was performed using the area under the curve from the select ion chromatogram. A significant fold change between groups was based on controlling the False Discovery Rate (FDR) at less than 5%. Results We identified and quantified 2,320 proteins from the analysis of the different protein pattern between HCV-cirrhosis and HCV-HCC samples. Gene ontology terms (GO) classified the more important biologic process related to these proteins as signal transduction, regulation of transcription DNA-dependent, protein amino acid phosphorylation, cell adhesion, transport, and immune response. Seven proteins showed significant expression changes with a FDR<5% between cirrhosis and tumor groups. Moreover, 18 proteins showed significant expression changes (FDR<5%) when plasma samples from HCV-cirrhosis were compared with early HCV-HCC. Conclusions Differential protein expression was observed between samples from HCV patients with cirrhosis with and without HCC. Also, differences were observed between early and advanced HCV-HCC samples. This study provides important information for discovery of potential biomarkers for early HCC diagnosis in HCV cirrhotic patients. PMID:19136905

  16. Tumor Regression in HCC Patient with Portal Vein Tumor Thrombosis after Intraportal Radiofrequency Thermal Ablation

    PubMed Central

    2016-01-01

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Portal vein tumor thrombosis (PVTT) is a frequent entity in HCC, which strictly limits the gold standard treatment options such as surgical resection and transarterial chemoembolization. Therefore, the prognosis of patients with PVTT is extremely poor and an emergence of seeking an alternative option for intervention is inevitable. We present a case of a 60-year-old male patient with HCC induced PVTT who was subjected to the intraportal RFA and stenting-VesOpen procedure. No additional medical intervention was performed. The repeated CT performed 5 months after the VesOpen procedure revealed significant decrease of the tumor size, patent right, and main portal vein and a recanalization of the left portal vein, which was not processed. At this time point, liver functional tests, appetite, and general condition of the patient were improved evidently. This report designates the RFA as an instrumental option of therapeutic intervention for HCC patients with PVTT. PMID:27579192

  17. Tumor Regression in HCC Patient with Portal Vein Tumor Thrombosis after Intraportal Radiofrequency Thermal Ablation.

    PubMed

    Mizandari, Malkhaz; Azrumelashvili, Tamta; Paksashvili, Natela; Kikodze, Nino; Pantsulaia, Ia; Janikashvili, Nona; Chikovani, Tinatin

    2016-01-01

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Portal vein tumor thrombosis (PVTT) is a frequent entity in HCC, which strictly limits the gold standard treatment options such as surgical resection and transarterial chemoembolization. Therefore, the prognosis of patients with PVTT is extremely poor and an emergence of seeking an alternative option for intervention is inevitable. We present a case of a 60-year-old male patient with HCC induced PVTT who was subjected to the intraportal RFA and stenting-VesOpen procedure. No additional medical intervention was performed. The repeated CT performed 5 months after the VesOpen procedure revealed significant decrease of the tumor size, patent right, and main portal vein and a recanalization of the left portal vein, which was not processed. At this time point, liver functional tests, appetite, and general condition of the patient were improved evidently. This report designates the RFA as an instrumental option of therapeutic intervention for HCC patients with PVTT. PMID:27579192

  18. The role of LDH serum levels in predicting global outcome in HCC patients treated with sorafenib: implications for clinical management

    PubMed Central

    2014-01-01

    Background In many tumour types serumlactate dehydrogenase (LDH) levels proved to represent an indirect marker of tumour hypoxia, neo-angiogenesis and worse prognosis. As we previously reported LDH is an important predictive factor in hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE). Sorafenib represents the therapeutic stronghold in advanced HCC patients. As a tyrosine kinase inhibitor (TKI) mainly directed against the angiogenetic pathway, the correlation of sorafenib administration with markers of hypoxia could be an important tool in patients management. Aim of our analysis was to evaluate the role of LDH pre-treatment levels and its variation during treatment in HCC patients receiving sorafenib. Methods 78 patients were available for our analysis. For all patients LDH values were collected within one month before the start of treatment and after the end of therapy. For study purposes we divided our patients into two groups, according to LDH pre-treatment levels, cut-off levels was determined with ROC curve analysis. Patients were, also, classified according to the variation in LDH serum levels pre- and post-treatment (increased vs decreased). Results Patients proved homogeneous for all clinical characteristics analyzed. In patients with LDH values under the cut-off median progression free survival (PFS) was 6.7 months, whereas it was 1.9 months in patients above the cut-off (p = 0.0002). Accordingly median overall survival (OS) was 13.2 months and 4.9 months (p = 0.0006). In patients with decreased LDH values after treatment median PFS was 6.8 months, and median OS was 21.0 months, whereas PFS was 2.9 months and OS 8.6 months in patients with increased LDH levels (PFS: p = 0.0087; OS: p = 0.0035). Conclusions In our experience, LDH seemed able to predict clinical outcome in terms of PFS and OS for HCC patients treated with sorafenib. Given the correlation between LDH levels and tumour

  19. Pretreatment glucose status determines HCC development in HCV patients with mild liver disease after curative antiviral therapy.

    PubMed

    Huang, Chung-Feng; Yeh, Ming-Lun; Huang, Cing-Yi; Tsai, Pei-Chien; Ko, Yu-Min; Chen, Kuan-Yu; Lin, Zu-Yau; Chen, Shinn-Cherng; Dai, Chia-Yen; Chuang, Wan-Long; Huang, Jee-Fu; Yu, Ming-Lung

    2016-07-01

    Although diabetes mellitus (DM) is known to increase the risk of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), the impact of dynamic glucose status on HCC occurrence in chronic hepatitis C (CHC) patients receiving antiviral therapy is unclear. In total, 1112 biopsy-proven patients treated with peginterferon/ribavirin were enrolled in this study. Both pretreatment and post-treatment glucose status, including 75 g oral glucose tolerance test (OGTT), were measured to evaluate the association between glucose status and the development of HCC. Of the 1112 patients evaluated, 93 (8.4%) developed HCC >5183.8 person-years of follow-up (annual incidence rate: 1.79%). DM only influenced the risk of developing CC in patients with mild liver disease (F0-2) and a sustained virological response (SVR) but not in other patient subpopulations. Cox-regression analysis demonstrated that the strongest factor associated with HCC in patients with mild liver disease and SVR was the presence of DM (hazard ratio [HR]/95 % confidence intervals [CI]: 3.79/1.420-10.136, P = 0.008), followed by age (HR/CI: 1.06/1.001-1.117, P = 0.046) and platelet count (HR/CI: 0.989/0.979-1.000, P = 0.05). The percentages of SVR patients with F0-2 with normoglycemia, pre-DM, sub-DM (pre-sDM), and DM before treatment were 45.3% (n = 267), 29.9% (n = 176), 15.6% (n = 92), and 9.2% (n = 54), respectively. The percentages of HCC in patients with normoglycemia, pre-sDM, and DM were 1.1%, 3.7%, and 11.1%, respectively (trend P < 0.001). Sixteen of the 19 (84.2 %) HCC patients possessed glucose abnormality (including 6 patients with DM and 10 patients with pre-sDM) before antiviral therapy. Compared to patients with normoglycemia, the incidence of HCC increased gradually from pre-sDM (HR: 3.6, P = 0.05) to DM (HR: 11.6, P = 0.001) (adjusted trend P = 0.004). We concluded that DM is a critical determinant for the development of HCC in SVR patients with mild liver disease. Pre-sDM status

  20. Increased Oxidative Stress and RUNX3 Hypermethylation in Patients with Hepatitis B Virus-Associated Hepatocellular Carcinoma (HCC) and Induction of RUNX3 Hypermethylation by Reactive Oxygen Species in HCC Cells.

    PubMed

    Poungpairoj, Poonsin; Whongsiri, Patcharawalai; Suwannasin, Surasit; Khlaiphuengsin, Apichaya; Tangkijvanich, Pisit; Boonla, Chanchai

    2015-01-01

    Promoter hypermethylation of the runt-related transcription factor 3 (RUNX3) gene is associated with increased risk of hepatocellular carcinoma (HCC). Oxidative stress plays a vital role in both carcinogenesis and progression of HCC. However, whether oxidative stress and RUNX3 hypermethylation in HCC have a cause- and-effect relationship is not known. In this study, plasma protein carbonyl and total antioxidant capacity (TAC) in patients with hepatitis B virus (HBV)-associated HCC (n=60) and age-matched healthy subjects (n=80) was determined. RUNX3 methylation in peripheral blood mononuclear cells (PBMC) of subjects was measured by methylation-specific PCR. Effect of reactive oxygen species (ROS) on induction of RUNX3 hypermethylation in HCC cells was investigated. Plasma protein carbonyl content was significantly higher, whereas plasma TAC was significantly lower, in HCC patients than healthy controls. Based on logistic regression, increased plasma protein carbonyl and decreased plasma TAC were independently associated with increased risk for HCC. PBMC RUNX3 methylation in the patient group was significantly greater than in the healthy group. RUNX3 methylation in hydrogen peroxide (H2O2)-treated HepG2 cells was significantly higher than in untreated control cells. In conclusion, increase in oxidative stress in Thai patients with HBV-associated HCC was demonstrated. This oxidative increment was independently associated with an increased risk for HCC development. RUNX3 in PBMC was found to be hypermethylated in the HCC patients. In vitro, RUNX3 hypermethylation was experimentally induced by H2O2. Our findings suggest that oxidative stress is a cause of RUNX3 promoter hypermethylation in HCC cells. PMID:26225676

  1. YAP inhibition restores hepatocyte differentiation in advanced HCC leading to tumor regression

    PubMed Central

    Fitamant, Julien; Kottakis, Filippos; Benhamouche, Samira; Tian, Helen S.; Chuvin, Nicolas; Parachoniak, Christine A.; Nagle, Julia M.; Perera, Rushika M.; Lapouge, Marjorie; Deshpande, Vikram; Zhu, Andrew X.; Lai, Albert; Min, Bosun; Hoshida, Yujin; Avruch, Joseph; Sia, Daniela; Campreciós, Genís; McClatchey, Andrea I.; Llovet, Josep M.; Morrissey, David; Raj, Lakshmi; Bardeesy, Nabeel

    2015-01-01

    SUMMARY Defective Hippo/YAP signaling in the liver results in tissue overgrowth and development of hepatocellular carcinoma (HCC). Here, we uncover mechanisms of YAP-mediated hepatocyte reprogramming and HCC pathogenesis. YAP functions as a rheostat maintaining metabolic specialization, differentiation and quiescence within the hepatocyte compartment. Increased or decreased YAP activity reprograms subsets of hepatocytes to different fates associated with deregulation of the HNF4A, CTNNB1, and E2F transcriptional programs controlling hepatocyte quiescence and differentiation. Importantly, treatment with siRNA-lipid nanoparticles (siRNA-LNPs) targeting YAP restores hepatocyte differentiation and causes pronounced tumor regression in a genetically engineered mouse HCC model. Furthermore, YAP targets are enriched in an aggressive human HCC subtype characterized by a proliferative signature and absence of CTNNB1 mutations. Thus, our work reveals Hippo signaling as a key regulator of positional identity of hepatocytes, supports targeting YAP using siRNA-LNPs as a paradigm of differentiation-based therapy, and identifies an HCC subtype potentially responsive to this approach. PMID:25772357

  2. CK19 and Glypican 3 Expression Profiling in the Prognostic Indication for Patients with HCC after Surgical Resection

    PubMed Central

    Chang, Chun; Yu, Lu; Cao, Fang; Zhu, Guohua; Chen, Feng; Xia, Hui; Lv, Fudong; Zhang, Shijie; Sun, Lin

    2016-01-01

    This retrospective study was designed to investigate the correlation between a novel immunosubtyping method for hepatocellular carcinoma (HCC) and biological behavior of tumor cells. A series of 346 patients, who received hepatectomy at two surgical centers from January 2007 to October 2010, were enrolled in this study. The expressions of cytokeratin 19 (CK19), glypican 3 (GPC3), and CD34 were detected by immunohistochemical staining. The clinical stage was assessed using the sixth edition tumor–node–metastasis (TNM) system (UICC/AJCC, 2010).Vascular invasion comprised both microscopic and macroscopic invasion. The tumor size, lymph node involvement, and metastasis were determined by pathological as well as imaging studies. Recurrence was defined as the appearance of new lesions with radiological features typical of HCC, seen by at least two imaging methods. Survival curves for the patients were plotted using the Kaplan–Meier method, and differences between the curves were assessed using the log-rank test. Significant differences in morphology, histological grading, and TNM staging were observed between groups. Based on the immunohistochemical staining, the enrolled cases were divided into CK19+/GPC3+, CK19−/GPC3+ and CK19−/GPC3− three subtypes. CK19+/GPC3+ HCC has the highest risk of multifocality, microvascular invasion, regional lymph node involvement, and distant metastasis, followed by CK19−/GPC3+ HCC, then CK19−/GPC3−HCC. CK19+/GPC3+ HCC has the shortest recurrence time compared to other immunophenotype HCCs. CK19 and GPC3 expression profiling is an independent prognostic indicator in patients with HCC, and a larger sample size is needed to further investigate the effect of this immunosubtyping model in stratifying the outcome of HCC patients. PMID:26977595

  3. Identification of Chromosomal Aberrations by Using Trypsin G-banding in Hepatocellular Carcinoma Patients (HCC) in Tamil Nadu, India.

    PubMed

    Mohana Devi, Subramaniam; Balachandar, Vellingiri; Murugan, Palanivel Vel; Sasikala, Keshavarao; Manikantan, Pappusamy; Venkatakrishnan, Leela Krishnan

    2010-08-01

    Hepatocellular carcinoma (HCC) (or liver cancer) is one of the most common human malignancies worldwide. Aetiologically, HCC is closely associated with chronic hepatitis B and C virus infection, cirrhosis and alcohol intake. The objective of the present study was to elucidate the chromosomal abberations (CA) in HCC patients using the trypsin G-banding technique. This study may help in understanding the pattern of the disease and to assess whether these aberrations are associated with HCC susceptibility. The study examined 51 HCC cases and an equal number (n = 51) of age and gender matched cancer-free controls recruited from the hospitals in Tamil Nadu. The HCC cases were grouped depending upon their age into group I (≤ 45 years) and group II (≥ 46 years). The development of effective markers for the detection of HCC could have an impact on cancer mortality and may have significant public health implications worldwide. Subjects were recruited based on their alpha-fetoprotein (AFP) serum level, which is an effective marker for HCC. In the HCC cases, a higher number of chromatid aberrations [group I 13(25.5%) and group II 43(84.3%)] and CA [group I 10(19.6%) and group II 28(54.9%)] were observed. In contrast, controls showed a lower number of chromatid [group I 5(9.8%) and group II 12(23.5%)] and CA [group I 4(7.8%) and group II 9(17.6%)]. In conclusion, the results of this study contribute to the validation of CA as an intermediate end point in carcinogenesis. Because many people are unaware of this lethal disease, this study will raise awareness of this cancer.

  4. Identification of Chromosomal Aberrations by Using Trypsin G-banding in Hepatocellular Carcinoma Patients (HCC) in Tamil Nadu, India

    PubMed Central

    Mohana Devi, Subramaniam; Balachandar, Vellingiri; Murugan, Palanivel Vel; Sasikala, Keshavarao; Manikantan, Pappusamy; Venkatakrishnan, Leela Krishnan

    2010-01-01

    Hepatocellular carcinoma (HCC) (or liver cancer) is one of the most common human malignancies worldwide. Aetiologically, HCC is closely associated with chronic hepatitis B and C virus infection, cirrhosis and alcohol intake. The objective of the present study was to elucidate the chromosomal abberations (CA) in HCC patients using the trypsin G-banding technique. This study may help in understanding the pattern of the disease and to assess whether these aberrations are associated with HCC susceptibility. The study examined 51 HCC cases and an equal number (n = 51) of age and gender matched cancer-free controls recruited from the hospitals in Tamil Nadu. The HCC cases were grouped depending upon their age into group I (≤ 45 years) and group II (≥ 46 years). The development of effective markers for the detection of HCC could have an impact on cancer mortality and may have significant public health implications worldwide. Subjects were recruited based on their alpha-fetoprotein (AFP) serum level, which is an effective marker for HCC. In the HCC cases, a higher number of chromatid aberrations [group I 13(25.5%) and group II 43(84.3%)] and CA [group I 10(19.6%) and group II 28(54.9%)] were observed. In contrast, controls showed a lower number of chromatid [group I 5(9.8%) and group II 12(23.5%)] and CA [group I 4(7.8%) and group II 9(17.6%)]. In conclusion, the results of this study contribute to the validation of CA as an intermediate end point in carcinogenesis. Because many people are unaware of this lethal disease, this study will raise awareness of this cancer. PMID:24575188

  5. Multimodality 3D Tumor Segmentation in HCC patients treated with TACE

    PubMed Central

    Wang, Zhijun; Chapiro, Julius; Schernthaner, Rüdiger; Duran, Rafael; Chen, Rongxin; Geschwind, Jean-François; Lin, MingDe

    2015-01-01

    Rationale and Objectives To validate the concordance of a semi-automated multimodality lesion segmentation technique between contrast-enhanced MRI (CE-MRI), cone-beam CT (CBCT) and multi-detector CT (MDCT) in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). Materials and methods This retrospective analysis included 45 patients with unresectable HCC that underwent baseline CE-MRI within one month before the treatment, intraprocedural CBCT during conventional TACE and MDCT within 24 hours post TACE. Fourteen patients were excluded due to atypical lesion morphology, portal vein invasion or small lesion size which precluded sufficient lesion visualization. 31 patients with a total of 40 target lesions were included into the analysis. A tumor segmentation software, based on non-Euclidean geometry and theory of radial basis functions, was used to allow for the segmentation of target lesions in 3D on all three modalities. The algorithm created image-based masks located in a 3D region whose center and size was defined by the user, yielding the nomenclature “semi-automatic”. Based on that, tumor volumes on all three modalities were calculated and compared using a linear regression model (R2 values). Residual plots were used to analyze drift and variance of the values. Results The mean value of tumor volumes was 18.72±19.13cm3 (range, 0.41-59.16cm3) on CE-MRI, 21.26±21.99 cm3 (range, 0.62-86.82 cm3) on CBCT and 19.88±20.88 cm3 (range, 0.45-75.24 cm3) on MDCT. The average volumes of the tumor were not significantly different between CE-MR and DP-CBCT, DP-CBCT and MDCT, MDCT and CE-MR (p=0.577, 0.770 and 0.794 respectively). A strong correlation between volumes on CE-MRI and CBCT, CBCT and MDCT, MDCT and CE-MRI was observed (R2=0.974, 0.992 and 0.983, respectively). When plotting the residuals, no drift was observed for all methods showing deviations of no more than 10% of absolute volumes (in cm3). Conclusion A semi

  6. Long-term outcomes of patients with advanced hepatocellular carcinoma who achieved complete remission after sorafenib therapy

    PubMed Central

    2015-01-01

    Background/Aims Sorafenib is currently the sole molecular targeted agent that improves overall survival in advanced hepatocellular carcinoma (HCC). Despite the efficacy of sorafenib, the response rate varies in patients with advanced HCC. We retrospectively analyzed a series of Korean patients with advanced HCC with complete remission (CR) after sorafenib therapy. Methods In total, 523 patients with advanced HCC were treated with sorafenib in 3 large tertiary referral hospitals in Korea. A survey was conducted to collect data on patients who experienced CR after sorafenib monotherapy, and their medical records and follow-up data were analyzed. The tumor response and recurrence rates were assessed by radiologic study, based on modified response evaluation criteria in solid tumors. Results Seven patients with advanced HCC experienced CR after sorafenib therapy. The median time to tumor disappearance and the median disease-free survival time were 3 months and 9 months, respectively. HCC recurrence was identified in three cases (42.9%). Of these, two patients discontinued sorafenib before or after achieving CR and the other patient continued sorafenib after achieving CR. HCC recurred at 3, 10, and 42 months after CR in these three patients. Three patients needed dose reduction for toxicity and adverse events. Conclusions Though CR was achieved after sorafenib therapy in patients with advanced HCC, the recurrence rate was relatively high. Subsequent strategies to reduce a chance of recurrence after sorafenib therapy are required to investigate. PMID:26527250

  7. Impact of multiple liver resections prior to salvage liver transplantation on survival in patients with recurrent HCC

    PubMed Central

    Hu, Zhenhua; Zhang, Qijun; Zhou, Jie; Li, Zhiwei; Xiang, Jie; Zhou, Lin; Wu, Jian; Zhang, Min; Zheng, Shusen

    2015-01-01

    Objectives Salvage liver transplantation (SLT) is a controversial technique that has been reported to be acceptable for the management of patients with recurrent hepatocellular carcinoma (HCC) after primary hepatic resection (HR). However, whether the number of times liver resection is performed has an impact on survival after SLT has not yet been reported. Design Retrospective study. Setting The level of care is primary and the study was carried out at only 1 centre. Participants The study included 59 patients who underwent SLT for HCC from September 2001 to December 2012. 51 patients underwent HR only once before SLT, while the remaining 8 patients underwent HR more than once before SLT (HR=2 [7], HR=3, [1]). Primary and secondary outcome measures In this study, the 1-year, 3-year and 5-year overall and tumour-free survival outcomes between the 2 groups were compared. Results There were no significant differences between patients who underwent HR once and those who underwent HR more than once with respect to overall or tumour-free survival after receiving SLT. The 1-year, 3-year and 5-year overall survival rates for patients who underwent HR once were 72.9%, 35.3% and 35.5% vs 50%, 50% and 50%, respectively (p=0.986), while the 1-year, 3-year and 5-year tumour-free survival rates for those who underwent HR more than once were 66.3%, 55.3% and 44.4% vs 40%, 40% and 40%, respectively (p=0.790). Conclusions There was no significant difference in the survival rate of patients who underwent HR once before SLT and those who underwent HR more than once. This suggests that SLT is a reasonable choice for patients who suffer from recurrent HCC after HR. Trial registration number This is a retrospective study and no registry or number is required. PMID:26353871

  8. Circulating microRNAs, miR-939, miR-595, miR-519d and miR-494, Identify Cirrhotic Patients with HCC

    PubMed Central

    Fornari, Francesca; Ferracin, Manuela; Trerè, Davide; Milazzo, Maddalena; Marinelli, Sara; Galassi, Marzia; Venerandi, Laura; Pollutri, Daniela; Patrizi, Clarissa; Borghi, Alberto; Foschi, Francesco G.; Stefanini, Giuseppe F.; Negrini, Massimo; Bolondi, Luigi; Gramantieri, Laura

    2015-01-01

    The performance of circulating biomarkers for the diagnosis of hepatocellular carcinoma (HCC) is sub-optimal. In this study we tested circulating microRNAs as biomarkers for HCC in cirrhotic patients by performing a two stage study: a discovery phase conducted by microarray and a validation phase performed by qRT-PCR in an independent series of 118 patients. Beside miRNAs emerged from the discovery phase, miR-21, miR-221, miR-519d were also tested in the validation setting on the basis of literary and tissue findings. Deregulated microRNAs were assayed in HCC-derived cells in the intracellular compartment, cell culture supernatant and exosomal fraction. Serum and tissue microRNA levels were compared in 14 patients surgically treated for HCC. From the discovery study, it emerged that seven circulating microRNAs were differentially expressed in cirrhotic patients with and without HCC. In the validation set, miR-939, miR-595 and miR-519d were shown to differentiate cirrhotic patients with and without HCC. MiR-939 and miR-595 are independent factors for HCC. ROC curves of miR-939, miR-595 and miR-519d displayed that AUC was higher than AFP. An exosomal secretion of miR-519d, miR-21, miR-221 and miR-1228 and a correlation between circulating and tissue levels of miR-519d, miR-494 and miR-21 were found in HCC patients. Therefore, we show that circulating microRNAs deserve attention as non-invasive biomarkers in the diagnostic setting of HCC and that exosomal secretion contributes to discharging a subset of microRNAs into the extracellular compartment. PMID:26509672

  9. Immunotherapy of HCC metastases with autologous T cell receptor redirected T cells, targeting HBsAg in a liver transplant patient.

    PubMed

    Qasim, Waseem; Brunetto, Maurizia; Gehring, Adam J; Xue, Shao-An; Schurich, Anna; Khakpoor, Atefeh; Zhan, Hong; Ciccorossi, Pietro; Gilmour, Kimberly; Cavallone, Daniela; Moriconi, Francesco; Farzhenah, Farzin; Mazzoni, Alessandro; Chan, Lucas; Morris, Emma; Thrasher, Adrian; Maini, Mala K; Bonino, Ferruccio; Stauss, Hans; Bertoletti, Antonio

    2015-02-01

    HBV-DNA integration frequently occurs in HBV-related hepatocellular carcinoma (HCC), but whether HBV antigens are expressed in HCC cells and can be targeted by immune therapeutic strategies remains controversial. Here, we first characterized HBV antigen expression in HCC metastases, occurring in a patient who had undergone liver transplantation for HBV-related HCC. We then deployed for the first time in HCC autologous T cells, genetically modified to express an HBsAg specific T cell receptor, as therapy against chemoresistant extrahepatic metastases. We confirmed that HBV antigens were expressed in HCC metastases (but not in the donor liver) and demonstrated that tumour cells were recognized in vivo by lymphocytes, engineered to express an HBV-specific T cell receptor (TCR). Gene-modified T cells survived, expanded and mediated a reduction in HBsAg levels without exacerbation of liver inflammation or other toxicity. Whilst clinical efficacy was not established in this subject with end-stage metastatic disease, we confirm the feasibility of providing autologous TCR-redirected therapy against HCC and advocate this strategy as a novel therapeutic opportunity in hepatitis B-associated malignancies.

  10. Systematic review and meta-analysis of outcomes after liver resection in patients with hepatocellular carcinoma (HCC) with and without bile duct thrombus

    PubMed Central

    Navadgi, Suresh; Chang, Chi-Chun; Bartlett, Adam; McCall, John; Pandanaboyana, Sanjay

    2016-01-01

    Introduction This meta-analysis aimed to compare perioperative and survival outcomes in patients who underwent hepatectomy with and without Bile Duct Tumour Thrombus (BDTT). Methods A comprehensive search of Cochrane Library, PubMed, MEDLINE and EMBASE was performed to identify relevant articles. The perioperative, postoperative and long term outcomes were compared. Results Eleven studies including 6051 patients met the inclusion criteria. The perioperative outcomes were comparable between the 2 groups. The BDTT group had higher proportion poorly differentiated tumours (OR = 1.87, X2 = 10.00, df = 6, p = 0.002, I2 = 40%), Lymphovascular invasion (LVI) (OR = 4.85, X2 = 28.21, df = 9, p = <0.001, I2 = 68%) and Macrovascular invasion (MVI) (OR = 5.41, X2 = 8.73, df = 9, p = <0.001, I2 = 0%). There was no difference in 1 and 3 year survival, however 5-yr survival was poorer in the BDTT group (OR = 0.37, X2 = 37.04, df = 7, p = <0.001, I2 = 81%). The mean difference (MD) in overall survival in the BDTT group was −20 months [−32.31, −7.06], p = 0.002, I2 = 95%. Conclusion Patients with HCC with BDTT had more advanced stage HCC with adverse histological features including higher rates of MVI, LVI and poor differentiation. Hepatectomy in this group of patients offers similar survival at 3 years but inferior long-term survival and should be considered when feasible. PMID:27037199

  11. Survival of Patients with Hepatocellular Carcinoma (HCC) Treated by Percutaneous Radio-Frequency Ablation (RFA) Is Affected by Complete Radiological Response

    PubMed Central

    Cabibbo, Giuseppe; Maida, Marcello; Genco, Chiara; Alessi, Nicola; Peralta, Marco; Butera, Giuseppe; Galia, Massimo; Brancatelli, Giuseppe; Genova, Claudio; Raineri, Maurizio; Orlando, Emanuele; Attardo, Simona; Giarratano, Antonino; Midiri, Massimo; Di Marco, Vito; Craxì, Antonio; Cammà, Calogero

    2013-01-01

    Background Radio-frequency ablation (RFA) has been employed in the treatment of Barcelona Clinic Liver Cancer (BCLC) early stage hepatocellular carcinoma (HCC) as curative treatments. Aim To assess the effectiveness and the safety of RFA in patients with early HCC and compensated cirrhosis. Methods A cohort of 151 consecutive patients with early stage HCC (122 Child-Pugh class A and 29 class B patients) treated with RFA were enrolled. Clinical, laboratory and radiological follow-up data were collected from the time of first RFA. A single lesion was observed in 113/151 (74.8%), two lesions in 32/151 (21.2%), and three lesions in 6/151 (4%) of patients. Results The overall survival rates were 94%, 80%, 64%, 49%, and 41% at 12, 24, 36, 48 and 60 months, respectively. Complete response (CR) at 1 month (p<0.0001) and serum albumin levels (p = 0.0004) were the only variables indipendently linked to survival by multivariate Cox model. By multivariate analysis, tumor size (p = 0.01) is the only variable associated with an increased likehood of CR. The proportion of major complications after treatment was 4%. Conclusions RFA is safe and effective for managing HCC with cirrhosis, especially for patients with HCC ≤3 cm and higher baseline albumin levels. Complete response after RFA significantly increases survival. PMID:23922893

  12. Circulating Levels of PAI-1 and SERPINE1 4G/4G Polymorphism Are Predictive of Poor Prognosis in HCC Patients Undergoing TACE1

    PubMed Central

    Divella, Rosa; Daniele, Antonella; Abbate, Ines; Savino, Eufemia; Casamassima, Porzia; Sciortino, Giancarlo; Simone, Giovanni; Gadaleta-Caldarola, Gennaro; Fazio, Vito; Gadaleta, Cosimo Damiano; Sabbà, Carlo; Mazzocca, Antonio

    2015-01-01

    Although several molecular markers have been proposed as prognostic of disease progression in Hepatocellular carcinoma (HCC), predictive markers of response to treatment are still unsatisfactory. Here, we propose a genetic polymorphism as a potential predictive factor of poor prognosis in HCC patients treated with transcatheter arterial chemoembolization (TACE). In particular, we show that the guanosine insertion/deletion polymorphism in the promoter region of SERPINE1 gene at the − 675 bp position, named 4G/4G, predicts poor prognosis in a cohort of 75 patients with HCC undergoing TACE. By a combination of ELISA and SERPINE1 promoter study, we found that the presence of elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) in patients with 4G/4G genotype is significantly associated with reduced overall survival compared to patients with 5G/5G or 4G/5G genotype in HCC patients after TACE. Our analysis provided evidence that variation in SERPINE1 gene plays a role in defining the outcome in patients treated with TACE. In addition to a poor disease outcome, the 4G/4G variant represents an unfavorable predictive factor for response to chemotherapy as well. PMID:26310373

  13. Elevated liver fibrosis index FIB-4 is not reliable for HCC risk stratification in predominantly non-Asian CHB patients.

    PubMed

    Demir, Münevver; Grünewald, Friederike; Lang, Sonja; Schramm, Christoph; Bowe, Andrea; Mück, Vera; Kütting, Fabian; Goeser, Tobias; Steffen, Hans-Michael

    2016-09-01

    We aimed to validate the liver fibrosis index FIB-4 as a model for risk stratification of hepatocellular carcinoma development in predominantly non-Asian patients with chronic hepatitis B infection seen at a tertiary referral center in Germany.We retrospectively analyzed 373 adult patients with chronic hepatitis B infection. Patient demographics, hepatitis B markers, antiviral treatment, laboratory parameters, results from liver imaging and histology were recorded. Patients were divided into 2 groups according to their FIB-4 levels and their hazard ratios for developing hepatocellular carcinoma were analyzed adjusted for age, sex, body mass index, alcohol consumption, and antiviral medication.Median follow-up was 8.7 years (range 1-21.3 years), 93% of patients were of non-Asian origin, and 64% were male. Compared with patients with a low FIB-4 (<1.25) patients with FIB-4 ≥1.25 showed a hazard ratio for incidence of hepatocellular carcinoma of 3.03 (95% confidence interval (CI): 1.24-7.41) and an adjusted hazard ratio of 1.75 (95% CI: 0.64-4.74). Notably, 68% of patients with liver cirrhosis and 68% of those who developed HCC during observation had a low FIB-4 (<1.25).We could not confirm that a FIB-4 value ≥1.25 is a reliable clinical indicator for incidence of hepatocellular carcinoma in predominantly non-Asian patients with chronic hepatitis B. Further studies in geographically and ethnically diverse populations are needed to prove its utility as a predictive tool.

  14. Elevated liver fibrosis index FIB-4 is not reliable for HCC risk stratification in predominantly non-Asian CHB patients.

    PubMed

    Demir, Münevver; Grünewald, Friederike; Lang, Sonja; Schramm, Christoph; Bowe, Andrea; Mück, Vera; Kütting, Fabian; Goeser, Tobias; Steffen, Hans-Michael

    2016-09-01

    We aimed to validate the liver fibrosis index FIB-4 as a model for risk stratification of hepatocellular carcinoma development in predominantly non-Asian patients with chronic hepatitis B infection seen at a tertiary referral center in Germany.We retrospectively analyzed 373 adult patients with chronic hepatitis B infection. Patient demographics, hepatitis B markers, antiviral treatment, laboratory parameters, results from liver imaging and histology were recorded. Patients were divided into 2 groups according to their FIB-4 levels and their hazard ratios for developing hepatocellular carcinoma were analyzed adjusted for age, sex, body mass index, alcohol consumption, and antiviral medication.Median follow-up was 8.7 years (range 1-21.3 years), 93% of patients were of non-Asian origin, and 64% were male. Compared with patients with a low FIB-4 (<1.25) patients with FIB-4 ≥1.25 showed a hazard ratio for incidence of hepatocellular carcinoma of 3.03 (95% confidence interval (CI): 1.24-7.41) and an adjusted hazard ratio of 1.75 (95% CI: 0.64-4.74). Notably, 68% of patients with liver cirrhosis and 68% of those who developed HCC during observation had a low FIB-4 (<1.25).We could not confirm that a FIB-4 value ≥1.25 is a reliable clinical indicator for incidence of hepatocellular carcinoma in predominantly non-Asian patients with chronic hepatitis B. Further studies in geographically and ethnically diverse populations are needed to prove its utility as a predictive tool. PMID:27661015

  15. Elevated liver fibrosis index FIB-4 is not reliable for HCC risk stratification in predominantly non-Asian CHB patients

    PubMed Central

    Demir, Münevver; Grünewald, Friederike; Lang, Sonja; Schramm, Christoph; Bowe, Andrea; Mück, Vera; Kütting, Fabian; Goeser, Tobias; Steffen, Hans-Michael

    2016-01-01

    Abstract We aimed to validate the liver fibrosis index FIB-4 as a model for risk stratification of hepatocellular carcinoma development in predominantly non-Asian patients with chronic hepatitis B infection seen at a tertiary referral center in Germany. We retrospectively analyzed 373 adult patients with chronic hepatitis B infection. Patient demographics, hepatitis B markers, antiviral treatment, laboratory parameters, results from liver imaging and histology were recorded. Patients were divided into 2 groups according to their FIB-4 levels and their hazard ratios for developing hepatocellular carcinoma were analyzed adjusted for age, sex, body mass index, alcohol consumption, and antiviral medication. Median follow-up was 8.7 years (range 1–21.3 years), 93% of patients were of non-Asian origin, and 64% were male. Compared with patients with a low FIB-4 (<1.25) patients with FIB-4 ≥1.25 showed a hazard ratio for incidence of hepatocellular carcinoma of 3.03 (95% confidence interval (CI): 1.24–7.41) and an adjusted hazard ratio of 1.75 (95% CI: 0.64–4.74). Notably, 68% of patients with liver cirrhosis and 68% of those who developed HCC during observation had a low FIB-4 (<1.25). We could not confirm that a FIB-4 value ≥1.25 is a reliable clinical indicator for incidence of hepatocellular carcinoma in predominantly non-Asian patients with chronic hepatitis B. Further studies in geographically and ethnically diverse populations are needed to prove its utility as a predictive tool. PMID:27661015

  16. Consideration of role of radiotherapy for lymph node metastases in patients with HCC: Retrospective analysis for prognostic factors from 125 patients

    SciTech Connect

    Zeng Zhaochong . E-mail: ZCZeng@ZSHospital.net; Tang Zhaoyou; Fan Jia; Qin Lunxiu; Ye Shenlong; Zhou Jian; Sun Huichuan; Wang Binliang; Wang Jianhua

    2005-11-15

    Objectives: To evaluate the role of radiotherapy (RT) for hepatocellular carcinoma (HCC) patients with abdominal lymph node (LN) metastasis at our institution in the past 7 years. Methods and Materials: We identified 125 patients with HCC metastasis to regional LNs treated with or without external beam RT (EBRT) between 1998 and 2004. Clinical characteristics collected included {alpha}-fetoprotein status, {gamma}-glutamyltransferase, status of intrahepatic tumors (size and number), previous therapy for intrahepatic tumors, metastatic LN status (location, number, and size), tumor thrombi, and Child-Pugh classification. Of the 125 patients, 62 received local limited EBRT and were classified as the EBRT group. They received locoregional LN irradiation. The tumor dose ranged from 40 to 60 Gy in daily 2.0-Gy fractions, 5 times weekly. Another 63 patients, who did not receive EBRT, were selected from hospitalized patients in the same period and were classified as the non-EBRT group. The parameters studied included survival rates and tumor response to EBRT both as demonstrated by clinical symptoms and as seen on CT. The Kaplan-Meier method was used to evaluate the survival rates, and the Cox regression model was used to identify predictors of outcome. Results: After EBRT, partial responses and complete responses were observed in 37.1% and 59.7% of patients, respectively. The median survival was 9.4 months (95% confidence interval 5.8-13.0) for the EBRT group and 3.3 months (95% confidence interval, 2.7-3.9) for the non-EBRT group (p < 0.001). Multivariate analysis showed that multiple intrahepatic primary tumors, occurrence of tumor thrombi, no therapy for intrahepatic tumors, and greater Child-Pugh classification were related to a poorer prognosis in all patients. In the EBRT group, the survival periods decreased as the distance of LN involvement from the liver increased (following the natural flow of lymph) and was also associated with the intrahepatic primary tumor

  17. Contrast Enhanced MRI in the Diagnosis of HCC

    PubMed Central

    Niendorf, Eric; Spilseth, Benjamin; Wang, Xiao; Taylor, Andrew

    2015-01-01

    Hepatocellular carcinoma (HCC) is the 6th most common cancer worldwide. Imaging plays a critical role in HCC screening and diagnosis. Initial screening of patients at risk for HCC is performed with ultrasound. Confirmation of HCC can then be obtained by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), due to the relatively high specificity of both techniques. This article will focus on reviewing MRI techniques for imaging HCC, felt by many to be the exam of choice for HCC diagnosis. MRI relies heavily upon the use of gadolinium-based contrast agents and while primarily extracellular gadolinium-based contrast agents are used, there is an emerging role of hepatobiliary contrast agents in HCC imaging. The use of other non-contrast enhanced MRI techniques for assessing HCC will also be discussed and these MRI strategies will be reviewed in the context of the pathophysiology of HCC to help understand the MR imaging appearance of HCC. PMID:26854161

  18. Surveillance of HCC Patients after Liver RFA: Role of MRI with Hepatospecific Contrast versus Three-Phase CT Scan-Experience of High Volume Oncologic Institute.

    PubMed

    Granata, Vincenza; Petrillo, Mario; Fusco, Roberta; Setola, Sergio Venanzio; de Lutio di Castelguidone, Elisabetta; Catalano, Orlando; Piccirillo, Mauro; Albino, Vittorio; Izzo, Francesco; Petrillo, Antonella

    2013-01-01

    Purpose. To compare the diagnostic accuracy of hepatospecific contrast-enhanced MRI versus triple-phase CT scan after radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC) patients. Methods. Thirty-four consecutive HCC patients (42 hepatic nodules) were treated with percutaneous RFA and underwent MR and CT scans. All patients were enrolled in a research protocol that included CT with iodized contrast medium injection and MR with hepatospecific contrast medium injection. All patients were restaged within four weeks and at 3 months from ablation. The images were reviewed by four different radiologists to evaluate tumor necrosis, residual or recurrence disease, and evidence of new foci. Results. Thirty-two nodules were necrotic after treatment; 10 showed residual disease. Six new HCCs were identified. At first month followup CT has identified 34 necrotic lesions and 8 residual diseases; no new foci were recognized. At MRI instead, 32 complete necrotic lesions were identified, 10 lesions showed residual disease, and 2 new HCCs were found. At three months, CT demonstrated 33 completely necrotic lesions, 9 residual diseases, and 2 new HCCs. MR showed 31 complete necrotic lesions, 11 cases of residual disease, and 6 new HCCs. Conclusions. Hepatospecific contrast-enhanced MRI is more effective than multiphase CT in assessment of HCC treated with RFA. PMID:24324487

  19. The effect of locoregional therapies in patients with advanced hepatocellular carcinoma treated with sorafenib

    PubMed Central

    Sarpel, Umut; Spivack, John H.; Berger, Yaniv; Heskel, Marina; Aycart, Samantha N.; Sweeney, Robert; Edwards, Martin P.; Labow, Daniel M.; Kim, Edward

    2016-01-01

    Background & aims It is unknown whether the addition of locoregional therapies (LRTx) to sorafenib improves prognosis over sorafenib alone in patients with advanced hepatocellular carcinoma (HCC). The aim of this study was to assess the effect of LRTx in this population. Methods A retrospective analysis was performed of patients with advanced HCC as defined by extrahepatic metastasis, lymphadenopathy >2 cm, or gross vascular invasion. Sorafenib therapy was required for inclusion. Survival of patients who received LRTx after progression to advanced stage was compared to those who did not receive LRTx. Results Using an intention to treat analysis of 312 eligible patients, a propensity weighted proportional hazards model demonstrated LRTx as a predictor of survival (HR = 0.505, 95% CI: 0.407–0.628; P < 0.001). The greatest benefit was seen in patients with the largest tumor burden (HR = 0.305, 95% CI: 0.236–0.393; P < 0.01). Median survival in the sorafenib arm was 143 days (95% CI: 118–161) vs. 247 days (95% CI: 220–289) in the sorafenib plus LRTx arm (P < 0.001). Conclusions These results demonstrate a survival benefit with the addition of LRTx to sorafenib for patients with advanced HCC. These findings should prompt a prospective clinical trial to further assess the role of LRTx in patients with advanced HCC. PMID:27154804

  20. Epidemiology of hepatocellular carcinoma (HCC) in hemophilia.

    PubMed

    Shetty, Shrimati; Sharma, Nitika; Ghosh, Kanjaksha

    2016-03-01

    Hepatocellular carcinoma (HCC) is an important cause of increasing mortality in elderly hemophilia population. Majority of the patients treated with virus non-inactivated factor concentrates prepared from large plasma pools prior to 1985 have been found to be infected with hepatitis C virus (HCV), a major risk factor for HCC. A PubMed search of articles published until February 2015 was performed utilizing the keywords hemophilia, malignancy, neoplasm, cancer, mortality, ageing hemophilia, epidemiology, hepatocellular carcinoma and liver cancer and the relevant articles were included. Contradictory reports are available in literature on the incidence of cancers in general in hemophilia population. Almost all the studies where the incidence of HCC or mortality due to HCC have been analyzed in hemophilia population show that a vast majority of these patients are HCV infected. The incidence of HCC though higher in hemophilic population is related to the higher incidence of HCV infection and not due to the hemophilia phenotype.

  1. Sneddon-Wilkinson disease induced by sorafenib in a patient with advanced hepatocellular carcinoma.

    PubMed

    Tajiri, Kazuto; Nakajima, Takahiko; Kawai, Kengo; Minemura, Masami; Sugiyama, Toshiro

    2015-01-01

    Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC), although it is known to cause a variety of dermatologic adverse events. Subcorneal pustular dermatosis (SCPD), also known as Sneddon-Wilkinson disease, is a rare skin eruption that accompanies various systemic disorders and may become chronically progressive. We herein describe the case of a patient who developed SCPD after sorafenib administration. The dermatologic reaction was improved by the cessation of sorafenib and worsened by its readministration. Clinicians treating HCC patients with sorafenib should be aware of the possibility of SCPD. PMID:25786448

  2. Sneddon-Wilkinson disease induced by sorafenib in a patient with advanced hepatocellular carcinoma.

    PubMed

    Tajiri, Kazuto; Nakajima, Takahiko; Kawai, Kengo; Minemura, Masami; Sugiyama, Toshiro

    2015-01-01

    Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC), although it is known to cause a variety of dermatologic adverse events. Subcorneal pustular dermatosis (SCPD), also known as Sneddon-Wilkinson disease, is a rare skin eruption that accompanies various systemic disorders and may become chronically progressive. We herein describe the case of a patient who developed SCPD after sorafenib administration. The dermatologic reaction was improved by the cessation of sorafenib and worsened by its readministration. Clinicians treating HCC patients with sorafenib should be aware of the possibility of SCPD.

  3. Therapeutic Strategies in HCC: Radiation Modalities.

    PubMed

    Gallicchio, R; Nardelli, A; Mainenti, P; Nappi, A; Capacchione, D; Simeon, V; Sirignano, C; Abbruzzi, F; Barbato, F; Landriscina, M; Storto, G

    2016-01-01

    Patients with hepatocellular carcinoma (HCC) comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE) and transarterial metabolic radiotherapy (TAMR) have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx) by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with (131)I Lipiodol or (90)Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment.

  4. Therapeutic Strategies in HCC: Radiation Modalities

    PubMed Central

    Gallicchio, R.; Nardelli, A.; Mainenti, P.; Nappi, A.; Capacchione, D.; Simeon, V.; Sirignano, C.; Abbruzzi, F.; Barbato, F.; Landriscina, M.

    2016-01-01

    Patients with hepatocellular carcinoma (HCC) comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE) and transarterial metabolic radiotherapy (TAMR) have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx) by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with 131I Lipiodol or 90Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment. PMID:27563661

  5. Therapeutic Strategies in HCC: Radiation Modalities.

    PubMed

    Gallicchio, R; Nardelli, A; Mainenti, P; Nappi, A; Capacchione, D; Simeon, V; Sirignano, C; Abbruzzi, F; Barbato, F; Landriscina, M; Storto, G

    2016-01-01

    Patients with hepatocellular carcinoma (HCC) comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE) and transarterial metabolic radiotherapy (TAMR) have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx) by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with (131)I Lipiodol or (90)Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment. PMID:27563661

  6. [Transarterial infusion chemotherapy using fine-powder cisplatin in patients with advanced hepatocellular carcinoma].

    PubMed

    Hatanaka, Takeshi; Kakizaki, Satoru; Ueno, Takashi; Takeuchi, Suguru; Takizawa, Daichi; Katakai, Kenji

    2014-02-01

    We investigated the therapeutic effects and safety of fine powder cisplatin for patients with advanced hepatocellular carcinoma( HCC). From January 2006 to March 2012, 123 patients with advanced HCC were treated by transarterial infusion chemotherapy(TAI)with fine-powder cisplatin(IA-call®, Nippon Kayaku Co. Ltd., Tokyo, Japan). The drug was infused into the liver through the feeding artery at a dose of 65 mg/m2. The treatment was repeated every 4 to 8 weeks until evidence of either tumor progression or unacceptable toxicity appeared. Treatment responses were classified as complete response(CR), partial response(PR), stable disease(SD), and progressive disease(PD)in 3.2%, 12.0%, 32.2%, and 52.4% of patients, respectively. The median survival durations were as follows: overall, 12.2 months; CR/PR patients, 23.8 months; and SD/PD patients, 10.6 months. The cumulative survival rates of CR/PR patients were significantly higher than those of SD/PD patients (p<0.05). Multivariate analyses revealed that treatment response, etiology, Child-Pugh grading, and level of protein induced by the vitamin K antagonist- II (PIVKA- II )were predictive factors of survival duration. Problematic adverse events were not observed in any of the patients. Our results suggest that TAI using fine-powder cisplatin can be safely administered for advanced HCC and can improve the prognosis of patients with advanced disease. PMID:24743198

  7. The adverse effects of sorafenib in patients with advanced cancers.

    PubMed

    Li, Ye; Gao, Zu-Hua; Qu, Xian-Jun

    2015-03-01

    Sorafenib is the first multi-kinase inhibitor (TKI) approved for the treatment of advanced hepatocellular cancer (HCC) and metastatic renal cell cancer (RCC) and is increasingly being used to treat patients with well-differentiated radioiodine-resistant thyroid cancer (DTC). Sorafenib demonstrates targeted activity on several families of receptor and non-receptor tyrosine kinases that are involved in angiogenesis, tumour growth and metastatic progression of cancer. Sorafenib treatment results in long-term efficacy and low incidence of life-threatening toxicities. Although sorafenib has demonstrated many benefits in patients, the adverse effects cannot be ignored. The most common treatment-related toxicities include diarrhoea, fatigue, hand-foot skin reaction and hypertension. Most of these toxicities are considered mild to moderate and manageable to varying degrees; however, cardiovascular events might lead to death. In this MiniReview, we summarize the adverse effects of sorafenib that commonly occur in patients with advanced cancers. PMID:25495944

  8. Impact of UCSF criteria according to pre- and post-OLT tumor features: analysis of 479 patients listed for HCC with a short waiting time.

    PubMed

    Decaens, Thomas; Roudot-Thoraval, Françoise; Hadni-Bresson, Solange; Meyer, Carole; Gugenheim, Jean; Durand, Francois; Bernard, Pierre-Henri; Boillot, Olivier; Sulpice, Laurent; Calmus, Yvon; Hardwigsen, Jean; Ducerf, Christian; Pageaux, Georges-Philippe; Dharancy, Sebastien; Chazouilleres, Olivier; Cherqui, Daniel; Duvoux, Christophe

    2006-12-01

    Orthotopic liver transplantation (OLT) indication for hepatocellular carcinoma (HCC) is currently based on the Milan criteria. The University of California, San Francisco (UCSF) recently proposed an expansion of the selection criteria according to tumors characteristics on the explanted liver. This study: 1) assessed the validity of these criteria in an independent large series and 2) tested for the usefulness of these criteria when applied to pre-OLT tumor evaluation. Between 1985 and 1998, 479 patients were listed for liver transplantation (LT) for HCC and 467 were transplanted. According to pre-OLT (imaging at date of listing) or post-OLT (explanted liver) tumor characteristics, patients were retrospectively classified according to both the Milan and UCSF criteria. The 5-yr survival statistics were assessed by the Kaplan-Meier method and compared by the log-rank test. Pre-OLT UCSF criteria were analyzed according to an intention-to-treat principle. Based on the pre-OLT evaluation, 279 patients were Milan+, 44 patients were UCSF+ but Milan- (subgroup of patients that might benefit from the expansion), and 145 patients were UCSF- and Milan-. With a short median waiting time of 4 months, 5-yr survival was 60.1 +/- 3.0%, 45.6 +/- 7.8%, and 34.7 +/- 4.0%, respectively (P < 0.001). The 5-yr survival was arithmetically lower in UCSF+ Milan- patients compared to Milan+ but this difference was not significant (P = 0.10). Based on pathological features of the explanted liver, 5-yr survival was 70.4 +/- 3.4%, 63.6 +/- 7.8%, and 34.1 +/- 3.1%, in Milan+ patients (n = 184), UCSF+ Milan- patients (n = 39), and UCSF- Milan- patients (n = 238), respectively (P < 0.001). However, the 5-yr survival did not differ between Milan+ and UCSF+ Milan- patients (P = 0.33). In conclusion, these results show that when applied to pre-OLT evaluation, the UCSF criteria are associated with a 5-yr survival below 50%. Their applicability is therefore limited, despite similar survival rates

  9. Safety and efficacy of sorafenib in patients with Child-Pugh B advanced hepatocellular carcinoma

    PubMed Central

    DA FONSECA, LEONARDO GOMES; BARROSO-SOUSA, ROMUALDO; BENTO, AFONSO DA SILVA ALVES; BLANCO, BRUNA PACCOLA; VALENTE, GABRIEL LUIS; PFIFFER, TULIO EDUARDO FLESCH; HOFF, PAULO MARCELO; SABBAGA, JORGE

    2015-01-01

    Sorafenib demonstrated a survival benefit in the treatment of advanced hepatocellular carcinoma (HCC) in phase III trials. However, almost all the patients included in those trials exhibited well-preserved liver function (Child-Pugh A). The aim of this study was to describe our experience with sorafenib in Child-Pugh B HCC patients. A database of patients with advanced HCC treated with sorafenib was retrospectively evaluated. The median overall survival of Child-Pugh B patients (n=20) was 2.53 months [95% confidence interval (CI): 0.33–5.92 months] and of Child-Pugh A patients (n=100) 9.71 months (95% CI: 6.22–13.04). Child-Pugh B patients had a significantly poorer survival compared to Child-Pugh A patients (P=0.002). The toxicities were similar between the two groups. Metastasis, vascular invasion and α-fetoprotein level >1,030 ng/ml were not associated with survival among Child-Pugh B patients (P=0.281, 0.189 and 0.996, respectively). Although the survival outcomes were worse in Child-Pugh B patients treated with sorafenib, the toxicity profile was manageable. Therefore, there remains the question of whether to treat this subgroup of patients and more data are required to define the role of sorafenib in the context of liver dysfunction. PMID:26171182

  10. Hepatocellular Carcinoma (HCC)

    NASA Astrophysics Data System (ADS)

    Helmberger, Thomas K.

    Hepatocellular carcinoma (HCC) is considered to be one of the most common malignancies worldwide, and the most common one in Africa and Asia. Over the last decade, a rising incidence of up to 10-15/100,000 per population has been seen in the Western world, with an estimate of 250,000 deaths and more than a million worldwide per year. By the year 2010, the World Health Organization expects that HCC will be the leading cause of cancer mortality surpassing lung cancer. This increasing incidence is most likely related to an increasing prevalence of chronic hepatitis C (HC) and B (HB) virus infections and other diseases inducing chronic inflammation (Befeler and Di Bisceglie 2002; Llovet et al. 2003).

  11. Sorafenib-induced acute interstitial pneumonia in patients with advanced hepatocellular carcinoma: report of three cases.

    PubMed

    Takeda, Haruhiko; Nishikawa, Hiroki; Iguchi, Eriko; Matsuda, Fumihiro; Kita, Ryuichi; Kimura, Toru; Osaki, Yukio

    2012-01-01

    Little is known about acute interstitial pneumonia (AIP) induced by sorafenib therapy in patients with advanced hepatocellular carcinoma (HCC). Here, we present three patients with advanced HCC who developed AIP during sorafenib therapy, with fatal complications in two cases. Case 1 was a 76-year-old man who developed dyspnea. Chest CT showed interstitial pneumonia. Sorafenib was discontinued immediately, and prednisolone was started. His pneumonia resolved. A drug-induced lymphocyte stimulation test for sorafenib was positive. Case 2 was a 75-year-old man and case 3 was a 77-year-old man, both of whom developed high-grade fever and hypoxemia during sorafenib therapy, and were diagnosed with AIP. In spite of high-dose steroid therapy, their respiratory failure worsened and both patients died. In all three cases, serum KL-6 or surfactant protein D concentrations were elevated, and blood and sputum cultures did not grow pathogens. All three patients were smokers with restrictive lung disease on preoperative respiratory function testing, but did not have respiratory symptoms before sorafenib therapy. The clinical features of these three cases suggest that male gender, older age, smoking history, and lung disease are associated with acute sorafenib-induced AIP in patients with advanced HCC.

  12. Association of abnormal plasma bilirubin with aggressive HCC phenotype

    PubMed Central

    Carr, Brian I.; Guerra, Vito; Giannini, Edoardo G.; Farinati, Fabio; Ciccarese, Francesca; Rapaccini, Gian Ludovico; Marco, Maria Di; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Caturelli, Eugenio; Chiaramonte, Maria; Trevisani, Franco

    2014-01-01

    Background Cirrhosis-related abnormal liver function is associated with predisposition to HCC, features in several HCC classification systems and is an HCC prognostic factor. Aims To examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. Methods A 2,416 patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely blood AFP levels, tumor size, presence of PVT and tumor multifocality. Results In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even for small tumor size patients. A multiple logistic regression model for PVT or tumor multifocality showed increased OddsRatios for elevated levels of GGTP, bilirubin and AFP and for larger tumor sizes. Conclusions HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had increased incidence of PVT and tumor multifocality and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness. PMID:24787296

  13. HBV is a risk factor for poor patient prognosis after curative resection of hepatocellular carcinoma

    PubMed Central

    Li, Zhonghu; Zhao, Xin; Jiang, Peng; Xiao, Senlin; Wu, Guo; Chen, Kai; Zhang, Xi; Liu, Hui; Han, Xiuguo; Wang, Shuguang; Li, Xiaowu

    2016-01-01

    Abstract Controversy exists regarding pathological factors affecting the prognosis of hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV-HCC). Their postoperative clinical behaviors and the exact HBV Deoxyribonucleic Acid (DNA) thresholds that distinguish good and poor prognoses are unknown. This study aimed to compare clinicopathological, pre- and postoperative clinical factors and overall and recurrence-free survival (RFS) between HBV-HCC patients and nonhepatitis B and nonhepatitis C HCC (NBC-HCC) patients to determine the optimal prognostic HBV DNA threshold. Data from 1440 patients with HBV-HCC and NBC-HCC who underwent curative hepatectomy were retrospectively analyzed. Liver function in the HBV-HCC group was significantly worse than in the NBC-HCC group. Compared with NBC-HCC patients, HBV-HCC patients had significantly more vascular invasion and advanced HCC. The HBV-HCC patients also had significantly worse liver function and more complications. Further survival analysis showed significantly lower overall and RFS rates and a higher early recurrence rate in the HBV-HCC group. Univariate analysis indicated that HBV was a risk factor for overall and RFS. Finally, X-tile analysis revealed that the optimal HBV DNA cutoff points for predicting RFS and overall survival in HCC patients were 10,100 and 12,800 IU/mL, respectively. After hepatectomy for HCC, HBV-HCC patients had more complications and a worse prognosis than NBC-HCC patients. Antiviral therapy should be considered before hepatectomy in patients with high (more than approximately 104 IU/mL) HBV DNA levels. PMID:27495026

  14. Effects of Oral L-Carnitine on Liver Functions after Transarterial Chemoembolization in Intermediate-Stage HCC Patients

    PubMed Central

    Hassan, Abeer; Tsuda, Yasuhiro; Asai, Akira; Yokohama, Keisuke; Nakamura, Ken; Sujishi, Tetsuya; Ohama, Hideko; Tsuchimoto, Yusuke; Fukunishi, Shinya; Abdelaal, Usama M.; Arafa, Usama A.; Hassan, Ali T.; Kassem, Ali M.; Higuchi, Kazuhide

    2015-01-01

    Transarterial chemoembolization (TACE) is usually followed by hepatic dysfunction. We evaluated the effects of L-carnitine on post-TACE impaired liver functions. Methods. 53 cirrhotic hepatocellular carcinoma patients at Osaka Medical College were enrolled in this study and assigned into either L-carnitine group receiving 600 mg oral L-carnitine daily or control group. Liver functions were evaluated at pre-TACE and 1, 4, and 12 weeks after TACE. Results. The L-carnitine group maintained Child-Pugh (CP) score at 1 week after TACE and exhibited significant improvement at 4 weeks after TACE (P < 0.01). Conversely, the control group reported a significant CP score deterioration at 1 week (P < 0.05) and 12 weeks after TACE (P < 0.05). L-carnitine suppressed serum albumin deterioration at 1 week after TACE. There were significant differences between L-carnitine and control groups regarding mean serum albumin changes from baseline to 1 week (P < 0.05) and 4 weeks after TACE (P < 0.05). L-carnitine caused prothrombin time improvement from baseline to 1, 4 (P < 0.05), and 12 weeks after TACE. Total bilirubin mean changes from baseline to 1 week after TACE exhibited significant differences between L-carnitine and control groups (P < 0.05). The hepatoprotective effects of L-carnitine were enhanced by branched chain amino acids combination. Conclusion. L-carnitine maintained and improved liver functions after TACE. PMID:26664151

  15. Challenges of advanced hepatocellular carcinoma.

    PubMed

    Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

    2016-09-14

    Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials. PMID:27678348

  16. Challenges of advanced hepatocellular carcinoma

    PubMed Central

    Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

    2016-01-01

    Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials.

  17. Challenges of advanced hepatocellular carcinoma

    PubMed Central

    Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

    2016-01-01

    Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials. PMID:27678348

  18. The Degree of Lipiodol Accumulation Can Be an Indicator of Successful Treatment for Unresectable Hepatocellular Carcinoma (HCC) Patients - in the Case of Transcatheter Arterial Chemoembolization (TACE) and External Beam Radiotherapy (EBRT)

    PubMed Central

    Yang, Ping; Zeng, Zhao-Chong; Wang, Bin-Liang; Zhang, Jian-Ying; Fan, Jia; Zhou, Jian; Hu, Yong

    2016-01-01

    Purpose: Transcatheter arterial chemoembolization (TACE) in combination with external beam radiotherapy (EBRT) results in improved survival due to better local control in patients with unresectable hepatocellular carcinoma (HCC). The purpose of this study was to investigate lipiodol accumulation, as it reflects tumor burden and is a potential prognostic factor, in HCC patients treated with TACE/EBRT. Methods and Materials: We retrospectively studied 147 patients with unresectable HCC treated with TACE and EBRT. Clinical features, adverse reactions, and prognostic factors were analyzed. All patients were treated with TACE 1-6 times in combination with EBRT (44-66 Gy) in dose of 2 Gy/fraction given once a day five times a week. Tumor status and laboratory findings were followed. The degree of lipiodol accumulation was assessed by computed tomography before EBRT, and was categorized as either complete/intense or low/moderate. Results: The response rate of tumor size after EBRT was 68.2%, median survival was 23.1 months, and overall survival rates were 86.6%, 49.2%, and 28.2% at 1, 2, and 3 years, respectively. Univariate analysis showed that lower hemoglobin levels, higher alkaline phosphatase levels, Child-Pugh B, negative alpha-fetoprotein (AFP) response after EBRT, poor treatment response after EBRT, tumor diameter >10 cm, and poor lipiodol accumulation were unfavorable prognostic factors. On multivariate analysis, higher hemoglobin levels, Child-Pugh A, decreased AFP levels after treatment, Helical Tomotherapy (HT) and intense lipiodol accumulation after TACE were significant favorable predictors. Conclusions: The degree of lipiodol accumulation before EBRT is a prognostic factor in patients with unresectable HCC. Increased AFP levels after EBRT are always associated with poor survival. HT is recommended as a potentially better EBRT modality than three-dimensional conformal radiation therapy (3D-CRT). PMID:27471557

  19. Rapid Virological Response After Early Treatment with a Combined Therapy of Ledipasvir and Sofosbuvir in HCV Genotype 4 After Living Donor Liver Transplantation in a HCC Downstaged Patient: Case Report and Review of the Literature

    PubMed Central

    Obed, Aiman; Bashir, Abdalla; Jarrad, Anwar

    2016-01-01

    Patient: Male, 54 Final Diagnosis: HCC with portal vein Symptoms: Liver failure Medication: — Clinical Procedure: Hepatitis c treatment • hcc tratment Specialty: Transplantology Objective: Unusual clinical course Background: Hepatitis C virus (HCV) genotype 4 (GT-4) is widespread in the Middle East, where it is responsible for the majority of HCV infections. It shows moderate treatment response rates when compared to other genotypes in the current era of interferon-based regimens. However, in the era of direct acting antiviral (DAA) drugs, its response is at least as good as observed for HCV genotypes 1–3. Case Report: We present a case of a 44-year-old patient with HCV cirrhosis. Since 2007, he has been treated for HCV infection with multiple ineffective regimens of interferon (INF) and ribavirin. A liver biopsy in 2010 revealed stage 5-6/6 indicating cirrhosis, which was later complicated by the occurrence of portal vein thrombosis and a large hepatocellular carcinoma (HCC) (maximum diameter 9 cm). The patient was successfully treated with sorafenib, transcatheter arterial chemoembolization (TACE), and radio-frequency ablation. After four TACE procedures, the patient’s AFP (alpha-fetoprotein) decreased remarkably and almost normalized. The HCC disappeared radiologically as shown by triple phase CT, MRI with contrast, and PET-CT. He successfully underwent a living donor liver transplantation. Four weeks post liver transplantation he started treatment with sorafenib, and switched from tacrolimus to Rapamune (sirolimus) as immunosuppressant therapy. Ten weeks after liver transplantation, HCV treatment was introduced along with ledipasvir and sofosbuvir due to his increasing liver enzyme levels. A rapid viral response was achieved after 14 days. In total, the patient received 12 weeks of this treatment. Conclusions: This case study might be of significance in informing early management and personalized treatment of patients with recurrent HCV GT-4 infections

  20. The Enhanced Metastatic Potential of Hepatocellular Carcinoma (HCC) Cells with Sorafenib Resistance

    PubMed Central

    Chow, Ariel Ka-Man; Ng, Lui; Lam, Colin Siu-Chi; Wong, Sunny Kit-Man; Wan, Timothy Ming-Hun; Cheng, Nathan Shiu-Man; Yau, Thomas Chung-Cheung; Poon, Ronnie Tung-Ping; Pang, Roberta Wen-Chi

    2013-01-01

    Acquired resistance towards sorafenib treatment was found in HCC patients, which results in poor prognosis. To investigate the enhanced metastatic potential of sorafenib resistance cells, sorafenib-resistant (SorR) cell lines were established by long-term exposure of the HCC cells to the maximum tolerated dose of sorafenib. Cell proliferation assay and qPCR of ABC transporter genes (ABCC1-3) were first performed to confirm the resistance of cells. Migration and invasion assays, and immunoblotting analysis on the expression of epithelial to mesenchymal transition (EMT) regulatory proteins were performed to study the metastatic potential of SorR cells. The expression of CD44 and CD133 were studied by flow cytometry and the gene expressions of pluripotency factors were studied by qPCR to demonstrate the enrichment of cancer stem cells (CSCs) in SorR cells. Control (CTL) and SorR cells were also injected orthotopically to the livers of NOD-SCID mice to investigate the development of lung metastasis. Increased expressions of ABCC1-3 were found in SorR cells. Enhanced migratory and invasive abilities of SorR cells were observed. The changes in expression of EMT regulatory proteins demonstrated an activation of the EMT process in SorR cells. Enriched proportion of CD44+ and CD44+CD133+ cells were also observed in SorR cells. All (8/8) mice injected with SorR cells demonstrated lung metastasis whereas only 1/8 mouse injected with CTL cells showed lung metastasis. HCC cells with sorafenib resistance demonstrated a higher metastatic potential, which may be due to the activated EMT process. Enriched CSCs were also demonstrated in the sorafenib resistant cells. This study suggests that advanced HCC patients with acquired sorafenib resistance may have enhanced tumor growth or distant metastasis, which raises the concern of long-term sorafenib treatment in advanced HCC patients who have developed resistance of sorafenib. PMID:24244338

  1. HBV is a risk factor for poor patient prognosis after curative resection of hepatocellular carcinoma: A retrospective case-control study.

    PubMed

    Li, Zhonghu; Zhao, Xin; Jiang, Peng; Xiao, Senlin; Wu, Guo; Chen, Kai; Zhang, Xi; Liu, Hui; Han, Xiuguo; Wang, Shuguang; Li, Xiaowu

    2016-08-01

    Controversy exists regarding pathological factors affecting the prognosis of hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV-HCC). Their postoperative clinical behaviors and the exact HBV Deoxyribonucleic Acid (DNA) thresholds that distinguish good and poor prognoses are unknown. This study aimed to compare clinicopathological, pre- and postoperative clinical factors and overall and recurrence-free survival (RFS) between HBV-HCC patients and nonhepatitis B and nonhepatitis C HCC (NBC-HCC) patients to determine the optimal prognostic HBV DNA threshold.Data from 1440 patients with HBV-HCC and NBC-HCC who underwent curative hepatectomy were retrospectively analyzed.Liver function in the HBV-HCC group was significantly worse than in the NBC-HCC group. Compared with NBC-HCC patients, HBV-HCC patients had significantly more vascular invasion and advanced HCC. The HBV-HCC patients also had significantly worse liver function and more complications. Further survival analysis showed significantly lower overall and RFS rates and a higher early recurrence rate in the HBV-HCC group. Univariate analysis indicated that HBV was a risk factor for overall and RFS. Finally, X-tile analysis revealed that the optimal HBV DNA cutoff points for predicting RFS and overall survival in HCC patients were 10,100 and 12,800 IU/mL, respectively.After hepatectomy for HCC, HBV-HCC patients had more complications and a worse prognosis than NBC-HCC patients. Antiviral therapy should be considered before hepatectomy in patients with high (more than approximately 10 IU/mL) HBV DNA levels.

  2. A Phase I Dose-Finding Study of Silybin Phosphatidylcholine (Milk Thistle) in Patients With Advanced Hepatocellular Carcinoma

    PubMed Central

    Siegel, Abby B.; Narayan, Rupa; Rodriguez, Rosa; Goyal, Abhishek; Jacobson, Judith S.; Kelly, Kara; Ladas, Elena; Lunghofer, Paul J.; Hansen, Ryan J.; Gustafson, Daniel L.; Flaig, Thomas W.; Tsai, Wei Yann; Wu, David P. H.; Lee, Valerie; Greenlee, Heather

    2013-01-01

    Purpose To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction. Experimental Design Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks. Results Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug. Conclusion Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests. PMID:23757319

  3. [A case of HCC with portal vein thrombosis treated with multidisciplinary treatment combined with preoperative SBRT and radical resection].

    PubMed

    Marubashi, Shigeru; Gotoh, Kunihito; Akita, Hirofumi; Takahashi, Hidenori; Sugimura, Keijiro; Miyoshi, Norikatsu; Motoori, Masaaki; Kishi, Kentaro; Noura, Shingo; Ohue, Masayuki; Fujiwara, Yoshiyuki; Yano, Masahiko; Ishikawa, Osamu; Sakon, Masato

    2014-11-01

    A 70s man with advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) (Vp-HCC) in the main trunk (Vp4) was referred to our hospital. He was negative for hepatitis C virus (HCV) and hepatitis B virus (HBV), and his liver function was well preserved. The main tumor was in the right lobe and exceeded 10 cm in diameter. There were no intrahepatic metastases to the left lobe. The patient underwent stereotactic body radiation therapy (SBRT) (48 Gy/4 fractions) to the area of the PVTT. Six days after SBRT, the patient underwent right lobectomy for removal of PVTT. The postoperative course was uneventful, and low-dose 5-fluorouracil and cisplatin(FP)intra-arterial chemotherapy was administered for 3 months. Histopathological findings for the tumor indicated a poorly differentiated HCC, vp4, with moderate to severe tumor necrosis or degeneration in the area that received SBRT. Tumor markers (alpha-fetoprotein [AFP], proteins induced by vitamin K absence [PIVKA-II]) decreased within the normal range, and there was no apparent HCC recurrence 6 months after the hepatectomy. Multidisciplinary treatment combined with preoperative SBRT and radical resection for Vp-HCC was feasible and effective in this case. PMID:25731445

  4. Quality of Life in Hepatocellular Carcinoma Patients Treated with Transarterial Chemoembolization

    PubMed Central

    Ahmed, Saleem; de Souza, Nurun Nisa; Qiao, Wang; Kasai, Meidai; Keem, Low Jee; Shelat, Vishal G.

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide. Majority of patients with HCC are diagnosed in the advanced stages of disease and hence they are only suitable for palliative therapy. TACE (transarterial chemoembolization) is the most commonly used treatment for unresectable HCC. It is however unclear if TACE improves the quality of life (QoL) in patients with HCC. The aim of this review is to evaluate the impact of TACE on QoL of HCC patients. PMID:27143815

  5. New advances in hepatocellular carcinoma.

    PubMed

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-03-28

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

  6. New advances in hepatocellular carcinoma

    PubMed Central

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-01-01

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

  7. Strengthening the Fight Against HCC.

    PubMed

    Berlin, Joey

    2016-03-01

    Primary care physicians have the resources they need to screen for a cancer that's growing in prevalence and hitting Texas harder than almost any other state. What's missing is awareness of what physicians can do to facilitate early detection of hepatocellular carcinoma (HCC), the most common form of primary liver cancer. That's what a TMA Foundation-funded workgroup, Texas HepCA, is trying to change as HCC rates in the state continue to rise, particularly among the Hispanic population in South Texas.

  8. Identifying the optimal criteria of radiotherapeutic parameters for patients with unresectable locally advanced hepatocellular carcinoma.

    PubMed

    Son, Seok Hyun; Jang, Hong Seok; Sung, Soo Yoon; Kang, Hye Jin; Lee, Sojung; Kay, Chul Seung

    2015-12-01

    The purpose of this study is to identify the optimal criteria of the radiotherapeutic parameters in patients with unresectable locally advanced hepatocellular carcinoma (HCC). 103 patients were enrolled in this study. All patients received RT delivered using the TomoTherapy Hi-Art system between March 2006 and February 2012. We evaluated the planning target volume (PTV), total dose (Gy10), and NTNL-V(BED20) (non-target normal liver volume receiving more than a biologically effective dose of 20 Gy8) as significant radiotherapeutic parameters associated with hepatic function deterioration and local progression-free survival (PFS). A PTV of 279 cm3 or 304 cm3, a total dose of 60 Gy10, and a NTNL-V(BED20) of 40.8% were identified as the optimal cut-off values of radiotherapeutic parameters to prevent hepatic function deterioration and prolong local PFS. Based on these findings, patients were divided in a favorable and an unfavorable prognosis group. The differences in median local PFS, overall survival, and incidence of deteriorated hepatic function between the two groups were 11.2 months, 11.1 months, and 71.7%, respectively (p < 0.001 in each case). In conclusion, we suggest that the optimal criteria of the radiotherapeutic parameters for patients with unresectable locally advanced HCC are: PTV ≤ 279 cm3, total dose > 60 Gy10, and NTNL-V(BED20) ≤ 40.8%. PMID:26510905

  9. Efficacy, Safety, and Biomarkers of Single-Agent Bevacizumab Therapy in Patients with Advanced Hepatocellular Carcinoma

    PubMed Central

    Malka, David; Bourredjem, Abderrahmane; Dromain, Clarisse; Baey, Charlotte; Jacques, Nathalie; Pignon, Jean-Pierre; Vimond, Nadege; Bouvet-Forteau, Nathalie; De Baere, Thierry; Ducreux, Michel; Farace, Françoise

    2012-01-01

    Objective. Hepatocellular carcinoma (HCC) is a highly vascularized tumor in which neoangiogenesis contributes to growth and metastasis. We assessed the safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced HCC. Methods. In this phase II trial, eligible patients received bevacizumab, 5 mg/kg or 10 mg/kg every 2 weeks. The disease-control rate at 16 weeks (16W-DCR) was the primary endpoint. Circulating endothelial cells (CECs) and plasma cytokines and angiogenic factors (CAFs) were measured at baseline and throughout treatment. Results. The 16W-DCR was 42% (95% confidence interval, 27%–57%). Six of the 43 patients who received bevacizumab achieved a partial response (objective response rate [ORR], 14%). Grade 3–4 asthenia, hemorrhage, and aminotransferase elevation occurred in five (12%), three (7%), and three (7%) patients, respectively. During treatment, placental growth factor markedly increased, whereas vascular endothelial growth factor (VEGF)-A dramatically decreased (p < .0001); soluble VEGF receptor-2 (p < .0001) and CECs (p = .03) transiently increased on day 3. High and increased CEC counts at day 15 were associated with the ORR (p = .04) and the 16W-DCR (p = .02), respectively. Lower interleukin (IL)-8 levels at baseline (p = .01) and throughout treatment (p ≤ .04) were associated with the 16W-DCR. High baseline IL-8 and IL-6 levels predicted shorter progression-free and overall survival times (p ≤ .04). Conclusion. Bevacizumab is active and well tolerated in patients with advanced HCC. The clinical value of CECs, IL-6, and IL-8 warrants further investigation. PMID:22707516

  10. Quantification of dynamic contrast-enhanced ultrasound in HCC: prediction of response to a new combination therapy of sorafenib and panobinostat in advanced hepatocellular carcinoma.

    PubMed

    Knieling, Ferdinand; Waldner, Maximilian J; Goertz, Ruediger S; Strobel, Deike

    2012-01-01

    Here, we report the case of a patient, who showed an antitumour response to a new combination therapy of sorafenib and the histon deacetylase inhibitor panobinostat (LBH-589). D-CEUS (Dynamic contrast-enhanced ultrasonography) was able to predict response to the new therapy regime and may be an interesting tool in the early evaluation of response to therapy. It might be especially useful to differentiate between responders and non-responders of new-targeted pharmaceuticals like multikinase inhibitors in hepatocellular carcinomas. PMID:23257272

  11. Comparison of hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and combined HCC-CC (CHC) with each other based on microarray dataset.

    PubMed

    Wang, Lishan; Zang, Weidong; Xie, Dongli; Ji, Weidong; Pan, Yaosheng; Li, Zhiqiang; Shen, Jiawei; Shi, Yongyong

    2013-06-01

    Liver carcinomas have been classified into three types: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and combined HCC-CC (CHC). We aim to find the common and different characteristic of these three types of liver cancer. The gene expression profiling of HCC, CC, and CHC were compared with each other, and enrichment pathways and processes in these three liver cancers were also identified. Using GSE15765 datasets downloaded from NCBI GEO database, the gene expression profiling of HCC, CC, and CHC were compared with each other (HCC compared with CC, HCC compared with CHC, and CC compared with HCC). Then, the differentially expressed genes (DEGs) were identified in these three groups respectively, and three PPI networks were constructed for DEGs in each group. Subsequently, the clusters in these networks were identified and further analyzed by ClusterONE and MCODE. Finally, gene set enrichment analysis enrichment analysis was performed to illustrate altered pathways and processes for each type of liver cancer. A total of 112, 530, and 64 DEGs were identified in three groups, respectively, and three PPI networks were constructed respectively for the corresponding group. Through the cluster analysis, we found some new differential marker genes for distinguishing the difference between these three types of liver cancer. We also indicated that we can distinguish HCC with CC through altered pathways and processes. Our findings develop new biomarkers for categorizing the primary liver cancer and may improve patient prognosis of these cancers. However, further validation is required since our results were based on microarray data derived from a small sample size.

  12. Rapid Virological Response After Early Treatment with a Combined Therapy of Ledipasvir and Sofosbuvir in HCV Genotype 4 After Living Donor Liver Transplantation in a HCC Downstaged Patient: Case Report and Review of the Literature.

    PubMed

    Obed, Aiman; Bashir, Abdalla; Jarrad, Anwar

    2016-09-20

    BACKGROUND Hepatitis C virus (HCV) genotype 4 (GT-4) is widespread in the Middle East, where it is responsible for the majority of HCV infections. It shows moderate treatment response rates when compared to other genotypes in the current era of interferon-based regimens. However, in the era of direct acting antiviral (DAA) drugs, its response is at least as good as observed for HCV genotypes 1-3. CASE REPORT We present a case of a 44-year-old patient with HCV cirrhosis. Since 2007, he has been treated for HCV infection with multiple ineffective regimens of interferon (INF) and ribavirin. A liver biopsy in 2010 revealed stage 5-6/6 indicating cirrhosis, which was later complicated by the occurrence of portal vein thrombosis and a large hepatocellular carcinoma (HCC) (maximum diameter 9 cm). The patient was successfully treated with sorafenib, transcatheter arterial chemoembolization (TACE), and radiofrequency ablation. After four TACE procedures, the patient's AFP (alpha-fetoprotein) decreased remarkably and almost normalized. The HCC disappeared radiologically as shown by triple phase CT, MRI with contrast, and PET-CT. He successfully underwent a living donor liver transplantation. Four weeks post liver transplantation he started treatment with sorafenib, and switched from tacrolimus to Rapamune (sirolimus) as immunosuppressant therapy. Ten weeks after liver transplantation, HCV treatment was introduced along with ledipasvir and sofosbuvir due to his increasing liver enzyme levels. A rapid viral response was achieved after 14 days. In total, the patient received 12 weeks of this treatment. CONCLUSIONS This case study might be of significance in informing early management and personalized treatment of patients with recurrent HCV GT-4 infections after liver transplantation, even in complex clinical surroundings.

  13. Rapid Virological Response After Early Treatment with a Combined Therapy of Ledipasvir and Sofosbuvir in HCV Genotype 4 After Living Donor Liver Transplantation in a HCC Downstaged Patient: Case Report and Review of the Literature.

    PubMed

    Obed, Aiman; Bashir, Abdalla; Jarrad, Anwar

    2016-01-01

    BACKGROUND Hepatitis C virus (HCV) genotype 4 (GT-4) is widespread in the Middle East, where it is responsible for the majority of HCV infections. It shows moderate treatment response rates when compared to other genotypes in the current era of interferon-based regimens. However, in the era of direct acting antiviral (DAA) drugs, its response is at least as good as observed for HCV genotypes 1-3. CASE REPORT We present a case of a 44-year-old patient with HCV cirrhosis. Since 2007, he has been treated for HCV infection with multiple ineffective regimens of interferon (INF) and ribavirin. A liver biopsy in 2010 revealed stage 5-6/6 indicating cirrhosis, which was later complicated by the occurrence of portal vein thrombosis and a large hepatocellular carcinoma (HCC) (maximum diameter 9 cm). The patient was successfully treated with sorafenib, transcatheter arterial chemoembolization (TACE), and radiofrequency ablation. After four TACE procedures, the patient's AFP (alpha-fetoprotein) decreased remarkably and almost normalized. The HCC disappeared radiologically as shown by triple phase CT, MRI with contrast, and PET-CT. He successfully underwent a living donor liver transplantation. Four weeks post liver transplantation he started treatment with sorafenib, and switched from tacrolimus to Rapamune (sirolimus) as immunosuppressant therapy. Ten weeks after liver transplantation, HCV treatment was introduced along with ledipasvir and sofosbuvir due to his increasing liver enzyme levels. A rapid viral response was achieved after 14 days. In total, the patient received 12 weeks of this treatment. CONCLUSIONS This case study might be of significance in informing early management and personalized treatment of patients with recurrent HCV GT-4 infections after liver transplantation, even in complex clinical surroundings. PMID:27647003

  14. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma.

    PubMed

    Kang, Tae Wook; Rhim, Hyunchul

    2015-09-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC.

  15. Radioembolization After Portal Vein Embolization in a Patient with Multifocal Hepatocellular Carcinoma

    SciTech Connect

    Burgmans, Mark C. Irani, Farah G. Chan, Wan Ying Teo, Terence K.; Kao, Yung Hsiang Goh, Anthony S.W.; Chow, Pierce K.; Lo, Richard H.

    2012-12-15

    Radioembolization is an effective locoregional therapy for patients with intermediate or advanced stage hepatocellular carcinoma (HCC). It has been shown that radioembolization is safe in patients with portal vein thrombosis. This case report describes safe radioembolization after portal vein embolization in a patient with multifocal HCC.

  16. Human hepatocellular carcinoma cell-specific miRNAs reveal the differential expression of miR-24 and miR-27a in cirrhotic/non-cirrhotic HCC

    PubMed Central

    SALVI, ALESSANDRO; ABENI, EDOARDO; PORTOLANI, NAZARIO; BARLATI, SERGIO; DE PETRO, GIUSEPPINA

    2013-01-01

    microRNAs (miRs) are 18–25 nucleotide non-coding RNAs that regulate gene expression in several physiological and pathological conditions. To gather more knowledge on microRNAs in human hepatocellular carcinoma (HCC) we generated a small RNA library in the human HCC cell line HA22T/VGH by cloning and sequencing the cDNA obtained following the size selection of 18–24 nucleotide RNAs. We determined the expression levels of the most frequently cloned microRNAs by qPCR in HCC tissues and in their peritumoral counterparts from biopsy specimens of 41 HCC patients. The most frequently cloned miRs were miR-24, miR-27a and miR-21, and their expression levels in human HCC tissues indicate that these miRs were dysregulated in HCC. We showed that miR-24 and miR-27a were significantly downregulated in HCCs from cirrhotic liver tissues in comparison to those from non-cirrhotic liver tissues. In cirrhotic HCCs the downregulation of miR-24 was correlated with poorer prognosis in patients with HBV and HCV virus infections. miR-21 was generally upregulated in HCC tissues versus the corresponding peritu-moral tissues, particularly in non-cirrhotic HCC. Furthermore, by sequence alignment we identified the human miR orthologue of Mus musculus miR-1199 not yet annotated. Our results outline the differential expression of miRs in cirrhotic and non-cirrhotic HCCs, thereby contributing to advances in the discovery and validation of novel molecular biomarkers of HCC progression. PMID:23229173

  17. Surgical and Locoregional Therapy of HCC: TACE

    PubMed Central

    Tsurusaki, Masakatsu; Murakami, Takamichi

    2015-01-01

    Transcatheter arterial chemoembolization (TACE) is performed worldwide for patients with intermediate-stage hepatocellular carcinoma (HCC). TACE has produced survival advantages in two randomized controlled trials and a meta-analysis, and is currently the mainstay of treatment for this stage of HCC. However, there are currently no global guidelines regarding the dose, choice or combination of cytotoxic agents for TACE; therefore, it is difficult to compare data from different TACE studies. In Japan, most of the TACE procedures have been based on iodized oil as conventional TACE, utilizing the microembolic and drug-carrying characteristic of iodized oil. Superselective TACE with lipiodol is the primary TACE procedure that has reported satisfactory levels of local control associated with a lower risk of complications. Conversely, TACE performed using drug-eluting beads has been widely used in western countries, and this has shown similar tumor response and median survival compared to conventional TACE. Moreover, the combination of TACE and molecular targeted agents is now ongoing to evaluate the synergistic effect. In this review, the indication, technical issues, and complications of TACE are reviewed. PMID:26675172

  18. Next big threat for Pakistan Hepatocellular Carcinoma (HCC).

    PubMed

    Parkash, Om; Hamid, Saeed

    2016-06-01

    In our country, world hepatitis day (28th May 2013) was observed as a liver cancer day to draw global attention on the global health menace caused by Hepatocellular carcinoma (HCC). This is the right time to write a review article to apprise the nation of this growing burden of HCC caused most commonly by viruses in our country. Pakistan is also recognized as one of the countries of the world where hepatitis C virus (HCV) is endemic. Recent large national surveys suggest an overall HCV prevalence of 4.8% and that of HBV as 2.5%. There are however communities where the sero-prevalence of HCV can be as high as 23%. No wonder that chronic liver disease is the fifth most common reason for morbidity and mortality in the country and Pakistan has been perhaps accurately called a "cirrhotic state". Hence majority of such patients are at risk of developing HCC.

  19. Next big threat for Pakistan Hepatocellular Carcinoma (HCC).

    PubMed

    Parkash, Om; Hamid, Saeed

    2016-06-01

    In our country, world hepatitis day (28th May 2013) was observed as a liver cancer day to draw global attention on the global health menace caused by Hepatocellular carcinoma (HCC). This is the right time to write a review article to apprise the nation of this growing burden of HCC caused most commonly by viruses in our country. Pakistan is also recognized as one of the countries of the world where hepatitis C virus (HCV) is endemic. Recent large national surveys suggest an overall HCV prevalence of 4.8% and that of HBV as 2.5%. There are however communities where the sero-prevalence of HCV can be as high as 23%. No wonder that chronic liver disease is the fifth most common reason for morbidity and mortality in the country and Pakistan has been perhaps accurately called a "cirrhotic state". Hence majority of such patients are at risk of developing HCC. PMID:27339578

  20. Recent advance in patient monitoring

    PubMed Central

    2010-01-01

    Recent advance in technology has developed a lot of new aspects of clinical monitoring. We can monitor sedation levels during anesthesia using various electroencephalographic (EEG) indices, while it is still not useful for anesthesia depth monitoring. Some attempts are made to monitor the changes in sympathetic nerve activity as one of the indicators of stress, pain/analgesia, or anesthesia. To know the balance of sympathetic and parasympathetic activity, heart rate or blood pressure variability is investigated. For trend of cardiac output, low invasive monitors have been investigated. Improvement of ultrasound enables us to see cardiac structure and function continuously and clearer, increases success rate and decreases complication of central venous puncture and various kinds of nerve blocks. Without inserting an arterial catheter, trends of arterial oxygen tension or carbon dioxide tension can be monitored. Indirect visualization of the airway decreases difficult intubation and makes it easier to teach tracheal intubation. The changes in blood volume can be speculated non-invasively. Cerebral perfusion and metabolism are not ordinary monitored yet, but some studies show their usefulness in management of critically ill. This review introduces recent advances in various monitors used in anesthesia and critical care including some studies of the author, especially focused on EEG and cardiac output. However, the most important is that these new monitors are not almighty but should be used adequately in a limited situation where their meaning is confirmed. PMID:20877698

  1. Aspirin in combination with TACE in treatment of unresectable HCC: a matched-pairs analysis

    PubMed Central

    Li, Jing-Huan; Wang, Yan; Xie, Xiao-Ying; Yin, Xin; Zhang, Lan; Chen, Rong-Xin; Ren, Zheng-Gang

    2016-01-01

    Transarterial chemoembolization (TACE) is the principal therapy for unresectable hepatocellular carcinoma (HCC). However, its efficacy is currently limited owing to tumor progression or treatment failure. It has been shown that aspirin reduces the incidence of multiple malignant tumors including HCC and plays a synergistic role with chemotherapy in the treatment of colon cancer. Therefore, we aimed to investigate the adjuvant effect of aspirin on patients with unresectable HCC who underwent TACE therapy. A retrospective matched-pairs analysis was performed to evaluate the efficacy of aspirin in combination with TACE therapy. A total of 120 patients with HCC, including 60 patients treated with aspirin for treatment of cardiovascular disease, transient ischemic attack, and arthritis, and 60 paired matching HCC patients without aspirin treatment in the same period, were enrolled. Compared with non-aspirin users, patients treated with aspirin showed improved OS (P = 0.050). Specifically, patients treated with a full dose of aspirin showed prolonged OS (P = 0.027), which was an independent factor associated with OS in multivariate analysis (hazard ratio 0.498, 95% confidence interval 0.280-0.888, P = 0.018). Aspirin in combination with TACE might improve OS in patients with unresectable HCC. Thus, the impact of aspirin on patients with HCC warrants further investigation prospectively. PMID:27725915

  2. Analgesia for patients with advanced disease: 2

    PubMed Central

    Hall, E; Sykes, N

    2004-01-01

    The first article in this series explored epidemiology and patterns of pain in advanced disease, non-pharmacological treatments, and the use of opioids to manage pain. This second article examines the use of non-opioid drugs and anaesthetic interventions for pain relief in advanced disease. It also discusses an approach to managing analgesia in dying patients and finally looks at future developments. PMID:15082837

  3. The Efficacy of Continued Sorafenib Treatment after Radiologic Confirmation of Progressive Disease in Patients with Advanced Hepatocellular Carcinoma

    PubMed Central

    2016-01-01

    Background Whether radiologically detected progressive disease (PD) is an accurate metric for discontinuing sorafenib treatment in patients with hepatocellular carcinoma (HCC) is unclear. We investigated the efficacy of sorafenib treatment after radiologic confirmation of PD in patients with advanced HCC. Methods We retrospectively analyzed HCC patients treated with sorafenib at Kyushu Medical Center. Six of the 92 patients with radiologically confirmed PD were excluded because they were classified as Child-Pugh C or had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3; 86 patients were ultimately enrolled. Results Among the 86 patients, 47 continued sorafenib treatment after radiologic confirmation of PD (the continuous group), whereas 39 did not (the discontinuous group). The median survival time (MST) in the continuous group after confirmation was 12.9 months compared with 4.5 months in the discontinuous group (p <0.01). The time to progression in the continuous group after confirmation was 2.6 months compared with 1.4 months in the discontinuous group (p <0.01); it was 4.2 months and 2.1 months in patients who had received sorafenib ≥4 months and <4 months, respectively, before confirmation (p = 0.03). In these subgroups, the post-PD MST was 16.7 months and 9.6 months, respectively (p < 0.01). Independent predictors of overall survival after radiologic detection of PD were (hazard ratio, confidence interval): ECOG PS <2 (0.290, 0.107–0.880), Barcelona Clinical Liver Cancer stage B (0.146, 0.047–0.457), serum α-fetoprotein level ≥400 ng/mL (2.801, 1.355–5.691), and post-PD sorafenib administration (0.279, 0.150–0.510). Conclusion Continuing sorafenib treatment after radiologic confirmation of PD increased survival in patients with advanced HCC. Therefore, radiologically detected PD is not a metric for discontinuation of sorafenib treatment in such patients. PMID:26745625

  4. Transcriptomic and Proteomic Investigation of HSP90A as a Potential Biomarker for HCC

    PubMed Central

    Zhou, Yi; Deng, Xiaofang; Zang, Ning; Li, Hongtao; Li, Gang; Li, Cuiping; He, Min

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer-related death in adults. Despite recent advances in the clinical technologies, the screening and diagnostic efficacy for HCC remains poor. Discovering novel and reliable HCC biomarkers is urgently needed. Material/Methods We performed a transcriptome-proteome integrated assay to track the possible HCC biomarkers from the process of HCC-derived gene expression in malignant cells to its protein product released into serum. Results Our screening results demonstrated that heat shock protein 90A (HSP90A), which participates in the PI3K-Akt signaling pathway and many other cancer-related pathways, warrants further investigation. The expression of HSP90A was increased in the HCC cells, serum, and tissues. Immunohistochemistry analysis on 76 clinical tissue samples also suggested the relevance between HSP90A expression and HCC metastatic behavior. Conclusions These findings suggest a role for HSP90A in HCC pathogenesis and the potential use of HSP90A for the screening and diagnosis of this malignancy. PMID:26704341

  5. Challenges of incorporating gene expression data to predict HCC prognosis in the age of systems biology

    PubMed Central

    Du, Yan; Cao, Guang-Wen

    2012-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. The recurrence of HCC after curative treatments is currently a major hurdle. Identification of subsets of patients with distinct prognosis provides an opportunity to tailor therapeutic approaches as well as to select the patients with specific sub-phenotypes for targeted therapy. Thus, the development of gene expression profiles to improve the prediction of HCC prognosis is important for HCC management. Although several gene signatures have been evaluated for the prediction of HCC prognosis, there is no consensus on the predictive power of these signatures. Using systematic approaches to evaluate these signatures and combine them with clinicopathologic information may provide more accurate prediction of HCC prognosis. Recently, Villanueva et al[13] developed a composite prognostic model incorporating gene expression patterns in both tumor and adjacent tissues to predict HCC recurrence. In this commentary, we summarize the current progress in using gene signatures to predict HCC prognosis, and discuss the importance, existing issues and future research directions in this field. PMID:22912544

  6. Plasma DCLK1 is a marker of hepatocellular carcinoma (HCC): Targeting DCLK1 prevents HCC tumor xenograft growth via a microRNA-dependent mechanism

    PubMed Central

    May, Randal; Qu, Dongfeng; Ali, Naushad; Fazili, Javid; Weygant, Nathaniel; Chandrakesan, Parthasarathy; Ding, Kai; Lightfoot, Stanley A.; Houchen, Courtney W.

    2015-01-01

    Tumor stem cell marker Doublecortin-like kinase1 (DCLK1) is upregulated in several solid tumors. The role of DCLK1 in hepatocellular carcinoma (HCC) is unclear. We immunostained tissues from human livers with HCC, cirrhosis controls (CC), and non-cirrhosis controls (NCC) for DCLK1. Western blot and ELISA analyses for DCLK1 were performed with stored plasma samples. We observed increased immunoreactive DCLK1 in epithelia and stroma in HCC and CCs compared with NCCs, and observed a marked increase in plasma DCLK1 from patients with HCC compared with CC and NCC. Analysis of the Cancer Genome Atlas’ HCC dataset revealed that DCLK1 is overexpressed in HCC tumors relative to adjacent normal tissues. High DCLK1-expressing cells had more epithelial-mesenchymal transition (EMT). Various tumor suppressor miRNAs were also downregulated in HCC tumors. We evaluated the effects of DCLK1 knockdown on Huh7.5-derived tumor xenograft growth. This was associated with growth arrest and a marked downregulation of cMYC, and EMT transcription factors ZEB1, ZEB2, SNAIL, and SLUG via let-7a and miR-200 miRNA-dependent mechanisms. Furthermore, upregulation of miR-143/145, a corresponding decrease in pluripotency factors OCT4, NANOG, KLF4, and LIN28, and a reduction of let-7a, miR-143/145, and miR-200-specific luciferase activity was observed. These findings suggest that the detection of elevated plasma DCLK1 may provide a cost-effective, less invasive tool for confirmation of clinical signs of cirrhosis, and a potential companion diagnostic marker for patients with cirrhosis and HCC. Our results support evaluating DCLK1 as a biomarker for detection and as a therapeutic target for eradicating HCC. PMID:26468984

  7. Asian consensus workshop report: expert consensus guideline for the management of intermediate and advanced hepatocellular carcinoma in Asia.

    PubMed

    Han, Kwang-Hyub; Kudo, Masatochi; Ye, Sheng-Long; Choi, Jong Young; Poon, Roonni Tung-Ping; Seong, Jinsil; Park, Joong-Won; Ichida, Takafumi; Chung, Jin Wook; Chow, Pierce; Cheng, Ann-Lii

    2011-01-01

    Hepatocellular carcinoma (HCC) is a highly prevalent disease in many Asian countries, accounting for 80% of victims worldwide. Screening programs improve the detection of early HCC and have a positive impact on survival, but the majority of HCC patients in Asia still present with advanced stage disease. The treatment outcomes of HCC are affected by multiple variables, including liver function, performance status of the patient, and tumor stage. Therefore, it is not easy to apply a multidisciplinary therapeutic approach for optimal management. At present, limited numbers of HCC patients are eligible for curative therapies such as surgery or ablation in Asia. Therefore, most patients are eligible for only palliative treatments. For optimal management, the treatment choice is guided by staging systems and treatment guidelines. Numerous staging systems have been proposed and treatment guidelines vary by region. According to the Barcelona Clinic Liver Cancer (BCLC) guideline based on evidence from randomized clinical trials, only transarterial chemoembolization (TACE) is recommended for intermediate stage HCC and sorafenib for advanced stage HCC. However, treatment guidelines from Asian countries have adopted several other therapeutic modalities such as a surgical approach, hepatic arterial infusion chemotherapy, external radiation, and their combinations based on clinical experiences for intermediate and advanced stage HCC. Although TACE is the main therapeutic modality in the intermediate stage, overall therapeutic outcomes depend on the tumor size. In the advanced stage, the prognosis depends on the tumor status, e.g. major vessel invasion or extrahepatic spread. Thus, a new staging system representing prognoses suitable for Asian HCC patients and a corresponding optimal treatment algorithm should be further investigated using evidence-based data, which will finally bring about an Asian consensus for the management of intermediate and advanced stage HCC.

  8. Hepatocellular Carcinoma in the Pediatric Population: A Population Based Clinical Outcomes Study Involving 257 Patients from the Surveillance, Epidemiology, and End Result (SEER) Database (1973-2011).

    PubMed

    Lau, Christine S M; Mahendraraj, Krishnaraj; Chamberlain, Ronald S

    2015-01-01

    Introduction. Hepatocellular carcinoma (HCC) is a rare pediatric cancer accounting for 0.5% of all pediatric malignancies. This study examines a large cohort of HCC patients in an effort to define the factors impacting clinical outcomes in pediatric HCC patients compared to adults. Methods. Demographic and clinical data on 63,771 HCC patients (257 pediatric patients ≤ 19 and 63,514 adult patients age ≥ 20) were abstracted from the SEER database (1973-2011). Results. HCC was more common among males (59.5% pediatric and 75.1% adults) and Caucasians (50.4% and 50.5%), p < 0.05. Children more often presented with fibrolamellar variant HCC (24.1% versus 0.3%, p = 0.71) and advanced HCC, including distant disease (33.1% versus 20.8%, p < 0.001), and tumors > 4 cm in size (79.6% versus 62.0%, p = 0.02). Pediatric HCC patients undergoing surgery (13.107 versus 8.324 years, p < 0.001) had longer survival than adult HCC patients. Overall mortality was lower (65.8% versus 82.0%, p < 0.001) in the pediatric HCC group. Conclusion. HCC is a rare pediatric malignancy that presents most often as an advanced tumor, >4 cm in Caucasian males. Children with HCC achieve significantly longer mean overall survival compared to adults with HCC, primarily attributable to the more favorable fibrolamellar histologic variant, and more aggressive surgical intervention, which significantly improves survival.

  9. Hepatocellular Carcinoma in the Pediatric Population: A Population Based Clinical Outcomes Study Involving 257 Patients from the Surveillance, Epidemiology, and End Result (SEER) Database (1973–2011)

    PubMed Central

    Lau, Christine S. M.; Mahendraraj, Krishnaraj; Chamberlain, Ronald S.

    2015-01-01

    Introduction. Hepatocellular carcinoma (HCC) is a rare pediatric cancer accounting for 0.5% of all pediatric malignancies. This study examines a large cohort of HCC patients in an effort to define the factors impacting clinical outcomes in pediatric HCC patients compared to adults. Methods. Demographic and clinical data on 63,771 HCC patients (257 pediatric patients ≤ 19 and 63,514 adult patients age ≥ 20) were abstracted from the SEER database (1973–2011). Results. HCC was more common among males (59.5% pediatric and 75.1% adults) and Caucasians (50.4% and 50.5%), p < 0.05. Children more often presented with fibrolamellar variant HCC (24.1% versus 0.3%, p = 0.71) and advanced HCC, including distant disease (33.1% versus 20.8%, p < 0.001), and tumors > 4 cm in size (79.6% versus 62.0%, p = 0.02). Pediatric HCC patients undergoing surgery (13.107 versus 8.324 years, p < 0.001) had longer survival than adult HCC patients. Overall mortality was lower (65.8% versus 82.0%, p < 0.001) in the pediatric HCC group. Conclusion. HCC is a rare pediatric malignancy that presents most often as an advanced tumor, >4 cm in Caucasian males. Children with HCC achieve significantly longer mean overall survival compared to adults with HCC, primarily attributable to the more favorable fibrolamellar histologic variant, and more aggressive surgical intervention, which significantly improves survival. PMID:26663981

  10. A20 inhibits the motility of HCC cells induced by TNF-α.

    PubMed

    Wang, Xianteng; Ma, Chao; Zong, Zhaoyun; Xiao, Ying; Li, Na; Guo, Chun; Zhang, Lining; Shi, Yongyu

    2016-03-22

    Metastasis of hepatocellular carcinoma (HCC) can be facilitated by TNF-α, a prototypical inflammatory cytokine in the HCC microenvironment. A20 is a negative regulator of NF-κB signaling pathway. In the present study we ask whether A20 plays a role in HCC metastasis. We found that A20 expression was downregulated in the invasive cells of microvascular invasions (MVI) compared with the noninvasive cells in 89 tissue samples from patients with HCC by immunochemistry methods. Overexpression of A20 in HCC cell lines inhibited their motility induced by TNF-α. Furthermore, the overexpression of A20 inhibited epithelial-mesenchymal transition (EMT), FAK activation and RAC1 activity. By contrast, knockdown of A20 in one HCC cell line results in the converse. In addition, the overexpression of A20 restrained the formation of MVI in HCC xenograft in nude mice treated with TNF-α. All the results suggested that A20 functioned as a negative regulator in motility of HCC cells induced by TNF-α. PMID:26909601

  11. A20 inhibits the motility of HCC cells induced by TNF-α

    PubMed Central

    Xiao, Ying; Li, Na; Guo, Chun; Zhang, Lining; Shi, Yongyu

    2016-01-01

    Metastasis of hepatocellular carcinoma (HCC) can be facilitated by TNF-α, a prototypical inflammatory cytokine in the HCC microenvironment. A20 is a negative regulator of NF-κB signaling pathway. In the present study we ask whether A20 plays a role in HCC metastasis. We found that A20 expression was downregulated in the invasive cells of microvascular invasions (MVI) compared with the noninvasive cells in 89 tissue samples from patients with HCC by immunochemistry methods. Overexpression of A20 in HCC cell lines inhibited their motility induced by TNF-α. Furthermore, the overexpression of A20 inhibited epithelial-mesenchymal transition (EMT), FAK activation and RAC1 activity. By contrast, knockdown of A20 in one HCC cell line results in the converse. In addition, the overexpression of A20 restrained the formation of MVI in HCC xenograft in nude mice treated with TNF-α. All the results suggested that A20 functioned as a negative regulator in motility of HCC cells induced by TNF-α. PMID:26909601

  12. Early sorafenib-related adverse events predict therapy response of TACE plus sorafenib: A multicenter clinical study of 606 HCC patients.

    PubMed

    Zhao, Yan; Li, Hailiang; Bai, Wei; Liu, Jueshi; Lv, Weifu; Sahu, Sonia; Guan, Sheng; Qin, Xiao; Wang, Wenhui; Ren, Weixin; Mu, Wei; Guo, Weidong; Gu, Shanzhi; Ma, Yilong; Yin, Zhanxin; Guo, Wengang; Wang, Wenjun; Wang, Yongji; Duran, Rafael; Fan, Daiming; Zhang, Zhuoli; Han, Guohong

    2016-08-15

    The purpose of our study was to test the hypothesis that sorafenib-related dermatologic adverse events (AEs) as an early biomarker can predict the long-term outcomes following the combination therapy of transarterial chemoembolization (TACE) plus sorafenib (TACE-S). The intermediate-stage hepatocellular carcinoma patients who received either TACE-S or TACE-alone treatment were consecutively included into analysis. In the TACE-S group, patients with ≥ grade 2 dermatologic AEs within the first month of sorafenib initiation were defined as responders; whereas those with < grade 2 were defined as nonresponders. In the TACE-S group, the median overall survival (OS) of the responders was significantly longer than that of nonresponders (28.9 months vs. 16.8 months, respectively; p = 0.004). Multivariate analysis demonstrated that nonresponders were significantly associated with an increased risk of death compared with responders (HR = 1.9; 95% confidence Interval-CI: 1.3-2.7; p = 0.001). The survival analysis showed that the median OS was 27.9 months (95% CI: 25.0-30.8) among responders treated with TACE-S vs.18.3 months (95% CI: 14.5-22.1) among those who received TACE-alone (p = 0.046). The median time to progression was 13.1 months (95% CI: 4.4-21.8) in the TACE-S group, a duration that was significantly longer than that in the TACE-alone group [5 months (95% CI: 6.4-13.3), p = 0.014]. This study demonstrated that sorafenib-related dermatologic AEs are clinical biomarkers to identify responders from all of the patients for TACE-S therapy. Sorafenib-related dermatologic AEs, clinical biomarkers, can predict the efficacy of TACE-S in future randomized controlled trials.

  13. Advances in Management of Hepatocellular Carcinoma.

    PubMed

    Intaraprasong, Pongphob; Siramolpiwat, Sith; Vilaichone, Ratha-Korn

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most frequent type of malignant liver tumor and a high impact health problem worldwide. The prevalence of HCC is particularly high in many Asian and African countries. Some HCC patients have no symptoms prior to diagnosis and many of them therefore present at late stage and have a grave prognosis. The well-established causes of HCC are chronic hepatitis B virus (HBV) or chronic hepatitis C virus (HCV) infection or alcoholic cirrhosis and nonalcoholic steatohepatitis. The Barcelona Clinic Liver Cancer (BCLC) Staging System remains the most widely used for HCC management guidelines. To date, the treatments for HCC are still very challenging for physicians due to limited resources in many parts of the world, but many options of management have been proposed, including hepatic resection, liver transplantation, ablative therapy, chemoembolization, sora nib and best supportive care. This review article describes the current evidence-based management of HCC with focus on early to advance stages that impact on patient overall survival. PMID:27644603

  14. How to Improve Therapeutic Ratio in Radiotherapy of HCC

    PubMed Central

    Tsai, Chiao-Ling; Hsu, Feng-Ming; Cheng, Jason Chia-Hsien

    2016-01-01

    Background During the past two decades, external-beam radiation technology has substantially changed from traditional two-dimensional to conformal three-dimensional to intensity-modulated planning and stereotactic body radiotherapy (SBRT). Summary Modern techniques of radiotherapy (RT) are highly focused and capable of delivering an ablative dose to targeted hepatocellular carcinoma (HCC) tumors. SBRT is an option for selected patients with limited tumor volume and non-eligibility for other invasive treatments. Moreover, RT combined with a radiation sensitizer (RS) to increase the therapeutic ratio has shown promising results in select studies, prompting further investigation of this combination. With the undetermined role of RT in treatment guidelines and variation in patterns of treatment failure after RT in patient with HCC, useful biomarkers to guide RT decision-making and selection of patients are needed and emerging. Key Message The objective of this review is to summarize the current RS with SBRT schemes and biomarkers for patient selection used to maximize the effect of RT on HCC. PMID:27493896

  15. Sorafenib for the treatment of advanced hepatocellular carcinoma with extrahepatic metastasis: a prospective multicenter cohort study.

    PubMed

    Nakano, Masahito; Tanaka, Masatoshi; Kuromatsu, Ryoko; Nagamatsu, Hiroaki; Tajiri, Nobuyoshi; Satani, Manabu; Niizeki, Takashi; Aino, Hajime; Okamura, Shusuke; Iwamoto, Hideki; Shimose, Shigeo; Shirono, Tomotake; Koga, Hironori; Torimura, Takuji

    2015-12-01

    Sorafenib, an oral multikinase inhibitor, is approved for advanced hepatocellular carcinoma (HCC) treatment. However, its therapeutic effect in advanced HCC patients with extrahepatic metastasis remains uncertain. This study aimed to prospectively assess the efficacy, safety, and survival risk factors and evaluate the prognostic impact of sorafenib treatment in advanced HCC patients with or without extrahepatic metastasis. Between May 2009 and March 2014, 312 consecutive advanced HCC patients who received sorafenib were enrolled in this study. We evaluated their characteristics and compared the clinical outcomes of those with and without extrahepatic metastasis. Of the enrolled patients, 245 (81%) received sorafenib treatment for more than 1 month, with a median duration of 3.6 months. Eighteen patients demonstrated partial response to sorafenib therapy, 127 had stable disease, and 134 had progressive disease at the first radiologic assessment. The median survival time (MST) and progression-free survival (PFS) were 10.3 and 3.6 months, respectively. Multivariate analysis identified gender, Child-Pugh class, baseline serum des-gamma-carboxy prothrombin level, and treatment duration as independent risk factors for survival. Extrahepatic metastasis was detected in 178 patients. However, the MST, PFS, and therapeutic effect were comparable between patients with and without extrahepatic metastasis. The independent risk factors for decreased overall survival in patients with extrahepatic metastasis were similar to those affecting all patients. Our results indicated that sorafenib could be administered for hepatic reserve and as long-term treatment for advanced HCC patients regardless of their extrahepatic metastasis status.

  16. Diabetes Drug Victoza Might Not Help Advanced Heart Failure Patients

    MedlinePlus

    ... html Diabetes Drug Victoza Might Not Help Advanced Heart Failure Patients Study participants may have been too sick ... to improve heart function in patients with advanced heart failure, a new study finds. The theory for this ...

  17. Lower serum soluble-EGFR is a potential biomarker for metastasis of HCC demonstrated by N-glycoproteomic analysis.

    PubMed

    Hu, Heng; Gao, Lingling; Wang, Cun; Li, Yan; Ma, Huiying; Chen, Long; Qin, Jie; Liu, Binbin; Liu, Yinkun; Liang, Chunmin

    2015-05-01

    Hepatocellular carcinoma (HCC) is one of the most deadly cancers in the world due to its high metastatic potential. By using the isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative N-glycoproteomic analysis, 26 differentially expressed serum glycoproteins derived from defined stages in orthotopic xenograft tumor model were identified. Among them, expression level of soluble EGFR (sEGFR) was verified in HCC cell lines. We found that non-metastasis HCC cell lines express significantly more sEGFR than HCC cell lines with metastasis potential both in cell lysates and culture media. Serum samples from 28 non-metastatic HCC patients and 28 metastatic HCC patients were assayed. Compared with the non-metastatic HCC group, serum level of sEGFR in metastatic HCC group was statistically lower (p<0.01). All these results provide evidence that sEGFR is a potential candidate for metastasis-associated biomarkers of HCC. The related molecular mechanism deserves to be further explored.

  18. Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell

    SciTech Connect

    Xu, Ning; Zhang, Jianjun; Shen, Conghuan; Luo, Yi; Xia, Lei; Xue, Feng; Xia, Qiang

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer miR-199a-5p levels were significantly decreased after cisplatin treatment. Black-Right-Pointing-Pointer Cisplatin treatment induced autophagy activation. Black-Right-Pointing-Pointer Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell. -- Abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Systemic chemotherapy plays an important role in the treatment of patients with advanced liver cancer. However, chemoresistance to cisplatin is a major limitation of cisplatin-based chemotherapy in the clinic, and the underlying mechanism of such resistance is not fully understood. In the study, we found that miR-199a-5p levels were significantly reduced in HCC patients treated with cisplatin-based chemotherapy. Cisplatin treatment also resulted in decreased miR-199a-5p levels in human HCC cell lines. Forced expression of miR-199a-5p promoted cisplatin-induced inhibition of cell proliferation. Cisplatin treatment activated autophagy in Huh7 and HepG2 cells, which increased cell proliferation. We further demonstrated that downregulated miR-199a-5p enhanced autophagy activation by targeting autophagy-associated gene 7 (ATG7). More important, autophagy inhibition abrogated miR-199a-5p downregulation-induced cell proliferation. These data demonstrated that miR-199a-5p/autophagy signaling represents a novel pathway regulating chemoresistance, thus offering a new target for chemotherapy of HCC.

  19. Phosphorylation of nucleophosmin at threonine 234/237 is associated with HCC metastasis.

    PubMed

    Ching, Rachel Hiu Ha; Lau, Eunice Yuen Ting; Ling, Patrick Ming Tat; Lee, Joyce Man Fong; Ma, Mark Kin Fai; Cheng, Bowie Yik Ling; Lo, Regina Cheuk Lam; Ng, Irene Oi Lin; Lee, Terence Kin Wah

    2015-12-22

    Hepatocellular carcinoma (HCC) is frequently complicated by the occurrence of intrahepatic and extrahepatic metastases, leading to poor prognosis. To improve the prognosis for HCC patients, there is an urgent need to understand the molecular mechanisms of metastasis in HCC. Since protein Serine/Threonine phosphorylation emerges to be an important posttranslational modification critical in signaling process associated with cell proliferation, survival and metastasis, we employed a pair of primary tumor-derived and corresponding lung-metastatic counterparts (PLC/PRF/5-PT and PLC/PRF/5-LM) and aimed to identify these changes using CelluSpot Serine/Threonine kinase peptide array. Upon analysis, we found phosphorylated level of nucleophosmin (NPM) at Threonine 234/237 (p-NPM-Thr234/237) had remarkably high level in metastatic HCC cells (PLC-LM) than the corresponding primary HCC cell line (PLC-PT). Similar observation was observed in another match primary and their metastatic counterparts (MHCC-97L and MHCC-97H). By immunohistochemical staining, p-NPM-Thr234/237 was consistently found to be preferentially expressed in metastatic HCCs when compared with primary HCC in 28 HCC cases (p < 0.0001). By overexpressing Flag-tagged NPM and its phosphorylation site mutant (Thr234/237A) into low p-NPM-Thr234/237 expressing cells (Hep3B and Huh7) using a lentiviral based approach, we demonstrated that p-NPM-Thr234/237 is critical in invasion and migration of HCC cells, and this effect was mediated by cyclin-dependent kinase 1 (CDK1). Wild-type NPM was found to physically interact with a metastatic gene, ROCK2, and defective in Thr234/237 phosphorylation decreased its binding affinity, resulting in decrease in ROCK2 mediated signaling pathway. Identification of CDK1/p-NPM/ROCK2 signaling pathway provides a novel target for molecular therapy against HCC metastasis.

  20. Phosphorylation of Nucleophosmin at Threonine 234/237 is associated with HCC metastasis

    PubMed Central

    Ha Ching, Rachel Hiu; Ting Lau, Eunice Yuen; Tat Ling, Patrick Ming; Fong Lee, Joyce Man; Fai Ma, Mark Kin; Ling Cheng, Bowie Yik; Lam Lo, Regina Cheuk; Lin Ng, Irene Oi; Wah Lee, Terence Kin

    2015-01-01

    Hepatocellular carcinoma (HCC) is frequently complicated by the occurrence of intrahepatic and extrahepatic metastases, leading to poor prognosis. To improve the prognosis for HCC patients, there is an urgent need to understand the molecular mechanisms of metastasis in HCC. Since protein Serine/Threonine phosphorylation emerges to be an important posttranslational modification critical in signaling process associated with cell proliferation, survival and metastasis, we employed a pair of primary tumor-derived and corresponding lung-metastatic counterparts (PLC/PRF/5-PT and PLC/PRF/5-LM) and aimed to identify these changes using CelluSpot™ Serine/Threonine kinase peptide array. Upon analysis, we found phosphorylated level of nucleophosmin (NPM) at Threonine 234/237 (p-NPM-Thr234/237) had remarkably high level in metastatic HCC cells (PLC-LM) than the corresponding primary HCC cell line (PLC-PT). Similar observation was observed in another match primary and their metastatic counterparts (MHCC-97L and MHCC-97H). By immunohistochemical staining, p-NPM-Thr234/237 was consistently found to be preferentially expressed in metastatic HCCs when compared with primary HCC in 28 HCC cases (p < 0.0001). By overexpressing Flag-tagged NPM and its phosphorylation site mutant (Thr234/237A) into low p-NPM-Thr234/237 expressing cells (Hep3B and Huh7) using a lentiviral based approach, we demonstrated that p-NPM-Thr234/237 is critical in invasion and migration of HCC cells, and this effect was mediated by cyclin-dependent kinase 1 (CDK1). Wild-type NPM was found to physically interact with a metastatic gene, ROCK2, and defective in Thr234/237 phosphorylation decreased its binding affinity, resulting in decrease in ROCK2 mediated signaling pathway. Identification of CDK1/p-NPM/ROCK2 signaling pathway provides a novel target for molecular therapy against HCC metastasis. PMID:26536659

  1. mTOR inhibitor therapy: Does it prevent HCC recurrence after liver transplantation?

    PubMed

    Duvoux, Christophe; Toso, Christian

    2015-07-01

    Prevention of hepatocellular carcinoma (HCC) recurrence after liver transplantation is a clinical priority. The importance of the mammalian target of rapamycin (mTOR) pathway in cell growth and survival makes it a logical target for antitumor strategies, as borne out by clinical data in various types of malignancy. A number of studies have indicated that the mTOR inhibitors everolimus and sirolimus suppress cell proliferation and tumor growth in animal models of HCC. Coadministration of an mTOR inhibitor could permit lower dosing of chemotherapeutic agents in HCC management, and trials in non-transplant HCC population are exploring combined used with various agents including sorafenib, the vascular endothelial growth factor inhibitor bevacizumab and conventional agents. In terms of a preventive effect after liver transplantation for HCC, data from retrospective studies and non-randomized prospective analyses in which patients received an mTOR inhibitor with concomitant calcineurin inhibitor therapy have indicated that HCC recurrence rates and overall survival may be improved compared to a standard calcineurin inhibitor regimen. Meta-analyses have supported these findings, but controlled trials are required before any firm conclusions can be drawn. In two of the three randomized trials which have assessed de novo mTOR inhibitor therapy after liver transplantation, there was a numerically lower rate of HCC recurrence by one year post-transplant in patients given an mTOR inhibitor versus the control arm, but absolute numbers were low. Overall, based on the available data from retrospective studies, meta-analyses, and post-hoc assessments of randomized trials, it appears advisable to consider mTOR inhibition-based immunosuppression after transplantation for HCC, particularly in patients who exceed the Milan criteria. Prospective data are awaited. PMID:26071984

  2. Current Treatment Approaches to HCC with a Special Consideration to Transplantation

    PubMed Central

    Perera, M. T. P. R.; Silva, M. A.

    2016-01-01

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. The mainstay of treatment of HCC has been both resectional and transplantation surgery. It is well known that, in selected, optimized patients, hepatectomy for HCC may be an option, even in patients with underlying cirrhosis. Resectable patients with early HCC and underlying liver disease are however increasingly being considered for transplantation because of potential for better disease-free survival and resolution of underlying liver disease, although this approach is limited by the availability of donor livers, especially in resectable patients. Outcomes following liver transplantation improved dramatically for patients with HCC following the implementation of the Milan criteria in the late 1990s. Ever since, the rather restrictive nature of the Milan criteria has been challenged with good outcomes. There has also been an increase in the donor pool with marginal donors including organs retrieved following cardiac death being used. Even so, patients still continue to die while waiting for a liver transplant. In order to reduce this attrition, bridging techniques and methods for downstaging disease have evolved. Additionally new techniques for organ preservation have increased the prospect of this potentially curative procedure being available for a greater number of patients. PMID:27413539

  3. Delirium in patients with advanced cancer.

    PubMed

    Lawlor, Peter G; Bruera, Eduardo D

    2002-06-01

    Managing delirium is of major importance in end-of-life care and frequently gives rise to controversies and to clinical and ethical dilemmas. These problems arise from a number of causes, including the sometimes-poor recognition or misdiagnosis of delirium despite its frequent occurrence. Delirium generates major symptomatic of distress for the patient, consequent stress for the patient's family, the potential to misinterpret delirium symptomatology, and behavioral management challenges for health care professionals. Paradoxically, delirium is potentially reversible in some episodes, but in many patients delirium presents a nonreversible terminal episode. Greater educational efforts are required to improve the recognition of delirium and lead to a better understanding of its impact in end-of-life care. Future research might focus on phenomenology, the development of low-burden instruments for assessment, communication strategies, and the family education regarding the manifestations of delirium. Further research is needed among patients with advanced cancer to establish a predictive model for reversibility that recognizes both baseline vulnerability factors and superimposed precipitating factors. Evidence-based guidelines should be developed to assist physicians in more appropriate use of sedation in the symptomatic management of delirium.

  4. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma.

    PubMed

    Kang, Tae Wook; Rhim, Hyunchul

    2015-09-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC. PMID:26674766

  5. Dietary intake of advanced cancer patients.

    PubMed

    Walsh, T D; Bowman, K B; Jackson, G P

    1983-02-01

    A state registered dietitian assessed the voluntary dietary intake of 13 advanced cancer inpatients on one ward of St. Christopher's Hospice for five consecutive days. There were 11 females, two males; median age 74 years (range 56 to 83). Two patients died on the fourth day of the study. A partially individualised weighed technique was used. Standard sized scoops and spoons were used to serve the food in small, medium or large standard portions (depending on appetite) and were weighed as served. Individual plate waste (by weight) was subtracted to give estimated individual intake. Foods provided by visitors was not included. The median and range of individual mean daily intakes (estimated) were: energy 5760 (938-8945) kJ, 1376 (224-2137) kcal; protein 44 (11-86) g; fat 52 (9-93) g; carbohydrate 169 (21-194) g; calcium 748 (268-1457) mg; iron 4.8 (0.5-21.0) mg; dietary fibre 5.0 (0.5-21.0) g. Compared to recommended amounts, energy, iron and dietary fibre intakes were low; calcium intake was high. Nutritional status may affect prognosis and/or subjective well-being in advanced cancer. The value of nutritional supplementation and the role of appetite stimulants in improving nutritional status needs investigation.

  6. Dietary intake of advanced cancer patients.

    PubMed

    Walsh, T D; Bowman, K B; Jackson, G P

    1983-02-01

    A state registered dietitian assessed the voluntary dietary intake of 13 advanced cancer inpatients on one ward of St. Christopher's Hospice for five consecutive days. There were 11 females, two males; median age 74 years (range 56 to 83). Two patients died on the fourth day of the study. A partially individualised weighed technique was used. Standard sized scoops and spoons were used to serve the food in small, medium or large standard portions (depending on appetite) and were weighed as served. Individual plate waste (by weight) was subtracted to give estimated individual intake. Foods provided by visitors was not included. The median and range of individual mean daily intakes (estimated) were: energy 5760 (938-8945) kJ, 1376 (224-2137) kcal; protein 44 (11-86) g; fat 52 (9-93) g; carbohydrate 169 (21-194) g; calcium 748 (268-1457) mg; iron 4.8 (0.5-21.0) mg; dietary fibre 5.0 (0.5-21.0) g. Compared to recommended amounts, energy, iron and dietary fibre intakes were low; calcium intake was high. Nutritional status may affect prognosis and/or subjective well-being in advanced cancer. The value of nutritional supplementation and the role of appetite stimulants in improving nutritional status needs investigation. PMID:6841131

  7. Galectin 3 Regulates HCC cell invasion by RhoA and MLCK activation

    PubMed Central

    Serizawa, Nobuko; Tian, Jijiang; Fukada, Hiroo; Baghy, Kornelia; Scott, Fiona; Chen, Xiangling; Kiss, Zsofia; Olson, Kristin; Hsu, Dan; Liu, Fu-Tong; Török, Natalie J; Zhao, Bin; Jiang, Joy X.

    2015-01-01

    Hepatocellular carcinoma (HCC) carries a poor prognosis with no effective treatment available other than liver transplantation for selected patients. Vascular invasion of HCC is one of the most important negative predictor of survival. As the regulation of invasion of HCC cells is not well understood, our aim was to study the mechanisms by which galectin 3, a β-galactosidase binding lectin mediates HCC cell migration. HCC was induced by N-diethylnitrosamine (DEN) in wild type and galectin 3−/− mice, and tumor formation, histology, and tumor cell invasion were assessed. The galectin 3−/− mice developed significantly smaller tumor burden with a less invasive phenotype than the wild type animals. Galectin 3 was upregulated in the wild type HCC tumor tissue, but not in the surrounding parenchyma. Galectin 3 expression in HCC was induced by NF-κB transactivation as determined by chromatin immunoprecipitation assays. In vitro studies assessed the pro-migratory effects of galectin 3. The migration of hepatoma cells was significantly decreased after transfection by the galectin 3 siRNA and also after using the Rho kinase (ROCK) inhibitor Y-27632. The reorganization of the actin cytoskeleton, RhoA GTP ase activity and the phosphorylation of MLC2 were decreased in the galectin 3 siRNA-transfected cells. In addition, in vitro and in vivo evidence showed that galectin 3 deficiency reduced hepatoma cell proliferation and increased their apoptosis rate. In conclusion, galectin 3 is an important lectin that is induced in HCC cells, and promotes hepatoma cell motility and invasion by an autocrine pathway. Targeting galectin 3 therefore could be an important novel treatment strategy to halt disease progression. PMID:26146960

  8. Radio-frequency ablation-based studies on VX2rabbit models for HCC treatment.

    PubMed

    Bimonte, Sabrina; Leongito, Maddalena; Piccirillo, Mauro; de Angelis, Cristina; Pivonello, Claudia; Granata, Vincenza; Izzo, Francesco

    2016-01-01

    Hepatocellular carcinoma (HCC) is the fifth most frequent cancer worldwide with high morbidity, mortality and increasing incidence. It is of note that the main curative therapies for HCC are hepatic resection and transplantation although the majority of patients at the time of presentation are not eligible for resection or orthotopic liver transplantation (OLT) due to the underlying cirrhosis. Currently, a variety of loco-regional therapies, including radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), microwave coagulation therapy (MCT), transarterial chemoembolization (TACE) and others, have been developed as alternative treatment options for HCC. Among these techniques, RFA is currently the most widely used treatment, due to its several advantages, such as safety and efficacy. To date, the effectiveness of RFA for HCC is reduced by the presence of residual tumor as a consequence of insufficient treatment. In order to ameliorate the effects of RFA on HCC, several in vivo studies, have been performed on its application as single or in combination treatment with drugs or others loco-regional therapies, by using rabbit VX2 liver model. This represents an ideal model of liver cancers and is widely used for imaging and other experimental studies due to the rapid growth of these tumors and their similarity to human hepatocellular carcinoma. In order to elucidate the therapeutic potential of RFA with adjuvant treatments for HCC, we reviewed the latest findings on the RFA-based studies in rabbit VX2 hepatocarcinoma models. PMID:27525037

  9. TLR4 signaling promotes a COX-2/PGE2/STAT3 positive feedback loop in hepatocellular carcinoma (HCC) cells

    PubMed Central

    Lin, Ang; Wang, Guan; Zhao, Huajun; Zhang, Yuyi; Han, Qiuju; Zhang, Cai; Tian, Zhigang; Zhang, Jian

    2016-01-01

    ABSTRACT Toll-like receptors (TLRs) can be expressed by tumor cells, and each TLR exhibits different biological functions. Evidences showed the activation of some certain TLRs could promote tumor progression. One of which TLR4 has been found to promote hepatocellular carcinoma (HCC) cells proliferation, but the detailed mechanism is still unknown. In the present study, we verified that TLR4 was functionally expressed on HCC cells, and TLR4 agonist lipopolysaccharide (LPS) could stimulate the proliferation and clone formation of HCC cells. Most importantly, we found a COX-2/PGE2/STAT3 positive feedback loop exists in HCC cells, which could be provoked by TLR4 activation. Consistently, the expression of TLR4, COX-2 and p-STAT3Y705 was positively correlated with each other in liver tumor tissues from patients with primary HCC. Further investigation demonstrated this loop played a dominant role in TLR4-induced HCC cell proliferation and multidrug resistance (MDR) to chemotherapy. Inhibition of TLR4 or COX-2/PGE2/STAT3 loop would attenuate LPS-induced inflammation and proliferation of HCC cells, and enhance the sensitivity of HCC cells to chemotherapeutics in vitro. By using a primary HCC model, we observed COX-2/PGE2/STAT3 loop was significantly blocked in TLR4−/− mice compared to wild type mice, and there was no obvious tumorgenesis sign in TLR4−/− mice. Therefore, these findings provided the precise molecular mechanism of TLR4 signaling pathway involved in HCC progress, and suggested that TLR4 may be a promising target for HCC treatment. PMID:27057441

  10. MiR-424-5p reversed epithelial-mesenchymal transition of anchorage-independent HCC cells by directly targeting ICAT and suppressed HCC progression

    PubMed Central

    Zhang, Ying; Li, Tao; Guo, Pengbo; Kang, Jia; Wei, Qing; Jia, Xiaoqing; Zhao, Wei; Huai, Wanwan; Qiu, Yumin; Sun, Lei; Han, Lihui

    2014-01-01

    Resistance to anoikis and Epithelial-mesenchymal transition (EMT) are two processes critically involved in cancer metastasis. In this study, we demonstrated that after anchorage deprival, hepatocellular carcinoma (HCC) cells not only resisted anoikis, but also exhibited EMT process. Microarray expression profiling revealed that expression of miR-424-5p was significantly decreased in anoikis-resistant HCC cells. Ectopic overexpression of miR-424-5p was sufficient to reverse resistance to anoikis, block EMT process and inhibit malignant behaviors of HCC cells. Target analysis showed that a potent β-catenin inhibitor, ICAT/CTNNBIP1 was a direct target of miR-424-5p. Further study demonstrated that miR-424-5p reversed resistance to anoikis and EMT of HCCs by directly targeting ICAT and further maintaining the E-cadherin/β-catanin complex on the cellular membrance. In vivo study further demonstrated that miR-424-5p significantly inhibited the tumorigenicity of HCC cells in nude mice. Clinical investigation demonstrated that miR-424-5p was significantly downregulated in HCC tissues compared with that of the non-cancerous liver tissues, and this decreased expression of miR-424-5p was significantly correlated with higher pathological grades and more advanced TNM stages. Therefore, aberrant expression of miR-424-5p is critically involved in resistance to anoikis and EMT during the metastatic process of HCC, and its downregulation significantly contributes to liver cancer progression. PMID:25175916

  11. Prediction of the Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Patients after Sustained Virological Response by Aspartate Aminotransferase to Platelet Ratio Index

    PubMed Central

    Lee, Keol; Sinn, Dong Hyun; Gwak, Geum-Youn; Cho, Hyun Chin; Jung, Sin-Ho; Paik, Yong-Han; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon

    2016-01-01

    Background/Aims Following sustained virological response (SVR) for chronic hepatitis C (CHC) infection, patients with advanced fibrosis require regular monitoring for hepatocellular carcinoma (HCC). The aspartate aminotransferase to platelet ratio index (APRI) is a simple noninvasive surrogate marker known to reflect fibrosis. Methods We retrospectively analyzed 598 patients who achieved SVR with interferon-based therapy for CHC. Results Over a median of 5.1 years of follow-up, there were eight patients diagnosed with HCC and a 5-year cumulative incidence rate of 1.3%. The median pretreatment APRI was 0.83, which decreased to 0.29 after achieving SVR (p<0.001). Both the pre- and posttreatment indices were associated with HCC development. The 5-year cumulative HCC incidence rates were 0% and 2.8% for patients with pretreatment APRI <1.0 and ≥1.0, respectively (p=0.001) and 0.8% and 12.8% for patients with posttreatment APRI <1.0 and ≥1.0, respectively (p<0.001). Pretreatment APRI at a cutoff of 1.0 had a 100% negative predictive value until 10 years after SVR. Conclusions HCC development was observed among CHC patients who achieved SVR. The pre- and post-treatment APRI could stratify HCC risk, indicating that the APRI could be a useful marker to classify HCC risk in CHC patients who achieved SVR. However, given the small number of HCC patients, this finding warrants further validation. PMID:27114418

  12. MicroRNA-616 promotes the migration, invasion and epithelial-mesenchymal transition of HCC by targeting PTEN.

    PubMed

    Zhang, Di; Zhou, Peihua; Wang, Wei; Wang, Xiaolong; Li, Junhui; Sun, Xuejun; Zhang, Li

    2016-01-01

    MicroRNAs, which can post-transcriptionally regulate gene expression by binding to the 3'-untranslated regions of the mRNAs, have been found to be the critical regulators of the development and progression of hepatocellular carcinoma (HCC). The present study demonstrated for the first time that microRNA-616 (miR-616) was markedly upregulated in HCC tissues, and was associated with the recurrence and metastasis of HCC. Elevated level of miR-616 was correlated with adverse clinicopathological features and poor prognosis of HCC patients. Gain- and loss-of-function studies revealed that miR-616 could potentiate the migration, invasion and the epithelial-mesenchymal transtion (EMT) phenotype of HCC cells. Phosphatase and tensin homolog (PTEN), the predicted target of miR-616 by bioinformatics analysis, was confirmed as a direct downstream target of miR-616 through western blotting, luciferase reporter and immunohistochemical assays. Furthermore, we demonstrated that miR-616 exerted the promoting effects on EMT and metastatic ability of HCC cells through suppressing PTEN expression. Based on these results, we conclude that miR-616 is a promising prognostic biomarker of HCC and targeting miR-616 may be a potential option to prevent the progression of HCC.

  13. Bevacizumab improves survival for patients with advanced cervical cancer

    Cancer.gov

    Patients with advanced, recurrent, or persistent cervical cancer that was not curable with standard treatment who received the drug bevacizumab (Avastin) lived 3.7 months longer than patients who did not receive the drug, according to an interim analysis

  14. Prediction of recurrence after HCC resection. Faint oily deposits on preoperative Lipiodol-CT of remnant liver tissue.

    PubMed

    Yamamoto, M; Iimuro, Y; Mogaki, M; Kachi, K; Fujii, H; Matsumoto, Y

    1994-07-01

    In trying to clarify the high recurrence rate after removal of small hepatocellular carcinoma (HCC), we assessed the postoperative evolution of minute hepatic Lipiodol deposits which had been diagnosed as artifacts on the preoperative Lipiodol-CT. Of 27 patients with solitary HCC less than 5 cm in diameter, 14 had such Lipiodol deposits in the preoperative CT and 9 of them (64%) developed recurrent tumors. On the other hand, 6 of the 13 patients without deposits (46%) suffered recurrence, but in 5 of these 6 patients the HCC was metachronous multicentric. The cumulative survival rate of the non-deposit group was better than that of the deposit group (p < 0.1). The present study suggested that, even in patients with small HCC, minute concomitant tumors invisible by conventional imaging techniques may exist at the time of surgery. Some of these lesions without sufficient tumor vasculature showing a hypervascular blush on angiography appear to retain small, vague Lipiodol deposits.

  15. Liver transplantation for advanced hepatocellular carcinoma

    PubMed Central

    Lee, Hae Won; Suh, Kyung-Suk

    2016-01-01

    There has been ongoing debate that the Milan criteria may be too strict that a significant number of patients who could benefit from liver transplantation (LT) might have been excluded. Based on this idea, various studies have been conducted to further expand the Milan criteria and give more HCC patients a chance of cure. In deceased donor LT (DDLT) setting, expansion of the criteria is relatively tempered because the results of LT for HCC should be comparable to those of patients with non-malignant indications. On the other hand, in living donor LT (LDLT) situation, liver grafts are not public resources. The acceptable target outcomes for LDLT might be much lower than those for DDLT. Patients with biologically favorable tumors might have excellent survivals after LT despite morphological advanced HCCs. Therefore, the significance and utility of biological tumor parameters for selecting suitable LT candidates have been increased to predict HCC recurrence after LT. Although there is no consensus regarding the use of prognostic biomarkers in LT selection criteria for HCC, the combination of conventional morphological parameters and new promising biomarkers could help us refine and expand the LT criteria for HCC in the near future. PMID:27729631

  16. Evolving Approaches to Patients with Advanced Differentiated Thyroid Cancer

    PubMed Central

    Sherman, Steven I.

    2013-01-01

    Advanced differentiated thyroid cancer (DTC), defined by clinical characteristics including gross extrathyroidal invasion, distant metastases, radioiodine (RAI) resistance, and avidity for 18-fluorodeoxyglucose (positron emission tomography-positive), is found in approximately 10–20% of patients with DTC. Standard therapy (surgery, RAI, TSH suppression with levothyroxine) is ineffective for many of these patients, as is standard chemotherapy. Our understanding of the molecular mechanisms leading to DTC and the transformation to advanced DTC has rapidly evolved over the past 15–20 years. Newer targeted therapy, specifically inhibitors of intracellular kinase signaling pathways, and cooperative multicenter clinical trials have dramatically changed the therapeutic landscape for patients with advanced DTC. In this review focusing on morbidities, molecules, and medicinals, we present a patient with advanced DTC, explore the genetics and molecular biology of advanced DTC, and review evolving therapies for these patients including multikinase inhibitors, selective kinase inhibitors, and combination therapies. PMID:23575762

  17. Preliminary efficacy, safety, pharmacokinetics, pharmacodynamics and quality of life study of pegylated recombinant human arginase 1 in patients with advanced hepatocellular carcinoma.

    PubMed

    Yau, Thomas; Cheng, Paul N; Chan, Pierre; Chen, Li; Yuen, Jimmy; Pang, Roberta; Fan, Sheung Tat; Wheatley, Denys N; Poon, Ronnie T

    2015-04-01

    This study was designed to evaluate the efficacy, safety profile, pharmacokinetics, pharmacodynamics and quality of life of pegylated recombinant human arginase 1 (Peg-rhAgr1) in patients with advanced hepatocellular carcinoma (HCC). Patients were given weekly doses of Peg-rhAgr1 (1600 U/kg). Tumour response was assessed every 8 weeks using RECIST 1.1 and modified RECIST criteria. A total of 20 patients were recruited, of whom 15 were deemed evaluable for treatment efficacy. Eighteen patients (90%) were hepatitis B carriers. Median age was 61.5 (range 30-75). Overall disease control rate was 13%, with 2 of the 15 patients achieving stable disease for >8 weeks. The median progression-free survival (PFS) was 1.7 (95% CI: 1.67-1.73) months, with median overall survival (OS) of all 20 enrolled patients being 5.2 (95% CI: 3.3-12.0) months. PFS was significantly prolonged in patients with adequate arginine depletion (ADD) >2 months versus those who had ≤2 months of ADD (6.4 versus 1.7 months; p = 0.01). The majority of adverse events (AEs) were grade 1/2 non-hematological toxicities. Transient liver dysfunctions (25%) were the most commonly reported serious AEs and likely due to disease progression. Pharmacokinetic and pharmacodynamic data showed that Peg-rhAgr1 induced rapid and sustained arginine depletion. The overall quality of life of the enrolled patients was well preserved. Peg-rhAgr1 is well tolerated with a good toxicity profile in patients with advanced HCC. A weekly dose of 1600 U/kg is sufficient to induce ADD. Significantly longer PFS times were recorded for patients who had ADD for >2 months.

  18. Chemotherapy and target therapy for hepatocellular carcinoma: New advances and challenges

    PubMed Central

    Deng, Gan-Lu; Zeng, Shan; Shen, Hong

    2015-01-01

    Primary liver cancer is one of the commonest causes of death. Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers. For patients with unresectable or metastatic HCC, conventional chemotherapy is of limited or no benefit. Sorafenib is the only systemic treatment to demonstrate a statistically significant but modest overall survival benefit, leading to an era of targeted agents. Many clinical trials of targeted drugs have been carried out with many more in progress. Some drugs like PTK787 showed potential benefits in the treatment of HCC. Despite these promising breakthroughs, patients with HCC still have a dismal prognosis. Recently, both a phase III trial of everolimus and a phase II clinical trial of trebananib failed to demonstrate effective antitumor activity in advanced HCC. Sorafenib still plays a pivotal role in advanced HCC, leading to further explorations to exert its maximum efficacy. Combinations targeted with chemotherapy or transarterial chemoembolization is now being tested and might bring about advances. New targeted agents such as mammalian target of rapamycin inhibitors are under investigation, as well as further exploration of the mechanism of hepatocarcinogenesis. PMID:25914779

  19. Patterns of treatment and costs of intermediate and advanced hepatocellular carcinoma management in four Italian centers

    PubMed Central

    Colombo, Giorgio Lorenzo; Cammà, Calogero; Attili, Adolfo Francesco; Ganga, Roberto; Gaeta, Giovanni Battista; Brancaccio, Giuseppina; Franzini, Jean Marie; Volpe, Marco; Turchetti, Giuseppe

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is a severe health condition associated with high hospitalizations and mortality rates, which also imposes a relevant economic burden. Purpose The aim of the present survey is to investigate treatment strategies and related costs for HCC in the intermediate and advanced stages of the disease. Patients and methods The survey was conducted in four Italian centers through structured interviews with physicians. Information regarding the stage of disease, treatments performed, and related health care resource consumption was included in the questionnaire. Direct health care cost per patient associated with the most relevant treatments such as sorafenib, transarterial chemoembolization (TACE), and transarterial radioembolization (TARE) was evaluated. Results Between 2013 and 2014, 285 patients with HCC were treated in the four participating centers; of these, 80 were in intermediate stage HCC (Barcelona Clinic Liver Cancer Classification [BCLC] B), and 57 were in the advanced stage of the disease (BCLC C). In intermediate stage HCC, the most frequent first-line treatment was TACE (63%) followed by sorafenib (15%), radiofrequency ablation (14%), and TARE (1.3%). In the advanced stage of HCC, the most frequently used first-line therapy was sorafenib (56%), followed by best supportive care (21%), TACE (18%), and TARE (3.5%). The total costs of treatment per patient amounted to €12,214.54 with sorafenib, €13,418.49 with TACE, and €26,106.08 with TARE. Both in the intermediate and in the advanced stage of the disease, variability in treatment patterns among centers was observed. Conclusion The present analysis raises for the first time the awareness of the overall costs incurred by the Italian National Healthcare System for different treatments used in intermediate and advanced HCC. Further investigations would be important to better understand the effective health care resource usage. PMID:26527877

  20. Hepatocellular Carcinoma Management in Nonalcoholic Fatty Liver Disease Patients

    PubMed Central

    Oliveira, Claudia P.; Alvares-da-Silva, Mario R.; Tani, Claudia M.; Diniz, Marcio A.; Stefano, Jose T.; Chagas, Aline L.; Alencar, Regiane S.S.M.; Vezozzo, Denise C.P.; Santos, Gilmar R.; Campos, Priscila B.; Alves, Venancio AF.; Ratziu, Vlad; Carrilho, Flair J.

    2016-01-01

    Background/Aims: Nonalcoholic fatty liver disease (NAFLD) has emerged as an important cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). The Barcelona Clinic Liver Cancer (BCLC) system is the preferred staging system to evaluate patients with HCC and links prognosis assessment with treatment recommendation. The aim of this retrospective study was to evaluate whether the BCLC staging system and its treatment algorithm are suitable for patients with HCC arising from NAFLD. Methods: Forty-two patients with HCC related to either to NAFLD or cryptogenic cirrhosis were retrieved retrospectively from 2 centers in Brazil. Patients were classified according to BCLC staging system. If the proposed HCC therapy could not be applied, the case was considered to represent deviations from the recommended BCLC guideline. Causes of treatment deviations were investigated. Results: There were 4 patients without evidence of cirrhosis according to liver biopsy and/or clinical evaluation. One (2%), 21 (50%), 10 (24%), 5 (12%), and 5 patients (12%) were classified initially to the very early (0), early (A), intermediate (B), advanced (C), and terminal (D) BCLC stages, respectively. Thirty-five patients (83%) were treated according to BCLC recommendations. There were 3 cases (of 5) of protocol deviation in BCLC C patients. The 1- and 2-year overall survival rates were 81% and 66%, respectively. Conclusions: The BCLC system is applied in most cases of NAFLD-related HCC cases. Deviation of BCLC is found more frequently in BCLC C stage patients. PMID:25268068

  1. Fewer Advanced Alzheimer's Patients on Feeding Tubes

    MedlinePlus

    ... at someone in the advanced stages of a terminal illness, a feeding tube doesn't make a ... of palliative care (keeping a person with a terminal illness as comfortable as possible), Mitchell said. As ...

  2. Inhibition of experimental HCC growth in mice by use of the kinase inhibitor DMAT.

    PubMed

    Sass, Gabriele; Klinger, Nina; Sirma, Hüseyin; Hashemolhosseini, Said; Hellerbrand, Claus; Neureiter, Daniel; Wege, Henning; Ocker, Matthias; Tiegs, Gisa

    2011-08-01

    The multi-kinase-inhibitor Sorafenib has been shown to prolong survival of patients suffering from hepatocellular carcinoma (HCC). We investigated effects of the serine/threonine kinase inhibitor 2-Dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT) on experimental HCC growth, and identified mechanisms and target kinases of DMAT. Our results show that DMAT application in vivo reduced tumor growth in a xenotransplant model by interference with tumor cell proliferation. Biochemical parameters and histology following DMAT administration revealed no alterations in liver tissue. Similar to Sorafenib, DMAT interfered with NFκB activation and Wnt-signaling. Of the kinases inhibited by DMAT at almost equimolar IC50, CK2 and PIM-3 were found to be over-expressed or more active in hepatoma cells and human HCC tissue. Knockdown of PIM-3 or CK2 by shRNA revealed that both kinases are important for hepatoma cell proliferation and survival. In conclusion, DMAT reduces HCC growth by interference with NFκB- and Wnt-signaling. PIM-3 and CK2 seem to be important target kinases. Inhibition of these kinases by application of inhibitors, e.g., DMAT, might represent a promising therapeutic approach in future HCC therapy.

  3. Recent advances in the surgical treatment of hepatocellular carcinoma.

    PubMed

    Morise, Zenichi; Kawabe, Norihiko; Tomishige, Hirokazu; Nagata, Hidetoshi; Kawase, Jin; Arakawa, Satoshi; Yoshida, Rie; Isetani, Masashi

    2014-10-21

    Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The treatment of HCC is complex and complicated by the severity of associated chronic liver disease, the stage of HCC, and the clinical condition of the patient. Liver resection (LR) is one of the most efficient treatments for patients with HCC, with an expected 5-year survival of 38%-61% depending on the stage of the disease. Improved liver function assessment, increased understanding of segmental liver anatomy from advanced imaging studies, and surgical technical progress are important factors that have led to reduced mortality in patients with HCC. The indication for LR may be expanded due to emerging evidences from laparoscopic hepatectomies and combined treatments with newly developed chemotherapies. Liver transplantation (LT) is considered as an ideal treatment for removal of existing tumors and the injured/preneoplastic underlying liver tissue with impaired liver function and the risk of multicentric carcinogenesis that results from chronically injured liver. However, LT is restricted to patients with minimal risk of tumor recurrence under immunosuppression. The expansion of criteria for LT in HCC patients is still under trial and discussion. Limited availability of grafts, as well as the risk and the cost of transplantation have led to considerable interest in expansion of the donor pool, living donor-related transplantation, and combined treatment involving LR and LT. This highlight presents evidence concerning recent studies evaluating LR and LT in HCC patients. In addition, alternative therapies for the treatment of early stage tumors and the management of patients on transplant waiting lists are discussed. PMID:25339825

  4. CXCL3 contributes to CD133+ CSCs maintenance and forms a positive feedback regulation loop with CD133 in HCC via Erk1/2 phosphorylation

    PubMed Central

    Zhang, Lin; Zhang, Lixing; Li, Hong; Ge, Chao; Zhao, Fangyu; Tian, Hua; Chen, Taoyang; Jiang, Guoping; Xie, Haiyang; Cui, Ying; Yao, Ming; Li, Jinjun

    2016-01-01

    Although the chemotactic cytokine CXCL3 is thought to play an important role in tumor initiation and invasion, little is known about its function in hepatocellular carcinoma (HCC). In our previous study, we found that Ikaros inhibited CD133 expression via the MAPK pathway in HCC. Here, we showed that Ikaros may indirectly down-regulate CXCL3 expression in HCC cells, which leads to better outcomes in patients with CD133+ cancer stem cell (CSC) populations. CD133 overexpression induced CXCL3 expression, and silencing of CD133 down-regulated CXCL3 in HCC cells. Knockdown of CXCL3 inhibited CD133+ HCC CSCs’ self-renewal and tumorigenesis. The serum CXCL3 level was higher in HCC patients’ samples than that in healthy individual. HCC patients with higher CXCL3 expression displayed a poor prognosis, and a high level of CXCL3 was significantly associated with vascular invasion and tumor capsule formation. Exogenous CXCL3 induced Erk1/2 and ETS1 phosphorylation and promoted CD133 expression, indicating a positive feedback loop between CXCL3 and CD133 gene expression in HCC cells via Erk1/2 activation. Together, our findings indicated that CXCL3 might be a potent therapeutic target for HCC. PMID:27255419

  5. Astrocyte Elevated Gene-1 (AEG-1) Contributes to Non-thyroidal Illness Syndrome (NTIS) Associated with Hepatocellular Carcinoma (HCC).

    PubMed

    Srivastava, Jyoti; Robertson, Chadia L; Gredler, Rachel; Siddiq, Ayesha; Rajasekaran, Devaraja; Akiel, Maaged A; Emdad, Luni; Mas, Valeria; Mukhopadhyay, Nitai D; Fisher, Paul B; Sarkar, Devanand

    2015-06-19

    Non-thyroidal illness syndrome (NTIS), characterized by low serum 3,5,3'-triiodothyronine (T3) with normal l-thyroxine (T4) levels, is associated with malignancy. Decreased activity of type I 5'-deiodinase (DIO1), which converts T4 to T3, contributes to NTIS. T3 binds to thyroid hormone receptor, which heterodimerizes with retinoid X receptor (RXR) and regulates transcription of target genes, such as DIO1. NF-κB activation by inflammatory cytokines inhibits DIO1 expression. The oncogene astrocyte elevated gene-1 (AEG-1) inhibits RXR-dependent transcription and activates NF-κB. Here, we interrogated the role of AEG-1 in NTIS in the context of hepatocellular carcinoma (HCC). T3-mediated gene regulation was analyzed in human HCC cells, with overexpression or knockdown of AEG-1, and primary hepatocytes from AEG-1 transgenic (Alb/AEG-1) and AEG-1 knock-out (AEG-1KO) mice. Serum T3 and T4 levels were checked in Alb/AEG-1 mice and human HCC patients. AEG-1 and DIO1 levels in human HCC samples were analyzed by immunohistochemistry. AEG-1 inhibited T3-mediated gene regulation in human HCC cells and mouse hepatocytes. AEG-1 overexpression repressed and AEG-1 knockdown induced DIO1 expression. An inverse correlation was observed between AEG-1 and DIO1 levels in human HCC patients. Low T3 with normal T4 was observed in the sera of HCC patients and Alb/AEG-1 mice. Inhibition of co-activator recruitment to RXR and activation of NF-κB were identified to play a role in AEG-1-mediated down-regulation of DIO1. AEG-1 thus might play a role in NTIS associated with HCC and other cancers. PMID:25944909

  6. Astrocyte Elevated Gene-1 (AEG-1) Contributes to Non-thyroidal Illness Syndrome (NTIS) Associated with Hepatocellular Carcinoma (HCC)*

    PubMed Central

    Srivastava, Jyoti; Robertson, Chadia L.; Gredler, Rachel; Siddiq, Ayesha; Rajasekaran, Devaraja; Akiel, Maaged A.; Emdad, Luni; Mas, Valeria; Mukhopadhyay, Nitai D.; Fisher, Paul B.; Sarkar, Devanand

    2015-01-01

    Non-thyroidal illness syndrome (NTIS), characterized by low serum 3,5,3′-triiodothyronine (T3) with normal l-thyroxine (T4) levels, is associated with malignancy. Decreased activity of type I 5′-deiodinase (DIO1), which converts T4 to T3, contributes to NTIS. T3 binds to thyroid hormone receptor, which heterodimerizes with retinoid X receptor (RXR) and regulates transcription of target genes, such as DIO1. NF-κB activation by inflammatory cytokines inhibits DIO1 expression. The oncogene astrocyte elevated gene-1 (AEG-1) inhibits RXR-dependent transcription and activates NF-κB. Here, we interrogated the role of AEG-1 in NTIS in the context of hepatocellular carcinoma (HCC). T3-mediated gene regulation was analyzed in human HCC cells, with overexpression or knockdown of AEG-1, and primary hepatocytes from AEG-1 transgenic (Alb/AEG-1) and AEG-1 knock-out (AEG-1KO) mice. Serum T3 and T4 levels were checked in Alb/AEG-1 mice and human HCC patients. AEG-1 and DIO1 levels in human HCC samples were analyzed by immunohistochemistry. AEG-1 inhibited T3-mediated gene regulation in human HCC cells and mouse hepatocytes. AEG-1 overexpression repressed and AEG-1 knockdown induced DIO1 expression. An inverse correlation was observed between AEG-1 and DIO1 levels in human HCC patients. Low T3 with normal T4 was observed in the sera of HCC patients and Alb/AEG-1 mice. Inhibition of co-activator recruitment to RXR and activation of NF-κB were identified to play a role in AEG-1-mediated down-regulation of DIO1. AEG-1 thus might play a role in NTIS associated with HCC and other cancers. PMID:25944909

  7. Astrocyte Elevated Gene-1 (AEG-1) Contributes to Non-thyroidal Illness Syndrome (NTIS) Associated with Hepatocellular Carcinoma (HCC).

    PubMed

    Srivastava, Jyoti; Robertson, Chadia L; Gredler, Rachel; Siddiq, Ayesha; Rajasekaran, Devaraja; Akiel, Maaged A; Emdad, Luni; Mas, Valeria; Mukhopadhyay, Nitai D; Fisher, Paul B; Sarkar, Devanand

    2015-06-19

    Non-thyroidal illness syndrome (NTIS), characterized by low serum 3,5,3'-triiodothyronine (T3) with normal l-thyroxine (T4) levels, is associated with malignancy. Decreased activity of type I 5'-deiodinase (DIO1), which converts T4 to T3, contributes to NTIS. T3 binds to thyroid hormone receptor, which heterodimerizes with retinoid X receptor (RXR) and regulates transcription of target genes, such as DIO1. NF-κB activation by inflammatory cytokines inhibits DIO1 expression. The oncogene astrocyte elevated gene-1 (AEG-1) inhibits RXR-dependent transcription and activates NF-κB. Here, we interrogated the role of AEG-1 in NTIS in the context of hepatocellular carcinoma (HCC). T3-mediated gene regulation was analyzed in human HCC cells, with overexpression or knockdown of AEG-1, and primary hepatocytes from AEG-1 transgenic (Alb/AEG-1) and AEG-1 knock-out (AEG-1KO) mice. Serum T3 and T4 levels were checked in Alb/AEG-1 mice and human HCC patients. AEG-1 and DIO1 levels in human HCC samples were analyzed by immunohistochemistry. AEG-1 inhibited T3-mediated gene regulation in human HCC cells and mouse hepatocytes. AEG-1 overexpression repressed and AEG-1 knockdown induced DIO1 expression. An inverse correlation was observed between AEG-1 and DIO1 levels in human HCC patients. Low T3 with normal T4 was observed in the sera of HCC patients and Alb/AEG-1 mice. Inhibition of co-activator recruitment to RXR and activation of NF-κB were identified to play a role in AEG-1-mediated down-regulation of DIO1. AEG-1 thus might play a role in NTIS associated with HCC and other cancers.

  8. Recent Advances in CT and MR Imaging for Evaluation of Hepatocellular Carcinoma

    PubMed Central

    Lee, Jeong Min; Yoon, Jeong-Hee; Joo, Ijin; Woo, Hyun Sik

    2012-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Accurate diagnosis and assessment of disease extent are crucial for proper management of patients with HCC. Imaging plays a crucial role in early detection, accurate staging, and the planning of management strategies. A variety of imaging modalities are currently used in evaluating patients with suspected HCC; these include ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), nuclear medicine, and angiography. Among these modalities, dynamic MRI and CT are regarded as the best imaging techniques available for the noninvasive diagnosis of HCC. Recent improvements in CT and MRI technology have made noninvasive and reliable diagnostic assessment of hepatocellular nodules possible in the cirrhotic liver, and biopsy is frequently not required prior to treatment. Until now, the major challenge for radiologists in imaging cirrhosis has been the characterization of small cirrhotic nodules smaller than 2 cm in diameter. Further technological advancement will undoubtedly have a major impact on liver tumor imaging. The increased speed of data acquisition in CT and MRI has allowed improvements in both spatial and temporal resolution, which have made possible a more precise evaluation of the hemodynamics of liver nodules. Furthermore, the development of new, tissue-specific contrast agents such as gadoxetic acid has improved HCC detection on MRI. In this review, we discuss the role of CT and MRI in the diagnosis and staging of HCC, recent technological advances, and the strengths and limitations of these imaging modalities. PMID:24159569

  9. CyberKnife Radiosurgery – Value as an Adjunct to Surgical Treatment of HCC?

    PubMed Central

    Schoenberg, Markus; Khandoga, Andrey; Stintzing, Sebastian; Trumm, Christoph; Schiergens, Tobias Simon; Angele, Martin; op den Winkel, Mark; Werner, Jens; Rentsch, Markus

    2016-01-01

    Introduction CyberKnife radiosurgery (CK) is an effective tool for the treatment of malignancies. Its greatest potential is in high-dose radiosurgery delivered to targets in organs that move with respiration, e.g., liver tumors. For hepatocellular carcinoma (HCC), however, surgical treatment (resection, transplantation) is most likely to produce long-term survival; for non-resectable tumors, therapies other than radiosurgery are typically recommended. This study evaluated the long-lasting anti-tumor effects of CK combined with surgery in patients with HCC. Materials and methods  Eighteen patients (three women, 15 men) were included in this prospective observational study. They received 21 single-fraction CK treatments (26 Gy). Patient characteristics, treatment effects, tumor response (according to the Response Evaluation Criteria In Solid Tumors (RECIST) grading) and survival were measured for a median period of 29 months. Results Local tumor control was achieved in 15 patients, with complete and partial remission observed in 10 and five patients, respectively. One patient was treated for two separate lesions in one session, and one received three treatments each separated by two-year intervals; both patients are tumor-free. Two patients showed minimal response, and in one patient local tumor viability could not be excluded by MRI. Nine patients had HCC recurrence, all distant to the treated site. Nine patients died during follow-up, including two with clear relation to tumor progress. Tumor-free survival was 79.4% after one year and 29.8% after three years, and the corresponding overall survival was 84.8% and 66%. Conclusion  This study shows the high effectiveness of single-session frameless CyberKnife radiosurgery for treatment of hepatocellular carcinoma and reconfirms previous results of fractioned radiotherapy of HCC. It also demonstrates the potential of radiosurgery to be combined with surgical concepts. PMID:27284498

  10. Sorafenib in advanced, heavily pretreated patients with soft tissue sarcomas.

    PubMed

    Brämswig, Kira; Ploner, Ferdinand; Martel, Alexandra; Bauernhofer, Thomas; Hilbe, Wolfgang; Kühr, Thomas; Leitgeb, Clemens; Mlineritsch, Brigitte; Petzer, Andreas; Seebacher, Veronika; Stöger, Herbert; Girschikofsky, Michael; Hochreiner, Gerhard; Ressler, Sigrun; Romeder, Franz; Wöll, Ewald; Brodowicz, Thomas

    2014-08-01

    Therapeutic options for patients with advanced pretreated soft tissue sarcomas are limited. However, in this setting, sorafenib has shown promising results. We reviewed the data of 33 patients with soft tissue sarcoma treated with sorafenib within a named patient program in Austria. Twelve physicians from eight different hospitals provided records for the analysis of data. Among the 33 patients, the predominant histological subtype of sarcoma was leiomyosarcoma (n=18, 55%). Other subtypes were represented by only one or two cases. Fifteen patients presented with metastases at the time of diagnosis. Another 17 patients developed metastases later in the course of the disease (data on one patient are missing). Most of the 33 patients had undergone resection of the primary (n=29, 88%) and half of the patients had received radiotherapy (n=17, 52%). Chemotherapy for metastatic disease had been administered to 30 patients (91%). The majority had received two or more regimens of chemotherapy (n=25, 76%) before sorafenib treatment. The use of sorafenib resulted in a median time to treatment failure of 92 days in patients with leiomyosarcoma and 45 days in patients with other histological subtypes. One-third of the patients derived benefits from treatment: four patients were documented with partial response and six with stabilized disease. In terms of treatment-related toxicity, skin problems of various degrees and gastrointestinal disturbances were frequently reported. In this retrospective analysis of heavily pretreated patients with advanced soft tissue sarcomas, sorafenib was associated with some antitumor activity and an acceptable toxicity profile. PMID:24667659

  11. Advances in non-surgical management of primary liver cancer

    PubMed Central

    Chen, Xiao; Liu, Hai-Peng; Li, Mei; Qiao, Liang

    2014-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. There have been great improvements in the diagnosis and treatment of HCC in recent years, but the problems, including difficult diagnosis at early stage, quick progression, and poor prognosis remain unsolved. Surgical resection is the mainstay of the treatment for HCC. However, 70%-80% of HCC patients are diagnosed at an advanced stage when most are ineligible for potentially curative therapies such as surgical resection and liver transplantation. In recent years, non-surgical management for unrespectable HCC, such as percutaneous ethanol injection, percutaneous microwave coagulation therapy, percutaneous radiofrequency ablation, transcatheter arterial chemoembolization, radiotherapy, chemotherapy, biotherapy, and hormonal therapy have been developed. These therapeutic options, either alone or in combination, have been shown to control tumor growth, prolong survival time, and improve quality of life to some extent. This review covers the current status and progress of non-surgical management for HCC. PMID:25469032

  12. Advanced nurse-patient communication system.

    PubMed

    Unluturk, Mehmet S

    2012-08-01

    Effective communication is the most important part of any healthcare organization. For many years, hospital nurse call solutions had been stand-alone systems with occasional integration to pocket paging for outputting patient call alerts to mobile staff. In the late 1990's, technology enabled in-building wireless phones to supplement or replace paging systems as a means of not only sending alerts, but also enabling voice communication between mobile staff and patients. Today's nurse call market requires integration of additional information from location and ADT (admit, discharge, transfer) systems into what have traditionally been nurse call applications. This system information is required not only at the nursing station, pagers, and phones, but also at PC's placed on each patient care floor in hallways, nurse stations, and offices, and at areas away from the patients, including administrator and clinical engineering offices. It is crucial that nurses have the latest patient information in their hand wherever they go in the hospital. In this paper, MatchMaker.NET has been developed to integrate all these technologies into the hospital's LAN to improve nurse-patient communication. PMID:21541690

  13. TLR3 Plays Significant Roles against HBV-Associated HCC

    PubMed Central

    Chen, Xiao-lan; Xu, Yu-yin; Chen, Li; Wang, Gui-lan; Shen, Yin

    2015-01-01

    Toll-like receptor 3 (TLR3) is a pattern-recognizing receptor that is involved in immune signaling and plays a crucial role in survival by being able to recognize various viral components including double-stranded RNA (dsRNA). The role of TLR3 in hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) infections is not well understood. To investigate the ability of TLR3 in regulating HBV replication in HCC, 80 cases of human HCC were collected and their tissue microarray was made. In HCC cells, the expression and location of TLR3, hepatitis-associated virus, and interstitial immunoreactive cells were assayed with immunohistochemical staining. The apoptosis of tumor cells was also detected by TUNEL stain. Correlations between TLR3 expression and HBV infection, interstitial immunoreactive cells, and cells apoptosis in HCC were investigated. In addition, we explored whether TLR3 agonist dsRNA can inhibit HepG2.2.15 cells secreting HBV. We found that the cytoplasmic expression of TLR3 in HCC is positively related to HBsAg infection and HCC with cirrhosis and promotes interstitial immunoreactive cells infiltration and cancer cells apoptosis. In HepG2.2.15 cells, dsRNA inhibited the secretion of HBV and induced apoptosis. These results indicate that TLR3 signaling activity may be involved in immune responses against HBV in HCC. PMID:25983748

  14. Palliative communications: addressing chemotherapy in patients with advanced cancer.

    PubMed

    Kadakia, K C; Moynihan, T J; Smith, T J; Loprinzi, C L

    2012-04-01

    Patients with advanced cancers often endure chemotherapy late in their disease course leading to unnecessary adverse effects, loss of quality of life, and delay in hospice referral. Compassionate and honest communication about the use of chemotherapy can facilitate better patient care. This manuscript will explore communication issues regarding palliative-intent chemotherapy.

  15. Profiling serologic biomarkers in cirrhotic patients via high-throughput Fourier transform infrared spectroscopy: toward a new diagnostic tool of hepatocellular carcinoma.

    PubMed

    Zhang, Xiaoqing; Thiéfin, Gérard; Gobinet, Cyril; Untereiner, Valérie; Taleb, Imane; Bernard-Chabert, Brigitte; Heurgué, Alexandra; Truntzer, Caroline; Ducoroy, Patrick; Hillon, Patrick; Sockalingum, Ganesh D

    2013-11-01

    Identification of novel serum biomarkers of hepatocellular carcinoma (HCC) is needed for early-stage disease detection and to improve patients' survival. The aim of this study was to evaluate the potential of serum Fourier transform infrared (FTIR) spectroscopy for differentiating sera from cirrhotic patients with and without HCC. Serum samples were collected from 2 sets of patients: cirrhotic patients with HCC (n = 39) and without HCC (n = 40). The FTIR spectra (10 per sample) were acquired in the transmission mode, and data homogeneity was tested by cluster analysis to exclude outliers. After data preprocessing by extended multiplicative signal correction and principal component analysis, the Support Vector Machine (SVM) method was applied using a leave-one-out cross-validation algorithm to classify the spectra into 2 classes of cirrhotic patients with and without HCC. When SVM was applied to all spectra (n = 790), the sensitivity and the specificity for the diagnosis of HCC were, respectively, 82.02% and 82.5%. When applied to the subset of spectra excluding the outliers (n = 739), SVM classification led to a sensitivity and specificity of 87.18% and 85%, respectively. Using median spectra for each patient instead of all replicates, the sensitivity and specificity were 84.62% and 82.50%, respectively. The overall accuracy rate was 82%-86%. In conclusion, this study suggests that FTIR spectroscopy combined with advanced methods of pattern analysis shows potential for differentiating sera from cirrhotic patients with and without HCC.

  16. Myofacial Trigger Points in Advanced Cancer Patients

    PubMed Central

    Hasuo, Hideaki; Ishihara, Tatsuhiko; Kanbara, Kenji; Fukunaga, Mikihiko

    2016-01-01

    Myofascial pain syndrome is started to be recognized as one of important factors of pain in cancer patients. However, no reports on features of myofascial trigger points were found in terminally-ill cancer populations. This time, we encountered 5 patients with myofascial pain syndrome and terminal cancer in whom delirium developed due to increased doses of opioid without a diagnosis of myofascial pain syndrome on initial presentation. The delirium subsided with dose reductions of opioid and treatment of myofascial pain syndrome. The common reason for a delayed diagnosis among the patients included an incomplete palpation of the painful sites, which led to unsuccessful myofascial trigger points identification. The features of myofascial trigger points included single onset in the cancer pain management site with opioid and the contralateral abdominal side muscles of the non-common sites. Withdrawal reflexes associated with cancer pain in the supine position, which are increasingly seen in the terminal cancer patients, were considered to have contributed to this siuation. We consider that careful palpation of the painful site is important, in order to obtain greater knowledge and understanding of the features of myofascial trigger points. PMID:26962285

  17. Radioembolization using 90Y-resin microspheres for patients with advanced hepatocellular carcinoma

    SciTech Connect

    Sangro, Bruno . E-mail: bsangro@unav.es; Bilbao, Jose I.; Boan, Jose; Martinez-Cuesta, Antonio; Benito, Alberto; Rodriguez, Javier; Panizo, Angel; Gil, Belen; Inarrairaegui, Mercedes; Herrero, Ignacio; Quiroga, Jorge; Prieto, Jesus

    2006-11-01

    Purpose: To investigate the antitumor effect of resin microspheres loaded with 90-yttrium against hepatocellular carcinoma and their safety in the setting of liver cirrhosis. Patients and Methods: Data from 24 consecutive patients with hepatocellular carcinoma (HCC) treated by radioembolization in the period from September 2003 to February 2005 were reviewed. Patients received no further antineoplastic therapy. A comprehensive evaluation was performed to prevent the risk of damage due to microsphere misplacing. Patients were discharged the day after microspheres injection. Results: Serious liver toxicity observed among cirrhotic patients in a first period was subsequently prevented by modifying the selection criteria and the method for calculating the activity to be administered. Among 21 patients evaluable for response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria, a reduction in size of target lesions was observed in all but 1 patient. When considering only target lesions, disease control rate and response rate were 100% and 23.8%, respectively. However, 43% of patients progressed in the liver in the form of new lesions appearing a median time of 3 months after radioembolization. Conclusion: Our experience in these series of patients indicates that radioembolization using resin microspheres has a significant antitumor effect against HCC and that using stringent selection criteria and conservative models for calculating Radiation activity to be administered, radioembolization can be performed safely even in cirrhotic patients.

  18. Measuring patient-reported outcomes in advanced gastric cancer

    PubMed Central

    Xu, Jianming; Evans, TR Jeffry; Coon, Cheryl; Copley-Merriman, Kati; Su, Yun

    2013-01-01

    Background Gastric cancer (GC), one of the most common cancers in the world, is often diagnosed at an advanced stage and associated with a poor prognosis. Quality of life and patient-reported outcomes (PROs) are important considerations when treating GC patients. The aim of this study was to identify existing PRO instruments that would be appropriate for use in GC trials. Methods Data were obtained from a systematic literature review and interviews with clinical experts. A literature search was conducted using OVID (EMBASE and MEDLINE) and yielded 1,008 abstracts; 92 assessed PROs in an advanced GC. Results Key symptoms and functional impacts identified through the literature and expert input included abdominal pain or pain at the site of distant metastases, dysphagia and other symptoms related to eating, and digestive symptoms. The liver and lungs were the most frequent locations of metastases, leading to dyspnea, abdominal fullness, and jaundice. Symptoms related to changes in bowel habits appeared to be more frequent and pronounced in Asian patients, possibly due to the higher prevalence of GC in the body of the stomach in this population. The five most commonly used PRO instruments were identified, but their validity in advanced-stage GC patients remains unclear. Conclusions The symptoms and functional impacts identified here should be confirmed with robust input from advanced-stage GC patients. Optimal measurement of PROs in GC should account for patient burden and possible differences between Asian and non-Asian patients. PMID:24062809

  19. Early Decreases in α-Fetoprotein and Des-γ-carboxy Prothrombin Predict the Antitumor Effects of Hepatic Transarterial Infusion Chemotherapy with Cisplatin (CDDP) Powder in Patients with Advanced Hepatocellular Carcinoma.

    PubMed

    Hatanaka, Takeshi; Kakizaki, Satoru; Shimada, Yasushi; Takizawa, Daichi; Katakai, Kenji; Yamazaki, Yuichi; Sato, Ken; Kusano, Motoyasu; Yamada, Masanobu

    2016-01-01

    Objective We retrospectively investigated the relationship between the tumor response and serial changes in α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) during hepatic arterial infusion of a cisplatin powder formulation (CDDP powder) in patients with advanced hepatocellular carcinoma (HCC). Methods Seventy-six advanced HCC patients were analyzed. All HCC patients received high-concentration cisplatin (1.43 mg/mL) via the haptic artery at a dose of 65 mg/m(2). AFP and DCP were measured at baseline and four to eight weeks after treatment, and the antitumor responses were evaluated according to the response evaluation criteria in solid tumours (RECIST) criteria after one or two courses of treatment. The patients were classified into two groups, a decreased group and a non-decreased group, according to the change in the serum levels of AFP and DCP at four to eight weeks compared to baseline. Results The response to treatment of the decreased group (n=16) and non-decreased group (n=60) was complete response/partial response/stable disease/progressive disease (CR/PR/SD/PD) in 4/4/5/3 and 1/11/8/40 patients, respectively. The response rate and disease control rate of the decreased group were significantly higher than those of the non-decreased group (p=0.016 and p<0.001, respectively). The median survival time (MST) of the decreased/non-decreased groups were 25.9/10.6 months, respectively. The cumulative survival rates for the decreased group were significantly higher than those of the non-decreased group (p=0.042). In the multivariate analysis, vascular invasion and the decreased group were significant factors that affected the therapeutic efficacy. Conclusion A decrease in the levels of AFP and DCP after the first treatment with CDDP powder is a good predictor for the antitumor effect and the prognosis. PMID:27522991

  20. Sarcopenia and physical function in overweight patients with advanced cancer.

    PubMed

    Prado, Carla M M; Lieffers, Jessica R; Bowthorpe, Lindsay; Baracos, Vickie E; Mourtzakis, Marina; McCargar, Linda J

    2013-01-01

    Advanced cancer is associated with numerous metabolic abnormalities that may lead to significant body composition changes, particularly muscle loss or sarcopenia. Sarcopenia in cancer has been associated with poor clinical outcomes, including poor physical function. Accurate tools to assess body composition are expensive and not readily available in clinical settings. Unfortunately, little is known about the efficacy of affordable and portable techniques to assess functional status in patients with cancer. We investigated the prevalence of sarcopenia and its association with different portable and low-cost functional status measurement tools (i.e., handgrip strength testing, a two-minute walking test, and a self-report questionnaire) in overweight/obese patients (body mass index ≥ 25 kg/m²) with advanced cancer. Twenty-eight patients (68% men) aged 64.5 ± 9.5 years with advanced lung or colorectal cancer were included. Sarcopenia was assessed by measuring appendicular skeletal muscle (ASM) adjusted by height (ASM index), using dual energy X-ray absorptiometry. Approximately 36% of patients had sarcopenia. Average handgrip strength was greater in men without sarcopenia than in men with it (p=0.035). In men, ASM index was positively correlated with average (r=0.535, p=0.018) and peak handgrip strength (r=0.457, p=0.049). No differences were observed among female patients. Handgrip strength was associated with sarcopenia in male patients with advanced cancer, and therefore it may be used as a portable and simple nutritional screening tool.

  1. Palliative care for patients with advance chronic kidney disease.

    PubMed

    Douglas, C A

    2014-01-01

    Over the past three decades there has been a dramatic rise in the number of patients with advanced chronic kidney disease. The fastest expanding group receiving dialysis has been the elderly. However, for those patients who are very elderly with co-morbidity, dialysis may not offer a survival advantage. Therefore, active conservative management is a growing service offered by many renal units in the UK and focuses on non-dialytic correction of fluid and electrolyes, management of renal anaemia, and assessment and management of symptoms. The five-year survival of a patient over 75 years of age starting dialysis is 20% and if a patient is over 75 years, has co-morbidity, or a poor performance status, dialysis may not offer any survival advantage. Whether a patient is managed by dialysis or by conservative management the symptom burden suffered is high. These symptoms are under-recognised and often managed poorly because of increased drug toxicity in renal failure. This complex group of patients require close working between renal, palliative care, medicine for the elderly, and community teams, to allow best quality of life and end of life care. This review describes some of the challenges in providing Advanced Care Planning for dialysis and conservatively managed patients, highlights the symptom burden of patients with advanced chronic kidney disease, and offers guidance in how to manage the symptoms effectively.

  2. [Integrated care for patients with advanced chronic obstructive pulmonary disease].

    PubMed

    Jassem, Ewa; Górecka, Dorota; Krakowiak, Piotr; Kozielski, Jerzy; Słomiński, J Marek; Krajnik, Małgorzata; Fal, Andrzej M

    2010-01-01

    Chronic obstructive pulmonary disease (COPD) is the third cause of mortality and disability (assessed by DALY) among patients above 60 year old. Severe and very severe COPD (FEV(1) = equal or less than 50% and 30% of expected value, respectively) is estimated at 20% of all COPD patients. Advanced COPD usually leads to physical and mental deterioration, the patients often manage with the problems caused by the disease and other comorbidities poorly. This leads to increased risk of COPD exacerbations and further deterioration of the patient's status, increased costs of medical care and eventually increased risk of death. Current organization of medical care for those patients does not provide adequate health and social support for them. However, it seems that introducing an integrated approach proposed by World Health Organization, could improve the situation of advanced COPD patients. In Poland, this kind of care has been provided in advanced cancer patients throughout stationary palliative care units and hospices during the last several years. This experience should be helpful in integrating actions of general practitioners and specialized nurses, as well as providing access for the specialists' consultations according to the individual needs of the patients. It should also allow for broad cooperation with auxiliary staff, such as social workers, medical assistants and volunteers, as well as psychologists and clergymen (especially in the terminal phase of the disease).

  3. Identification of IgM as a contaminant in lectin-FLISA assays for HCC detection.

    PubMed

    Wang, Mengjun; Comunale, Mary Ann; Herrera, Harmin; Betesh, Lucy; Kono, Yuko; Mehta, Anand

    2016-07-29

    Liver disease, in the form of hepatocellular carcinoma (HCC) accounts for > 700,000 deaths worldwide. A major reason for this is late diagnosis of HCC. The currently used biomarker, serum alpha-fetoprotein (AFP) is elevated in 40-60% of those with HCC and other markers that can either compliment or replace AFP are desired. Our previous work has identified a number of proteins that contain altered glycans in HCC. Specifically, these altered glycans were increased levels of core and outer arm fucosylation. To determine the clinical usefulness of those identified glycoproteins, a plate based assay was developed that allowed for the detection of fucosylated glycoforms. While this method was applicable to a number of independent patient sets, it was unable to specifically detect fucosylated glycoforms in many patient samples. That is, some material was present in serum that led to non-specific signal in the lectin- fluorescence -linked immunosorbent assay (lectin-FLISA). To address this issue, a systematic process was undertaken to identify the material. This material was found to be increased levels of lectin reactive IgM. Removal of both IgG and IgM using a multi-step protein A/G incubation and filtration step removed the contaminating signal and allowed for the analysis of specific protein glycoforms. This assay was subsequently used on two sample sets, one that was shown previously to be unable to be tested via a lectin FLISA and in a larger independent sample set. The clinical usefulness of this assay in the early detection of HCC is discussed.

  4. Identification of IgM as a contaminant in lectin-FLISA assays for HCC detection.

    PubMed

    Wang, Mengjun; Comunale, Mary Ann; Herrera, Harmin; Betesh, Lucy; Kono, Yuko; Mehta, Anand

    2016-07-29

    Liver disease, in the form of hepatocellular carcinoma (HCC) accounts for > 700,000 deaths worldwide. A major reason for this is late diagnosis of HCC. The currently used biomarker, serum alpha-fetoprotein (AFP) is elevated in 40-60% of those with HCC and other markers that can either compliment or replace AFP are desired. Our previous work has identified a number of proteins that contain altered glycans in HCC. Specifically, these altered glycans were increased levels of core and outer arm fucosylation. To determine the clinical usefulness of those identified glycoproteins, a plate based assay was developed that allowed for the detection of fucosylated glycoforms. While this method was applicable to a number of independent patient sets, it was unable to specifically detect fucosylated glycoforms in many patient samples. That is, some material was present in serum that led to non-specific signal in the lectin- fluorescence -linked immunosorbent assay (lectin-FLISA). To address this issue, a systematic process was undertaken to identify the material. This material was found to be increased levels of lectin reactive IgM. Removal of both IgG and IgM using a multi-step protein A/G incubation and filtration step removed the contaminating signal and allowed for the analysis of specific protein glycoforms. This assay was subsequently used on two sample sets, one that was shown previously to be unable to be tested via a lectin FLISA and in a larger independent sample set. The clinical usefulness of this assay in the early detection of HCC is discussed. PMID:27181357

  5. Phase I study of tivantinib in Japanese patients with advanced hepatocellular carcinoma: Distinctive pharmacokinetic profiles from other solid tumors.

    PubMed

    Okusaka, Takuji; Aramaki, Takeshi; Inaba, Yoshitaka; Nakamura, Shinichiro; Morimoto, Manabu; Moriguchi, Michihisa; Sato, Takashi; Ikawa, Yuta; Ikeda, Masafumi; Furuse, Junji

    2015-05-01

    A c-Met inhibitor tivantinib is a candidate anticancer agent for patients with hepatocellular carcinoma (HCC), and CYP2C19 is the key metabolic enzyme for tivantinib. Previous Japanese phase I studies in patients with solid tumors (except HCC) recommend 360 mg twice daily (BID) and 240 mg BID for CYP2C19 extensive metabolizers (EM) and poor metabolizers (PM), respectively. In this study, Japanese patients with HCC in whom sorafenib treatment has failed were enrolled to evaluate the safety, tolerability and pharmacokinetics of oral tivantinib as a single agent. The dose was escalated separately in EM and PM, from 120 mg BID to 240 mg BID, in both capsule and tablet formulations. A total of 28 patients (EM: 21, PM: 7) received tivantinib. At a dose of 120 mg BID, dose-limiting toxicities (DLT) did not develop in 12 EM (capsule: 6, tablet: 6) and 7 PM (capsule: 4, tablet: 3) during the DLT-observation period (for 29 days after first dosing). At this dose, the pharmacokinetic profiles of tivantinib (AUC0-12 and Cmax ) did not remarkably differ between EM and PM. When treated with 240 mg BID, 5 of 9 EM (capsule: 4 of 6, tablet: 1 of 3) developed neutropenia-related DLT accompanying plasma tivantinib concentration higher than expected from the previous studies. Consequently, PM did not receive 240 mg BID. In conclusion, 120 mg BID of tivantinib is recommended among Japanese patients with HCC regardless of CYP2C19 phenotype. PMID:25711511

  6. The direct and indirect roles of HBV in liver cancer: prospective markers for HCC screening and potential therapeutic targets.

    PubMed

    Ringelhan, Marc; O'Connor, Tracy; Protzer, Ulrike; Heikenwalder, Mathias

    2015-01-01

    Chronic hepatitis B virus (HBV) infection remains the number one risk factor for hepatocellular carcinoma (HCC), accounting for more than 600 000 deaths/year. Despite highly effective antiviral treatment options, chronic hepatitis B (CHB), subsequent end-stage liver disease and HCC development remain a major challenge worldwide. In CHB, liver damage is mainly caused by the influx of immune cells and destruction of infected hepatocytes, causing necro-inflammation. Treatment with nucleoside/nucleotide analogues can effectively suppress HBV replication in patients with CHB and thus decrease the risk for HCC development. Nevertheless, the risk of HCC in treated patients showing sufficient suppression of HBV DNA replication is significantly higher than in patients with inactive CHB, regardless of the presence of baseline liver cirrhosis, suggesting direct, long-lasting, predisposing effects of HBV. Direct oncogenic effects of HBV include integration in the host genome, leading to deletions, cis/trans-activation, translocations, the production of fusion transcripts and generalized genomic instability, as well as pleiotropic effects of viral transcripts (HBsAg and HBx). Analysis of these viral factors in active surveillance may allow early identification of high-risk patients, and their integration into a molecular classification of HCC subtypes might help in the development of novel therapeutic approaches.

  7. Loss of miR-532-5p in vitro promotes cell proliferation and metastasis by influencing CXCL2 expression in HCC

    PubMed Central

    Song, Xiaofei; Wang, Zie; Jin, Yan; Wang, Yong; Duan, Wenbing

    2015-01-01

    MicroRNAs (miRNAs) have been widely reported, which play important roles in cancer development. CXCL2 acts as an oncogene, however, its regulation by miRNAs is not clear in hepatocellular carcinoma (HCC). In our research, it is aimed to study the role of CXCL2 in HCC and the regulation of its expression by miRNAs. Firstly, we found that CXCL2 was up-regulated in the blood of patients with HCC and cell lines compared with the normal controls. CXCL2 could enhance HCC cell proliferation and metastasis. miR-532-5p was predicted as a regulatory miRNA of CXCL2 in HCC, and negatively associated with CXCL2 in HCC samples. It was also verified that miR-532-5p inhibited cell proliferation and metastasis of HCC cells by inhibition CXCL2. Collectively, our findings suggested that miR-532-5p may function as a tumor suppressor in HCC by targeting CXCL2. PMID:26807173

  8. Small molecule inhibitors of Late SV40 Factor (LSF) abrogate hepatocellular carcinoma (HCC): Evaluation using an endogenous HCC model

    PubMed Central

    Rajasekaran, Devaraja; Siddiq, Ayesha; Willoughby, Jennifer L.S.; Biagi, Jessica M.; Christadore, Lisa M.; Yunes, Sarah A.; Gredler, Rachel; Jariwala, Nidhi; Robertson, Chadia L.; Akiel, Maaged A.; Shen, Xue-Ning; Subler, Mark A.; Windle, Jolene J.; Schaus, Scott E.; Fisher, Paul B.; Hansen, Ulla; Sarkar, Devanand

    2015-01-01

    Hepatocellular carcinoma (HCC) is a lethal malignancy with high mortality and poor prognosis. Oncogenic transcription factor Late SV40 Factor (LSF) plays an important role in promoting HCC. A small molecule inhibitor of LSF, Factor Quinolinone Inhibitor 1 (FQI1), significantly inhibited human HCC xenografts in nude mice without harming normal cells. Here we evaluated the efficacy of FQI1 and another inhibitor, FQI2, in inhibiting endogenous hepatocarcinogenesis. HCC was induced in a transgenic mouse with hepatocyte-specific overexpression of c-myc (Alb/c-myc) by injecting N-nitrosodiethylamine (DEN) followed by FQI1 or FQI2 treatment after tumor development. LSF inhibitors markedly decreased tumor burden in Alb/c-myc mice with a corresponding decrease in proliferation and angiogenesis. Interestingly, in vitro treatment of human HCC cells with LSF inhibitors resulted in mitotic arrest with an accompanying increase in CyclinB1. Inhibition of CyclinB1 induction by Cycloheximide or CDK1 activity by Roscovitine significantly prevented FQI-induced mitotic arrest. A significant induction of apoptosis was also observed upon treatment with FQI. These effects of LSF inhibition, mitotic arrest and induction of apoptosis by FQI1s provide multiple avenues by which these inhibitors eliminate HCC cells. LSF inhibitors might be highly potent and effective therapeutics for HCC either alone or in combination with currently existing therapies. PMID:26313006

  9. An overview of advance care planning for patients with advanced chronic kidney disease: The basics.

    PubMed

    Wasylynuk, Betty Ann; Davison, Sara N

    2016-01-01

    As the number of Canadians living with end-stage kidney disease (ESKD) continues to grow, even higher numbers are living with advanced chronic kidney disease (CKD). Many of these people will eventually require renal replacement therapy (RRT), either dialysis or transplantation. More than 50% of patients starting RRT today are aged 65 or older, with the fastest growing group being patients 75 years and older. Despite advances to dialysis technology and dialysis care, the mortality rates remain high and dialysis patients' end-of-life care may not align with their preferences or values. Advance care planning (ACP) is an essential component of quality comprehensive kidney care. Kidney care teams develop strong relationships with their patients and are well positioned to integrate ACP into routine kidney care. This article defines ACP, outlines the essential components of ACP, and discusses the benefits, challenges, and special considerations of ACP. By enhancing the kidney care team's understanding of ACP, this article aims to assist in integrating ACP into routine kidney care for patients with advanced CKD. PMID:27215058

  10. Necrotising herpetic retinopathy in patients with advance HIV disease.

    PubMed Central

    Miller, R F; Brink, N S; Cartledge, J; Sharvell, Y; Frith, P

    1997-01-01

    OBJECTIVES: To describe the presenting features, clinical and laboratory diagnosis, response to treatment, and outcome of necrotising herpetic retinopathy (NHR) in HIV infected patients. METHODS: Retrospective case records/laboratory data review of five HIV infected patients presenting to the specialist HIV/AIDS unit at UCL Hospitals, London from April 1994 to August 1996 with a clinical diagnosis of NHR. RESULTS: All patients had advanced HIV disease with a median CD4 count of 20.10(6)/1. Three patients had cutaneous varicella zoster virus (VZV) infection within the preceding 8 weeks. All had uniocular loss of visual acuity; one also had headache and another ocular pain. All had typical retinal appearances. VZV DNA was detected in cerebrospinal fluid of four patients (and in vitreous fluid of one of the four) and in vitreous fluid of one other. One patient refused therapy and rapidly became blind. Four patients received intravenous foscarnet with intravenous aciclovir for 6 weeks: three subsequently received oral famciclovir and one oral valaciclovir; two patients also had intravitreal injections of foscarnet. In none of the four did treatment bring about improvement in visual acuity, but in all four visual loss from retinitis was halted. CONCLUSIONS: NHR occurs in HIV infected patients with advanced HIV disease and is strongly associated with evidence of VZV infection. With aggressive use of antiviral drugs the outcome is not uniformly poor. Images PMID:9582461

  11. Identification of Circulating Biomarker Candidates for Hepatocellular Carcinoma (HCC): An Integrated Prioritization Approach

    PubMed Central

    Awan, Faryal Mehwish; Naz, Anam; Obaid, Ayesha; Ali, Amjad; Ahmad, Jamil; Anjum, Sadia; Janjua, Hussnain Ahmed

    2015-01-01

    Hepatocellular carcinoma (HCC) is the world’s third most widespread cancer. Currently available circulating biomarkers for this silently progressing malignancy are not sufficiently specific and sensitive to meet all clinical needs. There is an imminent and pressing need for the identification of novel circulating biomarkers to increase disease-free survival rate. In order to facilitate the selection of the most promising circulating protein biomarkers, we attempted to define an objective method likely to have a significant impact on the analysis of vast data generated from cutting-edge technologies. Current study exploits data available in seven publicly accessible gene and protein databases, unveiling 731 liver-specific proteins through initial enrichment analysis. Verification of expression profiles followed by integration of proteomic datasets, enriched for the cancer secretome, filtered out 20 proteins including 6 previously characterized circulating HCC biomarkers. Finally, interactome analysis of these proteins with midkine (MDK), dickkopf-1 (DKK-1), current standard HCC biomarker alpha-fetoprotein (AFP), its interacting partners in conjunction with HCC-specific circulating and liver deregulated miRNAs target filtration highlighted seven novel statistically significant putative biomarkers including complement component 8, alpha (C8A), mannose binding lectin (MBL2), antithrombin III (SERPINC1), 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1), alcohol dehydrogenase 6 (ADH6), beta-ureidopropionase (UPB1) and cytochrome P450, family 2, subfamily A, polypeptide 6 (CYP2A6). Our proposed methodology provides a swift assortment process for biomarker prioritization that eventually reduces the economic burden of experimental evaluation. Further dedicated validation studies of potential putative biomarkers on HCC patient blood samples are warranted. We hope that the use of such integrative secretome, interactome and miRNAs target filtration approach will accelerate

  12. Prognosis of morbid obesity patients with advanced heart failure.

    PubMed

    Nagarajan, Vijaiganesh; Cauthen, Clay A; Starling, Randall C; Tang, Wai Hong Wilson

    2013-01-01

    Obese patients have been noted to have better prognosis in many conditions including heart failure. We hypothesize that this favorable prognosis for obesity may not be seen in patients with morbid obesity and advanced heart failure. A total of 501 consecutive patients with advanced heart failure referred for heart transplant evaluation to the Cleveland Clinic were studied. Patients were categorized into 3 groups based on their body mass index score as nonobese (≤30 kg/m(2) ), obese (30.1-40 kg/m(2) ), and morbidly obese (≥40 kg/m(2) ). There were fewer cardiovascular risk factors in the morbidly obese group. Unadjusted event-free survival rates were 48.4%, 57.4%, and 28.6% in the nonobese, obese, and morbidly obese groups, respectively (P=.02). In univariate analysis, both the nonobese group (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.09-1.91; P=.01) and the morbidly obese group (HR, 2.46; 95% CI, 1.40-4.30; P=.002) had significantly higher risk of all-cause mortality/transplantation compared with the obese group. This difference persisted in multivariate analysis after adjustment for confounding factors. Our study re-emphasizes the presence of an obesity paradox even in patients with very advanced heart failure. This favorable prognosis, however, may not be relevant in patients with morbidly obesity. Cardiovascular risk factors may not contribute to this phenomenon.

  13. Sorafenib combined with radiofrequency ablation in the treatment of a patient with renal cell carcinoma plus primary hepatocellular carcinoma.

    PubMed

    Gang, Guo; Hongkai, Yu; Xu, Zhang

    2015-01-01

    The combination of renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) is extremely rare, and the prognosis for patients with these two cancers is poor. In the past decade, molecular targeted therapy and radiofrequency ablation (RFA) have emerged and these treatments are now playing an increasingly important role in the management of patients with advanced primary RCC and HCC. In this case report, a 72-year-old male patient diagnosed as having RCC invading the renal vein and grade I-II HCC was treated with RFA and sorafenib (400 mg twice daily). After 3 months of this combination treatment, an evaluation of his target lesions showed stable disease (SD), and progression-free survival (PFS) times were 28 months weeks for RCC and 16 months weeks for HCC. Overall survival (OS) was 40 weeks. PMID:26881596

  14. Sorafenib combined with radiofrequency ablation in the treatment of a patient with renal cell carcinoma plus primary hepatocellular carcinoma.

    PubMed

    Gang, Guo; Hongkai, Yu; Xu, Zhang

    2015-01-01

    The combination of renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) is extremely rare, and the prognosis for patients with these two cancers is poor. In the past decade, molecular targeted therapy and radiofrequency ablation (RFA) have emerged and these treatments are now playing an increasingly important role in the management of patients with advanced primary RCC and HCC. In this case report, a 72-year-old male patient diagnosed as having RCC invading the renal vein and grade I-II HCC was treated with RFA and sorafenib (400 mg twice daily). After 3 months of this combination treatment, an evaluation of his target lesions showed stable disease (SD), and progression-free survival (PFS) times were 28 months weeks for RCC and 16 months weeks for HCC. Overall survival (OS) was 40 weeks.

  15. Bridging and downstaging treatments for hepatocellular carcinoma in patients on the waiting list for liver transplantation.

    PubMed

    Pompili, Maurizio; Francica, Giampiero; Ponziani, Francesca Romana; Iezzi, Roberto; Avolio, Alfonso Wolfango

    2013-11-21

    Several therapeutic procedures have been proposed as bridging treatments for patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT). The most used treatments include transarterial chemoembolization and radiofrequency ablation. Surgical resection has also been successfully used as a bridging procedure, and LT should be considered a rescue treatment in patients with previous HCC resection who experience tumor recurrence or post-treatment severe decompensation of liver function. The aims of bridging treatments include decreasing the waiting list dropout rate before transplantation, reducing HCC recurrence after transplantation, and improving post-transplant overall survival. To date, no data from prospective randomized studies are available; however, for HCC patients listed for LT within the Milan criteria, prolonging the waiting time over 6-12 mo is a risk factor for tumor spread. Bridging treatments are useful in containing tumor progression and decreasing dropout. Furthermore, the response to pre-LT treatments may represent a surrogate marker of tumor biological aggressiveness and could therefore be evaluated to prioritize HCC candidates for LT. Lastly, although a definitive conclusion can not be reached, the experiences reported to date suggest a positive impact of these treatments on both tumor recurrence and post-transplant patient survival. Advanced HCC may be downstaged to achieve and maintain the current conventional criteria for inclusion in the waiting list for LT. Recent studies have demonstrated that successfully downstaged patients can achieve a 5-year survival rate comparable to that of patients meeting the conventional criteria without requiring downstaging. PMID:24282343

  16. PET Imaging of Oncolytic VSV Expressing the Mutant HSV-1 Thymidine Kinase Transgene in a Preclinical HCC Rat Model

    PubMed Central

    Muñoz-Álvarez, Kim A; Altomonte, Jennifer; Laitinen, Iina; Ziegler, Sibylle; Steiger, Katja; Esposito, Irene; Schmid, Roland M; Ebert, Oliver

    2015-01-01

    Hepatocellular carcinoma (HCC) is the most predominant form of liver cancer and the third leading cause of cancer-related death worldwide. Due to the relative ineffectiveness of conventional HCC therapies, oncolytic viruses have emerged as novel alternative treatment agents. Our previous studies have demonstrated significant prolongation of survival in advanced HCC in rats after oncolytic vesicular stomatitis virus (VSV) treatment. In this study, we aimed to establish a reporter system to reliably and sensitively image VSV in a clinically relevant model of HCC for clinical translation. To this end, an orthotopic, unifocal HCC model in immune-competent Buffalo rats was employed to test a recombinant VSV vector encoding for an enhanced version of the herpes simplex virus 1 (HSV-1) thymidine kinase (sr39tk) reporter, which would allow the indirect detection of VSV via positron emission tomography (PET). The resulting data revealed specific tracer uptake in VSV-HSV1-sr39tk–treated tumors. Further characterization of the VSV-HSV1-sr39tk vector demonstrated its optimal detection time-point after application and its detection limit via PET. In conclusion, oncolytic VSV expressing the HSV1-sr39tk reporter gene allows for highly sensitive in vivo imaging via PET. Therefore, this imaging system may be directly translatable and beneficial in further clinical applications. PMID:25609160

  17. A Review of Recent Advances in Perioperative Patient Safety

    PubMed Central

    Fowler, Alexander J.

    2013-01-01

    Major complications in surgery affect up to 16% of surgical procedures. Over the past 50 years, many patient safety initiatives have attempted to reduce such complications. Since the formation of the National Patient Safety Agency in 2001, there have been major advances in patient safety. Most recently, the production and implementation of the Surgical Safety Checklist by the World Health Organisation (WHO), a checklist ensuring that certain ‘never events’ (wrong-site surgery, wrong operation etc.) do not occur, irrespective of healthcare allowance. In this review, a summary of recent advances in patient safety are considered – including improvements in communication, understanding of human factors that cause mistakes, and strategies developed to minimise these. Additionally, the synthesis of best medical practice and harm minimisation is examined, with particular emphasis on communication and appreciation of human factors in the operating theatre. This is based on the resource management systems developed in other high risk industries (e.g. nuclear), and has also been adopted for other high risk medical areas. The WHO global movement to reduce surgical mortality has been highly successful, especially in the healthcare systems of developing nations where mortality reductions of up to 50% have been observed, and reductions in patient complications of 4%. Incident reporting has long been a key component of patient safety and continues to be so; allowing reflection and improved guideline formation. All patients are placed at risk in the surgical environment. It is crucial that this risk is minimised, whilst optimising the patient's outcome. In this review, recent advances in perioperative patient safety are examined and placed in context. PMID:26977290

  18. Orphan symptoms in advanced cancer patients followed at home.

    PubMed

    Mercadante, Sebastiano; Porzio, Giampiero; Valle, Alessandro; Fusco, Flavio; Aielli, Federica; Adile, Claudio; Casuccio, Alessandra

    2013-12-01

    Orphan symptoms are rarely assessed, particularly at home. The aim of this multicenter prospective study was to assess the prevalence of these symptoms and eventual factors possibly associated in advanced cancer patients at admission of a home care program. A prospective study was performed at three home care programs in Italy. Patients' data were collected, including age, sex, diagnosis, and Karnofsky status. Possible contributing factors were analyzed; preexisting neurological diseases, cerebral metastases, hyperthermia, diabetes, a state of dehydration clinically evident and/or oliguria, possible biochemical parameters when available, data regarding recent chemotherapy, opioids and doses, use of neuroleptics, benzodiazepine or anticonvulsants, corticosteroids, anti-inflammatory, and antibiotics were collected. Myoclonus, hiccup, sweating, pruritus, and tenesmus, either rectal or vesical, were assessed, according to a preliminary definition, at time of home care program admission. Three hundred sixty-two patients were surveyed at the three home care programs. Globally, 48 patients presented one or more orphan symptoms in the period taken into consideration, and 7 patients presented more than 1 symptom. One patient presented occasional and diffuse myoclonus. Nineteen patients presented sweating, 13 patients presented pruritus, and 14 patients presented hiccup. Finally, nine patients presented rectal or vesical tenesmus. There was a significant correlation between sweating and transdermal fentanyl use (P = 0.044), fever (P = 0.001), hiccup (P < 0.0005), and vesical tenesmus (P = 0.028). Pruritus was not associated to any factor. Hiccup was associated with gender (males, P = 0.006) and sweating (P < 0.0005). Vesical tenesmus was associated with fever (P = 0.019) and sweating (P = 0.028). Although the symptoms examined have a low prevalence in advanced cancer patients admitted to home care, the distress for patients may be high and

  19. Nutritional management of the patient with advanced cancer.

    PubMed

    Theologides, A

    1977-02-01

    Protein-calorie malnutrition, vitamin and other deficiencies, and weight loss frequently develop in cancer patients. Although there is no evidence that aggressive nutritional management prolongs survival, it may improve the quality of life. Efforts should be made to maintain adequate daily caloric intake with appropriate food selection and with control of complications interfering with nutrition. In selected patients, intravenous hyperalimentation can provide adequate nutrition during potentially effective chemotherapy or radiotherapy. Elemental diets also may be a source of complete or supplemental nutrition. Further experience with both approaches will help to clarify their role in the nutritional management of the patient with advanced cancer.

  20. Modalities of palliative care in hospitalized patients with advanced AIDS.

    PubMed

    Vincent, I; D'Hérouville, D; Moulin, P; Bugler, C; Fraval, J; Mallet, D; Salamagne, M H; Vildé, J L; Jodelet, D; Leport, C

    2000-04-01

    This prospective multidisciplinary survey started in October 1994. The survey assessed the modalities of care of hospitalized patients with advanced AIDS in an Infectious and Tropical Diseases Unit with regards to the practices of palliative care in a Palliative Care Unit. Seventy-eight (78) AIDS patients with CD4 < or = 30/mm3 who had 102 consecutive hospitalizations were recruited. Types (symptomatic or curative) and number of drugs administered to the patients, as well as biological and radiological investigations performed were recorded. Symptoms were concomitantly assessed on a weekly basis by self-evaluation of the patients themselves and by physicians. The results showed that the practices of care were different in the two units according to the specific goals and norms of each unit. A higher density of care was delivered at the Infectious and Tropical Diseases Unit. Symptoms assessed by both patients and physicians were underestimated by physicians in frequency and in intensity. In conclusion, an integrated approach including objective and subjective criteria should enable a better adjustment of the palliative and curative therapeutic strategies in advanced AIDS. These would concomitantly take into account the wishes of the patient and the goals regarding care in the unit where the patient is hospitalized.

  1. Frequency of elevated biomarkers in patients with cryptogenic hepatocellular carcinoma

    PubMed Central

    Taura, Naota; Ichikawa, Tatsuki; Miyaaki, Hisamitsu; Ozawa, Eisuke; Tsutsumi, Takuya; Tsuruta, Shotaro; Kato, Yuji; Goto, Takashi; Kinoshita, Noboru; Fukushima, Masanori; Kato, Hiroyuki; Ohata, Kazuyuki; Ohba, Kazuo; Masuda, Junichi; Hamasaki, Keisuke; Yatsuhashi, Hiroshi; Nakao, Kazuhiko

    2013-01-01

    Background The incidence of hepatocellular carcinoma (HCC) continues to increase in Japan, but the clinical characteristics of Japanese patients with HCC have not been well described. The aim of this study was to determine the frequencies and utilities of elevated α-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) levels as biomarkers in cryptogenic HCC. Material/Methods A total of 2638 patients with HCC diagnosed between 1999 and 2010 in the Nagasaki Association Study of Liver (NASLD) were recruited for this study. The cause of HCC was categorized into 4 groups; HCC-B, HCC-C, HCC-BC, and HCC-nonBC. The significance of factors was examined for HCC-nonBC using logistic regression analysis in all patients. Results Multivariate analysis identified age, sex, BMI, alcohol consumption, platelet count, AST, ALT, AFP, DCP, and TNM stage as independent and significant risk factors for HCC-nonBC. According to TNM stage, the median AFP levels in HCC-nonBC with TNM stages I, II, and III were significantly lower than in either HCC-B or HCC-C. In TNM stage IV, the median AFP level in HCC-nonBC was significantly lower than in either HCC-B or HCC-BC. The median DCP levels in HCC-nonBC with TNM stages I and II were significantly higher than those in either HCC-B or HCC-C. In TNM stage III, the median DCP level in HCC-nonBC was significantly higher than that in HCC-C. Conclusions DCP was more sensitive than AFP for the diagnosis of early stage cryptogenic HCC. DCP should be used as the main serum test for cryptogenic HCC detection. PMID:24008520

  2. Febuxostat for hyperuricemia in patients with advanced chronic kidney disease.

    PubMed

    Akimoto, Tetsu; Morishita, Yoshiyuki; Ito, Chiharu; Iimura, Osamu; Tsunematsu, Sadao; Watanabe, Yuko; Kusano, Eiji; Nagata, Daisuke

    2014-01-01

    Febuxostat is a nonpurine xanthine oxidase (XO) inhibitor, which recently received marketing approval. However, information regarding the experience with this agent among advanced chronic kidney disease (CKD) patients is limited. In the current study, we investigated the effects of oral febuxostat in patients with advanced CKD with asymptomatic hyperuricemia. We demonstrated, for the first time, that not only the serum levels of uric acid (UA) but also those of 8-hydroxydeoxyguanosine, an oxidative stress marker, were significantly reduced after six months of febuxostat treatment, with no adverse events. These results encouraged us to pursue further investigations regarding the clinical impact of lowering the serum UA levels with febuxostat in advanced CKD patients in terms of concomitantly reducing oxidative stress via the blockade of XO. More detailed studies with a larger number of subjects and assessments of the effects of multiple factors affecting hyperuricemia, such as age, sex, and dietary habits, would shed light on the therapeutic challenges of treating asymptomatic hyperuricemia in patients with various stages of CKD. PMID:25210423

  3. Preservation of segment 4 inferior by distal middle hepatic vein reconstruction combined with extended right hepatectomy after portal vein embolization in a patient with a huge initially unresectable HCC.

    PubMed

    Nakano, Hiroshi; Kikuchi, Keita; Seta, Shin-ichi; Katayama, Masafumi; Yamamura, Takuya; Otsubo, Takehito

    2007-01-01

    An extended hepatectomy combined with preoperative portal venous embolization can offer curative resection in patients with initially unresectable hepatocellular carcinoma. However, hypertrophy of the future remnant liver is occasionally unsatisfactory after portal venous embolization in some patients to remove the initially unresectable tumor. In these patients, hepatic venous reconstruction to preserve hepatic parenchyma may contribute to the possibility of resection. The present case report shows a patient with an initially unresectable huge hepatocellular carcinoma in whom transarterial chemoembolization, portal vein embolization, and an extended right hepatectomy combined with distal middle hepatic venous reconstruction were performed to preserve Segment 4 inferior. The patient was a 66-year-old male. He presented with a huge hepatocellular carcinoma located at Segment 8, 7 and 4 superior, but the volume of the left lateral segment was only 267 mL. Transarterial chemoembolization was performed twice and right portal vein embolization was performed once, but the volume of the left lateral segment was only 318 mL compared to 487 mL which was a limit of future remnant liver volume. We therefore performed an extended right hepatectomy combined with distal middle hepatic venous reconstruction to preserve Segment 4 inferior. The left saphenous venous graft was used for this hepatic venous reconstruction. His postoperative course was almost uneventful. Postoperative abdominal computed tomography showed the satisfactorily preserved Segment 4 inferior. Distal hepatic venous reconstruction combined with an extended hepatectomy may further offer a chance of a curative resection for patients in whom enough hypertrophy of the future remnant liver is not obtained after portal venous embolization.

  4. Situs Inversus Totalis (SIT) with Hepatocellular Carcinoma (HCC): A Rare Case Report and Review of 12 Other Cases.

    PubMed

    Patel, Rajan B; Gupta, Natvar R; Vasava, Nitin C; Khambholja, Janak R; Chauhan, Sanjay; Desai, Amit

    2013-12-01

    Hepatocellular carcinoma (HCC) is the seventh-most common malignancy in males and ninth in females with incidence of one million new cases every year. Situs inversus totalis (SIT) is a rare congenital condition, in which there is a mirror-image transposition of both the abdominal and thoracic viscera. There are very few reported cases of HCC developing in people with SIT. In this review, we present a new case of HCC with SIT, and a review of literatures published between 1983 and 2011 on it. The literatures in English were searched through PubMed and Google Scholar, while those in Japanese language were accessed through J-EAST and translated in English with the help of Google translator on 22 April 2012. There are 6 English and 6 Japanese literatures showing 12 published cases, of which 10 cases were from Japan, 1 from Taiwan and 1 from China. Our case is probably the first case in the world beyond these regions. The articles containing adequate information, such as patient age and sex, investigations, diagnosis, type of congenital anomalies and methods of surgery, were reviewed. On reviewing the literature, we observed that clinical manifestations, laboratory findings and etiology correlate well with HCC, while anomalous hepatic vascularity correlates well with SIT. The reason for high incidence of HCC with SIT in Japan is not well correlated, but may be explained by higher incidence of SIT. All varieties of hepatic resection were feasible in cases of SIT. PMID:24465096

  5. [A Case of Multiple HCC with Vp2 and Vv3 Invasion Controlled by Multidisciplinary Treatment Including Surgery].

    PubMed

    Deguchi, Sota; Tsukamoto, Tadashi; Kanazawa, Akishige; Shimizu, Sadatoshi; Yamamoto, Satoshi; Murata, Akihiro; Nakajima, Takayoshi; Sakae, Masayuki; Tachimori, Akiko; Tamamori, Yutaka; Yamamoto, Atsushi; Inoue, Toru; Yamashita, Yoshito; Nishiguchi, Yukio

    2015-11-01

    The prognosis of HCC with vascular invasion is dismal, but surgery is elected when the hepatic reserve is adequate. The case involved a 68-year-old male HCV carrier. A 10 cm diameter tumor occupying the central 2 segments of the liver and liver metastasis in the left lobe were detected. The patient was diagnosed with multiple HCC with severe vascular invasion of Vp2 and Vv3. The tumor shrunk dramatically after starting HAIC therapy with cisplatin and oral administration of sorafenib. A laparoscopic partial hepatectomy was performed for the viable lesion. The tumor showed almost complete coagulative necrosis. Multiple hepatic metastases were found 4 months after surgery, but the tumor was under control at 25 months after the first HAIC due to HAIC, oral administration of sorafenib, and RFA. An improved prognosis for multiple HCC with severe vascular invasion can be expected by performing multidisciplinary treatments including surgery. PMID:26805192

  6. Natural killer cells phenotypic characterization as an outcome predictor of HCV-linked HCC after curative treatments.

    PubMed

    Cariani, Elisabetta; Pilli, Massimo; Barili, Valeria; Porro, Emanuela; Biasini, Elisabetta; Olivani, Andrea; Dalla Valle, Raffaele; Trenti, Tommaso; Ferrari, Carlo; Missale, Gabriele

    2016-08-01

    NK-cell number and function have been associated with cancer progression. A detailed analysis of phenotypic and functional characteristics of NK-cells in HCC is still lacking. NK-cell function is regulated by activating and inhibitory receptors determined by genetic factors and engagement with cognate ligands on transformed or infected cells. We evaluated phenotypic and functional characteristic of NK-cells in HCC patients undergoing curative treatment in relation to clinical outcome. NK-cells from 70 HCC patients undergoing resection or ablative treatment, 18 healthy volunteers and 12 cirrhotic patients with HCV-infection (controls) were phenotypically characterized. Unsupervised clustering based on the frequency of cells expressing different phenotypic NK-cell markers segregated HCC patients into different cohorts that were compared for outcome. NK-cell cytokine production and cytotoxicity were compared between cohorts with different overall survival (OS) and time to disease recurrence (TTR). By multivariate analysis, age, Child-Pugh class and NK-cell phenotypic clustering could independently identify patients with significantly different OS. NK-cells from patients with better outcome expressed higher levels of cytotoxic granules and CD3ζ and lower levels of natural cytotoxic receptors (NCRs) that were co-expressed with the inhibitory receptor NKG2A known to negatively regulate NCR function. Cytotoxic function and IFNγ production were significantly lower in the cohort of patients with worse outcome compared to controls (p < 0.05). Our results show a role for NK-cells in the control of HCC progression and survival providing the basis for the development of immunotherapeutic strategies to potentiate NK-cell response. PMID:27622055

  7. Natural killer cells phenotypic characterization as an outcome predictor of HCV-linked HCC after curative treatments.

    PubMed

    Cariani, Elisabetta; Pilli, Massimo; Barili, Valeria; Porro, Emanuela; Biasini, Elisabetta; Olivani, Andrea; Dalla Valle, Raffaele; Trenti, Tommaso; Ferrari, Carlo; Missale, Gabriele

    2016-08-01

    NK-cell number and function have been associated with cancer progression. A detailed analysis of phenotypic and functional characteristics of NK-cells in HCC is still lacking. NK-cell function is regulated by activating and inhibitory receptors determined by genetic factors and engagement with cognate ligands on transformed or infected cells. We evaluated phenotypic and functional characteristic of NK-cells in HCC patients undergoing curative treatment in relation to clinical outcome. NK-cells from 70 HCC patients undergoing resection or ablative treatment, 18 healthy volunteers and 12 cirrhotic patients with HCV-infection (controls) were phenotypically characterized. Unsupervised clustering based on the frequency of cells expressing different phenotypic NK-cell markers segregated HCC patients into different cohorts that were compared for outcome. NK-cell cytokine production and cytotoxicity were compared between cohorts with different overall survival (OS) and time to disease recurrence (TTR). By multivariate analysis, age, Child-Pugh class and NK-cell phenotypic clustering could independently identify patients with significantly different OS. NK-cells from patients with better outcome expressed higher levels of cytotoxic granules and CD3ζ and lower levels of natural cytotoxic receptors (NCRs) that were co-expressed with the inhibitory receptor NKG2A known to negatively regulate NCR function. Cytotoxic function and IFNγ production were significantly lower in the cohort of patients with worse outcome compared to controls (p < 0.05). Our results show a role for NK-cells in the control of HCC progression and survival providing the basis for the development of immunotherapeutic strategies to potentiate NK-cell response.

  8. Exchange of the H(CC) domain mediating double receptor recognition improves the pharmacodynamic properties of botulinum neurotoxin.

    PubMed

    Rummel, Andreas; Mahrhold, Stefan; Bigalke, Hans; Binz, Thomas

    2011-12-01

    The four-domain structure of botulinum neurotoxins (BoNTs) reflects their multistep intoxication process. The high toxicity of BoNTs primarily results from specific binding and uptake into neurons mediated by their 50-kDa cell-binding fragment (H(C) ). X-ray crystallography data have revealed that the H(C) fragment consists of two domains of equal size, named the 25-kDa N-terminal half of H(C) (H(CN) ) and the 25-kDa C-terminal half of H(C) (H(CC) ). In recent years, the ganglioside-binding sites of all seven BoNT serotypes have been allocated to the H(CC) domain. For BoNT/A, BoNT/B and BoNT/G, the protein receptor-binding site has been also been localized to the H(CC) domain. Here, we demonstrate that the H(CC) serotype can modulate the affinity of the H(C) fragment for neuronal membranes as well as the potency of full-length BoNT by replacing the BoNT/A H(CC) domain with the BoNT/B H(CC) , BoNT/C H(CC) and BoNT/E H(CC) domains, which exhibit higher affinity for synaptosomes. Indeed, the hybrids H(C) AB and H(C) AC display a higher affinity than wild-type H(C) A. Furthermore, the potency of a BoNT/A-based full-length hybrid containing the H(CC) B domain (AAAB; letters represent the serotype origin of the four domains) was quadrupled as compared with wild-type BoNT/A. Analogously, exchange of the H(C) fragment (AABB) yielded a neurotoxin with four-fold higher potency. As BoNT/A and BoNT/B are extensively used to treat neurological disorders, thereby facing the problem of BoNT neutralizing antibody formation, a BoNT with increased potency would lower the repeatedly administered protein dosage while maintaining the clinical benefit. Such a lowered protein load will delay the onset of neurotoxin antibody formation in patients.

  9. Prognostic Value of VEGF in Hepatocellular Carcinoma Patients Treated with Sorafenib: A Meta-Analysis

    PubMed Central

    Cao, Guangchao; Li, Xiaoyun; Qin, Chao; Li, Jie

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is characterized by rich vascularization in the tumor, and vascular endothelial growth factor (VEGF) plays important roles in vascularization. The results of the roles of VEGF in predicting efficacy of sorafenib in HCC are conflicting. In this meta-analysis, we aimed to investigate the prognostic and predictive value of VEGF in HCC patients receiving sorafenib. Material/Methods PubMed, Embase, and Cochrane library electronic databases were systematically searched for eligible studies. The baseline characteristics were recorded and overall qualities of the eligible studies were assessed by 2 reviewers independently. VEGF levels and data relevant to efficacy of sorafenib were extracted and used for meta-analysis. Results The comprehensive search yielded 9 studies that evaluated the relationship between VEGF level and clinical outcome in advanced HCC patients treated with sorafenib. Pooled estimates suggested that high level of VEGF was associated with poor overall survival (HR=1.85; 95% CI: 1.24–2.77; P=0.003) and poor progression-free survival (HR=2.09; 95% CI: 1.43–3.05; P<0.01) in HCC. Mutation of VEGF had a favorable effect on hand-foot skin reaction in HCC patients treated with sorafenib (P<0.05). Conclusions High level of VEGF is associated with poor outcomes in HCC patients treated with sorafenib, indicating that VEGF could be used as an indicator of clinical efficacy in patients with HCC. However, more well-designed studies are needed to strengthen our findings. PMID:26476711

  10. [Vital prognosis in advanced cancer patients: a systematic literature review].

    PubMed

    Tavares, Teresa; Gonçalves, Edna

    2013-01-01

    Prognostication is a critical medical task for the adequacy of treatment and management of priorities and expectations of patients and families. In 2005, the European Association of Palliative Care (EAPC) published recommendations on the formulation of vital prognosis in advanced cancer patients. The aim of this study is to analyze the literature subsequent to this review and to update the presented recommendations. Using the same strategy of the EAPC group, we performed a systematic literature search in the electronic databases PubMed and Scopus, which included original studies in adults with advanced cancer, without tumor-directed treatment, with a median survival of less than 90 days. The articles were analyzed and classified according to the level of evidence by two independent reviewers. The 41 articles analyzed allowed to keep grade A recommendations for clinical estimation of survival and Palliative Prognostic score and now also for Palliative Prognostic Index, performance status, dyspnea, lymphopenia and lactate dehydrogenase. Recommendations regarding the use of C-reactive protein, leukocytosis, azotemia, hypoalbuminemia and male gender as predictors reached grade B. To formulate the vital prognosis and to communicate it properly to the patient and family are core competencies of physicians, particularly of those who deal with end of life patients. The clinical impression combined with scientific evidence allows us to estimate more accurately the survival, allowing prioritizing and managing more appropriately the existing resources.

  11. Phase 2 Study of Combined Sorafenib and Radiation Therapy in Patients With Advanced Hepatocellular Carcinoma

    SciTech Connect

    Chen, Shang-Wen; Lin, Li-Ching; Kuo, Yu-Cheng; Liang, Ji-An; Kuo, Chia-Chun; Chiou, Jeng-Fong

    2014-04-01

    Purpose: This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC). Methods and Materials: Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter. Results: Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions ≥ grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade ≥2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progression-free survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score ≥2 was associated with an inferior outcome in overall survival. Six patients (15%) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase, and 3 of them were fatal. Conclusions: When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score ≥2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation.

  12. Radiotherapy Plus Transarterial Chemoembolization for Hepatocellular Carcinoma Invading the Portal Vein: Long-Term Patient Outcomes

    SciTech Connect

    Yoon, Sang Min; Lim, Young-Suk; Won, Hyung Jin; Kim, Jong Hoon; Kim, Kang Mo; Lee, Han Chu; Chung, Young-Hwa; Lee, Yung Sang; Lee, Sung Gyu; Park, Jin-hong; Suh, Dong Jin

    2012-04-01

    Purpose: We have evaluated the clinical outcomes of patients after transarterial chemoembolization (TACE) and 3-dimensional conformal radiotherapy for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Methods and Materials: A registry database of 412 patients treated with TACE and three-dimensional conformal radiotherapy for HCC with PVTT between August 2002 and August 2008 were analyzed retrospectively. The radiotherapy volume included the PVTT, with a 2- to 3-cm margin to cover adjacent HCC. Intrahepatic primary HCC was managed by TACE before or after radiotherapy. Results: Median patient age was 52 years old, and 88.1% of patients were male. Main or bilateral PVTT was observed in 200 (48.5%) patients. Median radiation dose was 40 Gy (range, 21-60 Gy) delivered in 2- to 5-Gy fractions. We found that 3.6% of patients achieved a complete response and that 24.3% of patients achieved a partial response. The response and progression-free rates of PVTT were 39.6% and 85.6%, respectively. Median patient survival was 10.6 months, and the 1- and 2-year survival rates were 42.5% and 22.8%, respectively. Significant independent variables associated with overall survival included advanced tumor stage, alpha-fetoprotein level, degree of PVTT, and response to radiotherapy. Forty-one patients (10.0%) showed grade 3-4 hepatic toxicity during or 3 months after completion of radiotherapy. Grades 2-3 gastroduodenal complications were observed in 15 patients (3.6%). Conclusions: Radiotherapy is a safe and effective treatment for PVTT in patients with HCC. These results suggested that the combination of TACE and radiotherapy is a treatment option for relieving and/or stabilizing PVTT in patients with advanced HCC.

  13. Tissue-Advanced Glycation End Product Concentration in Dialysis Patients

    PubMed Central

    McIntyre, Natasha J.; Chesterton, Lindsay J.; John, Stephen G.; Jefferies, Helen J.; Burton, James O.; Taal, Maarten W.; Fluck, Richard J.

    2010-01-01

    Background and objectives: Tissue-advanced glycation end products (AGE) are a measure of cumulative metabolic stress. Assessment of tissue AGE by skin autofluoresence (AF) correlates well with cardiovascular outcomes in hemodialysis (HD) patients. This study aimed to measure and compare tissue AGE levels in HD and peritoneal dialysis (PD) patients and to evaluate the impact of systemic PD glucose exposure. Design, setting, participants, & measurements: Tissue AGE were measured in 115 established dialysis patients (62 HD and 53 PD) using a cutaneous AF device (AGE Reader; DiagnOptics). Values were compared with an age-matched non–chronic kidney disease database. Review of all previous PD solution delivery/prescription data determined PD glucose exposure. Results: PD patients were similar in age to HD patients but had a shorter dialysis vintage. There were no differences in ischemic heart disease or smoking history, statin or angiotensin-converting enzyme inhibitor (ACEi) use, lipids, biochemistry, or prevalence of diabetes. More than 90% of both groups had met current dialysis adequacy targets. Skin AF values in PD and HD patients were similar and strongly correlated with historical PD glucose exposure. Skin AF correlated with age in both groups but with dialysis vintage only in PD patients Conclusions: Cumulative metabolic stress and transient hyperglycemia results in grossly elevated levels of tissue AGE in dialysis patients. In PD patients, this high level of AGE deposition is associated with historical glucose exposure. This observation provides a previously unappreciated potential link between PD exposure to glucose and systemic cardiovascular disease. PMID:19965551

  14. Pulmonary Rehabilitation in Advanced Lung Cancer Patients During Chemotherapy.

    PubMed

    Jastrzębski, D; Maksymiak, M; Kostorz, S; Bezubka, B; Osmanska, I; Młynczak, T; Rutkowska, A; Baczek, Z; Ziora, D; Kozielski, J

    2015-01-01

    The aim of this study was to investigate the utility of pulmonary rehabilitation for improving of exercises efficiency, dyspnea, and quality of life of patients with lung cancer during chemotherapy. After the enrollment selection, the study included 20 patients with newly diagnosed advanced lung cancer and performance status 0-2. There were 12 patients randomly allocated to the pulmonary rehabilitation group and another 8 constituted the control group that did not undergo physical rehabilitation. Both groups of patients had continual cycles of chemotherapy. Data were analyzed before and after 8 weeks of physical rehabilitation, and before and after 8 weeks of observation without rehabilitation in controls. The inpatient rehabilitation program was based on exercise training with ski poles and respiratory muscle training. We found a tendency for enhanced mobility (6 Minute Walk Test: 527.3 ± 107.4 vs. 563.9 ±64.6 m; p > 0.05) and a significant increase in forced expired volume in 1 s (66.9 ± 13.2 vs. 78.4 ± 17.7 %predicted; p = 0.016), less dyspnea (p = 0.05), and a tendency for improvement in the general quality of life questionnaire after completion of pulmonary rehabilitation as compared with the control group. This report suggests that pulmonary rehabilitation in advanced lung cancer patients during chemotherapy is a beneficial intervention to reduce dyspnea and enhance the quality of life and mobility.

  15. Advanced Hemodynamic Management in Patients with Septic Shock

    PubMed Central

    Huber, Wolfgang; Nierhaus, Axel; Kluge, Stefan; Reuter, Daniel A.; Wagner, Julia Y.

    2016-01-01

    In patients with sepsis and septic shock, the hemodynamic management in both early and later phases of these “organ dysfunction syndromes” is a key therapeutic component. It needs, however, to be differentiated between “early goal-directed therapy” (EGDT) as proposed for the first 6 hours of emergency department treatment by Rivers et al. in 2001 and “hemodynamic management” using advanced hemodynamic monitoring in the intensive care unit (ICU). Recent large trials demonstrated that nowadays protocolized EGDT does not seem to be superior to “usual care” in terms of a reduction in mortality in emergency department patients with early identified septic shock who promptly receive antibiotic therapy and fluid resuscitation. “Hemodynamic management” comprises (a) making the diagnosis of septic shock as one differential diagnosis of circulatory shock, (b) assessing the hemodynamic status including the identification of therapeutic conflicts, and (c) guiding therapeutic interventions. We propose two algorithms for hemodynamic management using transpulmonary thermodilution-derived variables aiming to optimize the cardiocirculatory and pulmonary status in adult ICU patients with septic shock. The complexity and heterogeneity of patients with septic shock implies that individualized approaches for hemodynamic management are mandatory. Defining individual hemodynamic target values for patients with septic shock in different phases of the disease must be the focus of future studies. PMID:27703980

  16. Genome sequesnce of lineage III Listeria monocytogenes strain HCC23

    Technology Transfer Automated Retrieval System (TEKTRAN)

    More than 98% of reported human listeriosis cases are caused by Listeria monocytogenes serotypes within lineages I and II. Serotypes within lineage III (4a and 4c) are commonly isolated from environmental and food specimens. We report the first complete genome sequence of a lineage III isolate, HCC2...

  17. Cellular apoptosis susceptibility (CAS) is linked to integrin β1 and required for tumor cell migration and invasion in hepatocellular carcinoma (HCC)

    PubMed Central

    Winkler, Juliane; Roessler, Stephanie; Sticht, Carsten; DiGuilio, Amanda L.; Drucker, Elisabeth; Holzer, Kerstin; Eiteneuer, Eva; Herpel, Esther; Breuhahn, Kai; Gretz, Norbert; Schirmacher, Peter; Ori, Alessandro; Singer, Stephan

    2016-01-01

    Importins and exportins represent an integral part of the nucleocytoplasmic transport machinery with fundamental importance for eukaryotic cell function. A variety of malignancies including hepatocellular carcinoma (HCC) show de-regulation of nuclear transport factors such as overexpression of the exportin Cellular Apoptosis Susceptibility (CAS). The functional implications of CAS in hepatocarcinogenesis remain, however, poorly understood. Here we integrated proteomics, transcriptomics and functional assays with patient data to further characterize the role of CAS in HCC. By analyzing ∼ 1700 proteins using quantitative mass spectrometry in HCC cells we found that CAS depletion by RNAi leads to de-regulation of integrins, particularly down-regulation of integrin β1. Consistent with this finding, CAS knockdown resulted in substantially reduced migration and invasion of HCC cell lines as analyzed by 2D ‘scratch’ and invasion chamber assays, respectively. Supporting the potential in vivo relevance, high expression levels of CAS in HCC tissue samples were associated with macroangioinvasion and poorer patient outcome. Our data suggest a previously unanticipated link between CAS and integrin signaling which correlates with an aggressive HCC phenotype. PMID:27015362

  18. [Molecular targeting agents for advanced or recurrent gastric cancer patients].

    PubMed

    Fuse, Nozomu

    2012-10-01

    The combination of fluoropyrimidine and platinum with or without epirubicin or docetaxel has been regarded as standard chemotherapy for advanced or recurrent gastric cancer patients. Recently, trastuzumab with conventional chemotherapy for human epidermal growth factor receptor(HER)2 positive gastric cancer patients was proved to be effective in terms of survival benefit and has become one of standard treatment options. Other molecular target agents, such as HER1, HER2, vascular endothelial growth factor, hepatocyte growth factor/c-Met, fibroblast growth factor and mammalian target of rapamycin inhibitors were and are being evaluated in clinical trials. However, no agents other than trastuzumab have shown clear survival benefit. The predictive biomarker seems to be necessary for developing new molecular targeting agents for gastric cancer with heterogeneity.

  19. Management of a patient with advanced BRAF-mutant melanoma.

    PubMed

    Ashworth, Michelle T; Daud, Adil

    2014-03-01

    A 49-year-old man initially diagnosed in 1995 with cutaneous melanoma presented to the authors' institution in 2009 with metastatic, BRAF V600E-mutant melanoma. His treatment course to date has included surgery, adjuvant radiotherapy, and interferon, metastasectomies, granulocyte-macrophage colony-stimulating factors, a clinical trial with the BRAF inhibitor vemurafenib (PLX-4032), clinical trial with combination BRAF plus MEK inhibition with vemurafenib plus GDC-0973, and combination targeted and immune therapy with vemurafenib plus the anti-CTLA4 antibody ipilimumab. This case report illustrates the long-term management of a patient with metastatic melanoma using targeted and immune therapy, evolution in treatment guidelines, next directions in research, and the critical role of clinical trials in advancement of patient care.

  20. Differential Patient-Caregiver Opinions of Treatment and Care For Advanced Lung Cancer Patients

    PubMed Central

    Zyzanski, Stephen J; Siminoff, Laura A

    2010-01-01

    This study examined the differences of opinion between cancer patients and caregivers with regard to treatment and care decisions. 184 advanced lung cancer patients and 171 primary caregivers were recruited as a convenience sample from clinics in Cleveland, Ohio. A telephone interview was conducted to collect data using a semi-structured questionnaire. Nonparametric tests and regression analysis were performed. The findings showed that patients and caregivers reported significant disagreement on three main issues: trade-off between treatment side effects and benefits; reporting treatment side effects to physicians, and hospice care. Caregivers were more concerned about patient’s quality of life and more willing to discuss hospice issues than were patients. Perceived family disagreement is associated with depression in both patients and caregivers. The study provided empirical evidence for patient-caregiver disagreement about treatment and care decisions and its significant adverse impact on both patients and caregivers. PMID:20137849

  1. [Advanced directives document and neurologist-patient relationship].

    PubMed

    Boada Rovira, M

    2004-12-01

    Perception of health and disease, pain and suffering, quality of life, personal relationships, privacy and intimacy, culture and social values, can now be stated in a written document, by way of a living will, giving legal legitimacy to each patient's way of being and understanding life, to be used when the subject cannot express it by him/herself. In this way, the patients will participate in the therapeutic process and will incorporate their desires and decisions through the Informed Consent and the Advanced Directives Document (ADD). Both documents translate and indicate how to treat and care for a patient who will progressively lose his/her cognitive faculties and others will decided for him/her, in the case of dementias. The basis of ADD is respect and promotion of the patient's autonomy, prolonging his/her right to decide in the stages in which he/she cannot do it. It consists in some instructions or orientations for the patient to be cared for in a certain way, according to his/her will. To this effect, a representative will be named who will act in the subject's name and who will help to interpret and make decisions when the patient cannot. Specifically, in Alzheimer's disease, ADD allows the patient to decide, in full lucidity, freedom and autonomy, how to live a progressive and irreversible disease. Explicit mention can be made to the will of making his/her disease known publically or not, the care of its aspect, privacy, type of care, whether institutionalized or home care, limitation of visits, treatment intensity and prolongation, palliative cares, donation of biological samples, participation in drug clinical trials. PMID:15719290

  2. [Combination Chemotherapy Using Sorafenib and Hepatic Arterial Infusion with a Fine-Powder Formulation of Cisplatin for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis--A Case Report].

    PubMed

    Tsukamoto, Tadashi; Kanazawa, Akishige; Shimizu, Sadatoshi; Murata, Akihiro; Sakae, Masayuki; Kurihara, Shigeaki; Tashima, Tetsuzo; Deguchi, Sota; Nakai, Takashi; Kawasaki, Yasuko; Kioka, Kiyohide

    2015-11-01

    Sorafenib has been a standard therapy for advanced hepatocellular carcinoma (HCC) with portal vein thrombosis. Hepatic arterial infusion chemotherapy (HAIC) is still preferably performed in Japan because of its relatively good tumor-shrinking effect. We report a case of advanced multiple HCC with portal thrombus that responded to combination chemotherapy with sorafenib and repeat hepatic arterial infusion with a fine-powder formulation of cisplatin (IA-call®). A 57-year-old man presented for the treatment of HCC with alcoholic cirrhosis. Multiple HCC were found to be rapidly progressing with portal thrombosis. HAIC with IA-call® was performed, but the tumors progressed. TAE was performed 3 times thereafter and the main tumor shrunk to some extent. A month after the last TAE, the HCC was found to progress again, and oral sorafenib was administered. A reservoir and catheter were placed and HAIC with low-dose 5-fluorouracil and cisplatin was performed for 3 cycles following 1 HAIC cycle with epirubicin and mitomycin C, which was not effective. For 10 months after initial therapy, HAIC using IA-call® has been performed once for 6 weeks. After performing HAIC with IA-call® 5 times, the serum levels of HCC tumor markers AFP and PIVKA-Ⅱdecreased, and the tumors continued to shrink and were not stained on enhanced CT scan. The patient has been alive for 23 months after the initial therapy and has maintained stable disease. PMID:26805203

  3. Serum metabolome profiles characterized by patients with hepatocellular carcinoma associated with hepatitis B and C

    PubMed Central

    Saito, Takafumi; Sugimoto, Masahiro; Okumoto, Kazuo; Haga, Hiroaki; Katsumi, Tomohiro; Mizuno, Kei; Nishina, Taketo; Sato, Sonoko; Igarashi, Kaori; Maki, Hiroko; Tomita, Masaru; Ueno, Yoshiyuki; Soga, Tomoyoshi

    2016-01-01

    AIM: To clarify the characteristics of metabolite profiles in virus-related hepatocellular carcinoma (HCC) patients using serum metabolome analysis. METHODS: The serum levels of low-molecular-weight metabolites in 68 patients with HCC were quantified using capillary electrophoresis chromatography and mass spectrometry. Thirty and 38 of the patients suffered from hepatitis B virus-related HCC (HCC-B) and hepatitis C virus-related HCC (HCC-C), respectively. RESULTS: The main metabolites characteristic of HCC were those associated with glutathione metabolism, notably 13 γ-glutamyl peptides, which are by-products of glutathione induction. Two major profiles, i.e., concentration patterns, of metabolites were identified in HCC patients, and these were classified into two groups: an HCC-B group and an HCC-C group including some of the HCC-B cases. The receiver operating characteristic curve for the multiple logistic regression model discriminating HCC-B from HCC-C incorporating the concentrations of glutamic acid, methionine and γ-glutamyl-glycine-glycine showed a highly significant area under the curve value of 0.94 (95%CI: 0.89-1.0, P < 0.0001). CONCLUSION: The serum levels of γ-glutamyl peptides, as well as their concentration patterns, contribute to the development of potential biomarkers for virus-related HCC. The difference in metabolite profiles between HCC-B and HCC-C may reflect the respective metabolic reactions that underlie the different pathogeneses of these two types of HCC. PMID:27468212

  4. CXCR4 inhibition in tumor microenvironment facilitates anti-PD-1 immunotherapy in sorafenib-treated HCC in mice

    PubMed Central

    Chen, Yunching; Ramjiawan, Rakesh R.; Reiberger, Thomas; Ng, Mei R.; Hato, Tai; Huang, Yuhui; Ochiai, Hiroki; Kitahara, Shuji; Unan, Elizabeth C.; Reddy, Tejaswini P.; Fan, Christopher; Huang, Peigen; Bardeesy, Nabeel; Zhu, Andrew X.; Jain, Rakesh K.; Duda, Dan G.

    2015-01-01

    Sorafenib—a broad tyrosine kinase inhibitor—is the only approved systemic therapy for advanced hepatocellular carcinoma (HCC), but provides limited survival benefits. Recently, immunotherapy has emerged as a promising treatment strategy, but its role remains unclear in HCCs, which are associated with decreased cytotoxic CD8+ T-lymphocyte infiltration in both murine and human tumors. Moreover, we have shown in mouse models that after sorafenib treatment, intratumoral hypoxia is increased and may fuel evasive resistance. Using orthotopic HCC models, we now show that increased hypoxia after sorafenib treatment promotes immunosuppression, characterized by increased intratumoral expression of the immune checkpoint inhibitor programmed death-ligand 1 (PD-L1) and accumulation of T-regulatory cells and M2-type macrophages. We also show that the recruitment of the immunosuppressive cells is mediated in part by hypoxia-induced upregulation of stromal cell-derived 1 alpha (SDF1α). Inhibition of the SDF1α receptor (C-X-C receptor type 4 or CXCR4) using AMD3100 prevented the polarization toward an immunosuppressive microenvironment after sorafenib treatment, inhibited tumor growth, reduced lung metastasis, and improved survival. However, combination of AMD3100 and sorafenib did not significantly change cytotoxic CD8+ T-lymphocyte infiltration into HCC tumors and did not modify their activation status. In separate experiments, antibody blockade of the PD-L1 receptor PD-1 showed anti-tumor effects in treatment-naïve tumors in orthotopic (grafted and genetically engineered) models of HCC. However, anti-PD-1 antibody treatment had additional anti-tumor activity only when combined with sorafenib and AMD3100, and not when combined with sorafenib alone. Conclusion Anti-PD-1 treatment can boost anti-tumor immune responses in HCC models. When used in combination with sorafenib, this immunotherapy approach shows efficacy only with concomitant targeting of the hypoxic and

  5. CD147 is increased in HCC cells under starvation and reduces cell death through upregulating p-mTOR in vitro.

    PubMed

    Gou, Xingchun; Tang, Xu; Kong, Derek Kai; He, Xinying; Gao, Xingchun; Guo, Na; Hu, Zhifang; Zhao, Zhaohua; Chen, Yanke

    2016-01-01

    Transarterial chemoembolization (TACE) is the standard of care for treatment of intermediate hepatocellular carcinoma (HCC), however, key molecules involved in HCC cell survival and tumor metastasis post-TACE remain unclear. CD147 is a member of the immunoglobulin superfamily that is overexpressed on the surface of HCC cells and is associated with malignant potential and poor prognosis in HCC patients. In this study, using an Earle's Balanced Salt Solution medium culture model that mimics nutrient deprivation induced by TACE, we investigated the regulation of CD147 expression on HCC cells under starvation conditions and its functional effects on HCC cell death. During early stages of starvation, the expression of CD147 was considerably upregulated in SMMC7721, HepG2 and HCC9204 hepatoma cell lines at the protein levels. Downregulation of CD147 by specific small interfering RNA (siRNA) significantly promoted starvation-induced cell death. In addition, CD147 siRNA-transfected SMMC7721 cells demonstrated significantly increased levels of both apoptosis and autophagy as compared to cells transfected with control siRNA under starvation conditions, whereas no difference was observed between the two treatment groups under normal culture conditions. Furthermore, silencing of CD147 resulted in a remarkable downregulation of phosphorylated mammalian target of rapamycin (p-mTOR) in starved SMMC7721 cells. Finally, the combined treatment of starvation and anti-CD147 monoclonal antibody exhibited a synergistic HCC cell killing effect. Our study suggests that upregulation of CD147 under starvation may reduce hepatoma cell death by modulating both apoptosis and autophagy through mTOR signaling, and that CD147 may be a novel potential molecular target to improve the efficacy of TACE.

  6. Peritoneal ultrafiltration in patients with advanced decompensated heart failure.

    PubMed

    Iadarola, Gian Maria; Lusardi, Paola; La Milia, Vincenzo; Amici, Gianpaolo; Santarelli, Stefano; Virga, Giovambattista; Basile, Carlo; Bertoli, Silvio; Bonofiglio, Renzo; Del Rosso, Goffredo; Feriani, Mariano; Galli, Emilio; Gallieni, Maurizio; Gambaro, Giovanni; Sandrini, Massimo; Sisca, Sergio; Cancarini, Giovanni

    2013-01-01

    The aim of the Best Practice guidelines on peritoneal ultrafiltration (UF) in patients with treatment-resistant advanced decompensated heart failure (TR-AHDF) is to achieve a common approach to the management of decompensated heart failure in those situations in which all conventional treatment options have been unsuccessful, and to stimulate a closer cooperation between nephrologists and cardiologists. The standardization of the case series of different centers would allow a better definition of the results published in the literature, without which they are nothing more than anecdotes. TR-AHDF is characterized by the persistence of severe symptoms even when all possible pharmacological and surgical options have been exhausted. These patients are often treated with methods that allow extracorporeal UF - slow continuous ultrafiltration (SCUF) and continuous renal replacement therapy (CRRT) - which have to be performed in hospital facilities. Peritoneal ultrafiltration (PUF) can be considered a treatment option in patients with TR-AHDF when, despite the fact that all treatment options have been used, patients meet the following criteria: • stage D decompensated heart failure (ACC/AHA classification); • INTERMACS level 4 decompensated heart failure; • INTERMACS frequent flyer profile; • chronic renal failure (estimated glomerular filtration rate <50 ml/min per 1.73 m2: KDOQI classification stage 3 chronic kidney disease); • no obvious contraindications to peritoneal UF. PUF treatment modes are derived from the treatment regimens proposed by various authors to obtain systemic UF in patients with severe decompensated heart failure, using manual and automated incremental peritoneal dialysis involving various glucose concentrations in addition to the single icodextrin exchange. These guidelines also identify a minimum set of tests and procedures for the follow-up phase, to be supplemented, according to the center's resources and policy, with other tests that

  7. Hepatocellular carcinoma: Advances in diagnosis, management, and long term outcome

    PubMed Central

    Bodzin, Adam S; Busuttil, Ronald W

    2015-01-01

    Hepatocellular carcinoma (HCC) remains a common and lethal malignancy worldwide and arises in the setting of a host of diseases. The incidence continues to increase despite multiple vaccines and therapies for viruses such as the hepatitis B and C viruses. In addition, due to the growing incidence of obesity in Western society, there is anticipation that there will be a growing population with HCC due to non-alcoholic fatty liver disease. Due to the growing frequency of this disease, screening is recommended using ultrasound with further imaging using magnetic resonance imaging and multi-detector computed tomography used for further characterization of masses. Great advances have been made to help with the early diagnosis of small lesions leading to potential curative resection or transplantation. Resection and transplantation maybe used in a variety of patients that are carefully selected based on underlying liver disease. Using certain guidelines and clinical acumen patients may have good outcomes with either resection or transplantation however many patients are inoperable at time of presentation. Fortunately, the use of new locoregional therapies has made down staging patients a potential option making them potential surgical candidates. Despite a growing population with HCC, new advances in viral therapies, chemotherapeutics, and an expanding population of surgical and transplant candidates might all contribute to improved long-term survival of these patients. PMID:26019732

  8. Analysis of Sorafenib Outcome: Focusing on the Clinical Course in Patients with Hepatocellular Carcinoma

    PubMed Central

    Ogasawara, Sadahisa; Chiba, Tetsuhiro; Ooka, Yoshihiko; Suzuki, Eiichiro; Inoue, Masanori; Wakamatsu, Toru; Tawada, Akinobu; Yokosuka, Osamu

    2016-01-01

    Background Treatment outcomes of sorafenib therapy may greatly vary depending not only on tumor spread but also on past clinical processes prior to sorafenib therapy and timing of sorafenib administration in the past clinical course of hepatocellular carcinoma (HCC). We evaluated the efficacy of sorafenib in patients with HCC, taking into account of their past clinical courses. Methods Patients with HCC treated with sorafenib as a first-line systemic therapy, whose courses documented from the time of the initial diagnosis, were retrospectively analyzed. Results Of the 123 patients receiving sorafenib therapy at an advanced-stage, baseline characteristics differed including the rate of hepatitis C virus, Child–Pugh class, and status of intrahepatic lesions according to stage progression processes. Overall survival (OS) in patients progressed directly from the early-stage (15.3 months) was significantly longer than that in patients diagnosed at the advanced-stage (5.3 months, P = 0.022) and progressed from the intermediate-stages (6.0 months, P = 0.041). Of 105 patients diagnosed at the intermediate-stage on past clinical courses, OS of starting sorafenib therapy before progression to the advanced-stage (67 patients) was significantly longer than for patients starting sorafenib therapy only after progression to the advanced-stage (38 patients) (P = 0.015). Conclusion Characteristic differences between past stage progression processes might affect prognosis in advanced-stage HCC patients receiving sorafenib. Switching to sorafenib therapy before progression to the advanced-stage appears more effective than that after progression to the advanced-stage in patients diagnosed in the intermediate-stage on past clinical courses prior to sorafenib administration. PMID:27537374

  9. Urinary Stone Disease: Advancing Knowledge, Patient Care, and Population Health.

    PubMed

    Scales, Charles D; Tasian, Gregory E; Schwaderer, Andrew L; Goldfarb, David S; Star, Robert A; Kirkali, Ziya

    2016-07-01

    Expanding epidemiologic and physiologic data suggest that urinary stone disease is best conceptualized as a chronic metabolic condition punctuated by symptomatic, preventable stone events. These acute events herald substantial future chronic morbidity, including decreased bone mineral density, cardiovascular disease, and CKD. Urinary stone disease imposes a large and growing public health burden. In the United States, 1 in 11 individuals will experience a urinary stone in their lifetime. Given this high incidence and prevalence, urinary stone disease is one of the most expensive urologic conditions, with health care charges exceeding $10 billion annually. Patient care focuses on management of symptomatic stones rather than prevention; after three decades of innovation, procedural interventions are almost exclusively minimally invasive or noninvasive, and mortality is rare. Despite these advances, the prevalence of stone disease has nearly doubled over the past 15 years, likely secondary to dietary and health trends. The NIDDK recently convened a symposium to assess knowledge and treatment gaps to inform future urinary stone disease research. Reducing the public health burden of urinary stone disease will require key advances in understanding environmental, genetic, and other individual disease determinants; improving secondary prevention; and optimal population health strategies in an increasingly cost-conscious care environment. PMID:26964844

  10. Integrative and complementary therapies for patients with advanced cancer.

    PubMed

    Marchand, Lucille

    2014-07-01

    In integrative medicine, well-being is emphasized, and in palliative care, quality of life (QOL) is a similar concept or goal. Both can occur despite advanced cancer. Integrative medicine serves to combine the best of alternative, complementary and conventional therapies to optimize well-being and QOL, whether or not a person is at the end of their life. When integrative medicine is combined with palliative care modalities, the toolbox to provide symptom control and well-being or QOL is increased or broadened. Palliative care and integrative medicine are best provided early in the trajectory of illness such as cancer, and increase in amount as the illness progresses toward end of life. In cancer care, symptoms of the cancer, as well as symptoms produced by cancer therapies, are addressed with conventional and integrative therapies. Goals of care change as the disease progresses, and a patient's unique situation creates a different balance of integrative and conventional therapies. Integrative therapies such as music, aromatherapy, and massage might appeal to more patients than more specific, less common integrative therapies that might be more expensive, or seem more unusual such as Ayurvedic medicine and energy modalities. Each person may be drawn to different integrative modalities depending on factors such as cultural traditions, beliefs, lifestyle, internet information, advice from family and friends, books, etc. This review focuses on how integrative and complementary modalities can be included in comprehensive palliative care for patients with advanced malignancies. Nutrition and movement, often neglected in conventional treatment strategies, will also be included in the larger context of integrative and palliative modalities. Both conventional and integrative modalities in palliative care help patients live with empowerment, hope, and well-being no matter how long their lives last. A comprehensive review of all integrative and complementary therapies is

  11. Down-Regulation of MiR-193a-3p Dictates Deterioration of HCC: A Clinical Real-Time qRT-PCR Study

    PubMed Central

    Liu, Yongru; Ren, Fanghui; Luo, Yihuan; Rong, Minhua; Chen, Gang; Dang, Yiwu

    2015-01-01

    Background Although some recent reports have shown that the expression level of miR-193a varied in different cancers, its role in hepatocellular carcinoma (HCC) remains unidentified. The aim of the current study was to validate the relationship between miR-193a-3p and clinicopathological characteristics in HCC patients. Material/Methods Expression of miR-193a-3p in 95 HCC cases and their corresponding peritumoral tissues (PT) was examined by using quantitative reverse transcription polymerase chain reaction (qRT-PCR). miR-193a-3p expression and its correlation with a variety of clinicopathological features and patient recurrence were analyzed. Results The relative level of miR-193a-3p was 3.2028±1.1951 in PT, significantly higher than its expression in HCC tissues (1.5941±0.7079, P<0.001). The area under the curve of underexpression of miR-193a-3p was 0.906 to distinguish HCC from normal liver (95% CI: 0.864–0.948, P<0.001). Expression of miR-193a-3p was negatively correlated to metastasis (r=−0.371, P=0.000), TNM (r=−0.321, P=0.002), respectively. Additionally, the recurrence time was 50.271±2.631 months for the low miR-193a-3p level group and 60.132±3.626 months for the high miR-193a-3p level group. However, no significant difference between them was found (chi-square=0.354, P=0.552). Conclusions MiR-193a-3p may be a tumor-suppressive miRNA which is down-regulated in HCC tissues. It could be regarded as a predictor for the deterioration of HCC patients. PMID:26263159

  12. Differences in antiproliferative effect of STAT3 inhibition in HCC cells with versus without HBV expression

    SciTech Connect

    Hong, Yun; Zhou, Lin; Xie, Haiyang; Wang, Weilin; Zheng, Shusen

    2015-06-05

    Chronic infection with hepatitis B virus (HBV) plays an important role in the etiology of hepatocellular carcinoma (HCC). Signal transducer and activator of transcription 3 (STAT3) inactivation could inhibit the tumor growth of HCC. In this study, differential antiproliferative effect of STAT3 inhibition was observed with HBV-related HCC cells being more resistant than non-HBV-related HCC cells. Resistance of HBV-related HCC cells to STAT3 inhibition was positively correlated to the expression of HBV. Enhanced ERK activation after STAT3 blockade was detected in HBV-related HCC cells but not in non-HBV-related HCC cells. Combined ERK and STAT3 inhibition eliminates the discrepancy between the two types of HCC cells. Moderate reduced HBV expression was found after STAT3 inhibition. These findings disclose a discrepancy in cellular response to STAT3 inhibition between non-HBV-related and HBV-related HCC cells and underscore the complexity of antiproliferative effect of STAT3 inactivation in HBV-related HCC cells. - Highlights: • HBV endows HCC cells with resistance to STAT3 inactivation on proliferation. • Abnormal ERK activation after STAT3 inhibition in HBV-related HCC cells. • Combined ERK and STAT3 inhibition eliminates the discrepancy. • STAT3 inhibition moderately reduces HBV expression.

  13. Unexpected remission of hepatocellular carcinoma (HCC) with lung metastasis to the combination therapy of thalidomide and cyproheptadine: report of two cases and a preliminary HCC cell line study.

    PubMed

    Feng, Yu-Min; Feng, Chin-Wen; Chen, Solomon Chih-Cheng; Hsu, Cheng-Da

    2012-10-12

    We reported two cases of hepatocellular carcinoma (HCC) with lung metastases who were treated with a combination of thalidomide and cyproheptadine. The use of cyproheptadine in these two cases was originally for skin itching. Follow-up CT images revealed a complete remission of HCC in both of them after treatment for 6 months and 6 weeks, respectively. A following experimental cell line study demonstrated that cyproheptadine effectively reduced the viability of two HCC cell lines.

  14. Investigation of long noncoding RNAs expression profile as potential serum biomarkers in patients with hepatocellular carcinoma.

    PubMed

    Kamel, Marwa M; Matboli, Marwa; Sallam, Maha; Montasser, Iman F; Saad, Amr S; El-Tawdi, Ahmed H F

    2016-02-01

    There is an increasing interest in using long noncoding RNAs (lncRNAs) as biomarkers in cancer. Predictive biomarkers in hepatocellular carcinoma (HCC) have great benefit in the choice of therapeutic modality for HCC. The aim of this study is to assess lncRNA-urothelial carcinoma associated-1 (lncRNA-UCA1) and WD repeat containing, antisense to TP53 (WRAP53) expression as novel noninvasive biomarkers for diagnosis of HCC in sera of HCC patients compared with chronic hepatitis C virus (HCV) patients and healthy volunteers and to analyze their relationship with respect to the clinicopathologic features. We retrieved HCC characteristic lncRNAs, lncRNA-UCA1 and lncRNA-WRAP53, based on the microarray signature profiling (released by LncRNADisease database). Quantitative reverse-transcriptase polymerase chain reaction assay (RT-qPCR) was then used to evaluate the expression of selected lncRNAs in the serum of 160 participants. Furthermore, in 20 of 82 HCC cases involved in the study, we examined the expression of lncRNA-UCA1 and lncRNA-WRAP53 in 20 HCC tissues and adjacent nontumor tissues and analyzed its correlation with the serum level of these lncRNAs. The prognostic significance of the investigated parameters in HCC patients was explored. We found that lncRNA-UCA1 and lncRNA-WRAP53 were significantly higher in sera of HCC than those with chronic HCV infection or healthy volunteers. Our data suggested that the increased expression of UCA1 and WRAP53 was associated with advanced clinical parameters in HCC. Of note, tissue levels of the chosen lncRNAs strongly correlate with their sera level. The combination of both lncRNAs with serum alpha fetoprotein resulted in improved sensitivity to 100%. The median follow-up period was 21.5 months. LncRNA-WRAP53 was significant independent prognostic markers in relapse-free survival. LncRNA-UCA1 and lncRNA-WRAP53 upregulation may serve as novel serum biomarkers for HCC diagnosis and prognosis. PMID:26551349

  15. Pembrolizumab for Treatment of Patients with Advanced or Unresectable Melanoma.

    PubMed

    Sullivan, Ryan J; Flaherty, Keith T

    2015-07-01

    From Coley's toxin to combination immune checkpoint inhibition, strategies to activate the immune system and generate anticancer immunity have been ongoing for well over a century. Over the past decade, the so-called immune checkpoint inhibitors, generally monoclonal antibodies that target key regulators of T-cell activation, emerged as the most effective immune-targeted agents. Pembrolizumab is the first anti-programmed death 1 (PD-1) antibody approved by the FDA for the treatment of metastatic melanoma. With responses seen in 25% to 40% of patients, depending on dose and setting (i.e., before or after ipilimumab), pembrolizumab specifically and anti-PD-1 antibodies generally are revolutionizing the treatment of melanoma. However, in the setting of other recent advances in the field, a number of practical issues are emerging that need to be addressed to optimize the care of patients with melanoma. First, the optimal sequencing of therapy (first-line immunotherapy over molecular targeted therapy, ipilimumab versus pembrolizumab as initial immune checkpoint inhibitor) is unknown and must be evaluated through randomized trials. Second, there is a strong rationale to combine immune checkpoint inhibitors (i.e., anti-PD-1 with ipilimumab) and to combine immune therapies with targeted therapy agents, so determining whether combination therapy is better than direct sequencing is another critical issue that needs to be addressed in carefully carried out studies.

  16. Prognostic value of fever grade combined with neutrophil percentage in hepatocellular carcinoma patients presenting fever as the initial manifestation

    PubMed Central

    Gong, Zi-Jun; Guo, Wei; Sun, Yun-Fan; Zhang, Xin; Qiu, Shuang-Jian; Zhou, Jian; Fan, Jia; Yang, Xin-Rong

    2016-01-01

    Background Hepatocellular carcinoma (HCC) patients with fever as the initial presentation are extremely rare. Our aim was to investigate the clinical characteristics and prognosis of patients with this disease. Patients and methods The clinical features were analyzed in a retrospective study of 63 HCC patients with fever as the first manifestation and 300 HCC patients without fever as the control group. Results HCC patients with fever had a higher neutrophil percentage, larger tumor size, worse tumor differentiation, advanced Barcelona Clinic Liver Cancer stage, and more hilar lymph node metastasis than HCC patients without fever (all P<0.05). Compared with HCC patients without fever, patients presenting with fever had shorter overall survival (OS, median: 13 months, P<0.001) and time to recurrence (TTR, median: 7.5 months, P<0.001). In addition, HCC patients with fever also had shorter OS and TTR than those without fever in all clinical subgroups with aggressive features (all P<0.05). Multivariate analysis showed that neutrophil percentage >70%, fever grade ≥38.5°C, tumor size >5 cm, and hilar lymph node metastasis were independent factors for OS and TTR. A positive correlation was observed between body temperature and serum neutrophil percentage (r=0.527, P<0.001). Patients with a fever grade ≥38.5°C had more incomplete encapsulation and larger tumor size, while those with a neutrophil percentage >70% presented with more incomplete encapsulation, vascular invasion, and worse tumor differentiation. Patients with a fever grade ≥38.5°C combined with a neutrophil percentage >70% had worse OS and TTR than other groups. Conclusion HCC patients presenting with fever have poorer prognosis than those without fever; however, their prognosis could be improved by timely surgical intervention. Patients with a neutrophil percentage >70% and a fever grade ≥38.5°C represent a rare HCC subgroup with an extremely dismal outcome and more aggressive clinical course. PMID

  17. The changing hope trajectory in patients with advanced-stage cancer: a nursing perspective.

    PubMed

    Sanders, Judith Brown; Seda, Julie S; Kardinal, Carl G

    2012-06-01

    As patients with advanced-stage cancer move from the initial diagnosis through treatment, remission, recurrence, and advanced-stage disease, the hope trajectory undergoes a dynamic transformation. By identifying the hope trajectory, nurses can help patients focus on obtainable hope objects while balancing the need to present a realistic prognosis. This, in turn, may help patients find meaning and purpose in advanced-stage cancer and facilitate realistic hope when faced with a life-threatening illness.

  18. HBV Induced HCC: Major Risk Factors from Genetic to Molecular Level

    PubMed Central

    Ayub, Ambreen; Ashfaq, Usman Ali; Haque, Asma

    2013-01-01

    Hepatocellular carcinoma (HCC) is a deadly and emerging disease leading to death in Asian countries. High hepatitis B virus (HBV) load and chronic hepatitis B (CHB) infection increase the risk of developing HCC. HBV is a DNA virus that can integrate DNA into host genome thereby increase the yield of transactivator protein HBxAg that may deregulate many pathways involving in metabolism of cells. Several monogenic and polygenic risk factors are also involved in HCC development. This review summarizes the mechanism involved in HCC development and discusses some promising therapies to make HCC curative. PMID:23991421

  19. FAK kinase activity is required for the progression of c-Met/β-catenin-driven HCC

    PubMed Central

    Shang, Na; Arteaga, Maribel; Zaidi, Ali; Cotler, Scott J.; Breslin, Peter; Ding, Xianzhong; Kuo, Paul; Nishimura, Michael; Zhang, Jiwang; Qiu, Wei

    2016-01-01

    Background & Aims There is an urgent need to develop new and more effective therapeutic strategies and agents to treat hepatocellular carcinoma (HCC). We have recently found that deletion of Fak in hepatocytes before tumors form inhibits tumor development and prolongs survival of animals in a c-Met (MET)/β-catenin (CAT)-driven HCC mouse model. However, it has yet to be determined whether FAK expression in hepatocytes promotes MET/CAT-induced HCC progression after tumor initiation. In addition, it remains unclear whether FAK promotes HCC development through its kinase activity. Methods We generated hepatocyte-specific inducible Fak-deficient mice (Alb-creERT2; Fakflox/flox) to examine the role of FAK in HCC progression. We re-expressed wild-type and mutant FAK in Fak-deficient mice to determine FAK’s kinase activity in HCC development. We also examined the efficacy of a FAK kinase inhibitor PF-562271 on HCC inhibition. Results We found that deletion of Fak after tumors form significantly repressed MET/CAT-induced tumor progression. Ectopic FAK expression restored HCC formation in hepatocyte-specific Fak-deficient mice. However, overexpression of a FAK kinase-dead mutant led to reduced tumor load compared to mice which express wild-type FAK. Furthermore, PF-562271 significantly suppressed progression of MET/CAT-induced HCC. Conclusion Fak kinase activity is important for MET/CAT-induced HCC progression. Inhibiting FAK kinase activity provides a potential therapeutic strategy to treat HCC. PMID:27142958

  20. Targeted therapy for advanced hepatocellular cancer in the elderly: focus on sorafenib.

    PubMed

    Germano, D; Tinessa, V; Barletta, E; Cannella, L; Daniele, B

    2013-11-01

    Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. Worldwide progressive population aging demands consensus development for decision making when treating elderly patients. Age itself might not be a critical determinant for the selection of a therapeutic option. In the past few years, the mechanisms of hepato-carcinogenesis have been elucidated, and the involvement of a number of pathways, including angiogenesis, aberrant signal transduction, and dysregulated cell cycle control, have been demonstrated, leading to evaluation of the activity and toxicity of some of the new molecularly targeted agents. Sorafenib was demonstrated to significantly increase the survival of patients with advanced HCC in two prospective, randomized, placebo-controlled trials. Subsequently, a number of retrospective or prospective studies have indicated that the effectiveness of sorafenib therapy in the treatment of HCC is similar in elderly and non-elderly patients. The aim of this review is to describe the impact of age on the effects of sorafenib-targeted therapy in patients with HCC, and the next treatment options with new targeted agents (everolimus, tivantinib, linifanib, etc.). PMID:24097332

  1. Interferon-gamma inducible protein 10 (IP10) induced cisplatin resistance of HCC after liver transplantation through ER stress signaling pathway

    PubMed Central

    Geng, Wei; Lo, Chung-Mau; Ng, Kevin T.P.; Ling, Chang-Chun; Qi, Xiang; Li, Chang-Xian; Zhai, Yuan; Liu, Xiao-Bing; Ma, Yuen-Yuen; Man, Kwan

    2015-01-01

    Tumor recurrence remains an obstacle after liver surgery, especially in living donor liver transplantation (LDLT) for patients with hepatocellular carcinoma (HCC). The acute-phase liver graft injury might potentially induce poor response to chemotherapy in recurrent HCC after liver transplantation. We here intended to explore the mechanism and to identify a therapeutic target to overcome such chemoresistance. The associations among graft injury, overexpression of IP10 and multidrug resistant genes were investigated in a rat liver transplantation model, and further validated in clinical cohort. The role of IP10 on HCC cell proliferation and tumor growth under chemotherapy was studied both in vitro and in vivo. The underlying mechanism was revealed by detecting the activation of endoplasmic reticulum (ER) stress signaling pathways. Moreover, the effect of IP10 neutralizing antibody sensitizing cisplatin treatment was further explored. In rat liver transplantation model, significant up-regulation of IP10 associated with multidrug resistant genes was found in small-for-size liver graft. Clinically, high expression of circulating IP10 was significant correlated with tumor recurrence in HCC patients underwent LDLT. Overexpression of IP10 promoted HCC cell proliferation and tumor growth under cisplatin treatment by activation of ATF6/Grp78 signaling. IP10 neutralizing antibody sensitized cisplatin treatment in nude mice. The overexpression of IP10, which induced by liver graft injury, may lead to cisplatin resistance via ATF6/Grp78 ER stress signaling pathway. IP10 neutralizing antibody could be a potential adjuvant therapy to sensitize cisplatin treatment. PMID:26336986

  2. Yttrium-90 Radioembolization of Hepatocellular Carcinoma-Performance, Technical Advances, and Future Concepts.

    PubMed

    Molvar, Christopher; Lewandowski, Robert

    2015-12-01

    Hepatocellular carcinoma (HCC) is a lethal tumor, claiming over half a million lives per year. Treatment of HCC is commonly performed without curative intent, and palliative options dominate, including catheter-based therapies, namely, transarterial chemoembolization and yttrium-90 ((90)Y) radioembolization. This review will showcase the performance of (90)Y radioembolization for the treatment of HCC, focusing on recent seminal data and technical advances. In particular, novel radioembolization treatment concepts are discussed and compared with conventional HCC therapy.

  3. Using Adult Learning Concepts To Assist Patients in Completing Advance Directives.

    ERIC Educational Resources Information Center

    Meyer, Rose Mary

    2000-01-01

    Advance directives that enable individuals to control their health care are underused due to lack of patient knowledge. Nurses can teach patients about them using adult learning principles, transformation theory, and skills for learning how to learn. (SK)

  4. Intraoperative Hyperthermic Intraperitoneal Chemotherapy in Patients With Advanced Ovarian Cancer.

    PubMed

    Oseledchyk, Anton; Zivanovic, Oliver

    2015-09-01

    Ovarian cancer, because it is largely confined to the peritoneal cavity, has a unique tumor biology and metastatic spread pattern. Its metastatic potential comes from detached tumor cells in the peritoneal cavity that re-attach to the mesothelial lining of the peritoneal surface. It is proposed that these micrometastases without neovasculature, as well as floating malignant cells, are drivers of early recurrence, since they can be neither resected nor adequately treated by systemic chemotherapy. This represents the major rationale for local treatment by means of postoperative intraperitoneal (IP) chemotherapy, which is the standard of care in the United States in patients with advanced-stage ovarian cancer who have minimal residual disease following cytoreductive surgery. An alternative loco-regional treatment strategy is the "HIPEC" procedure--hyperthermic IP chemoperfusion that is performed during the operation immediately following completion of gross tumor resection, and which provides improved tissue penetration and distribution of the chemotherapeutics. However, prospective data are limited and an outcomes benefit has yet to be shown. Here we discuss the advantages and pitfalls of HIPEC, as well as current data and ongoing prospective trials. PMID:26384807

  5. [Technological advances and micro-inflammation in dialysis patients].

    PubMed

    Ferro, Giuseppe; Ravaglia, Fiammetta; Ferrari, Elisa; Romoli, Elena; Michelassi, Stefano; Caiani, David; Pizzarelli, Francesco

    2015-01-01

    As currently performed, on line hemodiafiltration reduces, but does not normalize, the micro-inflammation of uremic patients. Recent technological advances make it possible to further reduce the inflammation connected to the dialysis treatment. 
Short bacterial DNA fragments are pro-inflammatory and can be detected in the dialysis fluids. However, their determination is not currently within normal controls of the quality of the dialysate. The scenario may change once the analysis of these fragments yields reliable, inexpensive, quick and easy to evaluate the results. At variance with standard bicarbonate dialysate, Citrate dialysate induces far less inflammation both for the well-known anti-inflammatory effect of such buffer and also because it is completely acetate free, e.g. a definitely pro-inflammatory buffer. However, the extensive use of citrate dialysate in chronic dialysis is prevented because of concerns about its potential calcium lowering effect. In our view, high convective exchange on line hemodiafiltration performed with dialysate, whose sterility and a-pirogenicity is guaranteed by increasingly sophisticated controls and with citrate buffer whose safety is certified, can serve as the gold standard of dialysis treatments in future.

  6. Astemizole-based anticancer therapy for hepatocellular carcinoma (HCC), and Eag1 channels as potential early-stage markers of HCC.

    PubMed

    de Guadalupe Chávez-López, María; Pérez-Carreón, Julio Isael; Zuñiga-García, Violeta; Díaz-Chávez, José; Herrera, Luis A; Caro-Sánchez, Claudia Haydee; Acuña-Macías, Isabel; Gariglio, Patricio; Hernández-Gallegos, Elizabeth; Chiliquinga, Andrea Jazmín; Camacho, Javier

    2015-08-01

    Hepatocellular carcinoma (HCC) has very poor prognosis. Astemizole has gained great interest as a potential anticancer drug because it targets several proteins involved in cancer including the Eag1 (ether à-go-go-1) potassium channel that is overexpressed in human HCC. Eag1 channels are regulated by cancer etiological factors and have been proposed as early tumor markers. Here, we found that HepG2 and HuH-7 HCC cells displayed Eag1 messenger RNA (mRNA) and protein expression, determined by real-time RT-PCR and immunochemistry, respectively. Astemizole inhibited human HCC cell proliferation (assessed by metabolic activity assay) and induced apoptosis (studied with flow cytometry) in both cell lines. The subcellular Eag1 protein localization was modified by astemizole in the HepG2 cells. The treatment with astemizole prevented diethylnitrosamine (DEN)-induced rat HCC development in vivo (followed by studying γ-glutamyl transpeptidase (GGT) activity). The Eag1 mRNA and protein levels were increased in most DEN-treated groups but decreased after astemizole treatment. GGT activity was decreased by astemizole. The Eag1 protein was detected in cirrhotic and dysplastic rat livers. Astemizole might have clinical utility for HCC prevention and treatment, and Eag1 channels may be potential early HCC biomarkers. These data provide significant basis to include astemizole in HCC clinical trials. PMID:25783527

  7. Distinguishing Symptoms of Grief and Depression in a Cohort of Advanced Cancer Patients

    ERIC Educational Resources Information Center

    Jacobsen, Juliet C.; Zhang, Baohui; Block, Susan D.; Maciejewski, Paul K.; Prigerson, Holly G.

    2010-01-01

    Several studies have shown that the symptoms of grief are different from symptoms of depression among bereaved family members. This study is an attempt to replicate this finding among advanced cancer patients and examine clinical correlates of patient grief and depression. Analyses were conducted on data from interviews with 123 advanced cancer…

  8. Evaluation of Instrumental Activities of Daily Living in Greek Patients with Advanced Cancer

    ERIC Educational Resources Information Center

    Mystakidou, Kyriaki; Parpa, Efi; Tsilika, Eleni; Panagiotoua, Irene; Roumeliotou, Anna; Symeonidi, Matina; Galanos, Antonis; Kouvaris, Ioannis

    2013-01-01

    Translation of the instrumental activities of daily living (IADL) was carried out and its psychometric properties were assessed in a Greek sample of patients with advanced cancer. The scale was translated with the forward-backward procedure into the Greek language. It was initially administered to 136 advanced cancer patients. To assess…

  9. Aptamer-based Sandwich Assay and its Clinical Outlooks for Detecting Lipocalin-2 in Hepatocellular Carcinoma (HCC)

    PubMed Central

    Lee, Kyeong-Ah; Ahn, Ji-Young; Lee, Sang-Hee; Singh Sekhon, Simranjeet; Kim, Dae-Ghon; Min, Jiho; Kim, Yang-Hoon

    2015-01-01

    We validated a single-stranded, DNA aptamer-based, diagnostic method capable of detecting Lipocalin-2 (LCN2), a biomarker from clinically relevant hepatocellular carcinoma (HCC) patient serum, in the sandwich assay format. Nine aptamers (LCN2_apta1 to LCN2_apta9) for LCN2 were screened with SELEX processes, and a sandwich pair (LCN2_apta2 and LCN2_apta4) was finally chosen using surface plasmon resonance (SPR) and dot blotting analysis. The result of the proposed aptamer sandwich construction shows that LCN2 was sensitively detected in the concentration range of 2.5–500 ng mL−1 with a limit of detection of 0.6 ng mL−1. Quantitative measurement tests in HCC patients were run on straight serum and were compared with the performance of the conventional antibody-based ELISA kit. The aptamer sandwich assay demonstrated an excellent dynamic range for LCN2 at clinically relevant serum levels, covering sub-nanogram per mL concentrations. The new approach offers a simple and robust method for detecting serum biomarkers that have low and moderate abundance. It consists of functionalization, hybridization and signal read-out, and no dilution is required. The results of the study demonstrate the capability of the aptamer sandwich assay platform for diagnosing HCC and its potential applicability to the point-of-care testing (POCT) system. PMID:26039737

  10. The Ontario Prehospital Advanced Life Support (OPALS) Study: rationale and methodology for cardiac arrest patients.

    PubMed

    Stiell, I G; Wells, G A; Spaite, D W; Lyver, M B; Munkley, D P; Field, B J; Dagnone, E; Maloney, J P; Jones, G R; Luinstra, L G; Jermyn, B D; Ward, R; DeMaio, V J

    1998-08-01

    The Ontario Prehospital Advanced Life Support Study represents the largest prehospital study yet conducted, worldwide. This study will involve more than 25,000 cardiac arrest, trauma, and critically ill patients over an 8-year period. The study will evaluate the incremental benefit of rapid defibrillation and prehospital Advanced Cardiac Life Support measures for cardiac arrest survival and the benefit of Advanced Life Support for patients with traumatic injuries and other critically ill prehospital patients. This article describes the OPALS study with regard to the rationale and methodology for cardiac arrest patients.

  11. Novel Pretreatment Scoring Incorporating C-reactive Protein to Predict Overall Survival in Advanced Hepatocellular Carcinoma with Sorafenib Treatment

    PubMed Central

    Nakanishi, Hiroyuki; Kurosaki, Masayuki; Tsuchiya, Kaoru; Yasui, Yutaka; Higuchi, Mayu; Yoshida, Tsubasa; Komiyama, Yasuyuki; Takaura, Kenta; Hayashi, Tsuguru; Kuwabara, Konomi; Nakakuki, Natsuko; Takada, Hitomi; Ueda, Masako; Tamaki, Nobuharu; Suzuki, Shoko; Itakura, Jun; Takahashi, Yuka; Izumi, Namiki

    2016-01-01

    Objectives This study aimed to build a prediction score of prognosis for patients with advanced hepatocellular carcinoma (HCC) after sorafenib treatment. Methods A total of 165 patients with advanced HCC who were treated with sorafenib were analyzed. Readily available baseline factors were used to establish a scoring system for the prediction of survival. Results The median survival time (MST) was 14.2 months. The independent prognostic factors were C-reactive protein (CRP) <1.0 mg/dL [hazard ratio (HR) =0.51], albumin >3.5 g/dL (HR =0.55), alpha-fetoprotein <200 ng/mL (HR =0.45), and a lack of major vascular invasion (HR =0.39). Each of these factors had a score of 1, and after classifying the patients into five groups, the total scores ranged from 0 to 4. Higher scores were linked to significantly longer survival (p<0.0001). Twenty-nine patients (17.6%) with a score of 4 had a MST as long as 36.5 months, whereas MST was as short as 2.4 and 3.7 months for seven (4.2%) and 22 (13.3%) patients with scores of 0 and 1, respectively. Conclusions A novel prognostic scoring system, which includes the CRP level, has the ability to stratify the prognosis of patients with advanced stage HCC after treatment with sorafenib. PMID:27781198

  12. Impact of more detailed categorization of shrinkage or progression ratio at initial imaging response after sorafenib treatment in advanced hepatocellular carcinoma patients

    PubMed Central

    Wada, Yoshiyuki; Takami, Yuko; Tateishi, Masaki; Ryu, Tomoki; Mikagi, Kazuhiro; Saitsu, Hideki

    2015-01-01

    Background Sorafenib therapy improves survival in unresectable hepatocellular carcinoma (HCC) patients without an objective response. The present study investigated whether the initial imaging response might be a prognostic indicator after administration of sorafenib therapy in HCC patients. Patients and methods This retrospective study reviewed unresectable HCC patients undergoing sorafenib therapy. Patients evaluated without complete response, partial response (PR), or progressive disease (PD) at the initial imaging response evaluation by modified Response Evaluation Criteria in Solid Tumors were divided into three groups according to more detailed categorization of the shrinkage/progression ratio in initial imaging response. A comparison of progression-free and overall survival among these groups was performed. Results Of the 43 non-PR non-PD patients with target lesions, ten (23.3%) exhibited mild response (MR; −30% to −5%), 14 (32.6%) exhibited no change (NC; −5% to +5%), and 19 (44.2%) exhibited mild-PD (MPD; +5% to +20%). There was no statistical difference in progression-free or overall survival between MR and NC patients. The median progression-free survivals in NC+MR and mild-PD patients were 15.0 and 5.3 months, respectively (P<0.01), and the median survival times were 31.9 and 17.1 months, respectively (P<0.001). In multivariate analysis, etiology (hepatitis C virus) and initial imaging response (MR+NC) was identified as an independently good prognostic factor. Conclusion More detailed categorization of shrinkage or progression at the initial imaging response evaluation may be a useful marker for predicting sorafenib treatment outcomes in HCC patients. If the initial imaging response is not progression but stability, sorafenib may have a survival benefit. PMID:26586953

  13. Quality Nursing Care for Hospitalized Patients with Advanced Illness: Concept Development

    PubMed Central

    Izumi, Shigeko; Baggs, Judith G.; Knafl, Kathleen A.

    2011-01-01

    The quality of nursing care as perceived by hospitalized patients with advanced illness has not been examined. A concept of quality nursing care for this population was developed by integrating the literature on constructs defining quality nursing care with empirical findings from interviews of 16 patients with advanced illness. Quality nursing care was characterized as competence and personal caring supported by professionalism and delivered with an appropriate demeanor. Although the attributes of competence, caring, professionalism, and demeanor were identified as common components of quality care across various patient populations, the caring domain increased in importance when patients with advanced illness perceived themselves as vulnerable. Assessment of quality nursing care for patients with advanced illness needs to include measures of patient perceptions of vulnerability. PMID:20572095

  14. Natural interferon-beta treatment for patients with chronic hepatitis C in Japan.

    PubMed

    Sasaki, Reina; Kanda, Tatsuo; Nakamoto, Shingo; Haga, Yuki; Nakamura, Masato; Yasui, Shin; Jiang, Xia; Wu, Shuang; Arai, Makoto; Yokosuka, Osamu

    2015-05-18

    Chronic hepatitis C virus (HCV) infection can cause liver cirrhosis and hepatocellular carcinoma (HCC). Several studies have demonstrated that the eradication of HCV reduces the occurrence of HCC. In Japan, as many people live to an advanced age, HCV-infected patients are also getting older, and the age at HCC diagnosis has also increased. Although older HCV-infected patients have a risk of developing HCC, the treatment response to peginterferon-alpha plus ribavirin therapy is relatively poor in these patients because of drop-out or discontinuation of this treatment due to adverse events. It is established that the mechanism of action between interferon-alpha and interferon-beta is slightly different. Short-term natural interferon-beta monotherapy is effective for patients with acute hepatitis C and patients infected with HCV genotype 2 and low viral loads. Natural interferon-beta plus ribavirin for 48 wk or for 24 wk are also effective for some patients with HCV genotype 1 or HCV genotype 2. Natural interferon-beta plus ribavirin has been used for certain "difficult-to-treat" HCV-infected patients. In the era of direct-acting anti-virals, natural interferon-beta plus ribavirin may be one of the therapeutic options for special groups of HCV-infected patients. In the near future, signal transduction pathways of interferon-beta will inform further directions. PMID:26052401

  15. Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma

    PubMed Central

    Trojan, Jörg; Waidmann, Oliver

    2016-01-01

    Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months). Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1) blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC. PMID:27703962

  16. Some Advanced Kidney Cancer Patients May Postpone Treatment

    MedlinePlus

    ... advanced kidney cancer that has spread require immediate, aggressive treatment, a small new study suggests. "A subset ... them the inconvenience and debilitating side effects of aggressive treatments for about a year, and in some ...

  17. Identification and Validation of HCC-specific Gene Transcriptional Signature for Tumor Antigen Discovery.

    PubMed

    Petrizzo, Annacarmen; Caruso, Francesca Pia; Tagliamonte, Maria; Tornesello, Maria Lina; Ceccarelli, Michele; Costa, Valerio; Aprile, Marianna; Esposito, Roberta; Ciliberto, Gennaro; Buonaguro, Franco M; Buonaguro, Luigi

    2016-07-08

    A novel two-step bioinformatics strategy was applied for identification of signatures with therapeutic implications in hepatitis-associated HCC. Transcriptional profiles from HBV- and HCV-associated HCC samples were compared with non-tumor liver controls. Resulting HCC modulated genes were subsequently compared with different non-tumor tissue samples. Two related signatures were identified, namely "HCC-associated" and "HCC-specific". Expression data were validated by RNA-Seq analysis carried out on unrelated HCC samples and protein expression was confirmed according to The Human Protein Atlas" (http://proteinatlas.org/), a public repository of immunohistochemistry data. Among all, aldo-keto reductase family 1 member B10, and IGF2 mRNA-binding protein 3 were found strictly HCC-specific with no expression in 18/20 normal tissues. Target peptides for vaccine design were predicted for both proteins associated with the most prevalent HLA-class I and II alleles. The described novel strategy showed to be feasible for identification of HCC-specific proteins as highly potential target for HCC immunotherapy.

  18. Concentration-dependent organization of DNA by the dinoflagellate histone-like protein HCc3

    PubMed Central

    Chan, Yuk-Hang; Wong, Joseph T. Y.

    2007-01-01

    The liquid crystalline chromosomes of dinoflagellates are the alternative to the nucleosome-based organization of chromosomes in the eukaryotes. These nucleosome-less chromosomes have to devise novel ways to maintain active parts of the genome. The dinoflagellate histone-like protein HCc3 has significant sequence identity with the bacterial DNA-binding protein HU. HCc3 also has a secondary structure resembling HU in silico. We have examined HCc3 in its recombinant form. Experiments on DNA-cellulose revealed its DNA-binding activity is on the C-terminal domain. The N-terminal domain is responsible for intermolecular oligomerization as demonstrated by cross-linking studies. However, HCc3 could not complement Escherichia coli HU-deficient mutants, suggesting functional differences. In ligation assays, HCc3-induced DNA concatenation but not ring closure as the DNA-bending HU does. The basic HCc3 was an efficient DNA condensing agent, but it did not behave like an ordinary polycationic compound. HCc3 also induced specific structures with DNA in a concentration-dependent manner, as demonstrated by atomic force microscopy (AFM). At moderate concentration of HCc3, DNA bridging and bundling were observed; at high concentrations, the complexes were even more condensed. These results are consistent with a biophysical role for HCc3 in maintaining extended DNA loops at the periphery of liquid crystalline chromosomes. PMID:17412706

  19. Identification and Validation of HCC-specific Gene Transcriptional Signature for Tumor Antigen Discovery

    PubMed Central

    Petrizzo, Annacarmen; Caruso, Francesca Pia; Tagliamonte, Maria; Tornesello, Maria Lina; Ceccarelli, Michele; Costa, Valerio; Aprile, Marianna; Esposito, Roberta; Ciliberto, Gennaro; Buonaguro, Franco M.; Buonaguro, Luigi

    2016-01-01

    A novel two-step bioinformatics strategy was applied for identification of signatures with therapeutic implications in hepatitis-associated HCC. Transcriptional profiles from HBV- and HCV-associated HCC samples were compared with non-tumor liver controls. Resulting HCC modulated genes were subsequently compared with different non-tumor tissue samples. Two related signatures were identified, namely “HCC-associated” and “HCC-specific”. Expression data were validated by RNA-Seq analysis carried out on unrelated HCC samples and protein expression was confirmed according to The Human Protein Atlas" (http://proteinatlas.org/), a public repository of immunohistochemistry data. Among all, aldo-keto reductase family 1 member B10, and IGF2 mRNA-binding protein 3 were found strictly HCC-specific with no expression in 18/20 normal tissues. Target peptides for vaccine design were predicted for both proteins associated with the most prevalent HLA-class I and II alleles. The described novel strategy showed to be feasible for identification of HCC-specific proteins as highly potential target for HCC immunotherapy. PMID:27387388

  20. Ambovex® as a novel immunological modulator drug for the treatment of hepatocellular carcinoma (HCC) in the liver: a Phase II clinical trial

    PubMed Central

    Salama, Hosny; Ahmad, Hassan; Elchagea, Ismail; Zekri, Abdel Rahman; Medhat, Eman; Bahnassy, Abeer; Lange, Michael; Rabbat, Mohammed; de la Torre, Andrew N; Punamiya, Pravin

    2015-01-01

    Hepatocellular carcinoma (HCC) is a global public health problem, based on it being the fifth most common cancer and third leading cause of cancer-related mortality worldwide. The approved conventional treatment methods for HCC have shown life-threatening side effects with limited or negligible success, especially in multifocal HCC. As a consequence, new therapeutic approaches are being explored, including immunoregulatory molecules that may have the potential to treat or delay the progression of HCC. A novel pharmaceutical botanical drug – Ambovex®, an immune-modulator molecule – was tested to treat or delay the progress of HCC. We conducted a 6-month randomized clinical trial with an additional 3-month washing period (no treatment) to evaluate the safety and efficacy of low-dose Ambovex oral spray in treating patients with HCC. The clinical study involved a total of 40 patients, with 33 in the treatment group and seven in the control group. The α-fetoprotein (AFP) levels were measured every month and ultrasound scans were performed at time zero and every 2 months thereafter. Computed tomography (CT) scans were performed for patients in the treatment group. Ambovex proved to be safe, as there were no significant side effects although some patients found that the drug has unpleasant taste. AFP analysis showed a significant decrease in its level (α=0.05; 95% confidence interval) in the treatment group when compared to the control group at 3 months (P=0.0031) and at 6 months (P=0.007). The ultrasound results showed improvement in the treated group, as evidenced by a significant decrease in the lesion numbers and sizes. The lesions in 38% of treated patients decreased from multiple to single with major improvements; 35% of patients exhibited a decrease from multiple lesions to multiple lesions with minor improvements, whereas 27% had stabilized lesions. CT scans in the treated group showed significant improvement, as there was complete disappearance of the

  1. CD86+/CD206+, Diametrically Polarized Tumor-Associated Macrophages, Predict Hepatocellular Carcinoma Patient Prognosis

    PubMed Central

    Dong, Pingping; Ma, Lijie; Liu, Longzi; Zhao, Guangxi; Zhang, Si; Dong, Ling; Xue, Ruyi; Chen, She

    2016-01-01

    Tumor-associated macrophages (TAMs), the most abundant infiltrating immune cells in tumor microenvironment, have distinct functions in hepatocellular carcinoma (HCC) progression. CD68+ TAMs represent multiple polarized immune cells mainly containing CD86+ antitumoral M1 macrophages and CD206+ protumoral M2 macrophages. TAMs expression and density were assessed by immunohistochemical staining of CD68, CD86, and CD206 in tissue microarrays from 253 HCC patients. Clinicopathologic features and prognostic value of these markers were evaluated. We found that CD68+ TAMs were not associated with clinicopathologic characteristics and prognosis in HCC. Low presence of CD86+ TAMs and high presence of CD206+ TAMs were markedly correlated with aggressive tumor phenotypes, such as multiple tumor number and advanced tumor-node-metastasis (TNM) stage; and were associated with poor overall survival (OS) (p = 0.027 and p = 0.024, respectively) and increased time to recurrence (TTR) (p = 0.037 and p = 0.031, respectively). In addition, combined analysis of CD86 and CD206 provided a better indicator for OS (p = 0.011) and TTR (p = 0.024) in HCC than individual analysis of CD86 and CD206. Moreover, CD86+/CD206+ TAMs predictive model also had significant prognosis value in α-fetoprotein (AFP)-negative patients (OS: p = 0.002, TTR: p = 0.005). Thus, these results suggest that combined analysis of immune biomarkers CD86 and CD206 could be a promising HCC prognostic biomarker. PMID:26938527

  2. SU-E-J-260: Quantitative Image Feature Analysis of Multiphase Liver CT for Hepatocellular Carcinoma (HCC) in Radiation Therapy

    SciTech Connect

    Choi, W; Wang, J; Lu, W; Kang, M

    2015-06-15

    Purpose: To identify the effective quantitative image features (radiomics features) for prediction of response, survival, recurrence and metastasis of hepatocellular carcinoma (HCC) in radiotherapy. Methods: Multiphase contrast enhanced liver CT images were acquired in 16 patients with HCC on pre and post radiation therapy (RT). In this study, arterial phase CT images were selected to analyze the effectiveness of image features for the prediction of treatment outcome of HCC to RT. Response evaluated by RECIST criteria, survival, local recurrence (LR), distant metastasis (DM) and liver metastasis (LM) were examined. A radiation oncologist manually delineated the tumor and normal liver on pre and post CT scans, respectively. Quantitative image features were extracted to characterize the intensity distribution (n=8), spatial patterns (texture, n=36), and shape (n=16) of the tumor and liver, respectively. Moreover, differences between pre and post image features were calculated (n=120). A total of 360 features were extracted and then analyzed by unpaired student’s t-test to rank the effectiveness of features for the prediction of response. Results: The five most effective features were selected for prediction of each outcome. Significant predictors for tumor response and survival are changes in tumor shape (Second Major Axes Length, p= 0.002; Eccentricity, p=0.0002), for LR, liver texture (Standard Deviation (SD) of High Grey Level Run Emphasis and SD of Entropy, both p=0.005) on pre and post CT images, for DM, tumor texture (SD of Entropy, p=0.01) on pre CT image and for LM, liver (Mean of Cluster Shade, p=0.004) and tumor texture (SD of Entropy, p=0.006) on pre CT image. Intensity distribution features were not significant (p>0.09). Conclusion: Quantitative CT image features were found to be potential predictors of the five endpoints of HCC in RT. This work was supported in part by the National Cancer Institute Grant R01CA172638.

  3. Combined sorafenib and yttrium-90 radioembolization for the treatment of advanced hepatocellular carcinoma

    PubMed Central

    Salman, A.; Simoneau, E.; Hassanain, M.; Chaudhury, P.; Boucher, L.M.; Valenti, D.; Cabrera, T.; Nudo, C.; Metrakos, P.

    2016-01-01

    Background and Aims In this pilot study, we assessed the safety and tolerability of combining sorafenib with 90Y radioembolization for the treatment of unresectable hepatocellular carcinoma (hcc). Methods The study, conducted prospectively during 2009–2012, included eligible patients with unresectable hcc and a life expectancy of at least 12 weeks. Each patient received sorafenib (400 mg twice daily) for 6–8 weeks before 90Y treatment. Safety and tolerability were assessed. Results Of the 40 patients enrolled, 29 completed treatment (combined therapy). In the initial cohort, the most common cause of hcc was hepatitis C (32.5%), and most patients were staged Child A (82.5%). The 29 patients who completed the study had similar baseline characteristics. Grades 1 and 2 toxicities accounted for 77.8% of all adverse events reported. The most common toxicities reported were fatigue (19.0%), alteration in liver function (7.9%), and diarrhea (6.3%). There were 12 grade 3 and 2 grade 4 toxicity events reported. One patient died of liver failure within 30 days after treatment. During the study, the sorafenib dose was reduced in 6 patients (20.7%), and sorafenib had to be interrupted in 4 patients (13.8%) and discontinued in 4 patients (13.8%). The disease control rate was 72.4% per the modified Response Evaluation Criteria in Solid Tumors, and tumour necrosis was observed in 82.8% of patients. Overall survival in patients undergoing combined therapy was 12.4 months. Conclusions Preliminary results demonstrate the safety and tolerability of combining 90Y radioembolization and sorafenib for advanced hcc. A larger prospective study is needed to determine the extent of the survival benefit. PMID:27803608

  4. Intraperitoneal radiolabeled OC 125 in patients with advanced ovarian cancer

    SciTech Connect

    Finkler, N.J.; Muto, M.G.; Kassis, A.I.; Weadock, K.; Tumeh, S.S.; Zurawski, V.R. Jr.; Knapp, R.C. )

    1989-09-01

    Twenty patients with recurrent or persistent epithelial ovarian cancer failing conventional therapies were treated with a single intraperitoneal injection of iodine-131-labeled OC 125 monoclonal antibody. Rare acute side effects were nausea and mild diarrhea. At doses up to 120 mCi of iodine-131, median white blood cell and platelet count nadirs were 3.6k/microliters and 187k/microliters, respectively. Two patients acquired thyroid toxicities despite thyroid blockage with cold iodine. One patient had transient TSH elevation while remaining clinically euthyroid, and 1 patient developed activation of a thyroid nodule and clinical hyperthyroidism. Dose-limiting toxicity has not yet been observed. Twelve of 20 patients are alive 3 to 17 months following therapy. Tumor progression was noted in the majority of patients, although 3 patients had documented decreases in tumor burden of short duration. We conclude that, at the doses examined, iodine-131 OC 125 can be safely administered intraperitoneally.

  5. Connexin-dependent gap junction enhancement is involved in the synergistic effect of sorafenib and all-trans retinoic acid on HCC growth inhibition

    PubMed Central

    YANG, YAN; QIN, SHU-KUI; WU, QIONG; WANG, ZI-SHU; ZHENG, RONG-SHENG; TONG, XU-HUI; LIU, HAO; TAO, LIANG; HE, XIAN-DI

    2014-01-01

    Increasing gap junction activity in tumor cells provides a target by which to enhance antineoplastic therapies. Previously, several naturally occurring agents, including all-trans retinoic acid (ATRA) have been demonstrated to increase gap junctional intercellular communication (GJIC) in a number of types of cancer cells. In the present study, we investigated in vitro whether ATRA modulates the response of human hepatocellular carcinoma (HCC) cells to sorafenib, the only proven oral drug for advanced HCC, and the underlying mechanisms. HepG2 and SMMC-7721 cells were treated with sorafenib and/or ATRA, and cell proliferation and apoptosis were analyzed; the role of GJIC was also explored. We found that ATRA, at non-toxic concentrations, enhanced sorafenib-induced growth inhibition in both HCC cell lines, and this effect was abolished by two GJIC inhibitors, 18-α-GA and oleamide. Whereas lower concentrations of sorafenib (5 μM) or ATRA (0.1 or 10 μM) alone modestly induced GJIC activity, the combination of sorafenib plus ATRA resulted in a strong enhancement of GJIC. However, the action paradigm differed in the HepG2 and SMMC-7721 cells, with the dominant effect of GJIC dependent on the cell-specific connexin increase in protein amounts and relocalization. RT-PCR assay further revealed a transcriptional modification of the key structural connexin in the two cell lines. Thus, a connexin-dependent gap junction enhancement may play a central role in ATRA plus sorafenib synergy in inhibiting HCC cell growth. Since both agents are available for human use, the combination treatment represents a future profitable strategy for the treatment of advanced HCC. PMID:24317203

  6. Sorafenib plus hepatic arterial infusion chemotherapy with cisplatin versus sorafenib for advanced hepatocellular carcinoma: randomized phase II trial

    PubMed Central

    Ikeda, M.; Shimizu, S.; Sato, T.; Morimoto, M.; Kojima, Y.; Inaba, Y.; Hagihara, A.; Kudo, M.; Nakamori, S.; Kaneko, S.; Sugimoto, R.; Tahara, T.; Ohmura, T.; Yasui, K.; Sato, K.; Ishii, H.; Furuse, J.; Okusaka, T.

    2016-01-01

    Background Sorafenib (Sor) is acknowledged as a standard therapy for advanced hepatocellular carcinoma (HCC). This trial was conducted to evaluate the effect of addition of hepatic arterial infusion chemotherapy with cisplatin (SorCDDP) to Sor for the treatment of advanced HCC. Patients and methods We conducted a multicenter open-labeled randomized phase II trial in chemo-naïve patients with advanced HCC with Child-Pugh scores of 5–7. Eligible patients were randomly assigned 2:1 to receive SorCDDP (sorafenib: 400 mg bid; cisplatin: 65 mg/m2, day 1, every 4–6 weeks) or Sor (400 mg bid). The primary end point was overall survival. Results A total of 108 patients were randomized (Sor, n = 42; SorCDDP, n = 66). The median survival in the Sor and SorCDDP arms were 8.7 and 10.6 months, respectively [stratified hazard ratio (95% confidence interval), 0.60 (0.38–0.96), P = 0.031]. The median time to progression and the response rate were, respectively, 2.8 months and 7.3% in the Sor arm and 3.1 months and 21.7% in the SorCDDP arm. The adverse events were more frequent in the SorCDDP arm than in the Sor arm, but well-tolerated. Conclusion SorCDDP yielded favorable overall survival when compared with Sor in patients with advanced HCC. Clinical Trial registration UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703. PMID:27573564

  7. Future care planning: a first step to palliative care for all patients with advanced heart disease.

    PubMed

    Denvir, M A; Murray, S A; Boyd, K J

    2015-07-01

    Palliative care is recommended for patients with end-stage heart failure with several recent, randomised trials showing improvements in symptoms and quality of life and more studies underway. Future care planning provides a framework for discussing a range of palliative care problems with patients and their families. This approach can be introduced at any time during the patient's journey of care and ideally well in advance of end-of-life care. Future care planning is applicable to a wide range of patients with advanced heart disease and could be delivered systematically by cardiology teams at the time of an unplanned hospital admission, akin to cardiac rehabilitation for myocardial infarction. Integrating cardiology care and palliative care can benefit many patients with advanced heart disease at increased risk of death or hospitalisation. Larger, randomised trials are needed to assess the impact on patient outcomes and experiences.

  8. Crizotinib Improves Progression-Free Survival in Some Patients with Advanced Lung Cancer

    MedlinePlus

    ... Prevention Lung Cancer Screening Research Crizotinib Improves Progression-Free Survival in Some Patients with Advanced Lung Cancer ( ... starting treatment without their disease getting worse (progression-free survival), as assessed by radiologic review. Results Progression- ...

  9. Prognostic Value of the Modified Glasgow Prognostic Score in Patients Undergoing Radical Surgery for Hepatocellular Carcinoma.

    PubMed

    Ni, Xiao-Chun; Yi, Yong; Fu, Yi-Peng; He, Hong-Wei; Cai, Xiao-Yan; Wang, Jia-Xing; Zhou, Jian; Cheng, Yun-Feng; Jin, Jian-Jun; Fan, Jia; Qiu, Shuang-Jian

    2015-09-01

    There is increasing and consistent evidence concerning the association of systemic inflammation and poor outcome in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify a superior inflammation-based prognostic scoring system for patients with HCC undergoing hepatectomy.We analyzed two independent cohorts of a total of 723 patients with HCC who underwent radical surgery between 2010 and 2012. The prognostic value of the inflammation scores, including the Glasgow Prognostic Score (GPS), modified GPS (mGPS), neutrophil-to-lymphocyte ratio, platelet lymphocyte ratio, prognostic index, and prognostic nutritional index, as well as the Barcelona Clinic Liver Cancer and Cancer of the Liver Italian Program staging systems was analyzed in a test cohort of 367 patients and validated in a validation cohort of 356 patients.A high score with the mGPS was associated with large tumor size, vascular invasion, and advanced clinical stage. Multivariate analysis showed that the mGPS was independently associated with overall survival and disease-free survival, and had a higher area under the curve value in comparison with other inflammation-based scores.The results of this study demonstrated that the mGPS is an independent marker of poor prognosis in patients with resectable HCC and is superior to other inflammation-based scores. PMID:26356714

  10. First In-human Intraoperative Imaging of HCC using Fluorescence Goggle System and Transarterial Delivery of Near-infrared Fluorescent Imaging Agent: a Pilot Study

    PubMed Central

    Akers, Walter; Tang, Zhao-You; Fan, Jia; Sun, Hui-Chuan; Ye, Qing-Hai; Wang, Lu; Achilefu, Samuel

    2013-01-01

    Surgical resections remain the primary curative interventions for hepatocellular carcinoma (HCC). However, lack of real-time intraoperative image guidance confines surgeons to subjective visual assessment of the surgical bed, leading to poor visualization of small positive nodules and the extension of diffuse HCC. To address this problem, we developed a wearable fluorescence imaging and display system (fluorescence goggle) for intraoperative imaging of HCCs in human patients. In this pilot study, both intravenous (i.v.) and transarterial hepatic (TAH) delivery of indocyanine green (ICG) were explored to facilitate fluorescence goggle-mediated HCC imaging. The results show that all primary tumors in patients (n=4) who received TAH delivery of ICG were successfully identified by the fluorescence goggle. In addition, 6 satellite tumors were also detected by the goggle, 5 of which were neither identifiable in pre-operative MRI and CT images nor by visual inspection and palpation. In the group (n=5) that received ICG by i.v., only 2 out of 6 tumors visible in the pre-operative MRI or CT images were identified with the fluorescence goggle, demonstrating the limitation of this delivery route for a non-tumor selective imaging agent. Comparative analysis shows that the HCC-to-liver florescence contrast detected by the goggle was significantly higher in patients that received TAH than i.v. delivery of ICG (P=0.013). This pilot study demonstrates the feasibility of using the fluorescence goggle to identify multifocal lesions and small tumor deposits using TAH ICG delivery in HCC patients. PMID:23747795

  11. Transcatheter Arterial Chemoembolization for Advanced Hepatocellular Carcinoma with Inferior Vena Cava and Right Atrial Tumors

    SciTech Connect

    Chern, M. C. Chuang, V. P. Cheng, T. Lin, Z. H. Lin, Y. M.

    2008-07-15

    Advanced hepatocelluar carcinoma (HCC) with invasion of venous systems usually indicates not only a poor prognosis but also a contraindication for transcatheter arterial chemoembolization (TACE). This study evaluated the feasibility of TACE for advanced HCC with inferior vena cava (IVC) and right atrium (RA) tumors and, also, to search for the ideal embolization particle size. Twenty-six patients who had HCC invasion into the IVC included five patients with coexistent RA tumors that were treated with TACE. The chemoembolization method was cisplatin, doxorubicin, and mitomycin C mixed with Lipiodol and Ivalon. The selection of Ivalon particles was divided into two groups based on their size: (A) >180 {mu}m, N = 9; and (B) 47-180 {mu}m, N = 17. The overall response rate was 53.8% (14/26). Based on the response to TACE, the median survival period of the entire group was 4.2 months (range, 1.5 to 76.7 months). The median survival period of the 14 responders was 13.5 months (1.5-76.7 months), and that of the 12 nonresponders, 3.3 months (2.1 to 24.3 months) (p < 0.002). Comparing the two Ivalon particle sizes, the response rate was 12.5% (1/9 patients) for group A and 76.5% for group B (13/17 patients) (p < 0.02). No serious complication was observed post-chemoembolization. In conclusion, TACE is a safe and effective treatment for advanced HCC with IVC and RA tumors, and small Ivalon particles (47-180 {mu}m) are superior to large ones (>180 {mu}m).

  12. Care of Patients at the End of Life: Advance Care Planning.

    PubMed

    Ackermann, Richard J

    2016-08-01

    Advance directives are legal documents that give instructions about how to provide care when patients develop life-threatening illnesses and can no longer communicate their wishes. Two types of documents are widely used-a living will and a durable power of attorney for health care. Most states also authorize physician orders for life-sustaining treatment. Physicians should encourage patients, particularly those with severe chronic or terminal conditions, to prepare advance directives. Medicare now reimburses billing codes for advance care consultations. Directions regarding cardiopulmonary resuscitation and artificial ventilation often are included in advance care plans, and use of artificial nutrition and hydration (ANH) also should be addressed, particularly for patients with advanced dementia. Evidence shows that in such patients, ANH does not prolong survival, increase comfort, or improve quality of life. Given the lack of benefit, physicians should recommend against use of ANH for patients with dementia. Finally, physicians should encourage use of hospice services by patients whose life expectancy is 6 months or less. Although Medicare and most other health care insurers cover hospice care, and despite evidence that patient and family satisfaction increase when hospice services are used, many patients do not use these services. PMID:27490070

  13. Hepatocyte SLAMF3 reduced specifically the multidrugs resistance protein MRP-1 and increases HCC cells sensitization to anti-cancer drugs.

    PubMed

    Fouquet, Grégory; Debuysscher, Véronique; Ouled-Haddou, Hakim; Eugenio, Mélanie Simoes; Demey, Baptiste; Singh, Amrathlal Rabbind; Ossart, Christèle; Al Bagami, Mohammed; Regimbeau, Jean-Marc; Nguyen-Khac, Eric; Naassila, Mickael; Marcq, Ingrid; Bouhlal, Hicham

    2016-05-31

    Multidrug resistance MDR proteins (MRPs) are members of the C family of a group of proteins named ATP binding cassette (ABC) transporters. MRPs can transport drugs including anticancer drugs, nucleoside analogs, antimetabolites and tyrosine kinase inhibitors. Drugs used in HCC therapy, such as tyrosine kinase inhibitor sorafenib, are substrates of uptake and/or efflux transporters. Variable expression of MRPs at the plasma membrane of tumor cells may contribute to drug resistance and subsequent clinical response. Recently, we reported that the hepatocyte SLAMF3 expression (Signaling Lymphocytic Activation Molecule Family member 3) was reduced in tumor cells from hepatocellular carcinoma (HCC) compared to its high expression in adjacent tissues. In the present study, we make a strong correlation between induced SLAMF3 overexpression and the specific loss of MRP-1 expression and its functionalities as a drugs resistance transporter. No changes were observed on expression of ABCG2 and MDR. More importantly, we highlight a strong inverse correlation between MRP-1 and SLAMF3 expression in patients with HCC. We propose that the SLAMF3 overexpression in cancerous cells could represent a potential therapeutic strategy to improve the drugs sensibility of resistant cells and thus control the therapeutic failure in HCC patients. PMID:27081035

  14. Advance care planning: thinking ahead to achieve our patients' goals.

    PubMed

    Cairns, Rosemary

    2011-09-01

    The End of Life Care Strategy for England describes advance care planning (ACP) as a 'voluntary process of discussion about future care...concerns and wishes...values or personal goals for care, their understanding of their illness and prognosis...wishes for types of care or treatment and the availability of these' (Department of Health (DH), 2008). In Scotland, Living and Dying Well: Building on Progress (Scottish Government (SG), 2011) referred to adopting a 'thinking ahead' philosophy.

  15. Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis after Concurrent Chemoradiation Therapy

    PubMed Central

    Han, Dai Hoon; Joo, Dong Jin; Kim, Myoung Soo; Choi, Gi Hong; Choi, Jin Sub; Park, Young Nyun; Seong, Jinsil

    2016-01-01

    Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate <10%. Localized concurrent chemoradiotherapy (CCRT), followed by hepatic arterial infusion chemotherapy (HAIC), was recently introduced in this setting. Here, we report our early experience with living donor liver transplantation (LDLT) in such patients after successful down-staging of HCC through CCRT and HAIC. Between December 2011 and September 2012, eight patients with locally advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3–12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10–22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis. PMID:27401662

  16. Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis after Concurrent Chemoradiation Therapy.

    PubMed

    Han, Dai Hoon; Joo, Dong Jin; Kim, Myoung Soo; Choi, Gi Hong; Choi, Jin Sub; Park, Young Nyun; Seong, Jinsil; Han, Kwang Hyub; Kim, Soon Il

    2016-09-01

    Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate <10%. Localized concurrent chemoradiotherapy (CCRT), followed by hepatic arterial infusion chemotherapy (HAIC), was recently introduced in this setting. Here, we report our early experience with living donor liver transplantation (LDLT) in such patients after successful down-staging of HCC through CCRT and HAIC. Between December 2011 and September 2012, eight patients with locally advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3-12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10-22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis. PMID:27401662

  17. Exosomes as potent regulators of HCC malignancy and potential bio-tools in clinical application

    PubMed Central

    Qu, Zhen; Jiang, Chunping; Wu, Junhua; Ding, Yitao

    2015-01-01

    Exosomes are small membranous vesicles about 30~100 nm in diameter and formed from inward budding of the limiting membrane of multi-vesicular bodies (MVB). Exosomes are secreted by most cell types (including hepatocellular carcinoma cells) into the extracellular environment and can be isolated from various body fluids. Exosomes have broad biological function through delivering contained molecules to the target cells. Although limited studies on hepatocellular carcinoma (HCC) exosomes, increasing observations suggest that exosomes are important in HCC metastatic and prognosis, and exosomes are potential new molecular biomarkers for diagnosis and prognosis of HCC. In this review, we briefly summarize the latest findings on HCC exosomes, and their potential functions for novel diagnostic and therapeutic approaches of HCC. PMID:26770301

  18. Contribution of the toxic advanced glycation end-products-receptor axis in nonalcoholic steatohepatitis-related hepatocellular carcinoma

    PubMed Central

    Takino, Jun-ichi; Nagamine, Kentaro; Hori, Takamitsu; Sakasai-Sakai, Akiko; Takeuchi, Masayoshi

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The main etiologies of HCC are hepatitis B virus and hepatitis C virus (HCV), and non-hepatitis B/non-hepatitis C HCC (NBNC-HCC) has also been identified as an etiological factor. Although the incidence of HCV-related HCC in Japan has decreased slightly in recent years, that of NBNC-HCC has increased. The onset mechanism of NBNC-HCC, which has various etiologies, remains unclear; however, nonalcoholic steatohepatitis (NASH), a severe form of nonalcoholic fatty liver disease, is known to be an important risk factor for NBNC-HCC. Among the different advanced glycation end-products (AGEs) formed by the Maillard reaction, glyceraldehyde-derived AGEs, the predominant components of toxic AGEs (TAGE), have been associated with NASH and NBNC-HCC, including NASH-related HCC. Furthermore, the expression of the receptor for AGEs (RAGE) has been correlated with the malignant progression of HCC. Therefore, TAGE induce oxidative stress by binding with RAGE may, in turn, lead to adverse effects, such as fibrosis and malignant transformation, in hepatic stellate cells and tumor cells during NASH or NASH-related HCC progression. The aim of this review was to examine the contribution of the TAGE-RAGE axis in NASH-related HCC. PMID:26483867

  19. Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients

    Cancer.gov

    A four-drug chemotherapy regimen has produced the longest improvement in survival ever seen in a phase III clinical trial of patients with metastatic pancreatic cancer, one of the deadliest types of cancer.

  20. Heading perception in patients with advanced retinitis pigmentosa

    NASA Technical Reports Server (NTRS)

    Li, Li; Peli, Eli; Warren, William H.

    2002-01-01

    PURPOSE: We investigated whether retinis pigmentosa (RP) patients with residual visual field of < 100 degrees could perceive heading from optic flow. METHODS: Four RP patients and four age-matched normally sighted control subjects viewed displays simulating an observer walking over a ground. In experiment 1, subjects viewed either the entire display with free fixation (full-field condition) or through an aperture with a fixation point at the center (aperture condition). In experiment 2, patients viewed displays of different durations. RESULTS: RP patients' performance was comparable to that of the age-matched control subjects: heading judgment was better in the full-field condition than in the aperture condition. Increasing display duration from 0.5 s to 1 s improved patients' heading performance, but giving them more time (3 s) to gather more visual information did not consistently further improve their performance. CONCLUSIONS: RP patients use active scanning eye movements to compensate for their visual field loss in heading perception; they might be able to gather sufficient optic flow information for heading perception in about 1 s.

  1. Attitudes towards and barriers to writing advance directives amongst cancer patients, healthy controls, and medical staff

    PubMed Central

    Sahm, S; Will, R; Hommel, G

    2005-01-01

    Objectives: After years of public discussion too little is still known about willingness to accept the idea of writing an advance directive among various groups of people in EU countries. We investigated knowledge about and willingness to accept such a directive in cancer patients, healthy controls, physicians, and nursing staff in Germany. Methods: Cancer patients, healthy controls, nursing staff, and physicians (n = 100 in each group) were surveyed by means of a structured questionnaire. Results: Only 18% and 19% of the patients and healthy controls respectively, and 10% of the medical staff had written an advance directive. However, 50–81% of those surveyed indicated that they wished to write one. This intention was associated with deteriorating health (p < 0.001). Only 29% of the healthy controls and 43% of the patients knew about the possibility of appointing a health care proxy. A majority in all groups believed that advance directives may influence the course of treatment (79–85%), yet half of those surveyed in all groups fear that patients could be pressurised into writing an advance directive, and 38–65% thought that relatives could abuse such documents. Conclusions: Only a minority of the participants had written an advance directive and knew about the possibility of authorising a health care proxy. Deteriorating health was associated with increasing willingness to make a directive. Despite a majority belief that advance directives may influence treatment at the end of life, other factors limit their employment, such as fear of abuse. PMID:16076965

  2. Lenvatinib and Capecitabine in Patients With Advanced Malignancies

    ClinicalTrials.gov

    2016-09-23

    Advanced Cancer; Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract

  3. Technology advances in hospital practices: robotics in treatment of patients.

    PubMed

    Rosiek, Anna; Leksowski, Krzysztof

    2015-06-01

    Laparoscopic cholecystectomy is widely considered as the treatment of choice for acute cholecystitis. The safety of the procedure and its minimal invasiveness made it a valid treatment option for a patient not responding to antibiotic therapy. Our research shows that patients positively assess this treatment method, but the world's tendency is to turn to a more sophisticated method utilizing robot-assisted surgery as a gold standard. Providing patient with minimally invasive surgical procedures that utilize the state-of-the-art equipment like the da Vinci Robotic Surgical System underscores the commitment to high-quality patient care while enhancing patient safety. The advantages include minimal invasive scarring, less pain and bleeding, faster recovery time, and shorter hospital stay. The move toward less invasive and less morbid procedures and a need to re-create the true open surgical experience have paved the way for the development and application of robotic and computer-assisted systems in surgery in Poland as well as the rest of the world.

  4. Technology advances in hospital practices: robotics in treatment of patients.

    PubMed

    Rosiek, Anna; Leksowski, Krzysztof

    2015-06-01

    Laparoscopic cholecystectomy is widely considered as the treatment of choice for acute cholecystitis. The safety of the procedure and its minimal invasiveness made it a valid treatment option for a patient not responding to antibiotic therapy. Our research shows that patients positively assess this treatment method, but the world's tendency is to turn to a more sophisticated method utilizing robot-assisted surgery as a gold standard. Providing patient with minimally invasive surgical procedures that utilize the state-of-the-art equipment like the da Vinci Robotic Surgical System underscores the commitment to high-quality patient care while enhancing patient safety. The advantages include minimal invasive scarring, less pain and bleeding, faster recovery time, and shorter hospital stay. The move toward less invasive and less morbid procedures and a need to re-create the true open surgical experience have paved the way for the development and application of robotic and computer-assisted systems in surgery in Poland as well as the rest of the world. PMID:25782187

  5. Effectiveness of the Mindfulness Art Therapy Short Version for Japanese Patients with Advanced Cancer

    ERIC Educational Resources Information Center

    Ando, Michiyo; Kira, Haruko; Hayashida, Shigeru; Ito, Sayoko

    2016-01-01

    The aim of this study was to investigate the feasibility of the Mindfulness Art Therapy Short Version for Japanese patients with advanced cancer. Patients learned mindfulness practices and then made art to express their feelings in the first session. After receiving instruction on practicing mindfulness 2 weeks later, they participated in a second…

  6. Balamuthia mandrillaris and Acanthamoeba Amebic Encephalitis with Neurotoxoplasmosis Coinfection in a Patient with Advanced HIV Infection

    PubMed Central

    Chan, Joseph C.; Castellano-Sanchez, Amilcar; Hirzel, Alicia; Laowansiri, Panthipa; Tuda, Claudio; Visvesvara, Govinda S.; Qvarnstrom, Yvonne; Ratzan, Kenneth R.

    2012-01-01

    We describe a patient with advanced HIV infection and Balamuthia mandrillaris and Acanthamoeba amebic encephalitis with Toxoplasma gondii coinfection. A multidisciplinary effort and state-of-the-art diagnostic techniques were required for diagnosis. Our patient is the first reported case of an HIV-infected person with dual Balamuthia mandrillaris and Acanthamoeba amebic encephalitis with neurotoxoplasmosis coinfection. PMID:22170911

  7. Phase II trial of bevacizumab and erlotinib as a second-line therapy for advanced hepatocellular carcinoma

    PubMed Central

    Kaseb, Ahmed O; Morris, Jeffrey S; Iwasaki, Michiko; Al-Shamsi, Humaid O; Raghav, Kanwal Pratap Singh; Girard, Lauren; Cheung, Sheree; Nguyen, Van; Elsayes, Khaled M; Xiao, Lianchun; Abdel-Wahab, Reham; Shalaby, Ahmed S; Hassan, Manal; Hassabo, Hesham M; Wolff, Robert A; Yao, James C

    2016-01-01

    Trial registry Clinicaltrials.gov #NCT01180959. Background Early clinical studies of bevacizumab and erlotinib in advanced hepatocellular carcinoma (HCC) have a tolerable toxicity and a promising clinical outcome. We evaluated the efficacy and tolerability of this combination as a second-line therapy for HCC refractory to sorafenib. Methods For this single-arm, Phase II study, we recruited patients with Child–Pugh class A or B liver disease, Eastern Cooperative Oncology Group performance status 0–2, and advanced HCC that was not amenable to surgical or regional therapies and treatment with sorafenib had failed (disease progressed or patient could not tolerate sorafenib). Patients received 10 mg/kg intravenous bevacizumab every 14 days and 150 mg oral erlotinib daily for 28-day cycles until progression. Tumor response was evaluated every two cycles using Response Evaluation Criteria in Solid Tumors. The primary end point was the 16-week progression-free survival rate. Secondary end points included time to progression and overall survival. Results A total of 44 patients were enrolled and had a median follow-up time of 33.8 months (95% confidence interval [CI]: 23.5 months – not defined). The 16-week progression-free survival rate was 43% (95% CI: 28%–59%), median time to progression was 3.9 months (95% CI: 2.0–8.3 months), and median overall survival duration was 9.9 months (95% CI: 8.3–15.5 months). Grade 3–4 adverse events included fatigue (13%), acne (11%), diarrhea (9%), anemia (7%), and upper gastrointestinal hemorrhage (7%). Conclusion Bevacizumab plus erlotinib was tolerable and showed a signal of survival benefit in the second-line setting for patients with advanced HCC. Because standard-of-care options are lacking in this setting, further studies to identify predictors of response to this regimen are warranted. PMID:26929648

  8. Expressed wishes and incidence of euthanasia in advanced lung cancer patients.

    PubMed

    Pardon, Koen; Deschepper, Reginald; Vander Stichele, Robert; Bernheim, Jan L; Mortier, Freddy; Schallier, Denis; Germonpré, Paul; Galdermans, Daniella; Van Kerckhoven, Willem; Deliens, Luc

    2012-10-01

    This study explores expressed wishes and requests for euthanasia (i.e. administration of lethal drugs at the explicit request of the patient), and incidence of end-of-life decisions with possible life-shortening effects (ELDs) in advanced lung cancer patients in Flanders, Belgium. We performed a prospective, longitudinal, observational study of a consecutive sample of advanced lung cancer patients and selected those who died within 18 months of diagnosis. Immediately after death, the pulmonologist/oncologist and general practitioner (GP) of the patient filled in a questionnaire. Information was available for 105 out of 115 deaths. According to the specialist or GP, one in five patients had expressed a wish for euthanasia; and three in four of these had made an explicit and repeated request. One in two of these received euthanasia. Of the patients who had expressed a wish for euthanasia but had not made an explicit and repeated request, none received euthanasia. Patients with a palliative treatment goal at inclusion were more likely to receive euthanasia. Death was preceded by an ELD in 62.9% of patients. To conclude, advanced lung cancer patients who expressed a euthanasia wish were often determined. Euthanasia was performed significantly more among patients whose treatment goal after diagnosis was exclusively palliative.

  9. Impact Factors for Microinvasion in Patients With Hepatocellular Carcinoma: Possible Application to the Definition of Clinical Tumor Volume

    SciTech Connect

    Wang Minhua; Ji Yuan; Zeng Zhaochong; Tang Zhaoyou; Fan Jia; Zhou Jian; Zeng Mengsu; Bi Aihong; Tan Yunshan

    2010-02-01

    Purpose: To evaluate the degree of invasion of hepatocellular carcinoma (HCC) microscopically that will provide a potential application for gross tumor volume to clinical tumor volume (GTV-to-CTV) expansion. Methods and Materials: From January 2002 to January 2006, 149 HCC patients were selected from those who had undergone surgical resection. Pathology slides and clinical data of all patients were reviewed, including platelet counts, serum alpha-fetoprotein (AFP) levels, degree of liver cirrhosis, tumor size, capsular status, portal vein invasion, TNM stage, and histologic tumor grade. The distance between the tumor margin (or fibrous capsule) and the invasive lesions was measured by senior pathologists. Results: Of these 149 patients, 79 (53.0%) patients presented with tumor microinvasion between 0.5 and 4 mm. This degree of microinvasion was inversely correlated with lower platelet counts and positively correlated with higher AFP levels, larger tumor sizes, portal vein invasion, and advanced TNM stage. Microinvasion distances less than or equal to 2 mm were found in 96.1% of patients (74/77) with tumor dimensions less than or equal to 5 cm and in 94.5% of patients (85/90) with AFP levels less than 400 mug/l. Conclusions: Based on our study findings, GTV-to-CTV expansions of 4 mm for HCC are required to conceal the gross tumor and any microscopic disease with 100% accuracy. Tumor size and AFP levels are the simplest indicators for determining the GTV-to-CTV distance for HCC.

  10. Using Standardized Patients in Advanced Practice Nursing Education.

    ERIC Educational Resources Information Center

    Vessey, Judith A.; Huss, Karen

    2002-01-01

    Graduating nurse practitioners (n=26) completed simulated clinical encounters with standardized patients. Their performance did not reflect their results on other clinical evaluations and national certifying examinations, suggesting that simulated encounters lack validity and reliability. They may be useful for formative learning. (Contains 38…

  11. Progress in systemic therapy of advanced hepatocellular carcinoma

    PubMed Central

    Gong, Xin-Lei; Qin, Shu-Kui

    2016-01-01

    Primary liver cancer, mainly consisting of hepatocellular carcinoma (HCC), is one of common malignancies worldwide, and prevalent among the Chinese population. A diagnosis of early stage HCC has proven to be very difficult because of its insidious feature in onset and development. At the time of diagnosis, most HCC cases are locally advanced and/or distant metastatic, which results in difficulty to be treated and poor prognosis. For advanced HCC, systemic therapy is frequently adopted as an important palliative method. In recent years, clinical studies and observations have often reported about systemic anti-cancer therapy of advanced HCC, including molecular target therapy, systemic chemotherapy and immunotherapy. In this article, we review these treatment modalities to provide a reference for clinicians. PMID:27547002

  12. Anxiety and depression in patients with advanced macular degeneration: current perspectives

    PubMed Central

    Cimarolli, Verena R; Casten, Robin J; Rovner, Barry W; Heyl, Vera; Sörensen, Silvia; Horowitz, Amy

    2016-01-01

    Age-related macular degeneration (AMD) – despite advances in prevention and medical treatment options – remains prevalent among older adults, often resulting in functional losses that negatively affect the mental health of older adults. In particular, the prevalence of both anxiety and depression in patients with AMD is high. Along with medical treatment options, low vision rehabilitation and AMD-specific behavioral and self-management programs have been developed and have demonstrated effectiveness in improving the mental health of AMD patients. This article reviews the prevalence of anxiety and depression in patients with advanced AMD, discusses potential mechanisms accounting for the development of depression and anxiety in AMD patients, presents the state-of the-art of available interventions for addressing anxiety and depression in AMD patients, and delineates recommendations for eye care professionals regarding how to screen for these two prevalent mental health problems and how to facilitate appropriate treatment for patients with AMD. PMID:26766899

  13. Type conversion of secretomes in a 3D TAM2 and HCC cell co-culture system and functional importance of CXCL2 in HCC

    PubMed Central

    Lu, Yu; Li, Shan; Ma, Liping; Li, Yan; Zhang, Xiaolian; Peng, Qiliu; Mo, Cuiju; Huang, Li; Qin, Xue; Liu, Yinkun

    2016-01-01

    Macrophages play important roles in the tumor microenvironment, driving cancer progression and metastasis, particularly in hepatocellular carcinoma (HCC). However, few studies have assessed the exact secretome composition in HCC. In the present study, the impact of different phenotype of macrophages on HCC cells was investigated. Alternatively activated macrophages (M2) were found to significantly increase the proliferation, migration, and invasion abilities of SMMC7721 cells (all P < 0.05). M2 were then co-cultured with SMMC7721 cells to reconstruct the tumor microenvironment. Conditioned medium from 3D single cultures of M2, SMMC7721 cells, and their co-culture system were analyzed using quantitative proteomics via iTRAQ labeling combined with mass spectrometric analysis. Secretome analysis revealed a total of 159 differential secreted proteins in the co-culture system compared to the single culture systems, with 63 being up-regulated (>1.3-fold) and 96 down-regulated (<0.7-fold). CXCL2 was confirmed to have higher expression in the co-culture system and HCC tissues, and was selected for further investigation. Functional effects data suggested that recombinant human CXCL2 significantly enhanced the migration, invasion ability of SMMC7721 cells, and weakened adhesion ability. While CXCL2 neutralization and CXCR2 blockage significantly inhibited the effects of CXCL2 on SMMC7721 cells, indicating that CXCL2 may play pivotal role in HCC metastasis. PMID:27117207

  14. Contradicting interplay between insulin-like growth factor-1 and miR-486-5p in primary NK cells and hepatoma cell lines with a contemporary inhibitory impact on HCC tumor progression.

    PubMed

    Youness, Rana Ahmed; Rahmoon, Mai Atef; Assal, Reem Amr; Gomaa, Asmaa Ibrahim; Hamza, Mohamed Tarif; Waked, Imam; El Tayebi, Hend Mohamed; Abdelaziz, Ahmed Ihab

    2016-08-01

    In this study, an impaired natural killer (NK) cell cytolytic activity in 135 hepatocellular carcinoma (HCC) patients parallel to a reduced expression level of insulin-like growth factor (IGF)-1 in NK cells of HCC patients has been revealed. Ectopic expression of miR-486-5p, a direct upstream regulator of IGF-1, restored the endogenous level of IGF-1 in NK cells of HCC patients, thus augmenting its cytolytic activity against Huh7 cells in an opposite manner to the IGF-1 siRNAs. Unorthodoxly, over-expression of miR-486-5p in target hepatocytes resulted in the repression of IGF-1, suppression of Huh7 cells proliferation and viability in a similar pattern to the IGF-1 siRNAs. Therefore, this study highlights a potential role of IGF-1 in modulating cytolytic potential of NK cells of HCC patients. miR-486-5p acts in a cell-specific manner, differentially modulating IGF-1 expression in NK cells and their target hepatocytes with a contemporary inhibitory impact on HCC progression.

  15. Cone-Beam Computed Tomography Correlates with Conventional Helical Computed Tomography in Evaluation of Lipiodol Accumulation in HCC after Chemoembolization

    PubMed Central

    Ishikawa, Toru; Abe, Satoshi; Hoshii, Asami; Yamada, Yumi; Iiduka, Akihiko; Nemoto, Takeo; Takeda, Keiko; Yoshida, Toshiaki

    2016-01-01

    Background & Aims The amount of drug-loaded lipiodol in an HCC tumor post-transarterial chemoembolization (TACE) correlates with the risk of local tumor recurrence. Lipiodol enhancement of a tumor on conventional CT, measured in Hounsfield units (HU), can predict tumor response. Here we investigate whether cone-beam CT (CBCT) can also be used to predict tumor response, providing the benefit of being able to optimize the patient’s treatment plan intra-procedurally. Methods A total of 82 HCC nodules (82 patients), ≤5 cm in diameter, were treated with balloon-occluded TACE using miriplatin between December 2013 and November 2014. For each patient, both CBCT and conventional CT images were obtained post-TACE. The degree of correlation between CBCT and conventional CT was determined by comparing identical regions of interest for each imaging modality using pixel values. Results The pixel values from conventional CT and CBCT were highly correlated, with a Pearson correlation coefficient of 0.912 (p<0.001). The location of the nodules within the liver did not affect the results; the correlation coefficient was 0.891 (p<0.001) for the left lobe and 0.926 (p<0.001) for the right lobe. The mean pixel value for conventional CT was 439 ± 279 HU, and the mean pixel value for CBCT was 416 ± 311 HU. Conclusions CBCT may be used as a substitute for conventional CT to quantitatively evaluate the amount of drug-loaded lipiodol within an HCC nodule and, hence, the efficacy of TACE treatment. The major benefit of using CBCT is the ability to predict the likelihood of local recurrence intra-procedurally, enabling subsequent treatment optimization. PMID:26752696

  16. Recent advances in MRI technology: Implications for image quality and patient safety

    PubMed Central

    Sobol, Wlad T.

    2012-01-01

    Recent advances in MRI technology are presented, with emphasis on how this new technology impacts clinical operations (better image quality, faster exam times, and improved throughput). In addition, implications for patient safety are discussed with emphasis on the risk of patient injury due to either high local specific absorption rate (SAR) or large cumulative energy doses delivered during long exam times. Patient comfort issues are examined as well. PMID:23961024

  17. Advances in Patient-Reported Outcomes: The NIH PROMIS® Measures

    PubMed Central

    Broderick, Joan E.; DeWitt, Esi Morgan; Rothrock, Nan; Crane, Paul K.; Forrest, Christopher B.

    2013-01-01

    Patient-reported outcomes (PRO) are questionnaire measures of patients’ symptoms, functioning, and health-related quality of life. They are designed to provide important clinical information that generally cannot be captured with objective medical testing. In 2004, the National Institutes of Health launched a research initiative to improve the clinical research enterprise by developing state-of-the-art PROs. The NIH Patient-Reported Outcomes Measurement System (PROMIS) and Assessment Center are the products of that initiative. Adult, pediatric, and parent-proxy item banks have been developed by using contemporary psychometric methods, yielding rapid, accurate measurements. PROMIS currently provides tools for assessing physical, mental, and social health using short-form and computer-adaptive testing methods. The PROMIS tools are being adopted for use in clinical trials and translational research. They are also being introduced in clinical medicine to assess a broad range of disease outcomes. Recent legislative developments in the United States support greater efforts to include patients’ reports of health experience in order to evaluate treatment outcomes, engage in shared decision-making, and prioritize the focus of treatment. PROs have garnered increased attention by the Food and Drug Administration (FDA) for evaluating drugs and medical devices. Recent calls for comparative effectiveness research favor inclusion of PROs. PROs could also potentially improve quality of care and disease outcomes, provide patient-centered assessment for comparative effectiveness research, and enable a common metric for tracking outcomes across providers and medical systems. PMID:25848562

  18. Bone disease in uremic patients: advances in PTH suppression.

    PubMed

    Brancaccio, Diego; Cozzolino, Mario; Gorio, Alfredo; Di Giulio, Anna Maria; Gallieni, Maurizio

    2002-01-01

    Chronic renal failure is often complicated by altered calcium and phosphate omeostasis. Many patients develop secondary hyperparathyroidism during the course of the disease. Therefore, both prevention and treatment of secondary hyperparathyroidism are central issues in the treatment of uremic patients. Active vitamin D metabolites are important agents in uremic patients, who have a defective activity of the renal 1alpha-hydroxylase responsible for calcitriol synthesis. Howewer, treatment with calcitriol has some limitations, namely an increase in intestinal phosphate absorption, a possible calcium overload and therefore an increase in CaxP ion product. These limitations stimulated an active research on the development of vitamin D analogs with reduced effects on intestinal transport as well as on bone mobilization of calcium and phosphate. Three vitamin D analogs, which have been used in humans, are reviewed in this article: 22-oxacalcitriol (Maxacalcitol), 19-nor-1alpha,25(OH)2 vitamin D2 (Paricalcitol), and 1alpha(OH) Vitamin D2 (Doxercalciferol). In addition, a new pharmacologic approach to the treatment of secondary hyperparathyroidism has been developed: the use of agonists for the parathyroid calcium sensing receptor, or calcimimetics. AMG O73, a second generation agent, is now under clinical evaluation in phase 3 studies, and it will soon be available in clinical practice. Given the different mechanism of action, it will be possible to use it along with vitamin D analogs and non calcemic phosphate binders. A broader spectrum of therapeutic approaches will enable the nephrologist to individually tailor the treatment of secondary hyperparathyroidism. PMID:12515379

  19. [Plasma Biomarkers as Predictive Factors for Advanced Hepatocellular Carcinoma with Sorafenib].

    PubMed

    Shiozawa, Kazue; Watanabe, Manabu; Ikehara, Takashi; Matsukiyo, Yasushi; Kogame, Michio; Shinohara, Mie; Kikuchi, Yoshinori; Igarashi, Yoshinori; Sumino, Yasukiyo

    2016-07-01

    We examined plasma biomarkers as predictive factors for advanced hepatocellular carcinoma(ad-HCC)patients treated with sorafenib. We analyzed a-fetoprotein(AFP), AFP-L3, des-g-carboxy prothrombin(DCP), neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), and vascular endothelial growth factor(VEGF)before sorafenib therapy, and changes in AFP-L3, NLR, PLR, and VEGF 1 month after sorafenib therapy in 16 patients. High AFP-L3(hazard ratio: 1.058, 95%CI: 1.019-1.098, p=0.003)and high NLR(hazard ratio: 1.475, 95%CI: 1.045-2.082, p=0.027)were significantly associated with poor prognosis in ad-HCC patients treated with sorafenib. There were no significant differences in changes in AFP-L3, NLR, PLR, and VEGF 1 month after sorafenib therapy. We suggest that AFP-L3 and NLR levels before sorafenib therapy in patients with ad-HCC are an important predictive factor for the therapeutic effect of sorafenib and patient survival. PMID:27431630

  20. Participation of patients in the development of advanced therapy medicinal products.

    PubMed

    Bignami, F; Kent, A J; Lipucci di Paola, M; Meade, N

    2011-07-01

    An increasing number of advanced therapy medicinal products (ATMPs) are under development and in clinical trials. Patients are central to this progress. In research, patients have funded, catalysed, coordinated and led projects. In regulation, patient groups have contributed to the creation of the political momentum for regulation of ATMPs, contributed to the debate and now participate in the regulatory process. Once licensed, patients will have a role in the pharmacovigilance, health technology assessment and reimbursement arrangements for these products. Patient groups contribute valuably as equal stakeholders at every step of the development of an ATMP.

  1. Progression of Hepatitis to Hcc: Immunological Cofactors and Genetic Biomarkers

    NASA Astrophysics Data System (ADS)

    Buonaguro, Franco M.

    2014-07-01

    Globally, an estimated 130-170 million persons (2%-3% of the world's population) are living with hepatitis C virus (HCV) infection. About 80% of individuals exposed to HCV develop chronic infection and 3-11% of people with chronic HCV infection will develop liver cirrhosis within 20 years with associated risks of liver failure and hepatocellular carcinoma. Region-specific estimates range from <1.0% in Northern Europe to >2.9% in Northern Africa. The lowest prevalence (0.01%-0.1%) has been reported from countries in the United Kingdom and Scandinavia; the highest prevalence (15%-20%) has been reported from Egypt. Germany and France show in the general population a low (<0.5%) and an intermediate (1-<2) prevalence, respectively. The worldwide highest prevalence is in the intra-venous drug users (IDU) groups, with over 60% prevalence. Incidence and prevalence of HCV infections show a peculiar geographical distribution with higher frequency in Asian, Northern Africa and Southern Italian regions, Italy (with United States, Australia, Turkey, Spain and Japan) belongs to the regions of the world with an overall intermediate prevalence of HCV infection (1.0%-1.9%), with a peculiar geographical and age-specific prevalence. In some areas of Southern Italy persons >50 years old account for most infections, with a HCV-prevalence peak >30% in subject over 65 years of age (Figure 1), suggesting a cohort effect in which the risk for HCV infection was higher in the distant past, i.e., 40-60 years previously. In the same areas, in fact, the HCV prevalence drops to <10% in the 30-35 years age group. All these data would support the role of specific events (including public-health related iatrogenic transmission) in circulation of the pathogen in each population. However a further issue is frequency and rate of chronic HCV infection as well as progression to HCC...

  2. Impact of Diabetes and Hyperglycemia on Survival in Advanced Breast Cancer Patients

    PubMed Central

    Villarreal-Garza, Cynthia; Shaw-Dulin, Robin; Lara-Medina, Fernando; Bacon, Ludwing; Rivera, Daniel; Urzua, Lorena; Aguila, Christian; Ramirez-Morales, Rebeca; Santamaria, Julieta; Bargallo, Enrique; Mohar, Alejandro; Herrera, Luis A.

    2012-01-01

    Purpose. We examined the impact of diabetes and hyperglycemia on cancer-specific survival of patients with metastatic or recurrent breast cancer (BC). Methods. We performed a retrospective analysis of 265 patients with advanced BC receiving palliative chemotherapy. BC-specific mortality was compared for diabetic and nondiabetic patients as well as for patients that presented hyperglycemia during treatment. Results. No difference was observed between the diabetic and nondiabetic patients in terms of overall survival (OS). A difference in OS was observed between nondiabetic patients and diabetic patients who had hyperglycemia. The OS was greater in diabetic patients with proper metabolic control than diabetic patients with hyperglycemia. The risk of death was higher in patients with mean glucose levels >130 mg/dL during treatment. Several factors were associated with poor OS: tumor stage, hormone-receptor-negative tumors, HER2 negative disease, multiple metastatic sites, presence of visceral metastases, and mean glucose >130 mg/dL. Conclusion. Elevated glucose levels are associated with a poor outcome in diabetic and nondiabetic patients in contrast to patients with normoglycemic levels, conferring an elevated risk of death. According to these results, clinicians should monitor glucose levels during treatment for advanced breast cancer disease and take action to maintain normal glucose levels. PMID:22919369

  3. Prognostic value of preoperative peripheral monocyte count in patients with hepatocellular carcinoma after liver transplantation.

    PubMed

    Ren, Qing-Qi; Fu, Shun-Jun; Zhao, Qiang; Guo, Zhi-Yong; Ji, Fei; Chen, Mao-Gen; Wu, Lin-Wei; He, Xiao-Shun

    2016-07-01

    Prognostic value of peripheral monocyte, as a member of inflammatory cells, was widely being investigated. The aim of this study was to evaluate the prognostic value of preoperative peripheral blood monocyte count for hepatocellular carcinoma (HCC) patients who underwent liver transplantation (LT) and the relationship between monocyte count and tumor-related characteristics. We retrospectively analyzed the clinical data of 101 HCC patients after LT. Preoperative monocyte count and demographic, clinical, and pathologic data were analyzed. The optimal cutoff value of monocyte count was 456/mm(3), with the sensitivity and specificity of 69.4 and 61.5 %, respectively. Elevated preoperative peripheral blood monocyte count was significantly associated with large tumor size. The 1-, 3-, and 5-year disease-free survival (DFS) (80.9, 70.1, and 53.3 % vs 55.1, 38.7, and 38.7 %, P = 0.007) and overall survival (OS) rates (95.7, 76.6, and 64.8 % vs 72.2, 44.1, and 36.1 %, P = 0.002) of HCC patients in the peripheral blood monocyte count ≤456/mm(3) group were higher than those in the peripheral blood monocyte count >456/mm(3) group. In conclusion, elevated preoperative peripheral blood monocyte count was significantly associated with advanced tumor stage and it can be considered as a prognostic factor for HCC patients after LT.

  4. Census Analysis: A Look at HCC Credit Students Based on the 1980 Census. Research Report Number 30.

    ERIC Educational Resources Information Center

    Nespoli, Lawrence A.; Radcliffe, Susan K.

    A study was conducted by Howard Community College (HCC) to identify the geographic make-up of HCC credit students and to examine importance factors influencing college attendance. Using census software, data on 93.4% of HCC's 1980 credit students (N=4,013) were compared with 1980 census data on Howard County to determine participation rates for…

  5. Investigation of the oral infections and manifestations seen in patients with advanced cancer

    PubMed Central

    Xu, Lihua; Zhang, Hualin; Liu, Jinsong; Chen, Xiaowei

    2013-01-01

    Objective: A prospective, observational study was undertaken to investigate the epidemiology of oral infection among the patients with advanced malignancies, and to investigate the effects of therapy strategies and risk factors on the incidence of oral infection. Methods: The patients with advanced malignancies were enrolled into the study. The incidence of oral infection with different malignant tumor groups or different treatment methods and the diagnoses of oral infection were confirmed. Demographic data on age, gender, bed rest time, nutritional status, smoking habit and the presence of oral prosthesis were also recorded. Results: Oral infection was prevalent in 46% (391/850) of all cancer patients, with the highest rate in oral and maxillofacial cancer group (67%), followed by Hematological malignancy group (58.6%) and other groups (ranging from 43.3% to 35.3%). Oral candidiasis, oral herpes simplex, and oral mucositis were the popular infectious diseases in the patients. Chemotherapy and radiotherapy, especially combined radio- and chemotherapy, resulted in more oral infections compared with palliative care and surgery. Poor nutritional status and oral prosthesis were identified as independent risk factors associated with oral infection. Conclusion: Oral infection is prevalent among advanced cancer patients and associated with therapy methods and risk factors. More oral health care should be carried out for the patients with advanced malignant tumor. PMID:24353702

  6. The desire to die: making treatment decisions for suicidal patients who have an advance directive.

    PubMed

    Salter, Erica K

    2014-01-01

    This article enumerates and critically examines the potential grounds on which we might treat the case of a patient with an advance directive who attempted suicide, differently from one whose injuries were the result of an accident. Grounds for differentiation are distilled into two potential justifications. The first addresses the concern that withholding or withdrawing care from a patient with self-inflicted injuries would be aiding and abetting suicide.The second examines concerns about the patient's decisionmaking capacity. Ultimately, it is argued that while there might be legitimate reasons to hold the advance directive of a suicidal patient to a different standard of scrutiny, the fact that the patient's medical state was self-inflicted should not, in and of itself, necessarily invalidate the guidance of the directive. Finally, four practical recommendations are offered for negotiating similar cases.

  7. Beneficial effects through aggressive coronary screening for type 2 diabetes patients with advanced vascular complications.

    PubMed

    Tsujimoto, Tetsuro; Sugiyama, Takehiro; Yamamoto-Honda, Ritsuko; Kishimoto, Miyako; Noto, Hiroshi; Morooka, Miyako; Kubota, Kazuo; Kamimura, Munehiro; Hara, Hisao; Kajio, Hiroshi; Kakei, Masafumi; Noda, Mitsuhiko

    2016-08-01

    Glycemic control alone does not reduce cardiovascular events in patients with type 2 diabetes (T2D), and routine screening of all T2D patients for asymptomatic coronary artery disease (CAD) is not effective for preventing acute cardiac events. We examined the effectiveness of an aggressive screening protocol for asymptomatic CAD in T2D patients with advanced vascular complications.We designed a 3-year cohort study investigating the effectiveness of the aggressive coronary screening for T2D patients with advanced vascular complications and no known coronary events using propensity score adjusted analysis at a national center in Japan. Eligibility criteria included T2D without known coronary events and with any 1 of the following 4 complications: advanced diabetic retinopathy, advanced chronic kidney disease, peripheral artery disease, or cerebrovascular disease. In the aggressive screening group (n = 122), all patients received stress single photon emission computed tomography and those exhibiting myocardial perfusion abnormalities underwent coronary angiography. In the conventional screening group (n = 108), patients were examined for CAD at the discretion of their medical providers. Primary endpoint was composite outcome of cardiovascular death and nonfatal cardiovascular events.Asymptomatic CAD with ≥70% stenosis was detected in 39.3% of patients completing aggressive screening. The proportions achieving revascularization and receiving intensive medical therapy within 90 days after the screening were significantly higher in the aggressive screening group than in the conventional screening group [19.7% vs 0% (P < 0.001) and 48.4% vs 9.3% (P < 0.001), respectively]. The cumulative rate of primary composite outcome was significantly lower in the aggressive screening group according to a propensity score adjusted Cox proportional hazards model (hazard ratio, 0.35; 95% confidence interval, 0.12-0.96; P = 0.04).Aggressive coronary screening for T2D patients

  8. Measuring therapeutic alliance between oncologists and patients with advanced cancer: The Human Connection Scale

    PubMed Central

    Mack, Jennifer W; Block, Susan D.; Nilsson, Matthew; Wright, Alexi; Trice, Elizabeth; Friedlander, Robert; Paulk, Elizabeth; Prigerson, Holly G

    2009-01-01

    Objectives Patients consider having a human connection with a physician to be an important aspect of end-of-life (EOL) care. We sought to develop and validate a measure of therapeutic alliance between advanced cancer patients and their physicians, and to evaluate the effects of therapeutic alliance on EOL experiences and care. Methods We developed The Human Connection (THC) scale to measure the extent to which patients felt a sense of mutual understanding, caring, and trust with their physicians. The scale was administered to 217 advanced cancer patients along with measures of attributes hypothesized to be related to therapeutic alliance, including emotional acceptance of terminal illness. EOL outcomes in 90 patients who died during the study were also examined. Results The 16-item THC questionnaire was internally consistent (Cronbach’s α =.90) and valid, based on its expected positive association with emotional acceptance of the terminal illness (r=.31, P<.0001). THC scores were inversely related to symptom burden (r=−.19, P=.006), functional status (Karnofsky score, r=.22, P=.001), and mental illness (THC score 50.69 for patients with any DSM diagnosis versus 55.22 for those without, P=.03). THC scores were not significantly associated with EOL discussions (P=.68). Among patients who had died, EOL ICU care was inversely associated with therapeutic alliance (THC score 46.5 for those with ICU care versus 55.5 for those without, P=.002), such that patients with higher THC scores were less likely to spend time in the ICU during the last week of life. Conclusion The THC scale is a valid and reliable measure of therapeutic alliance between advanced cancer patients and their physicians. In addition, we found no evidence to suggest that EOL discussions harm patients’ therapeutic alliance. A strong therapeutic alliance is associated with emotional acceptance of a terminal illness and with decreased ICU care at the end of life among patients with advanced cancer

  9. Research advances in traditional Chinese medicine syndromes in cancer patients.

    PubMed

    Ji, Qing; Luo, Yun-quan; Wang, Wen-hai; Liu, Xuan; Li, Qi; Su, Shi-bing

    2016-01-01

    Traditional Chinese medicine (TCM) syndrome, also known as TCM ZHENG or TCM pattern, is an integral and essential part of TCM theory that helps to guide the design of individualized treatments. A TCM syndrome, in essence, is a characteristic profile of all clinical manifestations in one patient that can be readily identified by a TCM practitioner. In this article, the authors reviewed the presentations of TCM syndromes in seven common malignancies (liver, lung, gastric, breast, colorectal, pancreatic and esophageal cancers), the objectivity and the standardization of TCM syndrome differentiation, the evaluation of TCM syndrome modeling in cancer research, and syndrome differentiation-guided TCM treatment of cancers. A better understanding of TCM syndrome theory, as well as its potential biological basis, may contribute greatly to the clinical TCM diagnosis and the treatment of cancer.

  10. Evaluation of Salivary Leptin Levels in Healthy Subjects and Patients with Advanced Periodontitis

    PubMed Central

    Khorsand, Afshin; Bayani, Mojtaba; Torabi, Sepehr; Kharrazifard, Mohammad Javad; Mohammadnejhad, Fatemeh

    2016-01-01

    Objectives: Leptin is a hormone-like protein produced by the adipose tissue. It plays an important role in protection of host against inflammation and infection. Some studies have reported changes in leptin levels in the gingival crevicular fluid (GCF), saliva and blood serum of patients with periodontal disease compared to healthy individuals. The aim of the present study was to compare the salivary leptin levels in patients with advanced periodontitis and healthy individuals. Materials and Methods: In this case-control study, the salivary samples of healthy individuals and patients with advanced periodontitis with clinical attachment loss >5mm were obtained using a standardized method and the leptin levels were measured in the salivary samples by means of ELISA. The effects of the periodontal status and sex on the salivary leptin levels of both groups were statistically analyzed by two-way ANOVA. Results: The means ± standard deviation (SD) of salivary leptin levels in healthy subjects and patients with advanced periodontitis were 34.27±6.88 and 17.87±5.89 pg/mL, respectively. Statistical analysis showed that the effect of sex on the salivary leptin levels was not significant (P=0.91), while the effect of advanced periodontitis on the salivary leptin levels was significant compared to healthy individuals (P<0.0001). Conclusions: In patients with advanced periodontitis, the salivary leptin levels were significantly lower compared to healthy individuals. Thus, assessment of salivary leptin can be done as a non-invasive and simple method to determine the susceptibility of patients to advanced periodontitis. PMID:27536322

  11. Current advances in targeted therapies for metastatic gastric cancer: improving patient care.

    PubMed

    Aguiar, Pedro Nazareth; Muniz, Thiago Pimentel; Miranda, Raelson Rodrigues; Tadokoro, Hakaru; Forones, Nora Manoukian; Monteiro, Ines-de-Paula; Castelo-Branco, Pedro; Janjigian, Yelena Y; Mello, Ramon Andrade de

    2016-03-01

    In this article, we review the literature on the current advances in targeted therapies for metastatic gastric cancer aimed at improving patient care. We conclude that the key to guiding targeted therapy is individual biomarkers, which are not completely elucidated. HER2 overexpression is the only predictive biomarker currently in use. Furthermore, it is necessary to understand that gastric tumors are heterogeneous; therefore, is impossible to evaluate a novel biological compound without evaluating personal biomarkers. The selection of patients who are able to receive each treatment is paramount for improving advanced gastric cancer survival and reducing unnecessary costs.

  12. The Meaning of Parenteral Hydration to Family Caregivers and Patients with Advanced Cancer Receiving Hospice Care

    PubMed Central

    Cohen, Marlene Z; Torres-Vigil, Isabel; Burbach, Beth E.; de Rosa, Allison; Bruera, Eduardo

    2012-01-01

    Context In the U.S., patients with advanced cancer who are dehydrated or have decreased oral intake virtually always receive parenteral hydration in acute care facilities but rarely in the hospice setting. Objectives To describe the meaning of hydration for terminally ill cancer patients in home hospice care and for their primary caregivers. Methods Phenomenological interviews were conducted at two time points with 85 patients and 84 caregivers enrolled in a randomized, double-blind, controlled trial examining the efficacy of parenteral hydration in patients with advanced cancer receiving hospice care in the southern U.S. Transcripts were analyzed hermeneutically by the interdisciplinary research team until consensus on the theme labels was reached. Results Patients and their family caregivers both saw hydration as meaning hope and comfort. Hope was the view that hydration might prolong a life of dignity and enhance quality of life by reducing symptoms such as fatigue and increasing patients’ alertness. Patients and caregivers also described hydration as improving patients’ comfort by reducing pain, enhancing the effectiveness of pain medication, and nourishing the body, mind and spirit. Conclusion These findings differ from traditional hospice beliefs that dehydration enhances patient comfort given that patients and their families in the study viewed fluids as enhancing comfort, dignity and quality of life. Discussion with patients and families about their preferences for hydration may help tailor care plans to meet specific patient needs. PMID:22459230

  13. Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015

    PubMed Central

    Gillessen, S.; Omlin, A.; Attard, G.; de Bono, J. S.; Efstathiou, E.; Fizazi, K.; Halabi, S.; Nelson, P. S.; Sartor, O.; Smith, M. R.; Soule, H. R.; Akaza, H.; Beer, T. M.; Beltran, H.; Chinnaiyan, A. M.; Daugaard, G.; Davis, I. D.; De Santis, M.; Drake, C. G.; Eeles, R. A.; Fanti, S.; Gleave, M. E.; Heidenreich, A.; Hussain, M.; James, N. D.; Lecouvet, F. E.; Logothetis, C. J.; Mastris, K.; Nilsson, S.; Oh, W. K.; Olmos, D.; Padhani, A. R.; Parker, C.; Rubin, M. A.; Schalken, J. A.; Scher, H. I.; Sella, A.; Shore, N. D.; Small, E. J.; Sternberg, C. N.; Suzuki, H.; Sweeney, C. J.; Tannock, I. F.; Tombal, B.

    2015-01-01

    The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged. PMID:26041764

  14. Optimal pharmacotherapeutic strategies for elderly patients with advanced non-small cell lung cancer.

    PubMed

    Quoix, Elisabeth

    2011-11-01

    Increases in both life expectancy and cancer incidence with age result in a significant rise in lung cancer rates among elderly patients, with a median age at diagnosis of between 63 and 70 years. However, elderly patients are under-represented in clinical trials and generally receive suboptimal treatment, mainly because of fears about increased toxicity of chemotherapy. Indeed, physiological modification of renal and haematopoietic functions with age together with co-morbidity and associated polypharmacy may alter the metabolism of chemotherapy drugs, resulting in greater toxicity. Moreover, performance status (PS), the main prognostic factor in younger patients, does not correlate well with geriatric indexes such as activities of daily living, cognition and physical performance, and comprehensive geriatric assessment is important in elderly patients. Until 2010, based on the small number of clinical trials designed for elderly patients, monotherapy was the recommended treatment for those with advanced non-small cell lung cancer (NSCLC), whereas for fit younger patients, a platinum-based doublet was and continues to be the recommended first-line therapy. However, at the plenary session of the 2010 Annual Meeting of the American Society of Clinical Oncology, results were presented from a randomized controlled trial conducted by the French Intergroup of Thoracic Oncology that demonstrated that in PS 0-2 patients aged≥70 years with advanced NSCLC, monthly carboplatin with weekly paclitaxel resulted in significantly longer survival than single-agent therapy (vinorelbine or gemcitabine). It should be noted that even in a priori unfavourable prognostic subgroups (patients with a PS score of 2, those aged>80 years or those with an activities of daily living scale score of <6), doublet therapy was associated with a survival advantage over monotherapy. Thus, the new paradigm of treatment of elderly patients with advanced NSCLC and a PS score of 0-2 should now be monthly

  15. Considerations and controversies in the management of older patients with advanced cancer.

    PubMed

    Mohile, Supriya Gupta; Klepin, Heidi D; Rao, Arati V

    2012-01-01

    The incidence of cancer increases with age. Oncologists need to be adept at assessing physiologic and functional capacity in older patients in order to provide safe and efficacious cancer treatment. Assessment of underlying health status is especially important for older patients with advanced cancer, for whom the benefits of treatment may be low and the toxicity of treatment high. The comprehensive geriatric assessment (CGA) is the criterion standard for evaluation of the older patient. The combined data from the CGA can be used to stratify patients into categories to better predict risk for chemotherapy toxicity as well as overall outcomes. The CGA can also be used to identify and follow-up on possible functional consequences from treatment. A variety of screening tools might be useful in the oncology practice setting to identify patients who may benefit from further testing and intervention. In this chapter, we discuss how the principles of geriatrics can help improve the clinical care of older adults with advanced cancer. Specifically, we discuss assessing tolerance for treatment, options for chemotherapy scheduling and dosing for older patients with advanced cancer, and management of under-recognized symptoms in older patients with cancer.

  16. STAT3 is a key transcriptional regulator of cancer stem cell marker CD133 in HCC

    PubMed Central

    Ghoshal, Sarani; Fuchs, Bryan C.

    2016-01-01

    Cancer stem cell (CSC) marker CD133 was found to be upregulated in many cancers including hepatocellular carcinoma (HCC). However, the molecular mechanism of CD133 regulation in the liver tumor microenvironment has remained elusive. In this study Won and colleagues report that interleukin-6 (IL-6) mediated signal transducer and activator of transcription factor 3 (STAT3) signaling and hypoxia enhance the expression of CD133 and promote the progression of HCC. PMID:27275460

  17. The role of neoadjuvant chemotherapy in patients with advanced (stage IIIC) epithelial ovarian cancer

    PubMed Central

    Škof, Erik; Merlo, Sebastjan; Pilko, Gasper

    2016-01-01

    Abstract Background Primary treatment of patients with advanced epithelial ovarian cancer consists of chemotherapy either before (neoadjuvant chemotherapy, NACT) or after primary surgery (adjuvant chemotherapy). The goal of primary treatment is no residual disease after surgery (R0 resection) what is associated with an improvement in survival of patients. There is, however, no evidence of survival benefits in patients with R0 resections after prior NACT. Methods We retrospectively reviewed the records of patients who were treated with diagnosis of epithelial ovarian cancer at Institute of Oncology Ljubljana in the years 2005–2007. The differences in the rates of R0 resections, progression free survival (PFS), overall survival (OS) and in five-year and eight-year survival rates between patients treated with NACT and patients who had primary surgery were compared. Results Overall 160 patients had stage IIIC epithelial ovarian cancer. Eighty patients had NACT and eighty patients had primary surgery. Patients in NACT group had higher rates of R0 resection (42% vs. 20%; p = 0.011) than patients after primary surgery. PFS was 14.1 months in NACT group and 17.7 months after primary surgery (p = 0.213). OS was 24.8 months in NACT group and 31.6 months after primary surgery (p = 0.012). In patients with R0 resections five-year and eight-year survival rates were 20.6% and 17.6% in NACT group compared to 62.5% and 62.5% after primary surgery (p < 0.0001), respectively. Conclusions Despite higher rates of R0 resections achieved by NACT, survival of patients treated with NACT was inferior to survival of patients who underwent primary surgery. NACT should only be offered to patients with advanced epithelial cancer who are not candidates for primary surgery. PMID:27679552

  18. The role of neoadjuvant chemotherapy in patients with advanced (stage IIIC) epithelial ovarian cancer

    PubMed Central

    Škof, Erik; Merlo, Sebastjan; Pilko, Gasper

    2016-01-01

    Abstract Background Primary treatment of patients with advanced epithelial ovarian cancer consists of chemotherapy either before (neoadjuvant chemotherapy, NACT) or after primary surgery (adjuvant chemotherapy). The goal of primary treatment is no residual disease after surgery (R0 resection) what is associated with an improvement in survival of patients. There is, however, no evidence of survival benefits in patients with R0 resections after prior NACT. Methods We retrospectively reviewed the records of patients who were treated with diagnosis of epithelial ovarian cancer at Institute of Oncology Ljubljana in the years 2005–2007. The differences in the rates of R0 resections, progression free survival (PFS), overall survival (OS) and in five-year and eight-year survival rates between patients treated with NACT and patients who had primary surgery were compared. Results Overall 160 patients had stage IIIC epithelial ovarian cancer. Eighty patients had NACT and eighty patients had primary surgery. Patients in NACT group had higher rates of R0 resection (42% vs. 20%; p = 0.011) than patients after primary surgery. PFS was 14.1 months in NACT group and 17.7 months after primary surgery (p = 0.213). OS was 24.8 months in NACT group and 31.6 months after primary surgery (p = 0.012). In patients with R0 resections five-year and eight-year survival rates were 20.6% and 17.6% in NACT group compared to 62.5% and 62.5% after primary surgery (p < 0.0001), respectively. Conclusions Despite higher rates of R0 resections achieved by NACT, survival of patients treated with NACT was inferior to survival of patients who underwent primary surgery. NACT should only be offered to patients with advanced epithelial cancer who are not candidates for primary surgery.

  19. 3-Tesla MRI Response to TACE in HCC (Liver Cancer)

    ClinicalTrials.gov

    2016-08-22

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Stage A Adult Primary Liver Cancer (BCLC); Stage B Adult Primary Liver Cancer (BCLC)

  20. Clinically Apparent Internal Mammary Nodal Metastasis in Patients With Advanced Breast Cancer: Incidence and Local Control

    SciTech Connect

    Zhang Yujing; Oh, Julia L.; Whitman, Gary J.

    2010-07-15

    Purpose: To investigate the incidence and local control of internal mammary lymph node metastases (IMN+) in patients with clinical N2 or N3 locally advanced breast cancer. Methods and Materials: We retrospectively reviewed the records of 809 breast cancer patients diagnosed with advanced nodal disease (clinical N2-3) who received radiation treatment at our institution from January 2000 December 2006. Patients were considered IMN+ on the basis of imaging studies. Results: We identified 112 of 809 patients who presented with IMN+ disease (13.8%) detected on ultrasound, computed tomography (CT), positron emission tomography/CT (PET/CT), and/or magnetic resonance imaging (MRI) studies. All 112 patients with IMN+ disease received anthracycline and taxane-based chemotherapy. Neoadjuvant chemotherapy (NCT) resulted in a complete response (CR) on imaging studies of IMN disease in 72.1% of patients. Excluding 16 patients with progressive disease, 96 patients received adjuvant radiation to the breast or the chest wall and the regional lymphatics including the IMN chain with a median dose of 60 Gy if the internal mammary lymph nodes normalized after chemotherapy and 66 Gy if they did not. The median follow-up of surviving patients was 41 months (8-118 months). For the 96 patients able to complete curative therapy, the actuarial 5-year IMN control rate, locoregional control, overall survival, and disease-free survival were 89%, 80%, 76%, and 56%. Conclusion: Over ten percent of patients with advanced nodal disease will have IMN metastases on imaging studies. Multimodality therapy including IMN irradiation achieves excellent rates of control in the IMN region and a DFS of more than 50% after curative treatment.

  1. The Infrared and Near-Infrared Spectra of HCC and DCC Trapped in Solid Neon

    NASA Astrophysics Data System (ADS)

    Forney, D.; Jacox, M. E.; Thompson, W. E.

    1995-03-01

    Spectra have been recorded from 700 to 12 000 cm -1 for HCC and DCC trapped in solid neon. In this region, which includes not only the ground state absorptions but also all of the absorptions of appreciable intensity in the highly perturbed Ã2Π state, all of the matrix shifts are to lower frequencies, and none of them exceeds 30 cm -1. The X˜(0 n0) and X˜(0 n1) progressions of HCC, recently reported in the photoelectron spectrum of HCC -, also appear in the infrared spectrum. The spectra of the singly and doubly carbon-13 substituted species of HCC and of doubly carbon-13 substituted DCC are presented. Except in a few regions of very strong mixing of energy levels of the X˜ and à states, correlations of the HCC and DCC bands with their carbon-13 substitution counterparts are possible, and the resulting isotopic shift data are useful in assigning the vibronic spectra. Assignments are proposed for a considerable number of HCC and DCC bands. These assignments are aided by the carbon-13 shift data, by the results of recent ab initio calculations, and, where they are available, by the upper-state symmetries of bands observed in the gas phase. Absorptions of C 2, C -2, C 4, HC 4, HCCO, and C 2H 3 isolated in a neon matrix are also identified.

  2. [Triple therapy in cirrhotic patients and those with advanced fibrosis: relevant aspects in clinical practice].

    PubMed

    Albillos, Agustín; Luis Calleja, José; Molina, Esther; Planas, Ramon; Romero-Gómez, Manuel; Turnes, Juan; Hernández-Guerra, Manuel

    2014-07-01

    The first-line option in the treatment of patients with advanced fibrosis and cirrhosis due to genotype 1 hepatitis C virus is currently triple therapy with boceprevir/telaprevir and pegylated interferon-ribavirin. However, certain limitations could constitute a barrier to starting treatment or achieving sustained viral response in these patients. These limitations include the patient's or physician's perception of treatment effectiveness in routine clinical practice-which can weight against the decision to start treatment-, the advanced stage of the disease with portal hypertension and comorbidity, treatment interruption due to poor adherence, and adverse effects, mainly anemia. In addition, it is now possible to identify patients who could benefit from a shorter therapeutic regimen with a similar cure rate. This review discusses these issues and their possible effect on the use of triple therapy. PMID:25907434

  3. Advanced practice nursing students in the patient-centered medical home: preparing for a new reality.

    PubMed

    Swartwout, Kathryn; Murphy, Marcia Pencak; Dreher, Melanie C; Behal, Raj; Haines, Alison; Ryan, Mary; Ryan, Norman; Saba, Mary

    2014-01-01

    Driven by reimbursement incentives for increased access, improved quality and reduced cost, the patient-centered medical home model of health care delivery is being adopted in primary care practices across the nation. The transition from traditional primary care models to patient-centered medical homes presents many challenges, including the assembly of a well-prepared, interprofessional provider team to achieve effective, well-coordinated care. In turn, advanced practice nursing education programs are challenged to prepare graduates who are qualified for practice in the new reality of health care reform. This article reviews the patient-centered medical home model and describes how one college of nursing joined 7 primary care physician practices to prepare advanced practice nursing students for the new realities of health care reform while supporting each practice in its transition to the patient-centered medical home. PMID:24720942

  4. Precision oncology for patients with advanced cancer: the challenges of malignant snowflakes

    PubMed Central

    Kurzrock, Razelle; Giles, Francis J

    2015-01-01

    Precision oncology implies customizing treatment to the unique molecular and biologic characteristics of each individual and their cancer. Its implementation is being facilitated by remarkable technological advances in genomic sequencing, as well as the increasing availability of targeted and immunotherapeutic drugs. Yet, next generation sequencing may be a disruptive technology in that its results suggest that classic paradigms for clinical research and practice are a poor fit with the complex reality encountered in metastatic malignancies. Indeed, it is evident that advanced tumors have heterogeneous molecular landscapes that mostly differ between patients. Traditional modes of clinical research/practice are drug centered, with a strategy of finding commonalities between patients so that they can be grouped together and treated similarly. However, if each patient with metastatic cancer has a unique molecular portfolio, a new patient-centered, N-of-one approach that utilizes individually tailored treatment is needed. PMID:26030337

  5. By reducing hexokinase 2, resveratrol induces apoptosis in HCC cells addicted to aerobic glycolysis and inhibits tumor growth in mice

    PubMed Central

    Xia, Yujing; He, Lei; Chen, Kan; Li, Jingjing; Li, Sainan; Liu, Tong; Zheng, Yuanyuan; Wang, Jianrong; Lu, Wenxia; Zhou, Yuqing; Yin, Qin; Abudumijiti, Huerxidan; Chen, Rongxia; Zhang, Rong; Zhou, Li; Zhou, Zheng; Zhu, Rong; Yang, Jing; Wang, Chengfen; Zhang, Huawei; Zhou, Yingqun; Xu, Ling; Guo, Chuanyong

    2015-01-01

    Cancer cells exhibit an altered metabolic phenotype known as the aerobic glycolysis. The expression of HK2 changes the metabolic phenotype of cells to support cancerous growth. In the present study, we investigated the inhibitory effect of resveratrol on HK2 expression and hepatocellular carcinoma (HCC) cell glycolysis. Aerobic glycolysis was observed in four HCC cell lines compared to the normal hepatic cells. Resveratrol sensitized aerobic glycolytic HCC cells to apoptosis, and this effect was attenuated by glycolytic inhibitors. The induction of mitochondrial apoptosis was associated with the decrease of HK2 expression by resveratrol in HCC cells. In addition, resveratrol enhanced sorafenib induced cell growth inhibition in aerobic glycolytic HCC cells. Combination treatment with both reagents inhibited the growth and promoted apoptosis of HCC-bearing mice. The reduction of HK2 by resveratrol provides a new dimension to clinical HCC therapies aimed at preventing disease progression. PMID:25938543

  6. The evolving role of health educators in advancing patient safety: forging partnerships and leading change.

    PubMed

    Mercurio, Annette

    2007-04-01

    At least 1.5 million preventable injuries because of adverse drug events occur in the United States each year, according to an Institute of Medicine report. IOM and other organizations at the forefront of health care improvement emphasize that stronger partnerships between patients, their families, and health care providers are necessary to make health care safer. Health educators possess a skill set and an ethical framework that effectively equip them to advance patient and family-centered care and contribute in other significant ways to a safer health care system. Health educators in clinical settings are playing varied and significant roles in advancing patient safety. They are removing barriers to clear communication and forging partnerships between patients, their families, and staff. Health educators are leading patient safety culture change within their institutions and contributing to the shift from provider-centric to patient-centric systems. To expand their impact in improving patient safety, health educators in clinical settings are participating in public awareness campaigns. In seeking to enhance patient safety, health educators face a number of challenges. To successfully manage those, health educators must expand their knowledge, broaden connections, and engage patients and families in meaningful ways.

  7. Treatment approaches in patients with advanced non-small cell lung cancer and poor performance status.

    PubMed

    Govindan, Ramaswamy; Garfield, David H

    2004-12-01

    It is estimated that 30% to 40% of patients with advanced non-small cell lung cancer (NSCLC) have a poor performance status (PS)-defined as a score of 2 or higher on the Eastern Cooperative Oncology Group scale-because of their disease burden, comorbidities, or both. Survival is shorter in these patients than in those with a better PS, and they do not tolerate chemotherapy as well. There is now evidence that PS2 patients with advanced NSCLC can benefit from single-agent chemotherapy with drugs such as vinorelbine, gemcitabine, paclitaxel, pemetrexed, and docetaxel and that combination chemotherapy may have additional advantages. The optimal treatment for PS2 patients with NSCLC, however, has yet to be determined. The case histories in this article demonstrate that PS2 patients are a heterogeneous group and that selecting the chemotherapy for each patient must take into consideration comorbidities and disease-related symptoms, as well as the potential toxicity of treatment. Large prospective clinical trials are needed to determine whether, and in which patients, combination chemotherapy or novel agents, such as the epidermal growth factor receptor inhibitors or paclitaxel poliglumex, have advantages. Three large phase III trials-Selective Targeting for Efficacy in Lung Cancer, Lower Adverse Reactions trials (STELLAR)-are now being conducted in PS2 patients with NSCLC. It is hoped that their findings will aid in determining the best treatment options for these patients.

  8. Advance directives and living wills: the role of patient's autonomy in the Brazilian experience.

    PubMed

    Dantas, Eduardo

    2013-12-01

    This paper aims to discuss the development of the notion that the patient has the right to refuse treatment, and how the Brazilian legal system is dealing with bioethical dilemmas, such as the possibility of exercising autonomy through advance directives. The paper discusses the lack of legislation to regulate important issues in the end of life healthcare, and what ethical guidelines exist, providing physicians with ethical and legal parameters to deal with the patient's will.

  9. Left atrial appendage closure for thromboembolism prevention in patients with atrial fibrillation: advances and perspectives

    PubMed Central

    Kong, Bin; Liu, Yu; Huang, He; Jiang, Hong

    2015-01-01

    Atrial fibrillation (AF) is a frequent cause of stroke. More than 90% of thrombi were found in the left atrial appendage (LAA) in non-valvular AF. Transcatheter LAA closure has been developed as a novel approach to reduce the risk of stroke in patients with AF over the last decade. In this article, we review the recent advances and propose the possible challenges regarding the LAA closure for thromboembolism prevention in patients with AF. PMID:25713737

  10. A prospective evaluation of an interdisciplinary nutrition–rehabilitation program for patients with advanced cancer

    PubMed Central

    Gagnon, B.; Murphy, J.; Eades, M.; Lemoignan, J.; Jelowicki, M.; Carney, S.; Amdouni, S.; Di Dio, P.; Chasen, M.; MacDonald, N.

    2013-01-01

    Background Cancer can affect many dimensions of a patient’s life, and in turn, it should be targeted using a multimodal approach. We tested the extent to which an interdisciplinary nutrition–rehabilitation program can improve the well-being of patients with advanced cancer. Methods Between January 10, 2007, and September 29, 2010, 188 patients with advanced cancer enrolled in the 10–12-week program. Body weight, physical function, symptom severity, fatigue dimensions, distress level, coping ability, and overall quality of life were assessed at the start and end of the program. Results Of the enrolled patients, 70% completed the program. Patients experienced strong improvements in the physical and activity dimensions of fatigue (effect sizes: 0.8–1.1). They also experienced moderate reductions in the severity of weakness, depression, nervousness, shortness of breath, and distress (effect sizes: 0.5–0.7), and moderate improvements in Six Minute Walk Test distance, maximal gait speed, coping ability, and quality of life (effect sizes: 0.5–0.7) Furthermore, 77% of patients either maintained or increased their body weight. Conclusions Interdisciplinary nutrition–rehabilitation can be advantageous for patients with advanced cancer and should be considered an integrated part of standard palliative care. PMID:24311946

  11. Urate calculi complicating orchidectomy in a patient with advanced prostatic cancer. Case report.

    PubMed

    Roosen, J U; Rungby, J A; Hvidt, V

    1991-01-01

    A patient passed 11 urate calculi after palliative orchidectomy for advanced prostatic cancer, and there was a simultaneous rise in urinary urate excretion. We believe that this rise could be the result of increased purine metabolism from lysis of tumour cells. To our knowledge this has not previously been reported.

  12. Technical advances in external radiotherapy for hepatocellular carcinoma

    PubMed Central

    Park, Shin-Hyung; Kim, Jae-Chul; Kang, Min Kyu

    2016-01-01

    Radiotherapy techniques have substantially improved in the last two decades. After the introduction of 3-dimensional conformal radiotherapy, radiotherapy has been increasingly used for the treatment of hepatocellular carcinoma (HCC). Currently, more advanced techniques, including intensity-modulated radiotherapy (IMRT), stereotactic ablative body radiotherapy (SABR), and charged particle therapy, are used for the treatment of HCC. IMRT can escalate the tumor dose while sparing the normal tissue even though the tumor is large or located near critical organs. SABR can deliver a very high radiation dose to small HCCs in a few fractions, leading to high local control rates of 84%-100%. Various advanced imaging modalities are used for radiotherapy planning and delivery to improve the precision of radiotherapy. These advanced techniques enable the delivery of high dose radiotherapy for early to advanced HCCs without increasing the radiation-induced toxicities. However, as there have been no effective tools for the prediction of the response to radiotherapy or recurrences within or outside the radiation field, future studies should focus on selecting the patients who will benefit from radiotherapy. PMID:27621577

  13. Technical advances in external radiotherapy for hepatocellular carcinoma

    PubMed Central

    Park, Shin-Hyung; Kim, Jae-Chul; Kang, Min Kyu

    2016-01-01

    Radiotherapy techniques have substantially improved in the last two decades. After the introduction of 3-dimensional conformal radiotherapy, radiotherapy has been increasingly used for the treatment of hepatocellular carcinoma (HCC). Currently, more advanced techniques, including intensity-modulated radiotherapy (IMRT), stereotactic ablative body radiotherapy (SABR), and charged particle therapy, are used for the treatment of HCC. IMRT can escalate the tumor dose while sparing the normal tissue even though the tumor is large or located near critical organs. SABR can deliver a very high radiation dose to small HCCs in a few fractions, leading to high local control rates of 84%-100%. Various advanced imaging modalities are used for radiotherapy planning and delivery to improve the precision of radiotherapy. These advanced techniques enable the delivery of high dose radiotherapy for early to advanced HCCs without increasing the radiation-induced toxicities. However, as there have been no effective tools for the prediction of the response to radiotherapy or recurrences within or outside the radiation field, future studies should focus on selecting the patients who will benefit from radiotherapy.

  14. Technical advances in external radiotherapy for hepatocellular carcinoma.

    PubMed

    Park, Shin-Hyung; Kim, Jae-Chul; Kang, Min Kyu

    2016-08-28

    Radiotherapy techniques have substantially improved in the last two decades. After the introduction of 3-dimensional conformal radiotherapy, radiotherapy has been increasingly used for the treatment of hepatocellular carcinoma (HCC). Currently, more advanced techniques, including intensity-modulated radiotherapy (IMRT), stereotactic ablative body radiotherapy (SABR), and charged particle therapy, are used for the treatment of HCC. IMRT can escalate the tumor dose while sparing the normal tissue even though the tumor is large or located near critical organs. SABR can deliver a very high radiation dose to small HCCs in a few fractions, leading to high local control rates of 84%-100%. Various advanced imaging modalities are used for radiotherapy planning and delivery to improve the precision of radiotherapy. These advanced techniques enable the delivery of high dose radiotherapy for early to advanced HCCs without increasing the radiation-induced toxicities. However, as there have been no effective tools for the prediction of the response to radiotherapy or recurrences within or outside the radiation field, future studies should focus on selecting the patients who will benefit from radiotherapy. PMID:27621577

  15. Surgery is an essential component of multimodality therapy for patients with locally advanced esophageal adenocarcinoma

    PubMed Central

    Murphy, Caitlin C.; Correa, Arlene M.; Ajani, Jaffer A.; Komaki, Ritsuko U.; Welsh, James W.; Swisher, Stephen G.; Hofstetter, Wayne L.

    2016-01-01

    Background Experience with neoadjuvant chemoradiation (CXRT) has raised questions regarding the additional benefit of surgery after locally advanced esophageal adenocarcinoma patients achieve a clinical response to CXRT. We sought to quantify the value of surgery by comparing the overall (OS) and disease-free survival (DFS) of trimodality eligible patients treated with definitive CXRT versus CXRT followed by esophagectomy. Methods We identified 143 clinical stage III esophageal adenocarcinoma patients that were eligible for trimodality therapy. All patients successfully completed neoadjuvant CXRT and were considered appropriate candidates for resection. Patients that were medically inoperable were excluded. Cox regression models were used to identify significant predictors of survival. Results Among the 143 patients eligible for surgery after completing CXRT, 114 underwent resection and 29 did not. Poorly differentiated tumors (HR=2.041, 95% CI 1.235–3.373) and surgical resection (HR=0.504, 95% CI 0.283–0.899) were the only independent predictors of OS. Patients treated with surgery had a 50% and 54% risk reduction in overall and cancer-specific mortality, respectively. Median OS (41.2 months vs. 20.3 months, p=0.012) and DFS (21.5 months vs. 11.4 months, p=0.007) were significantly improved with the addition of surgery compared to definitive CXRT. Conclusions Surgery provides a significant survival benefit to trimodality-eligible esophageal adenocarcinoma patients with locally advanced disease. PMID:23715646

  16. Case study of a chaplain's spiritual care for a patient with advanced metastatic breast cancer.

    PubMed

    Cooper, Rhonda S

    2011-01-01

    The case study seeks to describe an oncology chaplain's pastoral relationship with a 64-year-old woman with advanced metastatic breast cancer. The patient's distress was complicated by a history of anxiety and other chronic medical conditions. Approximately 16 pastoral encounters occurred during the last year of the patient's life. The patient, chaplain, and the pastoral conversations are presented as well as a retrospective assessment of them. The chaplain's interventions were appropriate for the patient's spiritual needs, particularly in regard to her fear of death, loneliness, grief that her life was "too short" and estrangement from her inherited faith tradition, with observable benefits for the patient. The oncology chaplain has a distinctive role in the healthcare team as one who can meet the patient at the point of their spiritual need, provide appropriate interventions and, thereby, ameliorate the distress, particularly in regard to death anxiety, peace of mind, and issues of meaning.

  17. The patient perspective: Quality of life in advanced heart failure with frequent hospitalisations.

    PubMed

    Nieminen, Markku S; Dickstein, Kenneth; Fonseca, Cândida; Serrano, Jose Magaña; Parissis, John; Fedele, Francesco; Wikström, Gerhard; Agostoni, Piergiuseppe; Atar, Shaul; Baholli, Loant; Brito, Dulce; Colet, Josep Comín; Édes, István; Gómez Mesa, Juan E; Gorjup, Vojka; Garza, Eduardo Herrera; González Juanatey, José R; Karanovic, Nenad; Karavidas, Apostolos; Katsytadze, Igor; Kivikko, Matti; Matskeplishvili, Simon; Merkely, Béla; Morandi, Fabrizio; Novoa, Angel; Oliva, Fabrizio; Ostadal, Petr; Pereira-Barretto, Antonio; Pollesello, Piero; Rudiger, Alain; Schwinger, Robert H G; Wieser, Manfred; Yavelov, Igor; Zymliński, Robert

    2015-07-15

    End of life is an unfortunate but inevitable phase of the heart failure patients' journey. It is often preceded by a stage in the progression of heart failure defined as advanced heart failure, and characterised by poor quality of life and frequent hospitalisations. In clinical practice, the efficacy of treatments for advanced heart failure is often assessed by parameters such as clinical status, haemodynamics, neurohormonal status, and echo/MRI indices. From the patients' perspective, however, quality-of-life-related parameters, such as functional capacity, exercise performance, psychological status, and frequency of re-hospitalisations, are more significant. The effects of therapies and interventions on these parameters are, however, underrepresented in clinical trials targeted to assess advanced heart failure treatment efficacy, and data are overall scarce. This is possibly due to a non-universal definition of the quality-of-life-related endpoints, and to the difficult standardisation of the data collection. These uncertainties also lead to difficulties in handling trade-off decisions between quality of life and survival by patients, families and healthcare providers. A panel of 34 experts in the field of cardiology and intensive cardiac care from 21 countries around the world convened for reviewing the existing data on quality-of-life in patients with advanced heart failure, discussing and reaching a consensus on the validity and significance of quality-of-life assessment methods. Gaps in routine care and research, which should be addressed, were identified. Finally, published data on the effects of current i.v. vasoactive therapies such as inotropes, inodilators, and vasodilators on quality-of-life in advanced heart failure patients were analysed.

  18. Limitation to Advanced Life Support in patients admitted to intensive care unit with integrated palliative care

    PubMed Central

    Mazutti, Sandra Regina Gonzaga; Nascimento, Andréia de Fátima; Fumis, Renata Rego Lins

    2016-01-01

    Objective To estimate the incidence of limitations to Advanced Life Support in critically ill patients admitted to an intensive care unit with integrated palliative care. Methods This retrospective cohort study included patients in the palliative care program of the intensive care unit of Hospital Paulistano over 18 years of age from May 1, 2011, to January 31, 2014. The limitations to Advanced Life Support that were analyzed included do-not-resuscitate orders, mechanical ventilation, dialysis and vasoactive drugs. Central tendency measures were calculated for quantitative variables. The chi-squared test was used to compare the characteristics of patients with or without limits to Advanced Life Support, and the Wilcoxon test was used to compare length of stay after Advanced Life Support. Confidence intervals reflecting p ≤ 0.05 were considered for statistical significance. Results A total of 3,487 patients were admitted to the intensive care unit, of whom 342 were included in the palliative care program. It was observed that after entering the palliative care program, it took a median of 2 (1 - 4) days for death to occur in the intensive care unit and 4 (2 - 11) days for hospital death to occur. Many of the limitations to Advanced Life Support (42.7%) took place on the first day of hospitalization. Cardiopulmonary resuscitation (96.8%) and ventilatory support (73.6%) were the most adopted limitations. Conclusion The contribution of palliative care integrated into the intensive care unit was important for the practice of orthothanasia, i.e., the non-extension of the life of a critically ill patient by artificial means. PMID:27626949

  19. The unified Huntington's Disease Rating Scale for advanced patients: validation and follow-up study.

    PubMed

    Youssov, Katia; Dolbeau, Guillaume; Maison, Patrick; Boissé, Marie-Françoise; Cleret de Langavant, Laurent; Roos, Raymund A C; Bachoud-Lévi, Anne-Catherine

    2013-12-01

    The Unified Huntington's Disease Rating Scale (UHDRS) adequately measures decline in patients at early and moderate stages of Huntington's disease (HD). In patients with advanced HD, floor effects hamper the evaluation, thus calling for an adjusted scale. We designed the UHDRS-For Advanced Patients (UHDRS-FAP) to improve longitudinal assessment of patients at the advanced disease stage. Sixty-nine patients with a Total Functional Capacity score ≤ 5 were recruited in France and the Netherlands. Among them, 45 patients were followed longitudinally (mean ± standard deviation, 1.6 ± 1.2 years) with the UHDRS-FAP; 30 patients also were assessed with the UHDRS. In cross-sectional analyses, the psychometric properties and inter-rater reliability of the scale were evaluated. Longitudinal analyses were used to evaluate the sensitivity to decline of the UHDRS-FAP compared with the UHDRS. Internal consistency was higher for motor (0.84) and cognitive (0.91) scores than for somatic (0.70) and behavioral (0.49) scores. Inter-rater reliability was ≥ 0.88 for all scores. The somatic score, which was specific to the UHDRS-FAP, declined over time along with motor and cognitive performance on both scales. Although performance with the two scales was correlated, the UHDRS-FAP appeared to be more sensitive to change and was the only scale that detected decline in patients with a Total Functional Capacity score ≤ 1. Neither scale detected a significant decline in behavioral scores. The results indicate that the UHDRS-FAP is reliable and more sensitive to change than the original UHDRS for cognitive and motor domains. It offers items that are relevant for daily care. Behavioral scores tended to decline, but this may reflect the decline in patients' communicative abilities.

  20. Evaluation of overall tumor cellularity after neoadjuvant chemotherapy in patient with locally advanced hypopharyngeal cancer.

    PubMed

    Chitose, Shun-ichi; Chijiwa, Hideki; Maeda, Akiteru; Umeno, Hirohito; Nakashima, Tadashi; Kiyokawa, Kensuke; Hayabuchi, Naofumi; Fujita, Hiromasa

    2012-11-01

    The aim of this study is to clarify the prognostic value of the pathological overall tumor cellularity after neoadjuvant chemotherapy for locally advanced hypopharyngeal cancer. In consecutive series of 45 operable patients with locally advanced hypopharyngeal cancer, neoadjuvant chemotherapy by cisplatin and 5-fluorouracil was administered. Pathological image analysis was performed in 30 patients using the large cross-section specimen after total resection to evaluate the overall tumor cellularity. The chemotherapeutic responses were classified according to the pathological grading scale by dividing into four categories; more than 70% overall tumor cellularity in Grade 1, between an estimated 10 and 70% in Grade 2, less than 10% in Grade 3, and no identifiable malignant tumor cells in Grade 4. The pathological grades were taken into account for analysis of the survival. In 30 available patients, 40% had Grade 1 pathological response, 30% had Grade 2, and 30% had Grade 3. There was no Grade 4 patient. The overall 5-year survival rate for these 30 patients was 53.33%. The survival rate (61.66%) for patients with Grade 2 and 3 responses was significantly higher than that (27.78%) for patients with Grade 1 response (p = 0.009). Cox regression analysis revealed that the increasing pathological grade was an independent predictor of a better survival in patients undergoing neoadjuvant chemotherapy. We have shown that the prognosis of patients with locally advanced hypopharyngeal cancer, who had been treated by neoadjuvant chemotherapy followed by total resection, can be predicted by evaluation of pathological overall tumor cellularity from the large section specimen.

  1. Prostate cancer patients may have an increased risk of coexisting advanced colorectal neoplasms

    PubMed Central

    Ko, Sun-Hye; Baeg, Myong Ki; Bae, Woong Jin; Kim, Pumsoo; Choi, Myung-Gyu

    2016-01-01

    Background/aims Patients being treated for prostate cancer (PCa) have an increased risk of developing colorectal cancer. However, whether PCa patients are inherently at a higher risk of colorectal neoplasms (CRNs) is unknown. We aimed to investigate the risk of CRNs in PCa patients. Materials and methods Patients who had been diagnosed with PCa at a tertiary medical center and had colonoscopy within 1 year of the PCa diagnosis were investigated. Patients were propensity-matched 1:2 by age and body mass index to asymptomatic control subjects who had undergone colonoscopy for routine health screening. CRN was defined as histological confirmation of an adenoma or adenocarcinoma component. Advanced CRN was defined as any of the following: 1) histological findings of high-grade dysplasia, 2) inclusion of villous features, 3) tumor ≥1 cm in size, or 4) presence of an adenocarcinoma. Risk factors for CRN and advanced CRN were evaluated by univariate and multivariate analysis. Results A total of 191 patients diagnosed with PCa had colonoscopies within 1 year of PCa diagnosis. Of these, 23 patients with a history of previous malignancy and seven with incomplete colonoscopies were excluded, leaving 161 patients in the PCa group. Although presence of PCa was not a significant risk factor for CRN by multivariate analysis, PCa was a significant risk factor for advanced CRN (odds ratio [OR] 3.300; 95% confidence interval [CI] 1.766–6.167; P<0.001). Other significant risk factors for advanced CRN were age (OR 1.050; 95% CI 1.003–1.009; P=0.036) and body mass index (OR 1.205; 95% CI 1.067–1.361; P=0.003), whereas aspirin use (OR 0.414; 95% CI 0.173–0.990; P=0.047) was a preventive factor. Conclusion The risk of advanced CRN may be significantly increased in patients with PCa. Patients with PCa should have a colonoscopy at the time of PCa diagnosis.

  2. Prostate cancer patients may have an increased risk of coexisting advanced colorectal neoplasms

    PubMed Central

    Ko, Sun-Hye; Baeg, Myong Ki; Bae, Woong Jin; Kim, Pumsoo; Choi, Myung-Gyu

    2016-01-01

    Background/aims Patients being treated for prostate cancer (PCa) have an increased risk of developing colorectal cancer. However, whether PCa patients are inherently at a higher risk of colorectal neoplasms (CRNs) is unknown. We aimed to investigate the risk of CRNs in PCa patients. Materials and methods Patients who had been diagnosed with PCa at a tertiary medical center and had colonoscopy within 1 year of the PCa diagnosis were investigated. Patients were propensity-matched 1:2 by age and body mass index to asymptomatic control subjects who had undergone colonoscopy for routine health screening. CRN was defined as histological confirmation of an adenoma or adenocarcinoma component. Advanced CRN was defined as any of the following: 1) histological findings of high-grade dysplasia, 2) inclusion of villous features, 3) tumor ≥1 cm in size, or 4) presence of an adenocarcinoma. Risk factors for CRN and advanced CRN were evaluated by univariate and multivariate analysis. Results A total of 191 patients diagnosed with PCa had colonoscopies within 1 year of PCa diagnosis. Of these, 23 patients with a history of previous malignancy and seven with incomplete colonoscopies were excluded, leaving 161 patients in the PCa group. Although presence of PCa was not a significant risk factor for CRN by multivariate analysis, PCa was a significant risk factor for advanced CRN (odds ratio [OR] 3.300; 95% confidence interval [CI] 1.766–6.167; P<0.001). Other significant risk factors for advanced CRN were age (OR 1.050; 95% CI 1.003–1.009; P=0.036) and body mass index (OR 1.205; 95% CI 1.067–1.361; P=0.003), whereas aspirin use (OR 0.414; 95% CI 0.173–0.990; P=0.047) was a preventive factor. Conclusion The risk of advanced CRN may be significantly increased in patients with PCa. Patients with PCa should have a colonoscopy at the time of PCa diagnosis. PMID:27672332

  3. [Immunomodulator Intensification of Etioropic Therapy in Patients with Advanced Pulmonary Tuberculosis].

    PubMed

    Kolomiets, V M; Abramov, A V; Rachina, N V; Rubleva, N V

    2015-01-01

    The study was aimed at possible increase of the therapy efficacy in patients with advanced tuberculosis by including immunomodulators to the treatment schemes. The data concerning 6034 patients with advanced tuberculosis, mainly fibrocavernous tuberculosis of the lungs, were analysed. Four groups of the patients were randomized. In group 1 the management of the patients included etiotropic therapy and some treatment and rehabilitation measures with the use of Cycloferon. The group 2 patients in addition to the etiotropic therapy and some treatment and rehabilitation measures were given Omega-3. In group 3 the management included the etiotropic therapy and some treatment and rehabilitation measures. In group 4 the etioropic therapy was used alone. The analysis showed that 3419 patients had primary pulmonary tuberculosis, 340 patients had relapsing tuberculosis and 2275 patients had long-term process. The etiotropic therapy efficacy was estimated after an intensive phase of not more than 3 months. In the cases with Mycobacterium tuberculosis drug resistance and some other unfavourable factors it was estimated after a 5-month intensive phase. The results confirmed that inclusion of immunomodulators to the treatment schemes allowed to increase the therapy efficacy and the patients' adherence to the treatment, as well as to shorten the period of the bacteria carriage. Thus, the use of Cycloferon in the schemes of the treatment of the patients with fibrocavernous pulmonary tuberculosis allowed to shorten the period of the pathogen carriage (as well as the drug resistant forms) in 94.1 ± 3.33% of the patients in spite of concomitant diseases. The effect of Cycloferon in such cases was likely due to both its direct immunoprotective action and the improvement of the general state of the patients and their higher adherence to the treatment.

  4. Predictors of psychological distress in advanced cancer patients under palliative treatments.

    PubMed

    Diaz-Frutos, D; Baca-Garcia, E; García-Foncillas, J; López-Castroman, J

    2016-07-01

    This work aims to investigate the factors associated with psychological distress in advanced cancer patients under palliative treatment. We comprehensively assessed the demographic, psychosocial and health factors of 158 advanced cancer patients. Patients with high and low distress, according to the Hospital Anxiety and Depression Scale, were compared. A regression analysis was built to identify the best predictors of distress. Patients with high psychological distress (81%) were more likely to have lung cancer, suicidal ideation, hopelessness, low quality of life and poor body image than those without. In the multivariate model, only poor emotional functioning (OR = .89; 95% CI = .83-.95; p ≤ .001), hopelessness (OR = .86; 95% CI = .78-.94; p ≤ .001) and body image distortions (OR = .77; 95% CI = .68-.85; p = .005) were retained. High levels of hopelessness, impaired emotional functioning and body image distortions are the main factors associated with psychological distress in patients with advanced cancer. Potential interventions to modify these factors in palliative units are discussed. PMID:27271213

  5. Tetanus neurotoxin HCC protein commits T cells to IFN-γ producing cells.

    PubMed

    Torabi Goudarzi, S; Hajivalili, M; Hosseini, M; Ghafari Khamene, M; Yazdani, Y; Sadreddini, S; Miahipour, A; Younesi, V; Yousefi, M

    2016-01-01

    A protective response against tetanus toxin and toxoid demands efficient specific T cell and B cell responses. Tetanus neurotoxin (TeNT), a 150 kDa polypeptide, is the main cause of tetanus disease. TeNT consists of two structurally distinct chains, a 50 kDa N-terminal light (L) and a 100 kDa C-terminal heavy (H) chain. C-terminal heavy (H) chain (fragment C) has two sub-domains named as proximal HCN and carboxy sub-domain or HCC. Beside neural binding property, HCC has been recently found as an immunodominant module of TeNT. In the present study, we investigated the effects of recombinant HCC (rHCC) on the expression of lineage specific transcription factors and secretion of a panel of functional cytokines including IFN-γ, IL-4, and IL-17 from purified human T cells. Our results revealed that T-bet transcript level, as TH1 specific transcription factor, was significantly increased in the cells treated with 10 and 20 µg/ml of rHCC following 48 h treatment(p<0.05). Treated purified human T cells with rHCC showed significant increase in IFN-γ mRNA level and cytokine secretion, but not IL-4 and IL-17, following 48 h treatment. In conclusion, our results showed that treatment of T cells with r HCC resulted in development of Th1 lineage phenotype, which might lead to a specific and protective antibody mediated response against tetanus toxin. PMID:27064869

  6. The Caring Connections Project: Providing palliative care to Medicaid patients with advanced cancer.

    PubMed

    Pfeifer, Mark P; Ritchie, Christine; Scharfenberger, Jennifer; Keeney, Cynthia; Hermann, Carla; Berwick, Marilyn; Head, Barbara

    2006-01-01

    Palliative care, with its focus on symptom management, patient-centered goals, preparation for life's end, and preservation of quality of life in the face of advancing illness, is a rapidly advancing component of mainstream American medicine. Yet, access to palliative care is often lacking in the community setting and may be further hindered by the presence of healthcare disparities that impact the poor. This article presents a unique approach to assuring the availability of palliative care to Medicaid patients receiving case management services. This descriptive article describes the evolution of a palliative care management pilot program, the Caring Connections Program, beginning with the initial planning and progressing through implementation and provision of services to 56 persons. "Lessons learned" are shared to enable other providers to develop similar programs with success. Patient profiles and intervention strategies are offered to illustrate the work accomplished.

  7. Tube feeding in patients with advanced dementia: a review of the evidence.

    PubMed

    Finucane, T E; Christmas, C; Travis, K

    1999-10-13

    Patients with advanced dementia frequently develop eating difficulties and weight loss. Enteral feeding tubes are often used in this situation, yet benefits and risks of this therapy are unclear. We searched MEDLINE, 1966 through March 1999, to identify data about whether tube feeding in patients with advanced dementia can prevent aspiration pneumonia, prolong survival, reduce the risk of pressure sores or infections, improve function, or provide palliation. We found no published randomized trials that compare tube feeding with oral feeding. We found no data to suggest that tube feeding improves any of these clinically important outcomes and some data to suggest that it does not. Further, risks are substantial. The widespread practice of tube feeding should be carefully reconsidered, and we believe that for severely demented patients the practice should be discouraged on clinical grounds.

  8. Surgery for Intermediate and Advanced Hepatocellular Carcinoma: A Consensus Report from the 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014)

    PubMed Central

    Ho, Ming-Chih; Hasegawa, Kiyoshi; Chen, Xiao-Ping; Nagano, Hiroaki; Lee, Young-Joo; Chau, Gar-Yang; Zhou, Jian; Wang, Chih-Chi; Choi, Young Rok; Poon, Ronnie Tung-Ping; Kokudo, Norihiro

    2016-01-01

    Background The Barcelona Clinic Liver Cancer (BCLC) staging and treatment strategy does not recommended surgery for treating BCLC stage B and C hepatocellular carcinoma (HCC). However, numerous Asia-Pacific institutes still perform surgery for this patient group. This consensus report from the 5th Asia-Pacific Primary Liver Cancer Expert Meeting aimed to share opinions and experiences pertaining to liver resection for intermediate and advanced HCCs and to provide evidence to issue recommendations for surgery in this patient group. Summary Thirteen experts from five Asia-Pacific regions were invited to the meeting; 10 of them (Japan: 2, Taiwan: 3, South Korea: 2, Hong Kong: 1, and China: 2) voted for the final consensus. The discussion focused on evaluating the preoperative liver functional reserve and surgery for large tumors, multiple tumors, HCCs with vascular invasion, and HCCs with distant metastasis. The feasibility of future prospective randomized trials comparing surgery with transarterial chemoembolization for intermediate HCC and with sorafenib for advanced HCC was also discussed. The Child-Pugh score (9/10 experts) and indocyanine green retention rate at 15 min (8/10) were the most widely accepted methods for evaluating the preoperative liver functional reserve. All (10/10) experts agreed that portal hypertension, tumor size >5 cm, portal venous invasion, hepatic venous invasion, and extrahepatic metastasis are not absolute contraindications for the surgical resection of HCC. Furthermore, 9 of the 10 experts agreed that tumor resection may be performed for patients with >3 tumors. The limitations of surgery are associated with a poor liver functional reserve, incomplete tumor resection, and a high probability of recurrence. Key Messages Surgery provides significant survival benefits for Asian-Pacific patients with intermediate and advanced HCCs, particularly when the liver functional reserve is favorable. However, prospective randomized controlled trials

  9. Clinical and radiographic evaluation of maxillary central incisors exposure in patients undergoing maxillary advancement

    PubMed Central

    Trento, Guilherme dos Santos; Bernabé, Felipe Bueno Rosettti; da Costa, Delson João; Rebellato, Nelson Luis Barbosa; Klüppel, Leandro Eduardo; Scariot, Rafaela

    2015-01-01

    Abstract Introduction: Patients with dentofacial deformities may undergo orthodontic or orthodontic-surgical treatment. Both modalities can affect esthetics. Objective: This study aims to evaluate clinical and radiographic changes in exposure of maxillary central incisors occurring after orthognathic surgery for maxillary advancement. Methods: A total of 17 patients who underwent orthognathic surgery for maxillary advancement between September, 2010 and July, 2011 were selected. Exposure of maxillary central incisors was evaluated clinically and by lateral cephalograms. Measurements were taken one week before and three months after surgery. Data were paired in terms of sex, age, nasolabial angle, height and thickness of the upper lip, the amount of maxillary advancement, clinical exposure and inclination of maxillary central incisor by statistical tests (CI 95%). Results: After maxillary advancement, incisor clinical exposure had increased even with relaxed lips and under forced smile. Moreover, there was a mean increase of 23.33% revealed by lateral cephalograms. There was an inverse correlation between upper lip thickness and incisors postsurgical exposure revealed by radiographic images (p = 0.002). Conclusions: Significant changes in the exposure of maxillary central incisors occur after maxillary advancement, under the influence of some factors, especially lip thickness. PMID:26691970

  10. Some aspects of allogeneic stem cell transplantation in patients with myelodysplastic syndrome: advances and controversy

    PubMed Central

    Blau, Olga; Blau, Igor Wolfgang

    2014-01-01

    Myelodysplastic syndrome (MDS) is a heterogeneous group of myeloid disorders. MDS remains a disease of elderly patients; moreover, the incidence of high risk MDS is proportionally greater in elderly patients, with increased frequency of secondary acute myeloid leukemia, as well as adverse cytogenetic abnormalities. Allogeneic stem cell transplantation is a therapeutic approach with known curative potential for patients with MDS that allows the achievement of long-term disease control. Numerous controversies still exist regarding transplantation in MDS: timing of transplantation, disease status at transplantation and comorbidity, conditioning intensity, pretransplant therapy, and stem cell source. Various transplant modalities of different intensities and alternative donor sources are now in use. Current advances in transplant technology are allowing the consideration of older patients. This should result in a greater number of older patients benefiting from this potentially curative treatment modality. Despite advances in transplantation technology, there is still considerable morbidity and mortality associated with this approach. Nevertheless, with the introduction of reduced-intensity conditioning and thereby reduced early mortality, transplant numbers in MDS patients have significantly increased. Moreover, recent new developments with innovative drugs, including hypomethylating agents, have extended the therapeutic alternatives for MDS patients. Hypomethylating agents allow the delay of allogeneic stem cell transplantation by serving as an effective and well-tolerated means to reduce disease burden. PMID:25506229

  11. Bilateral subthalamic stimulation monotherapy in advanced Parkinson's disease: long-term follow-up of patients.

    PubMed

    Valldeoriola, Francesc; Pilleri, Manuela; Tolosa, Eduardo; Molinuevo, José L; Rumià, Jordi; Ferrer, Enric

    2002-01-01

    Bilateral subthalamic nucleus stimulation (STN-DBS) is used to improve parkinsonian symptoms and attenuate levodopa-induced motor complications. In some patients, such clinical improvement allows antiparkinsonian medication (ApMed) withdrawal. We show the clinical outcome at the long-term follow-up of patients with advanced Parkinson's disease (PD) in which STN-DBS was used in monotherapy, and compare the clinical results of patients without medication with those obtained in parkinsonian patients in which ApMed were reduced but could not be totally displaced after surgery. We analyzed clinical outcome of ten patients with PD in which all ApMed was withdrawn after bilateral subthalamic stimulation and 16 parkinsonian patients still taking antiparkinsonian medication after surgery. After 1.5 years, STN-DBS monotherapy produced UPDRS motor scores similar to those observed in the on-drug condition before surgery without the inconvenience of motor fluctuations and dyskinesias. No significant differences were seen in most of clinical outcome measures when comparing patients still taking ApMed with patients in STN-DBS monotherapy but a few patients still taking ApMed presented mild dyskinesias and motor fluctuations and patients with STN-DBS monotherapy did not. STN-DBS is useful in the treatment of advanced PD and in some patients it is possible to maintain this therapy alone in the long term. The therapeutic effect of STN-DBS on motor signs can be equipotent to that of levodopa with the additional benefit of avoiding motor fluctuations and dyskinesias.

  12. Unified Huntington's disease rating scale for advanced patients: validation and follow-up study.

    PubMed

    Youssov, Katia; Dolbeau, Guillaume; Maison, Patrick; Boissé, Marie-Françoise; Cleret de Langavant, Laurent; Roos, Raymund A C; Bachoud-Lévi, Anne-Catherine

    2013-10-01

    The Unified Huntington's Disease Rating Scale (UHDRS) adequately measures decline in patients at early and moderate stages of Huntington's disease (HD). In advanced patients, floor effects hamper the evaluation, thus calling for an adjusted scale. We designed the UHDRS-For Advanced Patients (UHDRS-FAP), in order to improve longitudinal assessment of patients at advanced disease stage. Sixty-nine patients with a Total Functional Capacity (TFC)  ≤  5 were recruited in France and in the Netherlands. Among them, 45 patients were followed longitudinally (mean 1.6  ±  1.2 years) with the UHDRS-FAP; 30 were also assessed with the UHDRS. Cross-sectional analyses evaluated psychometric properties and interrater reliability of the scale. Longitudinal analyses evaluated the sensitivity to decline compared to the UHDRS. Internal consistency was higher for motor and cognitive scores than for somatic and behavioral scores (0.84, 0.91, 0.70, and 0.49, respectively). Interrater reliability was  ≥  0.88 in all scores. The somatic score, specific to the UHDRS-FAP, declined over time, as well as motor and cognitive performance with both scales. Although performance with the 2 scales correlated, the UHDRS-FAP appeared more sensitive to change and was the only scale that detected decline in patients with a TFC  ≤  1. Neither scale detected a significant decline in behavioral scores. The UHDRS-FAP is reliable and more sensitive to change than the original UHDRS for cognitive and motor domains. It offers items relevant for daily care. Behavioral scores tended to decline but this may reflect the decline in the communicative abilities of the patients.

  13. The association between malnutrition and psychological distress in patients with advanced head-and-neck cancer

    PubMed Central

    Ma, L.; Poulin, P.; Feldstain, A.; Chasen, M.R.

    2013-01-01

    Objective Malnutrition and psychological distress are often seen in patients with head-and-neck cancer, but little is known about the interrelationships between those two symptoms. The present study examined the relationship between malnutrition and psychological distress in patients with advanced head-and-neck cancer. Methods Using the Patient-Generated Subjective Global Assessment, 99 patients with advanced-stage head-and-neck cancer were screened for nutrition status. The patients were also screened for psychosocial distress (using the Distress Thermometer) and for psychosocial issues (using the Problem Checklist). Any relationship between malnutrition and psychosocial distress was determined by regression and correlation analysis. We also used t-tests to compare distress levels for patients with and without specific nutrition-related symptoms. Results The study group included 80 men and 19 women [mean age: 58.4 ± 10.9 years (range: 23–85 years)]. The correlation between poorer nutrition status and level of psychological distress was significant r = 0.37 (p < 0.001). Specifically, reduced food intake and symptoms were both positively associated with distress: r = 0.27 and r = 0.29 respectively, both significant at p < 0.01. After controlling for the effects of psychosocial problems and pain, nutrition status remained a significant predictor of distress, explaining 3.8% of the variance in the distress scores of the patients (p < 0.05). Conclusions Malnutrition and symptoms were strongly related to distress in patients with advanced head-and-neck cancer. Our results suggest the need for further research into the complex relationship between nutrition status and distress and into the management of both nutrition and distress in cancer care. PMID:24311956

  14. The effects of curcumin (diferuloylmethane) on body composition of patients with advanced pancreatic cancer

    PubMed Central

    Parsons, Henrique A.; Baracos, Vickie E.; Hong, David S.; Abbruzzese, James; Bruera, Eduardo; Kurzrock, Razelle

    2016-01-01

    Background Curcumin is a natural product that is often explored by patients with cancer. Weight loss due to fat and muscle depletion is a hallmark of pancreatic cancer and is associated with worse outcomes. Studies of curcumin's effects on muscularity show conflicting results in animal models. Methods and results Retrospective matched 1:2 case-control study to evaluate the effects of curcumin on body composition (determined by computerized tomography) of 66 patients with advanced pancreatic cancer (22 treated,44 controls). Average age (SEM) was 63(1.8) years, 30/66(45%) women, median number of prior therapies was 2, median (IQR) time from advanced pancreatic cancer diagnosis to baseline image was 7(2-13.5) months (p>0.2, all variables). All patients lost weight (3.3% and 1.3%, treated vs. control, p=0.13). Treated patients lost more muscle (median [IQR] percent change −4.8[−9.1,-0.1] vs. −0.05%[−4.2, 2.6] in controls,p<0.001) and fat (median [IQR] percent change −6.8%[−15,-0.6] vs. −4.0%[−7.6, 1.3] in controls,p=0.04). Subcutaneous fat was more affected in the treated patients. Sarcopenic patients treated with curcumin(n=15) had survival of 169(115-223) days vs. 299(229-369) sarcopenic controls(p=0.024). No survival difference was found amongst non-sarcopenic patients. Conclusions Patients with advanced pancreatic cancer treated with curcumin showed significantly greater loss of subcutaneous fat and muscle than matched untreated controls. PMID:26934122

  15. Pilot Randomized Controlled Trial of Individual Meaning-Centered Psychotherapy for Patients With Advanced Cancer

    PubMed Central

    Breitbart, William; Poppito, Shannon; Rosenfeld, Barry; Vickers, Andrew J.; Li, Yuelin; Abbey, Jennifer; Olden, Megan; Pessin, Hayley; Lichtenthal, Wendy; Sjoberg, Daniel; Cassileth, Barrie R.

    2012-01-01

    Purpose Spiritual well-being and sense of meaning are important concerns for clinicians who care for patients with cancer. We developed Individual Meaning-Centered Psychotherapy (IMCP) to address the need for brief interventions targeting spiritual well-being and meaning for patients with advanced cancer. Patients and Methods Patients with stage III or IV cancer (N = 120) were randomly assigned to seven sessions of either IMCP or therapeutic massage (TM). Patients were assessed before and after completing the intervention and 2 months postintervention. Primary outcome measures assessed spiritual well-being and quality of life; secondary outcomes included anxiety, depression, hopelessness, symptom burden, and symptom-related distress. Results Of the 120 participants randomly assigned, 78 (65%) completed the post-treatment assessment and 67 (56%) completed the 2-month follow-up. At the post-treatment assessment, IMCP participants demonstrated significantly greater improvement than the control condition for the primary outcomes of spiritual well-being (b = 0.39; P <.001, including both components of spiritual well-being (sense of meaning: b = 0.34; P = .003 and faith: b = 0.42; P = .03), and quality of life (b = 0.76; P = .013). Significantly greater improvements for IMCP patients were also observed for the secondary outcomes of symptom burden (b = −6.56; P < .001) and symptom-related distress (b = −0.47; P < .001) but not for anxiety, depression, or hopelessness. At the 2-month follow-up assessment, the improvements observed for the IMCP group were no longer significantly greater than those observed for the TM group. Conclusion IMCP has clear short-term benefits for spiritual suffering and quality of life in patients with advanced cancer. Clinicians working with patients who have advanced cancer should consider IMCP as an approach to enhance quality of life and spiritual well-being. PMID:22370330

  16. Interleukin-6 and leptin as markers of energy metabolicchanges in advanced ovarian cancer patients

    PubMed Central

    Macciò, Antonio; Madeddu, Clelia; Massa, Daniela; Astara, Giorgio; Farci, Daniele; Melis, Gian Benedetto; Mantovani, Giovanni

    2009-01-01

    The progression of the neoplastic disease is characterized by specific alterations of energy metabolism and by symptoms like fatigue, anorexia, nausea, anaemia, immunodepression and poor performance status (PS). The main cause of these symptoms and metabolic abnormalities is the chronic action of proinflammatory cytokines released both by tumour and immune cells. The present study aimed to assess the relationship between markers of inflammation (C-Reactive Protein, Fibrinogen, proinflammatory cytokines) and energy metabolic status (BMI, leptin, oxidative stress) according to clinical parameters in 104 ovarian cancer patients at different stage and, moreover, to evaluate prospectively the changes of these parameters in accordance to tumour response in a subgroup of 70 advanced stage ovarian cancer patients. Advanced stage and poor PS were associated to high-grade inflammation and impaired energy metabolism. Among inflammatory mediators, interleukin (IL)-6 had a central role as predictive factor of leptin, reactive oxygen species and glutathione peroxidase. In turn, leptin considered the key marker of the nutritional status and energy metabolism, was independently determined from stage and IL-6, not only from BMI. Moreover, the evaluation of the changes of these parameters during the course of the neoplastic disease in the subgroup of advanced ovarian cancer patients clearly unveils the central role of IL-6 and leptin as early markers of the metabolic alterations and symptoms associated to disease progression in advanced stage ovarian cancer. Their assessment should be included in monitoring disease outcome, especially when cancer is no longer curable and quality of life becomes the primary endpoint. PMID:18624749

  17. Interleukin-6 and leptin as markers of energy metabolic changes in advanced ovarian cancer patients.

    PubMed

    Macciò, Antonio; Madeddu, Clelia; Massa, Daniela; Astara, Giorgio; Farci, Daniele; Melis, Gian Benedetto; Mantovani, Giovanni

    2009-09-01

    The progression of the neoplastic disease is characterized by specific alterations of energy metabolism and by symptoms like fatigue, anorexia, nausea, anaemia, immunodepression and poor performance status (PS). The main cause of these symptoms and metabolic abnormalities is the chronic action of proinflammatory cytokines released both by tumour and immune cells. The present study aimed to assess the relationship between markers of inflammation (C-Reactive Protein, Fibrinogen, proinflammatory cytokines) and energy metabolic status (BMI, leptin, oxidative stress) according to clinical parameters in 104 ovarian cancer patients at different stage and, moreover, to evaluate prospectively the changes of these parameters in accordance to tumour response in a subgroup of 70 advanced stage ovarian cancer patients. Advanced stage and poor PS were associated to high-grade inflammation and impaired energy metabolism. Among inflammatory mediators, interleukin (IL)-6 had a central role as predictive factor of leptin, reactive oxygen species and glutathione peroxidase. In turn, leptin considered the key marker of the nutritional status and energy metabolism, was independently determined from stage and IL-6, not only from BMI. Moreover, the evaluation of the changes of these parameters during the course of the neoplastic disease in the subgroup of advanced ovarian cancer patients clearly unveils the central role of IL-6 and leptin as early markers of the metabolic alterations and symptoms associated to disease progression in advanced stage ovarian cancer. Their assessment should be included in monitoring disease outcome, especially when cancer is no longer curable and quality of life becomes the primary endpoint. PMID:18624749

  18. Prediction models of hepatocellular carcinoma development in chronic hepatitis B patients

    PubMed Central

    Lee, Hye Won; Ahn, Sang Hoon

    2016-01-01

    Chronic hepatitis B virus (HBV) infection is a major cause of cirrhosis and hepatocellular carcinoma (HCC). Applying the same strategies for antiviral therapy and HCC surveillance to all chronic hepatitis B (CHB) patients would be a burden worldwide. To properly manage CHB patients, it is necessary to identify and classify the risk for HCC development in such patients. Several HCC risk scores based on risk factors such as cirrhosis, age, male gender, and high viral load have been used, and have negative predictive values of ≥ 95%. Most of these have been derived from, and internally validated in, treatment-naïve Asian CHB patients. Herein, we summarized various HCC prediction models, including IPM (Individual Prediction Model), CU-HCC (Chinese University-HCC), GAG-HCC (Guide with Age, Gender, HBV DNA, Core Promoter Mutations and Cirrhosis-HCC), NGM-HCC (Nomogram-HCC), REACH-B (Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B), and Page-B score. To develop a noninvasive test of liver fibrosis, we also introduced a new scoring system that uses liver stiffness values from transient elastography, including an LSM (Liver Stiffness Measurement)-based model, LSM-HCC, and mREACH-B (modified REACH-B). PMID:27729738

  19. Cerebellar stroke in a low cardiovascular risk patient associated with sorafenib treatment for fibrolamellar hepatocellular carcinoma

    PubMed Central

    Vandewynckel, Yves-Paul; Geerts, Anja; Verhelst, Xavier; Van Vlierberghe, Hans

    2014-01-01

    Key Clinical Message Sorafenib is the standard treatment of hepatocellular carcinoma (HCC). However, fibrolamellar HCC was not included in sorafenib trials. The case is a 26-year-old man with fibrolamellar HCC, who had a cerebrovascular accident (CVA) while being treated with sorafenib. This illustrates a probable relationship between use of sorafenib and CVA in low cardiovascular risk patients. PMID:25356226

  20. A phase II study of TRC105 in patients with hepatocellular carcinoma who have progressed on sorafenib

    PubMed Central

    Duffy, AG; Ulahannan, SV; Cao, L; Rahma, OE; Makarova-Rusher, OV; Kleiner, DE; Fioravanti, S; Walker, M; Carey, S; Yu, Y; Venkatesan, AM; Turkbey, B; Choyke, P; Trepel, J; Bollen, KC; Steinberg, SM; Figg, WD

    2015-01-01

    Background Endoglin is an endothelial cell membrane receptor essential for angiogenesis and highly expressed on the vasculature of many tumor types, including hepatocellular carcinoma (HCC). TRC105 is a chimeric IgG1 anti-CD105 monoclonal antibody that inhibits angiogenesis and tumor growth by endothelial cell growth inhibition, ADCC and apoptosis, and complements VEGF inhibitors. Objective The aim of this phase II study was to evaluate the efficacy of anti-endoglin therapy with TRC105 in patients with advanced HCC, post-sorafenib. Methods Patients with HCC and compensated liver function (Childs-Pugh A/B7), ECOG 0/1, were enrolled to a single-arm, phase II study of TRC105 15 mg/kg IV every two weeks. Patients must have progressed on or been intolerant of prior sorafenib. A Simon optimal two-stage design was employed with a 50% four-month PFS target for progression to the second stage. Correlative biomarkers evaluated included DCE-MRI as well as plasma levels of angiogenic biomarkers and soluble CD105. Results A total accrual of 27 patients was planned. However, because of lack of efficacy and in accordance with the Simon two-stage design, 11 patients were enrolled. There were no grade 3/4 treatment-related toxicities. Most frequent toxicities were headache (G2; N = 3) and epistaxis (G1; N = 4). One patient had a confirmed partial response by standard RECIST criteria and biologic response on DCE-MRI but the four-month PFS was insufficient to proceed to the second stage of the study. Conclusions: TRC105 was well tolerated in this HCC population following sorafenib. Although there was evidence of clinical activity, this did not meet prespecified criteria to proceed to the second stage. TRC105 development in HCC continues as combination therapy with sorafenib. PMID:26535124

  1. Foreign travel for advanced cancer patients: a guide for healthcare professionals

    PubMed Central

    Perdue, Colin; Noble, Simon

    2007-01-01

    The opportunity for a patient with advanced cancer to travel abroad may, for some, be a life affirming event during a dark period in their life. For others, what they hoped to be a time of joy may become an unmitigated disaster if they become unwell while away from the safety net of local cancer services. The rise of low budget airlines and cheaper foreign travel has led to an increase in the number of people travelling by air. Health professionals are more likely to face requests by patients to advise them on travel plans. Although foreign travel is an unrealistic goal for some patients, appropriate forward planning and proactive management can allow some patients to make an important journey abroad. This paper looks at the practical issues facing cancer patients who intend to travel overseas and offers practical advice on considerations that need to be made. PMID:17621611

  2. Foreign travel for advanced cancer patients: a guide for healthcare professionals.

    PubMed

    Perdue, Colin; Noble, Simon

    2007-07-01

    The opportunity for a patient with advanced cancer to travel abroad may, for some, be a life affirming event during a dark period in their life. For others, what they hoped to be a time of joy may become an unmitigated disaster if they become unwell while away from the safety net of local cancer services. The rise of low budget airlines and cheaper foreign travel has led to an increase in the number of people travelling by air. Health professionals are more likely to face requests by patients to advise them on travel plans. Although foreign travel is an unrealistic goal for some patients, appropriate forward planning and proactive management can allow some patients to make an important journey abroad. This paper looks at the practical issues facing cancer patients who intend to travel overseas and offers practical advice on considerations that need to be made. PMID:17621611

  3. LATS2-mediated YAP1 phosphorylation is involved in HCC tumorigenesis

    PubMed Central

    Guo, Chao; Wang, Xintian; Liang, Lufeng

    2015-01-01

    YAP (yes-associated protein) is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes, including proliferation and apoptosis. Although YAP plays an important role in various tumors, the underlying mechanism in hepatocellular carcinoma (HCC) tumorigenesis remains unclear. In this study, we observed that the LATS2 was highly expressed in Bel-7402 and HepG2 cell lines, and LATS2 protein level was negatively correlated with YAP1 in HCC cells. And then, we inhibited LATS2 expression by transfecting with siRNA. Western blot and Immunofluorescent staining analysis demonstrated that LATS2 inhibition decreased the dephosphorylation of YAP1 protein and promoted YAP1 nuclear accumulation in HCC cells. Moreover, Immunoprecipitation assay results also indicated that Yap binds directly to TEAD2 and LATS2 inhibition-mediated dephosphorylation increased the YAP1/TEAD2 association, leading to YAP1/TEAD2 transcriptional activation, which in turn upregulated cell invasion in HCC cells. Taken together, our current data indicated a new regulatory mechanism of YAP1 by the LATS2-mediated phosphorylation that was involved in HCC tumorigenesis. PMID:25973055

  4. IL-2-Activated Killer Cells and Native Cytokines in Treatment of Patients with Advanced Cancer.

    PubMed

    Ostanin, Alexander A.; Chernykh, Helena R.; Leplina, Olga Y.; Shevela, Ekaterina Ya.; Niconov, Sergey D.; Kozlov, Vladimir A.

    1997-12-01

    We evaluated the efficiency/tolerability of and the immunological changes induced by the adoptive immunotherapy (AIT) with IL-2-activated killer cells, and preparation of native cytokines from swine spleen (PSS) in treatment of 20 patients with advanced cancer (10 patients with primary lung cancer; 3 with metastatic melanoma; 2 with advanced neuroblastoma; 2 with ovarian cancer; renal cancer; gastric adenocarcinoma; and colorectal cancer). The partial/minor response of duration period 2-10 months was observed in 20% of patients. 2/4 patients, who underwent partial surgical tumor resection and following AIT course, sustained the event-free survival for more than 24 months. The response to the therapy was revealed in 4/10 patients with lung cancer, 2/2 patients with neuroblastoma, of whom each had ovarian and colorectal cancers. The evaluation of a dose of infused LAKcells as well as combined i.v./local (endobronchial or endoperitoneal) LAK administration were necessary to assure positive response in patients. The cytokine and/or side effects were moderate and the combined LAK-PSS infusions were generally well tolerated by the patients. The treatment was followed by activation of the patient immune system that included: (i) rebound in amount of peripheral blood lymphocytes; (ii) gain in amount of CD3(+) T cells and those CD4(+) helper/inducer; (iii) enchantment of lymphocyte proliferation and cytokine production (IL-2, IL-1, TNF-alpha). Being injected to patients in combination with LAK cells, cytokines related to PSS action and/or those, either exogenous or secondary, and released by in vitro and in vivo, activated lymphocytes and could cause the therapeutic effects.

  5. Laser immunotherapy for treatment of patients with advanced breast cancer and melanoma

    NASA Astrophysics Data System (ADS)

    Li, Xiaosong; Hode, Tomas; Guerra, Maria C.; Ferrel, Gabriela L.; Nordquist, Robert E.; Chen, Wei R.

    2011-02-01

    Laser immunotherapy (LIT) was developed for the treatment of metastatic tumors. It combines local selective photothermal interaction and active immunological stimulation to induce a long-term, systemic anti-tumor immunity. During the past sixteen years, LIT has been advanced from bench-top to bedside, with promising outcomes. In our pre-clinical and preliminary clinical studies, LIT has demonstrated the capability in inducing immunological responses, which not only can eradicate the treated primary tumors, but also can eliminate untreated metastases at distant sites. Specifically, LIT has been used to treat advanced melanoma and breast cancer patients during the past five years. LIT was shown to be effective in controlling both primary tumors and distant metastases in late-stage patients, who have failed conventional therapies such as surgery, chemotherapy, radiation, and other more advanced approaches. The methodology and the development of LIT are presented in this paper. The patients' responses to LIT are also reported in this paper. The preliminary results obtained in these studies indicated that LIT could be an effective modality for the treatment of patients with late-stage, metastatic cancers, who are facing severely limited options.

  6. Disparities in the Use of Radiation Therapy in Patients With Local-Regionally Advanced Breast Cancer

    SciTech Connect

    Martinez, Steve R.; Beal, Shannon H.; Chen, Steven L.; Canter, Robert J.; Khatri, Vijay P.; Chen, Allen; Bold, Richard J.

    2010-11-01

    Background: Radiation therapy (RT) is indicated for the treatment of local-regionally advanced breast cancer (BCa). Hypothesis: We hypothesized that black and Hispanic patients with local-regionally advanced BCa would receive lower rates of RT than their white counterparts. Methods: The Surveillance Epidemiology and End Results database was used to identify white, black, Hispanic, and Asian patients with invasive BCa and {>=}10 metastatic lymph nodes diagnosed between 1988 and 2005. Univariate and multivariate logistic regression evaluated the relationship of race/ethnicity with use of RT. Multivariate models stratified for those undergoing mastectomy or lumpectomy. Results: Entry criteria were met by 12,653 patients. Approximately half of the patients did not receive RT. Most patients were white (72%); the remainder were Hispanic (10.4%), black (10.3%), and Asian (7.3%). On univariate analysis, Hispanics (odd ratio [OR] 0.89; 95% confidence interval [CI], 0.79-1.00) and blacks (OR 0.79; 95% CI, 0.70-0.89) were less likely to receive RT than whites. On multivariate analysis, blacks (OR 0.76; 95% CI, 0.67-0.86) and Hispanics (OR 0.80; 95% CI, 0.70-0.90) were less likely than whites to receive RT. Disparities persisted for blacks (OR 0.74; 95% CI, 0.64-0.85) and Hispanics (OR 0.77; 95% CI, 0.67-0.89) who received mastectomy, but not for those who received lumpectomy. Conclusions: Many patients with local-regionally advanced BCa do not receive RT. Blacks and Hispanics were less likely than whites to receive RT. This disparity was noted predominately in patients who received mastectomy. Future efforts at improving rates of RT are warranted. Efforts at eliminating racial/ethnic disparities should focus on black and Hispanic candidates for postmastectomy RT.

  7. Symptom clusters and quality of life among patients with advanced heart failure

    PubMed Central

    Yu, Doris SF; Chan, Helen YL; Leung, Doris YP; Hui, Elsie; Sit, Janet WH

    2016-01-01

    Objectives To identify symptom clusters among patients with advanced heart failure (HF) and the independent relationships with their quality of life (QoL). Methods This is the secondary data analysis of a cross-sectional study which interviewed 119 patients with advanced HF in the geriatric unit of a regional hospital in Hong Kong. The symptom profile and QoL were assessed by using the Edmonton Symptom Assessment Scale (ESAS) and the McGill QoL Questionnaire. Exploratory factor analysis was used to identify the symptom clusters. Hierarchical regression analysis was used to examine the independent relationships with their QoL, after adjusting the effects of age, gender, and comorbidities. Results The patients were at an advanced age (82.9 ± 6.5 years). Three distinct symptom clusters were identified: they were the distress cluster (including shortness of breath, anxiety, and depression), the decondition cluster (fatigue, drowsiness, nausea, and reduced appetite), and the discomfort cluster (pain, and sense of generalized discomfort). These three symptom clusters accounted for 63.25% of variance of the patients' symptom experience. The small to moderate correlations between these symptom clusters indicated that they were rather independent of one another. After adjusting the age, gender and comorbidities, the distress (β = −0.635, P < 0.001), the decondition (β = −0.148, P = 0.01), and the discomfort (β = −0.258, P < 0.001) symptom clusters independently predicted their QoL. Conclusions This study identified the distinctive symptom clusters among patients with advanced HF. The results shed light on the need to develop palliative care interventions for optimizing the symptom control for this life-limiting disease. PMID:27403150

  8. Selecting the best strategy of treatment in newly diagnosed advanced-stage ovarian cancer patients.

    PubMed

    Minig, Lucas; Zorrero, Cristina; Iserte, Pablo Padilla; Poveda, Andres

    2015-12-26

    Although it is assumed that the combination of chemotherapy and radical surgery should be indicated in all newly diagnosed advanced-stage ovarian cancer patients, one of the main raised questions is how to select the best strategy of initial treatment in this group of patients, neoadjuvant chemotherapy followed by interval debulking surgery or primary debulking surgery followed by adjuvant chemotherapy. The selection criteria to offer one strategy over the other as well as a stepwise patient selection for initial treatment are described. Selecting the best strategy of treatment in newly diagnosed advanced stage ovarian cancer patients is a multifactorial and multidisciplinary decision. Several factors should be taken into consideration: (1) the disease factor, related to the extension and localization of the disease as well as tumor biology; (2) the patient factor, associated with patient age, poor performance status, and co-morbidities; and (3) institutional infrastructure factor, related to the lack of prolonged operative time, an appropriate surgical armamentarium, as well as well-equipped intensive care units with well-trained personnel.

  9. Recent advances in managing chronic HCV infection: focus on therapy in patients with severe liver disease

    PubMed Central

    Maan, Raoel; van der Meer, Adriaan J.

    2016-01-01

    Chronic hepatitis C virus (HCV) infection still represents a major public health problem, as it is thought to be responsible for more than 350,000 deaths around the globe on a yearly basis. Fortunately, successful eradication of the virus has been associated with improved clinical outcome and reduced mortality rates. In the past few years, treatment has improved considerably by the implementation of direct-acting antivirals (DAAs). From 2014 onwards, sofosbuvir, simeprevir, daclatasvir, ledipasvir, paritaprevir, ombitasvir, and dasabuvir have been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Regimens with various combinations of these new drugs, without the use of interferon (IFN), proved to be very effective and well tolerated, even among patients with advanced liver disease. Moreover, treatment duration could be shortened to 12 weeks in the majority of patients. The high costs of these DAAs, however, limit the availability of IFN-free therapy worldwide. Even in wealthy countries, it is deemed necessary to prioritize DAA treatment in order to limit the immediate impact on the health budget. As patients with advanced liver disease are in most need of HCV clearance, many countries decided to treat those patients first. In the current review, we focus on the currently available IFN-free treatment options for patients with cirrhosis. We discuss the virological efficacy as well as the clinical relevance of these regimens among this specific patient population. PMID:27006761

  10. [Efficacy and safety of selective estrogen receptor modulators in patients with advanced chronic kidney disease].

    PubMed

    Nakai, Kentaro

    2016-09-01

    Selective estrogen receptor modulators(SERMs)have beneficial effects on the improvement of bone mineral density of the spine and hip, and decrease the vertebral fracture in postmenopausal women. Similar to patients with advanced chronic kidney disease, including dialysis patients, however, SERMs cannot decrease the risk of hip fracture, which is extremely high in Japanese dialysis patients. One of the most important disadvantages of SERMs is an increase in the risk of venous thromboembolic events and fatal stroke in high-risk groups of the Framingham Stroke Risk Score. On the other hand, SERMs may be used in unique osteoporosis drugs for reducing the incidence and progression of breast cancer. Moreover, SERMs attenuate oxidative stress and may lessen the deterioration of kidney function in patients with chronic kidney disease. The evidences for the efficacy and safety of SERMs in patients with advanced chronic kidney disease are insufficient, and knowledge concerning the selection and indication of osteoporosis drugs for those patients need to be developed. PMID:27561348

  11. Chemotherapy in elderly patients with advanced non-small cell lung cancer.

    PubMed

    Quoix, Elisabeth; Westeel, Virginie; Zalcman, Gérard; Milleron, Bernard

    2011-12-01

    Because of increasing life expectancy and of higher risk of cancer with ageing, lung cancer in elderly is a frequent disease. For a long time nihilism influenced treatment decisions in elderly patients with advanced non-small cell lung cancer. Since the beginning of the last decade single agent chemotherapy has been accepted as standard of care, vinorelbine and gemcitabine being the most frequently used drugs in Europe and US, docetaxel in Japan. Platinum-based doublets have been shown to be superior to monotherapy in young and fit patients with advanced non-small cell lung cancer. Although there were some indications from subgroup analyses of clinical trials not specifically dedicated to elderly patients that a platinum-based doublet might also benefit to older patients, there was no definitive proof of concept until ASCO meeting 2010. At this meeting results of a phase 3 trial showed that PS 0-2 patients, aged 70-89 years drove a significant benefit from a treatment with carboplatin associated to weekly paclitaxel compared to a monotherapy. Thus, the paradigm of treatment in elderly patients should perhaps be modified from a single agent to doublet chemotherapy. Whether other platinum-based doublets would provide the same benefit as the specific one studied remains to be evaluated. PMID:21893363

  12. Summary of bi-shRNA/GM-CSF augmented autologous tumor cell immunotherapy (FANG™) in advanced cancer of the liver.

    PubMed

    Nemunaitis, John; Barve, Minal; Orr, Douglas; Kuhn, Joseph; Magee, Mitchell; Lamont, Jeffrey; Bedell, Cynthia; Wallraven, Gladice; Pappen, Beena O; Roth, Alyssa; Horvath, Staci; Nemunaitis, Derek; Kumar, Padmasini; Maples, Phillip B; Senzer, Neil

    2014-01-01

    Therapies for advanced hepatocellular carcinoma (HCC) are limited. We carried out a phase I trial of a novel autologous whole-cell tumor cell immunotherapy (FANG™), which incorporates a dual granulocyte macrophage colony-stimulating factor (GM-CSF) expressive/bifunctional small hairpin RNA interference (bi-shRNAi) vector. The bi-shRNAi DNA targets furin, which is a proconvertase of transforming growth factors beta (TGFβ) 1 and 2. Safety, mechanism, immunoeffectiveness, and suggested benefit were previously shown [Senzer et al.: Mol Ther 2012;20:679-689; Senzer et al.: J Vaccines Vaccin 2013;4:209]. We now provide further follow-up of a subset of 8 HCC patients. FANG manufacturing was successful in 7 of 8 attempts (one failure due to insufficient cell yield). Median GM-CSF expression was 144 pg/10(6) cells, TGFβ1 knockdown was 100%, and TGFβ2 knockdown was 93% of the vector-transported cells. Five patients were vaccinated (1 or 2.5×10(7) cells/intradermal injection, 6-11 vaccinations). No FANG toxicity was observed. Three of these patients demonstrated evidence of an immune response to the autologous tumor cell sample. Long-term follow-up demonstrated survival of 319, 729, 784, 931+, and 1,043+ days of the FANG-treated patients. In conclusion, evidence supports further assessment of the FANG immunotherapy in HCC. PMID:24968881

  13. Summary of bi-shRNA/GM-CSF augmented autologous tumor cell immunotherapy (FANG™) in advanced cancer of the liver.

    PubMed

    Nemunaitis, John; Barve, Minal; Orr, Douglas; Kuhn, Joseph; Magee, Mitchell; Lamont, Jeffrey; Bedell, Cynthia; Wallraven, Gladice; Pappen, Beena O; Roth, Alyssa; Horvath, Staci; Nemunaitis, Derek; Kumar, Padmasini; Maples, Phillip B; Senzer, Neil

    2014-01-01

    Therapies for advanced hepatocellular carcinoma (HCC) are limited. We carried out a phase I trial of a novel autologous whole-cell tumor cell immunotherapy (FANG™), which incorporates a dual granulocyte macrophage colony-stimulating factor (GM-CSF) expressive/bifunctional small hairpin RNA interference (bi-shRNAi) vector. The bi-shRNAi DNA targets furin, which is a proconvertase of transforming growth factors beta (TGFβ) 1 and 2. Safety, mechanism, immunoeffectiveness, and suggested benefit were previously shown [Senzer et al.: Mol Ther 2012;20:679-689; Senzer et al.: J Vaccines Vaccin 2013;4:209]. We now provide further follow-up of a subset of 8 HCC patients. FANG manufacturing was successful in 7 of 8 attempts (one failure due to insufficient cell yield). Median GM-CSF expression was 144 pg/10(6) cells, TGFβ1 knockdown was 100%, and TGFβ2 knockdown was 93% of the vector-transported cells. Five patients were vaccinated (1 or 2.5×10(7) cells/intradermal injection, 6-11 vaccinations). No FANG toxicity was observed. Three of these patients demonstrated evidence of an immune response to the autologous tumor cell sample. Long-term follow-up demonstrated survival of 319, 729, 784, 931+, and 1,043+ days of the FANG-treated patients. In conclusion, evidence supports further assessment of the FANG immunotherapy in HCC.

  14. Advance Directives and Do-Not-Resuscitate Orders in Patients with Cancer with Metastatic Spinal Cord Compression: Advanced Care Planning Implications

    PubMed Central

    Palmer, J. Lynn; Bianty, Josephine; Konzen, Benedict; Shin, Ki; Bruera, Eduardo

    2010-01-01

    Abstract Objectives Communication about end-of-life decisions is crucial. Although patients with metastatic spinal cord compression (MSCC) have a median survival time of 3 to 6 months, few data are available concerning the presence of advance directives and do-not-resuscitate (DNR) orders in this population. The objective of this study was to determine presence of advance directives and DNR order among patients with MSCC. Methods We retrospectively reviewed data concerning advance directives for 88 consecutive patients with cancer who had MSCC and required rehabilitation consultation at The University of Texas M. D. Anderson Cancer Center from September 20, 2005 to August 29, 2008. We characterized the data using univariate descriptive statistics and used the Fisher exact test to find correlations. Results The mean age of this patient population was 55 years (range, 24–81). Thirty patients (33%) were female. Twenty patients (23%) had a living will, 27 patients (31%) had health care proxies, and 10 patients (11%) had either out-of-hospital DNR order and/or dictated DNR note. The median survival time for these patients was 4.3 months. Conclusion Despite strong evidence showing short survival times for MSCC patients, it seems many of these patients are not aware of the urgency to have an advance directive. This may be an indicator of delayed end-of-life palliative care and suboptimal doctor–patient communication. Using the catastrophic event of a diagnosis of MSCC to trigger communication and initiate palliative care may be beneficial to patients and their families. PMID:20192843

  15. Vascularized Free Lymph Node Flap Transfer in Advanced Lymphedema Patient after Axillary Lymph Node Dissection

    PubMed Central

    Cook, Kyung Hoon; Park, Myong Chul; Lim, Seong Yoon; Jung, Yong Sik

    2016-01-01

    Lymphedema is a condition characterized by tissue swelling caused by localized fluid retention. Advanced lymphedema is characterized by irreversible skin fibrosis (stage IIIb) and nonpitting edema, with leather-like skin, skin crypts, and ulcers with or without involvement of the toes (stage IVa and IVb, respectively). Recently, surgical treatment of advanced lymphedema has been a challenging reconstructive modality. Microvascular techniques such as lymphaticovenous anastomosis and vascularized lymph node flap transfer are effective for early stage lymphedema. In this study, we performed a two-stage operation in an advanced lymphedema patient. First, a debulking procedure was performed using liposuction. A vascularized free lymph node flap transfer was then conducted 10 weeks after the first operation. In this case, good results were obtained, with reduced circumferences in various parts of the upper extremity noted immediately postoperation. PMID:27064862

  16. Efficacy and Tolerability of ABT-869 Versus Sorafenib in Advanced Hepatocellular Carcinoma (HCC)

    ClinicalTrials.gov

    2012-09-07

    Hepatocellular Carcinoma Non-resectable; Hepatocellular Carcinoma Recurrent; Carcinoma, Hepatocellular; Liver Diseases; Neoplasms by Histologic Type; Digestive System Neoplasms; Carcinoma; Liver Neoplasms; Neoplasms; Neoplasms by Site; Digestive System Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial

  17. Treating Elderly Patients With Hormone Receptor–Positive Advanced Breast Cancer

    PubMed Central

    Riseberg, David

    2015-01-01

    As the overall population ages, the proportion of elderly patients (aged ≥65 years) with breast cancer also increases. Studies have shown that elderly patients with hormone receptor–positive breast cancer can derive as much benefit from treatment as do younger patients, yet they remain underrepresented in clinical trials and are often undertreated in clinical practice. Treatment decisions for older patients should not be based solely on chronologic age; a patient’s physiologic functioning and comorbidities must also be taken into consideration. For recurrent or metastatic disease, systemic treatment with endocrine therapies or chemotherapy may prolong a patient’s life and alleviate troublesome symptoms. Resistance to therapy remains a problem in the advanced breast cancer setting, with most patients eventually becoming resistant to additional treatment. New combination regimens that target multiple pathways, such as everolimus plus exemestane, have shown efficacy in elderly patients previously resistant to endocrine therapies, and future research may need to focus on such combinations in order to improve outcomes in this patient group. A number of investigational agents are in clinical development, although few studies identify their effects in the elderly patient population. Optimizing effective yet tolerable therapeutic regimens for elderly patients could improve their outcomes while ensuring that the goals of improved survival and quality of life are considered. PMID:26339192

  18. Estrogen Represses Hepatocellular Carcinoma (HCC) Growth via Inhibiting Alternative Activation of Tumor-associated Macrophages (TAMs)*

    PubMed Central

    Yang, Weiwei; Lu, Yan; Xu, Yichen; Xu, Lizhi; Zheng, Wei; Wu, Yuanyuan; Li, Long; Shen, Pingping

    2012-01-01

    Hepatocarcinoma cancer (HCC), one of the most malignant cancers, occurs significantly more often in men than in women; however, little is known about its underlying molecular mechanisms. Here we identified that 17β-estradiol (E2) could suppress tumor growth via regulating the polarization of macrophages. We showed that E2 re-administration reduced tumor growth in orthotopic and ectopic mice HCC models. E2 functioned as a suppressor for macrophage alternative activation and tumor progression by keeping estrogen receptor β (ERβ) away from interacting with ATP5J (also known as ATPase-coupling factor 6), a part of ATPase, thus inhibiting the JAK1-STAT6 signaling pathway. These studies introduce a novel mechanism for suppressing male-predominant HCC. PMID:22908233

  19. Advances in the pathogenesis and treatment of patients with stiff person syndrome.

    PubMed

    Dalakas, Marinos C

    2008-01-01

    Advances in the clinical diagnosis, prognosis, pathogenesis, and therapies for stiff person syndrome (SPS), based on observations in more than 50 consecutive patients, are presented. The syndrome varies from mild to severe, but if untreated it can be progressive and disabling. SPS remains a largely underdiagnosed condition. Anti-glutamic acid decarboxylase (GAD) antibodies provide an excellent diagnostic marker, but their role in disease pathogenesis is uncertain. Research focused on identifying new autoantigens has provided evidence that gamma-aminobutyric acid (GABA)(A) receptor-associated protein (GABARAP), a 14-kD protein localized at the postsynaptic regions of GABAergic synapses, is a new antigenic target. In up to 65% of SPS patients, there are circulating anti-GABARAP antibodies that inhibit the GABA(A) receptor expression on GABAergic neurons. This review examines the diagnostic criteria for SPS, SPS variants, common errors in diagnosis, and a step-by-step therapeutic approach, including new advances in therapy.

  20. Religious Coping is Associated with the Quality of Life of Patients with Advanced Cancer

    PubMed Central

    Tarakeshwar, Nalini; Vanderwerker, Lauren C.; Paulk, Elizabeth; Pearce, Michelle J.; Kasl, Stanislav V.; Prigerson, Holly G.

    2008-01-01

    Background For patients confronting a life-threatening illness such as advanced cancer, religious coping can be an important factor influencing their quality of life (QOL). Objective The study's main purpose was to examine the association between religious coping and QOL among 170 patients with advanced cancer. Both positive religious coping (e.g., benevolent religious appraisals) and negative religious coping (e.g., anger at God) and multiple dimensions of QOL (physical, physical symptom, psychological, existential, and support) were studied. Design Structured interviews were conducted with 170 patients recruited as part of an ongoing multi-institutional longitudinal evaluation of the prevalence of mental illness and patterns of mental health service utilization in advanced cancer patients and their primary informal caregivers. Measurements Patients completed measures of QOL (McGill QOL questionnaire), religious coping (Brief Measure of Religious Coping [RCOPE] and Multidimensional Measure of Religion/Spirituality), self-efficacy (General Self-Efficacy Scale), and sociodemographic variables. Results Linear regression analyses revealed that after controlling for sociodemographic variables, lifetime history of depression and self-efficacy, greater use of positive religious coping was associated with better overall QOL as well as higher scores on the existential and support QOL dimensions. Greater use of positive religious coping was also related to more physical symptoms. In contrast, greater use of negative religious coping was related to poorer overall QOL and lower scores on the existential and psychological QOL dimensions. Conclusions Findings show that religious coping plays an important role for the QOL of patients and the types of religious coping strategies used are related to better or poorer QOL. PMID:16752970

  1. End-of-life care in patients with advanced lung cancer.

    PubMed

    Lim, Richard B L

    2016-10-01

    Despite advances in the detection, pathological diagnosis and therapeutics of lung cancer, many patients still develop advanced, incurable and progressively fatal disease. As physicians, the duties to cure sometimes, relieve often and comfort always should be a constant reminder to us of the needs that must be met when caring for a patient with lung cancer. Four key areas of end-of-life care in advanced lung cancer begin with first recognizing 'when a patient is approaching the end of life'. The clinician should be able to recognize when the focus of care needs to shift from an aggressive life-sustaining approach to an approach that helps prepare and support a patient and family members through a period of progressive, inevitable decline. Once the needs are recognized, the second key area is appropriate communication, where the clinician should assist patients and family members in understanding where they are in the disease trajectory and what to expect. This involves developing rapport, breaking bad news, managing expectations and navigating care plans. Subsequently, the third key area is symptom management that focuses on the goals to first and foremost provide comfort and dignity. Symptoms that are common towards the end of life in lung cancer include pain, dyspnoea, delirium and respiratory secretions. Such symptoms need to be anticipated and addressed promptly with appropriate medications and explanations to the patient and family. Lastly, in order for physicians to provide quality end-of-life care, it is necessary to understand the ethical principles applied to end-of-life-care interventions. Misconceptions about euthanasia versus withholding or withdrawing life-sustaining treatments may lead to physician distress and inappropriate decision making. PMID:27585597

  2. Navigating Ethical Conflicts Between Advance Directives and Surrogate Decision-Makers' Interpretations of Patient Wishes.

    PubMed

    Bruce, Courtenay R; Bibler, Trevor; Childress, Andrew M; Stephens, Ashley L; Pena, Adam M; Allen, Nathan G

    2016-02-01

    There is little guidance on what clinicians should do when advance directives (or living wills, specifically) are challenged, particularly when surrogate decision-makers' interpretations of patients' wishes conflict with the living will. In our commentary, we make a controversial argument suggesting that overriding living wills can be ethically preferable to the alternative of strictly adhering to them. We propose four ethical considerations for determining whether it is ethically supportable to override living wills.

  3. Matrix stiffness-mediated effects on stemness characteristics occurring in HCC cells.

    PubMed

    You, Yang; Zheng, Qiongdan; Dong, Yinying; Xie, Xiaoying; Wang, Yaohui; Wu, Sifan; Zhang, Lan; Wang, Yingcong; Xue, Tongchun; Wang, Zhiming; Chen, Rongxin; Wang, Yanhong; Cui, Jiefeng; Ren, Zhenggang

    2016-05-31

    Matrix stiffness as an important physical attribute of extracellular matrix exerts significant impacts on biological behaviors of cancer cells such as growth, proliferation, motility, metabolism and invasion. However, its influence on cancer stemness still remains elusive. Here, we explore whether matrix stiffness-mediated effects on stemness characteristics occur in HCC cells. As the substrate stiffness increased, HCC cells exhibited high proportion of cells with CD133(+)/EpCAM(+), high expression levels of CD133, EpCAM, Nanog and SOX2, greater self-renewing ability and oxaliplatin resistance. Simultaneously, their phosphorylation levels of Akt and mTOR, as well as p-4E-BP and SOX2 expressions were also obviously upregulated. Conversely, knockdown of integrin β1 partially attenuated higher stiffness-mediated stemness characteristics in HCC cells, and reversed the phosphorylation levels of Akt and mTOR, and expressions of p-4E-BP and SOX2, suggesting that integrin β1 may deliver higher stiffness signal into HCC cells and activate mTOR signaling pathway. Additionally, mTOR inhibitor suppressed the mTOR phosphorylation level and expression levels of p-4E-BP and SOX2 in HCC cells grown on higher stiffness substrate, as well as depressed their stemness properties significantly, favoring a regulating role of mTOR signaling pathway in matrix stiffness-mediated effects on stemness. In summary, matrix stiffness may be involved in the process of stemness regulation via activating integrin β1/Akt/mTOR/SOX2 signaling pathway. To the best of our knowledge, this study first reveals a novel regulating pathway to direct the stemness characteristics in HCC cells.

  4. Prosthodontic treatment for a patient with advanced hydantoin-associated gingival hyperplasia: a case report.

    PubMed

    Hayakawa, I; Osada, E; Morisawa, M; Nakagawa, Y; Watanabe, I

    1996-04-01

    A patient in whom gingival hyperplasia was caused by prolonged use of an anticonvulsant drug (hydantoin) is described. Advanced gingival hyperplasia and significant displacement of the remaining teeth caused severe damage, especially to the patient's appearance. It was not possible to cure the problems completely with routine periodontal treatment. It was decided to extract all the remaining teeth and restore function and esthetics early with complete dentures. Cephalometric analysis was used to determine the degree to which the teeth had drifted. During fabrication of the dentures, the analysis was very useful in deciding the position of the anterior teeth and checking the vertical dimension of occlusion.

  5. Gross Hematuria and Bladder Tumor in a Patient with Advanced Thyroid Papillary Carcinoma

    PubMed Central

    Matsuo, Yuki; Ikeoka, Toshiyuki; Oba, Kojiro; Miyata, Yasuyoshi; Sakai, Hideki; Abe, Kuniko; Kawakami, Atsushi

    2013-01-01

    We present a 73-year-old female with advanced thyroid papillary carcinoma who complained of gross hematuria. We found a bladder tumor and considered it the cause of her symptom. Cystoscopic findings of the tumor were unusual, with peri-tumor vessel formation. Pathological examination of the bladder tumor was consistent with metastasis of thyroid papillary carcinoma. Therefore, we identified thyroid carcinoma metastasis to the urinary bladder as the cause of hematuria in our patient. Thyroid carcinoma metastasis to the bladder is extremely rare, but it should be included among differential diagnoses for gross hematuria in patients with a clinical history of thyroid carcinoma. PMID:23762664

  6. Intercostal nerves block for mastectomy in two patients with advanced breast malignancy.

    PubMed

    Kolawole, Israel K; Adesina, Michael D; Olaoye, Iyiade O

    2006-03-01

    Regional anesthesia is recognized as an alternative to general anesthesia for modern breast cancer surgery. Various techniques of block have been described. Each has its unique problems. Regional anesthesia was chosen for simple mastectomy in two patients with advanced breast malignancy, due to compromised pulmonary status resulting from widespread malignant infiltration of both lungs. We used intercostal nerves block. The block was supplemented with an infraclavicular infiltration to interrupt the branches of the superficial cervical plexus that provide sensation to the upper chest wall and subcutaneous infiltration in the midline to block the nerve supply from the contralateral side. Anesthesia was generally effective and the operations were uneventful. Both patients and surgeons expressed satisfaction. We conclude that where patients have significant comorbidities that make general anesthesia undesirable, the use of intercostal nerves block remains a safe and reliable anesthetic option that allows the patient access to surgery for simple mastectomy.

  7. Meaning-centered group psychotherapy for patients with advanced cancer: a pilot randomized controlled trial

    PubMed Central

    Breitbart, William; Rosenfeld, Barry; Gibson, Christopher; Pessin, Hayley; Poppito, Shannon; Nelson, Christian; Tomarken, Alexis; Timm, Anne Kosinski; Berg, Amy; Jacobson, Colleen; Sorger, Brooke; Abbey, Jennifer; Olden, Megan

    2013-01-01

    Objectives An increasingly important concern for clinicians who care for patients at the end of life is their spiritual well-being and sense of meaning and purpose in life. In response to the need for short-term interventions to address spiritual well-being, we developed Meaning Centered Group Psychotherapy (MCGP) to help patients with advanced cancer sustain or enhance a sense of meaning, peace and purpose in their lives, even as they approach the end of life. Methods Patients with advanced (stage III or IV) solid tumor cancers (N = 90) were randomly assigned to either MCGP or a supportive group psychotherapy (SGP). Patients were assessed before and after completing the 8-week intervention, and again 2 months after completion. Outcome assessment included measures of spiritual well-being, meaning, hopelessness, desire for death, optimism/pessimism, anxiety, depression and overall quality of life. Results MCGP resulted in significantly greater improvements in spiritual well-being and a sense of meaning. Treatment gains were even more substantial (based on effect size estimates) at the second follow-up assessment. Improvements in anxiety and desire for death were also significant (and increased over time). There was no significant improvement on any of these variables for patients participating in SGP. Conclusions MCGP appears to be a potentially beneficial intervention for patients’ emotional and spiritual suffering at the end of life. Further research, with larger samples, is clearly needed to better understand the potential benefits of this novel intervention. PMID:19274623

  8. Leukemia inhibitory factor receptor is a novel immunomarker in distinction of well-differentiated HCC from dysplastic nodules

    PubMed Central

    Wang, Ning; Jin, Guangzhi; Jin, Haojie; Gu, Dishui; Tao, Xuemei; Huo, Xisong; Ge, Tianxiang; Cong, Wenming; Wang, Cun; Qin, Wenxin

    2015-01-01

    Differential diagnosis of well-differentiated hepatocellular carcinoma (WD-HCC) and high-grade dysplastic nodules (HGDNs) represents a challenge for pathologists. Several immunohistochemistry markers have been identified to distinguish hepatocellular carcinoma (HCC) from HGDNs. However, sensitivity or specificity of the individual marker is still limited. In this study, we analyzed dynamic alteration of leukemia inhibitory factor receptor (LIFR) and CD34 during hepatocarcinogenesis from dysplastic nodules to small HCC. The diagnostic performance of LIFR and CD34 combination in WD-HCC and HGDNs was investigated by logistic regression models and validated in an independent validation cohort. LIFR was decreased and CD34 was increased along with stepwise progression of hepatocarcinogenesis from low-grade dysplastic nodules (LGDNs) to small HCC. The sensitivity and specificity of the LIFR and CD34 combination for WD-HCC detection were 93.5% and 90.5%, respectively. In addition, colony formation assay was used to explore the role of LIFR in tumorigenesis. Silencing of LIFR could significantly promote colony formation of HCC cells, whereas ectopic overexpression of LIFR resulted in impaired ability of colony formation of HCC cells. These findings indicate that LIFR and CD34 combination may be used as an available differential diagnostic model for WD-HCC from HGDNs in clinical practice. PMID:25749520

  9. Over expression of hyaluronan promotes progression of HCC via CD44-mediated pyruvate kinase M2 nuclear translocation

    PubMed Central

    Li, Jing-Huan; Wang, Ying-Cong; Qin, Cheng-Dong; Yao, Rong-Rong; Zhang, Rui; Wang, Yan; Xie, Xiao-Ying; Zhang, Lan; Wang, Yan-Hong; Ren, Zheng-Gang

    2016-01-01

    Hyaluronan is expressed in hepatocellular carcinoma (HCC) as HCC generally arises from a cirrhotic liver in which excessive production and accumulation of HA leads to developing cirrhosis. Though it has been suggested HA is involved in progression of HCC, the mechanisms underlying the connection between HA and HCC progression are unclear. Since increased aerobic glycolysis is a metabolic trait of malignant cells and HA-CD44 can modulate glucose metabolism, we aim to investigate the roles of PKM2, a key enzyme in glucose metabolism, in the HA-CD44 axis facilitated the progress of HCC. We shown PKM2 was required for HA-promoted HCC progression, which was not modulated by PKM2 kinase activity but by nuclear translocation of PKM2. PKM2 translocation was Erk (Thr202/Tyr204) phosphorylation dependent, which functioned at the downstream of HA-CD44 binding. Furthermore, elevated HA expression significantly correlated with PKM2 nuclear location and was an independent factors predicting poor HCC prognosis. In conclusions PKM2 nuclear translocation is required for mediating the described HA biological effects on HCC progression and our results imply that inhibition of HA may have therapeutic value in treating HCC. PMID:27186420

  10. [Incidence and Risk Assessment of Tumor Lysis Syndrome in Patients with Advanced Germ Cell Cancer].

    PubMed

    Kurobe, Masahiro; Kawai, Koji; Tanaka, Ken; Ichioka, Daishi; Yoshino, Takayuki; Kandori, Shuya; Kawahara, Takashi; Waku, Natsui; Takaoka, Ei-Ichirou; Kojima, Takahiro; Joraku, Akira; Suetomi, Takahiro; Miyazaki, Jun; Nishiyama, Hiroyuki

    2016-05-01

    Tumor lysis syndrome (TLS) is a major oncological emergency. TLS is common in patients with hematological malignancies, but it can occur across a spectrum of cancer types. Germ cell tumors (GCT) have rapid cancer cell turnover and often present with bulky metastasis. The international TLS expert consensus panel has recommended guidelines for a medical decision tree to assign low, intermediate and high risk to patients with cancer at risk for TLS. GCT is classified as intermediate risk for TLS, and the patients who have other TLS risks factors are classified to be at high risk for TLS. In this study, we retrospectively analyzed 67 patients with metastatic GCT who were treated with induction chemotherapy at Tsukuba University Hospital between 2000 and 2013. Thirty-one, 15 and 21 patients were classified with good-, intermediate- and poor-prognosis disease, respectively, according to the International Germ Cell Cancer Collaborative Group criteria. Twelve patients (18%) were classified to be at high risk for TLS, and two patients were treated with allopurinol or rasburicase as prophylaxes for TLS. They did not show progression to laboratory TLS (L-TLS). In the remaining 10 TLS high-risk patients, three (30%) patients developed L-TLS after chemotherapy and started receiving oral allopurinol. As a result, no patients developed clinical TLS (C-TLS). In this study, 30% of TLS-high risk patients developed L-TLS without prophylactic treatment. Therefore, it is important to conduct TLS-risk stratification and consider prophylaxis such as rasburicase for advanced GCT patients at induction chemotherapy. PMID:27320114

  11. Intermittent outpatient nesiritide infusion reduces hospital admissions in patients with advanced heart failure.

    PubMed

    Schwarz, Ernst R; Najam, Sabeen; Akel, Rami; Sulimanjee, Nasir; Bionat, Susan; Rosanio, Salvatore

    2007-09-01

    Recombinant B-type natriuretic peptide (BNP) is a therapeutic modality in patients with decompensated congestive heart failure. Retrospectively tested are the effects of intermittent outpatient nesiritide infusion on symptoms, hospital readmission rates, endogenous BNP, and renal function in patients with advanced heart failure. Twenty-four patients in heart failure in New York Heart Association (NYHA) classes III-IV received a 6- to 8-hour intermittent nesiritide outpatient infusion (0.01 mcg/kg/min continuously intravenously) once weekly for a total duration of 3 months in addition to standard medical therapy. Data were analyzed retrospectively to compare hospital readmission rates, endogenous BNP levels, blood urea nitrogen, and creatinine levels 1 year before and up to 12 months after starting treatment. All patients tolerated nesiritide infusions well with no significant adverse events. At the end of the observation period, NYHA classes had improved 1 class in 16 patients and 2 classes in 4 patients and remained unchanged in 4 patients. There was a significant reduction in hospital readmissions within 1 year with nesiritide treatment compared with the year before (0.94 +/- 0.8 vs 3.6 +/- 2.2, P < .005). No significant changes were seen regarding endogenous BNP levels (1002 +/- 870 vs 1092 +/- 978 pg/mL, P = .95), blood urea nitrogen levels (45 +/- 28 vs 45 +/- 26 mg/dL, P = .96), and a tendency of slightly elevated creatinine levels that did not differ significantly compared with prior levels (1.76 +/- 0.85 vs 1.1 +/- 0.56 mg/dL, P = .5). Intermittent outpatient nesiritide treatment resulted in improved symptoms and reduced hospital readmission rates without a significant decline in renal function in patients with advanced heart failure but did not alter endogenous BNP levels.

  12. The Experiences of Advanced Practice Nurses Caring for Patients with Substance Use Disorder and Chronic Pain.

    PubMed

    St Marie, Barbara

    2016-10-01

    Management of chronic pain is a challenge shared by healthcare providers in various clinical settings. The epidemic of opioid misuse has escalated this challenge. A gap exists in understanding barriers and facilitators to practices of advanced practice registered nurses (APRNs) caring for patients with chronic pain and substance use disorder (SUD). The purpose of this study was to examine the APRNs' experiences while caring for patients with coexisting SUD and chronic pain to help envision better ways to manage pain and direct educational initiatives. Qualitative narrative method. Telephone interviews. Twenty APRNs caring for patients with coexisting SUD and chronic pain were recruited nationwide through the American Society for Pain Management Nursing list serve. Semistructured interviews with thematic analysis. Participants identified 1) a shift of patients from other healthcare providers into the APRNs' practices; 2) barriers to accessing nonmedical modalities for managing pain, including insurance coverage, geographic location, and the patient's desire for only medication management; 3) the role of the APRN in caring for this population contained subthemes of educating and guiding patients through a process of change, applying risk strategies to keep patients safe, and educating colleagues on implementing risk management strategies while prescribing opioids. The APRNs identified barriers to providing care for patients with coexisting SUD and chronic pain. They also described the role of APRNs in providing focused education regarding risk management strategies for assessment, prescribing opioids to manage pain, and minimizing risk. PMID:27567096

  13. Advancing Patient-centered Outcomes in Emergency Diagnostic Imaging: A Research Agenda.

    PubMed

    Kanzaria, Hemal K; McCabe, Aileen M; Meisel, Zachary M; LeBlanc, Annie; Schaffer, Jason T; Bellolio, M Fernanda; Vaughan, William; Merck, Lisa H; Applegate, Kimberly E; Hollander, Judd E; Grudzen, Corita R; Mills, Angela M; Carpenter, Christopher R; Hess, Erik P

    2015-12-01

    Diagnostic imaging is integral to the evaluation of many emergency department (ED) patients. However, relatively little effort has been devoted to patient-centered outcomes research (PCOR) in emergency diagnostic imaging. This article provides background on this topic and the conclusions of the 2015 Academic Emergency Medicine consensus conference PCOR work group regarding "Diagnostic Imaging in the Emergency Department: A Research Agenda to Optimize Utilization." The goal was to determine a prioritized research agenda to establish which outcomes related to emergency diagnostic imaging are most important to patients, caregivers, and other key stakeholders and which methods will most optimally engage patients in the decision to undergo imaging. Case vignettes are used to emphasize these concepts as they relate to a patient's decision to seek care at an ED and the care received there. The authors discuss applicable research methods and approaches such as shared decision-making that could facilitate better integration of patient-centered outcomes and patient-reported outcomes into decisions regarding emergency diagnostic imaging. Finally, based on a modified Delphi process involving members of the PCOR work group, prioritized research questions are proposed to advance the science of patient-centered outcomes in ED diagnostic imaging. PMID:26574729

  14. Efficacy of prophylactic anti-diarrhoeal treatment in patients receiving Campto for advanced colorectal cancer.

    PubMed

    Duffour, J; Gourgou, S; Seitz, J F; Senesse, P; Boutet, O; Castera, D; Kramar, A; Ychou, M

    2002-01-01

    This study assessed the efficacy of combined prophylactic and curative anti-diarrhoeal medication in advanced colorectal patients treated by irinotecan. Thirty-four pre-treated eligible patients were evaluated. There were 44% women, the median age was 65 and 38% of the patients had a 0 performance status. The patients received sucralfate(4g/d) and nifuroxazide(600 mg/d) prophylactic treatment on days 0-7. In the case of severe diarrhoea, preventive treatment was replaced by loperamide(12 mg/d) and diosmectite (9 g/d). Grade 3 delayed diarrhoea occurred in 18% of patients (90% CI: [9.5-28.9]) and 4.6% of cycles. No grade 4 delayed diarrhoea was observed. Twenty-nine patients (85%) received the preventive treatment at cycle 1, while 14% (90% CI: [6.2-25.7]) experienced grade 3 delayed diarrhoea in 3.7% of cycles for a median 4.5 days. The objective response rate was 8% (90% CI [1.4-23.1]) among the 25 assessable patients. Preventive combined treatment is effective in reducing the incidence of severe delayed diarrhoea, and it should be proposed to patients treated with mono-therapy Campto(r) and evaluated in poly-chemotherapy protocols. PMID:12552984

  15. Home Palliative Care for Patients with Advanced Chronic Kidney Disease: Preliminary Results

    PubMed Central

    Teruel, José L.; Rexach, Lourdes; Burguera, Victor; Gomis, Antonio; Fernandez-Lucas, Milagros; Rivera, Maite; Diaz, Alicia; Collazo, Sergio; Liaño, Fernando

    2015-01-01

    Healthcare for patients with advanced chronic kidney disease (ACKD) on conservative treatment very often poses healthcare problems that are difficult to solve. At the end of 2011, we began a program based on the care and monitoring of these patients by Primary Care Teams. ACKD patients who opted for conservative treatment were offered the chance to be cared for mainly at home by the Primary Care doctor and nurse, under the coordination of the Palliative Care Unit and the Nephrology Department. During 2012, 2013, and 2014, 76 patients received treatment in this program (mean age: 81 years; mean Charlson age-comorbidity index: 10, and mean glomerular filtration rate: 12.4 mL/min/1.73 m2). The median patient follow-up time (until death or until 31 December 2014) was 165 days. During this period, 51% of patients did not have to visit the hospital’s emergency department and 58% did not require hospitalization. Forty-eight of the 76 patients died after a median time of 135 days in the program; 24 (50%) died at home. Our experience indicates that with the support of the Palliative Care Unit and the Nephrology Department, ACKD patients who are not dialysis candidates may be monitored at home by Primary Care Teams. PMID:27417813

  16. [Palliative surgery for malignant bowel obstruction in patients with advanced and recurrent gastroenterological cancer].

    PubMed

    Kitani, Kotaro; Yukawa, Masao; Fujiwara, Yoshinori; Tsujie, Masanori; Hara, Joji; Ikeda, Mitsunori; Sato, Katsuaki; Isono, Sayuri; Kawai, Kenji; Miura, Ken; Watatani, Masahiro; Inoue, Masatoshi

    2013-11-01

    We report the outcomes of palliative surgery for the treatment of malignant bowel obstruction in patients with advanced gastroenterological cancer. We studied 20 patients who had undergone palliative surgery over 3 years. We analyzed the clinical findings, surgical procedure, postoperative clinical course, and prognosis. The origin of the patients was colorectal cancer( 9 cases), gastric cancer( 4 cases), uterine cancer( 3 cases), pancreatic cancer( 2 cases), bladder( 1 case), and anal cancer (1 case). Small bowel obstruction was noted in 8 cases and colorectal obstruction was noted in 14 cases. Colostomy was performed in 13 cases, resection and reconstruction were performed in 6 cases, and bypass was performed in 4 cases. Ninety percent of the patients were able to eat solid food following the surgery, but 20% of the patients were forced to have bowel obstruction. The median survival time after palliative surgery was 3 (range, 0-15) months, and 6 patients (30%) died within 2 months. We concluded that palliative surgery for the treatment of malignant bowel obstruction could improve the patients' quality of life. The decision for performing palliative surgery should be made while considering the patient's prognosis, wishes, and potential for symptom improvement. PMID:24393893

  17. Preoperative docetaxel/cisplatin/5-fluorouracil chemotherapy in patients with locally advanced gastro-esophageal adenocarcinoma.

    PubMed

    Bayraktar, Ulas Darda; Bayraktar, Soley; Hosein, Peter; Chen, Emerson; Koniaris, Leonidas G; Rocha-Lima, Caio Max S; Montero, Alberto J

    2012-09-01

    Perioperative chemotherapy plus surgery improves survival compared to surgery alone in GE junctional (GEJ) and gastric adenocarcinomas. The docetaxel/cisplatin/5-fluorouracil (DCF) combination is superior to CF in patients with metastatic gastric cancer. We retrospectively evaluated the safety and efficacy of preoperative DCF chemotherapy in patients with locally advanced gastric and GEJ cancer. Twenty-one gastric and 10 gastroesophageal junctional (GEJ) cancer patients received 2-3 cycles of preoperative docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) on day 1, 5-FU 750 mg/m(2) (continuous infusion) on days 1-5 every 3 weeks. Clinical response was evaluated by comparing pre- and postchemotherapy CT scans. Overall survival (OS) and progression-free survival (PFS) were calculated from the initiation of chemotherapy. None of the patients achieved complete clinical remission while 11 (35%) patients achieved partial clinical remission. Ten patients with GEJ cancer (100%) and 13 with gastric cancer (62%) underwent curative surgery (P = 0.023). Seventeen (55%) patients experienced grade 3-4 chemotherapy-related adverse events. The most common adverse events were anemia, nausea/vomiting, diarrhea, and febrile neutropenia. At a median follow-up of 17.0 months, median OS and PFS were 26.1 months (95% CI: 22.7-29.5) and 18.8 months (95% CI: 9.9-27.7), respectively. The DCF regimen is active in patients with gastric and GEJ adenocarcinoma in the preoperative setting.

  18. Comparison of bevacizumab plus chemotherapy with chemotherapy alone in advanced non-small-lung cancer patients.

    PubMed

    Tang, Ning; Wang, Zhehai

    2016-01-01

    Bevacizumab plus chemotherapy was approved by the US Food and Drug Administration (FDA) as a first-line treatment for advanced nonsquamous, non-small-cell lung cancer (NSCLC) in 2006. This study retrospectively compared the efficacy of bevacizumab plus chemotherapy with chemotherapy alone as the first-line and second-line treatment as well as the maintenance treatment for advanced NSCLC patients. A total of 1,352 patients were included and we analyzed the efficacy evaluation according to the criteria of the Response Evaluation Criteria In Solid Tumors (RECIST), survival, and adverse reactions. The data showed that for bevacizumab plus chemotherapy as the first-line treatment, the median progression-free survival (mPFS) and median overall survival (mOS) were 11.5 and 17.0 months, respectively, compared to 7.0 and 14 months, respectively, in patients who received chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as maintenance treatment, the mPFS and mOS were 6.0 and 17.4 months, respectively, compared to 3.0 and 15.0 months, respectively, with chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as the second-line treatment, the mPFS was 3.0 months compared to only 2.0 months with chemotherapy alone (P<0.01). The overall responses to the different regimens showed that the remission rate with bevacizumab plus chemotherapy was higher than that with chemotherapy alone (31.8% vs 25.5%, P<0.05), although there was no statistical difference in the disease control rate with either first- or second-line treatment. In conclusion, chemotherapy plus bevacizumab as the first-line and maintenance treatment, led to better curative rates and tolerable adverse reactions compared with chemotherapy alone in advanced NSCLC patients. Bevacizumab combined with cytotoxic drugs was suitable as the second-line treatment for such patients.

  19. Comparison of bevacizumab plus chemotherapy with chemotherapy alone in advanced non-small-lung cancer patients.

    PubMed

    Tang, Ning; Wang, Zhehai

    2016-01-01

    Bevacizumab plus chemotherapy was approved by the US Food and Drug Administration (FDA) as a first-line treatment for advanced nonsquamous, non-small-cell lung cancer (NSCLC) in 2006. This study retrospectively compared the efficacy of bevacizumab plus chemotherapy with chemotherapy alone as the first-line and second-line treatment as well as the maintenance treatment for advanced NSCLC patients. A total of 1,352 patients were included and we analyzed the efficacy evaluation according to the criteria of the Response Evaluation Criteria In Solid Tumors (RECIST), survival, and adverse reactions. The data showed that for bevacizumab plus chemotherapy as the first-line treatment, the median progression-free survival (mPFS) and median overall survival (mOS) were 11.5 and 17.0 months, respectively, compared to 7.0 and 14 months, respectively, in patients who received chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as maintenance treatment, the mPFS and mOS were 6.0 and 17.4 months, respectively, compared to 3.0 and 15.0 months, respectively, with chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as the second-line treatment, the mPFS was 3.0 months compared to only 2.0 months with chemotherapy alone (P<0.01). The overall responses to the different regimens showed that the remission rate with bevacizumab plus chemotherapy was higher than that with chemotherapy alone (31.8% vs 25.5%, P<0.05), although there was no statistical difference in the disease control rate with either first- or second-line treatment. In conclusion, chemotherapy plus bevacizumab as the first-line and maintenance treatment, led to better curative rates and tolerable adverse reactions compared with chemotherapy alone in advanced NSCLC patients. Bevacizumab combined with cytotoxic drugs was suitable as the second-line treatment for such patients. PMID:27536131

  20. A Phase II Trial of the Proteasome Inhibitor Bortezomib in Patients with Advanced Biliary Tract Cancers*

    PubMed Central

    Denlinger, Crystal S.; Meropol, Neal J.; Li, Tianyu; Lewis, Nancy L.; Engstrom, Paul F.; Weiner, Louis M.; Cheng, Jonathan D.; Alpaugh, R. Katherine; Cooper, Harry; Wright, John J.; Cohen, Steven J.

    2014-01-01

    Background Patients with advanced biliary tract cancers have limited therapeutic options. Preclinical data suggest proteasome inhibition may be an effective therapeutic strategy. We thus evaluated the clinical efficacy of bortezomib in advanced biliary tract cancers. Patients and Methods Patients with locally advanced or metastatic cholangiocarcinoma or gallbladder adenocarcinoma who had received 0–2 prior therapies received bortezomib 1.3 mg/m2 days 1, 4, 8, and 11 of a 21-day cycle. The primary endpoint was objective response rate. A Simon two-stage design was employed (null response rate of < 5% and response rate of ≥ 20% of interest). Results Twenty patients enrolled: bile duct/gallbladder cancer (14/6), prior treatments 0/1/2 (10/6/3). The trial was discontinued early due to lack of confirmed partial responses. No unanticipated adverse events were noted. There was one unconfirmed partial response. Ten patients achieved stable disease as best response. Median time to progression was 5.8 months (95% CI 0.7–77.6 months). Median survival was 9 months (95% CI 4.6–18.5 months). The 6-month and 1-year survival rates were 70% and 38%. There was no difference in survival based on primary disease site. Conclusions Single agent bortezomib does not result in objective responses in biliary tract cancers. However, the rate of stable disease and time to progression benchmark is encouraging. Further development of bortezomib in combination with other therapies in this disease setting should be considered. PMID:24512954

  1. A sequential study of serum bacterial DNA in patients with advanced cirrhosis and ascites.

    PubMed

    Francés, Rubén; Benlloch, Susana; Zapater, Pedro; González, José M; Lozano, Beatriz; Muñoz, Carlos; Pascual, Sonia; Casellas, Juan A; Uceda, Francisco; Palazón, José M; Carnicer, Fernando; Pérez-Mateo, Miguel; Such, José

    2004-02-01

    Bacterial translocation is currently considered the main pathogenic mechanism leading to spontaneous bacterial peritonitis in patients with advanced cirrhosis and ascites. However, to the authors' knowledge there is no information regarding the characteristics of this process in humans. The goals of the current study were to pursue partially identified bacterial DNA in blood (what the authors consider molecular evidence of bacterial translocation) through its relative quantification in a 72-hour study period by using real-time polymerase chain reaction (PCR). A consecutive series of 17 patients with advanced cirrhosis and culture-negative, nonneutrocytic ascites were studied. Therapeutic paracentesis was performed at the time of admission, and blood samples were obtained at baseline and every 8 hours in a 3-day period. Bacterial DNA was detected by a PCR-based method, relatively quantified by real-time PCR, and identified by automated nucleotide sequencing. Seven of 17 patients demonstrated the simultaneous presence of bacterial DNA in blood and ascitic fluid at the time of admission. After therapeutic paracentesis was performed, bacterial DNA persisted in the blood for a minimum of 24 hours, and was reported to last as long as 72 hours in some patients. In addition, different patterns of bacterial DNA appearance and clearance from the blood were identified. The nucleotide sequencing process demonstrated that bacteria detected in the first sample were identical to those noted in subsequent detections over time. In conclusion, bacterial translocation is a single-species, dynamic process that appears to develop in a subgroup of patients with advanced cirrhosis.

  2. Comparison of bevacizumab plus chemotherapy with chemotherapy alone in advanced non-small-lung cancer patients

    PubMed Central

    Tang, Ning; Wang, Zhehai

    2016-01-01

    Bevacizumab plus chemotherapy was approved by the US Food and Drug Administration (FDA) as a first-line treatment for advanced nonsquamous, non-small-cell lung cancer (NSCLC) in 2006. This study retrospectively compared the efficacy of bevacizumab plus chemotherapy with chemotherapy alone as the first-line and second-line treatment as well as the maintenance treatment for advanced NSCLC patients. A total of 1,352 patients were included and we analyzed the efficacy evaluation according to the criteria of the Response Evaluation Criteria In Solid Tumors (RECIST), survival, and adverse reactions. The data showed that for bevacizumab plus chemotherapy as the first-line treatment, the median progression-free survival (mPFS) and median overall survival (mOS) were 11.5 and 17.0 months, respectively, compared to 7.0 and 14 months, respectively, in patients who received chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as maintenance treatment, the mPFS and mOS were 6.0 and 17.4 months, respectively, compared to 3.0 and 15.0 months, respectively, with chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as the second-line treatment, the mPFS was 3.0 months compared to only 2.0 months with chemotherapy alone (P<0.01). The overall responses to the different regimens showed that the remission rate with bevacizumab plus chemotherapy was higher than that with chemotherapy alone (31.8% vs 25.5%, P<0.05), although there was no statistical difference in the disease control rate with either first- or second-line treatment. In conclusion, chemotherapy plus bevacizumab as the first-line and maintenance treatment, led to better curative rates and tolerable adverse reactions compared with chemotherapy alone in advanced NSCLC patients. Bevacizumab combined with cytotoxic drugs was suitable as the second-line treatment for such patients. PMID:27536131

  3. Age Disparity in Palliative Radiation Therapy Among Patients With Advanced Cancer

    SciTech Connect

    Wong, Jonathan; Xu, Beibei; Yeung, Heidi N.; Roeland, Eric J.; Martinez, Maria Elena; Le, Quynh-Thu; Mell, Loren K.; Murphy, James D.

    2014-09-01

    Purpose/Objective: Palliative radiation therapy represents an important treatment option among patients with advanced cancer, although research shows decreased use among older patients. This study evaluated age-related patterns of palliative radiation use among an elderly Medicare population. Methods and Materials: We identified 63,221 patients with metastatic lung, breast, prostate, or colorectal cancer diagnosed between 2000 and 2007 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Receipt of palliative radiation therapy was extracted from Medicare claims. Multivariate Poisson regression analysis determined residual age-related disparity in the receipt of palliative radiation therapy after controlling for confounding covariates including age-related differences in patient and demographic covariates, length of life, and patient preferences for aggressive cancer therapy. Results: The use of radiation decreased steadily with increasing patient age. Forty-two percent of patients aged 66 to 69 received palliative radiation therapy. Rates of palliative radiation decreased to 38%, 32%, 24%, and 14% among patients aged 70 to 74, 75 to 79, 80 to 84, and over 85, respectively. Multivariate analysis found that confounding covariates attenuated these findings, although the decreased relative rate of palliative radiation therapy among the elderly remained clinically and statistically significant. On multivariate analysis, compared to patients 66 to 69 years old, those aged 70 to 74, 75 to 79, 80 to 84, and over 85 had a 7%, 15%, 25%, and 44% decreased rate of receiving palliative radiation, respectively (all P<.0001). Conclusions: Age disparity with palliative radiation therapy exists among older cancer patients. Further research should strive to identify barriers to palliative radiation among the elderly, and extra effort should be made to give older patients the opportunity to receive this quality of life-enhancing treatment at the end

  4. Incidence and Predictors of 30-Day Readmission Among Patients Hospitalized for Advanced Liver Disease

    PubMed Central

    BERMAN, KENNETH; TANDRA, SWETA; FORSSELL, KATE; VUPPALANCHI, RAJ; BURTON, JAMES R.; NGUYEN, JAMES; MULLIS, DEVONNE; KWO, PAUL; CHALASANI, NAGA

    2011-01-01

    BACKGROUND & AIMS The rate of readmission to the hospital 30 days after discharge (30-day readmission rate) is used as a quality measure for hospitalized patients, but it has not been studied adequately for patients with advanced liver disease. We investigated the incidence and factors that predict this rate and its relationship with mortality at 90 days. METHODS We analyzed data from patients with advanced liver disease who were hospitalized to an inpatient hepatology service at 2 large academic medical centers in 2008. Patients with elective admission and recipients of liver transplants were not included. During the study period, there were 447 patients and a total of 554 eligible admissions. Multivariate analyses were performed to identify variables associated with 30-day readmission and to examine its relationship with mortality at 90 days. RESULTS The 30-day readmission rate was 20%. After adjusting for multiple covariates, readmission within 30 days was associated independently with model for end-stage liver disease scores at discharge (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02–1.09; P = .002), the presence of diabetes (OR, 1.78; 95% CI, 1.07–2.95; P = .027), and male sex (OR, 1.73; 95% CI, 1.03–2.89; P = .038). After adjusting for age, sex, and model for end-stage liver disease score at discharge, the 90-day mortality rate was significantly higher among patients who were readmitted to the hospital within 30 days than those who were not (26.8% vs 9.8%; OR, 2.6; 95% CI, 1.36 –5.02; P = .004). CONCLUSIONS Patients with advanced liver disease frequently are readmitted to the hospital within 30 days after discharge; these patients have a higher 90-day mortality rate than those who are not readmitted in 30 days. These data might be used to develop strategies to reduce early readmission of hospitalized patients with cirrhosis. PMID:21092762

  5. Molecular pathogenesis of hepatocellular carcinoma and impact of therapeutic advances

    PubMed Central

    Dhanasekaran, Renumathy; Bandoh, Salome; Roberts, Lewis R.

    2016-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and has an increasing incidence worldwide. HCC can be induced by multiple etiologies, is influenced by many risk factors, and has a complex pathogenesis. Furthermore, HCCs exhibit substantial heterogeneity, which compounds the difficulties in developing effective therapies against this highly lethal cancer. With advances in cancer biology and molecular and genetic profiling, a number of different mechanisms involved in the development and progression of HCC have been identified. Despite the advances in this area, the molecular pathogenesis of hepatocellular carcinoma is still not completely understood. This review aims to elaborate our current understanding of the most relevant genetic alterations and molecular pathways involved in the development and progression of HCC, and anticipate the potential impact of future advances on therapeutic drug development. PMID:27239288

  6. Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma

    PubMed Central

    Kato, Hiroyuki; Yoshida, Hideo; Taniguch, Hiroyoshi; Nomura, Ryutaro; Sato, Kengo; Suzuki, Ichiro; Nakata, Ryo

    2015-01-01

    AIM: To investigate the safety and efficacy of the Cyberknife treatment for patients with advanced or terminal stage hepatocellular carcinoma (HCC). METHODS: Patients with HCC with extrahepatic metastasis or vascular or bile duct invasion were enrolled between May 2011 and June 2015. The Cyberknife was used to treat each lesion. Treatment response scores were based on Response Evaluation Criteria in Solid Tumors v1.1. The trends of tumor markers, including alpha fetoprotein (AFP) and proteins induced by vitamin K absence II (PIVKA II) were assessed. Prognostic factors for tumor response and tumor markers were evaluated with Fisher’s exact test and a logistic regression model. Survival was evaluated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Sixty-five patients with 95 lesions were enrolled. Based on the Barcelona Clinic Liver Cancer classification, all patients were either in the advanced or terminal stage of the disease. The target lesions were as follows: 52 were bone metastasis; 9, lung metastasis; 7, brain metastasis; 9, portal vein invasion; 4, hepatic vein invasion; 4, bile duct invasion; and 10 other lesion types. The response rate and disease control rate were 34% and 53%, respectively. None of the clinical factors correlated significantly with tumor response. Fiducial marker implantation was associated with better control of both AFP (HR = 0.152; 95%CI: 0.026-0.887; P = 0.036) and PIVKA II (HR = 0.035; 95%CI: 0.003-0.342; P = 0.004). The median survival time was 9 mo (95%CI: 5-15 mo). Terminal stage disease (HR = 9.809; 95%CI: 2.589-37.17, P < 0.001) and an AFP of more than 400 ng/mL (HR = 2.548; 95%CI: 1.070-6.068, P = 0.035) were associated with worse survival. A radiation dose higher than 30 Gy (HR = 0.274; 95%CI: 0.093-0.7541, P = 0.012) was associated with better survival. In the 52 cases of bone metastasis, 36 patients (69%) achieved pain relief. One patient had cerebral

  7. Mechanisms Underpinning Increased Plasma Creatinine Levels in Patients Receiving Vemurafenib for Advanced Melanoma

    PubMed Central

    Hurabielle, Charlotte; Pillebout, Evangéline; Stehlé, Thomas; Pagès, Cécile; Roux, Jennifer; Schneider, Pierre; Chevret, Sylvie; Chaffaut, Cendrine; Boutten, Anne; Mourah, Samia; Basset-Seguin, Nicole; Vidal-Petiot, Emmanuelle; Lebbé, Céleste; Flamant, Martin

    2016-01-01

    Context Serum creatinine has been reported to increase in patients receiving Vemurafenib, yet neither the prevalence nor the mechanism of this adverse event are known. Objective We aimed to evaluate the frequency and the mechanisms of increases in plasma creatinine level in patients receiving Vemurafenib for advanced melanoma. Methods We performed a retrospective monocentric study including consecutive patients treated with Vemurafenib for an advanced melanoma. We collected clinical and biological data concerning renal function before introduction of Vemurafenib and in the course of monthly follow-up visits from March 2013 to December 2014. Cystatin C-derived glomerular filtration rate was evaluated before and after Vemurafenib initiation, as increase in serum cystatin C is specific to a decrease in the glomerular filtration rate. We also performed thorough renal explorations in 3 patients, with measurement of tubular secretion of creatinine before and after Vemurafenib initiation and a renal biopsy in 2 patients. Results 70 patients were included: 97% of them displayed an immediate, and thereafter stable, increase in creatinine (+22.8%) after Vemurafenib initiation. In 44/52 patients in whom Vemurafenib was discontinued, creatinine levels returned to baseline. Serum cystatin C increased, although proportionally less than serum creatinine, showing that creatinine increase under vemurafenib was indeed partly due to a renal function impairment. In addition, renal explorations demonstrated that Vemurafenib induced an inhibition of creatinine tubular secretion. Conclusion Thus, Vemurafenib induces a dual mechanism of increase in plasma creatinine with both an inhibition of creatinine tubular secretion and slight renal function impairment. However, this side effect is mostly reversible when Vemurafenib is discontinued, and should not lead physicians to discontinue the treatment if it is effective. PMID:26930506

  8. EXCESS MORTALITY IN PATIENTS WITH ADVANCED CHRONIC HEPATITIS C TREATED WITH LONG-TERM PEGINTERFERON

    PubMed Central

    Di Bisceglie, Adrian M.; Stoddard, Anne M.; Dienstag, Jules L.; Shiffman, Mitchell L.; Seeff, Leonard B.; Bonkovsky, Herbert L.; Morishima, Chihiro; Wright, Elizabeth C.; Snow, Kristin K.; Lee, William M.; Fontana, Robert J.; Morgan, Timothy R.; Ghany, Marc G.

    2011-01-01

    Background/Aims Chronic hepatitis C virus infection can cause chronic liver disease, cirrhosis and liver cancer. The HALT-C Trial was a prospective, randomized controlled study of long-term, low-dose peginterferon therapy in patients with advanced chronic hepatitis C who had failed to respond to a previous course of optimal antiviral therapy. The aim of this follow-up analysis was to describe the frequency and causes of death among this cohort of patients. Methods Deaths occurring during and after the HALT-C Trial were reviewed by a committee of investigators to determine the cause of death and to categorize each death as liver- or non-liver-related and as related or not to complications of peginterferon. Rates of liver transplantation were also assessed. Results Over a median of 5.7 years, 122 deaths occurred among 1,050 randomized patients (12%) of which 76 were considered liver-related (62%) and 46 non-liver-related (38%); 74 patients (7%) underwent liver transplantation. At 7 years, the cumulative mortality rate was higher in the treatment compared to the control group (20% versus 15%, p=0.049); the primary difference in mortality was in patients in the fibrosis compared to the cirrhosis stratum (14% versus 7%, p=0.01); comparable differences were observed when liver transplantation was included. Excess mortality, emerging after 3 years of treatment, was related largely to non-liver-related death; liver-related mortality was similar in the treatment and control groups. No specific cause of death accounted for the excess mortality, and only one death was suspected to be a direct complication of peginterferon. Conclusions Long-term maintenance peginterferon in patients with advanced chronic hepatitis C is associated with an excess overall mortality, which was primarily due to non-liver-related causes among patients with bridging fibrosis. PMID:21480316

  9. Challenges and Management of Liver Cirrhosis: Practical Issues in the Therapy of Patients with Cirrhosis due to NAFLD and NASH.

    PubMed

    Traussnigg, Stefan; Kienbacher, Christian; Halilbasic, Emina; Rechling, Christian; Kazemi-Shirazi, Lili; Hofer, Harald; Munda, Petra; Trauner, Michael

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and comprises a liver disease spectrum ranging from steatosis to nonalcoholic steatohepatitis (NASH) with risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Associated metabolic conditions and comorbidities such as obesity, diabetes and cardiovascular diseases are common and require concerted management. Adiponutrin (PNPLA3) variants may help to identify NAFLD patients at higher risk for liver disease progression towards advanced fibrosis and HCC. The therapeutic options in NAFLD/NASH include lifestyle modification, pharmacological treatment, bariatric surgery for patients with morbid obesity and treatment of complications of liver cirrhosis and HCC, including liver transplantation. Insulin sensitizers and antioxidative treatment strategies with vitamin E are among the best-established pharmacological approaches, but both drugs have long-term safety issues and there is limited evidence in cirrhotic patients. Treatment of concomitant/underlying metabolic conditions with statins or metformin may also have beneficial effects on portal hypertension, complications of liver cirrhosis and HCC prevention. The bile acid receptor FXR may be a promising novel therapeutic target for the treatment of NAFLD/NASH, fibrosis and portal hypertension, but the prognostic implications of associated changes in low- and high-density lipoprotein cholesterol require further studies. Morbidly obese NASH patients can benefit from bariatric surgery which may reduce liver fibrosis but carries a risk of decompensation in patients with advanced liver cirrhosis. When carefully selected, patients with NASH cirrhosis undergoing liver transplantation have a good outcome. This review summarizes recent progress in the management of patients with liver cirrhosis due to NASH. PMID:26159280

  10. Challenges and Management of Liver Cirrhosis: Practical Issues in the Therapy of Patients with Cirrhosis due to NAFLD and NASH.

    PubMed

    Traussnigg, Stefan; Kienbacher, Christian; Halilbasic, Emina; Rechling, Christian; Kazemi-Shirazi, Lili; Hofer, Harald; Munda, Petra; Trauner, Michael

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and comprises a liver disease spectrum ranging from steatosis to nonalcoholic steatohepatitis (NASH) with risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Associated metabolic conditions and comorbidities such as obesity, diabetes and cardiovascular diseases are common and require concerted management. Adiponutrin (PNPLA3) variants may help to identify NAFLD patients at higher risk for liver disease progression towards advanced fibrosis and HCC. The therapeutic options in NAFLD/NASH include lifestyle modification, pharmacological treatment, bariatric surgery for patients with morbid obesity and treatment of complications of liver cirrhosis and HCC, including liver transplantation. Insulin sensitizers and antioxidative treatment strategies with vitamin E are among the best-established pharmacological approaches, but both drugs have long-term safety issues and there is limited evidence in cirrhotic patients. Treatment of concomitant/underlying metabolic conditions with statins or metformin may also have beneficial effects on portal hypertension, complications of liver cirrhosis and HCC prevention. The bile acid receptor FXR may be a promising novel therapeutic target for the treatment of NAFLD/NASH, fibrosis and portal hypertension, but the prognostic implications of associated changes in low- and high-density lipoprotein cholesterol require further studies. Morbidly obese NASH patients can benefit from bariatric surgery which may reduce liver fibrosis but carries a risk of decompensation in patients with advanced liver cirrhosis. When carefully selected, patients with NASH cirrhosis undergoing liver transplantation have a good outcome. This review summarizes recent progress in the management of patients with liver cirrhosis due to NASH.

  11. Distribution of KRAS and BRAF mutations in Moroccan patients with advanced colorectal cancer.

    PubMed

    Marchoudi, N; Amrani Hassani Joutei, H; Jouali, F; Fekkak, J; Rhaissi, H

    2013-12-01

    Targeted therapies have an increasing importance in digestive oncology. To our knowledge, we are the first to report the distribution of KRAS and BRAF mutations in Moroccan patients with advanced colorectal cancer (CRC) in order to introduce targeted therapy in the arsenal of therapeutic modalities for management of this cancer in Morocco. In this study, 92 samples obtained from patients with CRC were tested for the presence of the nine most common mutations in the KRAS gene and BRAF gene. Among the tested patients, 76.09% of patients had wt-KRAS genotype and 23.91% were KRAS mutants and the majority of mutations would result in an amino acid substitution of glycine by aspartic acid (68.2%) The predominant mutations are G>A transitions and G>T transversions. Around 5% (5.43%) of the tested patients bore the V600E mutation in BRAF gene. Only one patient showing to have the V600E mutation in BRAF was also mutated-KRAS. Summing up the results about the KRAS and the BRAF mutation carriers from our study, the portion of potentially non responsive patients for the anti-EGFR treatment is 28.26%.

  12. 89Zr-cetuximab PET imaging in patients with advanced colorectal cancer

    PubMed Central

    Huisman, Marc C.; Vugts, Danielle J.; Roth, Chantal; Luik, Anne Marije; Mulder, Emma R.; Schuit, Robert C.; Boellaard, Ronald; Hoekstra, Otto S.; van Dongen, Guus AMS; Verheul, Henk M.W.

    2015-01-01

    Monoclonal antibodies (mAbs) against the epidermal growth factor receptor (EGFR) are used in the treatment of advanced colorectal cancer (mCRC). Approximately 50% of patients benefit despite patient selection for RAS wild type (wt) tumors. Based on the hypothesis that tumor targeting is required for clinical benefit of anti-EGFR treatment, biodistribution and tumor uptake of 89Zr-cetuximab by Positron Emission Tomography (PET), combining the sensitivity of PET with the specificity of cetuximab for EGFR was evaluated. Ten patients with wt K-RAS mCRC received 37 ± 1 MBq 89Zr-cetuximab directly (<2 h) after the first therapeutic dose of cetuximab. PET-scans were performed from 1 hour to 10 days post injection (p.i.). Biodistribution was determined for blood and organs. Uptake in tumor lesions was quantified by Standardized Uptake Value (SUV) and related to response. In 6 of 10 patients 89Zr-cetuximab uptake in tumor lesions was detected. Four of 6 patients with 89Zr-cetuximab uptake had clinical benefit, while progressive disease was observed in 3 of 4 patients without 89Zr-cetuximab uptake. Taken together, tumor uptake of 89Zr-cetuximab can be visualized by PET imaging. The strong relation between uptake and response warrants further clinical validation as an innovative selection method for cetuximab treatment in patients with wt RAS mCRC. PMID:26309164

  13. 89Zr-cetuximab PET imaging in patients with advanced colorectal cancer.

    PubMed

    Menke-van der Houven van Oordt, Catharina Willemien; Gootjes, Elske C; Huisman, Marc C; Vugts, Danielle J; Roth, Chantal; Luik, Anne Marije; Mulder, Emma R; Schuit, Robert C; Boellaard, Ronald; Hoekstra, Otto S; van Dongen, Guus Ams; Verheul, Henk M W

    2015-10-01

    Monoclonal antibodies (mAbs) against the epidermal growth factor receptor (EGFR) are used in the treatment of advanced colorectal cancer (mCRC). Approximately 50% of patients benefit despite patient selection for RAS wild type (wt) tumors. Based on the hypothesis that tumor targeting is required for clinical benefit of anti-EGFR treatment, biodistribution and tumor uptake of (89)Zr-cetuximab by Positron Emission Tomography (PET), combining the sensitivity of PET with the specificity of cetuximab for EGFR was evaluated. Ten patients with wt K-RAS mCRC received 37 ± 1 MBq (89)Zr-cetuximab directly (<2 h) after the first therapeutic dose of cetuximab. PET-scans were performed from 1 hour to 10 days post injection (p.i.). Biodistribution was determined for blood and organs. Uptake in tumor lesions was quantified by Standardized Uptake Value (SUV) and related to response. In 6 of 10 patients (89)Zr-cetuximab uptake in tumor lesions was detected. Four of 6 patients with (89)Zr-cetuximab uptake had clinical benefit, while progressive disease was observed in 3 of 4 patients without (89)Zr-cetuximab uptake. Taken together, tumor uptake of 89Zr-cetuximab can be visualized by PET imaging. The strong relation between uptake and response warrants further clinical validation as an innovative selection method for cetuximab treatment in patients with wt RAS mCRC.

  14. Cancer Related Fatigue and Quality of Life in Patients with Advanced Prostate Cancer Undergoing Chemotherapy

    PubMed Central

    Charalambous, Andreas; Kouta, Christiana

    2016-01-01

    Cancer related fatigue (CRF) is a common and debilitating symptom that can influence quality of life (QoL) in cancer patients. The increase in survival times stresses for a better understanding of how CRF affects patients' QoL. This was a cross-sectional descriptive study with 148 randomly recruited prostate cancer patients aiming to explore CRF and its impact on QoL. Assessments included the Cancer Fatigue Scale, EORTC QLQ-C30, and EORTC QLQ-PR25. Additionally, 15 in-depth structured interviews were performed. Quantitative data were analyzed with simple and multiple regression analysis and independent samples t-test. Qualitative data were analyzed with the use of thematic content analysis. The 66.9% of the patients experienced CRF with higher levels being recorded for the affective subscale. Statistically significant differences were found between the patients reporting CRF and lower levels of QoL (mean = 49.1) and those that did not report fatigue and had higher levels of QoL (mean = 72.1). The interviews emphasized CRF's profound impact on the patients' lives that was reflected on the following themes: “dependency on others,” “loss of power over decision making,” and “daily living disruption.” Cancer related fatigue is a significant problem for patients with advanced prostate cancer and one that affects their QoL in various ways. PMID:26981530

  15. Health, economic, psychological and social impact of educating carers of patients with advanced pulmonary disease (protocol).

    PubMed

    Sladek, R M; Jones, T; Phillips, P A; Luszcz, M; Rowett, D; Eckermann, S; Woodman, R J; Frith, P

    2011-09-01

    People with advanced pulmonary disease (APD), such as those with chronic obstructive pulmonary disease, have markedly impaired quality of life. Home Oxygen Therapy (HOT) itself is burdensome, although it often improves survival duration and quality of life in these patients. The exact burdens on informal caregivers of these patients are unknown. The central purpose of the pragmatic randomized controlled study described in this protocol is to determine the effectiveness of improving the skills and knowledge of carers of patients with APD who use HOT. Specifically we aimed to estimate the incremental impact of this carer intervention above usual care on health, economic, psychological and social domains for patient and carer dyads relative to the level of current burden. Eligible patients and their carers were recruited through three major hospitals, and randomized to an intervention or control group. The carers in the intervention group received two home-delivered education sessions based on the principles of academic detailing. Participants are currently being followed over 12 months. The primary outcome will be the proportion of patients surviving without a chronic obstructive pulmonary disease-related readmission / residential (non respite) care over 12 months. Carer secondary outcomes include perceived caregiver burden, level of expected and received social support, perceived level of mastery, self esteem, health related quality of life and disability, and ability to conduct domestic chores and household maintenance, social activities and provide service to others, and fatigue. Secondary patient outcomes include health related quality of life and disability, and current respiratory health status.

  16. Evaluation of ExPress glaucoma filtration device in Indian patients with advanced glaucoma.

    PubMed

    Angmo, Dewang; Sharma, Reetika; Temkar, Shreyas; Dada, Tanuj

    2015-05-01

    ExPress glaucoma filtration device (GFD) has recently become available in India as a surgical option for glaucoma patients. We retrospectively evaluated the outcome of ExPress GFD in 12 eyes with advanced glaucoma with intraocular pressures (IOPs) not controlled on maximal tolerable medical therapy. The mean preoperative IOP of 29.58 ± 7.13 mmHg decreased to 17.0 ± 2.67 and 17.40 ± 0.89 mmHg at 6 and 12 months after surgery. Absolute success (IOP ≤ 18 mmHg, with no additional glaucoma medications) was achieved in eight cases (66.7%) and qualified success (IOP ≤ 18 mmHg, with additional glaucoma medications) in two cases (16.7%) at 1-year after surgery. Early intervention was needed in 4 patients; two underwent anterior chamber reformation while the other two required needling. Two patients required resurgery. There was no significant change in the best corrected visual acuity postoperatively (P = 0.37). ExPress GFD does not seem to offer a benefit over standard trabeculectomy in patients with advanced glaucomatous disease in terms of IOP control or complication rate. However, due to the small sample size with a heterogeneous mixture of primary and secondary glaucoma's, we await further studies with a larger sample size and long-term follow-up, to see how the device performs.

  17. Assessment of anxiety and depression in advanced cancer patients and their relationship with quality of life.

    PubMed

    Mystakidou, K; Tsilika, E; Parpa, E; Katsouda, E; Galanos, A; Vlahos, L

    2005-10-01

    The growing interest in the mental health and quality of life of cancer patients, has been the major reason for conducting this study. The aims were to compare advanced cancer patients' responses to Hospital Anxiety and Depression (HAD) scale with those to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30, version 3.0), as well as the impact of quality of life dimensions (as measured by EORTC QLQ-C30) on the levels of anxiety and depression. The analysis, conducted in 120 advanced cancer patients, showed that the most significant associations were found between emotional functioning and HAD-T (total sum of scores) (r=-0.747; p < 0.0005), HAD-A (anxiety) (r=-0.725; p < 0.0005) and HAD-D (depression) (r=-0.553; p < 0.0005). In the prediction of HAD-T, the contribution of physical, emotional, role, and social functioning along with nausea-vomiting, dyspnea, sleep disturbance and gender is high. For anxiety, the predictor variables were physical, role, cognitive, emotional, and social functioning, followed by dyspnea, sleep disturbance, and appetite loss, while depression was predicted by physical, role, emotional, and social functioning, the symptoms of nausea-vomiting, pain, sleep disturbance, constipation, as well as the variables of age, gender, anticancer treatment and performance status. Concluding, psychological morbidity, in this patient population, was predominantly predicted by the emotional functioning dimension of EORTC QLQ-C30. PMID:16155770

  18. Evaluation of ExPress glaucoma filtration device in Indian patients with advanced glaucoma

    PubMed Central

    Angmo, Dewang; Sharma, Reetika; Temkar, Shreyas; Dada, Tanuj

    2015-01-01

    ExPress glaucoma filtration device (GFD) has recently become available in India as a surgical option for glaucoma patients. We retrospectively evaluated the outcome of ExPress GFD in 12 eyes with advanced glaucoma with intraocular pressures (IOPs) not controlled on maximal tolerable medical therapy. The mean preoperative IOP of 29.58 ± 7.13 mmHg decreased to 17.0 ± 2.67 and 17.40 ± 0.89 mmHg at 6 and 12 months after surgery. Absolute success (IOP ≤ 18 mmHg, with no additional glaucoma medications) was achieved in eight cases (66.7%) and qualified success (IOP ≤ 18 mmHg, with additional glaucoma medications) in two cases (16.7%) at 1-year after surgery. Early intervention was needed in 4 patients; two underwent anterior chamber reformation while the other two required needling. Two patients required resurgery. There was no significant change in the best corrected visual acuity postoperatively (P = 0.37). ExPress GFD does not seem to offer a benefit over standard trabeculectomy in patients with advanced glaucomatous disease in terms of IOP control or complication rate. However, due to the small sample size with a heterogeneous mixture of primary and secondary glaucoma's, we await further studies with a larger sample size and long-term follow-up, to see how the device performs. PMID:26139813

  19. Current therapeutic strategies of anti-HER2 treatment in advanced breast cancer patients

    PubMed Central

    Nowara, Elżbieta

    2016-01-01

    The HER2/neu (ERBB2) oncogene is amplified and/or overexpressed in approximately 20% of breast cancers, and is a strong prognostic factor for relapse and poor overall survival, particularly in node-positive patients. It is also an important predictor for response to trastuzumab, which has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. Treatment with the anti-HER2 humanized monoclonal antibody – trastuzumab significantly improves progression-free and overall survival among patients with HER2-positive breast cancer. However, in most patients with HER2-positive metastatic breast cancer, the disease progresses occurred, what cause the need for new targeted therapies for advanced disease. In clinical trials, there are tested new drugs to improve the results of treatment for this group of patients. This paper presents new drugs introduced into clinical practice for treatment of advanced breast cancer, whose molecular target are receptors of the HER2 family. In addition, new therapeutic strategies and drugs that are currently in clinical researches are discussed. PMID:27095932

  20. Needs of family caregivers of advanced cancer patients: a survey in Shanghai of China.

    PubMed

    Cui, J; Song, L J; Zhou, L J; Meng, H; Zhao, J J

    2014-07-01

    It is important to understand the unmet needs of family caregivers of advanced cancer patients for developing and refining services to address the identified gaps in cancer care. To explore their needs in Chinese mainland and the possible factors associated with their needs, a self-developed questionnaire was used to survey a sample of 649 participants in 15 hospitals of Shanghai. The data were analysed using descriptive statistics, factor analysis, t-test, one-way ANOVA, and Fishers least significant difference t-test. All statistical analyses were performed using SPSS 13.0. Seven dimensions of needs (maintaining health, support from healthcare professionals, knowledge about the disease and treatment, support on funeral, information on hospice care, psychological support for patients and symptoms control for patients) were extracted from the results by factor analysis. The dimension with the highest score was 'knowledge about the disease and treatment' (4.37), and that with the lowest score named 'support on funeral' (2.85). The results showed that the factors including burden of payment for treatment, former caregiving experience of family caregivers and length of caregiving time were associated with their needs. Cancer services need to consider how to tailor resources and interventions to meet these needs of family caregivers of advanced cancer patients.

  1. Refeeding syndrome in a patient with advanced kidney failure due to nephronophthisis.

    PubMed

    El-Reshaid, Kamel

    2013-11-01

    Refeeding syndrome (RS) is a serious and potentially fatal disorder. It is caused by a shift of fluids, sodium, potassium, magnesium and phosphorus as well changes in the metabolism of glucose, protein, fat and vitamins following the refeeding of malnourished patients, whether enterally or parenterally. RS has rarely been reported in patients with advanced kidney disease probably due to the pre-existing hyperphosphatemia, hypermagnesemia and hyperkalemia in these patients. In the following report, we present a patient with nephronophthisis type 1 deletion syndrome in whom her main previous nutrition was limited to simply rehydration to avoid renal replacement therapy. On presentation, she was cachectic and dehydrated with advanced kidney failure. She was treated with medical nephrectomy using non-steroidal anti-inflammatory drugs and then placed on maintenance hemodialysis. Percutaneous endoscopic gastrostomy was used for her initial feeding. Care was exercised during her early refeeding with regard to correction of fluids and essential electrolytes, viz. potassium, phosphorus and magnesium, as well as multivitamins to avoid the cardiovascular and neurological complications of RS. However, the changes in the gut, pancreas and liver as well as her hyperlipidemia were a clear obstacle. Fortunately, the ileus and pancreatitis she developed on refeeding improved dramatically with a decrease of the feeding dose to half; however, the liver abnormalities and hyperlipidemia were severe and slow to recover. These improved after addition of ursodeoxycholic acid and permitted successful increase of the dose of feeding subsequently.

  2. Trends in the Aggressiveness of End-of-Life Care for Advanced Stomach Cancer Patients

    PubMed Central

    Hong, Ji Hyung; Rho, Sang-Young

    2013-01-01

    Purpose It is important to balance the appropriateness of active cancer treatments and end-of-life care to improve the quality of life for terminally ill cancer patients. This study describes the treatment patterns and end-of-life care in terminal gastric cancer patients. Materials and Methods We retrospectively analyzed the records of 137 patients with advanced gastric cancer receiving chemotherapy and dying between June 1, 2006 and May 31, 2011. We recorded interval between last chemotherapy dose and death; frequency of emergency room visits or admission to the intensive care unit in the last month before death; rate of hospice referral and agreement with written do-not-resuscitate orders; and change in laboratory values in the last three months before death. Results During the last six months of life, 130 patients (94.9%) received palliative chemotherapy; 86 (62.7%) during the final two months; 41 (29.9%) during the final month. During the final month, 53 patients (38.7%) visited an emergency room more than once; 21 (15.3%) were admitted to the intensive care unit. Hospice referral occurred in 54% (74 patients) of the patients; 93.4% (128 patients) gave written do-not-resuscitate orders. Platelets, aspartate aminotransferase and creatinine changed significantly two weeks before death; total bilirubin, one month before; and C-reactive protein, between four and two weeks before death. Conclusion Our results demonstrated that a significant proportion of gastric cancer patients received palliative chemotherapy to the end of life and the patients who stopped the chemotherapy at least one month before death had a lower rate of intensive care unit admission and longer overall survival than those who sustained aggressive chemotherapy until the last months of their lives. PMID:24453999

  3. Clinical profile of patients with advanced age and inflammatoric dilated cardiomyopathy on endomyocardial biopsy

    PubMed Central

    Ohlow, Marc-Alexander; Chen, Ting-Hui; Schmidt, Andreas; Saenger, Joerg; Lauer, Bernward

    2015-01-01

    Background Endomyocardial biopsy (EMB) is an important tool when patients with inflammatoric cardiomyopathy (DCMi) are evaluated. We aimed to assess the clinical profile of elderly patients with DCMi on EMB. Methods Retrospective study of all consecutive patients hospitalized from January 2007 to December 2011 with clinical suspicion of DCMi undergoing EMB. Patients with evidence of DCMi on EMB (Group 1 ≥ 70 years, n = 85; Group 3 < 70 years; n = 418) were compared to patients of the same age group without evidence of DCMi on EMB (Group 2 ≥ 70 years, n = 45; Group 4 < 70 years; n = 147). Results Among 24,275 patients treated at our institution during the study period, 695 had clinical suspicion of DCMi and underwent EMB; 503 (2.1%) patients had DCMi on EMB. There were more male patients in Group 1, mean age was 74 ± 2.8 years, mean ejection fraction was 38% ± 14%. On presentation, signs of hemodynamic compromise (NYHA functional class III/IV, low cardiac output/index, and low cardiac power index) were more frequent in Group 1. EMB revealed viral genome in 78% of the patients, parvovirus B19 (PVB) was frequently encountered in both age groups (Group 1: 69.4% vs. Group 2: 59.6%); detection of more than one viral genome was more frequent in Group 1 (21.2% vs. 11.2%; P = 0.02) whereas the extent of immune response was significantly lower in individuals with advanced age. Conclusions In patients ≥ 70 years with DCMi on EMB signs of hemodynamic compromise, detection of multiple viral genomes together with an overall lower extent of immune response were more frequently observed. PMID:26788036

  4. Outcome of unilateral pallidotomy in advanced Parkinson's disease: cohort study of 32 patients

    PubMed Central

    de Bie, R M A; Schuurman, P; Bosch, D; de Haan, R J; Schmand, B; Speelman, J

    2001-01-01

    OBJECTIVES—In a randomised trial to study the efficacy of unilateral pallidotomy in patients with advanced Parkinson's disease, patients having pallidotomy within 1 month after randomisation were compared with patients having pallidotomy 6 months after the primary outcome assessment. Of the 37 patients enrolled 32 had a unilateral pallidotomy. The follow up study of these patients is presented to report (1) clinical outcome; (2) adverse effects; (3) cognitive and behavioural effects; (4) relation between lesion location and outcome; and (5) preoperative patient characteristics predictive for good outcome.
METHODS—Outcome measures were the motor section of the unified Parkinson's disease rating scale (UPDRS), levodopa induced dyskinesias, disability, quality of life, and a comprehensive neuropsychological assessment. Multivariate logistic regression was used to identify preoperative patient characteristics independently associated with good outcome.
RESULTS—Off phase assessment showed a reduction in parkinsonism from 49 to 36.5 points on the UPDRS 6 months after surgery. Improvements were also demonstrated for activities of daily living and quality of life. In the on phase dyskinesias were reduced. All effects lasted up to 12 months after surgery. Three patients had major permanent adverse effects. Besides worsening of verbal fluency after left sided surgery, systematic cognitive deterioration was not detected. Patients taking less than 1000 levodopa equivalent units (LEU)/day were more likely to improve.
CONCLUSIONS—The positive effects of unilateral pallidotomy are stable up to 1 year after surgery. Patients taking less than 1000 LEU per day were most likely to improve.

 PMID:11511714

  5. [The quality of life after chemotherapy in advanced non-small cell lung cancer patients].

    PubMed

    Słowik-Gabryelska, A; Szczepanik, A; Kalicka, A

    1999-01-01

    The intensity of complains, short survival and great number of patients makes many oncologists to apply chemotherapy in advanced non-small cell lung cancer/NSCLC/. The achieved median duration of life after chemotherapy was 6 to 12 month. From the other hand non small cell lung cancer chemotherapy is a big burden even to healthy persons. It can worsen the quality of life. That was the reason we evaluated the quality of life after chemotherapy in advanced non small cell lung cancer patients. Taking into account, that the evaluation of quality of life, used in most diseases is useless in advanced NSCLC patients, for appreciation the quality of life in these cases the lung cancer symptoms scale/LCSS/was adopted. In 110 non small cell lung cancer patients in stage IIIB and IV, who received combined chemotherapy by Le Chevalier/Vindesine, Cisplatin, Cyclophosphamide, Lomustin/or by Rosell/Mitomycin, Cyclophosphamide, Cisplatin/the quality of life was evaluated. In 20-persons control group all patients received the symptomatic treatment. In observed group of 110 patients, tumor regressions after 4 courses of chemotherapy allowed to resect cancer in 14 cases, to apply radiotherapy in 42 and to continue chemiotherapy in 23 persons. In every person from above mentioned group the quality of life was evaluated on the basis of intensity of cancer symptoms, accordingly to LCSS. The intensity of cancer symptoms was compared before and after treatment. There were compared; the innensity of complains, weakness, appetite, malnutrition, and hematological, neurological, performans state as well as respiratory sufficiency, infections, cardiac disorders and pain. Apart it, the side effects of applied therapy were assessed in 5 degree scale. The level of hemoglobin, the number of leucocytes, thrombocytes, bilirubine and transaminases in peripheral blood, hematurie, proteinurie, bleedings, appetite, nausea, vomitings, diarrhea, mucosal lesions, infections, skin lesions, cardiac lesions

  6. A proposed predictive model for advanced fibrosis in patients with chronic hepatitis B and its validation.

    PubMed

    Nishikawa, Hiroki; Hasegawa, Kunihiro; Ishii, Akio; Takata, Ryo; Enomoto, Hirayuki; Yoh, Kazunori; Kishino, Kyohei; Shimono, Yoshihiro; Iwata, Yoshinori; Nakano, Chikage; Nishimura, Takashi; Aizawa, Nobuhiro; Sakai, Yoshiyuki; Ikeda, Naoto; Takashima, Tomoyuki; Iijima, Hiroko; Nishiguchi, Shuhei

    2016-08-01

    We created a predictive model using serum-based biomarkers for advanced fibrosis (F3 or more) in patients with chronic hepatitis B (CHB) and to confirm the accuracy in an independent cohort.A total of 249 CHB patients were analyzed. To achieve our study aim, a training group (n = 125) and a validation group (n = 124) were formed. In the training group, parameters related to the presence of advanced fibrosis in univariate and multivariate analyses were examined, and a formula for advanced fibrosis was created. Next, we verified the applicability of the predictive model in the validation group.Multivariate analysis identified that gamma-glutamyl transpeptidase (GGT, P = 0.0343) and platelet count (P = 0.0034) were significant predictors of the presence of advanced fibrosis, while Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA-M2BP, P = 0.0741) and hyaluronic acid (P = 0.0916) tended to be significant factors. Using these 4 parameters, we created the following formula: GMPH score = -0.755 - (0.015 × GGT) - (0.268 × WFA-M2BP) + (0.167 × platelet count) + (0.003 × hyaluronic acid). In 8 analyzed variables (WFA-M2BP, aspartate aminotransferase-to-platelet ratio index, FIB-4 index, prothrombin time, platelet count, hyaluronic acid, Forns index, and GMPH score), GMPH score had the highest area under the receiver operating characteristic (AUROC) curve for advanced fibrosis with a value of 0.8064 in the training group and in the validation group, GMPH score also had the highest AUROC (0.7782). In all subgroup analyses of the hepatitis B virus (HBV) status (HB surface antigen quantification, HBV-DNA quantification, and HBe antigen seropositivity), GMPH score in F3 or F4 was significantly lower than that in F0 to F2. In the above mentioned 8 variables, differences between the liver fibrosis stages (F0 to F1 vs F2, F2 vs F3, F3 vs F4, F0 to F1 vs F3, F0 to F1 vs F4, and F2 vs F4) for the entire

  7. A proposed predictive model for advanced fibrosis in patients with chronic hepatitis B and its validation

    PubMed Central

    Nishikawa, Hiroki; Hasegawa, Kunihiro; Ishii, Akio; Takata, Ryo; Enomoto, Hirayuki; Yoh, Kazunori; Kishino, Kyohei; Shimono, Yoshihiro; Iwata, Yoshinori; Nakano, Chikage; Nishimura, Takashi; Aizawa, Nobuhiro; Sakai, Yoshiyuki; Ikeda, Naoto; Takashima, Tomoyuki; Iijima, Hiroko; Nishiguchi, Shuhei

    2016-01-01

    Abstract We created a predictive model using serum-based biomarkers for advanced fibrosis (F3 or more) in patients with chronic hepatitis B (CHB) and to confirm the accuracy in an independent cohort. A total of 249 CHB patients were analyzed. To achieve our study aim, a training group (n = 125) and a validation group (n = 124) were formed. In the training group, parameters related to the presence of advanced fibrosis in univariate and multivariate analyses were examined, and a formula for advanced fibrosis was created. Next, we verified the applicability of the predictive model in the validation group. Multivariate analysis identified that gamma-glutamyl transpeptidase (GGT, P = 0.0343) and platelet count (P = 0.0034) were significant predictors of the presence of advanced fibrosis, while Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP, P = 0.0741) and hyaluronic acid (P = 0.0916) tended to be significant factors. Using these 4 parameters, we created the following formula: GMPH score = −0.755 − (0.015 × GGT) − (0.268 × WFA+-M2BP) + (0.167 × platelet count) + (0.003 × hyaluronic acid). In 8 analyzed variables (WFA+-M2BP, aspartate aminotransferase-to-platelet ratio index, FIB-4 index, prothrombin time, platelet count, hyaluronic acid, Forns index, and GMPH score), GMPH score had the highest area under the receiver operating characteristic (AUROC) curve for advanced fibrosis with a value of 0.8064 in the training group and in the validation group, GMPH score also had the highest AUROC (0.7782). In all subgroup analyses of the hepatitis B virus (HBV) status (HB surface antigen quantification, HBV-DNA quantification, and HBe antigen seropositivity), GMPH score in F3 or F4 was significantly lower than that in F0 to F2. In the above mentioned 8 variables, differences between the liver fibrosis stages (F0 to F1 vs F2, F2 vs F3, F3 vs F4, F0 to F1 vs F3, F0 to F1 vs F4, and F2 vs

  8. Quality of life in patients with venous stasis ulcers and others with advanced venous insufficiency.

    PubMed

    Tracz, Edyta; Zamojska, Ewa; Modrzejewski, Andrzej; Zaborski, Daniel; Grzesiak, Wilhelm

    2015-01-01

    The quality of life (QoL) in patients with advanced venous insufficiency (including venous stasis ulcers, skin discoloration, stasis eczema, and lipodermatosclerosis) assessed using the Clinical Etiological Anatomical Pathophysiological (CEAP) and Venous Clinical Severity Score (VCSS) classifications is presented. Also, disease features such as: intensity of pain, edema and inflammatory response that exerted the most profound effect on different domains of QoL are reported. The global QoL in patients with lower leg venous ulcerations was relatively similar to that observed in other patients with chronic venous insufficiency. The presence of venous ulcerations was associated with lower QoL in a Physical domain. Significant correlations were found between pain intensity and the values of Physical, Physiological, Level of Independence and Environmental domains, between edema intensity and Social domain as well as between the intensity of inflammatory response and Physical and Spiritual domains.

  9. A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinoma.

    PubMed

    Sangro, B; Mazzolini, G; Ruiz, M; Ruiz, J; Quiroga, J; Herrero, I; Qian, C; Benito, A; Larrache, J; Olagüe, C; Boan, J; Peñuelas, I; Sádaba, B; Prieto, J

    2010-12-01

    The aim of this phase I clinical trial was to assess the feasibility and safety of intratumoral administration of a first-generation adenoviral vector encoding herpes simplex virus thymidine kinase (HSV-TK) gene (Ad.TK) followed by systemic ganciclovir to patients with advanced hepatocellular carcinoma (HCC). Secondarily, we have analyzed its antitumor effect. Ten patients were enrolled in five dose-level cohorts that received from 10¹⁰ to 2 × 10¹² viral particles (vp). Ad.TK was injected intratumorally and patients received up to three doses at 30-day intervals. Positron emission tomography was used to monitor TK gene expression. Ad.TK injection was feasible in 100% of cases. Treatment was well tolerated and dose-limiting toxicity was not achieved. Cumulative toxicity was not observed. Hepatic toxicity was absent even in cirrhotic patients. Fever, flu-like syndrome, pain at the injection site and pancytopenia were the most common side effects. No partial responses were observed and 60% of patients showed tumor stabilization of the injected lesion. Importantly, two patients who received the highest dose showed signs of intratumoral necrosis by imaging procedures. One of them achieved a sustained stabilization and survived for 26 months. In conclusion, Ad.TK can be safely administered by intratumoral injection to patients with HCC up to 2 × 10¹² vp per patient. PMID:20689572

  10. Physical activity in patients with advanced-stage cancer: a systematic review of the literature.

    PubMed

    Albrecht, Tara A; Taylor, Ann Gill

    2012-06-01

    The importance of physical activity for chronic disease prevention and management has become generally well accepted. The number of research interventions and publications examining the benefits of physical activity for patients with cancer has been rising steadily. However, much of that research has focused on the impact of physical activity either prior to or early in the cancer diagnosis, treatment, and survivorship process. Research focusing on the effects of physical activity, specifically for patients with advanced-stage cancer and poorer prognostic outcomes, has been addressed only recently. The purpose of this article is to examine the state of the science for physical activity in the advanced-stage disease subset of the cancer population. Exercise in a variety of intensities and forms, including yoga, walking, biking, and swimming, has many health benefits for people, including those diagnosed with cancer. Research has shown that, for people with cancer (including advanced-stage cancer), exercise can decrease anxiety, stress, and depression while improving levels of pain, fatigue, shortness of breath, constipation, and insomnia. People diagnosed with cancer should discuss with their oncologist safe, easy ways they can incorporate exercise into their daily lives. PMID:22641322

  11. Relationship between PTEN and VEGF expression and clinicopathological characteristics in HCC.

    PubMed

    Mi, Denghai; Yi, Jilin; Liu, Enyu; Li, Xingrui

    2006-01-01

    To investigate the expressions and significance of the tumor suppressor gene phosphatase and tensin homolog deleted on chromosome ten protein (PTEN) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC), and to analyze the relationship between their expressions and the tumor's invasion and their peri-carcinomatous tissues, the correlation of their expressions with the tumor's clinicopathological characteristics and invasion potential were studied. Our study showed that the expression level of PTEN in HCC was remarkably lower than that in peri-carcinomatous liver tissues, while the expressions of both VEGF and MVD were higher than that in peri-carcinomatous liver tissues. Correlation analysis revealed that the expression of PTEN was negatively related to the progression of the pathological differentiation and invasion of tumor, whereas the expressions of VEGF and MVD were positively related. Moreover, there was a negative relationship between the expression of PTEN and the expressions of VEGF and MVD, and a positive one between VEGF and MVD. The expressions of PTEN and VEGF may reveal the degree of differentiation and the invasive potential of HCC tissues. The mechanism by which the lack of PTEN expression probably induces abnormal hyperexpression of VEGF may play an important role in the invasion and metastasis of HCC.

  12. Factors Affecting Students' Choice to Enroll at HCC: Implications for Marketing, Recruitment, and Advising.

    ERIC Educational Resources Information Center

    Quinley, John W.

    A study was conducted to analyze the factors which affect students' decisions to enroll at Harford Community College (HCC), Harford County, Maryland. An entrant follow-up survey was sent in spring 1984 to all students who were enrolled in a Maryland community college for the first time in fall 1982. The survey sought to evaluate the extent to…

  13. 3rd International Conference on Ecohydrology, Soil and Climate Change, EcoHCC'14

    NASA Astrophysics Data System (ADS)

    Andrade, Cristina; Hughes, Samantha; Santos, João A.

    2016-08-01

    The International Conference on Ecohydrology and Climate Change (EcoHCC) series began in 2009 and aims at sharing experiences and promoting discussion, in a multidisciplinary framework, towards a better understanding of the climate change consequences in a global and regional context.

  14. Quality of life and palliative care needs of elderly patients with advanced heart failure

    PubMed Central

    Chan, Helen YL; Yu, Doris SF; Leung, Doris YP; Chan, Aileen WK; Hui, Elsie

    2016-01-01

    Objective To examine the quality of life and palliative care needs of elderly patients with advanced heart failure (HF). Methods This was a correlation descriptive study conducted at a 650-bed sub-acute hospital. Patients who were aged 65 or over, diagnosed with HF of New York Heart Association Class III or IV symptoms, and mentally sound were eligible to the study. The Edmonton Symptom Assessment Scale, the overall quality of life single item scale, and the McQill Quality of Life Questionnaire (MQoL), were used for measurement. Multiple regression analysis was performed to determine factors for predicting quality of life. Results A convenience sample of 112 patients was recruited. Their age was 81.5 ± 8.5 years. The three most distressing symptoms reported by the patients were tiredness (5.96 ± 2.78), drowsiness (5.47 ± 2.93), and shortness of breath (5.34 ± 2.96). Their mean overall quality of life single item scale score was 4.72 ± 2.06 out of 10. The mean MQoL physical subscale score was the lowest (4.20 ± 1.767), whereas their mean psychological subscale was the highest (7.14 ± 2.39). However, in a multivariate analysis model, quality of life was significantly associated with existential wellbeing, physical wellbeing, psychological wellbeing and educational level. Conclusions The findings highlight that spiritual concerns are significant palliative care needs among elderly patients with advanced HF, in addition to symptom management. This is in line with the argument that palliative care that places great emphasis on holistic care should be integrated to the care of this group of patients. PMID:27594869

  15. Hypermetabolism and symptom burden in advanced cancer patients evaluated in a cachexia clinic

    PubMed Central

    Dev, Rony; Hui, David; Chisholm, Gary; Delgado-Guay, Marvin; Dalal, Shalini; Del Fabbro, Egidio; Bruera, Eduardo

    2015-01-01

    Background Elevated resting energy expenditure (REE) may contribute to weight loss and symptom burden in cancer patients. Aims The aim of this study was to compare the velocity of weight loss, symptom burden (fatigue, insomnia, anxiety, and anorexia—combined score as measured by the Edmonton Symptom Assessment Score), high-sensitivity C-reactive protein, and survival among cancer patients referred to a cachexia clinic with hypermetabolism, elevated REE > 110% of predicted, with normal REE. Methods A retrospective analysis of 60 advanced cancer patients evaluated in a cachexia clinic for either >5% weight loss or anorexia who underwent indirect calorimetry to measure REE. Patients were dichotomized to either elevated or normal REE. Descriptive statistics were generated, and a two-sample Student's t-tests were used to compare the outcomes between the groups. Kaplan–Meier and Cox regression methodology were used to examine the survival times between groups. Results Thirty-seven patients (62%) were men, 41 (68%) were White, 59 (98%) solid tumours, predominantly 23 gastrointestinal cancers (38%), with a median age of 60 (95% confidence interval 57.0–62.9). Thirty-five patients (58%) were hypermetabolic. Non-Caucasian patients were more likely to have high REE [odds ratio = 6.17 (1.56, 24.8), P = 0.01]. No statistical difference regarding age, cancer type, gender, active treatment with chemotherapy, and/or radiation between hypermetabolic and normal REE was noted. The velocity of weight loss over a 3 month period (−8.5 kg vs. −7.2 kg, P = 0.68), C-reactive protein (37.3 vs. 55.6 mg/L, P = 0.70), symptom burden (4.2 vs. 4.5, P = 0.54), and survival (288 vs. 276 days, P = 0.68) was not significantly different between high vs. normal REE, respectively. Conclusion Hypermetabolism is common in cancer patients with weight loss and noted to be more frequent in non-Caucasian patients. No association among velocity of weight loss

  16. [Respecting patient's end of life wishes: feasibility study of an information on surrogate and advance directives].

    PubMed

    Vinant, Pascale; Rousseau, Isabelle; Huillard, Olivier; Goldwasser, François; Guillard, Marie-Yvonne; Colombet, Isabelle

    2015-03-01

    This prospective interventional study aims to show the feasibility and impact of information procedure on surrogate and advance directives (AD), for patients with incurable lung or gastrointestinal cancer. The intervention consisted of two semi-structured interviews. The first included: collection of preferences for prognostic information and involvement in decision-making, initial assessment of knowledge, information and surrogate and DA. The second assessed the impact of the first interview on knowledge, surrogate designation and DA writing, the assessment procedure by the patient and assessment of anxiety generated. Among 77 eligible patients, 23 (30 %) were included, 6/29 (21 %) refused to participate, 20/23 (87 %) completed both interviews. Patients not included had a higher 4-month death rate than included ones (39 % vs. 4 %, P=0.002). Patients included had high expectations of information and appreciated it be delivered early, by someone not involved in their care. The study shows the feasibility of the procedure and its impact on the use of surrogate and DA by patients, however, revealing the complexity of approaching end-of-life wills and the importance of a process of anticipated discussion.

  17. [Respecting patient's end of life wishes: feasibility study of an information on surrogate and advance directives].

    PubMed

    Vinant, Pascale; Rousseau, Isabelle; Huillard, Olivier; Goldwasser, François; Guillard, Marie-Yvonne; Colombet, Isabelle

    2015-03-01

    This prospective interventional study aims to show the feasibility and impact of information procedure on surrogate and advance directives (AD), for patients with incurable lung or gastrointestinal cancer. The intervention consisted of two semi-structured interviews. The first included: collection of preferences for prognostic information and involvement in decision-making, initial assessment of knowledge, information and surrogate and DA. The second assessed the impact of the first interview on knowledge, surrogate designation and DA writing, the assessment procedure by the patient and assessment of anxiety generated. Among 77 eligible patients, 23 (30 %) were included, 6/29 (21 %) refused to participate, 20/23 (87 %) completed both interviews. Patients not included had a higher 4-month death rate than included ones (39 % vs. 4 %, P=0.002). Patients included had high expectations of information and appreciated it be delivered early, by someone not involved in their care. The study shows the feasibility of the procedure and its impact on the use of surrogate and DA by patients, however, revealing the complexity of approaching end-of-life wills and the importance of a process of anticipated discussion. PMID:25732047

  18. [Physicians' views and perspectives on advanced directives in patients with incipient dementia].

    PubMed

    Mattiussi, Mercedes; Dawidowski, Adriana; Restibo, Jimena; Pollán, Javier; Pezzano, Laura; Cámera, Luis

    2012-01-01

    Dementia is a progressive disease in which patients lose their ability to decide and communicate. Advance directives (AD) allow patients to express their preferences on end of life care in the early stages of the disease. Primary care practitioners (PCP) are in the best position to promote AD. The aim of this study was to elicit PCPs views about the discussion of AD with early stage dementia patients. A qualitative approach was taken, focus groups and individual interviews to elderly patients' PCPs from the Hospital italiano de buenos aires were conducted. A purposive sampling was performed, conforming homogeneous groups according to age and seniority. The discussion was stimulated by a vignette. We performed thematic content analysis in an interdisciplinary team. Twelve PCPs = 30 year of age, 32 middle-aged and 8 over 45 years participated of the study. The youngest group favored the discussion of AD while those over 45 regarded the family as the decision maker, and thus, the discussion as useless. Besides, they expressed that our society is not mature enough to discuss AD. Difficulties in AD implementation, in predicting the evolution of a patient's disease, the span of time between the discussion and AD implementation, lack of legislation and specific institutional policies were other factors that conditioned the discussion. Younger PCPs expressed concern on the lack of communication skills and difficulties to broach this subject with patients. PCPs perspectives on AD vary, their age should be taken into account when designing strategies to their implementation.

  19. Fatigue is the Most Important Symptom for Advanced Cancer Patients Who Have Had Chemotherapy

    PubMed Central

    Butt, Zeeshan; Rosenbloom, Sarah K.; Abernethy, Amy P.; Beaumont, Jennifer L.; Paul, Diane; Hampton, Debra; Jacobsen, Paul B.; Syrjala, Karen L.; Von Roenn, Jamie H.; Cella, David

    2016-01-01

    Cancer fatigue has been defined and described as an important problem. However, few studies have assessed the relative importance of fatigue compared with other patient symptoms and concerns. To explore this issue, the authors surveyed 534 patients and 91 physician experts from 5 NCCN member institutions and community support agencies. Specifically, they asked patients with advanced bladder, brain, breast, colorectal, head and neck, hepatobiliary/pancreatic, kidney, lung, ovarian, or prostate cancer or lymphoma about their “most important symptoms or concerns to monitor.” Across the entire sample, and individually for patients with 9 cancer types, fatigue emerged as the top-ranked symptom. Fatigue was also ranked most important among patients with 10 of 11 cancer types when asked to rank lists of common concerns. Patient fatigue ratings were most strongly associated with malaise (r = 0.50) and difficulties with activities of daily living, pain, and quality of life. Expert ratings of how much fatigue is attributable to disease versus treatment mostly suggested that both play an important role, with disease-related factors predominant in hepatobiliary and lung cancer, and treatment-related factors playing a stronger role in head and neck cancer. PMID:18492460

  20. Predicting compliance for mandible advancement splint therapy in 96 obstructive sleep apnea patients.

    PubMed

    Ingman, Tuula; Arte, Sirpa; Bachour, Adel; Bäck, Leif; Mäkitie, Antti

    2013-12-01

    The treatment of choice in obstructive sleep apnea (OSA) is continuous positive airway pressure (CPAP). Mandible advancement splint (MAS) offers an option for patients with mild or moderate OSA, who refuse or are unable to tolerate CPAP. The aim of the study was to find predictive factors in OSA for MAS therapy. The study group comprised 96 consecutive OSA patients who were sent for MAS therapy during 2008. Data were collected on the patients' general and dental condition, diagnosis, and treatment for OSA. Panoramic and cephalometric radiographs were analysed. The treatment compliance rate and problems with the use of the MAS were recorded. This rate was 57% and the significant affecting factors were protrusion of the mandible with MAS during the adaptation to the appliance as well as shorter maxillary and mandible lengths. The compliance of the MAS therapy was best in patients with short maxilla and mandible, which should be taken into consideration when planning MAS therapy for OSA patients. Finally, a sleep study should be part of the follow-up in this patient population. PMID:23159421

  1. The best timing for administering systemic chemotherapy in patients with locally advanced rectal cancer

    PubMed Central

    Shimodaira, Yusuke; Harada, Kazuto; Lin, Quan

    2016-01-01

    Over the past several decades, outcomes for patients with rectal cancer have improved considerably. However, several questions have emerged as survival times have lengthened and quality of life has improved for these patients. Currently patients with locally advanced rectal cancer (LARC) are often recommended multimodality therapy with fluoropyrimidine-based chemotherapy (CT) and radiation followed by total mesorectal excision (TME), with consideration given to FOLFOX before chemoradiotherapy (CRT). Recently, Garcia-Aguilar and colleagues reported in Lancet Oncology that the addition of mFOLFOX6 administered between CRT and surgery affected the number of patients achieving pathologic complete response (pathCR), which is of great interest from the standpoint of pursuit of optimal timing of systemic CT delivery. This was a multicenter phase II study consisting of 4 sequential treatment groups of patients with LARC, and they reported that patients given higher number CT cycles between CRT and surgery achieved higher rates of pathCR than those given standard treatment. There was no association between response improvement and tumor progression, increased technical difficulty, or surgical complications. Ongoing phase III clinical trial further assessing this strategy might result in a paradigm shift. PMID:26889491

  2. Concurrent cisplatin, 5-FU, paclitaxel, and radiation therapy in patients with locally advanced esophageal cancer

    SciTech Connect

    Roof, Kevin S. . E-mail: kroof@sero.net; Coen, John; Lynch, Thomas J.; Wright, Cameron; Fidias, Panos; Willett, Christopher G.; Choi, Noah C.

    2006-07-15

    Purpose: Phase I-II data regarding neoadjuvant cisplatin, 5-fluorouracil (5-FU), paclitaxel, and radiation (PFT-R) from our institution demonstrated encouraging pathologic complete response (pCR) rates. This article updates our experience with PFT-R, and compares these results to our experience with cisplatin, 5-FU, and radiation therapy (PF-R) in locally advanced esophageal cancer. Patients and Methods: We searched the Massachusetts General Hospital cancer registry for esophageal cancer patients treated with radiation therapy and chemotherapy between 1994-2002. Records of patients treated with curative, neoadjuvant therapy were examined for chemotherapeutic regimen. Outcomes of patients treated with PF-R or PFT-R were assessed for response to therapy, toxicity, and survival. Results: A total of 177 patients were treated with neoadjuvant therapy with curative intent; 164 (93%) received PF-R (n = 81) or PFT-R (n = 83). Median overall survival was 24 months. After a median follow-up of 54 months for surviving patients, 3-year overall survival was 40% with no significant difference between PF-R (39%) and PFT-R (42%). Conclusions: Our findings failed to demonstrate an improvement in pCR or survival with PFT-R vs. PF-R. These results do not support this regimen of concurrent neoadjuvant PFT-R in esophageal cancer, and suggest that further investigations into alternative regimens and novel agents are warranted.

  3. Telomere length is a prognostic biomarker in elderly advanced ovarian cancer patients: a multicenter GINECO study

    PubMed Central

    Falandry, Claire; Horard, Béatrice; Bruyas, Amandine; Legouffe, Eric; Cretin, Jacques; Meunier, Jérôme; Alexandre, Jérôme; Delecroix, Valérie; Fabbro, Michel; Certain, Marie-Noëlle; Maraval-Gaget, Raymonde; Pujade-Lauraine, Eric; Gilson, Eric; Freyer, Gilles

    2015-01-01

    Purpose Age induces a progressive decline in functional reserve and impacts cancer treatments. Telomere attrition leads to tissue senescence. We tested the hypothesis that telomere length (TL) could predict patient vulnerability and outcome with cancer treatment. Patients and methods An ancillary study in the Elderly Women GINECO Trial 3 was performed to evaluate the impact of geriatric covariates on survival in elderly advanced ovarian cancer patients receiving six cycles of carboplatin. TL was estimated from peripheral blood at inclusion using standard procedures. Results TL (in base pairs) was estimated for 109/111 patients (median 6.1 kb; range [4.5-8.3 kb]). With a cut-off of 5.77 kb, TL discriminated two patient groups, long telomere (LT) and short telomeres (ST), with significantly different treatment completion rates of 0.80 (95%CI [0.71-0.89]) and 0.59 (95%CI [0.41-0.76]), respectively (odds ratio [OR]=2.8, p=0.02). ST patients were at higher risk of serious adverse events (SAE, OR=2.7; p=0.02) and had more unplanned hospital admissions (OR=2.1; p=0.08). After adjustment on FIGO stage, TL shorter than 6 kb was a risk factor of premature death (HR=1.57; p=0.06). Conclusion This exploratory study identifies TL as predictive factor of decreased treatment completion, SAE risk, unplanned hospital admissions and OS after adjustment on FIGO stage. PMID:26638179

  4. Predicting compliance for mandible advancement splint therapy in 96 obstructive sleep apnea patients.

    PubMed

    Ingman, Tuula; Arte, Sirpa; Bachour, Adel; Bäck, Leif; Mäkitie, Antti

    2013-12-01

    The treatment of choice in obstructive sleep apnea (OSA) is continuous positive airway pressure (CPAP). Mandible advancement splint (MAS) offers an option for patients with mild or moderate OSA, who refuse or are unable to tolerate CPAP. The aim of the study was to find predictive factors in OSA for MAS therapy. The study group comprised 96 consecutive OSA patients who were sent for MAS therapy during 2008. Data were collected on the patients' general and dental condition, diagnosis, and treatment for OSA. Panoramic and cephalometric radiographs were analysed. The treatment compliance rate and problems with the use of the MAS were recorded. This rate was 57% and the significant affecting factors were protrusion of the mandible with MAS during the adaptation to the appliance as well as shorter maxillary and mandible lengths. The compliance of the MAS therapy was best in patients with short maxilla and mandible, which should be taken into consideration when planning MAS therapy for OSA patients. Finally, a sleep study should be part of the follow-up in this patient population.

  5. Advance Care Planning: A Qualitative Study of Dialysis Patients and Families

    PubMed Central

    Eneanya, Nwamaka D.; Feinberg, Rebecca; Germain, Michael J.; Marr, Lisa; Berzoff, Joan; Cohen, Lewis M.; Unruh, Mark

    2015-01-01

    Background and objectives More than 90,000 patients with ESRD die annually in the United States, yet advance care planning (ACP) is underutilized. Understanding patients’ and families’ diverse needs can strengthen systematic efforts to improve ACP. Design, setting, participants, & measurements In-depth interviews were conducted with a purposive sample of patients and family/friends from dialysis units at two study sites. Applying grounded theory, interviews were audiotaped, professionally transcribed, and analyzed in an iterative process. Emergent themes were identified, discussed, and organized into major themes and subthemes. Results Thirteen patients and nine family/friends participated in interviews. The mean patient age was 63 years (SD 14) and five patients were women. Participants identified as black (n=1), Hispanic (n=4), Native American (n=4), Pacific Islander (n=1), white (n=11), and mixed (n=1). Three major themes with associated subthemes were identified. The first theme, “Prior experiences with ACP,” revealed that these discussions rarely occur, yet most patients desire them. A potential role for the primary care physician was broached. The second theme, “Factors that may affect perspectives on ACP,” included a desire for more of a connection with the nephrologist, positive and negative experiences with the dialysis team, disenfranchisement, life experiences, personality traits, patient-family/friend relationships, and power differentials. The third theme, “Recommendations for discussing ACP,” included thoughts on who should lead discussions, where and when discussions should take place, what should be discussed and how. Conclusions Many participants desired better communication with their nephrologist and/or their dialysis team. A number expressed feelings of disenfranchisement that could negatively impact ACP discussions through diminished trust. Life experiences, personality traits, and relationships with family and friends may

  6. In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma

    PubMed Central

    Philipp-Abbrederis, Kathrin; Herrmann, Ken; Knop, Stefan; Schottelius, Margret; Eiber, Matthias; Lückerath, Katharina; Pietschmann, Elke; Habringer, Stefan; Gerngroß, Carlos; Franke, Katharina; Rudelius, Martina; Schirbel, Andreas; Lapa, Constantin; Schwamborn, Kristina; Steidle, Sabine; Hartmann, Elena; Rosenwald, Andreas; Kropf, Saskia; Beer, Ambros J; Peschel, Christian; Einsele, Hermann; Buck, Andreas K; Schwaiger, Markus; Götze, Katharina; Wester, Hans-Jürgen; Keller, Ulrich

    2015-01-01

    CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination and poor prognosis. We evaluated the novel CXCR4 probe [68Ga]Pentixafor for in vivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [68Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [68Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [18F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34+ flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [68Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases. PMID:25736399

  7. Prognostic significance of CT-emphysema score in patients with advanced squamous cell lung cancer

    PubMed Central

    Kim, Young Saing; Ahn, Hee Kyung; Cho, Eun Kyung; Jeong, Yu Mi; Kim, Jeong Ho

    2016-01-01

    Background Although emphysema is a known independent risk factor of lung cancer, no study has addressed the prognostic impact of computed tomography (CT)-emphysema score in advanced stage lung cancer. Methods For 84 consecutive patients with stage IIIB and IV squamous cell lung cancer that underwent palliative chemotherapy, severity of emphysema was semi-quantitatively scored using baseline chest CT images according to the Goddard scoring system (possible scores range, 0–24). The cutoff of high CT-emphysema score was determined using the maximum chi-squared test and the prognostic significance of the high CT-emphysema score was evaluated using Kaplan-Meier analysis and Cox proportional hazards analysis. Results The median CT-emphysema score was 5 (range, 0–22). Patients with a high CT-emphysema score (≥4) tended to have poorer overall survival (OS) (median: 6.3 vs. 13.7 months) than those with a score of <4 (P=0.071). Multivariable analysis revealed that a higher CT-emphysema score was a significant independent prognostic factor for poor OS [hazard ratio (HR) =2.06; 95% confidence interval (CI), 1.24–3.41; P=0.005), along with no response to first-line therapy (P=0.009) and no second-line therapy (P<0.001). Conclusions CT-emphysema score is significantly associated with poor prognosis in patients with advanced squamous cell lung cancer. PMID:27621848

  8. Advance care planning in nursing homes: pre- and post-Patient Self-Determination Act.

    PubMed Central

    Castle, N G; Mor, V

    1998-01-01

    OBJECTIVES: (1) To identify resident and organizational factors associated with the use of advance care plans pre- and post-implementation of the Patient Self-Determination Act (PSDA), and (2) to identify changes (pre- and post-implementation of the PSDA) in the relationship between these factors and the use of advance care plans. DESIGN: Complex, multistage cluster sampling. SETTING: Ten states were selected for variation in geographic location, Medicaid reimbursement rate, and average staffing patterns. Participants were 4,215 nursing home residents in 268 facilities. PRINCIPAL FINDINGS: Seventeen resident and organizational factors were associated with the use of do-not-resuscitate (DNR) orders in 1990, and 12 resident and organizational factors were associated with their use in 1993. Five factors showed a significant change from 1990 to 1993: activities of daily living (ADL) scores, race, cognitive performance scale (CPS) scores, full-time equivalent (FTE) nurse aides per resident, and bed size. Ten resident and organizational factors were associated with use of do-not-hospitalize (DNH) orders in 1990 and six resident and organizational factors were associated with DNH orders in 1993. Four factors showed a significant change from 1990 to 1993: legal guardian, FTE LPNs per resident, Medicaid census, and forprofit ownership. Five resident and organizational factors were associated with the use of living wills in 1990 and seven resident and organizational factors were associated with the use of living wills in 1993. Four factors showed a significant change from 1990 to 1993: ADL scores, race, length of stay, and for-profit ownership. CONCLUSION: The results indicate that the PSDA may have been successful in increasing the use of advance care plans and in changing the types of residents who use advance care plans. However, they also show that the use of advance care plans is associated with organizational characteristics, indicating that some types of facilities

  9. The prognosis in cases of hepatocellular carcinoma after hepatectomy: young patients versus older patients

    PubMed Central

    Lee, Ji Soo; Lee, Seunghwan; Choi, Jin-Yong; Cho, Wontae; Choi, Gyu-Seoung; Park, Jae Berm; Kwon, Choon Hyuck David; Kim, Sung Joo; Joh, Jae-Won

    2015-01-01

    Backgrounds/Aims Hepatocellular carcinoma (HCC) is uncommon in young adults and the prognosis of these patients is still unclear. In this retrospective study, we compared the clinicopathological characteristics and outcomes of young patients with HCC with those of older patients with HCC. Methods We retrospectively reviewed the clinicopathological characteristics of a total of 1,124 patients with HCC who underwent hepatectomy at our institution between 2006 and 2010. Patients ≤40 years of age at the time of HCC diagnosis were classified in the younger group. Results One hundred and three patients (9.2%) were classified in the younger group. whereas, 1021 patients were classified in the older group. The incidences of hepatitis B virus infection, alpha-fetoprotein (AFP) levels, and indocyanine green retention test were all higher in younger patients than in older patients (p<0.05). Disease-free survival and overall survival were longer in older patients than in younger patients, without statistical significance. In younger patients, increased levels of protein induced by vitamin K antagonist-II (PIVKA-II) and alkaline phosphatase, portal vein tumor thrombosis, and intrahepatic metastasis were all predisposing factors for tumor recurrence after hepatectomy. Conclusions Although the AFP levels were higher in younger patients with HCC than in older patients with HCC, disease-free survival and overall survival after liver resection were not significantly different between the two groups. PMID:26693234

  10. Perceptions of palliative care among patients with advanced cancer and their caregivers

    PubMed Central

    Zimmermann, Camilla; Swami, Nadia; Krzyzanowska, Monika; Leighl, Natasha; Rydall, Anne; Rodin, Gary; Tannock, Ian; Hannon, Breffni

    2016-01-01

    Background: Early palliative care is increasingly recommended but seldom practised. We sought to examine perceptions of palliative care among patients with advanced cancer and their caregivers. Methods: After conducting a cluster randomized controlled trial of early palliative care versus standard care for patients with advanced cancer, we approached patients and their caregivers to participate in semistructured interviews seeking to assess, qualitatively, their attitudes and perceptions about palliative care. We used the grounded theory method for data collection and analysis. Results: A total of 48 patients (26 intervention, 22 control) and 23 caregivers (14 intervention, 9 control) completed interviews. Participants’ initial perceptions of palliative care in both trial arms were of death, hopelessness, dependency and end-of-life comfort care for inpatients. These perceptions provoked fear and avoidance, and often originated from interactions with health care professionals. During the trial, those in the intervention arm developed a broader concept of palliative care as “ongoing care” that improved their “quality of living” but still felt that the term itself carried a stigma. Participants in the intervention group emphasized the need for palliative care to be reframed and better explained by health care professionals. Participants in the control group generally considered it pointless to rename palliative care, but many in the intervention group stated emphatically that a different name was necessary in the early outpatient setting. Interpretation: There is a strong stigma attached to palliative care, which may persist even after positive experiences with an early palliative care intervention. Education of the public, patients and health care providers is paramount if early integration of palliative care is to be successful. PMID:27091801

  11. A Cognitive Behavioral Intervention for Symptom Management in Patients With Advanced Cancer

    PubMed Central

    Sherwood, Paula; Given, Barbara A.; Given, Charles W.; Champion, Victoria L.; Doorenbos, Ardith Z.; Azzouz, Faouzi; Kozachik, Sharon; Wagler-Ziner, Kim; Monahan, Patrick O.

    2006-01-01

    Purpose/Objectives: To evaluate the effectiveness of a cognitive behavioral intervention in decreasing symptom severity in patients with advanced cancer undergoing chemotherapy. Design: Prospective, randomized clinical trial based on cognitive behavioral theory. Setting: Six urban cancer centers in the midwestern United States. Sample: 124 patients 21 years of age or older were recruited and randomized to receive conventional care or conventional care and an intervention. Participants were newly diagnosed with stage III, stage IV, or recurrent cancer (solid tumor or non-Hodgkin lymphoma), undergoing chemotherapy, cognitively intact, and able to read and speak English. Methods: Data were gathered via telephone interviews at baseline and 10 and 20 weeks after randomization. Nurses with experience in oncology delivered a five-contact, eight-week intervention aimed at teaching patients problem-solving techniques to affect symptom severity. Main Research Variables: Gender, site of cancer, age, symptom severity and depressive symptoms at baseline, group (i.e., experimental versus control), and total symptom severity. Findings: Patients in the experimental group and those with lower symptom severity at baseline had significantly lower symptom severity at 10 and 20 weeks; the experimental difference at 20 weeks occurred primarily in those 60 years of age and younger. Depressive symptoms at baseline predicted symptom severity at 20 weeks; however, age, gender, and site of cancer did not affect symptom severity at either time point. Conclusions: Implications for Nursing: Problem-solving strategies should be included in educational programs for patients with advanced cancer, particularly those 60 years of age and younger. PMID:16270114

  12. Efficacy and Factors Affecting Outcome of Gemcitabine Concurrent Chemoradiotherapy in Patients With Locally Advanced Pancreatic Cancer

    SciTech Connect

    Huang, P.-I.; Chao, Yee; Li, C.-P.; Lee, R.-C.; Chi, K.-H.; Shiau, C.-Y.; Wang, L.-W.; Yen, S.-H.

    2009-01-01

    Purpose: To evaluate the efficacy and prognostic factors of gemcitabine (GEM) concurrent chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer. Methods and Materials: Between January 2002 and December 2005, 55 patients with locally advanced pancreatic cancer treated with GEM (400 mg/m{sup 2}/wk) concurrently with radiotherapy (median dose, 50.4 Gy; range, 26-61.2) at Taipei Veterans General Hospital were enrolled. GEM (1,000 mg/m{sup 2}) was continued after CCRT as maintenance therapy once weekly for 3 weeks and repeated every 4 weeks. The response, survival, toxicity, and prognostic factors were evaluated. Results: With a median follow-up of 10.8 months, the 1- and 2-year survival rate was 52% and 19%, respectively. The median overall survival (OS) and median time to progression (TTP) was 12.4 and 5.9 months, respectively. The response rate was 42% (2 complete responses and 21 partial responses). The major Grade 3-4 toxicities were neutropenia (22%) and anorexia (19%). The median OS and TTP was 15.8 and 9.5 months in the GEM CCRT responders compared with 7.5 and 3.5 months in the nonresponders, respectively (both p < 0.001). The responders had a better Karnofsky performance status (KPS) (86 {+-} 2 vs. 77 {+-} 2, p = 0.002) and had received a greater GEM dose intensity (347 {+-} 13 mg/m{sup 2}/wk vs. 296 {+-} 15 mg/m{sup 2}/wk, p = 0.02) than the nonresponders. KPS and serum carbohydrate antigen 19-9 were the most significant prognostic factors of OS and TTP. Conclusion: The results of our study have shown that GEM CCRT is effective and tolerable for patients with locally advanced pancreatic cancer. The KPS and GEM dose correlated with response. Also, the KPS and CA 19-9 level were the most important factors affecting OS and TTP.

  13. Multi-purpose utility of circulating plasma DNA testing in patients with advanced cancers.

    PubMed

    Perkins, Geraldine; Yap, Timothy A; Pope, Lorna; Cassidy, Amy M; Dukes, Juliet P; Riisnaes, Ruth; Massard, Christophe; Cassier, Philippe A; Miranda, Susana; Clark, Jeremy; Denholm, Katie A; Thway, Khin; Gonzalez De Castro, David; Attard, Gerhardt; Molife, L Rhoda; Kaye, Stan B; Banerji, Udai; de Bono, Johann S

    2012-01-01

    Tumor genomic instability and selective treatment pressures result in clonal disease evolution; molecular stratification for molecularly targeted drug administration requires repeated access to tumor DNA. We hypothesized that circulating plasma DNA (cpDNA) in advanced cancer patients is largely derived from tumor, has prognostic utility, and can be utilized for multiplex tumor mutation sequencing when repeat biopsy is not feasible. We utilized the Sequenom MassArray System and OncoCarta panel for somatic mutation profiling. Matched samples, acquired from the same patient but at different time points were evaluated; these comprised formalin-fixed paraffin-embedded (FFPE) archival tumor tissue (primary and/or metastatic) and cpDNA. The feasibility, sensitivity, and specificity of this high-throughput, multiplex mutation detection approach was tested utilizing specimens acquired from 105 patients with solid tumors referred for participation in Phase I trials of molecularly targeted drugs. The median cpDNA concentration was 17 ng/ml (range: 0.5-1600); this was 3-fold higher than in healthy volunteers. Moreover, higher cpDNA concentrations associated with worse overall survival; there was an overall survival (OS) hazard ratio of 2.4 (95% CI 1.4, 4.2) for each 10-fold increase in cpDNA concentration and in multivariate analyses, cpDNA concentration, albumin, and performance status remained independent predictors of OS. These data suggest that plasma DNA in these cancer patients is largely derived from tumor. We also observed high detection concordance for critical 'hot-spot' mutations (KRAS, BRAF, PIK3CA) in matched cpDNA and archival tumor tissue, and important differences between archival tumor and cpDNA. This multiplex sequencing assay can be utilized to detect somatic mutations from plasma in advanced cancer patients, when safe repeat tumor biopsy is not feasible and genomic analysis of archival tumor is deemed insufficient. Overall, circulating nucleic acid

  14. Prognostic Significance of Concurrent Hypovascular and Hypervascular Nodules in Patients with Hepatocellular Carcinoma

    PubMed Central

    Ogasawara, Sadahisa; Chiba, Tetsuhiro; Motoyama, Tenyu; Kanogawa, Naoya; Saito, Tomoko; Shinozaki, Yusuke; Suzuki, Eiichiro; Ooka, Yoshihiko; Tawada, Akinobu; Kato, Hideyuki; Okabe, Shinichiro; Kanai, Fumihiko; Yoshikawa, Masaharu; Yokosuka, Osamu

    2016-01-01

    Background Hypovascular nodules often occur together with hypervascular hepatocellular carcinoma (HCC). However, it remains controversial whether hypovascular nodules associated with hypervascular HCC have any prognostic value. This study evaluated the prognostic impact of hypovascular nodules co-existing with hypervascular HCC as diagnosed by computed tomography during arterial portography (CTAP) and computed tomography during hepatic arteriography (CTHA), which can sensitively capture the dynamic changes in blood flow through the portal vein and hepatic artery in patients with early stage HCC. Methods A total of 152 patients with hypervascular HCC (≤ 30 mm, ≤ 3 nodules), who underwent initial local ablation, were analyzed retrospectively. All patients received CTAP and CTHA prior to treatment. Overall survival (OS) was compared among group A (hypervascular HCC only, 107 patients) and group B (hypovascular nodules and hypervascular HCC, 45 patients). Results Among all hypovascular nodules, 81% (46 of 57) developed hypervascularization within the follow-up period. The 1- and 2-year hypervascularization rates were 17% and 51%, respectively. OS was significantly longer for group A than for group B (P < 0.001). A Cox proportional-hazards model identified the presence of hypovascular nodules concurrent with hypervascular HCC as an independent poor prognostic factor. Conclusion The prognosis of hypervascular HCC patients with hypovascular nodules detected during CTAP and CTHA is poor. Clinical HCC categories seem to be dissimilar between patients with and without hypovascular nodules. PMID:27649084

  15. Uterine preservation for advanced pelvic organ prolapse repair: Anatomical results and patient satisfaction

    PubMed Central

    Fink, Keshet; Shachar, Inbar Ben; Braun, Naama Marcus

    2016-01-01

    ABSTRACT Objective: The aims of the current study were to evaluate outcomes and patient satisfaction in cases of uterine prolapse treated with vaginal mesh, while preserving the uterus. Materials and Methods: This is a retrospective cohort study that included all patients operated for prolapse repair with trocar-less vaginal mesh while preserving the uterus between October 2010 and March 2013. Data included: patients pre-and post-operative symptoms, POP-Q and operative complications. Success was defined as prolapse < than stage 2. A telephone survey questionnaire was used to evaluate patient's satisfaction. Results: Sixty-six patients with pelvic organ prolapse stage 3, including uterine pro-lapse of at least stage 2 (mean point C at+1.4 (range+8-(-1)) were included. Mean follow-up was 22 months. Success rate of the vaginal mesh procedure aimed to repair uterine prolapse was 92% (61/66), with mean point C at −6.7 (range (-1) - (-9)). No major intra-or post-operative complication occurred. A telephone survey questionnaire was conducted post-operatively 28 months on average. Ninety-eight percent of women were satisfied with the decision to preserve their uterus. Eighteen patients (34%) received prior consultation elsewhere for hysterectomy due to their prolapse, and decided to have the operation at our center in order to preserve the uterus. Conclusions: Uterine preservation with vaginal mesh was found to be a safe and effective treatment, even in cases with advanced uterine prolapse. Most patients prefer to keep their uterus. Uterus preservation options should be discussed with every patient before surgery for pelvic organ prolapse. PMID:27564289

  16. The Prevalence and Contents of Advance Directives in Patients With Pacemakers

    PubMed Central

    Pasalic, Dario; Tajouri, Tanya H.; Ottenberg, Abigale L.; Mueller, Paul S.

    2013-01-01

    Background Little is known about the use of advance directives (ADs) in patients who have implantable cardiac pacemakers (PMs). Methods We conducted a retrospective review of the medical records of residents of Olmsted County, Minnesota, who underwent implantation of a cardiac PM at Mayo Clinic (Rochester, Minnesota) during 2006 and 2007 and determined the prevalence and contents of ADs in these patients. Results During the study period, 205 residents of Olmsted County (men, 53%) underwent PM implantation (mean age [SD] at implantation, 77 [15] years). Overall, 120 patients (59%) had ADs. Of these, 63 ADs (53%) were executed more than 12 months before and 33 (28%) were executed after PM implantation. Many patients specifically mentioned life-prolonging treatments in their ADs: cardiopulmonary resuscitation, 76 (63%); mechanical ventilation, 56 (47%); and hemodialysis, 31 (26%). Pain control was mentioned in 79 ADs (66%) and comfort measures were mentioned in 42 ADs (35%). Furthermore, the AD of many patients contained a general statement about end-of-life care (eg, no “heroic measures”). However, only 1 AD (1%) specifically addressed the end-of-life management of the PM. Conclusions More than half of the patients with PMs in our study had executed an AD, but only 1 patient specifically mentioned her PM in her AD. These results suggest that patients with PMs should be encouraged to execute ADs and, specifically address end-of-life device management in their ADs. Doing so may prevent end-of-life ethical dilemmas related to PM management. PMID:24215172

  17. Identification of characteristic TRB V usage in HBV-associated HCC by using differential expression profiling analysis

    PubMed Central

    Han, Yingxin; Liu, Xing; Wang, Yuqi; Wu, Xiaolei; Guan, Yanfang; Li, Hongmei; Chen, Xinchun; Zhou, Boping; Yuan, Qing; Ou, Ying; Wu, Renhua; Huang, Wanqiu; Wang, Yun; Zhang, Ming; Zhang, Yinxin; Zhu, Dongxing; Zhu, Hongmei; Yang, Ling; Yi, Xin; Huang, Chen; Huang, Jian

    2015-01-01

    Liver cancer is one of the most common cancers worldwide. CDR3 sequencing-based immune repertoire can be closely associated with cancer prognosis and development. Identifying the specific interaction between the TCR and cellular antigens is important for developing novel immunotherapeutic approaches for the treatment of cancer. The rearranged TCRβ loci amplified using Vβ- and Jβ-specific primers by multi-PCR and sequenced using high-throughput sequencing (HTS) in liver cancers were compared with those of T cells from healthy adult peripheral blood and from adjacent liver tissue. The T-cell repertoires within each tumor show strong similarity to one another but are distinct from those of the circulating T-cell repertoire. In addition, our results demonstrate that there are significant differences in the T-cell repertoires of HCC (hepatocellular carcinoma), ICC (intrahepatic cholangiocarcinoma), and MHC (mixed hepatocellular and cholangiocellular carcinoma). Furthermore, we found that the highly expanded clone (HEC) ratio in blood samples from liver cancer patients differed significantly from those in the blood of healthy adults and hepatitis patients (p < 0.001). The above results suggest that comparison of the T-cell repertoires of tissue and blood could be used to distinguish liver cancer patients from healthy adults and from hepatitis patients. In the future, the diversity of CDR3 sequences in liver cancer may prove to be a useful and novel biomarker for detecting aggressive tumors with high invasive or metastatic capacity. PMID:26405574

  18. Advances in Liposuction: Five Key Principles with Emphasis on Patient Safety and Outcomes

    PubMed Central

    Tabbal, Geo N.; Ahmad, Jamil; Lista, Frank

    2013-01-01

    Summary: Since Illouz’s presentation of a technique for lipoplasty at the 1982 Annual Meeting of the American Society of Plastic and Reconstructive Surgeons, liposuction has become one of the most commonly performed aesthetic surgery procedures. The evolution of liposuction has seen refinements in technique and improvement of patient safety-related standards of care. Based on long-term experience with body contouring surgery, 5 principles of advanced liposuction are presented: preoperative evaluation and planning, intraoperative monitoring—safety measures, the role of wetting solutions and fluid resuscitation, circumferential contouring and complication prevention, and outcomes measurement. PMID:25289270

  19. Acute hypertension during ramucirumab infusion in two patients with advanced oesophagogastric cancer.

    PubMed

    van der Woude, Stephanie O; van Laarhoven, Hanneke W M

    2016-08-18

    Ramucirumab, a monoclonal antibody targeting the vascular endothelial growth factor (VEGF) pathway, in combination with paclitaxel is becoming part of standard second-line systemic therapy for advanced oesophagogastric cancer, based on the results of the REGARD and RAINBOW trials. Common well-known side effects of VEGF pathway inhibitors are hypertension and infusion-related reactions. Here, we describe hypertension as the predominant feature of an infusion-related reaction in 2 patients with metastasised oesophagogastric carcinoma treated with ramucirumab and paclitaxel as second-line treatment and propose possible explanations of this side effect previously undescribed for ramucirumab.

  20. Acute hypertension during ramucirumab infusion in two patients with advanced oesophagogastric cancer.

    PubMed

    van der Woude, Stephanie O; van Laarhoven, Hanneke W M

    2016-01-01

    Ramucirumab, a monoclonal antibody targeting the vascular endothelial growth factor (VEGF) pathway, in combination with paclitaxel is becoming part of standard second-line systemic therapy for advanced oesophagogastric cancer, based on the results of the REGARD and RAINBOW trials. Common well-known side effects of VEGF pathway inhibitors are hypertension and infusion-related reactions. Here, we describe hypertension as the predominant feature of an infusion-related reaction in 2 patients with metastasised oesophagogastric carcinoma treated with ramucirumab and paclitaxel as second-line treatment and propose possible explanations of this side effect previously undescribed for ramucirumab. PMID:27539134

  1. Meta-analysis of gene expression profiles indicates genes in spliceosome pathway are up-regulated in hepatocellular carcinoma (HCC).

    PubMed

    Xu, Weijin; Huang, Huixing; Yu, Long; Cao, Lihuan

    2015-04-01

    Hepatocellular carcinoma (HCC) is among the commonest kind of malignant tumors, which accounts for more than 500,000 cases of newly diagnosed cancer annually. Many microarray studies for identifying differentially expressed genes (DEGs) in HCC have been conducted, but results have varied across different studies. Here, we performed a meta-analysis of publicly available microarray Gene Expression Omnibus datasets, which covers five independent studies, containing 753 HCC samples and 638 non-tumor liver samples. We identified 192 DEGs that were consistently up-regulated in HCC vs. normal liver tissue. For the 192 up-regulated genes, we performed Kyoto Encyclopedia of Genes and Genomes pathway analysis. To our surprise, besides several cell growth-related pathways, spliceosome pathway was also up-regulated in HCC. For further exploring the relationship between spliceosome pathway and HCC, we investigated the expression data of spliceosome pathway genes in 15 independent studies in Nextbio database ( https://www.nextbio.com/b/nextbioCorp.nb ). It was found that many genes of spliceosome pathway such as HSPA1A, SNRPE, SF3B2, SF3B4 and TRA2A genes which we identified to be up-regulated in our meta-analysis were generally overexpressed in HCC. At last, using real-time PCR, we also found that BUD31, SF3B2, SF3B4, SNRPE, SPINK1, TPA2A and HSPA1A genes are significantly up-regulated in clinical HCC samples when compared to the corresponding non-tumorous liver tissues. Our study for the first time indicates that many genes of spliceosome pathway are up-regulated in HCC. This finding might put new insights for people's understanding about the relationship of spliceosome pathway and HCC.

  2. The Attitudes of Chinese Cancer Patients and Family Caregivers toward Advance Directives.

    PubMed

    Zhang, Qiu; Xie, Chuanbo; Xie, Shanghang; Liu, Qing

    2016-01-01

    Advance directives (ADs) have been legislated in many countries to protect patient autonomy regarding medical decisions at the end of life. China is facing a serious cancer burden and cancer patients' quality at the end of life should be a concern. However, limited studies have been conducted locally to gather information about attitudes toward ADs. The purpose of this study was to investigate the attitudes of Chinese cancer patients and family caregivers toward ADs and to explore the predictors that are associated with attitudes. The study indicated that although there was low awareness of ADs, most cancer patients and family caregivers had positive attitudes toward ADs after related information was explained to them. Participants preferred to discuss ADs with medical staff when they were diagnosed with a life-threatening disease. Preferences for refusing life-sustaining treatment and choosing Hospice-Palliative Care (HPC) at the end of life would increase the likelihood of agreeing with ADs. This suggests that some effective interventions to help participants better understand end-of-life treatments are helpful in promoting ADs. Moreover, the development of HPC would contribute to Chinese cancer patients and family caregivers agreeing with ADs. PMID:27529264

  3. Prognostic Impact of Pretreatment Plasma Fibrinogen in Patients with Locally Advanced Oral and Oropharyngeal Cancer

    PubMed Central

    Holzinger, Daniel; Danilovic, Ivan; Seemann, Rudolf; Kornek, Gabriela; Engelmann, Johannes; Pillerstorff, Robert; Holawe, Simone; Psyrri, Amanda; Erovic, Boban M.; Farwell, Gregory; Perisanidis, Christos

    2016-01-01

    Background We aimed to determine the prognostic significance of pretreatment plasma fibrinigen in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). Methods A cohort of 183 patients with locally advanced OOSCC receiving preoperative chemoradiotherapy was retrospectively examined. Using ROC curve analysis, a pretreatment plasma fibrinogen cutoff value of 447mg/dL was determined. The primary endpoints were overall survival and recurrence-free survival. A secondary endpoint was to determine whether pretreatment plasma fibrinogen could predict treatment response to neoadjuvant chemoradiotherapy. Cox regression models and Kaplan–Meier curves were used for survival analyses. Results Seventy-one patients had an elevated pretreatment plasma fibrinogen (fibrinogen >447mg/dL). Patients with high fibrinogen showed significantly higher pathologic stages after neoadjuvant treatment than those with low fibrinogen (p = 0.037). In univariate analysis, elevated fibrinogen was associated with poor overall survival (p = 0.005) and recurrence-free survival (p = 0.008) Multivariate analysis revealed that elevated fibrinogen remained an independent risk factor for death (hazard ratio 1.78, 95% CI 1.09–2.90, p = 0.021) and relapse (hazard ratio 1.78, 95% CI 1.11–2.86, p = 0.016). Conclusion Elevated pretreatment plasma fibrinogen is associated with lack of response to neoadjuvant chemoradiotherapy and reduced OS and RFS in patients with OOSCC. Thus, plasma fibrinogen may emerge as a novel prognostic indicator and a potential therapeutic target in OOSCC. PMID:27362659

  4. A phase I study of indoximod in patients with advanced malignancies

    PubMed Central

    Soliman, Hatem H.; Minton, Susan E.; Han, Hyo Sook; Ismail-Khan, Roohi; Neuger, Anthony; Khambati, Fatema; Noyes, David; Lush, Richard; Chiappori, Alberto A.; Roberts, John D.; Link, Charles; Vahanian, Nicholas N.; Mautino, Mario; Streicher, Howard; Sullivan, Daniel M.; Antonia, Scott J.

    2016-01-01

    Purpose Indoximod is an oral inhibitor of the indoleamine 2,3-dioxygenase pathway, which causes tumor-mediated immunosuppression. Primary endpoints were maximum tolerated dose (MTD) and toxicity for indoximod in patients with advanced solid tumors. Secondary endpoints included response rates, pharmacokinetics, and immune correlates. Experimental Design Our 3+3 phase I trial comprised 10 dose levels (200, 300, 400, 600, and 800 mg once/day; 600, 800, 1200, 1600, and 2000 mg twice/day). Inclusion criteria were measurable metastatic solid malignancy, age ≥18 years, and adequate organ/marrow function. Exclusion criteria were chemotherapy ≤ 3 weeks prior, untreated brain metastases, autoimmune disease, or malabsorption. Results In 48 patients, MTD was not reached at 2000 mg twice/day. At 200 mg once/day, 3 patients previously treated with checkpoint inhibitors developed hypophysitis. Five patients showed stable disease >6 months. Indoximod plasma AUC and Cmax plateaued above 1200mg. Cmax (∼12 μM at 2000 mg twice/day) occurred at 2.9 hours, and half-life was 10.5 hours. C reactive protein (CRP) levels increased across multiple dose levels. Conclusions Indoximod was safe at doses up to 2000 mg orally twice/day. Best response was stable disease >6 months in 5 patients. Induction of hypophysitis, increased tumor antigen autoantibodies and CRP levels were observed. PMID:27008709

  5. Phase 1 Study of Intravenous Oncolytic Poxvirus (vvDD) in Patients With Advanced Solid Cancers

    PubMed Central

    Downs-Canner, Stephanie; Guo, Zong Sheng; Ravindranathan, Roshni; Breitbach, Caroline J; O'Malley, Mark E; Jones, Heather L; Moon, Anne; McCart, Judith Andrea; Shuai, Yongli; Zeh, Herbert J; Bartlett, David L

    2016-01-01

    We have conducted a phase 1 study of intravenous vvDD, a Western Reserve strain oncolytic vaccinia virus, on 11 patients with standard treatment-refractory advanced colorectal or other solid cancers. The primary endpoints were maximum tolerated dose and associated toxicity while secondary endpoints were pharmacokinetics, pharmacodynamics, immune responses, and antitumor activity. No dose-limiting toxicities and treatment related severe adverse events were observed. The most common adverse events were grades 1/2 flu-like symptoms. Virus genomes were detectable in the blood 15–30 minutes after virus administration in a dose-dependent manner. There was evidence of a prolonged virus replication in tumor tissues in two patients, but no evidence of virus replication in non-tumor tissues, except a healed injury site and an oral thrush. Over 100-fold of anti-viral antibodies were induced in patients' sera. A strong induction of inflammatory and Th1, but not Th2 cytokines, suggested a potent Th1-mediated immunity against the virus and possibly the cancer. One patient showed a mixed response on PET-CT with resolution of some liver metastases, and another patient with cutaneous melanoma demonstrated clinical regression of some lesions. Given the confirmed safety, further trials evaluating intravenous vvDD in combination with therapeutic transgenes, immune checkpoint blockade or complement inhibitors, are warranted. PMID:27203445

  6. Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer

    PubMed Central

    Brahmer, Julie R.; Tykodi, Scott S.; Chow, Laura Q.M.; Hwu, Wen-Jen; Topalian, Suzanne L.; Hwu, Patrick; Drake, Charles G.; Camacho, Luis H.; Kauh, John; Odunsi, Kunle; Pitot, Henry C.; Hamid, Omid; Bhatia, Shailender; Martins, Renato; Eaton, Keith; Chen, Shuming; Salay, Theresa M.; Alaparthy, Suresh; Grosso, Joseph F.; Korman, Alan J.; Parker, Susan M.; Agrawal, Shruti; Goldberg, Stacie M.; Pardoll, Drew M.; Gupta, Ashok; Wigginton, Jon M.

    2013-01-01

    BACKGROUND Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host’s immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. METHODS In this multicenter phase 1 trial, we administered intravenous anti–PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti–PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. RESULTS As of February 24, 2012, a total of 207 patients — 75 with non–small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer — had received anti–PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal-cell cancer, 5 of 49 with non–small-cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up. CONCLUSIONS Antibody-mediated blockade of PD-L1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non–small-cell lung cancer, melanoma, and renal-cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00729664.) PMID:22658128

  7. Efficacy of a self-management plan in exacerbations for patients with advanced COPD

    PubMed Central

    Sánchez-Nieto, Juan Miguel; Andújar-Espinosa, Rubén; Bernabeu-Mora, Roberto; Hu, Chunshao; Gálvez-Martínez, Beatriz; Carrillo-Alcaraz, Andrés; Álvarez-Miranda, Carlos Federico; Meca-Birlanga, Olga; Abad-Corpa, Eva

    2016-01-01

    Background Self-management interventions improve different outcome variables in various chronic diseases. Their role in COPD has not been clearly established. We assessed the efficacy of an intervention called the self-management program on the need for hospital care due to disease exacerbation in patients with advanced COPD. Methods Multicenter, randomized study in two hospitals with follow-up of 1 year. All the patients had severe or very severe COPD, and had gone to either an accident and emergency (A&E) department or had been admitted to a hospital at least once in the previous year due to exacerbation of COPD. The intervention consisted of a group education session on the main characteristics of the disease, an individual training session on inhalation techniques, at the start and during the 3rd month, and a written action plan containing instructions for physical activity and treatment for stable phases and exacerbations. We determined the combined number of COPD-related hospitalizations and emergency visits per patient per year. Secondary endpoints were number of patients with visits to A&E and the number of patients hospitalized because of exacerbations, use of antibiotics and corticosteroids, length of hospital stay, and all-cause mortality. Results After 1 year, the rate of COPD exacerbations with visits to A&E or hospitalization had decreased from 1.37 to 0.89 (P=0.04) and the number of exacerbations dropped from 52 to 42 in the group of patients who received the intervention. The numbers of patients hospitalized, at 19 (40.4%) versus 20 (52.6%) (P=0.26), and those who went to A&E, at 9 (19.1%) versus 14 (36.8%) (P=0.06), due to exacerbation of COPD were also lower in this group. Intake of antibiotics was higher in the intervention group, whereas use of glucocorticoids was slightly lower, though there were no significant differences (P=0.30). There were also no differences between groups in the length of hospital stay (P=0.154) or overall mortality (P=0

  8. Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a tissue biomarker for detection of early Hepatocellular carcinoma in patients with cirrhosis

    PubMed Central

    2012-01-01

    Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors occurring mainly in patients with chronic liver disease. Detection of early HCC is critically important for treatment of these patients. Methods We employed a proteomic profiling approach to identify potential biomarker for early HCC detection. Based on Barcelona Clinic Liver Cancer (BCLC) staging classification, 15 early HCC and 25 late HCC tissue samples from post-operative HCC patients and their clinicopathological data were used for the discovery of biomarkers specific for the detection of early HCC. Differential proteins among cirrhotic, early, and late tissue samples were separated by two-dimensional gel electrophoresis (2-DE) and subsequently identified by mass spectrometry (MS). Receiver operating characteristic (ROC) curves analysis were performed to find potential biomarkers associated with early HCC. Diagnosis performance of the biomarker was obtained from diagnosis test. Results Protein spot SSP2215 was found to be significantly overexpressed in HCC, particularly in early HCC, and identified as heterogeneous nuclear ribonucleoprotein K (hnRNP K) by tandem mass spectrometry (MALDI TOF/TOF). The overexpression in HCC was subsequently validated by western blot and immunohistochemistry. ROC curve analysis showed that hnRNP K intensity could detect early HCC at 66.67 % sensitivity and 84 % specificity, which was superior to serum α-fetoprotein (AFP) in detection of early HCC. Furthermore, the diagnosis test demonstrated, when combined with hnRNP K and serum AFP as biomarker panel to detect early HCC at different cut-off value, the sensitivity and specificity could be enhanced to 93.33 % and 96 %, respectively. Conclusions hnRNP K is a potential tissue biomarker, either alone or in combination with serum AFP, for detection of early HCC. High expression of hnRNP K could be helpful to discriminate early HCC from a nonmalignant nodule, especially for patients with liver

  9. [Application of chemiluminescence immunoassay method in detection of serum index for liver fibrosis in patients with advanced schistosomiasis].

    PubMed

    Luo, Jiang-Long

    2011-02-01

    The method of chemiluminescence immunoassay (CLIA) was adopted to detect the levels of hyaluronic acid (HA), laminin (LN), III procollagen (CP III), IV collagen (IV-C) in the sera of 102 cases of advanced schistosomiasis. The results showed that the levels of the 4 indexes of advanced schistosomiasis patients were significantly higher than those of healthy people. It is suggested that the application of CLIA to detect the related serum indexes in patients with advanced schistosomiasis is useful in the diagnosis of liver fibrosis. PMID:22164394

  10. Combination chemotherapy followed by surgery or radiotherapy in patients with locally advanced cervical cancer.

    PubMed

    Kirsten, F; Atkinson, K H; Coppleson, J V; Elliott, P M; Green, D; Houghton, R; Murray, J C; Russell, P; Solomon, H J; Friedlander, M

    1987-06-01

    Forty-seven patients with locally advanced cervical cancer at high risk of relapse received three cycles of chemotherapy with PVB (cisplatin, vinblastine and bleomycin) before definitive local treatment with either radical surgery or radiotherapy. Thirty-one of the 47 patients (66%) responded to initial chemotherapy, and 11 of them have relapsed compared with 13 of the 16 non-responders. Median time to recurrence was 31 weeks for PVB non-responders but has not yet been reached for PVB responders. After a median follow-up of 128 weeks, 14 of the 31 responders (45%) are alive and disease free compared with 3 of the 16 non-responders (19%). There was a positive correlation between response to chemotherapy and subsequent response to radiotherapy. PVB was in general well tolerated although one death is probably attributable to chemotherapy. A randomized study comparing radiotherapy alone with initial PVB chemotherapy followed by radiotherapy is in progress. PMID:2441736

  11. Effectiveness of prophylactic retropharyngeal lymph node irradiation in patients with locally advanced head and neck cancer

    PubMed Central

    2012-01-01

    Background The aim of the study is to assess the effectiveness of intensity-modulated radiotherapy (IMRT) or image-guided radiotherapy (IGRT) for the prevention of retropharyngeal nodal recurrences in locally advanced head and neck cancer. Methods A retrospective review of 76 patients with head and neck cancer undergoing concurrent chemoradiation or postoperative radiotherapy with IMRT or IGRT who were at risk for retropharyngeal nodal recurrences because of anatomic site (hypopharynx, nasopharynx, oropharynx) and/or the presence of nodal metastases was undertaken. The prevalence of retropharyngeal nodal recurrences was assessed on follow-up positron emission tomography (PET)-CT scans. Results At a median follow-up of 22 months (4–53 months), no patient developed retropharyngeal nodal recurrences. Conclusion Prophylactic irradiation of retropharyngeal lymph nodes with IMRT or IGRT provides effective regional control for individuals at risk for recurrence in these nodes. PMID:22708791

  12. Bilateral ureteral complete obstruction with huge spontaneous urinoma formation in a patient with advanced bladder cancer.

    PubMed

    Jou, Yeong-Chin; Shen, Cheng-Huang; Cheng, Ming-Chin; Lin, Chang-Te; Chen, Pi-Che

    2012-02-01

    Spontaneous rupture of the collecting system with extravasation of urine and urinoma formation is usually associated with urinary tract obstruction by a ureteral calculus. Tumor growth is an extremely rare cause of urinary extravasation. Here we report a case of bilateral obstructive uropathy with a huge spontaneous left retroperitoneal urinoma caused by advanced infiltrative transitional cell carcinoma of the urinary bladder. The point of leakage was located in the left renal pelvis. The urinary leakage ceased after percutaneous nephrostomy drainage, and the patient subsequently underwent radical cystoprostatectomy. Histopathology revealed a high-grade urothelial carcinoma of the urinary bladder with pelvic lymph node metastasis. The patient refused any adjuvant treatment and expired 6 months after the operation from disseminated metastasis from bladder cancer.

  13. Determinants of Quality Care and Mortality for Patients With Locally Advanced Cervical Cancer in Virginia

    PubMed Central

    Showalter, Timothy N.; Camacho, Fabian; Cantrell, Leigh A.; Anderson, Roger T.

    2016-01-01

    Abstract Outcomes for patients with locally advanced cervical cancer are influenced by receipt of all indicated components of quality care: early diagnosis and receipt of external beam radiation therapy, chemotherapy, and brachytherapy. We performed an observational cohort study to evaluate receipt of quality cancer care and mortality after cancer diagnosis among patients with locally advanced cervical cancer in Virginia. We queried the Virginia state cancer registry to identify patients with International Federation of Gynecology and Obstetrics Stage IB-IVA cervical cancer who were diagnosed during 2002 to 2012. We evaluated the influence of tumor-related, demographic, and geospatial factors on the receipt of indicated therapies and mortality. Treatment quality score of 0 to 3 was defined based upon the extent of receipt of the components of indicated therapy. A total of 1048 patients were identified; 33.1% received all 3 components of treatment and only 54.0% received brachytherapy. Predictors of higher quality score included younger age group versus 66+ years at diagnosis (18–42 odds ratio [OR] = 12.3, 95% confidence interval: 6.6, 23.0; 42–53 OR = 5.6, CI: 3.3, 9.5; 53–66 OR = 5.5, CI: 3.3, 9.1), lower tumor stages versus IVA (IB2 OR = 3.3, CI: 1.8, 6.2; II OR = 2.7, CI: 1.6, 4.5; IIIx OR = 2.1, CI: 1.3, 3.6), and treatment at a high-volume facility (OR 2.2, CI: 1.2, 4.2). Predictors of increased mortality included earlier year of diagnosis, higher tumor stage, treatment at a lower volume facility, and lower treatment quality score. In a cohort of locally advanced cervical cancer patients in Virginia, we identified a low rate of receipt of complete quality care for cervical cancer and a strong effect of facility volume on quality treatment and survival. Further research is needed to develop strategies to improve access to quality treatment and outcomes for cervical cancer. PMID:26937934

  14. Friction Coefficient and Superficial Zone Protein are Increased in Patients with Advanced Osteoarthritis

    PubMed Central

    Neu, C.P.; Reddi, A.H.; Komvopoulos, K.; Schmid, T.M.; Di Cesare, P.E.

    2010-01-01

    Objective To quantify the concentration of superficial zone protein (SZP) in articular cartilage and synovial fluid of patients with advanced osteoarthritis (OA), and to further correlate the SZP content with the friction coefficient, OA severity, and levels of inflammatory cytokines. Methods Samples of articular cartilage and synovial fluid were obtained from patients undergoing elective total knee replacement surgery. Additional normal samples were obtained from donated body program and tissue bank sources. Regional SZP expression in cartilage obtained from the femoral condyles was quantified by enzyme-linked immunosorbant assay and visualized by immunohistochemistry. Friction coefficient measurements were obtained from cartilage plugs slid in the boundary lubrication regime. OA severity was graded using histochemical analyses. The concentration of SZP and inflammatory cytokines in synovial fluid were determined by enzyme-linked immunosorbant assays. Results A pattern of SZP localization in knee cartilage was identified, with load-bearing regions exhibiting high SZP expression. SZP patterns correlated to friction coefficient and OA severity; however SZP expression was observed in all samples at the articular surface, regardless of OA severity. SZP expression and aspirate volume of synovial fluid were higher in OA patients compared to normal controls. Expressions of cytokines were elevated in the synovial fluid of some patients. Conclusion The results reveal a mechano-chemical coupling in which physical forces regulate OA severity and joint lubrication. The findings of this study also suggest that SZP may be ineffective in reducing joint friction in the boundary lubrication regime at an advanced OA stage where other mechanisms may dominate the observed tribological behavior. PMID:20499384

  15. Surprise Questions for Survival Prediction in Patients With Advanced Cancer: A Multicenter Prospective Cohort Study

    PubMed Central

    Hamano, Jun; Morita, Tatsuya; Inoue, Satoshi; Ikenaga, Masayuki; Matsumoto, Yoshihisa; Sekine, Ryuichi; Yamaguchi, Takashi; Hirohashi, Takeshi; Tajima, Tsukasa; Tatara, Ryohei; Watanabe, Hiroaki; Otani, Hiroyuki; Takigawa, Chizuko; Matsuda, Yoshinobu; Nagaoka, Hiroka; Mori, Masanori; Yamamoto, Naoki; Shimizu, Mie; Sasara, Takeshi

    2015-01-01

    Background. Predicting the short-term survival in cancer patients is an important issue for patients, family, and oncologists. Although the prognostic accuracy of the surprise question has value in 1-year mortality for cancer patients, the prognostic value for short-term survival has not been formally assessed. The primary aim of the present study was to assess the prognostic value of the surprise question for 7-day and 30-day survival in patients with advanced cancer. Patients and Methods. The present multicenter prospective cohort study was conducted in Japan from September 2012 through April 2014, involving 16 palliative care units, 19 hospital-based palliative care teams, and 23 home-based palliative care services. Results. We recruited 2,425 patients and included 2,361 for analysis: 912 from hospital-based palliative care teams, 895 from hospital palliative care units, and 554 from home-based palliative care services. The sensitivity, specificity, positive predictive value, and negative predictive value of the 7-day survival surprise question were 84.7% (95% confidence interval [CI], 80.7%–88.0%), 68.0% (95% CI, 67.3%–68.5%), 30.3% (95% CI, 28.9%–31.5%), and 96.4% (95% CI, 95.5%–97.2%), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for the 30-day surprise question were 95.6% (95% CI, 94.4%–96.6%), 37.0% (95% CI, 35.9%–37.9%), 57.6% (95% CI, 56.8%–58.2%), and 90.4% (95% CI, 87.7%–92.6%), respectively. Conclusion. Surprise questions are useful for screening patients for short survival. However, the high false-positive rates do not allow clinicians to provide definitive prognosis prediction. Implications for Practice: The findings of this study indicate that clinicians can screen patients for 7- or 30-day survival using surprise questions with 90% or more sensitivity. Clinicians cannot provide accurate prognosis estimation, and all patients will not always die within the defined periods. The

  16. Advance Directives and Communication Skills of Prehospital Physicians Involved in the Care of Cardiovascular Patients.

    PubMed

    Gigon, Fabienne; Merlani, Paolo; Ricou, Bara

    2015-12-01

    Advance directives (AD) were developed to respect patient autonomy. However, very few patients have AD, even in cases when major cardiovascular surgery is to follow. To understand the reasons behind the low prevalence of AD and to help decision making when patients are incompetent, it is necessary to focus on the impact of prehospital practitioners, who may contribute to an increase in AD by discussing them with patients. The purpose of this study was to investigate self-rated communication skills and the attitudes of physicians potentially involved in the care of cardiovascular patients toward AD.Self-administered questionnaires were sent to general practitioners, cardiologists, internists, and intensivists, including the Quality of Communication Score, divided into a General Communication score (QOCgen 6 items) and an End-of-life Communication score (QOCeol 7 items), as well as questions regarding opinions and practices in terms of AD.One hundred sixty-four responses were received. QOCgen (mean (±SD)): 9.0/10 (1.0); QOCeol: 7.2/10 (1.7). General practitioners most frequently start discussions about AD (74/149 [47%]) and are more prone to designate their own specialty (30/49 [61%], P < 0.0001). Overall, only 57/159 (36%) physicians designated their own specialty; 130/158 (82%) physicians ask potential cardiovascular patients if they have AD and 61/118 (52%) physicians who care for cardiovascular patients talk about AD with some of them.The characteristics of physicians who do not talk about AD with patients were those who did not personally have AD and those who work in private practices.One hundred thirty-three (83%) physicians rated the systematic mention of patients' AD in the correspondence between physicians as good, while 114 (71%) at the patients' first registration in the private practice.Prehospital physicians rated their communication skills as good, whereas end-of-life communication was rated much lower. Only half of those surveyed speak about AD

  17. Nutritional rehabilitation in patients with advanced head and neck cancer receiving radiation therapy.

    PubMed

    Daly, J M; Hearne, B; Dunaj, J; LePorte, B; Vikram, B; Strong, E; Green, M; Muggio, F; Groshen, S; DeCosse, J J

    1984-10-01

    maintained mean mid-arm circumference and recovered mean serum albumin levels after radiation therapy in contrast with the orally fed group. Intensive outpatient tube-feeding nutritional support during radiation therapy in patients with advanced inoperable squamous cancer of the oropharynx significantly improved mean weight maintenance, mean caloric and protein intake, and mean serum albumin levels compared with patients who received optimal oral nutrition. Tumor response to radiation therapy, however, was unchanged.

  18. Advance statement of consent from patients with primary CNS tumours to organ donation and elective ventilation.

    PubMed

    Patel, Umang Jash

    2013-03-01

    A deficit in the number of organs available for transplantation persists even with an increase in donation rates. One possible choice of donor for organs that appears under-referred and/or unaccepted is patients with primary brain tumours. In spite of advances in the treatment of high-grade primary central nervous system (CNS) tumours, the prognosis remains dire. A working group on organs from donors with primary CNS tumours showed that the risk of transmission is small and outweighs the benefits of waiting for a normal donor, in survival and organ life-years, with caveats. This paper explores the possibility that, if information on organ donation were made available to patients and their families with knowledge of their inevitable fate, perhaps some will choose to donate. It would be explained that to achieve this, elective ventilation would be performed in their final moments. This would obviate the consent question because of an advance statement. It is accepted that these are sensitive matters and there will be logistic issues. This will need discussion with the public and other professionals, but it could increase the number of donors and can be extrapolated to encompass other primary CNS tumours. PMID:23303178

  19. Coping strategies for existencial and spiritual suffering in Israeli patients with advanced cancer

    PubMed Central

    2014-01-01

    Coping with existential and spiritual concerns is inescapable in end-of-life care although not enough is known about the strategies and mechanisms involved. This pilot study focused on identifying the strategies for coping with existential and spiritual suffering at the end of life of secular Jews with advanced-stage cancer. U