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Sample records for melanoma receiving first-line

  1. Integrating first-line treatment options into clinical practice: what's new in advanced melanoma?

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    Dummer, Reinhard; Schadendorf, Dirk; Ascierto, Paolo A; Larkin, James; Lebbé, Celeste; Hauschild, Axel

    2015-12-01

    Melanoma remains a serious form of skin cancer in Europe and worldwide. Localized, early-stage melanomas can usually be treated with surgical excision. However, the prognosis is poorer for patients with advanced disease. Before 2011, treatment for advanced melanoma included palliative surgery and/or radiotherapy, and chemotherapy with or without immunotherapy, such as interleukin-2. As none of these treatments had shown survival benefits in patients with advanced melanoma, European guidelines had recommended that patients be entered into clinical trials. The lack of approved first-line options and varying access to clinical trials meant that European clinicians relied on experimental regimens and chemotherapy-based treatments when no other options were available. Since 2011, ipilimumab, an immuno-oncology therapy, and vemurafenib and dabrafenib, targeted agents that inhibit mutant BRAF, have been approved by the European Medicines Agency for the treatment of advanced melanoma. More recently, the MEK inhibitor, trametinib, received European marketing authorization for use in patients with BRAF mutation-positive advanced melanoma. In 2014, the anti-PD-1 antibody nivolumab was approved as a first-line therapy in Japan. Whereas nivolumab and another anti-PD-1 antibody, pembrolizumab, were approved as second-line therapies in the USA, their recent approval in Europe are for first-line use based on new clinical trial data in this setting. Together these agents are changing clinical practice and making therapeutic decisions more complex. Here, we discuss current and emerging therapeutic options for the first-line treatment of advanced melanoma, and how these therapies can be optimized to provide the best possible outcomes for patients.

  2. Do Veterans With Posttraumatic Stress Disorder Receive First-Line Pharmacotherapy? Results From the Longitudinal Veterans Health Survey

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    Greenbaum, Mark A.; Rosen, Craig S.

    2012-01-01

    Objective: Guidelines addressing the treatment of veterans with posttraumatic stress disorder (PTSD) strongly recommend a therapeutic trial of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). This study examined veteran characteristics associated with receiving such first-line pharmacotherapy, as well as how being a veteran of the recent conflicts in Afghanistan and Iraq impact receipt of pharmacotherapy for PTSD. Method: This was a national study of 482 Veterans Affairs (VA) outpatients between the ages of 18 and 69 years who had been newly diagnosed with PTSD (DSM-IV criteria: 309.81) during a VA outpatient visit between May 31, 2006, and December 7, 2007. Participants completed a mailed survey between August 11, 2006, and April 6, 2008. Veterans from the Afghanistan and Iraq conflicts and female veterans were intentionally oversampled. Logistic regression models were developed to predict 2 dependent variables: odds of initiating an SSRI/SNRI and, among veterans who initiated an SSRI/SNRI, odds of receiving an adequate therapeutic trial. Each dependent variable was regressed on a variety of sociodemographic and survey characteristics. Results: Of the 377 veterans prescribed a psychotropic medication, 73% (n = 276) received an SSRI/SNRI, of whom 61% (n = 168) received a therapeutic trial. Afghanistan and Iraq veterans were less likely to receive a therapeutic trial (odds ratio [OR] = 0.45; 95% CI, 0.27–0.75; P < .01), with presence of a comorbid depression diagnosis in the year after the index episode moderating this relationship, which further decreased the odds of completing a therapeutic trial (OR = 0.29; 95% CI, 0.09–0.95; P < .05). Conclusions: Reduced levels of receipt of first-line pharmacotherapy among recent veteran returnees parallel previous findings of less mental health treatment utilization in this population and warrant investigation. PMID:22943028

  3. Outcomes for Children Receiving Noninvasive Ventilation as the First-Line Mode of Mechanical Ventilation at Intensive Care Admission: A Propensity Score-Matched Cohort Study.

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    Morris, JV; Ramnarayan, P; Parslow, RC; Fleming, SJ

    2017-01-01

    Objectives: To compare outcomes of children receiving noninvasive ventilation with those receiving invasive ventilation as first-line mode of mechanical ventilation following unplanned intensive care admission. Design: Propensity score-matched cohort study analyzing data prospectively collected by the Pediatric Intensive Care Audit Network over 8 years (2007?2014). Setting: Thirty-one PICUs in the United Kingdom and Ireland; twenty-one of whom submitted Pediatric Critical Care Minimum Dataset...

  4. More than 5000 patients with metastatic melanoma in Europe per year do not have access to recommended first-line innovative treatments

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    Kandolf Sekulovic, L.; Peris, Ketty; Hauschild, A.

    2017-01-01

    treated with innovative medicines and a number of reimbursed medicines. Conclusions Great discrepancy exists in metastatic melanoma treatment across Europe. It is crucial to increase the awareness of national and European policymakers, oncological societies, melanoma patients' associations and pharma...

  5. Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration

    Directory of Open Access Journals (Sweden)

    Soo-Yon Rhee

    2017-04-01

    Full Text Available Tenofovir disoproxil fumarate (TDF genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT mutations selected in individuals with VF on such a regimen is not known. To identify TDF regimen-associated mutations (TRAMs, we compared the proportion of each RT mutation in 2873 individuals with VF on a WHO-recommended first-line TDF-containing regimen to its proportion in a cohort of 50,803 antiretroviral-naïve individuals. To identify TRAMs specifically associated with TDF-selection pressure, we compared the proportion of each TRAM to its proportion in a cohort of 5805 individuals with VF on a first-line thymidine analog-containing regimen. We identified 83 TRAMs including 33 NRTI-associated, 40 NNRTI-associated, and 10 uncommon mutations of uncertain provenance. Of the 33 NRTI-associated TRAMs, 12 – A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and Y115F – were more common among individuals receiving a first-line TDF-containing compared to a first-line thymidine analog-containing regimen. These 12 TDF-selected TRAMs will be important for monitoring TDF-associated transmitted drug-resistance and for determining the extent of reduced TDF susceptibility in individuals with VF on a TDF-containing regimen.

  6. Outcomes for Children Receiving Noninvasive Ventilation as the First-Line Mode of Mechanical Ventilation at Intensive Care Admission: A Propensity Score-Matched Cohort Study.

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    Morris, Jenny V; Ramnarayan, Padmanabhan; Parslow, Roger C; Fleming, Sarah J

    2017-06-01

    To compare outcomes of children receiving noninvasive ventilation with those receiving invasive ventilation as first-line mode of mechanical ventilation following unplanned intensive care admission. Propensity score-matched cohort study analyzing data prospectively collected by the Pediatric Intensive Care Audit Network over 8 years (2007-2014). Thirty-one PICUs in the United Kingdom and Ireland; twenty-one of whom submitted Pediatric Critical Care Minimum Dataset data for the entire study period. Children consecutively admitted to study PICUs. Planned admissions following surgery, unplanned admissions from other hospitals, those on chronic ventilation, and those who did not receive mechanical ventilation on the day of PICU admission were excluded. Use of noninvasive ventilation, rather than invasive ventilation, as the first-line mode of mechanical ventilation. PICU mortality, length of ventilation, length of PICU stay, and ventilator-free days at day 28. During the study period, there were 151,128 PICU admissions. A total of 15,144 admissions (10%) were eligible for analysis once predefined exclusion criteria were applied: 4,804 (31.7%) received "noninvasive ventilation first," whereas 10,221 (67.5%) received "invasive ventilation first"; 119 (0.8%) admissions could not be classified. Admitting PICU site explained 6.5% of the variation in first-line mechanical ventilation group (95% CI, 2.0-19.0%). In propensity score-matched analyses, receiving noninvasive ventilation first was associated with a significant reduction in mortality by 3.1% (95% CI, 1.7-4.6%), length of ventilation by 1.6 days (95% CI, 1.0-2.3), and length of PICU stay by 2.1 days (95% CI, 1.3-3.0), as well as an increase in ventilator-free days at day 28 by 3.7 days (95% CI, 3.1-4.3). Use of noninvasive ventilation as first-line mode of mechanical ventilation in critically ill children admitted to PICU in an unplanned fashion may be associated with significant clinical benefits. Further high

  7. Prevalence of metabolic syndrome in HIV-infected patients naive to antiretroviral therapy or receiving a first-line treatment.

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    Calza, Leonardo; Colangeli, Vincenzo; Magistrelli, Eleonora; Rossi, Nicolo'; Rosselli Del Turco, Elena; Bussini, Linda; Borderi, Marco; Viale, Pierluigi

    2017-05-01

    The combination antiretroviral therapy (cART) has dramatically improved the life expectancy of patients with HIV infection, but may lead to several long-term metabolic abnormalities. However, data about the frequency of metabolic syndrome (MS) in HIV-infected people vary considerably across different observational studies. The prevalence of MS among HIV-infected patients was evaluated by a cross-sectional study conducted among subjects naive to cART or receiving the first antiretroviral regimen and referring to our Clinics from January 2015 to December 2015. The diagnosis of MS was made based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), and International Diabetes Federation (IDF) criteria. The study recruited 586 patients: 98 naive to cART and 488 under the first antiretroviral treatment. The prevalence of MS, according to NCEP-ATP III criteria, was significantly higher among treated patients than among naive ones (20.9% vs. 7.1%; p = 0.014). The most frequently reported components of MS among treated patients were high triglycerides (44.3%), low high-density lipoprotein cholesterol (41.1%), and hypertension (19.7%). On multivariate analysis, long duration of HIV infection, low nadir of CD4 lymphocytes, high body mass index, current use of one protease inhibitor, and long duration of cART were significantly associated with a higher risk of MS, while current use of one integrase inhibitor was significantly associated with a lower risk of MS. The non-negligible prevalence of MS among HIV-infected patients under cART requires a careful and periodic monitoring of its components, with particular attention to dyslipidemia and hypertension.

  8. Magnitude and correlates of moderate to severe anemia among adult HIV patients receiving first line HAART in Northwestern Tanzania: a cross sectional clinic based study

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    Gunda, Daniel Wilfred; Kilonzo, Semvua Bukheti; Mpondo, Bonaventura Cornel

    2016-01-01

    Introduction Moderate to severe anemia is an important clinical problem in HIV patients on Highly Active Antiretroviral Therapy. The rate of progression and mortality in this sub group of patients is high compared to non anemic patients. In sub Saharan Africa with scale up of Anti retroviral therapy, the magnitude of this problem is not known especially in Tanzania. This study aimed at determining the magnitude and correlates of moderate to severe anemia in HIV patients receiving first line ART in northwestern Tanzania. Methods This was a cross sectional clinic based study, involving adult HIV patients on first line Highly Active Antiretroviral Therapy at Bugando Medical Centre Care and Treatment Center. The patients’ data were analyzed using STATA version 11 to determine the prevalence of moderate to severe anemia and risk factors that could predict occurrence of anemia. Results In this study 346 patients on Highly Active Anti-Retroviral Therapy were enrolled, of whom 100(40.46%) had moderate to severe anemia. The odds of being anemic were strongly predicted by Zidovudine based regime, low baseline CD4 count (100fl. Conclusion The prevalence of moderate to severe anemia is significantly high in this cohort of HIV-infected patients on first line Anti Retroviral Therapy and it is strongly predicted by Zidovudine based regime, low baseline CD4 and HIV stage 3 and 4. On clinical grounds this suggests that patients who are initiated on Zidovudine based regimen and those in advanced HIV at enrollment should have regular haemoglobin follow up to identify anemia at its earliest stage to improve the clinical outcome of these patients. PMID:27200131

  9. Cost-Effectiveness of Nivolumab-Ipilimumab Combination Therapy Compared with Monotherapy for First-Line Treatment of Metastatic Melanoma in the United States.

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    Oh, Anna; Tran, Dang M; McDowell, Leann C; Keyvani, Dor; Barcelon, Jay Andrew; Merino, Oscar; Wilson, Leslie

    2017-06-01

    The approval of new immunotherapies has dramatically changed the treatment landscape of metastatic melanoma. These survival gains come with trade-offs in side effects and costs, as well as important considerations for third-party payer systems, physicians, and patients. To develop a Markov model to determine the cost-effectiveness of nivolumab, ipilimumab, and nivolumab-ipilimumab combination as firstline therapy in metastatic melanoma, while accounting for differential effectiveness in programmed death-ligand 1 (PD-L1) positive and negative patients. A 3-state Markov model (PD-L1 positive stable disease, PD-L1 negative stable disease, and progression and/or death) was developed using a U.S. societal perspective with a lifetime time horizon of 14.5 years. Transition probabilities were calculated from progression-free (PF) survival data reported in the CheckMate-067 trial. Costs were expressed in 2015 U.S. dollars and were determined using national sources. Adverse event (AE) management was determined using immune-related AE (irAE) data from CheckMate-067, irAE management guides for nivolumab and ipilimumab, and treatment guidelines. Utilities were obtained from published literature, using melanoma-specific studies when available, and were weighted based on incidence and duration of irAEs. Base case, one-way sensitivity, and probabilistic sensitivity analyses were conducted. Nivolumab-ipilimumab combination therapy was not the cost-effective choice ($454,092 per PF quality-adjusted life-year [QALY]) compared with nivolumab monotherapy in a base case analysis at a willingness-to-pay threshold of $100,000 per PFQALY. Combination therapy and nivolumab monotherapy were cost-effective choices compared with ipilimumab monotherapy. PD-L1 positive status, utility of nivolumab and combination therapy, and medication costs contributed the most uncertainty to the model. In a population of 100% PD-L1 negative patients, nivolumab was still the optimal treatment, but combination

  10. Geriatric assessment and biomarkers in patients with metastatic breast cancer receiving first-line mono-chemotherapy: Results from the randomized phase III PELICAN trial.

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    Honecker, Friedemann; Harbeck, Nadia; Schnabel, Claudia; Wedding, Ulrich; Waldenmaier, Dirk; Saupe, Steffen; Jäger, Elke; Schmidt, Marcus; Kreienberg, Rolf; Müller, Lothar; Otremba, Burkhard; Dorn, Julia; Warm, Mathias; Al-Batran, Salah-Eddin; de Wit, Maike

    2018-03-01

    To determine predictive/prognostic factors for patients with metastatic breast cancer (MBC) receiving first-line monochemotherapy using biomarker analysis and geriatric assessment (GA). Karnofsky Performance Status (KPS) and GA as clinical parameters, and prognostic inflammatory and nutritional index (PINI), and Glasgow prognostic score (GPS) as biomarkers were analyzed for association with clinical outcome within the randomized phase III PEg-LIposomal Doxorubicin vs. CApecitabin iN MBC (PELICAN) trial of first-line pegylated liposomal doxorubicin (PLD) or capecitabine. Of 210 patients, 38% were >65years old. GA (n=152) classified 74% as fit, 10% as compromised, and 16% as frail. Biomarkers showed no age dependency. In multivariate analysis (n=70) KPS, GA, cumulative illness rating scale-geriatrics (CIRS-G), and GPS were significantly associated with time to progression, and KPS, CIRS-G, and instrumental activities of daily living (IADL) from GA, and PINI showed a significant correlation with overall survival. GA evaluation was feasible. KPS significantly correlated with efficacy outcomes. Items of a GA and biomarkers of inflammation and nutrition may have prognostic significance in patients with MBC. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Tumor markers CEA and CA 19-9 correlate with radiological imaging in metastatic colorectal cancer patients receiving first-line chemotherapy.

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    Michl, M; Koch, J; Laubender, R P; Modest, D P; Giessen, C; Schulz, Ch; Heinemann, V

    2014-10-01

    In patients with metastatic colorectal cancer (mCRC), radiological imaging represents the current standard to evaluate the efficacy of chemotherapy. However, with growing knowledge about tumor biology, other diagnostic tools become of interest which can supplement radiology. The aim of the present study was to examine the correlation of tumor and serum markers with radiological imaging in patients with mCRC receiving first-line therapy. Patients were included if tumor (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9)) and serum marker (lactatdehydrogenase (LDH), γ-glutamyltransferase (γGT), alkaline phosphatase (AP), C-reactive protein (CRP), leucocyte count (WBC), hemoglobin (Hb)) levels were available at baseline and at least two times during treatment. The decline and increase of tumor and serum markers over time were approximated for each patient by estimating slopes depending on the radiological assessment. A linear mixed effects multiple regression model for each subject was used to evaluate the intra-class correlation of these slopes modeling tumor and serum marker changes with radiological imaging. Data of 124 patients (41 female, 83 male; median age 62.9 years, range 27-85) who received first-line chemotherapy for mCRC from 11/2007 to 04/2010 were analyzed retrospectively. CEA level slopes (n = 49; slopes = 102) differed between radiologically determined progressive disease (PD) and partial response (PR) (p = 0.005) and between PD and stable disease (SD) (p = 0.042). CA 19-9 level slopes (n = 57; slopes = 127) also showed a significant difference between PD and PR (p = 0.002) and PD and SD (p = 0.058). Furthermore, CRP slopes (n = 62; slopes = 134) differed significantly between PD and PR (p = 0.009). For LDH, ALP, γGT, Hb, and WBC, no correlations were observed. The results indicate the correlation of the tumor markers CEA, CA 19-9, and the serum marker CRP with radiological imaging in

  12. Medical Decision-Making Incapacity among Newly Diagnosed Older Patients with Hematological Malignancy Receiving First Line Chemotherapy: A Cross-Sectional Study of Patients and Physicians.

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    Koji Sugano

    Full Text Available Decision-making capacity to provide informed consent regarding treatment is essential among cancer patients. The purpose of this study was to identify the frequency of decision-making incapacity among newly diagnosed older patients with hematological malignancy receiving first-line chemotherapy, to examine factors associated with incapacity and assess physicians' perceptions of patients' decision-making incapacity.Consecutive patients aged 65 years or over with a primary diagnosis of malignant lymphoma or multiple myeloma were recruited. Decision-making capacity was assessed using the Structured Interview for Competency and Incompetency Assessment Testing and Ranking Inventory-Revised (SICIATRI-R. Cognitive impairment, depressive condition and other possible associated factors were also evaluated.Among 139 eligible patients registered for this study, 114 completed the survey. Of these, 28 (25%, 95% confidence interval [CI]: 17%-32% were judged as having some extent of decision-making incompetency according to SICIATRI-R. Higher levels of cognitive impairment and increasing age were significantly associated with decision-making incapacity. Physicians experienced difficulty performing competency assessment (Cohen's kappa -0.54.Decision-making incapacity was found to be a common and under-recognized problem in older patients with cancer. Age and assessment of cognitive impairment may provide the opportunity to find patients that are at a high risk of showing decision-making incapacity.

  13. Melanoma

    Science.gov (United States)

    ... Lentigo maligna melanoma; Melanoma in situ; Superficial spreading melanoma; Nodular melanoma; Acral lentiginous melanoma ... and brown. It is most common in Caucasians. Nodular melanoma usually starts as a raised area that is ...

  14. Mutational correlates of virological failure in individuals receiving a WHO-recommended tenofovir-containing first-line regimen: An international collaboration

    NARCIS (Netherlands)

    S.Y. Rhee (Soo Yoon); V. Varghese (Vici); Holmes, S.P. (Susan P.); Van Zyl, G.U. (Gert U.); Steegen, K. (Kim); Boyd, M.A. (Mark A.); D.A. Cooper (David); Nsanzimana, S. (Sabin); Saravanan, S. (Shanmugam); C. Charpentier (Charlotte); T. de Oliveira (Tulio); Etiebet, M.A.A. (Mary-Ann A.); F. Garcia; D. Goedhals; Gomes, P. (Perpetua); H.F. Günthard; R.L. Hamers (Raph); Hoffmann, C.J. (Christopher J); G.M. Hunt (Gillian M.); Jiamsakul, A. (Awachana); P. Kaleebu (Pontiano); P.J. Kanki; R. Kantor (Rami); B. Kerschberger; V.C. Marconi; D'amour Ndahimana, J. (Jean); N. Ndembi (Nicaise); Ngo-Giang-Huong, N. (Nicole); C. Rokx (Casper); M.M. Santoro (Maria); J.M. Schapiro (Jonathan); D. Schmidt; Seu, L. (Lillian); K.C. Sigaloff (Kim); S. Sirivichayakul (Sunee); Skhosana, L. (Lindiwe); H. Sunpath; M. Tang; Yang, C. (Chunfu); Carmona, S. (Sergio); Gupta, R.K. (Ravindra K.); R.W. Shafer (Robert)

    2017-01-01

    textabstractTenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT) mutations selected

  15. Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration

    NARCIS (Netherlands)

    Rhee, Soo-Yon; Varghese, Vici; Holmes, Susan P.; van Zyl, Gert U.; Steegen, Kim; Boyd, Mark A.; Cooper, David A.; Nsanzimana, Sabin; Saravanan, Shanmugam; Charpentier, Charlotte; de Oliveira, Tulio; Etiebet, Mary-Ann A.; Garcia, Federico; Goedhals, Dominique; Gomes, Perpetua; Günthard, Huldrych F.; Hamers, Raph L.; Hoffmann, Christopher J.; Hunt, Gillian; Jiamsakul, Awachana; Kaleebu, Pontiano; Kanki, Phyllis; Kantor, Rami; Kerschberger, Bernhard; Marconi, Vincent C.; D'amour Ndahimana, Jean; Ndembi, Nicaise; Ngo-Giang-Huong, Nicole; Rokx, Casper; Santoro, Maria M.; Schapiro, Jonathan M.; Schmidt, Daniel; Seu, Lillian; Sigaloff, Kim C. E.; Sirivichayakul, Sunee; Skhosana, Lindiwe; Sunpath, Henry; Tang, Michele; Yang, Chunfu; Carmona, Sergio; Gupta, Ravindra K.; Shafer, Robert W.

    2017-01-01

    Tenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT) mutations selected in

  16. Predictors of treatment failure and time to detection and switching in HIV-infected Ethiopian children receiving first line anti-retroviral therapy

    Directory of Open Access Journals (Sweden)

    Bacha Tigist

    2012-08-01

    Full Text Available Abstract Background The emergence of resistance to first line antiretroviral therapy (ART regimen leads to the need for more expensive and less tolerable second line drugs. Hence, it is essential to identify and address factors associated with an increased probability of first line ART regimen failure. The objective of this article is to report on the predictors of first line ART regimen failure, the detection rate of ART regime failure, and the delay in switching to second line ART drugs. Methods A retrospective cohort study was conducted from 2005 to 2011. All HIV infected children under the age of 15 who took first line ART for at least six months at the four major hospitals of Addis Ababa, Ethiopia were included. Data were collected, entered and analyzed using Epi info/ENA version 3.5.1 and SPSS version 16. The Cox proportional-hazard model was used to assess the predictors of first line ART failure. Results Data of 1186 children were analyzed. Five hundred seventy seven (48.8% were males with a mean age of 6.22 (SD = 3.10 years. Of the 167(14.1% children who had treatment failure, 70 (5.9% had only clinical failure, 79 (6.7% had only immunologic failure, and 18 (1.5% had both clinical and immunologic failure. Patients who had height for age in the third percentile or less at initiation of ART were found to have higher probability of ART treatment failure [Adjusted Hazard Ratio (AHR, 3.25 95% CI, 1.00-10.58]. Patients who were less than three years old [AHR, 1.85 95% CI, 1.24-2.76], chronic diarrhea after initiation of antiretroviral treatment [AHR, 3.44 95% CI, 1.37-8.62], ART drug substitution [AHR, 1.70 95% CI, 1.05-2.73] and base line CD4 count below 50 cells/mm3 [AHR, 2.30 95% CI, 1.28-4.14] were also found to be at higher risk of treatment failure. Of all the 167 first line ART failure cases, only 24 (14.4% were switched to second line ART with a mean delay of 24 (SD = 11.67 months. The remaining 143 (85.6% cases were diagnosed

  17. Melanoma

    Science.gov (United States)

    Melanoma is the most serious type of skin cancer. Often the first sign of melanoma is a change in the size, shape, color, or feel of a mole. Most melanomas have a black or black-blue area. Melanoma ...

  18. Role of Kras status in patients with metastatic colorectal cancer receiving first-line chemotherapy plus bevacizumab: a TTD group cooperative study.

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    Eduardo Díaz-Rubio

    Full Text Available In the MACRO study, patients with metastatic colorectal cancer (mCRC were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS, overall survival (OS and response rates.KRAS data (tumour KRAS status and type of mutation were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1% in the MACRO study. Wild-type (WT KRAS tumours were found in 219 patients (56% and mutant (MT KRAS in 175 patients (44%. Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p=0.0038; HR: 1.40; 95% CI:1.12-1.77. The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p=0.0002; HR: 1.55; 95% CI: 1.23-1.96. Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5% with WT KRAS tumours and 76 patients (43.4% with MT KRAS tumours (p=0.0054; OR: 1.77; 95% CI: 1.18-2.64.This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses.

  19. Value of {sup 18}F-FDG PET/CT for therapeutic assessment of patients with polymyalgia rheumatica receiving tocilizumab as first-line treatment

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    Palard-Novello, X. [Brest University Hospital, Department of Nuclear Medicine, Brest Cedex (France); Querellou, S.; Abgral, R.; Salauen, P.Y. [Brest University Hospital, Department of Nuclear Medicine, Brest Cedex (France); Brest University, EA3878, GETBO, IFR148, Brest (France); Gouillou, M. [Institut National de la Sante et de la Recherche Medicale (INSERM), Clinical Investigation Centre (CIC) 1412, Brest (France); Saraux, A.; Devauchelle-Pensec, V. [Brest University Hospital, Department of Rheumatology, Brest (France); Brest University, EA 2216, ESPRI 29, Brest (France); Marhadour, T. [Brest University Hospital, Department of Rheumatology, Brest (France); Garrigues, F. [Brest University Hospital, Department of Radiology, Brest (France)

    2016-04-15

    To evaluate the use of {sup 18}F-FDG PET/CT for the assessment of tocilizumab (TCZ) as first-line treatment in patients with polymyalgia rheumatica (PMR). Patients with PMR were prospectively enrolled in a multicentre clinical trial assessing TCZ therapy (the TENOR trial). The patients underwent FDG PET/CT at baseline, after the first infusion of TCZ (TCZ 1) and after the last infusion of TCZ (TCZ 3). Responses to treatment were evaluated in terms of the PMR activity score (PMR-AS), and the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) laboratory tests. Maximal standardized uptake value (SUVmax) was used for assessment of FDG uptake in regions usually affected in PMR (spinous processes, hips, shoulders, sternoclavicular region and ischial tuberosities). The Wilcoxon test was applied to evaluate the changes in parameters after the infusions and Spearman's rank correlation test was applied to assess the correlations between SUVmax and PMR-AS, CRP and ESR. Of 21 patients included in the trial, 18 were evaluated. The median bioclinical parameter values decreased after TCZ 1 (PMR-AS from 38.2 to 15.7, CRP from 65.2 to 0.4 mg/l and ESR from 49 to 6.5 mm; all p < 0.05) as did the median SUVmax (from 5.8 to 5.2; p < 0.05). All values also decreased after TCZ 3 (PMR-AS from 38.2 to 3.9, CRP from 65.2 to 0.2, ESR from 49 to 2, and SUVmax from 5.8 to 4.7; p < 0.05). In a region-based analysis, all SUVmax were significantly reduced after TCZ 3, except the values for the cervical spinous processes and shoulder regions. With regard to correlations, few significant differences were found between ∇SUVmax and the other parameters including ∇PMR-AS, ∇CRP and ∇ESR in the patient-based and region-based analysis. FDG uptake decreased significantly but moderately after TCZ therapy in PMR patients, and might reflect disease activity. (orig.)

  20. Value of 18F-FDG PET/CT for therapeutic assessment of patients with polymyalgia rheumatica receiving tocilizumab as first-line treatment

    International Nuclear Information System (INIS)

    Palard-Novello, X.; Querellou, S.; Abgral, R.; Salauen, P.Y.; Gouillou, M.; Saraux, A.; Devauchelle-Pensec, V.; Marhadour, T.; Garrigues, F.

    2016-01-01

    To evaluate the use of 18 F-FDG PET/CT for the assessment of tocilizumab (TCZ) as first-line treatment in patients with polymyalgia rheumatica (PMR). Patients with PMR were prospectively enrolled in a multicentre clinical trial assessing TCZ therapy (the TENOR trial). The patients underwent FDG PET/CT at baseline, after the first infusion of TCZ (TCZ 1) and after the last infusion of TCZ (TCZ 3). Responses to treatment were evaluated in terms of the PMR activity score (PMR-AS), and the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) laboratory tests. Maximal standardized uptake value (SUVmax) was used for assessment of FDG uptake in regions usually affected in PMR (spinous processes, hips, shoulders, sternoclavicular region and ischial tuberosities). The Wilcoxon test was applied to evaluate the changes in parameters after the infusions and Spearman's rank correlation test was applied to assess the correlations between SUVmax and PMR-AS, CRP and ESR. Of 21 patients included in the trial, 18 were evaluated. The median bioclinical parameter values decreased after TCZ 1 (PMR-AS from 38.2 to 15.7, CRP from 65.2 to 0.4 mg/l and ESR from 49 to 6.5 mm; all p < 0.05) as did the median SUVmax (from 5.8 to 5.2; p < 0.05). All values also decreased after TCZ 3 (PMR-AS from 38.2 to 3.9, CRP from 65.2 to 0.2, ESR from 49 to 2, and SUVmax from 5.8 to 4.7; p < 0.05). In a region-based analysis, all SUVmax were significantly reduced after TCZ 3, except the values for the cervical spinous processes and shoulder regions. With regard to correlations, few significant differences were found between ∇SUVmax and the other parameters including ∇PMR-AS, ∇CRP and ∇ESR in the patient-based and region-based analysis. FDG uptake decreased significantly but moderately after TCZ therapy in PMR patients, and might reflect disease activity. (orig.)

  1. Comparison of the Serum Tumor Markers S100 and Melanoma-inhibitory Activity (MIA) in the Monitoring of Patients with Metastatic Melanoma Receiving Vaccination Immunotherapy with Dendritic Cells.

    Science.gov (United States)

    Uslu, Ugur; Schliep, Stefan; Schliep, Klaus; Erdmann, Michael; Koch, Hans-Uwe; Parsch, Hans; Rosenheinrich, Stina; Anzengruber, Doris; Bosserhoff, Anja Katrin; Schuler, Gerold; Schuler-Thurner, Beatrice

    2017-09-01

    In patients with melanoma, early dissemination via lymphatic and hematogenous routes is frequently seen. Thus, besides clinical follow-up examination and imaging, reliable melanoma-specific serological tumor markers are needed. We retrospectively compared two serum markers for melanoma, S100 and melanoma-inhibitory activity (MIA), for monitoring of patients with metastatic melanoma under either adjuvant or therapeutic vaccination immunotherapy with dendritic cells (DC). Serum was obtained from a total of 100 patients (28 patients in stage III and 72 patients in stage IV, according to the American Joint Committee on Cancer 2002) at regular intervals during therapy, accompanied by follow-up imaging. When relapse was detected, both markers often remained within normal range. In contrast, in patients with metastatic measurable disease receiving therapeutic and not adjuvant DC vaccination, an increase of both markers was a strong indicator for disease progression. When comparing both markers in the whole study population, MIA showed a superior sensitivity to detect disease progression. S100 and MIA are highly sensitive tumor markers for monitoring of patients with melanoma with current metastases, but less sensitive for monitoring of tumor-free patients. In the current study, MIA had a slightly superior sensitivity to detect progressive disease compared to S100 and seems to be more useful in monitoring of patients with metastatic melanoma receiving immunotherapy. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  2. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab.

    Science.gov (United States)

    Topalian, Suzanne L; Sznol, Mario; McDermott, David F; Kluger, Harriet M; Carvajal, Richard D; Sharfman, William H; Brahmer, Julie R; Lawrence, Donald P; Atkins, Michael B; Powderly, John D; Leming, Philip D; Lipson, Evan J; Puzanov, Igor; Smith, David C; Taube, Janis M; Wigginton, Jon M; Kollia, Georgia D; Gupta, Ashok; Pardoll, Drew M; Sosman, Jeffrey A; Hodi, F Stephen

    2014-04-01

    Programmed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued. Patients with advanced melanoma (N = 107) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation. Median overall survival in nivolumab-treated patients (62% with two to five prior systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62% and 43%, respectively. Among 33 patients with objective tumor regressions (31%), the Kaplan-Meier estimated median response duration was 2 years. Seventeen patients discontinued therapy for reasons other than disease progression, and 12 (71%) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to 56+ weeks). Objective response and toxicity rates were similar to those reported previously; in an extended analysis of all 306 patients treated on this trial (including those with other cancer types), exposure-adjusted toxicity rates were not cumulative. Overall survival following nivolumab treatment in patients with advanced treatment-refractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Long-term safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma.

  3. Managing first-line failure.

    Science.gov (United States)

    Cooper, David A

    2014-01-01

    WHO standard of care for failure of a first regimen, usually 2N(t)RTI's and an NNRTI, consists of a ritonavir-boosted protease inhibitor with a change in N(t)RTI's. Until recently, there was no evidence to support these recommendations which were based on expert opinion. Two large randomized clinical trials, SECOND LINE and EARNEST both showed excellent response rates (>80%) for the WHO standard of care and indicated that a novel regimen of a boosted protease inhibitor with an integrase inhibitor had equal efficacy with no difference in toxicity. In EARNEST, a third arm consisting of induction with the combined protease and integrase inhibitor followed by protease inhibitor monotherapy maintenance was inferior and led to substantial (20%) protease inhibitor resistance. These studies confirm the validity of the current recommendations of WHO and point to a novel public health approach of using two new classes for second line when standard first-line therapy has failed, which avoids resistance genotyping. Notwithstanding, adherence must be stressed in those failing first-line treatments. Protease inhibitor monotherapy is not suitable for a public health approach in low- and middle-income countries.

  4. Melanoma

    Science.gov (United States)

    ... if they're dark skinned, young, and have no family history. Even for them, behaviors like too much sun exposure and not enough skin protection are important risk factors. How Do People Know They Have It? Many melanomas start out as a mole or a bump ...

  5. First line management in the public sector

    DEFF Research Database (Denmark)

    Voxted, Søren

    first-line managers’ work and to illuminate differences between first-line managers from different occupational groups. The second question relates to current debate about the degree of professionalized management among the municipal first-line managers. In both the international and Danish management......The paper will examines and discusses the results from a structured observational study, wherein 50 first-line managers from the public sector in Denmark in five areas of employment where observed. These observational studies are a key contribution in the ‘greenhouse for management’ project...

  6. The incidence of first-line antiretroviral treatment changes and ...

    African Journals Online (AJOL)

    The review included records of HIV-infected patients aged ≥ 18 years, who received either stavudine or zidovudine or tenofovir disoproxil fumarate-based regimens. Using systematic random sampling, the study selected 1 500 records and censoring targeted the first incident of a drug change from the first-line cART.

  7. Stereotactic Radiosurgery for Melanoma Brain Metastases in Patients Receiving Ipilimumab: Safety Profile and Efficacy of Combined Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Kiess, Ana P. [Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland (United States); Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wolchok, Jedd D. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Barker, Christopher A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Postow, Michael A. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Tabar, Viviane [Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Huse, Jason T. [Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Chan, Timothy A.; Yamada, Yoshiya [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Beal, Kathryn, E-mail: bealk@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2015-06-01

    Purpose: Ipilimumab (Ipi), a monoclonal antibody against cytotoxic T-lymphocyte antigen-4, has been shown to improve survival in patients with metastatic melanoma. In this single-institution study, we investigated the safety and efficacy of stereotactic radiosurgery (SRS) for patients with melanoma brain metastases (BMs) who also received Ipi. Methods and Materials: From 2005 to 2011, 46 patients with melanoma received Ipi and underwent single-fraction SRS for BMs. A total of 113 BMs (91% intact, 9% postoperative) were treated with a median dose of 21 Gy (range, 15-24 Gy). Ipi was given at 3 mg/kg (54%) or 10 mg/kg (46%) for a median of 4 doses (range, 1-21). Adverse events were recorded with the use of the Common Terminology Criteria for Adverse Events 3.0. Kaplan-Meier methods were used to estimate survival, and Cox regression was used to investigate associations. Results: Fifteen patients received SRS during Ipi, 19 received SRS before Ipi, and 12 received SRS after Ipi. Overall survival (OS) was significantly associated with the timing of SRS/Ipi (P=.035) and melanoma-specific graded prognostic assessment (P=.013). Patients treated with SRS during or before Ipi had better OS and less regional recurrence than did those treated with SRS after Ipi (1-year OS 65% vs 56% vs 40%, P=.008; 1-year regional recurrence 69% vs 64% vs 92%, P=.003). SRS during Ipi also yielded a trend toward less local recurrence than did SRS before or after Ipi (1-year local recurrence 0% vs 13% vs 11%, P=.21). On magnetic resonance imaging, an increase in BM diameter to >150% was seen in 50% of patients treated during or before Ipi but in only 13% of patients treated after Ipi. Grade 3 to 4 toxicities were seen in 20% of patients. Conclusion: Overall, the combination of Ipi and SRS appears to be well tolerated. Concurrent delivery of Ipi and SRS is associated with favorable locoregional control and possibly longer survival. It may also cause a temporary increase in tumor size, possibly

  8. Surveillance for brain metastases in patients receiving systemic therapy for advanced melanoma.

    Science.gov (United States)

    Wang, Jennifer; Wei, Caimiao; Noor, Rahat; Burke, Anahit; McIntyre, Susan; Bedikian, Agop Y

    2014-02-01

    The objectives of this study were to determine the cumulative incidence and timing of new brain metastases over the course of systemic therapy for metastatic melanoma and to identify prognostic factors for brain metastases. Chemo-naive patients underwent computed tomography or MRI of the brain every 6 weeks. The cumulative incidence of confirmed brain metastases was calculated at 12-week intervals. Univariable and multivariable competing risk regression models were used to assess the association between the development of brain metastases and potential risk factors of interest. Cumulative incidence with competing risk and competing risk regression was used to assess the brain metastasis-free interval from the time of diagnosis of stage IV disease. The clinical characteristics of the 315 patients with brain metastases were compared with those of 370 brain metastasis-free patients. Among patients with brain metastases, a significantly higher proportion had stage M1b and M1c disease at diagnosis compared with stage M1a and a greater proportion had metastatic disease in three or more visceral sites. Significantly shorter brain metastasis-free intervals were found in these patients compared with patients with M1a disease and those with no visceral metastases. More than 80% of the 230 patients who developed brain metastases during systemic therapy had their brain metastases confirmed within 60 weeks from the onset of advanced melanoma. Imaging studies at 12-week intervals for 60 weeks after the diagnosis of advanced melanoma will detect brain metastases in most of the patients who will eventually develop them.

  9. First-line drugs for hypertension.

    Science.gov (United States)

    Wright, James M; Musini, Vijaya M; Gill, Rupam

    2018-04-18

    This is the first update of a review published in 2009. Sustained moderate to severe elevations in resting blood pressure leads to a critically important clinical question: What class of drug to use first-line? This review attempted to answer that question. To quantify the mortality and morbidity effects from different first-line antihypertensive drug classes: thiazides (low-dose and high-dose), beta-blockers, calcium channel blockers, ACE inhibitors, angiotensin II receptor blockers (ARB), and alpha-blockers, compared to placebo or no treatment.Secondary objectives: when different antihypertensive drug classes are used as the first-line drug, to quantify the blood pressure lowering effect and the rate of withdrawal due to adverse drug effects, compared to placebo or no treatment. The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to November 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We contacted authors of relevant papers regarding further published and unpublished work. Randomized trials (RCT) of at least one year duration, comparing one of six major drug classes with a placebo or no treatment, in adult patients with blood pressure over 140/90 mmHg at baseline. The majority (over 70%) of the patients in the treatment group were taking the drug class of interest after one year. We included trials with both hypertensive and normotensive patients in this review if the majority (over 70%) of patients had elevated blood pressure, or the trial separately reported outcome data on patients with elevated blood pressure. The outcomes assessed were mortality, stroke, coronary heart disease (CHD), total cardiovascular events (CVS), decrease in systolic and diastolic blood pressure, and

  10. Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Eshini Perera

    2013-12-01

    Full Text Available Melanomas are a major cause of premature death from cancer. The gradual decrease in rates of morbidity and mortality has occurred as a result of public health campaigns and improved rates of early diagnosis. Survival of melanoma has increased to over 90%. Management of melanoma involves a number of components: excision, tumor staging, re-excision with negative margins, adjuvant therapies (chemo, radiation or surgery, treatment of stage IV disease, follow-up examination for metastasis, lifestyle modification and counseling. Sentinel lymph node status is an important prognostic factor for survival in patients with a melanoma >1 mm. However, sentinel lymph node biopsies have received partial support due to the limited data regarding the survival advantage of complete lymph node dissection when a micrometastasis is detected in the lymph nodes. Functional mutations in the mitogen-activated pathways are commonly detected in melanomas and these influence the growth control. Therapies that target these pathways are rapidly emerging, and are being shown to increase survival rates in patients. Access to these newer agents can be gained by participation in clinical trials after referral to a multidisciplinary team for staging and re-excision of the scar.

  11. Reappraising first-line treatment in glaucoma management.

    Science.gov (United States)

    Phelan, Peter

    2002-09-01

    Despite treatment, glaucoma patients may still suffer vision loss because of inadequate control of intraocular pressure or late presentation. This article reviews the latest evidence supporting a reappraisal of first-line treatment in the management of glaucoma, including a review of latanoprost, recently approved for first-line treatment of glaucoma and ocular hypertension.

  12. Asymptomatic brain metastases in patients with cutaneous metastatic malignant melanoma

    DEFF Research Database (Denmark)

    Zukauskaite, Ruta; Schmidt, Henrik; Asmussen, Jon Thor

    2013-01-01

    The aim of the study was to identify the frequency of asymptomatic brain metastases detected by computed tomography (CT) scans in patients with metastatic cutaneous melanoma referred to first-line systemic treatment. Between 1995 and 2009, 697 Danish patients were screened with a contrast......-enhanced CT scan of the brain before the start of interleukin-2 (IL-2)-based immunotherapy. Among the 697 patients, 80 had asymptomatic brain metastases (12%). Patients' characteristics did not differ significantly between groups with and without brain metastases. Patients received systemic treatment (IL-2...

  13. Immune monitoring of the circulation and the tumor microenvironment in patients with regionally advanced melanoma receiving neoadjuvant ipilimumab.

    Directory of Open Access Journals (Sweden)

    Ahmad A Tarhini

    Full Text Available We evaluated neoadjuvant ipilimumab in patients with surgically operable regionally advanced melanoma in order to define markers of activity in the blood and tumor as assessed at baseline (before ipilimumab and early on-treatment. Patients were treated with ipilimumab (10 mg/kg intravenously every 3 weeks ×2 doses bracketing surgery. Tumor and blood biospecimens were obtained at baseline and at surgery. Flow cytometry and immunohistochemistry for select biomarkers were performed. Thirty five patients were enrolled; IIIB (3; N2b, IIIC (32; N2c, N3, IV (2. Worst toxicities included Grade 3 diarrhea/colitis (5; 14%, hepatitis (2; 6%, rash (1; 3%, elevated lipase (3; 9%. Median follow up was 18 months: among 33 evaluable patients, median progression free survival (PFS was 11 months, 95% CI (6.2-19.2. There was a significant decrease in circulating myeloid derived suppressor cells (MDSC. Greater decrease in circulating monocyte gate MDSC Lin1-/HLA-DR-/CD33⁺/CD11b⁺ was associated with improved PFS (p = 0.03. There was a significant increase in circulating regulatory T cells (Treg; CD4⁺CD25hi⁺Foxp3⁺ that, unexpectedly, was associated with improved PFS (HR = 0.57; p = 0.034. Baseline evidence of fully activated type I CD4⁺ and CD8⁺ antigen-specific T cell immunity against cancer-testis (NY-ESO-1 and melanocytic lineage (MART-1, gp100 antigens was detected and was significantly potentiated after ipilimumab. In tumor, there was a significant increase in CD8⁺ T cells after ipilimumab (p = 0.02. Ipilimumab induced increased tumor infiltration by fully activated (CD69⁺ CD3⁺/CD4⁺ and CD3⁺/CD8⁺ T cells with evidence of induction/potentiation of memory T cells (CD45RO⁺. The change in Treg observed within the tumor showed an inverse relationship with clinical benefit and greater decrease in tumor MDSC subset Lin1-/HLA-DR-/CD33⁺/CD11b⁺ was associated with improved PFS at one year. Neoadjuvant evaluation revealed a

  14. Survival of melanoma patients treated with novel drugs: retrospective analysis of real-world data.

    Science.gov (United States)

    Polkowska, Marta; Ekk-Cierniakowski, Paweł; Czepielewska, Edyta; Wysoczański, Wojciech; Matusewicz, Wojciech; Kozłowska-Wojciechowska, Małgorzata

    2017-10-01

    Recently, several new drugs have been licensed for advanced melanoma therapy, significantly changing the therapeutic landscape. Ipilimumab and vemurafenib were the first drugs that demonstrated a survival benefit over the long-standing standard therapy with dacarbazine. However, the comparative efficacy of these novel drugs has not been properly assessed yet. We conducted a retrospective analysis of all the Polish population treated between January 2012 and October 2016 with one of the following agents: ipilimumab (IPI), vemurafenib (VEM), dabrafenib (DAB), and classic chemotherapy (CTH). The main objective was to assess the overall survival of melanoma patients treated in real-world conditions, taking into account sequences of treatment. We identified 3397 patients with malignant melanoma treated for the first line and the second line. Patients receiving CTH were significantly older than those treated with the novel drugs. At the same time, the population treated with immunotherapy and targeted therapy was well balanced. Overall survival was significantly better for the novel drugs compared to classic chemotherapy in both lines (for the first line, VEM vs CTH HR = 0.72, 95% CI 0.65-0.81; p melanoma provide a significant advantage in survival over classic chemotherapy. Comparative assessment of IPI and VEM indicated no difference, but only immunotherapy-treated patients achieved long-lasting results. Our data on sequential treatment indicate that immunotherapy might be a better option for the first line rather than targeted therapy, but that conclusion requires further studies of the best way to manage the treatment of melanoma patients.

  15. First line chemotherapy plus trastuzumab in metastatic breast cancer ...

    African Journals Online (AJOL)

    Breast cancer is the most common malignant disease and among the most frequent causes of cancer mortality in females worldwide. Metastatic breast cancer (MBC) is conventionally considered to be incurable. In first-line treatment of HER-2 positive MBC, randomized trials have demonstrated that trastuzumab when ...

  16. Overall Survival in Patients With Advanced Melanoma Who Received Nivolumab Versus Investigator's Choice Chemotherapy in CheckMate 037: A Randomized, Controlled, Open-Label Phase III Trial.

    Science.gov (United States)

    Larkin, James; Minor, David; D'Angelo, Sandra; Neyns, Bart; Smylie, Michael; Miller, Wilson H; Gutzmer, Ralf; Linette, Gerald; Chmielowski, Bartosz; Lao, Christopher D; Lorigan, Paul; Grossmann, Kenneth; Hassel, Jessica C; Sznol, Mario; Daud, Adil; Sosman, Jeffrey; Khushalani, Nikhil; Schadendorf, Dirk; Hoeller, Christoph; Walker, Dana; Kong, George; Horak, Christine; Weber, Jeffrey

    2018-02-01

    Purpose Until recently, limited options existed for patients with advanced melanoma who experienced disease progression while receiving treatment with ipilimumab. Here, we report the coprimary overall survival (OS) end point of CheckMate 037, which has previously shown that nivolumab resulted in more patients achieving an objective response compared with chemotherapy regimens in ipilimumab-refractory patients with advanced melanoma. Patients and Methods Patients were stratified by programmed death-ligand 1 expression, BRAF status, and best prior cytotoxic T-lymphocyte antigen-4 therapy response, then randomly assigned 2:1 to nivolumab 3 mg/kg intravenously every 2 weeks or investigator's choice chemotherapy (ICC; dacarbazine 1,000 mg/m 2 every 3 weeks or carboplatin area under the curve 6 plus paclitaxel 175 mg/m 2 every 3 weeks). Patients were treated until they experienced progression or unacceptable toxicity, with follow-up of approximately 2 years. Results Two hundred seventy-two patients were randomly assigned to nivolumab (99% treated) and 133 to ICC (77% treated). More nivolumab-treated patients had brain metastases (20% v 14%) and increased lactate dehydrogenase levels (52% v 38%) at baseline; 41% of patients treated with ICC versus 11% of patients treated with nivolumab received anti-programmed death 1 agents after randomly assigned therapy. Median OS was 16 months for nivolumab versus 14 months for ICC (hazard ratio, 0.95; 95.54% CI, 0.73 to 1.24); median progression-free survival was 3.1 months versus 3.7 months, respectively (hazard ratio, 1.0; 95.1% CI, 0.78 to 1.436). Overall response rate (27% v 10%) and median duration of response (32 months v 13 months) were notably higher for nivolumab versus ICC. Fewer grade 3 and 4 treatment-related adverse events were observed in patients on nivolumab (14% v 34%). Conclusion Nivolumab demonstrated higher, more durable responses but no difference in survival compared with ICC. OS should be interpreted with

  17. Flecainide as first-line treatment for fetal supraventricular tachycardia.

    Science.gov (United States)

    Ekiz, Ali; Kaya, Basak; Bornaun, Helen; Acar, Deniz Kanber; Avci, Muhittin Eftal; Bestel, Aysegul; Yildirim, Gokhan

    2018-02-01

    The aim of this study was to evaluate utilization, efficacy, and side effects of flecainide treatment as first-line agent in patients with fetal supraventricular tachycardia (SVT). This retrospective review was conducted on 23 consecutive fetal tachyarrhythmia cases that met inclusion criteria. If the treatment was necessary, then flecainide was used as first-line treatment in all cases. Among the study group, there were 21 (91.3%) cases of SVT and 2 (8.6%) cases of Atrial Flutter (AF). Sixteen fetuses had persistent SVT and five fetuses had intermittent SVT. We treated 17 fetuses with flecainide monotherapy and 15 of them converted to sinus rhythm and remaining two fetuses were refractory to monotherapy. The median time to conversion to sinus rhythm was 3.8 ± 1.6 days. Only one fetus (20%) among the intermittent SVT cases required anti-arrhythmic treatment. Our study has demonstrated that flecainide is an effective first-line treatment for fetal SVT with high success rate (88.2%), low side effect profile and relatively easy utilization. Based on the current study and recently published article results, flecainide can be recommended as the drug of first choice for treatment of fetal SVT cases.

  18. First Line Treatment of Meniere’s Disease

    Directory of Open Access Journals (Sweden)

    Anup Acharya

    2016-12-01

    Full Text Available Introduction: There is no consensus on the first line medical treatment of Meniere disease to produce symptomatic improvement and slow the disease progress. Dietary salt restriction, diuretics, and vasodilators like betahistine are among the first line drugs that have been used for long. There is lack of evidence due to paucity of quality studies to support their effectiveness and advocate their use. This study is done to evaluate the effectiveness of three first line treatment of Meniere disease i.e. salt restriction, oral diuretics, and betahistine. Methods: Double blind randomized controlled trial was carried out in out-patient clinic of Ear Nose and Throat department of Lumbini Medical College Teaching Hospital. Cases were randomized into three groups; dietary salt restriction, diuretics as amiloride and furosemide, and vasodilator as betahistine. Pre and post treatment evaluation was done in terms of number and severity of vertigo, tinnitus, and hearing outcome. Results: There were a total of 97 cases with F:M ratio of 1.1:1. Mean age of patients was 47.86 yr (SD=12.7. Twenty-nine (30% were treated with dietary sodium restriction alone (Group A, 35 (36% were treated with diuretics (Group B and the rest 33 (34% were treated with vasodilator (betahistine, Group C. There was no significant difference in hearing outcome in any group. Tinnitus was significantly improved in Group B. Number of vertigo attack was significantly decreased in Group B and Group C. Severity of vertigo was significantly decreased in Group B. Conclusion: Dietary salt restriction alone was not effective in controlling any aspect of the disease whereas diuretics were effective in reducing tinnitus and number and severity of vertigo. Betahistine was effective in reducing the number of vertigo attacks but not effective on other aspects of the disease.

  19. Diagnostic and therapeutic approaches in Italian hospitals: adjuvant and metastatic therapy in melanoma.

    Science.gov (United States)

    Chiarion-Sileni, Vanna; Guida, Michele; Romanini, Antonella; Bernengo, Maria Grazia; Ascierto, Paolo; Queirolo, Paola; Mandalà, Mario; Maio, Michele; Ferraresi, Virginia; Stanganelli, Ignazio; Testori, Alessandro; Ridolfi, Ruggero

    2013-01-01

    Melanoma incidence and mortality rates are rising in Italy, indicating that more effective treatments are required both in the adjuvant and metastatic settings. We analyzed clinical practices in the adjuvant and metastatic settings by conducting a nationwide survey of clinicians responsible for managing melanoma treatment and follow-up in a representative sample of Italian hospitals. 95% of participating hospitals completed the panel of questions on adjuvant and metastatic treatment, making it likely that these results give a realistic picture of treatment and follow-up of melanoma patients in Italy. In low-volume hospitals (<25 new melanoma diagnoses yearly) adjuvant therapy was significantly more used than in large-volume hospitals for patients in stage III and IV (82 versus 66% and 56 versus 30%, respectively), and only 11% of patients were enrolled in clinical trials. In the metastatic setting dacarbazine was the preferred first-line treatment (32%) followed by polychemotherapy (23%); 12% of patients were enrolled in clinical trials and less than 10% received interleukin-2, usually subcutaneously. The information provided by this study was used by the Italian Melanoma Intergroup to improve the quality of care and to redirect financial resources. Copyright © 2013 S. Karger AG, Basel.

  20. Melanoma genetics

    DEFF Research Database (Denmark)

    Read, Jazlyn; Wadt, Karin A W; Hayward, Nicholas K

    2015-01-01

    Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of herita......Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence...... in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely...... polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed...

  1. Evaluation of six CTLA-4 polymorphisms in high-risk melanoma patients receiving adjuvant interferon therapy in the He13A/98 multicenter trial

    Directory of Open Access Journals (Sweden)

    Fountzilas George

    2010-11-01

    Full Text Available ABSTRACT Purpose Interferon is approved for adjuvant treatment of patients with stage IIb/III melanoma. The toxicity and uncertainty regarding survival benefits of interferon have qualified its acceptance, despite significant durable relapse prevention in a fraction of patients. Predictive biomarkers that would enable selection of patients for therapy would have a large impact upon clinical practice. Specific CTLA-4 polymorphisms have previously shown an association with response to CTLA-4 blockade in patients with metastatic melanoma and the development of autoimmunity. Experimental design 286 melanoma patients and 288 healthy controls were genotyped for six CTLA-4 polymorphisms previously suggested to be important (AG 49, CT 318, CT 60, JO 27, JO30 and JO 31. Specific allele frequencies were compared between the healthy and patient populations, as well as presence or absence of these in relation to recurrence. Alleles related to autoimmune disease were also investigated. Results No significant differences were found between the distributions of CTLA-4 polymorphisms in the melanoma population compared with healthy controls. Relapse free survival (RFS and overall survival (OS did not differ significantly between patients with the alleles represented by these polymorphisms. No correlation between autoimmunity and specific alleles was shown. The six polymorphisms evaluated where strongly associated (Fisher's exact p-values Conclusion No polymorphisms of CTLA-4 defined by the SNPs studied were correlated with improved RFS, OS, or autoimmunity in this high-risk group of melanoma patients.

  2. Vinorelbine as first-line or second-line therapy for advanced breast cancer

    DEFF Research Database (Denmark)

    Langkjer, Sven T; Ejlertsen, Bent; Mouridsen, Henning

    2008-01-01

    INTRODUCTION: This study was conducted to establish the maximum tolerated dose (MTD) of intravenous vinorelbine and on the determined dose to assess efficacy and safety in patients with metastatic breast cancer previously treated with epirubicin. PATIENTS AND METHODS: Patients had histologically...... proven breast cancer and had received a prior epirubicin based regimen either adjuvant or as first line therapy for advanced disease. Vinorelbine was administered intravenously day 1 and 8 in a 3 weeks' schedule. Subsequently 48 additional patients were treated at one dose-level below MTD. RESULTS: Fifty...

  3. Efficacy and Toxicity of Intrathecal Liposomal Cytarabine in First-line Therapy of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Harila-Saari, Arja; Grell, Kathrine

    2016-01-01

    We investigated efficacy and toxicity of replacing conventional triple (cytarabine, methotrexate, and hydrocortisone) intrathecal therapy (TIT) with liposomal cytarabine during maintenance therapy among 40 acute lymphoblastic leukemia patients. Twenty-eight of 29 patients in the TIT arm received ...... as first-line prevention of relapse....

  4. First-line treatment of acute lymphoblastic leukemia with pegasparaginase

    Directory of Open Access Journals (Sweden)

    Riccardo Masetti

    2009-07-01

    Full Text Available Riccardo Masetti, Andrea PessionPediatric Oncology and Hematology Unit “Lalla Seràgnoli”, University of Bologna, Bologna, ItalyAbstract: Acute lymphoblastic leukemia (ALL accounts for almost 4000 cases annually in the United States, approximately two thirds of which are in children and adolescents. Treatment results of ALL have improved considerably in the past decade, due to an optimal stratification of patients and a rational use of different antileukemic agents among which L-asparaginase (L-ASNase plays a fundamental role. This drug has been used in pediatric ALL chemotherapy protocols for almost 3 decades. In the 1970s and 1980s a chemically modified form of this enzyme called pegasparaginase (PEG-ASNase was rationally synthesized to decrease immunogenicity of the enzyme and prolong its half-life. The different advantages of PEG-ASNase have been demonstrated in many clinical studies, the last of which underline the utility of this drug in front-line therapy of ALL. In this review, we discuss the pharmacological advantages and clinical potential of PEG-ASNase and its important use in first-line treatment of ALL.Keywords: pegasparaginase, acute, lymphoblastic leukemia, pegylation

  5. Gemcitabine plus paclitaxel as first-line chemotherapy for patients with advanced breast cancer.

    Science.gov (United States)

    Delfino, Carlos; Caccia, Graciela; Gonzáles, Luis Riva; Mickiewicz, Elizabeth; Rodger, Jeannette; Balbiani, Luis; Morales, Daniel Flores; Comba, Alberto Zori; Brosio, Celia

    2004-01-01

    To assess the efficacy and tolerability of gemcitabine and paclitaxel as first-line treatment in advanced breast cancer. Patients with histologically confirmed metastatic or metastatic plus locally advanced breast cancer received gemcitabine 1,200 mg/m(2) on days 1 and 8 and paclitaxel 175 mg/m(2) on day 1 every 21 days for 8 cycles. From December 1999 to August 2001, 45 patients, with a median age of 53.5 years (range, 22-77), received a total of 260 cycles. All were assessable for response and toxicity. Twenty-seven patients had prior adjuvant therapy. Hormonal receptor status was positive in 31.1% and negative in 40.0% of patients. Main metastatic sites included soft tissue (62.2%) and lung (53.3%). The objective response rate was 66.7%; complete response, 22.2%; partial response, 44.4%; stable disease, 15.6%; progressive disease, 17.8%. Median duration of response was 18 months and median time to tumor progression was 11 months. Grade 3/4 leukopenia, neutropenia, and thrombocytopenia developed in 13.3% of patients, and 15.5% developed grade 3/4 mucositis. No treatment-related deaths occurred. Median overall survival was 19 months. Gemcitabine plus paclitaxel is an active combination with a favorable toxicity profile as first-line treatment for patients with advanced breast cancer. Copyright 2004 S. Karger AG, Basel

  6. Thin melanoma.

    Science.gov (United States)

    Elder, David E

    2011-03-01

    The incidence of malignant melanoma is increasing and a preponderance of the melanomas diagnosed today are "thin in terms of Breslow criteria. Although thin melanomas, as a group, are associated with a very good prognosis, a subset of these tumors may metastasize and cause death. These cases can be identified by using prognostic models, including the "standard" American Joint Committee on Cancer criteria, and other attributes identified in follow-up studies. To review the history of concepts of prognostic modeling in melanoma, focusing on thin melanomas. Selected literature. About 40 years ago, it was realized that malignant melanoma, once almost uniformly fatal, could be divided into categories with better or worse prognosis through the use of prognostic models. The first simple models, Clark levels of invasion and Breslow thickness, are still in use. Thickness remains the single most useful variable. Breslow recognized that melanomas less than 0.76 mm in thickness were associated with a very good prognosis, with no metastases in his limited initial study. The American Joint Committee on Cancer selected a cutoff of 1.0 mm, which achieves a similar result, with stage modifiers, although some metastases and deaths do occur with stage I lesions. Clark demonstrated an almost equally good prognosis for his level II invasive melanomas and recognized that most of these lesions, although invasive, lacked the ability to form tumors or to undergo mitosis in the dermis and were therefore "nontumorigenic" and "nonmitogenic" and lacked competence for metastasis. Studies of these low-risk melanomas have led to the development of criteria for earlier diagnosis and a steady, but still inadequate, improvement in prognosis for melanoma overall. Multivariable models currently can identify groups of patients within the "thin melanoma" category whose prognosis varies, from a disease-free survival of close to 100% to about 70%. Prognosis declines more or less linearly with increasing

  7. Underreporting of side effects of standard first-line ART in the routine ...

    African Journals Online (AJOL)

    Malawi Medical Journal; 23(4): 116-118 December 2011. Side effects of standard first line in ART 116. Underreporting of side effects of standard first-line. ART in the routine setting in Blantyre, Malawi. Abstract. Introduction. In the Malawi ART programme, 92% of 250,000 patients are using the standard first-line regime of ...

  8. Clinical outcome of patients who reduced sunitinib or pazopanib during first-line treatment for advanced kidney cancer.

    Science.gov (United States)

    Iacovelli, Roberto; Cossu Rocca, Maria; Galli, Luca; De Giorgi, Ugo; Sabbatini, Roberto; Santoni, Matteo; Mosca, Alessandra; Fornarini, Giuseppe; Massari, Francesco; Masini, Cristina; Bersanelli, Melissa; Biasco, Elisa; Lolli, Cristian; Guida, Annalisa; Berardi, Rossana; Terrone, Carlo; Pastorino, Alessandro; Ardizzoni, Andrea; Pinto, Carmine; Buti, Sebastiano; Nolè, Franco; Tortora, Giampaolo

    2017-09-01

    To investigate the different outcomes in patients with metastatic renal cell carcinoma (mRCC) who receive a reduced first-line dose of sunitinib or pazopanib compared to those who continue at the standard dose. All the patients treated in 11 oncological centers in Italy for mRCC who started first-line treatment with sunitinib or pazopanib at the standard dose. Descriptive statistical tests were used to highlight differences among groups. Survival was estimated by the Kaplan-Meier method and compared across the groups using log-rank tests, the Cox proportional hazards model adjusted for statistically significant variables was also done. A total of 591 patients were included in the study. Of these, 45.7% received a reduced dose of sunitinib or pazopanib after a median treatment time of 3.6 months at the standard dose. The median overall survival in the patients who continued to receive the standard dose was 24.0 months compared to 49.4 months for those who received a reduced dose (hazard ratio = 1.80; 95% CI: 1.42-2.29; P<0.001). Only 45% of the patients received second-line therapy: 42.5% had an mTOR and 54.1% a tyrosine kinase inhibitor. Second-line overall survival was 19.8 and 11.8 months, respectively, in the patients who received, or did not, a reduced dose during first-line therapy (P = 0.007). Toxicity-related dose reduction is a common event in mRCC patients who have started first-line therapy with either sunitinib or pazopanib. This is positively related to the outcomes of both first- and second-line therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Ocular Melanoma

    Science.gov (United States)

    ... also occur on the conjunctiva . Because most eye melanomas form in the part of the eye you can’t see when looking in a mirror, they can be difficult to detect. Also, eye melanoma typically doesn’t cause early signs or symptoms . ...

  10. Malignant melanoma

    NARCIS (Netherlands)

    de Braud, Filippo; Khayat, David; Kroon, Bin B. R.; Valdagni, Riccardo; Bruzzi, Paolo; Cascinelli, Natale

    2003-01-01

    In the European Community cutaneous melanoma accounts for 1 and 1.8% of cancers occurring in men and women, respectively. The incidence rate is increasing faster than that of any other tumour. Sun exposure, patient's phenotype, family history, and history of a previous melanoma are the major risk

  11. Patterns and determinants of new first-line antihyperglycaemic drug use in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Geier, A S; Wellmann, I; Wellmann, J; Kajüter, H; Heidinger, O; Hempel, G; Hense, H W

    2014-10-01

    We evaluated the patterns and determinants that influence the selection, timing and duration of first-line antihyperglycaemic drug (AHD) treatment in patients with type 2 diabetes in Germany, focusing specifically on treatment-naive AHD initiators. Pharmacy dispensing claims data were linked with a cohort of patients newly enrolled in a German Disease Management Program for type 2 diabetes (DMP-DM2) between 2003 and 2009. We examined uptake of first-line pharmacotherapy in previously unmedicated patients and identified predictors of receiving AHD therapy in general and metformin in particular using multivariable regression analyses. There were 27,138 unmedicated patients with type 2 diabetes and 47.0% of them were started on AHD treatment within 5 years after enrollment. Initial severity of diabetes was the major predictor of receiving first-line pharmacotherapy. Metformin accounted for 63% of newly prescribed AHD in 2003 and more than 80% in 2009 while sulfonylureas accounted for only 10%. Initiating metformin as first-line AHD was associated with younger age, higher BMI, lower HbA1c, and shorter diabetes duration (multivariate p<0.001 for all). Therapy switch or step-up was less frequent among metformin initiators than sulfonylurea initiators. The majority of patients were not started on AHD therapy within 5 years after enrollment. In line with recent therapy guidelines, current first-line antihyperglycaemic treatment was increasingly based on metformin. AHD initiators started on sulfonylurea were generally more advanced in their disease and were started later on primary pharmacotherapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Ketamine as a first-line treatment for severely agitated emergency department patients.

    Science.gov (United States)

    Riddell, Jeff; Tran, Alexander; Bengiamin, Rimon; Hendey, Gregory W; Armenian, Patil

    2017-07-01

    Emergency physicians often need to control agitated patients who present a danger to themselves and hospital personnel. Commonly used medications have limitations. Our primary objective was to compare the time to a defined reduction in agitation scores for ketamine versus benzodiazepines and haloperidol, alone or in combination. Our secondary objectives were to compare rates of medication redosing, vital sign changes, and adverse events in the different treatment groups. We conducted a single-center, prospective, observational study examining agitation levels in acutely agitated emergency department patients between the ages of 18 and 65 who required sedation medication for acute agitation. Providers measured agitation levels on a previously validated 6-point sedation scale at 0-, 5-, 10-, and 15-min after receiving sedation. We also assessed the incidence of adverse events, repeat or rescue medication dosing, and changes in vital signs. 106 patients were enrolled and 98 met eligibility criteria. There was no significant difference between groups in initial agitation scores. Based on agitation scores, more patients in the ketamine group were no longer agitated than the other medication groups at 5-, 10-, and 15-min after receiving medication. Patients receiving ketamine had similar rates of redosing, changes in vital signs, and adverse events to the other groups. In highly agitated and violent emergency department patients, significantly fewer patients receiving ketamine as a first line sedating agent were agitated at 5-, 10-, and 15-min. Ketamine appears to be faster at controlling agitation than standard emergency department medications. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Metastatic melanoma and vemurafenib: novel approaches

    Directory of Open Access Journals (Sweden)

    Ramon Andrade De Mello

    2012-04-01

    Full Text Available Metastatic melanoma (MM presents a treatment challenge to oncologists worldwide. Dacarbazine is the first line chemotherapy treatment for MM, though the overall response rates are very poor. Recently, the v-raf murine sarcoma viral oncogene homolog B1 (BRAF V600 mutation was found to play a main role in MM. This mutation is present in 40-60% of melanoma patients. Vemurafenib is a BRAF kinase inhibitor that showed impressive results in phase I-III trials and was thus recently approved for the treatment of MM. This paper will briefly focus on vemurafenib in the treatment of MM and highlight concerns.

  14. Delayed pressure urticaria - dapsone heading for first-line therapy?

    Science.gov (United States)

    Grundmann, Sonja Alexandra; Kiefer, Sabine; Luger, Thomas Anton; Brehler, Randolf

    2011-11-01

    Pressure urticaria as a subform of physical urticaria is rare and treatment is often difficult. Established therapeutic regimes include antihistamines (generally exceeding approved dosages in order to achieve a therapeutic benefit) or antihistamines combined with montelukast. Complete relief of symptoms is difficult. We used dapsone as an early therapeutic alternative in the event of treatment failure and established a standardized therapeutic regime at our clinic. We surveyed 31 patients retrospectively who had received dapsone between 2003-2009. In 74 % of patients in whom symptoms persisted despite established therapies, the results of treatment with dapsone were good or very good. Longer-term pressure urticaria and the co-existence of a chronic spontaneous urticaria were associated with a smaller benefit (pdapsone in patients with pressure urticaria has such a good risk-benefit ratio that we support early treatment initiation. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.

  15. Gemcitabine/paclitaxel as first-line treatment of advanced breast cancer.

    Science.gov (United States)

    Delfino, Carlos; Caccia, Graciela; Riva Gonzáles, Luis; Mickiewicz, Elizabeth; Rodger, Jeannette; Balbiani, Luis; Flores Morales, Daniel; Zori Comba, Alberto; Brosio, Celia

    2003-12-01

    Gemcitabine (Gemzar) and paclitaxel exhibit good activity and good safety profiles when used alone and together in the treatment of advanced breast cancer. In a phase II trial, 45 patients with metastatic breast cancer received gemcitabine at 1,200 mg/m2 on days 1 and 8 and paclitaxel at 175 mg/m2 on day 1 every 21 days. Twenty-seven patients (60.0%) had prior adjuvant therapy. Objective response was observed in 30 patients (objective response rate 66.7%, 95% confidence interval [CI] = 52%-71%), including complete response in 10 (22.2%) and partial response in 20 (44.4%). Median duration of response was 18 months (95% CI = 11-26.7 months), median time to tumor progression for the entire population was 11 months (95% CI = 7.1-18.7 months), median overall survival was 19 months (95% CI = 17.3-21.7 months), and the 1-year survival rate was 69%. Treatment was well tolerated, with grade 3/4 toxicities being infrequent. Grade 3/4 leukopenia, neutropenia, and thrombocytopenia were each observed in six patients (13.3%). No patient was discontinued from the study due to hematologic or nonhematologic toxicity. Thus, the gemcitabine/paclitaxel combination shows promising activity and tolerability when used as first-line treatment in advanced disease. The combination recently has been shown to be superior to paclitaxel alone as first-line treatment in anthracycline-pretreated advanced disease according to interim results of a phase III trial and it should be further evaluated in comparative trials in breast cancer.

  16. Intratympanic Methylprednisolone Injection as First Line Therapy for Idiopathic Sudden Sensorineural Hearing Loss

    Directory of Open Access Journals (Sweden)

    Mukul Patar

    2017-08-01

    Full Text Available Introduction Steroid therapy is considered to be the gold standard for sudden sensorineural hearing loss (SSNHL. Delivering steroids by intratympanic injection is more efficient than systemic injections with minimum or no side effects. The present study was aimed to evaluate the efficacy and safety of intratympanic methylprednisolone injections as initial first line therapy for unilateral idiopathic SSNHL and the ease of giving it by otoendoscopy. Materials and Methods A prospective analysis was performed for the patients diagnosed as unilateral idiopathic SSNHL from April 2014 to April 2016 and receiving intratympanic steroids injections as first line therapy. Patients with unilateral sensorineural hearing loss of at least 30 dB at 3 contiguous frequencies occurring within a period of not more than 3 days are only included. All of the intratympanic steroid (ITS injections were administered as OPD procedures. Each patient was treated by 3 injections given at 3 days interval.  Results A total of 22 patients who underwent primary intratympanic steroid (ITS injection for unilateral SSNHL during the study period were included in the study. The mean age was 42.22 years (+ 9.79 and age ranged from 27 to 68 years. Patients included in our study came within 2nd to 27th day of occurrence of deafness and the mean duration (days from onset of disease to start of ITS was 7.86 days. The average hearing gain in our study was 44.22 dB. In the present study 11 patients (50% showed complete hearing improvement and 10 cases (45.45% had partial and one (4.54% showed no hearing recovery at 3 weeks follow up period. Conclusion Minimal systemic absorption with minimum or no systemic effects and high percentage of success rate encouraged the surgeons to prefer ITS as primary therapy for idiopathic unilateral SSNHL. It is effective, cheap, well-tolerated and can be performed as OPD procedure.

  17. First-line chemotherapy with pemetrexed plus cisplatin for malignant peritoneal mesothelioma.

    Science.gov (United States)

    Fujimoto, Eriko; Kijima, Takashi; Kuribayashi, Kozo; Negi, Yoshiki; Kanemura, Shingo; Mikami, Koji; Doi, Hiroshi; Kitajima, Kazuhiro; Nakano, Takashi

    2017-09-01

    Mesothelioma of peritoneal origin has wider variation in treatment outcomes than mesothelioma of pleural origin, likely because peritoneal mesothelioma comprises borderline malignant variants and aggressive malignant peritoneal mesothelioma (MPeM). This study retrospectively evaluates the efficacy of first-line systemic pemetrexed and cisplatin chemotherapy in MPeM. Twenty-four patients with histologically proven MPeM were treated with pemetrexed plus cisplatin as a first-line systemic chemotherapy. The response was evaluated radiologically according to standard Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Twenty-two patients underwent 18 F-fluorodeoxyglucose positron emission tomography/(FDG-PET)/computed tomography(CT) at baseline, and 13 were eligible for metabolic assessment. Two complete responses and 9 partial responses were achieved. Overall response rate and disease control rate were 45.8% and 91.7%, respectively. Median progression-free survival and median overall survival were 11.0 months and 15.8 months, respectively. Wet- type MPeM had significantly longer survival (40.9 months median) than other clinical types (15.5 months) (P = 0.045). The baseline maximum standardized uptake value in 22 patients was 8.93 (range, 2.5-16.77). Systemic pemetrexed plus cisplatin is active for MPeM. Disparity with the outcome of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) needs to receive more emphasis, since peritoneal mesothelioma has a 5-year survival rate of 50%.

  18. First-line Bismuth-containing Five-day Concomitant Quintuple Therapy for Helicobacter Pylori Eradication.

    Science.gov (United States)

    Dolapcioglu, Can; Sayiner, Mehmet; Akkus, Esra Elif; Kural, Abdulaziz; Dolapcioglu, Hatice; Dabak, Resat; Ahishali, Emel

    2016-04-01

    Widespread use of antibiotics has resulted in increased rates of antibiotic resistance and decreased rates of Helicobacter pylori (H. pylori) eradication, leading to a search for newer therapeutic options. This study aimed to examine the efficacy, tolerability, and patient compliance of a first-line bismuth-containing 5-day concomitant quintuple therapy. This prospective study included 144 eradication treatment naïve H. pylori positive patients with dyspeptic complaints. Patients received the following concomitant quintuple therapy for 5 days: bismuth subcitrate 300 mg q.i.d, omeprazole 20 mg b.i.d, clarithromycin 500 mg b.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg t.i.d. Eradication was assessed with H. pylori stool antigen test or urea-breath test 6 weeks after the completion of therapy. Treatment compliance rate in this study was 97.2%. Intention to treat and per-protocol eradication rates were 134/144 (93.1%, 95% CI, 88.9-97.2) and 134/140 (95.7%, 95% CI, 92.2-98.6), respectively. Side effect was reported by 8.5% of the patients that attended follow-up visits, including epigastric pain (2.8%), nausea/vomiting (2.1%), diarrhea (1.4%), taste disturbance (1.4%), and fatigue (0.7%). Bismuth-containing, short course, quintuple concomitant therapy appears to be an effective and safe therapeutic option for the first-line H. pylori eradication, particularly in populations with high resistance. © 2015 John Wiley & Sons Ltd.

  19. Genetic alterations and markers of melanoma

    Directory of Open Access Journals (Sweden)

    N. N. Mazurenko

    2014-01-01

    progress in melanoma studies allow to receive the positive results in melanoma treatment in particularly with targeted therapy. The molecular targets and future perspectives for targeted therapy of metastatic skin melanoma are discussed.

  20. Absolute number of new lesions on 18F-FDG PET/CT is more predictive of clinical response than SUV changes in metastatic melanoma patients receiving ipilimumab.

    Science.gov (United States)

    Anwar, Hoda; Sachpekidis, Christos; Winkler, Julia; Kopp-Schneider, Annette; Haberkorn, Uwe; Hassel, Jessica C; Dimitrakopoulou-Strauss, Antonia

    2018-03-01

    Evaluation of response to immunotherapy is a matter of debate. The aim of the present study was to evaluate the response of metastatic melanoma to treatment with ipilimumab by means of 18 F-FDG PET/CT, using the patients' clinical response as reference. The final cohort included in the analyses consisted of 41 patients with metastatic melanoma who underwent 18 F-FDG PET/CT before and after administration of ipilimumab. After determination of the best clinical response, the PET/CT scans were reviewed and a separate independent analysis was performed, based on the number and functional size of newly emerged 18 F-FDG-avid lesions, as well as on the SUV changes after therapy. The median observation time of the patients after therapy was 21.4 months (range 6.3-41.9 months). Based on their clinical response, patients were dichotomized into those with clinical benefit (CB) and those without CB (No-CB). The CB group (31 patients) included those with stable disease, partial remission and complete remission, and the No-CB group (10 patients) included those with progressive disease. The application of a threshold of four newly emerged 18 F-FDG-avid lesions on the posttherapy PET/CT scan led to a sensitivity (correctly predicting CB) of 84% and a specificity (correctly predicting No-CB) of 100%. This cut-off was lower for lesions with larger functional diameters (three new lesions larger than 1.0 cm and two new lesions larger than 1.5 cm). SUV changes after therapy did not correlate with clinical response. Based on these findings, we developed criteria for predicting clinical response to immunotherapy by means of 18 F-FDG PET/CT (PET Response Evaluation Criteria for Immunotherapy, PERCIMT). Our results show that a cut-off of four newly emerged 18 F-FDG-avid lesions on posttherapy PET/CT gives a reliable indication of treatment failure in patients under ipilimumab treatment. Moreover, the functional size of the new lesions plays an important role in predicting the clinical

  1. Implementing Human Resource Management Successfully: A First-Line Management Challenge

    NARCIS (Netherlands)

    Bos-Nehles, Anna Christina; van Riemsdijk, Maarten; Looise, Jan C.

    2006-01-01

    In this paper we will address the success of Human Resource Management (HRM) implementation, concentrating not on the HR function but on first-line managers. First-line managers find implementing HR practices at the operational level difficult and show reluctance with their HR responsibilities.

  2. Determinants of durability of first-line antiretroviral therapy regimen and time from first-line failure to second-line antiretroviral therapy initiation

    DEFF Research Database (Denmark)

    Desmonde, Sophie; Eboua, François T; Malateste, Karen

    2015-01-01

    BACKGROUND: We described reasons for switching to second-line antiretroviral treatment (ART) and time to switch in HIV-infected children failing first-line ART in West Africa. METHODS: We included all children aged 15 years or less, starting ART (at least three drugs) in the paediatric Ie...... post-ART initiation, 188 (7%) had switched to second-line. The most frequent reasons were drug stock outs (20%), toxicity (18%), treatment failure (16%) and poor adherence (8%). Over the 24-month follow-up period, 322 (12%) children failed first-line ART after a median time of 7 months...... rare and switches after an immunological failure were insufficient. These gaps reveal that it is crucial to advocate for both sustainable access to first-line and alternative regimens to provide adequate roll-out of paediatric ART programmes....

  3. First-line HIV treatment: evaluation of backbone choice and its budget impact

    Directory of Open Access Journals (Sweden)

    Orietta Zaniolo

    2013-06-01

    Full Text Available OBJECTIVE: The gradual increase of persons living with HIV, mainly due to the reduced mortality achieved with effective antiretroviral therapies, calls for increased rationality and awareness in health resources consumption also during the early illness phases. Aim of this work is the estimation of the budget impact related to the variation in backbone prescribing trends in naïve patients.METHODS: Target population is the number of patients starting antiretroviral therapy each year, according to the Italian HIV surveillance registry, excluding patients receiving non-authorized or non-recommended regimens. We modeled 3-year mortality and durability rates on a dynamic cohort, basing on international literature. A prevalent patients analysis has also been conducted, for which the model is fed by a closed cohort consisting of all the patients without experience of virologic failure. The aim of this collateral analysis is to estimate the difference in current annual expenditures if the past prescription trends for patients starting therapy would have led to the evaluated hypothetical scenarios. Current Italian market shares of triple regimens containing first-choice or alternative backbones (tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine are compared to three hypothetical scenarios (base-case, minimum and maximum in which increasing shares of patients eligible to abacavir/lamivudine start first line treatment with this backbone. Annual cost for each regimen comprises drugs acquisition under hospital pricing rules, monitoring exams and preventive tests, valued basing on regional reimbursement tariffs.RESULTS: According to current prescribing trends, in the next three years about 13,000 patients starting HIV therapy will receive tenofovir/emtricitabine (83% of the target population, and minor portions other regimens (9% abacavir/lamivudine, 8% zidovudine/lamivudine. Patients that would be eligible to

  4. Uveal Melanoma

    International Nuclear Information System (INIS)

    Papastefanou, V. P.; Cohen, V. M. L.; Cohen, V. M. L.

    2011-01-01

    Uveal melanoma is the most common primary intraocular malignancy and the leading primary intraocular disease which can be fatal in adults. In this paper epidemiologic, pathogenetic, and clinical aspects of uveal melanoma are discussed. Despite the advance in local ocular treatments, there has been no change in patient survival for three decades. Development of metastases affects prognosis significantly. Current survival rates, factors predictive of metastatic potential and metastatic screening algorithms are discussed. Proposed and emerging treatments for uveal melanoma metastases are also overviewed. Current advances in genetics and cytogenetics have provided a significant insight in tumours with high metastatic potential and the molecular mechanisms that underlie their development. Biopsy of those lesions may prove to be important for prognostication and to allow further research into genetic mutations and potential new therapeutic targets in the future

  5. First-line treatment of pemphigus vulgaris with a combination of rituximab and high-potency topical corticosteroids.

    Science.gov (United States)

    Ingen-Housz-Oro, Saskia; Valeyrie-Allanore, Laurence; Cosnes, Anne; Ortonne, Nicolas; Hüe, Sophie; Paul, Muriel; Wolkenstein, Pierre; Chosidow, Olivier

    2015-02-01

    The main component of the first-line treatment of pemphigus vulgaris is high doses of systemic corticosteroids, but adverse effects of these drugs are frequent and sometimes severe. Rituximab has shown effectiveness as a corticosteroid-sparing agent or in case of relapse. To our knowledge, the effectiveness of rituximab as a first-line treatment without systemic corticosteroids has not been evaluated. Five women in their 50s, 60s, or 70s with pemphigus vulgaris (Pemphigus Disease Area Index score, 15-84 at diagnosis) and contraindications to systemic corticosteroid treatment received rituximab with high-potency topical corticosteroids as first-line treatment. All patients experienced a favorable response, with a mean time to healing of skin and mucosal lesions of 15 weeks. Two patients, with 42- and 48-month follow-up evaluations, did not experience relapse. Three patients developed 2 to 4 relapses, with effective retreatment achieved using rituximab and topical corticosteroids. No severe adverse effects were observed. Considering the high rate of severe adverse effects induced by prolonged administration of high doses of systemic corticosteroids, new therapeutic options are warranted in the treatment of pemphigus vulgaris. The combination of rituximab and topical corticosteroids could be considered in mild to severe cutaneous disease. Larger long-term studies are needed to evaluate the optimal treatment strategies according to the severity of the disease and the benefit-risk ratio of rituximab.

  6. [A study of leadership training program demands of first-line nurse managers in university hospitals].

    Science.gov (United States)

    Koh, M S

    1998-01-01

    There is an important concern regarding the First-line nurse manager's leadership because of the recognition that effectiveness of Leadership in this position results in benefits for the whole health care organization. So knowledge and practice of effective leadership behavior are now more essential to nursing than ever before. First-line Nurse Managers must be effective leaders to meet today's challenge because staff nurse, patient are affected by them. So the purpose of this study was to identify and to analyse the need for Leadership program of First Line nurse managers in university hospitals. There were three major purposes of this study. First, identify First-line nurse managers general characteristic, second, identify their experience of leadership training, third, identify and analysis their demands for leadership training program. The subjects for this study was 167 First-line nurse manager randomly from 18 university hospitals in Korea. The data were collected through questionnaires from Oct. 13th to Nov. 20th, 1997, data was analysed using frequencies and percentages. Especially the steps of analysis of descriptions were as follows: Initial analysis centered on the identification of the demands of first-line nurse managers. Later analysis collapsed the demands into broad categories. From the collect data, 283 demands of first-line nurse managers were identified. These demands were then sorted into 3 broad categories that included: Self development as first-line nurse managers, relationship with others, and practice The result of the study were as follows: 1) Most of nurse managers (79.6%) had leadership training course and had good experience to improve self leadership. 2) Their demands of leadership training course are as follows: First, for self as first-line nurse managers, they want to learn leadership theory, identify their leadership style and then develop their leadership skill. Second, for others as first-line nurse managers, they want to improve

  7. First-Line Helicobacter pylori Eradication in Patients with Chronic Kidney Diseases in Taiwan

    Directory of Open Access Journals (Sweden)

    Chih-Ming Liang

    2017-01-01

    Full Text Available Aims. Patients with chronic kidney disease (CKD and Helicobacter pylori (H. pylori infection have a higher incidence of gastroduodenal diseases and therefore are recommended to receive eradication therapies. This study aimed to assess the efficacy of a 7-day standard triple therapy in patients with CKD (eGFR < 60 ml/min/1.73 m2 and to investigate the clinical factors influencing the success of eradication. Methods. A total of 758 patients with H. pylori infection receiving a 7-day standard first-line triple therapy between January 1, 2013, and December 31, 2014, were recruited. Patients were divided into two groups: CKD group (N=130 and non-CKD group (N=628. Results. The eradication rates attained by the CKD and non-CKD groups were 85.4% and 85.7%, respectively, in the per-protocol analysis (p=0.933. The eradication rate in CKD stage 3 was 84.5% (82/97, in stage 4 was 88.2% (15/17, and in those who received hemodialysis was 87.5% (14/16. There were no significant differences in the various stages of CKD (p=0.982. The adverse events were similar between the two groups (3.1% versus 4.6%, p=0.433. Compliance between the two groups was good (100.0% versus 99.8%, p=0.649. There was no significant clinical factor influencing the H. pylori eradication rate in the non-CKD and CKD groups. Conclusions. This study suggests that the H. pylori eradication rate and adverse rate in patients with CKD are comparable to those of non-CKD patients.

  8. Caring behaviour perceptions from nurses of their first-line nurse managers.

    Science.gov (United States)

    Peng, Xiao; Liu, Yilan; Zeng, Qingsong

    2015-12-01

    Nursing is acknowledged as being the art and science of caring. According to the theory of nursing as caring, all persons are caring but not every behaviour of a person is caring. Caring behaviours in the relationship between first-line nurse managers and Registered Nurses have been studied to a lesser extent than those that exist between patients and nurses. Caring behaviour of first-line nurse managers from the perspective of Registered Nurses is as of yet unknown. Identifying caring behaviours may be useful as a reference for first-line nurse managers caring for nurses in a way that nurses prefer. To explore first-line nurse managers' caring behaviours from the perspective of Registered Nurses in mainland China. Qualitative study, using descriptive phenomenological approach. Fifteen Registered Nurses recruited by purposive sampling method took part in in-depth interviews. Data were analysed according to Colaizzi's technique. Three themes of first-line nurse managers' caring behaviours emerged: promoting professional growth, exhibiting democratic leadership and supporting work-life balance. A better understanding of the first-line nurse managers' caring behaviours is recognised. The three kinds of behaviours have significant meaning to nurse managers. Future research is needed to describe what first-line nurse managers can do to promote nurses' professional growth, increase the influence of democratic leadership, as well as support their work-life balance. © 2015 Nordic College of Caring Science.

  9. Malignant Melanoma of the Foot

    Science.gov (United States)

    ... Javascript in your browser. Malignant Melanoma of the Foot What Is Malignant Melanoma? Melanoma is a cancer ... age groups, even the young. Melanoma in the Foot Melanoma that occurs in the foot or ankle ...

  10. Genital melanoma: prognosis factors and treatment modality.

    Science.gov (United States)

    Ferraioli, Domenico; Lamblin, Gery; Mathevet, Patrice; Hetu, Jessika; Berakdar, Isabelle; Beurrier, Frederic; Chopin, Nicolas

    2016-11-01

    Genital melanoma is a rare pathology. We present the experience of two comprehensive cancer centers in Lyon (France) in the management of genital melanoma in order to identify prognostic factors and optimal treatments. Between April 1992 and Mars 2014, 16 patients with a primary genital melanoma were referred to our department. Nine patients presented a vaginal melanoma, six vulvar melanomas and only one cervical melanoma. The median dimension of the lesion was 33.7 mm (5-100 mm). The AJCC stage ranged from IB to IIIC. 12 cases were the classic dark-blue flat melanoma and the other 4 cases were an atypical amelanotic tumor. Wide local surgery was performed in nine patients. A radical surgery was performed in six patients. In the large cervical melanoma, radiotherapy was performed as first-line treatment. In all the patients regional lymph node staging was performed. Adjuvant treatment was realized in nine patients. Two patients are alive without recurrence. Only one patient was lost to the first follow-up. The other 13 patients experienced a rapid recurrence. The median disease-free survival and the median overall survival were 11.8 months (2-49 m) and of 30.4 m (11-144 m), respectively. The disease-free survival and overall survival could be linked to a clinical presentation (Breslow thickness and morphology of lesion) associated to the early diagnosis. In our small series, the most important prognosis factor remains the tumor thickness. These rare lesions should be treated in experienced centers in order to improve their prognostic.

  11. The Ceremonial Side of Training--Of What Value to First-Line Supervisors?

    Science.gov (United States)

    Adams, Fred P.

    1976-01-01

    A case study to determine whether the recognition of being selected for a training program and the satisfactory completion of it result in increased job satisfaction using 56 first-line supervisors from a textile company. (WL)

  12. Long-term efficacy of catheter ablation as first-line therapy for paroxysmal atrial fibrillation

    DEFF Research Database (Denmark)

    Nielsen, Jens Cosedis; Johannessen, Arne; Raatikainen, Pekka

    2016-01-01

    OBJECTIVE: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial compared radiofrequency catheter ablation (RFA) with antiarrhythmic drug therapy (AAD) as first-line treatment for paroxysmal atrial fibrillation (AF). Endpoint of ablat......OBJECTIVE: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial compared radiofrequency catheter ablation (RFA) with antiarrhythmic drug therapy (AAD) as first-line treatment for paroxysmal atrial fibrillation (AF). Endpoint...

  13. Resilience and Work-life Balance in First-line Nurse Manager

    OpenAIRE

    Kim, Miyoung; Windsor, Carol

    2015-01-01

    Purpose: The aim of this study was to explore how first-line nurse managers constructed the meaning of resilience and its relationship to work-life balance for nurses in Korea. Methods: Participants were 20 first-line nurse managers working in six university hospitals. Data were collected through in-depth interviews from December 2011 to August 2012, and analyzed using Strauss and Corbin's grounded theory method. Results: Analysis revealed that participants perceived work-life balance a...

  14. Rabeprazole, Minocycline, Amoxicillin, and Bismuth as First-Line and Second-Line Regimens for Helicobacter pylori Eradication.

    Science.gov (United States)

    Song, Zhiqiang; Suo, Baojun; Zhang, Lingyun; Zhou, Liya

    2016-12-01

    Because of general unavailability of tetracycline, common adverse effects, and complicated administration, the clinical application of bismuth quadruple therapy often faces difficulties. Whether the combination of minocycline and amoxicillin can replace tetracycline and metronidazole for Helicobacter pylori eradication remains unclear. This study was to determine the efficacy, compliance, and safety of rabeprazole, minocycline, amoxicillin, and bismuth (RMAB) therapy as first-line and second-line regimens. Between July 2013 and December 2015, a total of 160 patients in first-line and 70 patients in second-line therapies received rabeprazole 10 mg, minocycline 100 mg, amoxicillin 1000 mg, and bismuth potassium citrate 220 mg twice daily for 14 days. Eradication status was assessed 6-12 weeks after treatment. RMAB therapy achieved the eradication rates of 87.5% (95% confidence interval, 81.9-92.5%, intention-to-treat analysis), 90.9% (85.7-95.5%, modified intention-to-treat analysis), and 92.6% (88.5-96.6%, per-protocol analysis) in first-line therapy in a setting with high antibiotic resistance rates (amoxicillin 3.4%, clarithromycin 39.7%, metronidazole 60.3%, levofloxacin 36.2%, tetracycline 3.4%, and minocycline 6.9%). As for second-line therapy, the eradication rates were 82.9% (74.3-91.4%, intention-to-treat analysis), 86.6% (77.6-94.0%, modified intention-to-treat analysis), and 89.1% (81.3-95.3%, per-protocol analysis). Totally, 24.0% patients had adverse effects, 2.2% discontinued medications, and good compliance was achieved in 94.7%. Poor compliance and minocycline resistance were identified as the risk factors for treatment failure. Significant differences in efficacy existed among the groups of both sensitive (48/51 and 18/20), isolated amoxicillin resistance (1/1 and 0/0), isolated minocycline resistance (2/3 and 1/1), and dual resistance (0/1 and 0/1) in both first-line (p = .004) and second-line (p = .035) therapies. The eradication efficacies of RMAB

  15. Monitoring the effect of first line treatment in RAS/RAF mutated metastatic colorectal cancer by serial analysis of tumor specific DNA in plasma

    DEFF Research Database (Denmark)

    Brenner Thomsen, Caroline Emilie; Hansen, T F; Andersen, R F

    2018-01-01

    BACKGROUND: Precision medicine calls for an early indicator of treatment efficiency. Circulating tumor DNA (ctDNA) is a promising marker in this setting. Our prospective study explored the association between disease development and change of ctDNA during first line chemotherapy in patients...... with RAS/RAF mutated metastatic colorectal cancer (mCRC). METHODS: The study included 138 patients with mCRC receiving standard first line treatment. In patients with RAS/RAF mutated tumor DNA the same mutation was quantified in the plasma using droplet digital PCR. The fractional abundance of ct...... on continuous treatment. The first increase in ctDNA level occurred at a median of 51 days before radiologically confirmed progression. CONCLUSIONS: The results indicate that the ctDNA level holds potential as a clinically valuable marker in first line treatment of mCRC. A rapid decrease was associated...

  16. Photodynamic Therapy in Melanoma - Where do we stand?

    Science.gov (United States)

    Baldea, Ioana; Giurgiu, Lorin; Teacoe, Ioana Diana; Olteanu, Diana Elena; Olteanu, Florin Catalin; Clichici, Simona; Filip, Gabriela Adriana

    2017-12-25

    Malignant melanoma is one of the most aggressive malignant tumors with unpredictable evolution. Photodynamic therapy has been successfully used as the first line or palliative therapy for the treatment of lung, esophageal, bladder, non melanoma skin and head and neck cancers. However, classical photodynamic therapy has shown some drawbacks that limit its clinical application in melanoma. The most important challenge is to overcome melanoma resistance, due to melanosomal trapping, presence of melanin, enhanced oxidative stress defense, defects in the apoptotic pathways, immune evasion, neoangiogenesis stimulation. In this review we considered: (1) main signaling molecular pathways deregulated in melanoma as potential targets for personalized therapy, including photodynamic therapy, (2) results of the clinical studies regarding the photodynamic therapy of melanoma, especially advanced metastatic stage, (3) progresses made in the design of anti-melanoma photosensitizers (4) inhibition of tumor neoangiogenesis, as well as (5) advantages of the derived therapies like photothermal therapy, sonodynamic therapy. Moreover, the possibility of combined therapeutical regimens, such as photodynamic therapy and immune stimulation or theranostic approaches may increase the potential beneficial role of photodynamic therapy as an adjuvant in melanoma treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Balloon Cell Urethral Melanoma: Differential Diagnosis and Management

    Directory of Open Access Journals (Sweden)

    M. McComiskey

    2015-01-01

    Full Text Available Introduction. Primary malignant melanoma of the urethra is a rare tumour (0.2% of all melanomas that most commonly affects the meatus and distal urethra and is three times more common in women than men. Case. A 76-year-old lady presented with vaginal pain and discharge. On examination, a 4 cm mass was noted in the vagina and biopsy confirmed melanoma of a balloon type. Preoperative CT showed no distant metastases and an MRI scan of the pelvis demonstrated no associated lymphadenopathy. She underwent anterior exenterative surgery and vaginectomy also. Histology confirmed a urethral nodular malignant melanoma. Discussion. First-line treatment of melanoma is often surgical. Adjuvant treatment including chemotherapy, radiotherapy, or immunotherapy has also been reported. Even with aggressive management, malignant melanoma of the urogenital tract generally has a poor prognosis. Recurrence rates are high and the mean period between diagnosis and recurrence is 12.5 months. A 5-year survival rate of less than 20% has been reported in balloon cell melanomas along with nearly 20% developing local recurrence. Conclusion. To the best of our knowledge, this case is the first report of balloon cell melanoma arising in the urethra. The presentation and surgical management has been described and a literature review provided.

  18. Sinclair swine melanoma

    International Nuclear Information System (INIS)

    Hook, R.R.; Berkelhammer, J.; Hamby, C.V.

    1986-01-01

    Sinclair(S-1) miniature swine spontaneously develop melanomas which have many biologic and histologic features in common with human superficial spreading melanoma. Host control of this neoplasm was indicated by the high incidence of spontaneous regression, a decrease in tumor development with age and a decrease in progressive growth of the tumor as age of tumor development increases. Immunologic mechanisms were implicated in host control by histologic observation of a mononuclear inflammatory infiltration of tumors which lead to depigmentation and fibrosis. In vitro immunologic studies revealed that leukocytes from melanoma swine were sensitized specifically to a tumor associated antigen like substance present in extracts of cutaneous melanomas and cultured swine melanoma cells and that melanoma swine leukocytes were cytotoxic for swine melanoma cells. Furthermore, these studies suggested the existence of a common cross reactive, melanoma associated antigen shared by human and swine melanomas. Antigenic analyses of swine melanomas with mouse monoclonal antibodies developed to a single swine melanoma cell culture and with rabbit antisera developed to pooled extracts of cutaneous melanomas demonstrated the presence of tumor associated antigens in swine melanoma cell culture and cutaneous melanomas. The failure of mouse monoclonal antibodies to detect antigens in cutaneous melanoma extracts and the failure of rabbit antisera to detect antigens in melanoma cell culture extracts suggested a differential in antigen expression between swine melanoma cells grown in vitro and in vivo

  19. First-Line Nursing Home Managers in Sweden and their Views on Leadership and Palliative Care.

    Science.gov (United States)

    Håkanson, Cecilia; Cronfalk, Berit Seiger; Henriksen, Eva; Norberg, Astrid; Ternestedt, Britt-Marie; Sandberg, Jonas

    2014-01-01

    The aim of this study was to investigate first-line nursing home managers' views on their leadership and related to that, palliative care. Previous research reveals insufficient palliation, and a number of barriers towards implementation of palliative care in nursing homes. Among those barriers are issues related to leadership quality. First-line managers play a pivotal role, as they influence working conditions and quality of care. Nine first-line managers, from different nursing homes in Sweden participated in the study. Semi-structured interviews were conducted and analysed using qualitative descriptive content analysis. In the results, two categories were identified: embracing the role of leader and being a victim of circumstances, illuminating how the first-line managers handle expectations and challenges linked to the leadership role and responsibility for palliative care. The results reveal views corresponding to committed leaders, acting upon demands and expectations, but also to leaders appearing to have resigned from the leadership role, and who express powerlessness with little possibility to influence care. The first line managers reported their own limited knowledge about palliative care to limit their possibilities of taking full leadership responsibility for implementing palliative care principles in their nursing homes. The study stresses that for the provision of high quality palliative care in nursing homes, first-line managers need to be knowledgeable about palliative care, and they need supportive organizations with clear expectations and goals about palliative care. Future action and learning oriented research projects for the implementation of palliative care principles, in which first line managers actively participate, are suggested.

  20. Choroidal melanoma

    International Nuclear Information System (INIS)

    Hernandez Quesada, Flora

    2013-01-01

    A useful and practical guide is developed to better track to the uveal melanoma, due to its highly malignant character. Melanoma of the uveal tract (choroid, iris, ciliary body) has been the intraocular tumor most frequent in adults. The biopsy has been inaccessible, due to its location; therefore, the diagnostic should be based on clinical examination and the correct utilization of the diagnostic procedures (ultrasound, fluorescent angiography, computed axial tomography and magnetic resonance). The cases are diagnosed in the histological examination of the operatory piece post-enucleation for other causes. Epidemiological research has been key to determine the associated factors and better to understand the mechanisms of onset of the disease. Anatomopathological studies of choroidal melanoma have permitted to know the natural history of the disease. The decrease of the visual acuity, pain or inflammation are presented as a defect in the visual field. Different techniques to diagnose the disease are explained. Ultrasound in mode A and B, computed axial tomography and magnetic resonance are the diagnostic method of election. Ultrasound has been the primary method of diagnostic, giving the size and vascularisation, useful in tracking, when they are treated in shape conservatively, showing changes in echogenicity and less vascularisation as good response to treatment. The treatments of choroidal melanoma are specified. The correct interpretation of the clinical symptoms and early utilization of diagnostic imaging methods, have permitted to establish the adequate therapeutic and to avoid local and distant metastasis. The uveal melanoma, depending on their size and location, traditionally has been treated by enucleation. Data from the literature and authors, have promoted the conservation of the ocular globe, depending on the size of the tumor. Transpupillary thermotherapy has been an available alternative for small tumors in Costa Rica and level of social security

  1. First-line Helicobacter pylori eradication among patients with chronic liver diseases in Taiwan

    Directory of Open Access Journals (Sweden)

    Cheng-En Tsai

    2016-08-01

    Full Text Available Helicobacter pylori eradication in patients with chronic liver diseases (CLDs and liver cirrhosis is seldom reported. This study aimed to assess the efficacy of 7-day standard triple therapy in patients with CLD including cirrhosis and to investigate the clinical factors influencing the success of eradication. A total of 592 H. pylori-infected patients, who received 7-day standard first-line triple therapy between January 1, 2014, and December 31, 2014, were recruited. Patients were divided into two groups: CLD group (N = 136 and non-CLD group (N = 456. The eradication rates attained by the CLD and non-CLD groups were 86.0% and 84.2%, respectively, in the per-protocol analysis (p = 0.606. The eradication rates of liver cirrhosis and noncirrhosis CLD were 88.5% and 84.3%, respectively (p = 0.783. The adverse events were similar between the two groups (8.8% vs. 9.2%, p = 0.891. Compliance between the two groups was good (99.3% vs. 99.6%, p = 0.670. The univariate analysis showed male sex to be the significant clinical factor in the non-CLD group (p = 0.001 and alcohol consumption to be the significant clinical factor influencing H. pylori eradication rate in patients with CLD (p = 0.022. Alcohol consumption was the only significant factor influencing H. pylori eradication in multivariate analysis (odds ratio = 3.786, p = 0.031. The results of this study suggest that H. pylori eradication rates in patients with CLD may be comparable with non-CLD patients. Alcohol consumption was the significant factor influencing H. pylori eradication in patients with CLD.

  2. Early stage follicular lymphoma: what is the clinical impact of the first-line treatment strategy?

    Science.gov (United States)

    Michallet, Anne-Sophie A S; Lebras, Laure L; Bauwens, Deborah D; Bouafia-Sauvy, Fadhela F; Berger, Françoise F; Tychyj-Pinel, Christelle C; D'Hombres, Anne A; Salles, Gilles G; Coiffier, Bertrand B

    2013-07-01

    Less than 20% of patients with follicular lymphoma (FL) present with Ann Arbor Stage I or II disease at diagnosis. Numerous therapeutic options exist, however radiation therapy is considered the standard of care for early-stage disease based on single-institution or retrospective series. Our aim was to revisit the outcome of patients with localized FL in the rituximab era. We analyzed the characteristics and outcomes of 145 early-stage FL patients, who were retrospectively divided into six groups according to their initial treatment: watchful waiting (WW), chemotherapy alone (CT), radiotherapy alone (RT), combined radiotherapy and chemotherapy (RT-CT), rituximab alone (Ri), and immunochemotherapy (Ri-CT). Of the 145 patients, 84 (57.9%) had stage I disease and 61 (42.1%) stage II. The complete response (CR) rate varied from 57% for the Ri group to 95% for the RT-CT group. Overall survival (OS) at 7.5 y of patients treated after 2000 was better than that of those treated prior to 2000. OS did not significantly differ from one treatment to another. In contrast, a significant difference was found for progression-free survival (PFS) at 7.5 y, which favored Ri-CT (60%) therapy versus the others (p=0.00135). Delayed therapy initiation was associated with a similar OS than that observed in patients receiving immediate intervention. The "watchful waiting" strategy may thus be proposed as first-line therapy, similar to stage III and IV FL patients with a low tumor burden. However, when treatment is required, immunochemotherapy appears to be the best option.

  3. Role of lapatinib in the first-line treatment of patients with metastatic breast cancer

    International Nuclear Information System (INIS)

    Oakman, Catherine; Pestrin, Marta; Zafarana, Elena; Cantisani, Egidia; Di Leo, Angelo

    2010-01-01

    Lapatinib is a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER2/ErbB2). EGFR and HER2 overexpression is associated with aggressive breast cancer with a high risk of disease relapse and death. Although lapatinib targets both EGFR and HER2, its effects on HER2 appear to be more critical. The role of lapatinib in the first-line setting remains unclear. A phase II first-line monotherapy lapatinib trial in HER2-therapy-naïve metastatic breast cancer (MBC) patients confirms efficacy in HER2-positive tumors. Retrospective analysis of a phase III, first-line MBC study confirmed incremental benefit from lapatinib and paclitaxel over paclitaxel alone in HER2-positive disease. A prospective phase III study confirms superiority of letrozole and lapatinib over letrozole alone in HER2-positive MBC. Further investigation is required to define the potential first-line role for lapatinib. Particular strengths appear to be its manageable toxicity profile, lack of cross resistance with trastuzumab, activity in central nervous system disease, and synergy in combination with other anticancer therapy. Current limitations are lack of dosing recommendations from early trials, lack of predictive biomarkers beyond HER2 status, and lack of large prospective phase III trials for HER2-positive disease in the first-line setting. The role of lapatinib in HER2-negative disease is unclear

  4. Targeted erlotinib for first-line treatment of advanced non-small cell lung cancer: a budget impact analysis.

    Science.gov (United States)

    Bajaj, Preeti S; Veenstra, David L; Goertz, Hans-Peter; Carlson, Josh J

    2014-08-01

    A recent phase III trial showed that patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor specific EGFR mutations significantly benefit from first-line treatment with erlotinib compared to chemotherapy. This study sought to estimate the budget impact if coverage for EGFR testing and erlotinib as first-line therapy were provided in a hypothetical 500,000-member managed care plan. The budget impact model was developed from a US health plan perspective to evaluate administration of the EGFR test and treatment with erlotinib for EGFR-positive patients, compared to non-targeted treatment with chemotherapy. The eligible patient population was estimated from age-stratified SEER incidence data. Clinical data were derived from key randomized controlled trials. Costs related to drug, administration, and adverse events were included. Sensitivity analyses were conducted to assess uncertainty. In a plan of 500,000 members, it was estimated there would be 91 newly diagnosed advanced NSCLC patients annually; 11 are expected to be EGFR-positive. Based on the testing and treatment assumptions, it was estimated that 3 patients in Scenario 1 and 6 patients in Scenario 2 receive erlotinib. Overall health plan expenditures would increase by $0.013 per member per month (PMPM). This increase is largely attributable to erlotinib drug costs, in part due to lengthened progression-free survival and treatment periods experienced in erlotinib-treated patients. EGFR testing contributes slightly, whereas adverse event costs mitigate the budget impact. The budget impact did not exceed $0.019 PMPM in sensitivity analyses. Coverage for targeted first-line erlotinib therapy in NSCLC likely results in a small budget impact for US health plans. The estimated impact may vary by plan, or if second-line or maintenance therapy, dose changes/interruptions, or impact on patients' quality-of-life were included.

  5. Communication Among Melanoma Family Members

    Science.gov (United States)

    Bowen, Deborah J; Albrecht, Terrance; Hay, Jennifer; Eggly, Susan; Harris-Wei, Julie; Meischke, Hendrika; Burke, Wylie

    2017-01-01

    Interventions to improve communication among family members may facilitate information flow about familial risk and preventive health behaviors. This is a secondary analysis of the effects of an interactive website intervention aimed at increasing communication frequency and agreement about health risk among melanoma families. Participants were family units, consisting of one family member with melanoma identified from a previous research study (the case) and an additional first degree relative and a parent of a child 0–17. Family triads were randomized to receive access to the website intervention or to serve as control families. Family communication frequency and agreement about melanoma prevention behaviors and beliefs were measured at baseline and again at one year post randomization. Intervention participants of all three types significantly increased the frequency of communication to their first degree relatives (Parents, siblings, children; range =14–18 percentage points; all pcommunication about cancer risk. PMID:28248624

  6. Improving first-line antiretroviral therapy in resource-limited settings.

    Science.gov (United States)

    Ford, Nathan; Calmy, Alexandra

    2010-01-01

    Access to first-line antiretroviral therapy in resource-limited settings has increased rapidly in the last 5 years. Newer medicines with greater potency and better safety profiles open the possibility for improving first-line antiretroviral therapy for developing countries. Several medicines offer the potential to improve the simplicity, safety and efficacy of first-line antiretroviral therapy in resource-limited settings. These include tenofovir, raltegravir, elvitegravir, rilpivirine and protease inhibitors. A number of clinical questions are outstanding, particularly regarding safety in pregnancy and compatibility with drugs to treat common coinfections including tuberculosis. Simple, affordable regimens were key to the initial emergency response, but the long-term response to HIV calls for a reconsideration of current treatment options. Preconditions for widespread use in developing countries include affordability, simplicity and answers to relevant research questions. In the absence of strong pharmacovigilance systems, cohort monitoring will be critical to assessing the safety profile of new drugs in such settings.

  7. Paclitaxel/carboplatin with or without belinostat as empiric first-line treatment for patients with carcinoma of unknown primary site

    DEFF Research Database (Denmark)

    Hainsworth, John D; Daugaard, Gedske; Lesimple, Thierry

    2015-01-01

    : The addition of belinostat to paclitaxel/carboplatin did not improve the PFS of patients with CUP who were receiving first-line therapy, although the patients who received belinostat had a higher investigator-assessed response rate. Future trials in CUP should focus on specific subsets, defined either......BACKGROUND: The objective of this study was to evaluate the efficacy of belinostat, a histone deacetylase inhibitor, when added to paclitaxel/carboplatin in the empiric first-line treatment of patients with carcinoma of unknown primary site (CUP). METHODS: In this randomized phase 2 trial......, previously untreated patients with CUP were randomized to receive belinostat plus paclitaxel/carboplatin (group A) or paclitaxel/carboplatin alone (group B) repeated every 21 days. Patients were re-evaluated every 2 cycles, and those without disease progression continued treatment for 6 cycles. Patients...

  8. Developing a predictive risk model for first-line antiretroviral therapy failure in South Africa.

    Science.gov (United States)

    Rohr, Julia K; Ive, Prudence; Horsburgh, C Robert; Berhanu, Rebecca; Shearer, Kate; Maskew, Mhairi; Long, Lawrence; Sanne, Ian; Bassett, Jean; Ebrahim, Osman; Fox, Matthew P

    A substantial number of patients with HIV in South Africa have failed first-line antiretroviral therapy (ART). Although individual predictors of first-line ART failure have been identified, few studies in resource-limited settings have been large enough for predictive modelling. Understanding the absolute risk of first-line failure is useful for patient monitoring and for effectively targeting limited resources for second-line ART. We developed a predictive model to identify patients at the greatest risk of virologic failure on first-line ART, and to estimate the proportion of patients needing second-line ART over five years on treatment. A cohort of patients aged ≥18 years from nine South African HIV clinics on first-line ART for at least six months were included. Viral load measurements and baseline predictors were obtained from medical records. We used stepwise selection of predictors in accelerated failure-time models to predict virologic failure on first-line ART (two consecutive viral load levels >1000 copies/mL). Multiple imputations were used to assign missing baseline variables. The final model was selected using internal-external cross-validation maximizing model calibration at five years on ART, and model discrimination, measured using Harrell's C-statistic. Model covariates were used to create a predictive score for risk group of ART failure. A total of 72,181 patients were included in the analysis, with an average of 21.5 months (IQR: 8.8-41.5) of follow-up time on first-line ART. The final predictive model had a Weibull distribution and the final predictors of virologic failure were men of all ages, young women, nevirapine use in first-line regimen, low baseline CD4 count, high mean corpuscular volume, low haemoglobin, history of TB and missed visits during the first six months on ART. About 24.4% of patients in the highest quintile and 9.4% of patients in the lowest quintile of risk were predicted to experience treatment failure over five years on

  9. Review of first line supervisory positions in nuclear power plants - Phase II

    International Nuclear Information System (INIS)

    Mackenzie, C.W.; Huntley, M.

    1995-10-01

    This report provides an overview of first line supervisory activities at Ontario Hydro nuclear generating stations (Pickering 'A' and Bruce 'B') and the Point Lepreau nuclear generating station in New Brunswick. Activity profiles describing the range of first line supervisory roles and responsibilities for nuclear operators have been developed from survey data and flowcharting methods. These activity profiles have then been compared with formal job responsibilities as identified in job descriptions, supervisory training provided and assessment criteria used to evaluate supervisors. Finally, this report relates the findings of supervisory practices in the group under study with the findings in the current literature relating to supervisory functioning. (author). 32 tabs., 2 figs

  10. Clinicopathological characteristics, diagnosis and treatment of melanoma in Serbia: The Melanoma Focus Study

    Directory of Open Access Journals (Sweden)

    Kandolf-Sekulović Lidija

    2015-01-01

    Full Text Available Background/Aim. Treatment options for metastatic melanoma in Serbia are limited due to the lack of newly approved biologic agents and the lack of clinical studies. Also, there is a paucity of data regarding the treatment approaches in different tertiary centers and efficacy of available chemotherapy protocols. The aim of this study was to obtain more detailed data about treatment protocols in Serbia based on structured survey in tertiary oncology centers. Methods. Data about the melanoma patients treated in 2011 were analyzed from hospital databases in 6 referent oncology centers in Serbia, based on the structured survey, with the focus on metastatic melanoma patients (unresectable stage IIIC and IV. Results. A total of 986 (79-315 in different centers patients were treated, with 320 (32.45% newly diagnosed patients. There were 317 patients in stage IIIC/IV, 77/317 aged 60 years. At initial diagnosis 12.5% of patients were in stage III and 4.5% in stage IV. The most common type was superficial spreading melanoma (50-66%, followed by nodular melanoma (23.5-50%. Apart from the regional and distant lymph node metastases, the most frequent organs involved in stage IV disease were distant skin and soft tissues (12-55%, lungs (19-55.5%, liver (10-60%, and bones (3-10%. The first line therapy in stage IV metastatic melanoma was dacarbazine (DTIC dimethyl-triazeno-imidozole-carboxamide in 61-93% of the patients, while the second line varied between the centers. Disease control (complete response + partial response + stable disease was achieved in 25.7% of the patients treated with the first line chemotherapy and 23.1% of the patients treated with the second line therapy, but the duration of response was short, in first-line therapy 6.66 ± 3.36 months (median 6.75 months. More than 90% of patients were treated outside the clinical trials. Conclusion. Based on this survey, there is a large unmet need for the new treatment options for metastatic melanoma

  11. Intratympanic steroid injection as a first-line therapy in uremia patients with sudden sensorineural hearing loss.

    Science.gov (United States)

    Tsai, Hsun-Tien; Hsueh, Naiwei; Huang, Chih-Ming; Lin, Hung-Ching

    2015-08-01

    ITSI as a first-line therapy in uremia patients with SSNHL offers a valid and safe treatment compared with intravenous systemic steroid treatment. A specific pathophysiology caused by possible sodium pump paralysis may be explained for uremia patients with SSNHL. To compare the efficacy of intratympanic steroid injection (ITSI) with that of systemic intravenous steroids as a first-line therapy in uremia patients with sudden sensorineural hearing loss (SSNHL). A total of 23 consecutive uremia patients with SSNHL were enrolled in this study. Patients were divided into two groups: the ITSI group (n = 15) and the non-ITSI group (n = 8), in which patients received intravenous systemic steroid treatment. The two groups were homogeneous in all respects. The hearing improvement and relative gain were statistically significant between the two groups. The value of hearing gain (ΔPTA = PTA pre - PTA post) in the ITSI group and the non-ITSI group was 24.6 ± 16.4dB and 8.4 ± 19.3dB. The value of relative gain (ΔPTA/PTApre) in the ITIS group and the non-ITSI group was 31.1 ± 22% and 9.4 ± 20.5%. In the ITSI group, 11 patients (73.3%) exhibited hearing recovery (ΔPTA > 10 dB).

  12. PML as a potential predictive factor of oxaliplatin/fluoropyrimidine-based first line chemotherapy efficacy in colorectal cancer patients.

    Science.gov (United States)

    Vincenzi, Bruno; Santini, Daniele; Perrone, Giuseppe; Graziano, Francesco; Loupakis, Fotios; Schiavon, Gaia; Frezza, Anna Maria; Ruzzo, Anna Maria; Rizzo, Sergio; Crucitti, Pierfilippo; Galluzzo, Sara; Zoccoli, Alice; Rabitti, Carla; Muda, Andrea Onetti; Russo, Antonio; Falcone, Alfredo; Tonini, Giuseppe

    2012-03-01

    PML regulates a wide range of pathways involved in tumorigenesis, such as apoptosis, which is also one of the main mechanisms through which oxaliplatin and fluoropyrimidine exert their antineoplastic activity. The present study aims to investigate PML expression as a predictive factor of oxaliplatin/fluoropyrimidine therapy efficacy. Seventy-four metastatic colorectal cancer patients who received oxaliplatin/floropyrimidine-based first line therapy have been included in this retrospective study. PML expression was assessed by immunohistochemistry. PML down-regulation was detected in 39 (52.7%) patients (14 complete and 25 partial PML loss). RR was significantly lower (25.6%) in patients with PML down-regulation than in patients with preserved PML expression (60%) (P = 0.006). Median TTP was 5.5 months when PML was down-regulated versus 11.9 months in case of preserved PML expression (P < 0.0001). A statistical significant difference was also detected in OS (15.6 and 24.5 months, respectively, P = 0.003). The impact of PML down-regulation on TTP and OS was statistically significant also in a multivariate model. This study represents the first evidence of a possible correlation between PML protein expression and outcome of metastatic colorectal cancer patients treated with oxaliplatin/fluoropyrimidine-based first line therapy. Copyright © 2011 Wiley Periodicals, Inc.

  13. Brachytherapy of choroidal melanomas

    International Nuclear Information System (INIS)

    Brady, L.W.; Hernandez, J.C.

    1992-01-01

    In a compilation of nine reported series consisting of 2,024 enucleations, the five- and ten-year survivals following surgery were 63% and 43%, respectively. The 25-year survival has been reported to be 40%. In 1974 at Wills Eye Hospital and Hahnemann University, the cobalt-60 plaques technique was introduced. During the following years, other radioactive isotopes were introduced including irridium-192, iodine-125, ruthenium-106/rhodium-106 and more recently palladium-103. At the present time, iodine-125 is the most widely used radionuclide. Until now, 302 patients treated with plaque brachytherapy showed an actuarial survival of 77% and 67.8% at five and eight years, respectively. There was no significant survival difference when compared with a similar group of patients undergoing enucleation. Other retrospective studies show similar excellent results. In spite of these convincing results, the decision making process in management melanoma remains unsettled primarily due to the absence of prospective randomized trials. Because of this, the Collaborative Ocular Melanoma Study was initiated. From the standpoint of toxicity, the data are available on ocular radiation toxicity. In an analysis of 77 patients from the Wills Eye Hospital with pretreatment visual acuities of 20/25 or better, it was noted that 90% of patients who had received less than 500 Gy to the fovea retained visual acuity of 20/200 or better while only 52% of patients receiving more than 5,000 Gy to the fovea had vision of 20/200 or better. A serious late effect of radioactivity plaque treatment is scleral necrosis which may require repair or enucleation even in the absence of tumor progression. Enucleation may be necessary in approximately 10% of patients. We conclude that malignant melanoma of the uvea can be safely treated with radioactive plaques. (orig./MG) [de

  14. Success rates of first-line antibiotics for culture-negative sub-acute and chronic septic arthritis.

    Science.gov (United States)

    Chuckpaiwong, Bavornrit; Phoompoung, Saravut

    2014-09-01

    A combination of surgical and medical treatment is normally required for patients with septic arthritis. Antibiotics selected for use on these patients are normally based on tissue culture results. However, in sub-acute and chronic septic arthritis cases, the results of the culture are usually negative as a result of prior treatment. The present study will investigate the incidence of culture-negative septic arthritis and the outcomes based on the use of first-line drug antibiotics for the treatment of sub-acute and chronic septic arthritis. For the present study, the authors retrospectively reviewed medical records of surgically treated septic arthritis cases over the past 10 years at Siriraj Hospital. The patient culture results, the antibiotics used, and the results of treatment were all recorded and analyzed. One hundredfifty-three septic arthritis patients were reviewed. Sixty-two patients were classified as having been diagnosed with either sub-acute or chronic septic arthritis. Thirty-six of 62 patients (58.1%) had a negative culture result. In the culture-positive patients, 42.3% had Streptococcus, 26.9% had Staphylococcus aureus, 11.5% had other gram positive bacteria, 15.4% had gram-negative bacteria, and 3.8% had tuberculus infection. In the culture-negative sub-acute and chronic group (36 of 62), 23 patients received Cefazolin, nine patients received Cloxacillin, and four patients received Clindamycin. Successful results were 69.9%, 66.7% and 75%, respectively. The present study reflects that the incidence ofculture-negative, sub-acute and chronic septic arthritis is approximately 58.1%. The first-line class of antibiotics remains the appropriate antibiotic choice for these patients because they are still effective for treatment of septic arthritis in up to 70% of all cases.

  15. Tratamento de primeira linha no Mieloma Múltiplo First line treatment in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Gisele W. B. Colleoni

    2007-03-01

    Full Text Available A presente revisão tem por objetivo avaliar o estado atual do tratamento de primeira linha dos pacientes com MM. O paciente com MM assintomático não deve receber tratamento ao diagnóstico, mas apenas quando surgirem indicações. Para o paciente sintomático (anemia, hipercalcemia, alteração da função renal, presença de lesões líticas ou plasmocitoma extramedular, aumento progressivo do componente-M no soro e/ou urina, o tratamento deverá ser rapidamente instituído. Aqueles pacientes com menos de 65-70 anos, com bom performance status, sem comorbidades e com função renal próxima do normal são potencialmente candidatos à consolidação com altas doses de quimioterapia seguidas de transplante autólogo de células-tronco hematopoéticas. Portanto, não devem utilizar drogas alquilantes para evitar prejuízos à mobilização das células-tronco. São opções: dexametasona, VAD e talidomida (com ou sem dexametasona. Os pacientes com mais de 65-70 anos, com performance status ruim, comorbidades e com função renal alterada podem receber tratamento com agentes alquilantes (por exemplo, melfalano e prednisona, com ou sem talidomida pois não serão submetidos a transplante. O principal objetivo nesses casos é atingir resposta com mínima toxicidade.The aim of this review is to evaluate the current status of first line treatment in multiple myeloma. Asymptomatic patients should not receive treatment at diagnosis. However, symptomatic patients (anemia, hypercalcemia, deterioration in renal function, lytic lesions or extramedullary plasmacytomas, increase of M-component in serum or urine should receive treatment as soon as possible. Patients younger than 65-70 years old with good performance status, no concurrent diseases and normal renal function are possible candidates for consolidation using high-dose chemotherapy followed by stem-cell transplantation. Therefore, they should not receive drugs that could potentially interfere with

  16. Cixutumumab in Treating Patients With Metastatic Melanoma of the Eye

    Science.gov (United States)

    2015-06-25

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Iris Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Stage IV Intraocular Melanoma

  17. The use of first line Highly Active Anti-Retroviral Therapy (HAART) is ...

    African Journals Online (AJOL)

    The use of first line Highly Active Anti-Retroviral Therapy (HAART) is not associated with QTC prolongation in HIV patients. ... Mean QTc was significantly longer among patients with CD4 count 200 cells/mm3 0.445 + 0.03secs vs 0.421 + 0.03secs (P<0.001). QTc prolongation was ...

  18. First-line treatment with cephalosporins in spontaneous bacterial peritonitis provides poor antibiotic coverage

    DEFF Research Database (Denmark)

    Novovic, Srdan; Semb, Synne; Olsen, Henrik

    2012-01-01

    Abstract Objective. Spontaneous bacterial peritonitis is a common infection in cirrhosis, associated with a high mortality. Third-generation cephalosporins are recommended as first-line treatment. The aim was to evaluate the epidemiology of microbiological ascitic fluid findings and antimicrobial...

  19. Choice of nasal nitric oxide technique as first-line test for primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Marthin, J K; Nielsen, K G

    2011-01-01

    as first-line tests for PCD. Healthy subjects, confirmed PCDs, consecutive referrals with PCD-like symptoms and patients with cystic fibrosis (CF) had nNO sampled during breath hold (BH-nNO), oral exhalation against resistance (OE-R-nNO) and tidal breathing (TB-nNO) aiming to expand age range into infancy...

  20. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer.

    NARCIS (Netherlands)

    Carbone, D.P.; Reck, M.; Paz-Ares, L.; Creelan, B.; Horn, L.; Steins, M.; Felip, E.; Heuvel, M. van den; Ciuleanu, T.E.; Badin, F.; Ready, N.; Hiltermann, T.J.N.; Nair, S.; Juergens, R.; Peters, S.; Minenza, E.; Wrangle, J.M.; Rodriguez-Abreu, D.; Borghaei, H.; umenschein GR, J.r. Bl; Villaruz, L.C.; Havel, L.; Krejci, J.; rral Jaime, J. Co; Chang, H.; Geese, W.J.; Bhagavatheeswaran, P.; Chen, A.C.; Socinski, M.A.

    2017-01-01

    BACKGROUND: Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1

  1. Male first-line managers' experiences of the work situation in elderly care: an empowerment perspective.

    Science.gov (United States)

    Hagerman, Heidi; Engström, Maria; Häggström, Elisabeth; Wadensten, Barbro; Skytt, Bernice

    2015-09-01

    To describe male first-line managers' experiences of their work situation in elderly care. First-line managers' work is challenging. However, less attention has been paid to male managers' work situation in health care. Knowledge is needed to empower male managers. Fourteen male first-line managers were interviewed. The interview text was subjected to qualitative content analysis. Work situations were described as complex and challenging; challenges were the driving force. They talked about 'Being on one's own but not feeling left alone', 'Having freedom within set boundaries', 'Feeling a sense of satisfaction and stimulation', 'Feeling a sense of frustration' and 'Having a feeling of dejection and resignation'. Although the male managers report deficiencies in the support structure, they largely experience their work as a positive challenge. To meet increasing challenges, male first-line managers need better access to supportive structural conditions. Better access to resources is needed in particular, allowing managers to be more visible for staff and to work with development and quality issues instead of administrative tasks. Regarding organisational changes and the scrutiny of management and the media, they lack and thus need support and information from superiors. © 2013 John Wiley & Sons Ltd.

  2. Bismuth, lansoprazole, amoxicillin and metronidazole or clarithromycin as first-line Helicobacter pylori therapy.

    Science.gov (United States)

    Zhang, Wei; Chen, Qi; Liang, Xiao; Liu, Wenzhong; Xiao, Shudong; Graham, David Y; Lu, Hong

    2015-11-01

    To evaluate the efficacy and tolerability of replacing tetracycline with amoxicillin in bismuth quadruple therapy. Subjects who were infected with Helicobacter pylori and naïve to treatment were randomly (1:1) assigned to receive a 14-day modified bismuth quadruple therapy: lansoprazole 30 mg, amoxicillin 1 g, bismuth potassium citrate 220 mg (elemental bismuth), twice a day with metronidazole 400 mg four times a day (metronidazole group) or clarithromycin 500 mg twice a day (clarithromycin group). Six weeks after treatment, H. pylori eradication was assessed by 13C-urea breath test. Antimicrobial susceptibility was assessed by the twofold agar dilution method. This was a non-inferiority trial. Two hundred and fifteen subjects were randomised. Metronidazole and clarithromycin containing regimens achieved high cure rates: 94 of 97 (96.9%, 95% CI 93.5% to 100%) and 93 of 98 (94.9%, 95% CI 90.5% to 99.3%) by per-protocol and 88.9% (95% CI 83.0% to 94.8%) and 88.8% (95% CI 82.8% to 94.8%) by intention-to-treat, respectively. Amoxicillin, metronidazole and clarithromycin resistance rates were 1.5%, 45.5% and 26.5%, respectively. Only clarithromycin resistance reduced treatment success (e.g., susceptible 98.6%, resistant 76.9%, p=0.001). Adverse events were more common in the metronidazole group. These results suggest that amoxicillin can substitute for tetracycline in modified 14 day bismuth quadruple therapy as first-line treatment and still overcome metronidazole resistance in areas with high prevalence of metronidazole and clarithromycin resistance. Using clarithromycin instead of metronidazole was only effective in the presence of susceptible strains. NCT02175901. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Retrospective analysis of first-line treatment for follicular lymphoma based on outcomes and medical economics.

    Science.gov (United States)

    Muneishi, Manaka; Nakamura, Ayaka; Tachibana, Katsumi; Suemitsu, Junko; Hasebe, Shinji; Takeuchi, Kazuto; Yakushijin, Yoshihiro

    2018-04-01

    Follicular lymphoma (FL) is the most common type of non-Hodgkin lymphoma (NHL), with indolent progression. Several treatment options are selected, based not only on disease status, quality of life (QOL), and age of patient, but also on recent increasing medical costs. We retrospectively analysed the first-line treatment of FL with regard to treatment outcomes and medical economics, and discuss the appropriate strategies for FL. Data on a total of 69 newly-diagnosed patients with FL was retrospectively collected from 2001 to 2015. The median age of the patients was 60 years and the median follow-up was 58 months. A total of 25 cases with FL were treated with R monotherapy, and 28 cases were treated with R-CHOP as first-line treatment. The factors affecting the decision of physicians to use R or R-CHOP treatment were serum level of lactate dehydrogenase (LDH) and disease stage. The first-line treatment-associated survival did not show any statistical differences between R and R-CHOP. The average hospitalization and average of all medical costs during the first-line treatment were 4.1 days (R) versus 55.7 days (R-CHOP), and JPY 1,707,693 (USD 15,324) (R) versus JPY 2,136,117 (USD 19,170) (R-CHOP), respectively. R monotherapy for patients whose diseases show low tumor burden and who are not candidates for local treatment has benefits as a first-line treatment compared to R-CHOP, based on the patients' QOL and medical economics.

  4. Expanding first-line therapy options for children with partial seizures.

    Science.gov (United States)

    Glauser, T A

    2000-01-01

    Carbamazepine and phenytoin are considered first-line therapies for children with partial seizures on the basis of the adult Veterans Administration studies, open-label controlled and uncontrolled pediatric studies, and clinical experience. Although many new antiepileptic drugs (AEDs) have demonstrated efficacy in controlled trials in adults with partial seizures, additional issues must be examined before these new AEDs are considered as first-line therapy for children with partial seizures. This article proposes three criteria for assessing the suitability of a new AED as first-line therapy for pediatric partial seizures: (a) demonstrated efficacy against pediatric partial seizures in two or more randomized, double-blind controlled trials involving patients less than 12 years old (with at least one of the trials utilizing a monotherapy design); (b) a favorable safety profile in monotherapy trials and no severe idiosyncratic reactions; and (c) ease of use in children across a wide range of ages. On the basis of these criteria, two new AEDs, oxcarbazepine (OXC) and topiramate (TPM), are suitable for consideration. OXC has demonstrated efficacy in monotherapy and adjunctive therapy in pediatric partial seizures, along with good tolerability and the ability to be titrated rapidly. TPM has also demonstrated efficacy and tolerability in pediatric partial seizures but should be titrated slowly. In addition, gabapentin (GBP) can be considered as first-line therapy for pediatric partial seizures if the preliminary analysis of a monotherapy trial is confirmed. There are not yet enough data on efficacy to support consideration of lamotrigine, tiagabine, felbamate, levetiracetam, or zonisamide as first-line therapy for pediatric partial seizures.

  5. Sarcoidosis in Melanoma Patients: Case Report and Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Beutler, Bryce D., E-mail: brycebeutler@hotmail.com [School of Allied Health Sciences, University of Nevada, Las Vegas, 1060 Wiegand Road, Encinitas, CA 92024 (United States); Cohen, Philip R., E-mail: brycebeutler@hotmail.com [Department of Dermatology, University of California San Diego, 10991 Twinleaf Court, San Diego, CA 92131 (United States)

    2015-06-15

    Sarcoidosis is a systemic inflammatory disease characterized by the development of noncaseating granulomas in multiple organ systems. Many hematologic malignancies and solid tumors, including melanoma, have been associated with sarcoidosis. We describe the clinical and pathologic findings of a 54-year-old man with melanoma-associated sarcoidosis. In addition, we not only review the literature describing characteristics of other melanoma patients with sarcoidosis, but also the features of melanoma patients with antineoplastic therapy-associated sarcoidosis. Sarcoidosis has been described in 80 melanoma patients; sufficient information for analysis was provided in 39 of these individuals. In 43.6% of individuals (17 out of 39), sarcoidosis was directly associated with melanoma; in 56.4% of oncologic patients (22 out of 39), sarcoidosis was induced by antineoplastic therapy that had been administered for the treatment of their metastatic melanoma. The discovery of melanoma preceded the development of sarcoidosis in 12 of the 17 (70.5%) individuals who did not receive systemic treatment. Pulmonary and/or cutaneous manifestations of sarcoidosis were common among both groups of patients. Most patients did not require treatment for sarcoidosis. Melanoma patients—either following antineoplastic therapy or without systemic treatment—may be at an increased risk to develop sarcoidosis. In antineoplastic therapy naive melanoma patients, a common etiologic factor—such as exposure to ultraviolet light—may play a role in their developing melanoma and sarcoidosis.

  6. Skin cancer and melanoma

    International Nuclear Information System (INIS)

    Moylan, D.J.

    1991-01-01

    In this chapter, the author discusses various types of non-melanoma malignant skin cancer, as well as malignant melanoma. Non-melanoma skin cancer, such as basal cell and squamous cell carcinomas, occasionally metastasize, but only late in the course of the disease. On the other hand, even relatively small primary melanomas tend to disseminate to regional lymph nodes and to distant sites. The author presents various treatment plans, including radiation therapy. Cutaneous melanomas have been considered relatively radioresistant. This is the rationale for the use of large fraction radiation therapy in the treatment of melanomas with the fraction sizes varying from 4--8 Gy

  7. Ceftaroline fosamil as first-line versus second-line treatment for acute bacterial skin and skin structure infections (ABSSSI) or community-acquired bacterial pneumonia (CABP).

    Science.gov (United States)

    Guervil, David J; Kaye, Keith S; Hassoun, Ali; Cole, Phillip; Huang, Xing-Yue; Friedland, H David

    2016-06-01

    The Clinical Assessment Program and Teflaro(®) Utilization Registry (CAPTURE) is a multicenter registry study of acute bacterial skin and skin structure infection (ABSSSI) and community-acquired bacterial pneumonia (CABP) patients treated with ceftaroline fosamil in the US. Data for this analysis were collected between August 2011 and February 2013 at US study centres by randomly ordered chart review. Clinical success rates among ABSSSI patients were >81% when ceftaroline fosamil was used as first- or second-line therapy, including monotherapy and concurrent therapy. Among CABP patients, clinical success rates were >77% among first-line and second-line patients and patients who received first-line concurrent therapy or second line monotherapy or concurrent therapy. For CABP patients treated with ceftaroline fosamil as first-line monotherapy, the clinical success rate was 70%. Ceftaroline fosamil is an effective treatment option for patients with ABSSSI or CABP with similar clinical success rates when used as first-line or second-line treatment.

  8. Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: A phase II trial.

    Science.gov (United States)

    Argilés, Guillem; Saunders, Mark P; Rivera, Fernando; Sobrero, Alberto; Benson, Al; Guillén Ponce, Carmen; Cascinu, Stefano; Van Cutsem, Eric; Macpherson, Iain R; Strumberg, Dirk; Köhne, Claus-Henning; Zalcberg, John; Wagner, Andrea; Luigi Garosi, Vittorio; Grunert, Julia; Tabernero, Josep; Ciardiello, Fortunato

    2015-05-01

    The oral multikinase inhibitor regorafenib improves overall survival (OS) in patients with metastatic colorectal cancer (CRC) for which all standard treatments have failed. This study investigated regorafenib plus modified FOLFOX (mFOLFOX6) as first-line treatment of metastatic CRC. In this single-arm, open-label, multicentre, phase II study, patients received mFOLFOX6 on days 1 and 15, and regorafenib 160 mg orally once daily on days 4-10 and 18-24 of each 28-day cycle. The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included disease control rate (DCR), OS, progression-free survival (PFS) and safety. Median overall treatment duration with any study drug was 9.9 months (range 0.6-19.6); median treatment duration with regorafenib was 7.7 months (range 0.1-19.5); six patients remained on regorafenib for more than 1 year. Fifty-three patients received at least one dose of regorafenib. ORR was 43.9% (all partial responses); DCR was 85.4%; median OS was not reached; median PFS was 8.5months. Treatment-emergent adverse events were experienced by all patients but were manageable with dose modifications. Regorafenib+mFOLFOX6 as first-line treatment in patients with metastatic CRC did not improve ORR over historical controls. Regorafenib plus mFOLFOX6 did not appear to be associated with a markedly worse tolerability profile versus mFOLFOX6 alone. Copyright © 2015. Published by Elsevier Ltd.

  9. Treatment Option Overview (Melanoma)

    Science.gov (United States)

    ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Funding for ... the skin far away from where it first started. Recurrent Melanoma Recurrent melanoma is cancer that has ...

  10. General Information about Melanoma

    Science.gov (United States)

    ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Funding for ... the skin far away from where it first started. Recurrent Melanoma Recurrent melanoma is cancer that has ...

  11. Stages of Melanoma

    Science.gov (United States)

    ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Funding for ... the skin far away from where it first started. Recurrent Melanoma Recurrent melanoma is cancer that has ...

  12. Melanoma - neck (image)

    Science.gov (United States)

    This melanoma on the neck is variously colored with a very darkly pigmented area found centrally. It has irregular ... be larger than 0.5 cm. Prognosis in melanoma is best defined by its depth on resection.

  13. Primary ovarian malignant melanoma

    Directory of Open Access Journals (Sweden)

    Kostov Miloš

    2010-01-01

    Full Text Available Background. Primary ovarian malignant melanoma is extremely rare. It usually appears in the wall of a dermoid cyst or is associated with another teratomatous component. Metastatic primary malignant melanoma to ovary from a primary melanoma elsewhere is well known and has been often reported especially in autopsy studies. Case report. We presented a case of primary ovarian malignant melanoma in a 45- year old woman, with no evidence of extraovarian primary melanoma nor teratomatous component. The tumor was unilateral, macroscopically on section presented as solid mass, dark brown to black color. Microscopically, tumor cells showed positive immunohistochemical reaction for HMB-45, melan-A and S-100 protein, and negative immunoreactivity for estrogen and progesteron receptors. Conclusion. Differentiate metastatic melanoma from rare primary ovarian malignant melanoma, in some of cases may be a histopathological diagnostic problem. Histopathological diagnosis of primary ovarian malignant melanoma should be confirmed by immunohistochemical analyses and detailed clinical search for an occult primary tumor.

  14. Molecular Classification of Melanoma

    Science.gov (United States)

    Tissue-based analyses of precursors, melanoma tumors and metastases within existing study populations to further understanding of the heterogeneity of melanoma and determine a predictive pattern of progression for dysplastic nevi.

  15. Melanoma International Foundation

    Science.gov (United States)

    ... the state of Pennsylvania, certificate #29498 © 2013 Melanoma International Foundation. All Rights Reserved. Privacy Policy | Terms of Use Toll-free: 866-463-6663 International: 610-942-3432 Melanoma International Foundation 250 Mapleflower ...

  16. [Ocular melanomas : An update].

    Science.gov (United States)

    Kalirai, H; Müller, P L; Jaehne, D; Coupland, S E

    2017-11-01

    Melanoma is the most common type of primary cancer to affect the adult eye. Approximately 95% of ocular melanomas are intraocular and arise from the uvea (i. e. iris, ciliary body, and choroid), while the remaining 5% are located in the conjunctiva. Although both uveal and conjunctival melanomas are thought to derive from malignantly transformed melanocytes, uveal melanoma is clinically and biologically distinct from conjunctival melanoma, and indeed from its more common cutaneous counterpart. Intense efforts have been recently made to understand the molecular biology involved in the development of ocular melanomas, and in their progression. Molecular advances, particularly for uveal melanoma, have enhanced prognostication and the identification of rational therapeutic targets for disseminated disease. In this review, recent advances in the molecular characterisation of both uveal and conjunctival melanomas are discussed, and how these may be used to develop personalised therapeutic strategies.

  17. Optimal First-Line Treatment for Helicobacter pylori Infection: Recent Strategies

    Directory of Open Access Journals (Sweden)

    Ju Yup Lee

    2016-01-01

    Full Text Available A new treatment strategy is needed, as the efficacy of triple therapy containing clarithromycin—the current standard treatment for Helicobacter pylori infection—is declining. Increasing antibiotic resistance of H. pylori is the most significant factor contributing to eradication failure. Thus, selecting the most appropriate regimen depending on resistance is optimal, but identifying resistance to specific antibiotics is clinically challenging. In a region suspected to have high clarithromycin resistance, bismuth quadruple therapy and so-called nonbismuth quadruple therapies (sequential, concomitant, and sequential-concomitant hybrid are some first-line regimen options. However, more research is needed regarding appropriate second-line treatments after first-line treatment failure. Tailored therapy, which is based on antibiotic sensitivity testing, would be optimal but has several limitations for clinical use, and an alternative technique is required. A novel potassium-competitive acid blocker-based eradication regimen could be a valuable eradication option in the near future.

  18. Interventions to improve adherence to first-line antibiotics in respiratory tract infections

    DEFF Research Database (Denmark)

    Llor, Carl; Monedero, María José; García, Guillermo

    2015-01-01

    intervention (II), aimed to improve the adherence to recommendations on first-line antibiotics in patients with respiratory tract infections (RTIs). Methods: General practitioners (GPs) from different regions of Spain were offered two different interventions on antibiotic prescribing. They registered all...... included training and access to point-of-care tests in practice. Results: The GPs registered 15 073 RTIs before the intervention and 12 760 RTIs after. The antibiotic prescribing rate reduced from 27.7% to 19.8%. Prescribing of first-choice antibiotics increased after the intervention in both groups....... In the group of GPs following the BI, first-line antibiotics accounted for 23.8% of antibiotics before the intervention and 29.4% after (increase 5.6%, 95% confidence interval (CI): 1.2-10%), while in the group of GPs following the II these figures were 26.2% and 48.6% (increase 22.4%, 95% CI: 18...

  19. PENGARUH PSYCHOLOGICAL EMPOWERMENT, EMPOWERING LEADERSHIP, SISTEM PENGUKURAN KINERJA PADA MOTIVASI INTRINSIK FIRST-LINE EMPLOYEES PERBANKAN

    Directory of Open Access Journals (Sweden)

    I Gusti Ayu Purnamawati

    2016-10-01

    Full Text Available Penelitian ini bertujuan untuk mengetahui pengaruh Psychological Empowerment, Empowering Leadership, dan Sistem Pengukuran Kinerja Pada Motivasi Intrinsik First-Line Employees Perbankan. Penelitian ini adalah penelitian kuantitatif. Data yang digunakan adalah data primer berupa kuesioner yang menggunakan skala likert 1-5 dan terdiri atas 36 item pertanyaan. Responden pada penelitian ini adalah manajemen lini garis pertama pada sektor perbankan yaitu sejumlah 35 orang yang berasal dari 7 BPR yang ada di Kabupaten Buleleng. Metode analisis data menggunakan model regresi linear berganda dengan bantuan alat statistik SPSS. Hasil penelitian menunjukkan bahwa  Psychological Empowerment, Empowering Leadership, dan Sistem Pengukuran Kinerja berpengaruh positif dan signifikan pada Motivasi Intrinsik First-Line Employees Perbankan dengan menggunakan taraf signifikansi 5%.

  20. Rapid first-line discrimination of methicillin resistant Staphylococcus aureus strains using MALDI-TOF MS

    DEFF Research Database (Denmark)

    Østergaard, Claus; Grønvall Kjær Hansen, Sanne; Møller, Jens K

    2015-01-01

    used for this purpose. These methods are all relatively time-consuming and not performed routinely in all laboratories. The aim of this study is to examine whether MALDI-TOF MS can be used as a fast, simple and easily implemented method for first-line discrimination of MRSA isolates. Mass spectra from....../z-values (peaks) and used a concept of arranging these peaks into pairs or small clusters within a small mass range, allowing for quality control of the spectra obtained. Using this concept we could reproducibly characterise and arrange the isolates into 26 MALDI-TOF groups, which strongly correlated with spa...... types and clonal complexes. The results of this study clearly show that MALDI-TOF MS can be used for first-line discrimination of MRSA isolates, using a simple and fast method that is easy to implement as part of routine testing....

  1. Bevacizumab-Based Therapies in the First-Line Treatment of Metastatic Colorectal Cancer

    Science.gov (United States)

    Hurwitz, Herbert I.

    2012-01-01

    Since its approval for the first-line treatment of metastatic colorectal cancer (mCRC), bevacizumab has become a standard treatment option in combination with chemotherapy for patients with mCRC. Bevacizumab has demonstrated efficacy in combination with a number of different backbone chemotherapy regimens, and its widespread use has introduced several important questions regarding the selection and optimization of bevacizumab-based treatment regimens, its use in various patient populations, and the identification of associated adverse events. This review discusses the results of several phase II and phase III clinical trials, as well as large observational studies, to address the use of bevacizumab in the treatment of patients with mCRC in the first-line setting. PMID:22477726

  2. Systematic review: What is the best first-line approach for cesarean section ectopic pregnancy?

    Directory of Open Access Journals (Sweden)

    Mine Kanat-Pektas

    2016-04-01

    Hysteroscopy and laparoscopic hysterotomy are safe and efficient surgical procedures that can be adopted as primary treatment modalities for CSEP. Uterine artery embolization should be reserved for cases with significant bleeding and/or a high suspicion index for arteriovenous malformation. Systemic methotrexate and D&C are not recommended as first-line approaches for CSEP, as these procedures are associated with high complication and hysterectomy rates.

  3. First-line tracheal resection and primary anastomosis for postintubation tracheal stenosis.

    Science.gov (United States)

    Elsayed, H; Mostafa, A M; Soliman, S; Shoukry, T; El-Nori, A A; El-Bawab, H Y

    2016-07-01

    Introduction Tracheal stenosis following intubation is the most common indication for tracheal resection and reconstruction. Endoscopic dilation is almost always associated with recurrence. This study investigated first-line surgical resection and anastomosis performed in fit patients presenting with postintubation tracheal stenosis. Methods Between February 2011 and November 2014, a prospective study was performed involving patients who underwent first-line tracheal resection and primary anastomosis after presenting with postintubation tracheal stenosis. Results A total of 30 patients (20 male) were operated on. The median age was 23.5 years (range: 13-77 years). Seventeen patients (56.7%) had had previous endoscopic tracheal dilation, four (13.3%) had had tracheal stents inserted prior to surgery and one (3.3%) had undergone previous tracheal resection. Nineteen patients (63.3%) had had a tracheostomy. Eight patients (26.7%) had had no previous tracheal interventions. The median time of intubation in those developing tracheal stenosis was 20.5 days (range: 0-45 days). The median length of hospital stay was 10.5 days (range: 7-21 days). The success rate for anastomoses was 96.7% (29/30). One patient needed a permanent tracheostomy. The in-hospital mortality rate was 3.3%: 1 patient died from a chest infection 21 days after surgery. There was no mortality or morbidity in the group undergoing first-line surgery for de novo tracheal lesions. Conclusions First-line tracheal resection with primary anastomosis is a safe option for the treatment of tracheal stenosis following intubation and obviates the need for repeated dilations. Endoscopic dilation should be reserved for those patients with significant co-morbidities or as a temporary measure in non-equipped centres.

  4. First-line treatment of advanced ALK-positive non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Gandhi S

    2015-09-01

    Full Text Available Shipra Gandhi,1 Hongbin Chen,2 Yujie Zhao,2 Grace K Dy2 1Department of Internal Medicine, State University of New York, 2Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA Abstract: Non-small-cell lung cancer (NSCLC is one of the leading causes of cancer deaths, both within the US and worldwide. There have been major treatment advances in NSCLC over the past decade with the discovery of molecular drivers of NSCLC, which has ushered in an era of personalized medicine. There are several actionable genetic aberrations in NSCLC, such as epidermal growth factor receptor and anaplastic lymphoma kinase (ALK. In 3%–7% of NSCLC, a chromosomal inversion event in chromosome 2 leads to fusion of a portion of the ALK gene with the echinoderm microtubule–associated protein-like 4 (EML4 gene. The constitutive activation of the ALK fusion oncogene renders it vulnerable to therapeutic intervention. This review focuses on the first-line treatment of advanced ALK-positive NSCLC using ALK inhibitors. Crizotinib was the first agent proven to be efficacious as first-line treatment for ALK-positive NSCLC. However, acquired resistance inevitably develops. The central nervous system is a sanctuary site that represents a common site for disease progression as well. Hence, more potent, selective next-generation ALK inhibitors that are able to cross the blood–brain barrier have been developed for treatment against crizotinib-resistant ALK-positive NSCLC and are also currently being evaluated for first-line therapy as well. In this review, we provide summary of the clinical experience with these drugs in the treatment of ALK-positive NSCLC. Keywords: non-small-cell lung cancer, ALK, first line, crizotinib, pemetrexed

  5. Has the time come to abandon efavirenz for first-line antiretroviral therapy?

    Science.gov (United States)

    Raffi, Francois; Pozniak, Anton L; Wainberg, Mark A

    2014-07-01

    Efavirenz has been recommended as a preferred third agent together with two nucleos(t)ides for first-line combination antiretroviral therapy (ART) for >15 years. The availability of efavirenz in a fixed-dose combination makes it very attractive. However, because of (i) adverse events associated with efavirenz, (ii) a poorer overall efficacy of efavirenz compared with newer antiretrovirals, (iii) the ranking of efavirenz as FDA Pregnancy Category D and (iv) the relatively high prevalence of transmitted drug-resistance mutations, there is a need to reconsider the role of efavirenz in first-line ART. We review the available evidence that challenges efavirenz's current position in first-line HIV treatment guidelines. Apart from its animal teratogenic potential, and moderate neuropsychiatric adverse events associated with its use, efavirenz has recently been associated with an increased risk of suicidality when compared with other antiretroviral drugs. Most importantly, efavirenz has demonstrated overall inferior efficacy to various comparator drugs, which include rilpivirine, raltegravir and dolutegravir, in antiretroviral-naive patients. Furthermore, epidemiological data indicate that the prevalence of non-nucleoside reverse transcriptase inhibitor resistance has reached 5%-8% in various parts of the world, and minority transmitted non-nucleoside reverse transcriptase inhibitor resistance-associated mutations can have a negative impact on the outcome of first-line efavirenz-based ART. Based on considerations of efficacy, toxicity and resistance, it is time to reconsider the routine use of efavirenz in ART. This, of course, presupposes that other antiretrovirals will be available in place of efavirenz, and may not be applicable in certain developing country settings where this is not the case. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e

  6. Power in health care organizations: contemplations from the first-line management perspective.

    Science.gov (United States)

    Isosaari, Ulla

    2011-01-01

    The aim of this paper is to examine health care organizations' power structures from the first-line management perspective. What liable power structures derive from the theoretical bases of bureaucratic, professional and result based organizations, and what power type do health care organizations represent, according to the empirical data? The paper seeks to perform an analysis using Mintzberg's power configurations of instrument, closed system, meritocracy and political arena. The empirical study was executed at the end of 2005 through a survey in ten Finnish hospital districts in both specialized and primary care. Respondents were all first-line managers in the area and a sample of staff members from internal disease, surgical and psychiatric units, as well as out-patient and primary care units. The number of respondents was 1,197 and the response percentage was 38. The data were analyzed statistically. As a result, it can be seen that a certain kind of organization structure supports the generation of a certain power type. A bureaucratic organization generates an instrument or closed system organization, a professional organization generates meritocracy and also political arena, and a result-based organization has a connection to political arena and meritocracy. First line managers regarded health care organizations as instruments when staff regarded them mainly as meritocracies having features of political arena. Managers felt their position to be limited by rules, whereas staff members regarded their position as having lots of space and influence potential. If the organizations seek innovative and active managers at the unit level, they should change the organizational structure and redistribute the work so that there could be more space for meaningful management. This research adds to the literature and gives helpful suggestions that will be of interest to those in the position of first-line management in health care.

  7. Review of the first line supervisory positions in nuclear power plants

    International Nuclear Information System (INIS)

    Mullin, D.; Mackenzie, C.W.

    1995-10-01

    The authors review the nature of the tasks performed by first line maintenance supervisors in three nuclear power plants. They compare these tasks to core supervisory training curriculum, supervisory job descriptions, and both the process related to performance appraisals, and the criteria applied in carrying out these performance evaluations. Recommendations have been made concerning methods of increasing the relevancy of training and improving the performance appraisal process. ( author). 5 figs

  8. First-line nurse leaders' health-care change management initiatives.

    Science.gov (United States)

    Macphee, Maura; Suryaprakash, Nitya

    2012-03-01

    To examine nurse leaders' change management projects within British Columbia, Canada. British Columbia Nursing Leadership Institute 2007-10 attendees worked on year-long change management initiatives/projects of importance to their respective health-care institutions. Most leaders were in first-line positions with initiatives. Constant change is a global reality. Change management, a universal competency, must be included in leadership development programmes. © 2011 Blackwell Publishing Ltd.

  9. [Indications for methotrexate in gynecology outside the first-line treatment of ectopic tubal pregnancies].

    Science.gov (United States)

    Misme, H; Agostini, A; Dubernard, G; Tourette, C

    2015-03-01

    The objective of this work is to discuss the indications for methotrexate in gynecology outside the first-line treatment of tubal ectopic pregnancy. In tubal ectopic pregnancy, the prophylactic use of systemic methotrexate can be discussed when performing laparoscopic salpingotomy. In case of failure of salpingotomy, administration seems justified especially if it avoids re-intervention. The combination of methotrexate with other therapies such as mifepristone, potassium chloride or gefitinib is not recommended in the treatment of ectopic pregnancy. For non-tubal ectopic pregnancy, the intramuscular or local administration of methotrexate is an acceptable treatment for uncomplicated interstitial pregnancies. For uncomplicated cervical or cesarean scar pregnancies, the local administration of methotrexate should be considered as a first-line treatment. For ovarian pregnancies, methotrexate should not be a first-line treatment, surgical treatment remains the standard. Asymptomatic women presenting with a pregnancy of unknown location and plateauing serum hCG concentration<2000 UI/L can be managed expectantly: it is recommended to take an additional quantitative hCG serum level after 48 hours. Thus, methotrexate is not recommended in the first intention. Other gynecological indications were discussed: methotrexate is not recommended in the management of first-trimester miscarriages or in the management of placenta accreta. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  10. First-line treatment for chronic myeloid leukemia: dasatinib, nilotinib, or imatinib

    Directory of Open Access Journals (Sweden)

    Rafiyath Shamudheen

    2010-11-01

    Full Text Available Abstract Imatinib, a tyrosine kinase inhibitor (TKI of BCR-ABL, was the standard first-line therapy for chronic myeloid leukemia (CML for almost 10 years. Dasatinib and nilotinib, two newer drugs with higher potency than imatinib against BCR-ABL and activity against most imatinib-resistant BCR-ABL mutations, have each shown superior efficacy compared with imatinib for first-line treatment of chronic-phase CML in randomized phase 3 trials. With 14 months follow-up time, available data suggest no obvious differences in efficacy between dasatinib and nilotinib. Compared with imatinib, dasatinib is associated with higher rates of pleural effusion and thrombocytopenia, but lower rates of edema, gastrointestinal AEs, musculoskeletal AEs, and rash. Nilotinib is associated with higher rates of dermatologic toxicity, headache, and biochemical abnormalities associated with hepatic and pancreatic toxicity compared with imatinib, but lower rates of edema, gastrointestinal AEs, muscle spasm, and neutropenia. Several studies have shown that poor adherence to imatinib detrimentally affects responses and should be considered in patients with a suboptimal response. The different dosing requirements of dasatinib (once daily with or without food and nilotinib (twice daily with fasting may be an additional factor in selecting frontline agents. This review compares and contrasts the three FDA approved first line TKI agents.

  11. Resilience and work-life balance in first-line nurse manager.

    Science.gov (United States)

    Kim, Miyoung; Windsor, Carol

    2015-03-01

    The aim of this study was to explore how first-line nurse managers constructed the meaning of resilience and its relationship to work-life balance for nurses in Korea. Participants were 20 first-line nurse managers working in six university hospitals. Data were collected through in-depth interviews from December 2011 to August 2012, and analyzed using Strauss and Corbin's grounded theory method. Analysis revealed that participants perceived work-life balance and resilience to be shaped by dynamic, reflective processes. The features consisting resilience included "positive thinking", "flexibility", "assuming responsibility", and "separating work and life". This perception of resilience has the potential to facilitate a shift in focus from negative to positive experiences, from rigidity to flexibility, from task-centered to person-centered thinking, and from the organization to life. Recognizing the importance of work-life balance in producing and sustaining resilience in first-line nurse managers could increase retention in the Korean nursing workforce. Copyright © 2015. Published by Elsevier B.V.

  12. Managerial competence of first-line nurse managers: A concept analysis.

    Science.gov (United States)

    Gunawan, Joko; Aungsuroch, Yupin

    2017-02-01

    A variety of terms are used interchangeably to define managerial competence of first-line nurse managers. This has resulted in a degree of ambiguity in the way managerial competence is described. The aim of this concept analysis is to clarify what is meant by managerial competence of first-line nurse managers internationally, what attributes signify it, and what its antecedents and consequences are. The Walker and Avant concept analysis approach was applied. The attributes of managerial competence include developing self, planning, organizing, leading, managing legal and ethical issues, and delivering health care. Antecedents to managerial competence include internal and external factors. Consequences include nurse performances, nurse and patient outcomes, intention to stay of nurses, and nurse and patient satisfaction. This analysis helps first-line nurse managers to understand the concept and determine where the responsibility lies in establishing a definition of managerial competence. It is recommended that middle and top managers should be aware of the internal and external factors as antecedents of the concept. Further research is needed to illuminate the attributes of managerial competence in relation to antecedents and the potential effect upon the consequences, and the need to establish managerial competence evaluation. © 2017 John Wiley & Sons Australia, Ltd.

  13. Drug effects on melanoma

    NARCIS (Netherlands)

    Koomen, Elsje Rosalie

    2010-01-01

    Cutaneous melanoma is the most aggressive form of skin cancer and its incidence among Caucasian populations has increased whereas mortality rates are stabilizing or decreasing. The total burden of melanoma is expected to be increasing. As effective treatment options for advanced melanoma are

  14. Burden of Melanoma

    NARCIS (Netherlands)

    C. Holterhues (Cynthia)

    2011-01-01

    markdownabstract__Abstract__ Melanoma is a type of skin cancer that arises from melanocytes. More than 95% of all melanomas occur in the skin, but rarely in the pigmented cells of the eye, meninges or mucosa. This thesis will only regard the invasive cutaneous malignant melanomas.

  15. Genetics of familial melanoma

    DEFF Research Database (Denmark)

    Aoude, Lauren G; Wadt, Karin A W; Pritchard, Antonia L

    2015-01-01

    Twenty years ago, the first familial melanoma susceptibility gene, CDKN2A, was identified. Two years later, another high-penetrance gene, CDK4, was found to be responsible for melanoma development in some families. Progress in identifying new familial melanoma genes was subsequently slow; however...

  16. Cutaneous melanoma in women

    Directory of Open Access Journals (Sweden)

    Mi Ryung Roh, MD

    2017-03-01

    Conclusions: The published findings on gender disparities in melanoma have yielded many advances in our understanding of this disease. Biological, environmental, and behavioral factors may explain the observed gender difference in melanoma incidence and outcome. Further research will enable us to learn more about melanoma pathogenesis, with the goal of offering better treatments and preventative advice to our patients.

  17. Cutaneous melanoma in women

    Directory of Open Access Journals (Sweden)

    Mi Ryung Roh, MD

    2015-02-01

    Conclusions: The published findings on gender disparities in melanoma have yielded many advances in our understanding of this disease. Biological, environmental, and behavioral factors may explain the observed gender difference in melanoma incidence and outcome. Further research will enable us to learn more about melanoma pathogenesis, with the goal of offering better treatments and preventative advice to our patients.

  18. First-line antiretroviral therapy and dyslipidemia in people living with HIV-1 in Cameroon: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Kengne André

    2011-09-01

    Full Text Available Abstract Background Data on lipid profile derangements induced by antiretroviral treatment in Africa are scarce. The aim of this study was to determine the prevalence and characteristics of lipid profile derangements associated with first-line highly active antiretroviral therapy (ART among Cameroonians living with human immunodeficiency virus (HIV infection. Methods This cross-sectional study was conducted between November 2009 and January 2010, and involved 138 HIV patients who had never received ART (ART-naive group and 138 others treated for at least 12 months with first line triple ART regimens that included nevirapine or efavirenz (ART group. Lipid profile was determined after overnight fast and dyslipidemia diagnosed according to the US National Cholesterol Education Program III criteria. Data comparison used chi-square test, Student t-test and logistic regressions. Results The prevalence of total cholesterol ≥ 200 mg/dl was 37.6% and 24.6% respectively in ART group and ART-naive groups (p = 0.019. The equivalents for LDL-cholesterol ≥ 130 mg/dl were 46.4% and 21% (p ≤ 0.001. Proportions of patients with total cholesterol/HDL-cholesterol ratio ≥ 5 was 35.5% in ART group and 18.6% in ART-naive group (p ≤ 0.001. The distribution of HDL-cholesterol and triglycerides was similar between the two groups. In multivariable analysis adjusted for age, sex, body mass index, CD4 count and co-infection with tuberculosis, being on ART was significantly and positively associated with raised total cholesterol, LDL-cholesterol and TC/HDL cholesterol. The adjusted odd ratios (95% confidence interval, p-value ART-treated vs. ART-naïve was 1.82 (1.06-1.12, p = 0.02 for TC ≥ 200 mg/dl; 2.99 (1.74-5.15, p Conclusions First-line antiretroviral therapy that includes nonnucleoside reverse transcriptase inhibitors is associated with pro-atherogenic adverse lipid profile in people with HIV-1 infection compared to untreated HIV-infected subjects in

  19. Antimicrobial susceptibility testing before first-line treatment for Helicobacter pylori infection in patients with dual or triple antibiotic resistance.

    Science.gov (United States)

    Cosme, Angel; Montes, Milagrosa; Ibarra, Begoña; Tamayo, Esther; Alonso, Horacio; Mendarte, Usua; Lizasoan, Jacobo; Herreros-Villanueva, Marta; Bujanda, Luis

    2017-05-14

    To evaluate the efficacy of antimicrobial susceptibility-guided therapy before first-line treatment for infection in patients with dual or triple antibiotic resistance. A total of 1034 patients infected by Helicobacter pylori ( H. pylori ) during 2013-2014 were tested for antimicrobial susceptibility. 157 of 1034 (15%) patients showed resistance to two (127/1034; 12%) and to three (30/1034; 3%) antibiotics. Sixty-eight patients with dual H. pylori -resistance (clarithromycin, metronidazole or levofloxacin) were treated for 10 d with triple therapies: OAL (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and levofloxacin 500 mg b.i.d.) 43 cases, OAM (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg b.i.d.) 12 cases and OAC (omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d.) 13 cases based on the antimicrobial susceptibility testing. Twelve patients showed triple H. pylori -resistance (clarithromycin, metronidazole and levofloxacin) and received for 10 d triple therapy with OAR (omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and rifabutin 150 mg b.i.d.). Eradication was confirmed by 13C-urea breath test. Adverse effects and compliance were assessed by a questionnaire. Intention-to-treat eradication rates were: OAL (97.6%), OAM (91.6%), OAC (92.3%) and OAR (58.3%). Cure rate was significantly higher in naïve patients treated with OAR-10 compared to patients who had two or three previous treatment failures (83% vs 33%). Adverse events rates for OAL, OAM, OAC and OAR were 22%, 25%, 23% and 17%, respectively, all of them mild-moderate. Antimicrobial susceptibility-guided triple therapies during 10 d for first-line treatment leads to an eradication rate superior to 90% in patients with dual antibiotic H. pylori resistance.

  20. Rituximab as first-line treatment for the management of adult patients with non-severe hemophilia A and inhibitors.

    Science.gov (United States)

    Lim, M Y; Nielsen, B; Lee, K; Kasthuri, R S; Key, N S; Ma, A D

    2014-06-01

    The role of immunosuppression in the management of patients with congenital hemophilia and inhibitors is uncertain. The use of rituximab has been limited to case reports and case series. In most reports, rituximab was used as second-line or third-line treatment following failure of conventional immune tolerance induction therapy, and more commonly in pediatric patients. The objective of this study was to describe our experience with rituximab for the eradication of factor VIII inhibitors in adult patients with non-severe hemophilia A. We retrospectively reviewed the medical records of adult patients with non-severe hemophilia A and a diagnosis of FVIII inhibitor treated with rituximab (four weekly doses of 375 mg m(-2) ) as first-line treatment at our hemophilia center. We identified nine consecutive adult patients with hemophilia A (moderate, n = 5; mild, n = 4) at our institution between 2000 and 2013, with a median age of 54 years (range, 24-77 years) at the time of inhibitor diagnosis. No patient received concomitant immune tolerance induction therapy. All nine patients had successful eradication of FVIII inhibitors. The median time from the first dose of rituximab to a clinical response was 95 days (range, 12-278 days). The median follow-up was 56 months (range, 13-139 months). Following inhibitor eradication, eight patients were rechallenged with FVIII concentrates. Two patients developed inhibitor recurrence associated with surgery. This case series demonstrates that rituximab is a useful first-line treatment to achieve sustained inhibitor eradication in adult patients with non-severe hemophilia A. © 2014 International Society on Thrombosis and Haemostasis.

  1. Putative contribution of CD56 positive cells in cetuximab treatment efficacy in first-line metastatic colorectal cancer patients

    International Nuclear Information System (INIS)

    Maréchal, Raphaël; De Schutter, Jef; Nagy, Nathalie; Demetter, Pieter; Lemmers, Arnaud; Devière, Jacques; Salmon, Isabelle; Tejpar, Sabine; Van Laethem, Jean-Luc

    2010-01-01

    Activity of cetuximab, a chimeric monoclonal antibody targeting the epidermal growth factor receptor, is largely attributed to its direct antiproliferative and proapoptotic effects. Antibody-dependent cell-mediated cytotoxicity (ADCC) could be another possible mechanism of cetuximab antitumor effects and its specific contribution on the clinical activity of cetuximab is unknown. We assessed immune cells infiltrate (CD56, CD68, CD3, CD4, CD8, Foxp3) in the primary tumor of metastatic colorectal cancer (mCRC) patients treated with a first-line cetuximab-based chemotherapy in the framework of prospective trials (treatment group) and in a matched group of mCRC patients who received the same chemotherapy regimen without cetuximab (control group). The relationship between intra-tumoral immune effector cells, the K-ras status and the efficacy of the treatment were investigated. We also evaluated in vitro, the ADCC activity in healthy donors and chemonaive mCRC patients and the specific contribution of CD56 + cells. ADCC activity against DLD1 CRC cell line is maintained in cancer patients and significantly declined after CD56 + cells depletion. In multivariate analysis, K-ras wild-type (HR: 4.7 (95% CI 1.8-12.3), p = 0.001) and tumor infiltrating CD56 + cells (HR: 2.6, (95%CI:1.14-6.0), p = 0.019) were independent favourable prognostic factors for PFS and response only in the cetuximab treatment group. By contrast CD56 + cells failed to predict PFS and response in the control group. CD56 + cells, mainly NK cells, may be the major effector of ADCC related-cetuximab activity. Assessment of CD56 + cells infiltrate in primary colorectal adenocarcinoma may provide additional information to K-ras status in predicting response and PFS in mCRC patients treated with first-line cetuximab-based chemotherapy

  2. Interpretation of Melanoma Risk Feedback in First-Degree Relatives of Melanoma Patients

    Directory of Open Access Journals (Sweden)

    Jennifer L. Hay

    2012-01-01

    Full Text Available Little is known about how individuals might interpret brief genetic risk feedback. We examined interpretation and behavioral intentions (sun protection, skin screening in melanoma first-degree relatives (FDRs after exposure to brief prototypic melanoma risk feedback. Using a 3 by 2 experimental pre-post design where feedback type (high-risk mutation, gene environment, and nongenetic and risk level (positive versus negative findings were systematically varied, 139 melanoma FDRs were randomized to receive one of the six scenarios. All scenarios included an explicit reminder that melanoma family history increased their risk regardless of their feedback. The findings indicate main effects by risk level but not feedback type; positive findings led to heightened anticipated melanoma risk perceptions and anticipated behavioral intentions. Yet those who received negative findings often discounted their family melanoma history. As such, 25%, 30%, and 32% of those who received negative mutation, gene-environment, and nongenetic feedback, respectively, reported that their risk was similar to the general population. Given the frequency with which those who pursue genetic testing may receive negative feedback, attention is needed to identify ideal strategies to present negative genetic findings in contexts such as direct to consumer channels where extensive genetic counseling is not required.

  3. Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy

    DEFF Research Database (Denmark)

    Eggermont, Alexander M M; Chiarion-Sileni, Vanna; Grob, Jean-Jacques

    2016-01-01

    undergone complete resection of stage III melanoma. Methods After patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months...

  4. Uveal melanoma: relatively rare but deadly cancer

    Science.gov (United States)

    Kaliki, S; Shields, C L

    2017-01-01

    Although it is a relatively rare disease, primarily found in the Caucasian population, uveal melanoma is the most common primary intraocular tumor in adults with a mean age-adjusted incidence of 5.1 cases per million per year. Tumors are located either in iris (4%), ciliary body (6%), or choroid (90%). The host susceptibility factors for uveal melanoma include fair skin, light eye color, inability to tan, ocular or oculodermal melanocytosis, cutaneous or iris or choroidal nevus, and BRCA1-associated protein 1 mutation. Currently, the most widely used first-line treatment options for this malignancy are resection, radiation therapy, and enucleation. There are two main types of radiation therapy: plaque brachytherapy (iodine-125, ruthenium-106, or palladium-103, or cobalt-60) and teletherapy (proton beam, helium ion, or stereotactic radiosurgery using cyber knife, gamma knife, or linear accelerator). The alternative to radiation is enucleation. Although these therapies achieve satisfactory local disease control, long-term survival rate for patients with uveal melanoma remains guarded, with risk for liver metastasis. There have been advances in early diagnosis over the past few years, and with the hope survival rates could improve as smaller tumors are treated. As in many other cancer indications, both early detection and early treatment could be critical for a positive long-term survival outcome in uveal melanoma. These observations call attention to an unmet medical need for the early treatment of small melanocytic lesions or small melanomas in the eye to achieve local disease control and vision preservation with the possibility to prevent metastases and improve overall patient survival. PMID:27911450

  5. First-line treatment disruption among post-menopausal women with HR+/HER2- metastatic breast cancer: a retrospective US claims study.

    Science.gov (United States)

    Tang, Derek H; Li, Nanxin; Du, Ella X; Peeples, Miranda; Chu, Lihao; Xie, Jipan; Barghout, Victoria

    2017-12-01

    This study assessed disruption of first-line treatments initiated after the approval of the first CDK 4/6 inhibitor, palbociclib, among post-menopausal women with HR+/HER2- metastatic breast cancer (mBC) in the US. Post-menopausal women with HR+/HER2- mBC who initiated first-line endocrine therapy or chemotherapy (index therapy) between February 3, 2015 (palbociclib approval date) and February 29, 2016 (end of data) were identified from the Symphony Source Lx database. Patients were required to have continuous quarterly activity (defined as ≥1 pharmacy or medical claim) for 12 months prior to and 1 month after the initiation of the index therapy (index date). Treatment disruption was defined as a treatment gap of ≥60 days or adding an agent after the original therapy. Kaplan-Meier analyses were conducted to estimate treatment disruption rates during the 6 months following the index date. Patients without treatment disruption were censored at the end of continuous quarterly activity or end of data. A total of 8,160 and 2,153 eligible patients initiated endocrine therapy or chemotherapy as their first-line mBC treatment, with a median follow-up of 6.7 and 7.6 months, respectively. The three most prevalent metastatic sites were bone (28.1-42.2%), liver (8.8-17.3%), and lung (8.6-9.5%). Overall, 37.7% (n = 3,074) of patients receiving endocrine therapy and 86.1% (n = 1,852) of patients receiving chemotherapy encountered treatment disruption at 6 months (log-rank test p disruption rates of first-line therapies were sub-optimal among post-menopausal women with HR+/HER2- mBC, primarily driven by chemotherapy users. New therapies or interventions are needed to reduce treatment disruption in this patient population.

  6. Tumor progression in uveal melanoma

    NARCIS (Netherlands)

    C.M. Mooij (Cornelia)

    1995-01-01

    textabstractOphthalmic melanomas can be divided in extra-ocular (conjunctiva, caruncle) and intraocular uveal melanomas (iris, ciliary body and choroid). Uveal melanomas account for 95% of ocular melanomas, while only 5% are conjunctival in origin. The extra-ocular and intra-ocular melanomas differ

  7. Impact of First-Line Antifungal Agents on the Outcomes and Costs of Candidemia

    Science.gov (United States)

    Ha, Young Eun; Joo, Eun-Jeong; Kim, Shin Woo; Jung, Sook-In; Chang, Hyun Ha; Park, Kyong Hwa; Han, Sang Hoon

    2012-01-01

    Candida species are the leading causes of invasive fungal infection among hospitalized patients and are responsible for major economic burdens. The goals of this study were to estimate the costs directly associated with the treatment of candidemia and factors associated with increased costs, as well as the impact of first-line antifungal agents on the outcomes and costs. A retrospective study was conducted in a sample of 199 patients from four university-affiliated tertiary care hospitals in Korea over 1 year. Only costs attributable to the treatment of candidemia were estimated by reviewing resource utilization during treatment. Risk factors for increased costs, treatment outcome, and hospital length of stay (LOS) were analyzed. Approximately 65% of the patients were treated with fluconazole, and 28% were treated with conventional amphotericin B. The overall treatment success rate was 52.8%, and the 30-day mortality rate was 47.9%. Hematologic malignancy, need for mechanical ventilation, and treatment failure of first-line antifungal agents were independent risk factors for mortality. The mean total cost for the treatment of candidemia was $4,743 per patient. Intensive care unit stay at candidemia onset and antifungal switch to second-line agents were independent risk factors for increased costs. The LOS was also significantly longer in patients who switched antifungal agents to second-line drugs. Antifungal switch to second-line agents for any reasons was the only modifiable risk factor of increased costs and LOS. Choosing an appropriate first-line antifungal agent is crucial for better outcomes and reduced hospital costs of candidemia. PMID:22526315

  8. Resistance of uropathogenic bacteria to first-line antibiotics in mexico city: A multicenter susceptibility analysis.

    Science.gov (United States)

    Arredondo-García, José Luis; Soriano-Becerril, Diana; Solórzano-Santos, Fortino; Arbo-Sosa, Antonio; Coria-Jiménez, Rafael; Arzate-Barbosa, Patricia

    2007-03-01

    Abstract. Growing antibiotic resistance demands the constant reassessment of antimicrobial efficacy, particularly in countries with wide antibiotic abuse, where higher resistance prevalence is often found. Knowledge of resistance trends is particularly important when prescribing antibiotics empirically, as is usually the case for urinary tract infections (UTIs). Currently, in Mexico City, ampicillin, cotrimoxazole (trimethoprim/sulfamethoxazole), and ciprofloxacin are used as "first-line" antibiotic treatment for UTI. The aim of this study was to analyze the resistance of bacterial isolates to antibiotics, with a focus on first-line antibiotics, in Mexican pediatric patients and sexually active or pregnant female outpatients. In this multicenter susceptibility analysis, bacterial isolates from urine samples collected from pediatric patients and sexually-active or pregnant female outpatients presenting with acute, uncomplicated UTIs in Mexico City from January 2006 through June 2006, were included in the study. Samples were tested for susceptibility to 10 antibiotics by the disk-diffusion method. Four-hundred and seventeen bacterial isolates were derived from sexually active or pregnant female outpatients (324 Escherichia coli) and pediatric patients (93 Klebsiella pneumoniae). We found a high prevalence of resistance towards the drugs used as "first-line" when treating UTIs: ampicillin, cotrimoxazole, and ciprofloxacin (79%, 60%, and 24% resistance, respectively). Ninety-eight percent of K pneumoniae isolates were resistant to ampicillin, whereas 66% of the E coli isolates were resistant to cotrimoxazole. Resistance towards third-generation cephalosporins was also high (6%-8% of E coli and 10%-28% of K pneumoniae). This was possibly caused by chromosomal β-lactamases, as 30% of all isolates were also resistant to amoxicillin/clavulanate. In contrast, 98% of the E coli isolates and 84% of the K pneumoniae strains (96% of all isolates) were found to be susceptible

  9. Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Stage IV Melanoma

    Science.gov (United States)

    2016-05-06

    Acral Lentiginous Malignant Melanoma; Lentigo Maligna Malignant Melanoma; Nodular Malignant Melanoma; Recurrent Melanoma; Solar Radiation-related Skin Melanoma; Stage IV Melanoma; Superficial Spreading Malignant Melanoma

  10. Complete and sustained response of adult medulloblastoma to first-line sonic hedgehog inhibition with vismodegib.

    Science.gov (United States)

    Lou, Emil; Schomaker, Matthew; Wilson, Jon D; Ahrens, Mary; Dolan, Michelle; Nelson, Andrew C

    2016-08-12

    Medulloblastoma is an aggressive primitive neuroectodermal tumor of the cerebellum that is rare in adults. Medulloblastomas fall into 4 prognostically significant molecular subgroups that are best defined by experimental gene expression profiles: the WNT pathway, sonic hedgehog (SHH) pathway, and subgroups 3 and 4 (non-SHH/WNT). Medulloblastoma of adults belong primarily to the SHH category. Vismodegib, an SHH-pathway inhibitor FDA-approved in 2012 for treatment of basal cell carcinoma, has been used successfully in the setting of chemorefractory medulloblastoma, but not as a first-line therapy. In this report, we describe a sustained response of an unresectable multifocal form of adult medulloblastoma to vismodegib. Molecular analysis in this case revealed mutations in TP53 and a cytogenetic abnormality, i17q, that is prevalent and most often associated with subgroup 4 rather than the SHH-activated form of medulloblastoma. Our findings indicate that vismodegib may also block alternate, non-canonical forms of downstream SHH pathway activation. These findings provide strong impetus for further investigation of vismodegib in clinical trials in the first-line setting for pediatric and adult forms of medulloblastoma.

  11. First-line medications for alcohol use disorders among public drug plan beneficiaries in Ontario.

    Science.gov (United States)

    Spithoff, Sheryl; Turner, Suzanne; Gomes, Tara; Martins, Diana; Singh, Samantha

    2017-05-01

    To examine use of first-line alcohol use disorder (AUD) medications (naltrexone and acamprosate) among public drug plan beneficiaries in the year following an AUD diagnosis. Retrospective population-based cohort study. Ontario. Individuals eligible for public drug plan benefits who had an AUD diagnosis at a hospital visit between April 1, 2011, and March 31, 2012. Number of AUD medications dispensed to public drug plan beneficiaries who had a recent hospital visit with an AUD diagnosis, and number of prescriptions dispensed per person. A total of 10 394 Ontarians between 18 and 65 years of age were identified who had a hospital visit with an AUD diagnosis and were eligible for public drug plan benefits. The rate of AUD medications dispensed in the subsequent year was 3.56 per 1000 population (95% CI 2.51 to 4.91; n = 37). This rate did not differ significantly by sex ( P = .83). Very few public drug plan beneficiaries are dispensed first-line AUD medications in the year following an AUD diagnosis. Copyright© the College of Family Physicians of Canada.

  12. First-line managers' descriptions and reflections regarding their staff's access to empowering structures.

    Science.gov (United States)

    Skytt, Bernice; Hagerman, Heidi; Strömberg, Annika; Engström, Maria

    2015-11-01

    To elucidate first-line managers' descriptions and reflections regarding their staff's access to empowering structures using Kanter's theory of structural empowerment. Good structural conditions within workplaces are essential to employees' wellbeing, and their ability to access empowerment structures is largely dependent on the management. Twenty-eight first-line managers in elderly care were interviewed. Deductive qualitative content analysis was used to analyse data. Managers perceived that staff had varying degrees of access to the empowering structures described in Kanter's theory - and that they possessed formal power in their roles as contact persons and representatives. The descriptions mostly started from the managers' own actions, although some started from the needs of staff members. All managers described their staff's access to the empowering structures in Kanter's theory as important, yet it seemed as though this was not always reflected on and discussed as a strategic issue. Managers could make use of performance and appraisal dialogues to keep up to date on staff's access to empowering structures. Recurrent discussions in the management group based on such current information could promote staff's access to power through empowering structures and make job definitions a strategic issue in the organisation. © 2014 John Wiley & Sons Ltd.

  13. TIMP-1 and VEGF-165 serum concentration during first-line therapy of ovarian cancer patients

    Directory of Open Access Journals (Sweden)

    Jaenicke Fritz

    2010-04-01

    Full Text Available Abstract Background Angiogenesis appears to play an important role in ovarian cancer. Vascular endothelial growth factor (VEGF has recently been implicated as a therapeutic target in ovarian cancer. The tissue inhibitor of metalloproteinase 1 (TIMP-1 is involved in tissue invasion and angiogenesis. The application of serum TIMP-1 and VEGF to monitor primary therapy and predict clinical outcome of patients with ovarian cancer is unclear. Methods Patients with epithelial ovarian cancer who presented for primary surgery were included in this study. A total of 148 serum samples from 37 patients were analyzed. Samples were prospectively collected at 4 predefined time points: 1. before radical debulking surgery, 2. after surgery and before platinum/taxane based chemotherapy, 3. during chemotherapy, 4. after chemotherapy. Serum VEGF-165 and TIMP-1 as well as CA-125 were quantified by ELISA or ECLIA and correlation with response and long-term clinical outcome was analyzed. Results Serum levels of all markers changed substantially during first-line therapy. High CA-125 (p = 0.002, TIMP-1 (p = 0.007 and VEGF-165 (p = 0.02 after chemotherapy were associated with reduced overall survival. In addition, elevated CA-125 (p Conclusions TIMP-1 and VEGF serum levels changed significantly during first-line therapy of ovarian cancer patients and predicted prognosis. These findings support the role of angiogenesis in ovarian cancer progression and the use of antiangiogenic therapy.

  14. Intratumoral Approaches for the Treatment of Melanoma.

    Science.gov (United States)

    Bommareddy, Praveen K; Silk, Ann W; Kaufman, Howard L

    There have been significant advances in the immunotherapy of melanoma over the last decade. The tumor microenvironment is now known to promote an immune-suppressive milieu that can block effective immune-mediated tumor rejection. Several novel strategies designed to overcome local immunosuppression hold promise for treatment of melanoma and other cancers. These approaches include oncolytic viruses, plasmid DNA delivery, Toll-like receptor agonists, inflammatory dyes, cytokines, checkpoint inhibitors, immunomodulatory agents, and host and pathogenic cell-based vectors. In addition, there are several novel methods for local drug delivery, including direct injection, image-guided, electroporation, and nanodelivery techniques under study. The approval of talimogene laherparepvec (Imlygic), an attenuated, recombinant oncolytic herpesvirus, for melanoma treatment is the first intratumoral agent to receive regulatory approval for the treatment of patients with melanoma. This review will focus on the rationale for intratumoral treatment in melanoma, describe the clinical and safety data for some of the agents in clinical development, and provide a perspective for future clinical investigation with intratumoral approaches. Melanoma has been a paradigm tumor for progress in targeted therapy and immunotherapy and will likely also be the tumor to establish the therapeutic role of intratumoral treatment for cancer.

  15. Recurrent glioblastomas in the elderly after maximal first-line treatment: does preserved overall condition warrant a maximal second-line treatment?

    Science.gov (United States)

    Zanello, Marc; Roux, Alexandre; Ursu, Renata; Peeters, Sophie; Bauchet, Luc; Noel, Georges; Guyotat, Jacques; Le Reste, Pierre-Jean; Faillot, Thierry; Litre, Fabien; Desse, Nicolas; Emery, Evelyne; Petit, Antoine; Peltier, Johann; Voirin, Jimmy; Caire, François; Barat, Jean-Luc; Vignes, Jean-Rodolphe; Menei, Philippe; Langlois, Olivier; Dezamis, Edouard; Carpentier, Antoine; Dam Hieu, Phong; Metellus, Philippe; Pallud, Johan

    2017-11-01

    A growing literature supports maximal safe resection followed by standard combined chemoradiotherapy (i.e. maximal first-line therapy) for selected elderly glioblastoma patients. To assess the prognostic factors from recurrence in elderly glioblastoma patients treated by maximal safe resection followed by standard combined chemoradiotherapy as first-line therapy. Multicentric retrospective analysis comparing the prognosis and optimal oncological management of recurrent glioblastomas between 660 adult patients aged of patients aged of ≥70 years (elderly group) harboring a supratentorial glioblastoma treated by maximal first-line therapy. From recurrence, both groups did not significantly differ regarding Karnofsky performance status (KPS) (p = 0.482). Oncological treatments from recurrence significantly differed: patients of the elderly group received less frequently oncological treatment from recurrence (p oncological treatment from recurrence (p patients had substandard care from recurrence whereas age did not impact overall survival from recurrence contrary to KPS at recurrence <70. Treatment options from recurrence should include repeat surgery, second line chemotherapy and anti-angiogenic agents.

  16. Impact of tumour RAS/BRAF status in a first-line study of panitumumab + FOLFIRI in patients with metastatic colorectal cancer

    Science.gov (United States)

    Karthaus, Meinolf; Hofheinz, Ralf-Dieter; Mineur, Laurent; Letocha, Henry; Greil, Richard; Thaler, Josef; Fernebro, Eva; Oliner, Kelly S; Boedigheimer, Michael; Twomey, Brian; Zhang, Ying; Demonty, Gaston; Köhne, Claus-Henning

    2016-01-01

    Background: To investigate tumour biomarker status and efficacy of first-line panitumumab+FOLFIRI for metastatic colorectal carcinoma (mCRC). Methods: 154 patients received first-line panitumumab + FOLFIRI every 14 days. Primary end point was objective response rate (ORR). Data were analysed by tumour RAS (KRAS/NRAS) and BRAF status, and baseline amphiregulin (AREG) expression. Results: Objective responses occurred more frequently in RAS wild type (WT) (59%) vs RAS mutant (MT) (41%) mCRC and in RAS WT/BRAF WT (68%) vs RAS or BRAF MT (37%) disease. Median response duration was longer in RAS WT (13.0 months) vs RAS MT (5.8 months) (hazard ratio (HR): 0.16). Median progression-free survival was longer in RAS WT vs MT (11.2 vs 7.3 months; HR, 0.37) and was also longer in RAS WT/BRAF WT vs RAS or BRAF MT (13.2 vs 6.9 months; HR, 0.25). Incidence of adverse events was similar regardless of RAS/BRAF status, and no new safety signals were noted. Among patients with RAS WT tumours, ORR was 67% with high AREG expression and 38% with low AREG expression. Conclusions: First-line panitumumab+FOLFIRI was associated with favourable efficacy in patients with RAS WT and RAS WT/BRAF WT vs MT mCRC tumours and was well tolerated. PMID:27764839

  17. Decoding Melanoma Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Damsky, William E. Jr. [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States); Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont (United States); Rosenbaum, Lara E.; Bosenberg, Marcus, E-mail: Marcus.Bosenberg@yale.edu [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States)

    2010-12-30

    Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis.

  18. Primary malignant melanoma

    Directory of Open Access Journals (Sweden)

    A. Ferhat Mısır

    2016-04-01

    Full Text Available Malignant melanomas (MM of the oral cavity are extremely rare, accounting for 0.2% to 8.0% of all malignant melanomas. Malignant melanomas is more frequently seen at the level of the hard palate and gingiva. Early diagnosis and treatment are important for reducing morbidity. Malignant melanoma cells stain positively with antibodies to human melanoma black 45, S-100 protein, and vimentin; therefore, immunohistochemistry can play an important role in evaluating the depth of invasion and the location of metastases. A 76-year-old man developed an oral malignant melanoma, which was originally diagnosed as a bluish reactive denture hyperplasia caused by an ill-fitting lower denture. The tumor was removed surgically, and histopathological examination revealed a nodular-type MM. There was no evidence of recurrence over a 4-year follow-up period.

  19. Diagnosis and clinical management of melanoma patients at higher risk of a new primary melanoma: A population-based study in New South Wales, Australia.

    Science.gov (United States)

    Watts, Caroline G; Madronio, Christine M; Morton, Rachael L; Goumas, Chris; Armstrong, Bruce K; Curtin, Austin; Menzies, Scott W; Mann, Graham J; Thompson, John F; Cust, Anne E

    2017-11-01

    To describe the method of diagnosis, clinical management and adherence to clinical practice guidelines for melanoma patients at high risk of a subsequent primary melanoma, and compare this with melanoma patients at lower risk. The Melanoma Patterns of Care study was a population-based, observational study based on doctors' reported clinical management of melanoma patients in New South Wales, Australia, diagnosed with in situ or invasive melanoma over a 12-month period from October 2006. Of 2605 patients with localised melanoma, 1019 (39%) were defined as at higher risk due to the presence of one or more of the following factors: a family history of melanoma (11%), multiple primary melanomas (17%), or many naevi (24%). Compared to patients at lower risk, high risk patients were more likely to receive their initial care from a primary care physician (56% vs 50%, P = 0.002), have their melanoma detected during a routine skin check (40% vs 33%, P < 0.001), have their lesion assessed with dermoscopy (63% vs 56%, P = 0.002), and be encouraged to have skin surveillance (84% vs 77%, P < 0.001) and skin self-examination (87% vs 83%, P = 0.03). Higher socioeconomic status and urban residence were associated with patients at higher risk receiving initial treatment from a specialist doctor. Clinical management of higher risk patients was more likely to conform to clinical practice guidelines for diagnosis and skin surveillance than to melanoma patients at lower risk. © 2016 The Australasian College of Dermatologists.

  20. CASE REPORT: NODULAR MELANOMA

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    Tina Zupančič

    2015-05-01

    Full Text Available Nodular melanoma is a rare type of cutaneous melanoma with an increased risk of death. It often mimics benign cutaneous tumors and inflammatory lesions. It has pronounced vertical growth phase and greater thickness at the time of diagnosis which caries ominous prognostic value. Nodular melanoma quickly develops metastases which are often present before the disease is clinically recognised. Here, we report a case of nodular melanoma clinically mimicking seborrheic keratosis. Therapy and 36 months follow-up after primal excision are also presented.

  1. Use of Oncept melanoma vaccine in 69 canine oral malignant melanomas in the UK.

    Science.gov (United States)

    Verganti, S; Berlato, D; Blackwood, L; Amores-Fuster, I; Polton, G A; Elders, R; Doyle, R; Taylor, A; Murphy, S

    2017-01-01

    Oral malignant melanomas carry a poor-to-guarded prognosis because of their local invasiveness and high metastatic propensity. The Oncept melanoma vaccine is licensed to treat dogs with stage II or III locally-controlled oral malignant melanoma and this retrospective study aimed to assess survival of affected dogs treated with the vaccine in the UK. Medical records of dogs with histopathologically-confirmed oral malignant melanoma that received the vaccine as part of their treatment were evaluated. Survival analyses for potential prognostic factors were performed. Sixty-nine dogs were included; 56 dogs, staged I to III, and with previous locoregional therapy, had a median survival time of 455 days (95% CI: 324 to 586 days). Based on Kaplan-Meier survival analysis with associated log-rank testing, no significant prognostic factors were identified for this population. Of the 13 patients with macroscopic disease treated with vaccine alone or in combination therapy, eight showed clinical response. Three patients with stage IV oral malignant melanoma survived 171, 178 and 288 days from diagnosis. Patients treated with the melanoma vaccine in our study had survival times similar to their counterparts receiving the vaccine in the USA. There were observed responses in patients with macroscopic disease and so the vaccine could be considered as palliative treatment in dogs with stage IV disease. © 2017 British Small Animal Veterinary Association.

  2. THROMBOCYTOSIS AS PROGNOSTIC FACTOR FOR SURVIVAL IN PATIENTS WITH ADVANCED NON SMALL CELL LUNG CANCER TREATED WITH FIRST- LINE CHEMOTHERAPY.

    Directory of Open Access Journals (Sweden)

    Deyan Davidov

    2014-12-01

    Full Text Available Objective: The aim of this study was to evaluate elevated platelet count as a prognostic factor for survival in patients with advanced (stage IIIB/ IV non- small cell lung cancer (NSCLC receiving first- line chemotherapy. Methods: From 2005 to 2009 three hundreds forty seven consecutive patients with stage IIIB or IV NSCLC, treated in Department of Medical Oncology, UMHAT "Dr Georgi Stranski" entered the study. The therapeutic regimens included intravenous administration of platinum- based doublets. Survival analysis was evaluated by Kaplan- Meier test. The influence of pretreatment thrombocytosis as prognostic factor for survival was analyzed using multivariate stepwise Cox regression analyses. Results: Elevated platelet counts were found in 78 patients. The overall survival for patients without elevated platelet counts was 9,6 months versus 6,9 months for these with thrombocytosis. In multivariate analysis as independent poor prognostic factors were identified: stage, performance status and elevated platelet counts. Conclusions: These results indicated that platelet counts as well as some clinical pathologic characteristics could be useful prognostic factors in patients with unresectable NSCLC.

  3. Voriconazole as a first-line treatment against potentially pathogenic Acanthamoeba strains from Peru.

    Science.gov (United States)

    Cabello-Vílchez, Alfonso Martín; Martín-Navarro, Carmen M; López-Arencibia, Atteneri; Reyes-Batlle, María; Sifaoui, Ines; Valladares, Basilio; Piñero, José E; Lorenzo-Morales, Jacob

    2014-02-01

    Pathogenic strains of Acanthamoeba genus are the causative agents of fatal granulomatous amoebic encephalitis and a serious sight-threatening infection of the eye known as Acanthamoeba keratitis. In a previous study, Acanthamoeba strains were isolated from nasal swabs collected from healthy individuals in Peru. In the present study, the pathogenic potential of the isolated strains was established based on temperature and osmotolerance assays as well as the secretion rate of extracellular proteases. Based on these experiments, four strains that showed the highest pathogenic potential were selected for sensitivity assays against two molecules (voriconazole and chlorhexidine) which are currently used for the treatment of Acanthamoeba infections. After performing sensitivity and activity assays, it was found that both drugs were active against the tested strains. However, voriconazole showed higher activity against the studied strains compared to chlorhexidine. Therefore, voriconazole should be established as a first-line treatment against Acanthamoeba infections at least in the studied region of Peru.

  4. Major complications of bariatric surgery: endoscopy as first-line treatment.

    Science.gov (United States)

    Eisendrath, Pierre; Deviere, Jacques

    2015-12-01

    Leaks are the most frequent early postoperative complication in the two most popular bariatric procedures, Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy. Multimodal therapy based on self-expandable stent insertion 'to cover' the defect is the most widely documented technique to date with a reported success rate >80%. Additional experimental techniques 'to close' the defect or 'to drain' the paradigestive cavity have been reported with encouraging results. The role of endoscopy in early postoperative bleeding is limited to management of bleeds arising from fresh sutures and the diagnosis of chronic sources of bleeding such as marginal ulcer after RYGB. Post-RYGB stricture is a more delayed complication than leaks and the role of endoscopic dilation as a first-line treatment in this indication is well documented. Ring and band placement are outdated procedures for obesity treatment, but might still be an indication for endoscopic removal, a technique which does not compromise further surgery, if needed.

  5. Human african trypanosomiasis diagnosis in first-line health services of endemic countries, a systematic review.

    Directory of Open Access Journals (Sweden)

    Patrick Mitashi

    Full Text Available While the incidence of Human African Trypanosomiasis (HAT is decreasing, the control approach is shifting from active population screening by mobile teams to passive case detection in primary care centers. We conducted a systematic review of the literature between 1970 and 2011 to assess which diagnostic tools are most suitable for use in first-line health facilities in endemic countries. Our search retrieved 16 different screening and confirmation tests for HAT. The thermostable format of the Card Agglutination Test for Trypanosomiasis (CATT test was the most appropriate screening test. Lateral flow antibody detection tests could become alternative screening tests in the near future. Confirmation of HAT diagnosis still depends on visualizing the parasite in direct microscopy. All other currently available confirmation tests are either technically too demanding and/or lack sensitivity and thus rather inappropriate for use at health center level. Novel applications of molecular tests may have potential for use at district hospital level.

  6. FIRST-LINE TREATMENT IN PATIENTS WITH INOPERABLE METASTATIC COLON CANCER

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2014-01-01

    Full Text Available First-line therapy for metastatic colon cancer is most important for a patient. Its median time to progression constitutes the bulk of the patient’s survival. Clearly, it is necessary to choose the most effective combinations of targeted drugs and chemotherapy regimens. The choice of therapy for patients with colon cancer is governed by both the clinical characteristics of the disease and the molecular changes of a tumor. In recent literature, there has been a great deal of evidence for the use of targeted drugs in different clinical situations; the results of comparative trials of different treatment combinations have been published. This all determines the reconsideration of the choice of a treatment regimen in patients with metastatic colon cancer; it is the topic of the present review.

  7. Physical therapists as first-line diagnosticians for traumatic acute rotator cuff tears: a prospective study.

    Science.gov (United States)

    Aagaard, Knut E; Hänninen, Jonas; Abu-Zidan, Fikri M; Lunsjö, Karl

    2017-11-29

    Early diagnosis of traumatic acute full-thickness rotator cuff tears (FTRCT) is important to offer early surgical repair. Late repairs following fatty infiltration of the rotator cuff muscles have less favorable results. We think that physical therapists are valuable diagnosticians in a screening process. The objective of this study was to evaluate the usefulness of physical therapists as first-line diagnosticians in detecting acute traumatic FTRCT. Between November 2010 and January 2014, 394 consecutive patients having an age between 18 and 75 years who sought medical care because of acute shoulder trauma with acute onset of pain, limited abduction and negative plain radiographs were included in the study. A clinical assessment was conducted by a physical therapist 1 week after the trauma. The patients were divided into three groups by the physical therapist according to the findings: FTRCT (Group I, n = 122); sprain (Group II, n = 62); or other specific diagnoses (Group III, n = 210). Group III patients were discharged and excluded from the study. Magnetic Resonance Imaging shoulder was performed for all Group I patients and for all patients with persistent symptoms in Group II. 79/184 patients had FTRCTs documented by MRI in groups I and II. The clinical assessment of the physical therapist had a sensitivity of 85%, specificity of 68%, and usefulness index of 0.45 (> 0.35 considered useful) for diagnosing FTRCT. Physical therapists can be useful as first-line diagnosticians in detecting traumatic FTRCT.

  8. Systematic review: What is the best first-line approach for cesarean section ectopic pregnancy?

    Science.gov (United States)

    Kanat-Pektas, Mine; Bodur, Serkan; Dundar, Ozgur; Bakır, Vuslat Lale

    2016-04-01

    This systematic review aims to analyze the case reports, case series, or clinical studies describing the women with cesarean scar ectopic pregnancy (CSEP), and thus, to determine the efficacy and safety of different primary treatment modalities in the management of CSEP. A thorough search of electronic databases showed that 274 articles on CSEP were published between January 1978 and April 2014. Systemic methotrexate, uterine artery embolization, dilatation and curettage (D&C), hysterotomy, and hysteroscopy were the most frequently adopted first-line approaches. The success rates of systemic methotrexate, uterine artery embolization, hysteroscopy, D&C, and hysterotomy were 8.7%, 18.3%, 39.1%, 61.6%, and 92.1%, respectively. The hysterectomy rates were 3.6%, 1.1%, 0.0%, 7.3%, and 1.7% in CSEP cases that were treated by systemic methotrexate, uterine artery embolization, hysteroscopy, D&C, and hysterotomy, respectively. The ability to achieve a subsequent term pregnancy is related to successful systemic methotrexate treatment (p = 0.001) or hysterotomy (p = 0.009). Future term pregnancy was significantly more frequent in the hysterotomy group (p = 0.001). Hysteroscopy and laparoscopic hysterotomy are safe and efficient surgical procedures that can be adopted as primary treatment modalities for CSEP. Uterine artery embolization should be reserved for cases with significant bleeding and/or a high suspicion index for arteriovenous malformation. Systemic methotrexate and D&C are not recommended as first-line approaches for CSEP, as these procedures are associated with high complication and hysterectomy rates. Copyright © 2016. Published by Elsevier B.V.

  9. Vigabatrin as First-Line Treatment for Infantile Spasms Not Related to Tuberous Sclerosis Complex.

    Science.gov (United States)

    Jones, Kevin; Go, Cristina; Boyd, Jennifer; Ochi, Ayako; McCoy, Blathnaid; Puka, Klajdi; Snead, O Carter

    2015-08-01

    Infantile spasms are a rare, catastrophic, age-specific seizure disorder of infancy. Adrenocorticotropic hormone or vigabatrin have been recommended for the short-term treatment of infantile spasms by the Child Neurology Society/American Academy of Neurology practice parameter. This retrospective study reviewed the Hospital for Sick Children's experience with the short-term efficacy of vigabatrin as first-line treatment for infantile spasms not related to tuberous sclerosis complex. We performed a single-center, retrospective analysis of all cases of newly diagnosed infantile spasms between January 2010 and September 2013. Duration of follow-up was at least 6 months from treatment initiation. Eighteen of the 61 infants (30%) had a clinical and electrographic response to vigabatrin therapy within 4 weeks of treatment. Of the vigabatrin responders, 2/18 (11%) relapsed. At final follow-up after initiation of vigabatrin therapy, 17/61 (27%) of the vigabatrin responders were free of all clinical seizure types. Normal development at the time of infantile spasms diagnosis was statistically associated with vigabatrin response. These findings do not support our hypothesis that vigabatrin is effective as first-line, short-term treatment of infantile spasms in non-tuberous sclerosis complex patients. However, when used in this setting, vigabatrin is most effective in children with normal development at the time of diagnosis. These findings may assist clinicians in the optimal treatment choice for children at the first presentation of infantile spasms not related to tuberous sclerosis complex. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Hybrid Therapy as First-Line Regimen for Helicobacter pylori Eradication in Populations with High Antibiotic Resistance Rates.

    Science.gov (United States)

    Song, Zhiqiang; Zhou, Liya; Zhang, Jianzhong; He, Lihua; Bai, Peng; Xue, Yan

    2016-10-01

    Hybrid therapy has recently attracted widespread attention. However, many issues require further exploration. For example, research in regions with high antibiotic resistance rates is limited, and the correlation between eradication efficacy and antibiotic resistance remains unclear. The aim of this study was to determine the efficacy, compliance, safety, and risk factors of hybrid therapy as first-line regimen in a region with high antibiotic resistance rates. This prospective study was conducted in a tertiary hospital between January 2014 and June 2015. A total of 196 patients with dyspepsia but without prior eradication therapy received hybrid regimen (esomeprazole 20 mg and amoxicillin 1000 mg twice daily for 14 days with the addition of clarithromycin 500 mg and tinidazole 500 mg twice daily for the final 7 days). All patients underwent Helicobacter pylori culture, antibiotic susceptibility testing and cytochrome P450 isoenzyme 2C19 polymorphism testing. Hybrid therapy achieved eradication rates of 77.0% (95% confidence interval (CI), 70.9-83.7%) in intention-to-treat (ITT), 83.9% (78.9-88.9%) in modified ITT and 86.0% (80.2-91.3%) in per-protocol analyses in a setting with high antibiotic resistance rates (amoxicillin 2.0%, clarithromycin 44.9%, metronidazole 67.3% and dual clarithromycin and metronidazole 33.3%). Adverse reactions occurred in 31.9% patients and 2.7% discontinued medications due to adverse reactions. Good compliance was achieved by 92.0%. Multivariate analyses identified clarithromycin resistance (odds ratio, 3.494; 95% CI, 1.237-9.869), metronidazole resistance (3.012; 1.013-12.054) and poor compliance (5.840; 1.126-30.296) as independent predictors of treatment failure. The eradication rate with dual clarithromycin and metronidazole resistance (70.2%) was markedly decreased compared to isolated clarithromycin resistance (87.5%), isolated metronidazole resistance (88.6%), or dual susceptibility (96.4%) (p = .014). Despite good compliance and

  11. Trends in First-Line Antiretroviral Therapy in Asia: Results from the TREAT Asia HIV Observational Database

    Science.gov (United States)

    Boettiger, David Charles; Kerr, Stephen; Ditangco, Rossana; Merati, Tuti Parwati; Pham, Thuy Thi Thanh; Chaiwarith, Romanee; Kiertiburanakul, Sasisopin; Li, Chung Ki Patrick; Kumarasamy, Nagalingeswaran; Vonthanak, Saphonn; Lee, Christopher; Van Kinh, Nguyen; Pujari, Sanjay; Wong, Wing Wai; Kamarulzaman, Adeeba; Zhang, Fujie; Yunihastuti, Evy; Choi, Jun Yong; Oka, Shinichi; Ng, Oon Tek; Kantipong, Pacharee; Mustafa, Mahiran; Ratanasuwan, Winai; Sohn, Annette; Law, Matthew

    2014-01-01

    Background Antiretroviral therapy (ART) has evolved rapidly since its beginnings. This analysis describes trends in first-line ART use in Asia and their impact on treatment outcomes. Methods Patients in the TREAT Asia HIV Observational Database receiving first-line ART for ≥6 months were included. Predictors of treatment failure and treatment modification were assessed. Results Data from 4662 eligible patients was analysed. Patients started ART in 2003–2006 (n = 1419), 2007–2010 (n = 2690) and 2011–2013 (n = 553). During the observation period, tenofovir, zidovudine and abacavir use largely replaced stavudine. Stavudine was prescribed to 5.8% of ART starters in 2012/13. Efavirenz use increased at the expense of nevirapine, although both continue to be used extensively (47.5% and 34.5% of patients in 2012/13, respectively). Protease inhibitor use dropped after 2004. The rate of treatment failure or modification declined over time (22.1 [95%CI 20.7–23.5] events per 100 patient/years in 2003–2006, 15.8 [14.9–16.8] in 2007–2010, and 11.6 [9.4–14.2] in 2011–2013). Adjustment for ART regimen had little impact on the temporal decline in treatment failure rates but substantially attenuated the temporal decline in rates of modification due to adverse event. In the final multivariate model, treatment modification due to adverse event was significantly predicted by earlier period of ART initiation (hazard ratio 0.52 [95%CI 0.33–0.81], p = 0.004 for 2011–2013 versus 2003–2006), older age (1.56 [1.19–2.04], p = 0.001 for ≥50 years versus ART regimen (11.36 [6.28–20.54], pART use in Asia reflect changes in drug availability, global treatment recommendations and prescriber preferences over the past decade. These changes have contributed to a declining rate of treatment modification due to adverse event, but not to reductions in treatment failure. PMID:25184314

  12. The influence of patient beliefs and treatment satisfaction on the discontinuation of current first-line antiretroviral regimens.

    Science.gov (United States)

    Casado, J L; Marín, A; Romero, V; Bañón, S; Moreno, A; Perez-Elías, M J; Moreno, S; Rodriguez-Sagrado, M A

    2016-01-01

    Large cohort studies have shown a high rate of first-line combination antiretroviral therapy (cART) regimen discontinuation in HIV-infected patients, attributed to characteristics of the cART regimen or toxicity. A cohort study of 274 patients receiving a first-line regimen was carried out. Patients' perceptions and beliefs prior to initiation were assessed using an attitude towards medication scale (0-15 points), and their satisfaction during therapy was assessed using an HIV treatment satisfaction questionnaire (HIVTSQ). Treatment discontinuation was defined as any switch in the cART regimen. During 474.8 person-years of follow-up, 63 (23%) patients changed their cART regimen, mainly because of toxicity/intolerance (42; 67%). The overall rate of change was 13.2 per 100 patient-years [95% confidence interval (CI) 11.1-16.4 per 100 patient-years]. An efavirenz (EFV)-based single tablet regimen showed the highest rate of adverse events (27%), but the lowest rate of change (16%; 7.44 per 100 patient-years). Cox regression revealed a decreased hazard of first regimen termination with better initial attitude towards drugs [hazard ratio (HR) 0.76; 95% CI 0.62-0.93; P satisfaction (HR 0.94; 95% CI 0.89-0.99; P = 0.01), and an increased hazard of termination with the presence of adverse events (HR 7.7; 95% CI 2.4-11.6; P patients (18 of 59; 31%) with mild/moderate adverse events (which were mainly central nervous system symptoms) continued the regimen; these patients, compared with those discontinuing therapy, showed better perception of therapy (mean score 14.4 versus 12.1, respectively; P = 0.05) and greater satisfaction during therapy (mean score 50.6 versus 44.6, respectively; P = 0.04). Patients' beliefs and satisfaction with therapy influence the durability of the first antiretroviral regimen. These patient-related factors modulate the impact of mild adverse events, and could explain differences in the rate of discontinuation. © 2015 British HIV

  13. Pharmacokinetics of First-Line Antituberculosis Drugs Using WHO Revised Dosage in Children With Tuberculosis With and Without HIV Coinfection.

    Science.gov (United States)

    Kwara, Awewura; Enimil, Anthony; Gillani, Fizza S; Yang, Hongmei; Sarfo, Anima M; Dompreh, Albert; Ortsin, Antoinette; Osei-Tutu, Lawrence; Kwarteng Owusu, Sandra; Wiesner, Lubbe; Norman, Jennifer; Kurpewski, Jaclynn; Peloquin, Charles A; Ansong, Daniel; Antwi, Sampson

    2016-12-01

    Pharmacokinetic data on the first-line antituberculosis drugs using the World Health Organization (WHO) revised dosages for children are limited. We investigated the pharmacokinetics of these drugs in children who were mostly treated with revised dosages. Children with tuberculosis on first-line therapy for at least 4 weeks had blood samples collected at predose, 1, 2, 4, and 8 hours postdose. Drug concentrations were determined by validated liquid chromatography mass spectrometry methods, and pharmacokinetic parameters were calculated using noncompartmental analysis. Factors associated with plasma peak concentration (C max ) and the area under the time-concentration curve 0-8 hours (AUC 0-8h ) of each drug was examined using univariate and multivariate analysis. Of the 62 children, 32 (51.6%) were male, 29 (46.8%) were younger than 5 years old, and 28 (45.2%) had human immunodeficiency virus (HIV) coinfection. Three patients had undetectable pyrazinamide and ethambutol concentrations. The median (interquartile range) AUC 0-8h for isoniazid was 17.7 (10.2-23.4) µg·h mL -1 , rifampin was 26.0 (15.3-36.1) µg·h mL -1 , pyrazinamide was 144.6 (111.5-201.2) µg·h mL -1 , and ethambutol was 6.7 (3.8-10.4) µg·h mL -1 . Of the children who received recommended weight-band dosages, 44/51 (86.3%), 46/56 (82.1%), 27/56 (48.2%), and 21/51 (41.2%) achieved target C max for isoniazid, pyrazinamide, ethambutol, and rifampin, respectively. In multivariate analysis, age, sex, HIV coinfection status, and drug dosage in milligrams per kilogram were associated with the drugs' plasma drug C max or AUC 0-8h . The revised dosages appeared to be adequate for isoniazid and pyrazinamide, but not for rifampin or ethambutol in this population. Higher dosages of rifampin and ethambutol than currently recommended may be required in most children. © The Author 2015. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For

  14. Radiotherapy in the cerebral metastatic malignant melanoma

    International Nuclear Information System (INIS)

    Novaes, P.E.R.S.; Albuquerque, L.F.; Salvajoli, J.V.; Peres, O.; Bandeira, D.C.; Calvis, L.A.; Santos, I.D.A.O.; Belfort, F.A.

    1985-01-01

    A retrospective analysis of 21 patients with cerebral metastasis from malignant melanoma was done. Two groups of patients were defined: patients receiving cranial radiation therapy with total dose higher than 20 Gy with or without other Kinds of therapy and patients not irradiated. (M.A.C.) [pt

  15. Phase I/II Trial of Sorafenib in Combination with Vinorelbine as First-Line Chemotherapy for Metastatic Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Cristiano Ferrario

    Full Text Available Preclinical models have reported a synergistic interaction between sorafenib and vinorelbine. We investigated the toxicity, efficacy, and pharmacokinetics interaction of this combination as first-line treatment for patients with metastatic breast cancer.Patients were HER2-negative and treated with vinorelbine 30 mg/m2 IV days 1,8 every 21 plus daily oral sorafenib. In the phase I portion (3+3 design patients received sorafenib 200 mg BID (cohort 1 or 400 mg BID (cohort 2. In the phase II expansion, 21 more evaluable patients were planned to receive the maximum tolerated dose (MTD. Pharmacokinetic analysis was performed in 6 patients: blood concentrations were compared for each drug in the presence or absence of the other drug.In cohort 1, one patient experienced a dose-limiting toxicity (DLT (grade 3 pancreatitis, requiring the expansion of this cohort to 6 patients, without further documented DLTs. In cohort 2, one patient of six experienced a grade 4 DLT (asymptomatic rise in amylase not requiring drug discontinuation, establishing this dose level as the MTD (sorafenib 400 mg BID. After expansion at the MTD, a total of 27 patients (median age 57 were treated for a median of 8 cycles. One grade 5 febrile neutropenia occurred. With repeated cycles, 52% of patients required at least 1 dose reduction of either drug. One patient experienced a sustained grade 3 fatigue resulting in treatment discontinuation. The response rate was 30%. Median PFS was 5.7 months (95% CI 4.4-7.6, and clinical benefit (absence of disease progression at 6 months was 48%. PK analysis showed a significant interaction between the two drugs, resulting in a higher Cmax of vinorelbine in the presence of sorafenib.The combination of sorafenib and vinorelbine at full doses is feasible but not devoid of toxicity, likely also due to a significant PK interaction.ClinicalTrials.gov NCT00764972.

  16. Staging of cutaneous melanoma

    NARCIS (Netherlands)

    P. Mohr (P.); A.M.M. Eggermont (Alexander); A. Hauschild (Axel); A. Buzaid (A.)

    2009-01-01

    textabstractThe American Joint Committee on Cancer (AJCC) staging of cutaneous melanoma is a continuously evolving system. The identification of increasingly more accurate prognostic factors has led to major changes in melanoma staging over the years, and the current system described in this review

  17. Canine oral melanoma.

    Science.gov (United States)

    Bergman, Philip J

    2007-05-01

    Melanoma is the most common oral malignancy in the dog. Oral and/or mucosal melanoma has been routinely considered an extremely malignant tumor with a high degree of local invasiveness and high metastatic propensity. Primary tumor size has been found to be extremely prognostic. The World Health Organization staging scheme for dogs with oral melanoma is based on size, with stage I = or = 4cm tumor and/or lymph node metastasis, and stage IV = distant metastasis. Median survival times for dogs with oral melanoma treated with surgery are approximately 17 to 18, 5 to 6, and 3 months with stage I, II, and III disease, respectively. Significant negative prognostic factors include stage, size, evidence of metastasis, and a variety of histologic criteria. Standardized treatments such as surgery, coarse-fractionation radiation therapy, and chemotherapy have afforded minimal to modest stage-dependent clinical benefits and death is usually due to systemic metastasis. Numerous immunotherapeutic strategies have been employed to date with limited clinical efficacy; however, the use of xenogeneic DNA vaccines may represent a leap forward in clinical efficacy. Oral melanoma is a spontaneous syngeneic cancer occurring in outbred, immunocompetent dogs and appears to be a more clinically faithful therapeutic model for human melanoma; further use of canine melanoma as a therapeutic model for human melanoma is strongly encouraged. In addition, the development of an expanded but clinically relevant staging system incorporating the aforementioned prognostic factors is also strongly encouraged.

  18. Uveal melanoma: estimating prognosis.

    Science.gov (United States)

    Kaliki, Swathi; Shields, Carol L; Shields, Jerry A

    2015-02-01

    Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms "uvea," "iris," "ciliary body," "choroid," "melanoma," "uveal melanoma" and "prognosis," "metastasis," "genetic testing," "gene expression profiling." Relevant English language articles were extracted, reviewed, and referenced appropriately.

  19. Uveal melanoma: Estimating prognosis

    Directory of Open Access Journals (Sweden)

    Swathi Kaliki

    2015-01-01

    Full Text Available Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms "uvea," "iris," "ciliary body," "choroid," "melanoma," "uveal melanoma" and "prognosis," "metastasis," "genetic testing," "gene expression profiling." Relevant English language articles were extracted, reviewed, and referenced appropriately.

  20. Bronchial malignant melanoma.

    Science.gov (United States)

    Weshler, Z; Sulkes, A; Kopolovitch, J; Leviatan, A; Shifrin, E

    1980-01-01

    We describe a case of malignant melanoma presenting initially as an endobronchial lesion located in the left main bronchus causing total atelectasis. This resolved with radiation therapy. Widespread metastases developed shortly thereafter. The differential diagnosis of primary and metastatic bronchial malignant melanoma is discussed. Other isolated case reports are reviewed.

  1. Melanoma do aparelho ungueal Nail apparatus melanoma

    Directory of Open Access Journals (Sweden)

    Ignez Regina dos Santos Muri Mendonça

    2004-10-01

    Full Text Available O melanoma do aparelho ungueal é apresentação relativamente rara dessa neoplasia, muitas vezes diagnosticada como nevo juncional, hematoma subungueal ou mesmo onicomicose. Esse fato leva a um atraso no diagnóstico e, conseqüentemente, na instituição da terapêutica específica, contribuindo para agravar o prognóstico de uma doença que por si só já é muito agressiva. Os autores relatam um caso de melanoma no primeiro quirodáctilo esquerdo de uma paciente negra com evolução de um ano, ressaltando a importância de avaliar certos critérios clínicos para obter o diagnóstico em fases mais precoces da doença.Nail apparatus melanoma is a rare presentation of melanoma and may be misdiagnosed as junctional nevus, subungual hematoma or onychomycosis. This fact often leads initially to inappropriate treatment and significant delays in appropriately managing such an aggressive disease. The authors report a case of melanoma on the left thumb of a black patient evolving for a year. Emphasis was placed on the importance of assessing certain clinical characteristics in order to reach an early diagnosis.

  2. Analysis of the cost-effectiveness of using vonoprazan-amoxicillin-clarithromycin triple therapy for first-line Helicobacter pylori eradication.

    Science.gov (United States)

    Kajihara, Yusaku; Shimoyama, Tadashi; Mizuki, Ichiro

    2017-02-01

    Vonoprazan (VPZ)-based triple therapy has been reported to have greater efficacy than a proton pump inhibitor (PPI)-based triple therapy for Helicobacter pylori (H. pylori) eradication. However, because VPZ is more expensive than PPIs such as rabeprazole (RPZ), economic evaluation is essential. We performed a retrospective study on 209 patients who underwent first-line eradication of H. pylori infection in Fuyoukai Murakami Hospital from 1 March 2015 to 31 March 2016. Patients who received VPZ, amoxicillin (AMPC) and clarithromycin (CAM) were assigned to the VPZ/AC group (n = 111) and patients who received RPZ, AMPC and CAM to the RPZ/AC group (n = 98). We compared the patients' backgrounds, including age, gender, use of high-dose CAM, past history of peptic ulcer, smoking and drug-related adverse events between the two groups. We defined cost as direct medical costs per patient and effectiveness as the first-line eradication rate in the intention-to-treat (ITT) analysis and analyzed the cost-effectiveness using the cost-effectiveness ratio (CER) and incremental cost-effectiveness ratio (ICER). There was no significant difference in the patients' backgrounds. The ITT analysis revealed an eradication rate of 94.6% for VPZ/AC and 86.7% for RPZ/AC. VPZ/AC cost 1155.4 Japanese yen (JPY) higher than RPZ/AC (34063.4 vs. 32908.0, JPY). CER of VPZ/AC was less than that of RPZ/AC (360.1 vs. 379.4, JPY per percent) and ICER of VPZ/AC was 147.0 JPY (1.28 Euro (EUR), 1 EUR =115 JPY) per percent. VPZ/AC was more cost-effective than RPZ/AC as first-line therapy for H. pylori eradication.

  3. Design of a randomized trial to evaluate the influence of mobile phone reminders on adherence to first line antiretroviral treatment in South India--the HIVIND study protocol.

    Science.gov (United States)

    De Costa, Ayesha; Shet, Anita; Kumarasamy, Nagalingeswaran; Ashorn, Per; Eriksson, Bo; Bogg, Lennart; Diwan, Vinod K

    2010-03-26

    Poor adherence to antiretroviral treatment has been a public health challenge associated with the treatment of HIV. Although different adherence-supporting interventions have been reported, their long term feasibility in low income settings remains uncertain. Thus, there is a need to explore sustainable contextual adherence aids in such settings, and to test these using rigorous scientific designs. The current ubiquity of mobile phones in many resource-constrained settings, make it a contextually appropriate and relatively low cost means of supporting adherence. In India, mobile phones have wide usage and acceptability and are potentially feasible tools for enhancing adherence to medications. This paper presents the study protocol for a trial, to evaluate the influence of mobile phone reminders on adherence to first-line antiretroviral treatment in South India. 600 treatment naïve patients eligible for first-line treatment as per the national antiretroviral treatment guidelines will be recruited into the trial at two clinics in South India. Patients will be randomized into control and intervention arms. The control arm will receive the standard of care; the intervention arm will receive the standard of care plus mobile phone reminders. Each reminder will take the form of an automated call and a picture message. Reminders will be delivered once a week, at a time chosen by the patient. Patients will be followed up for 24 months or till the primary outcome i.e. virological failure, is reached, whichever is earlier. Self-reported adherence is a secondary outcome. Analysis is by intention-to-treat. A cost-effectiveness study of the intervention will also be carried out. Stepping up telecommunications technology in resource-limited healthcare settings is a priority of the World Health Organization. The trial will evaluate if the use of mobile phone reminders can influence adherence to first-line antiretrovirals in an Indian context.

  4. Design of a randomized trial to evaluate the influence of mobile phone reminders on adherence to first line antiretroviral treatment in South India - the HIVIND study protocol

    Directory of Open Access Journals (Sweden)

    Kumarasamy Nagalingeswaran

    2010-03-01

    Full Text Available Abstract Background Poor adherence to antiretroviral treatment has been a public health challenge associated with the treatment of HIV. Although different adherence-supporting interventions have been reported, their long term feasibility in low income settings remains uncertain. Thus, there is a need to explore sustainable contextual adherence aids in such settings, and to test these using rigorous scientific designs. The current ubiquity of mobile phones in many resource-constrained settings, make it a contextually appropriate and relatively low cost means of supporting adherence. In India, mobile phones have wide usage and acceptability and are potentially feasible tools for enhancing adherence to medications. This paper presents the study protocol for a trial, to evaluate the influence of mobile phone reminders on adherence to first-line antiretroviral treatment in South India. Methods/Design 600 treatment naïve patients eligible for first-line treatment as per the national antiretroviral treatment guidelines will be recruited into the trial at two clinics in South India. Patients will be randomized into control and intervention arms. The control arm will receive the standard of care; the intervention arm will receive the standard of care plus mobile phone reminders. Each reminder will take the form of an automated call and a picture message. Reminders will be delivered once a week, at a time chosen by the patient. Patients will be followed up for 24 months or till the primary outcome i.e. virological failure, is reached, whichever is earlier. Self-reported adherence is a secondary outcome. Analysis is by intention-to-treat. A cost-effectiveness study of the intervention will also be carried out. Discussion Stepping up telecommunications technology in resource-limited healthcare settings is a priority of the World Health Organization. The trial will evaluate if the use of mobile phone reminders can influence adherence to first-line

  5. Role of radiotherapy in melanoma management

    International Nuclear Information System (INIS)

    Strojan, Primoz

    2010-01-01

    In melanoma, radiotherapy has generally been considered as a palliative treatment option indicated only for advanced cases or disseminated disease. In the 70s of the previous century, the technological advances in radiotherapy, linked to rapid development of computer sciences, resulted in restored interest for radiotherapy in melanoma management. Although a fundamental lack of well designed prospective and/or randomized clinical trials critically influenced the integration of radiotherapy into treatment strategies in melanoma, radiotherapy was recently recognized as an indispensable part in the multidisciplinary management of patients with melanoma. Altogether, approximately 23% of melanoma patients should receive at least one course of radiotherapy during the course of the disease. In this review, radiobiological properties of melanoma that govern the decisions for the fractionation patterns used in the treatment of this disease are described. Moreover, the indications for irradiation and the results of pertinent clinical studies from the literature, creating a rationale for the use of radiotherapy in the management of this disease, are reviewed and a brief description of radiotherapy techniques is given. Basic treatment modality in melanoma is surgery. However, whenever surgery is not radical or there are adverse prognostic factors identified on histopathological examination of resected tissue specimen, it needs to be supplemented. Also, in patients with unresectable disease or in those not being suitable for major surgery or who refuse proposed surgical intervention, other effective mode(s) of therapy need to be implemented. From this perspective, supported by clinical experiences and literature results, radiotherapy is a valuable option: it is effective and safe, in curative and palliative setting

  6. Melanoma during pregnancy

    DEFF Research Database (Denmark)

    de Haan, Jorine; Lok, Christianne A; de Groot, Christianne J M

    2017-01-01

    The management of melanoma during pregnancy is challenging as maternal benefits and fetal risks need to be balanced. Here, we present an overview of the incidence, the demographic and clinical characteristics and the treatment modalities used. After analysis of obstetric, fetal and maternal outcome......, recommendations for clinical practice are provided. From the 'International Network on Cancer, Infertility and Pregnancy' database, pregnant patients with melanoma were identified and analysed. Sixty pregnancies were eligible for analysis. Fifty percent of the patients presented with advanced melanoma during...... pregnancy (14 stage III and 16 stage IV), and 27% were diagnosed with recurrent melanoma. Surgery was the main therapeutic strategy during pregnancy. Only four patients with advanced melanoma were treated during pregnancy with systemic therapy (n=1) or radiotherapy (n=3). Premature delivery was observed...

  7. Economic evaluation of first-line adjuvant chemotherapies for resectable gastric cancer patients in China.

    Science.gov (United States)

    Tan, Chongqing; Peng, Liubao; Zeng, Xiaohui; Li, Jianhe; Wan, Xiaomin; Chen, Gannong; Yi, Lidan; Luo, Xia; Zhao, Ziying

    2013-01-01

    First-line postoperative adjuvant chemotherapies with S-1 and capecitabine and oxaliplatin (XELOX) were first recommended for resectable gastric cancer patients in the 2010 and 2011 Chinese NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer; however, their economic impact in China is unknown. The aim of this study was to compare the cost-effectiveness of adjuvant chemotherapy with XELOX, with S-1 and no treatment after a gastrectomy with extended (D2) lymph-node dissection among patients with stage II-IIIB gastric cancer. A Markov model, based on data from two clinical phase III trials, was developed to analyse the cost-effectiveness of patients in the XELOX group, S-1 group and surgery only (SO) group. The costs were estimated from the perspective of Chinese healthcare system. The utilities were assumed on the basis of previously published reports. Costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER) were calculated with a lifetime horizon. One-way and probabilistic sensitivity analyses were performed. For the base case, XELOX had the lowest total cost ($44,568) and cost-effectiveness ratio ($7,360/QALY). The relative scenario analyses showed that SO was dominated by XELOX and the ICERs of S-1 was $58,843/QALY compared with XELOX. The one-way sensitivity analysis showed that the most influential parameter was the utility of disease-free survival. The probabilistic sensitivity analysis predicted a 75.8% likelihood that the ICER for XELOX would be less than $13,527 compared with S-1. When ICER was more than $38,000, the likelihood of cost-effectiveness achieved by S-1 group was greater than 50%. Our results suggest that for patients in China with resectable disease, first-line adjuvant chemotherapy with XELOX after a D2 gastrectomy is a best option comparing with S-1 and SO in view of our current study. In addition, S-1 might be a better choice, especially with a higher value of willingness-to-pay threshold.

  8. Cutaneous manifestations associated with melanoma.

    Science.gov (United States)

    Vyas, Ritva; Selph, Jacqueline; Gerstenblith, Meg R

    2016-06-01

    Melanoma is a malignancy most commonly arising from the skin; therefore, primary melanoma characteristics are usually the first cutaneous manifestations of melanoma. Cutaneous metastases, which can occur locally or diffusely, are important to detect in a timely manner as treatments for advanced melanoma that impact survival are now available. Melanoma can be associated with local or diffuse pigmentation changes, including depigmentation associated with the leukodermas and hyperpigmentation associated with diffuse melanosis cutis. The leukodermas occur frequently, illustrate the immunogenic nature of melanoma, and may impact prognosis. Paraneoplastic syndromes in association with melanoma are rare, though can occur. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Leadership and management skills of first-line managers of elderly care and their work environment.

    Science.gov (United States)

    Abdelrazek, Fathya; Skytt, Bernice; Aly, Magda; El-Sabour, Mona Abd; Ibrahim, Naglaa; Engström, Maria

    2010-09-01

    To study the leadership and management skills of first-line managers (FLMs) of elderly care and their work environment in Egypt and Sweden. FLMs in Egypt and Sweden are directly responsible for staff and quality of care. However, FLMs in Sweden, in elderly care, have smaller units/organizations to manage than do their colleagues in Egypt. Furthermore, family care of the elderly has been the norm in Egypt, but in recent years institutional care has increased, whereas in Sweden, residential living homes have existed for a longer period. A convenience sample of FLMs, 49 from Egypt and 49 from Sweden, answered a questionnaire measuring leadership and management skills, structural and psychological empowerment, job satisfaction and psychosomatic health. In both countries, FLMs' perceptions of their leadership and management skills and psychological empowerment were quite high, whereas scores for job satisfaction and psychosomatic health were lower. FLMs had higher values in several factors/study variables in Egypt compared with in Sweden. The work environment, both in Egypt and Sweden, needs to be improved to increase FLMs' job satisfaction and decrease stress. The cultural differences and levels of management have an effect on the differences between the two countries. © 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.

  10. PROGNOSTIC FACTORS FOR SURVIVAL IN PATIENTS WITH METASTATIC COLORECTAL CANCER TREATED WITH FIRST - LINE CHEMOTHERAPY

    Directory of Open Access Journals (Sweden)

    Deyan Davidov

    2017-05-01

    Full Text Available Objective: The aim of this study was to investigate the prognostic significance for survival of certain clinical and pathological factors in patients with advanced or metastatic colorectal carcinoma (CRC treated with first- line chemotherapy. Methods: From 2002 to 2011 seventy- four consecutive patients with advanced or metastatic CRC, treated in UMHAT- Dr. G. Stranski, Department of Medical Oncology entered the study. Some patient’s characteristics, hematological and pathological parameters, were evaluated for their role as predictors of overall survival. The therapeutic regimens included FOLFOX or FOlFIRI. Survival analysis was evaluated by Kaplan- Meier test. The influence of pretreatment characteristics as prognostic factor for survival was analyzed using multivariate stepwise Cox regression analyses. Results: In multivariate analysis a significant correlation was exhibited between survival, poor performance status and multiple sites of metastasis. Variables significantly associated with overall survival in univariate analysis were performance status>1, thrombocytosis, anemia and number of metastatic sites >1. Conclusion: These results indicated that poor performance status, anemia, thrombocytosis as well as multiple site of metastasis could be useful prognostic factors in patients with metastatic CRC.

  11. Respiratory tract lining fluid antioxidants: the first line of defence against gaseous pollutants.

    Science.gov (United States)

    Kelly, F J; Cotgrove, M; Mudway, I S

    1996-01-01

    All tissues are vulnerable to oxidant damage, but by virtue of its location, anatomy and function, the epithelial surface of the lung is one of the most vulnerable targets in the body. Recent studies have shown that epithelial lining fluid (ELF), a thin layer of fluid which covers the epithelial surface of the respiratory tract, contains an interesting complement of antioxidants, some of which, like glutathione, are present in concentrations much higher than those found in plasma. It is likely that ELF forms the first line of defence against inhaled toxins such as ozone and nitrogen dioxide. By employing an ex vivo exposure system we have demonstrated that when lung lining fluid is in contact with environmentally relevant concentrations of ozone or nitrogen dioxide, there is differential consumption of the water-soluble antioxidants in the order, uric acid > ascorbic acid > glutathione. Given that the majority of ozone and nitrogen dioxide reacts within the ELF compartment, the antioxidant composition of this fluid is critically important in determining an individual's sensitivity to gaseous pollutants.

  12. Introduction of dermatome shaving as first line treatment of chronic tattoo reactions.

    Science.gov (United States)

    Sepehri, Mitra; Jørgensen, Bo; Serup, Jørgen

    2015-10-01

    Chronic tattoo reactions requiring treatment have increased. Laser removal is not ideal for removal of allergic reactions. Surgical removal of culprit pigment situated in the outer dermis by dermatome shaving is rational and need to be revisited. Fifty four tattoos with chronic reactions in 50 patients were treated with dermatome shaving. Tattoos with red/red nuances dominated the material. In total, 52 operations were performed in infiltration and 2 in general anaesthesia. Shaving was performed to the level in the dermis free of tattoo pigment as assessed visually by the surgeon. Operative complications were few. Healing occurred over weeks as normal for this procedure. On a rating scale from 0 to 4, 4 as most severe, the patient's severity rating of symptoms in their tattoo declined from 3.2 pre-operatively to 1.0, 0.8 and 0.7 after 3, 6 and 12 months, respectively. Burden of operation was rated low. Patient satisfaction was high. Dermatome shaving is efficient and with few complications, and is proposed as first line treatment of chronic tattoo reactions. Shaving of such reactions apparently has been neglected during enthusiastic introduction of laser approaches, which in the treatment of allergic tattoo reactions may be relatively contra indicated and of special risk.

  13. Electrochemotherapy as First Line Cancer Treatment: Experiences from Veterinary Medicine in Developing Novel Protocols.

    Science.gov (United States)

    Spugnini, E P; Azzarito, T; Fais, S; Fanciulli, M; Baldi, A

    2016-01-01

    Tumor microenvironment is one of the major obstacles to the efficacy of chemotherapy in cancer patients. The abnormal blood flow within the tumor results in uneven drug distribution. Electrochemotherapy (ECT) is a tumor treatment that adopts the systemic or local delivery of anticancer drugs with the application of permeabilizing electric pulses having appropriate amplitude and waveforms. This allows the use of lipophobic drugs that frequently have a narrow therapeutic index maintaining at the same time a reduced patient morbidity and preserving appropriate anticancer efficacy. Its use in humans is addressed to the treatment of cutaneous neoplasms or the palliation of skin tumor metastases, and a standard operating procedure has been devised. On the other hand, in veterinary oncology this approach is gaining popularity, thus becoming a first line treatment for different cancer histotypes, in a variety of clinical conditions due to its high efficacy and low toxicity. This review summarizes the state of the art in veterinary oncology as a preclinical model and reports the new protocols in terms of drugs and therapy combination that have been developed.

  14. The efficacy of levofloxacin-based triple therapy for first-line Helicobacter pylori eradication

    Directory of Open Access Journals (Sweden)

    Yusuf Aydın

    2011-06-01

    Full Text Available Standard triple therapy composed of a proton pump inhibitor, clarithromycin and amoxicillin has been widely preferred for H. pylori eradication in Turkey and World. Alternative therapies are currently under investigation because of an increase in clarithromycin resistance. The aim of this study was to evaluate the efficacy of a levoflox-acin-containing triple therapy.Materials and methods: The study was carried out in 81 H. pylori-infected patients (52 female, 29 male with nonul-cer dyspepsia. The mean age was found 46.3 ± 13.9. Treatment was indicated with lansoprazol 30 mg b.d., amoxicil-lin 1 g b.d., and levofloxacin 500 mg daily for 7 days. H. pylori status was rechecked by (14C urea breath test 6-8 weeks after the end of therapy.Results: Totally 81 patients could complete the treatment and follow-up protocol. Effectiveness was 68%. The distrib-tions of age, gender and smoking were similar between eradicated and non-eradicated groups (p > 0.05.Conclusion: Seven-day levofloxacin based triple therapy is not very effective in the first-line treatment of H. pylori in-fection. The new treatment modalities should be investigated.

  15. New developments in cognitive behavioral therapy as the first-line treatment of insomnia

    Directory of Open Access Journals (Sweden)

    Allison T Siebern

    2011-02-01

    Full Text Available Allison T Siebern, Rachel ManberSleep Medicine Center, Stanford University School of Medicine, Redwood City, California, USAAbstract: Insomnia is the most common sleep disorder. Psychological, behavioral, and biological factors are implicated in the development and maintenance of insomnia as a disorder, although the etiology of insomnia remains under investigation, as it is still not fully understood. Cognitive behavioral therapy for insomnia (CBTI is a treatment for insomnia that is grounded in the science of behavior change, psychological theories, and the science of sleep. There is strong empirical evidence that CBTI is effective. Recognition of CBTI as the first-line treatment for chronic insomnia (National Institutes of Health consensus, British Medical Association was based largely on evidence of its efficacy in primary insomnia. The aim of this article is to provide background information and review recent developments in CBTI, focusing on three domains: promising data on the use of CBTI when insomnia is experienced in the presence of comorbid conditions, new data on the use of CBTI as maintenance therapy, and emerging data on the delivery of CBTI through the use of technology and in primary care settings.Keywords: insomnia, CBTI, nonpharmacological treatment

  16. First-Line Helicobacter pylori Eradication with Vonoprazan, Clarithromycin, and Metronidazole in Patients Allergic to Penicillin

    Directory of Open Access Journals (Sweden)

    Soichiro Sue

    2017-01-01

    Full Text Available Aim. To assess the efficacy of 7-day first-line Helicobacter pylori eradication with vonoprazan (VPZ, clarithromycin (CAM, and metronidazole (MNZ in patients with penicillin allergy. Methods. Patients with penicillin allergy, diagnosed with Helicobacter pylori infection and did not have history of Helicobacter pylori eradication, were eligible for the study. Twenty patients were prospectively treated with 20 mg VPZ twice daily, 200 or 400 mg CAM twice daily, and 250 mg MNZ twice daily for 7 days. We also collected the data from 30 patients retrospectively treated with proton pump inhibitor (PPI, CAM, and MNZ. Safety was evaluated in patients completing an adverse effect questionnaire. Results. Both the intention-to-treat and per-protocol effectiveness of VPZ-based eradication were 100% (95% CI: 86.1–100%; n=20. The eradication rates of PPI-based regimen were 83.3% (95% CI: 65.3–94.4% in the ITT and 82.7% (95% CI: 64.2–94.2% in the PP analyses. Abdominal fullness was more frequent in VCM compared to PCM. However, all patients with VCM regimen had taken 100% of their course of medication. Conclusion. Triple therapy with VPZ, CAM, and MNZ is well tolerated and effective for eradicating Helicobacter pylori in patients allergic to penicillin. This study was registered in the UMIN Clinical Trials Registry as UMIN000016335.

  17. Pyruvate Accumulation Is the First Line of Cell Defense against Heat Stress in a Fungus.

    Science.gov (United States)

    Zhang, Xing; St Leger, Raymond J; Fang, Weiguo

    2017-09-05

    Heat tolerance is well known to be key to fungal survival in many habitats, but our mechanistic understanding of how organisms adapt to heat stress is still incomplete. Using Metarhizium robertsii , an emerging model organism for assessing evolutionary processes, we report that pyruvate is in the vanguard of molecules that scavenge heat-induced reactive oxygen species (ROS). We show that, as well as inducing a rapid burst of ROS production, heat stress also downregulates genes for pyruvate consumption. The accumulating pyruvate is the fastest acting of several M. robertsii ROS scavengers, efficiently reducing protein carbonylation, stabilizing mitochondrial membrane potential, and promoting fungal growth. The acetate produced from pyruvate-ROS reactions itself causes acid stress, tolerance to which is regulated by Hog1 mitogen-activated protein kinase. Heat stress also induces pyruvate accumulation in several other fungi, suggesting that scavenging of heat-induced ROS by pyruvate is widespread. IMPORTANCE Heat is a dangerous challenge for most organisms, as it denatures proteins and induces the production of ROS that inactivate proteins, lipid membranes, and DNA. How organisms respond to this stress is not fully understood. Using the experimentally tractable insect pathogen Metarhizium robertsii as a model organism, we show for the first time that heat stress induces pyruvate production and that this functions as the first line of defense against heat-induced ROS. Heat stress also induces rapid pyruvate accumulation in other fungi, suggesting that pyruvate is a common but unappreciated defense against stress. Copyright © 2017 Zhang et al.

  18. Colorectal stenting as first-line treatment in acute colonic obstruction.

    Science.gov (United States)

    García-Cano, Jesús

    2013-10-16

    Tumoral obstructions in almost the entire gastrointestinal tract can be resolved with interventional digestive endoscopy techniques. Self-expanding metal stent (SEMS) insertion in the obstructed colon is a minimally invasive and relatively simple procedure providing an effective first-line treatment for relief of acute malignant obstruction symptoms and serving either as a preoperative or "bridge to surgery" procedure or as palliative definitive care. This technique was introduced in the early 1990s. Although there is still debate about its real value, a lot of reports have been published since then and the procedure is advocated by many surgical groups as the method of choice for the initial treatment of left-sided tumoral colonic obstruction. Before the procedure, colonic obstruction has to be diagnosed by abdominal radiographs, water contrast enema and/or a computed tomography scan. The greatest information is provided by the latter and it is perhaps the method of choice prior to stenting. Skills and training are mandatory, as in all interventional procedures. The key step for success is to cross the malignant stricture with a guidewire. Care must be taken not to over insufflate an obstructed colon during the procedure. SEMS slide over the guidewire through the endoscope working channel or in parallel, outside the endoscope. An average 7% perforation rate has been reported during the procedure and other minor complications can appear in the follow up. However, as a whole, this technique seems to compare favorably with surgery.

  19. Clozapine-induced tardive dyskinesia in schizophrenic patients taking clozapine as a first-line antipsychotic drug.

    Science.gov (United States)

    Li, Chun-Rong; Chung, Young-Chul; Park, Tae-Won; Yang, Jong-Chul; Kim, Kee-Won; Lee, Keon-Hak; Hwang, Ik-Keun

    2009-01-01

    Clozapine causes few extrapyramidal symptoms and is recommended as a treatment drug for severe tardive dyskinesia (TD). However, several case reports have suggested that clozapine could also cause TD. We investigated whether clozapine used as a first-line antipsychotic drug can cause TD. We identified 101 patients at Yanbian Socio-Mental Hospital and Yanbian Brain Hospital in China who had received clozapine as a primary antipsychotic drug since their first episode of illness and evaluated the prevalence rate, type, and severity of TD using the Extrapyramidal Symptoms Rating Scale (ESRS). The criterion for TD was a score of > or = 3 on one item or 2 on two or more items of the ESRS. The mean age and duration of illness of the patients were 38.93+/-8.36 and 12.88+/-6.90 years, respectively. The mean duration of clozapine treatment was 12.10+/-6.26 years. The prevalence of TD was 3.96% (4/101). Compared to patients without TD, patients with TD had a long duration of illness and clozapine treatment; all had the orolingual type of TD. TD was relatively mild, with a mean score of 4.75, and tended to accentuate with an activation procedure of rapid pronation and supination of the hands. These results suggest that clozapine may cause TD; however, the prevalence is low and the severity is relatively mild, with no or mild self-reported discomfort. Therefore, we recommend that regular examination for TD using the activation procedure should be performed in patients who use clozapine on a long-term basis.

  20. [Retrospective Study of Efficacy in BIM Gene Polymorphism on First-line EGFR-TKIs Treatment for Advanced Lung Adenocarcinoma].

    Science.gov (United States)

    Qian, Kun; Zhang, Yi; Zhi, Xiuyi

    2017-08-20

    The aim of this study is to detect the BIM polymorphism in 85 formalin-fixed and parrffin-embedded (FFPE) and some blood samples of advanced lung adenocarcinoma patients and study the relativity betweenthe BIM polymorphism and tyrosine kinase inhibitor (TKI). The correlation between BIM detection of different types of specimens was discussed. There were 85 patients who were diagnosed as advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) 19 or 21 exon mutation in thoracic surgery of Xuanwu Hospital from February 2013 to November 2014, all of who were received EGFR-TKI as first-line treatment in the study. FFPE and some blood were used to detect the BIM polymorphism. The objective response rate (ORR) and progression-free survival (PFS) of two groups were compared. According to smoking, sex, EGFR mutation and other factors, the single factor analysis was performed, and the correlation between paraffin samples and blood test BIM was compared. The ORR in BIM polymorphism and non-polymorphism groups was no significant differences (P>0.05). The median PFS in BIM polymorphism and non-polymorphism group was 7.1 months and 12.8 months, respectively (P=0.013). Univariate analysis the median PFS, women were longer than men (12.1 months vs 10.7 months, P=0.835); Non-smokers were longer than smokers (12.1 months vs 9.7 months, P=0.974). Group in EGFR exon 21 is longer than group in EGFR exon 19 (12.2 months vs 8.7 months, P=0.303). Detection of BIM gene polymorphism in lung cancer patients with EGFR-TKIs treatment might be helpful for predicting prognosis. But a large sample study is needed.

  1. Treatment patterns in advanced melanoma: findings from a survey of European oncologists.

    Science.gov (United States)

    Jones, C; Zhao, Z; Barber, B; Bagijn, M; Corrie, P; Saltman, D

    2015-11-01

    With the emergence of new therapies, established patterns of treating advanced melanoma are changing. The aim of this study was to understand how advanced melanoma is treated in clinical practice in Europe following the introduction of ipilimumab and vemurafenib. An online survey was conducted between August and November 2012 with 150 oncologists and dermatologists, from France, Germany, Italy, Spain and the U.K.; respondents reported treating the majority of patients with one or two lines of therapy. For BRAF mutant melanoma, the most frequently used first-line treatments were vemurafenib and dacarbazine. For BRAF wild-type melanoma, the most frequently used first-line treatment was dacarbazine. There was no single preferred agent for the second-line treatment of BRAF mutant or BRAF wild-type disease. Most sequencing from first- to second-line was from conventional dacarbazine to newer agents such as ipilimumab and vemurafenib. The treatment of advanced melanoma is rapidly evolving due to the introduction of new agents. This study presents an early insight into access to the new agents, ipilimumab and vemurafenib, and clinical practice in several European countries. © 2015 John Wiley & Sons Ltd.

  2. Characterization of melanoma associated spongiform scleropathy

    DEFF Research Database (Denmark)

    Alyahya, Ghassan Ayish Jabur; Heegaard, Steffen; Prause, J.U.

    2002-01-01

    ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology......ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology...

  3. Management of Melanoma Families

    Directory of Open Access Journals (Sweden)

    Wilma Bergman

    2010-04-01

    Full Text Available In this review we have aimed to focus on the clinical management of familial melanoma patients and their relatives. Along this line three major topics will be discussed: (1 management/screening of familial melanoma families: what is advised and what is the evidence thereof; (2 variability of families worldwide with regard to clinical phenotype, including cancer spectrum and likelihood of finding germline mutations and (3 background information for clinicians on the molecular biology of familial melanoma and recent developments in this field.

  4. Economic Outcomes of First-Line Regimen Switching Among Stable Patients with HIV.

    Science.gov (United States)

    Rosenblatt, Lisa; Buikema, Ami R; Seare, Jerry; Bengtson, Lindsay G S; Johnson, Jonathan; Cao, Feng; Villasis-Keever, Angelina

    2017-07-01

    Although switching of antiretroviral therapy (ART) is a valid approach for addressing treatment failure in patients with human immunodeficiency virus (HIV), ART changes among those who are well maintained on their current regimens may lead to the development of new side effects or resistance. To examine the effect of first-line regimen switching on subsequent health care utilization and cost among stable HIV patients. This was a retrospective claims data study of adult patients with HIV who initiated ART between 2007 and 2013 and had been treated with their initial regimens for at least 6 continuous months. Those with evidence of pregnancy or HIV-2 were excluded. Patients who underwent an ART change were assigned to a switcher cohort; a nonswitcher cohort was then generated by matching up to 20 nonswitchers for each switcher, with replacement. The index date was the date of the first ART change for switchers and was the claim date closest to the corresponding switcher's switch date for nonswitchers. Patient characteristics at baseline and post-index annualized health care utilization and costs were analyzed descriptively and with multivariable models. Analyses were performed in the full population and among patients designated as virologically stable (had undetectable viral ribonucleic acid [RNA] for 90 days pre-index) and virologically and clinically stable (had undetectable viral RNA and no apparent clinical reason for switching ART). The study population consisted of 6,983 individuals, which included 927 switchers (168 virologically stable; 55 virologically+clinically stable), who were matched with replacement with 18,511 nonswitcher comparators. The switcher cohort was 88.8% male (mean age 43.8 years). Mean preindex and follow-up treatment durations for switchers and nonswitchers were 1.8 years and 1.5 years, respectively; demographic characteristics, pre-index treatment duration, and follow-up duration were similar between cohorts. Significantly more

  5. Melanocytes and melanin represent a first line of innate immunity against Candida albicans.

    Science.gov (United States)

    Tapia, Cecilia V; Falconer, Maryanne; Tempio, Fabián; Falcón, Felipe; López, Mercedes; Fuentes, Marisol; Alburquenque, Claudio; Amaro, José; Bucarey, Sergio A; Di Nardo, Anna

    2014-07-01

    Melanocytes are dendritic cells located in the skin and mucosae that synthesize melanin. Some infections induce hypo- or hyperpigmentation, which is associated with the activation of Toll-like receptors (TLRs), especially TLR4. Candida albicans is an opportunist pathogen that can switch between blastoconidia and hyphae forms; the latter is associated with invasion. Our objectives in this study were to ascertain whether C. albicans induces pigmentation in melanocytes and whether this process is dependent on TLR activation, as well as relating this with the antifungal activity of melanin as a first line of innate immunity against fungal infections. Normal human melanocytes were stimulated with C. albicans supernatants or with crude extracts of the blastoconidia or hyphae forms, and pigmentation and TLR2/TLR4 expression were measured. Expression of the melanosomal antigens Melan-A and gp100 was examined for any correlation with increased melanin levels or antifungal activity in melanocyte lysates. Melanosomal antigens were induced earlier than cell pigmentation, and hyphae induced stronger melanization than blastoconidia. Notably, when melanocytes were stimulated with crude extracts of C. albicans, the cell surface expression of TLR2/TLR4 began at 48 h post-stimulation and peaked at 72 h. At this time, blastoconidia induced both TLR2 and TLR4 expression, whereas hyphae only induced TLR4 expression. Taken together, these results suggest that melanocytes play a key role in innate immune responses against C. albicans infections by recognizing pathogenic forms of C. albicans via TLR4, resulting in increased melanin content and inhibition of infection. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. A cost-utility comparison of four first-line medications in painful diabetic neuropathy.

    Science.gov (United States)

    O'Connor, Alec B; Noyes, Katia; Holloway, Robert G

    2008-01-01

    Painful diabetic neuropathy is common and adversely affects patients' quality of life and function. Several treatment options exist, but their relative efficacy and value are unknown. To determine the relative efficacy, costs and cost effectiveness of the first-line treatment options for painful diabetic neuropathy. Published and unpublished clinical trial and cross-sectional data were incorporated into a decision analytic model to estimate the net health and cost consequences of treatment for painful diabetic peripheral neuropathy over 3-month (base case), 1-month and 6-month timeframes. Efficacy was measured in QALYs, and costs were measured in $US, year 2006 values, using a US third-party payer perspective. The patients included in the model were outpatients with moderate to severe pain associated with diabetic peripheral neuropathy and no contraindications to treatment with tricyclic antidepressants. Four medications were compared: desipramine 100 mg/day, gabapentin 2400 mg/day, pregabalin 300 mg/day and duloxetine 60 mg/day. Desipramine and duloxetine were both more effective and less expensive than gabapentin and pregabalin in the base-case analysis and through a wide range of sensitivity analyses. Duloxetine offered borderline value compared with desipramine in the base case ($US47,700 per QALY), but not when incorporating baseline-observation-carried-forward analyses of the clinical trial data ($US867,000 per QALY). The results were also sensitive to the probability of obtaining pain relief with duloxetine. Desipramine (100 mg/day) and duloxetine (60 mg/day) appear to be more cost effective than gabapentin or pregabalin for treating painful diabetic neuropathy. The estimated value of duloxetine relative to desipramine depends on the assumptions made in the statistical analyses of clinical trial data.

  7. Therapeutic compliance of first line disease-modifying therapies in patients with multiple sclerosis. COMPLIANCE Study.

    Science.gov (United States)

    Saiz, A; Mora, S; Blanco, J

    2015-05-01

    Non-adherence to disease-modifying therapies (DMTs) in multiple sclerosis may be associated with reduced efficacy. We assessed compliance, the reasons for non-compliance, treatment satisfaction, and quality of life (QoL) of patients treated with first-line therapies. A cross-sectional, multicenter study was conducted that included relapsing multiple sclerosis patients. Compliance in the past month was assessed using Morisky-Green test. Seasonal compliance and reasons for non-compliance were assessed by an ad-hoc questionnaire. Treatment satisfaction and QoL were evaluated by means of TSQM and PRIMUS questionnaires. A total of 220 patients were evaluated (91% relapsing-remitting); the mean age was 39.1 years, 70% were female, and the average time under treatment was 5.4 years. Subcutaneous interferon (IFN) β-1b was used in 23% of the patients, intramuscular IFN β-1a in 21%, subcutaneous IFN β-1a in 37%, and with glatiramer acetate in 19%. The overall compliance was 75%, with no significant differences related to the therapy, and 81% did not report any seasonal variation. Compliant patients had significantly lower disability scores and time of diagnosis, and greater satisfaction with treatment and its effectiveness. Discomfort and flu-like symptoms were the most frequent reasons for non-compliance. The satisfaction and QoL were associated with less disability and number of therapeutic switches. The rate of compliance, satisfaction and QoL in multiple sclerosis patients under DMTs is high, especially for those newly diagnosed, less disabled, and with fewer therapeutic switches. Discomfort and flu-like symptoms associated with injected therapies significantly affect adherence. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  8. A Randomized, Controlled, Multicenter Clinical Trial Comparing Pemetrexed/Cisplatin and Gemcitabine/Cisplatin as First-line Treatment for Advanced Nonsquamous Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yan HUANG

    2012-10-01

    Full Text Available Background and objective Platinum-based doublet chemotherapy is still the standard first-line treatment for non-small cell lung cancer (NSCLC. Previous studies have demonstrated that pemetrexed combined with platinum had promising efficacy and safety profile in NSCLC, especially in patients with nonsquamous NSCLC. This trial was conducted to evaluate the efficacy and safety of pemetrexed made in China as first-line treatment. Methods The present study was a randomized, controlled, multicenter clinical trial. Patients were randomly assigned (1:1 to receive cisplatin plus pemetrexed chemotherapy (PC group or gemcitabine plus cisplatin (GC group every 3 weeks. The primary end point was progression free survival (PFS and the secondary end points included 1 year survival rate, objective response rate (ORR, survival without grade 3/4 toxicity (SWT3/4 and safety profile. Results A total of 288 patients from 20 institutions across China were enrolled into the study. Based on the Full Analyses Set (FAS, the PFS was 168 days (5.6 months vs 140 days (4.7 months (P=0.16, one year survival rate was 50.0% vs 54.9% (P=0.47, ORR was 24.4% vs 14.2% (P=0.06 in the PC group and the GC group, respectively; Survival without grade 3/4 toxicity was 11.3 months in GC group vs 8.1 months in PC group (P=0.23. In terms of the safety, side effects were less observed on the PC group (81.95% vs 93.75%, P=0.003. The main side effects included leukopenia, neutropenia, emesis, anemia, thrombopenia. Conclusion The both regimens have similar efficacy as the treatment for advanced nonsquamous NSCLC, but pemetrexed plus cisplatin regimen has better safety profile and seems to have longer PFS, which makes it a new option as the first line setting.

  9. Adoption of new HIV treatment guidelines and drug substitutions within first-line as a measure of quality of care in rural Lesotho: health centers and hospitals compared.

    Science.gov (United States)

    Labhardt, Niklaus D; Sello, Motlalepula; Lejone, Thabo; Ehmer, Jochen; Mokhantso, Mohlaba; Lynen, Lutgarde; Pfeiffer, Karolin

    2012-10-01

    In 2007, Lesotho launched new national antiretroviral treatment (ART) guidelines, prioritising tenofovir and zidovudine over stavudine as a backbone together with lamivudine. We compared the rate of adoption of these new guidelines and substitution of first-line drugs by health centers (HC) and hospitals in two catchment areas in rural Lesotho. Retrospective cohort analysis. Patients aged ≥16 years were stratified into a HC- and a hospital-group. Type of backbone at ART-initiation (i), substitutions within first line (ii) and type of backbone among patients retained by December 2010 (iii). A multiple logistic regression model including HC vs. hospital, patient characteristics (sex, age, WHO-stage, baseline CD4-count, concurrent pregnancy, concurrent tuberculosis treatment) and year of ART-start, was used. Of 3936 adult patients initiated on ART between 2007 and 2010, 1971 started at hospitals and 1965 at HCs. Hospitals were more likely to follow the new guidelines as measured by prescription of backbones without stavudine (Odds-ratio 1.55; 95%CI: 1.32-1.81) and had a higher rate of drug substitutions while on first-line ART (2.39; 1.83-3.13). By December 2010, patients followed at health centres were more likely to still receive stavudine (2.28; 1.83-2.84). Health centers took longer to adopt the new guidelines and substituted drugs less frequently. Decentralised ART-programmes need close support, supervision and mentoring to absorb new guidelines and to adhere to them. © 2012 Blackwell Publishing Ltd.

  10. Intravital Microscopy for Identifying Tumor Vessels in Patients With Stage IA-IV Melanoma That is Being Removed by Surgery

    Science.gov (United States)

    2017-06-05

    Recurrent Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  11. [Correlation between Serum Tumor Markers and Efficacy of First-line EGFR-TKIs in Patients with Advanced Lung Adenocarcinoma].

    Science.gov (United States)

    Chen, Hanxiao; Yang, Xue; Liu, Huijun; Ma, Kun; Zhong, Jia; Dong, Zhi; Zhuo, Minglei; Wang, Yuyan; Li, Jianjie; An, Tongtong; Wu, Meina; Wang, Ziping; Zhao, Jun

    2017-09-20

    Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) significantly improve the survival of advanced lung adenocarcinoma patients harboring EGFR mutation. Limited to the standards of tumor tissue samples and detection methods, still some people can't receive target therapy following genetic guidance. This study was to explore the relevance between serum tumor markers and treatment of EGFR-TKIs. We retrospectively collected the clinical information of advanced lung adenocarcinoma patients harboring EGFR mutation, who received EGFR-TKIs as first-line therapy from June 2009 to June 2014 in Peking University Cancer Hospital, analyzed the relationship between serum tumor markers and efficacy of EGFR-TKIs. The objective response rate (ORR) was 52.8% and the disease control rate (DCR) was 89.3%. The results showed that, patients with high CEA level before treatment responded better to TKIs (ORR 61.3% vs 35.9%, DCR 95.2% vs 74.4%, PCEA decreased 1 month later (61.5% vs 25%, P=0.002). Progression-free survival (PFS) significantly prolonged in patients with elevated baseline CEA (mPFS 9.8 mo vs 5.9 mo, P=0.027). To the opposite, PFS was significantly shorter in patients with elevated baseline CYFRA21-1 and CA125 (mPFS 9.0 mo vs 11.4 mo, P=0.029; 9.0 mo vs 11.5 mo, P=0.023, respectively). Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) score of 0-1, normal baseline CYFRA21-1 and CEA decline predicted longer PFS. The overall survival (OS) was highly associated with elevated CYFRA21-1 and CA125 (median OS 25.1 mo vs 52.5 mo, P=0.003; 22.7 mo vs 55.0 mo, PCEA. High level of baseline CEA and decline 1 month after treatment could predict the efficacy of EGFR-TKIs in patients with advanced lung adenocarcinoma. While high levels of baseline CYFRA21-1 and CA125 indicated shortened survival.

  12. The Danish Melanoma Database

    DEFF Research Database (Denmark)

    Hölmich, Lisbet Rosenkrantz; Klausen, Siri; Spaun, Eva

    2016-01-01

    AIM OF DATABASE: The aim of the database is to monitor and improve the treatment and survival of melanoma patients. STUDY POPULATION: All Danish patients with cutaneous melanoma and in situ melanomas must be registered in the Danish Melanoma Database (DMD). In 2014, 2,525 patients with invasive......-node-metastasis stage. Information about the date of diagnosis, treatment, type of surgery, including safety margins, results of lymphoscintigraphy in patients for whom this was indicated (tumors > T1a), results of sentinel node biopsy, pathological evaluation hereof, and follow-up information, including recurrence......, nature, and treatment hereof is registered. In case of death, the cause and date are included. Currently, all data are entered manually; however, data catchment from the existing registries is planned to be included shortly. DESCRIPTIVE DATA: The DMD is an old research database, but new as a clinical...

  13. Proteomics in uveal melanoma.

    LENUS (Irish Health Repository)

    Ramasamy, Pathma

    2014-01-01

    Uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence of 5-7 per million per year. It is associated with the development of metastasis in about 50% of cases, and 40% of patients with uveal melanoma die of metastatic disease despite successful treatment of the primary tumour. The survival rates at 5, 10 and 15 years are 65%, 50% and 45% respectively. Unlike progress made in many other areas of cancer, uveal melanoma is still poorly understood and survival rates have remained similar over the past 25 years. Recently, advances made in molecular genetics have improved our understanding of this disease and stratification of patients into low risk and high risk for developing metastasis. However, only a limited number of studies have been performed using proteomic methods. This review will give an overview of various proteomic technologies currently employed in life sciences research, and discuss proteomic studies of uveal melanoma.

  14. Primary leptomeningeal melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Aichner, F.; Schuler, G.

    1982-11-01

    A case of primary leptomeningeal melanoma is presented in which the diagnosis was made by ultrastructural demonstration of melanoma cells from the cerebrospinal fluid (CSF) at a time when cranial computed tomography (CT) still gave negative results. Later CT examinations documented the emergence of a tumor mass of the left temporoparietal lobe. This case clearly illustrates the complementary role of these investigational procedures for the diagnosis of cerebrospinal melanoma: leptomeningeal involvement, characterized by two-dimensional diffuse spread of melanoma tissue (''leptomeningeal melanomatosis''), is invisible with CT, but easily recognisable by CSF cytology; in contrast, nodular parenchymal tumor deposits can be readily detected by CT. Identification of pigmented cells recovered from the CSF requires ultrastructural confirmation.

  15. Primary Anorectal Melanoma: An Update

    Directory of Open Access Journals (Sweden)

    P Carcoforo, M.T Raiji, G.M Palini, M Pedriali, U Maestroni, G Soliani, A Detroia, M.V Zanzi, A.L Manna, J.G Crompton, R.C Langan, A Stojadinovic, I Avital

    2012-01-01

    Full Text Available The anorectum is a rare anatomic location for primary melanoma. Mucosal melanoma is a distinct biological and clinical entity from the more common cutaneous melanoma. It portrays worse prognosis than cutaneous melanoma, with distant metastases being the overwhelming cause of morbidity and mortality. Surgery is the treatment of choice, but significant controversy exists over the extent of surgical resection. We present an update on the state of the art of anorectal mucosal melanoma. To illustrate the multimodality approach to anorectal melanoma, we present a typical patient.

  16. A survey of ATRIPLA use in clinical practice as first-line therapy in HIV-positive persons in Europe

    DEFF Research Database (Denmark)

    Mocroft, A; Reiss, P; Rakhmanova, A

    2014-01-01

    ATRIPLA is licensed for use only in HIV-positive persons whose viral loads therapy (ART) in EuroSIDA using a web-based survey performed in Autumn 2012. 96/112 clinics (85.7 %) completed the survey. Recommendations...... when initiating first-line ART was TRUVADA plus efavirenz in 36 (37.5 %), ATRIPLA in 35 (36.5 %), a different first-line regimen in 12 clinics (12.5 %), and no recommendation in 7 clinics (7.3 %). ATRIPLA was commonest in Northern (15/21 clinics; 71.4 %), and least common in Eastern Europe (2....../31 clinics; 6.5 %; p therapy, despite EMA recommendations....

  17. An empirical evaluation of competency requirements for first-line managers to deal with resistance to change.

    OpenAIRE

    2007-01-01

    The point of departure of this study is that first-line managers play a pivotal role in the facilitation of change initiatives in organisations world-wide. Resistance to change is one of the primary reasons why change interventions fail or why success is not achieved in the change process. More specific, the inability of first-line managers to deal with resistance to change has been cited as a primary cause for change projects to fail. There is no evidence that any research has been conducted...

  18. Responsibilities and commitment of top management and first line management in organizational-level interventions - what difference does it make?

    DEFF Research Database (Denmark)

    Gish, Liv; Ipsen, Christine; Poulsen, Signe

    Researchers advocate that interventions should apply a participatory approach i.e. employee participation. It is also widely recognized that top management’s support is an important part of a successful intervention implementation. Lately there has been a request for multi-level intervention stud...... line managers embraced the responsibility and stayed loyal to the intervention model. Our findings suggest that both top management’s and first line management’s commitment to interventions is crucial, but first line managers are especially responsible for the daily implementation....

  19. Radiosensitivity of malignant melanomas. Part II. Clinical studies

    International Nuclear Information System (INIS)

    Trott, K.R.; von Lieven, H.; Kummermehr, J.; Skopal, D.; Lukacs, S.; Braun-Falco, O.; Kellerer, A.M.

    1981-01-01

    Forty-four lymph node or skin metastases of malignant melanomas received definite radiotherapy. Twenty were locally controlled for 2 or more years. Local control rate increased with dose. TCD-50 was about 1800 ret. The effectiveness of radiotherapy was more dependent on overall treatment time than on fraction size or number of fractions. Radiotherapy is suggested to decrease the high rate of locoregional failure of surgery of nodular melanomas in the foot and face

  20. Genetics of Melanoma

    Directory of Open Access Journals (Sweden)

    Janet eWangari-Talbot

    2013-01-01

    Full Text Available Genomic variation is a trend observed in various human diseases including cancer. Genetic studies have set out to understand how and why these variations result in cancer, why some populations are predisposed to the disease, and also how genetics affect drug responses. The melanoma incidence has been increasing at an alarming rate worldwide. The burden posed by melanoma has made it a necessity to understand the fundamental signaling pathways involved in this deadly disease. Signaling cascades such as MAPK and PI3K/AKT have been shown to be crucial in the regulation of processes that are commonly dysregulated during cancer development such as aberrant proliferation, loss of cell cycle control, impaired apoptosis and altered drug metabolism. Understanding how these and other oncogenic pathways are regulated has been integral in our challenge to develop potent anti-melanoma drugs. With advances in technology and especially in next generation sequencing, we have been able to explore melanoma genomes and exomes leading to the identification of previously unknown genes with functions in melanomagenesis such as GRIN2A and PREX2. The therapeutic potential of these novel candidate genes is actively being pursued with some presenting as druggable targets while others serve as indicators of therapeutic responses. In addition, the analysis of the mutational signatures of melanoma tumors continues to cement the causative role of UV exposure in melanoma pathogenesis. It has become distinctly clear that melanomas from sun exposed skin areas have distinct mutational signatures including C to T transitions indicative of UV-induced damage. It is thus necessary to continue spreading awareness on how to decrease the risk factors of developing the disease while at the same time working for a cure. Given the large amount of information gained from these sequencing studies, it is likely that in the future, treatment of melanoma will follow a highly personalized route

  1. Perforating metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Takenobu Ohashi

    2015-01-01

    Full Text Available We describe a case of metastatic malignant melanoma on the thigh with comedo-like appearance, which histologically showed elimination of tumor cells. A 70 year-old man was diagnosed with a nodular type malignant melanoma involving the lower back with satellite lesions (stage IIIB, T4b N2c M0, Breslow’s tumor thickness; 10.3 mm, Clark’s level; IV.

  2. Disseminated malignant melanoma

    Directory of Open Access Journals (Sweden)

    Verma Kaushal

    1999-01-01

    Full Text Available A 25-year-old man had multiple asymptomatic, nodular lesions on the trunk, extremities and the face for 3 months. He also had left facial palsy with severe headache and vomiting. There were no other systemic or constitutional symptoms. Skin biopsy from a nodular lesion showed features of malignant melanoma, confirmed by Fontana Masson and S-100 protein staining. A diagnosis of disseminated malignant melanoma was made and the patient was treated symptomatically. The patient died in 4 months.

  3. Survival outcomes for first-line antiretroviral therapy in India's ART program.

    Science.gov (United States)

    Dandona, Rakhi; Rewari, Bharat B; Kumar, G Anil; Tanwar, Sukarma; Kumar, S G Prem; Vishnumolakala, Venkata S; Duber, Herbert C; Gakidou, Emmanuela; Dandona, Lalit

    2016-10-11

    Little is known about survival outcomes of HIV patients on first-line antiretroviral therapy (ART) on a large-scale in India, or facility level factors that influence patient survival to guide further improvements in the ART program in India. We examined factors at the facility level in addition to patient factors that influence survival of adult HIV patients on ART in the publicly-funded ART program in a high- and a low-HIV prevalence state. Retrospective chart review in public sector ART facilities in the combined states of Andhra Pradesh and Telangana (APT) before these were split in 2014 and in Rajasthan (RAJ), the high- and a low-HIV prevalence states, respectively. Records of adults initiating ART between 2007-12 and 2008-13 in APT and RAJ, respectively, were reviewed and facility-level information collected at all ART centres and a sample of link ART centres. Survival probability was estimated using Kaplan-Meier method, and determinants of mortality explored with facility and patient-level factors using Cox proportional hazard model. Based on data from 6581 patients, the survival probability of ART at 60 months was 76.3 % (95 % CI 73.0-79.2) in APT and 78.3 % (74.4-81.7) in RAJ. The facilities with cumulative ART patient load above the state average had lower mortality in APT (Hazard ratio [HR] 0.74, 0.57-0.95) but higher in RAJ (HR 1.37, 1.01-1.87). Facilities with higher proportion of lost to follow-up patients in APT had higher mortality (HR 1.47, 1.06-2.05), as did those with higher ART to pre-ART patient ratio in RAJ (HR 1.62, 1.14-2.29). In both states, there was higher hazard for mortality in patients with CD4 count 100 cells/mm 3 or less at ART initiation, males, and in patients with TB co-infection. These data from the majority of facilities in a high- and a low-HIV burden state of India over 5 years reveal reasonable and similar survival outcomes in the two states. The facilities with higher ART load in the longer established ART program in

  4. Radioimmunoscintigraphy in ocular melanoma

    International Nuclear Information System (INIS)

    Kovacs, J.; Chatterton, B.E.; Muecke, J.; Penglis, S.

    1999-01-01

    Full text: Malignant choroidal melanoma is one of the most common primary intraocular neoplasms. Despite significant advances in indirect ophthalmology, ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and fluoroescein angiography, choroidal melanomas may be difficult to distinguish from other malignant and non-malignant eye lesions. Radioimmunoscintigraphy (RIS) with 99 Tc m -labelled monoclonal antibody F(ab')2 fragments was performed on three patients (2 females, 1 male) who were suspected of having a choroidal melanoma. Patients were injected with 240-420 MBq Technemab-K-1 and scanned 6 and 22 h post-injection. Both planar and single photon emission tomographic (SPET) imaging were performed. RIS was faintly positive in one patient in whom the diagnosis of choroidal melanoma was confirmed by enucleation of the left eye. In the other two patients, immunoscintigraphy was negative. One patient had a benign choroidal haemangioma and the other an amelanotic melanoma. This was confirmed on clinical follow-up. These preliminary results indicate that this procedure may have utility for choroidal melanoma

  5. Efficacy and Safety of the Triple Therapy Containing Ilaprazole, Levofloxacin, and Amoxicillin as First-Line Treatment in Helicobacter pylori Infections

    Directory of Open Access Journals (Sweden)

    Hyo Jun Ahn

    2017-01-01

    Full Text Available Background and Aims. To establish the efficacy and safety of ilaprazole, levofloxacin, and amoxicillin as a first-line eradication treatment for Helicobacter pylori. Methods. Patients with gastric ulcer, duodenal ulcer, or gastritis, as detected by esophagogastroduodenoscopy with confirmed H. pylori infection between September 2014 and November 2015, were enrolled in the study. All participants received ilaprazole (10 mg bid, levofloxacin (500 mg bid, and amoxicillin (1000 mg bid for 10 days. H. pylori eradication was confirmed by a 13C-urea breath test at 6–8 weeks after the end of treatment. Results. Of 84 patients included in the analysis, the eradication rate was 88.8% in the per protocol group (n=80. Demographic factors such as age, gender, body mass index (BMI, alcohol, smoking, hypertension, diabetes mellitus, and peptic ulcer did not affect the eradication rate. However, multivariate analysis showed that overweight patients and patients with cerebrovascular accident (CVA had a significantly lower eradication rate than patients with normal BMI and without CVA. Laboratory test results did not change significantly after treatment. A total of six (7.5% patients developed eight adverse reactions. Conclusions. A 10-day triple therapy containing ilaprazole, levofloxacin, and amoxicillin is a safe alternative first-line eradication treatment for H. pylori.

  6. High expression of microRNA-625-3p is associated with poor response to first-line oxaliplatin based treatment of metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Rasmussen, Mads Heilskov; Jensen, Niels Frank; Tarpgaard, Line Schmidt

    2013-01-01

    The backbone of current cytotoxic treatment of metastatic colorectal cancer (mCRC) consists of a fluoropyrimidine together with either oxaliplatin (XELOX/FOLFOX) or irinotecan (XELIRI/FOLFIRI). With an overall objective response rate of approximately 50% for either treatment combination, a major...... unsolved problem is that no predictors of response to these treatments are available. To address this issue, we profiled 742 microRNAs in laser-capture microdissected cancer cells from responding and non-responding patients receiving XELOX/FOLFOX as first-line treatment for mCRC, and identified, among...... HCT116/oxPt (miR-625-3p, miR-181b and miR-27b) and LoVo/oxPt (miR-181b) colon cancer cell lines as compared with their isogenic parental cells. Altogether, our results suggest an association between miR-625-3p and response to first-line oxaliplatin based chemotherapy of mCRC....

  7. Three Weekly Irinotecan and Bolus 5-Fluorouracil Combination in the First Line Treatment of Advanced Gastric Cancer - A Single Institution Experience

    Directory of Open Access Journals (Sweden)

    Mohamed Mesmoudi

    2016-06-01

    Full Text Available Background: The goal of this study is to determine the efficacy and toxicity of a non-platinum based chemotherapy combination using irinotecan associated to bolus 5-FU as first line treatment in advanced gastric cancer. Materiel and methods: Retrospective analysis of a population of patients treated for metastatic and locally advanced gastric cancer with irinotecan and 5-FU as upfront chemotherapy. Results: Thirteen patients were enrolled. The median age was 56 years. Seven patients were males and six were of females. Ten patients had a metastatic disease and three patients had a locally advanced disease. Patients received a total number of 43 cycles of chemotherapy. Overall response rate was 38,4%, median time to progression (TTP was 3 months, and median overall survival was 4 months. Three patients (23,1% presented grade 3 /4 neutropenia complicated with an infectious episode with fever in two cases, three patients (23,1% required blood transfusion for a grade 4 anemia, and one patient (7,6% was hospitalized for a severe episode of diarrhea. Conclusion: Three weekly irinotecan and bolus 5-FU is an interesting combination as first line treatment of advanced gastric cancer; designed clinical trials are needed to confirm the activity of this combination.

  8. Current status of first-line therapy for elderly patients with proatate cancer in Kyushu and Okinawa areas. A questionnaire study

    International Nuclear Information System (INIS)

    Nishiyama, Kenryu; Nakagawa, Masayuki; Koga, Hirofumi

    2005-01-01

    A survey based on a questionnaire to urologists in Kyushu and Okinawa areas was carried out to assess the current status of first-line therapy for elderly patients with prostate cancer. Ninety-three urologists from 93 institutes answered the questionnaire. Endocrine therapy is widely performed as first-line therapy for elderly patients with prostate cancer. They mostly receive immediate-continuous therapy regardless of their clinical factors. Only 8 (9%) and 7 (8%) institutes have the options of deferred and intermittent therapy, respectively. LH-RH analogue and non-steroidal anti-androgens are commonly used. Chemoendocrine therapy is performed in 33 (35%) institutes for selected patients. Estramustine and 5-fluorouracil (5-FU) derivatives are commonly used as chemotherapeutic agents. Sixty (65%) institutes do not have this modality as a treatment option. Risks arising from the treatment and quality of life (QOL) disturbance are the main reasons for this. Radiation therapy and radical prostatectomy are performed in 53 (57%) and 47 (51%) institutes, respectively, for selected patients with loco-regional disease. However, 22 (24%) institutes do not have these definitive therapies as treatment options. QOL and risks arising from the treatments are the main factors for selecting definitive or non-definitive therapy. In elderly patients with prostate cancer, cancer control is not always the goal of treatment. QOL within a relatively shorter life expectancy is an important factor for decision making in the management of these patients. (authors)

  9. Safety of administering the canine melanoma DNA vaccine (Oncept) to cats with malignant melanoma - a retrospective study.

    Science.gov (United States)

    Sarbu, Luminita; Kitchell, Barbara E; Bergman, Philip J

    2017-02-01

    Objectives A xenogeneic human tyrosinase DNA vaccine was developed for treatment of dogs with oral malignant melanoma (Oncept; Merial). No studies have evaluated the safety or efficacy of this vaccine in cats. The purpose of this study was to evaluate the safety of the canine melanoma vaccine in cats diagnosed with melanoma. Methods Medical records were reviewed from cats diagnosed with malignant melanoma and treated with the canine melanoma DNA vaccine (Oncept). Data regarding signalment, melanoma location, treatments received, vaccine adverse effects and cause of death were collected. Results A total of 114 melanoma vaccines were administered to 24 cats. Seven cats (11.4%) had clinical adverse effects from a total of 13 vaccines classified as grade 1 or 2 based on the Veterinary Cooperative Oncology Group's common terminology criteria for adverse events v1.1. These included pain on vaccine administration, brief muscle fasciculation, transient inappetence, depression, nausea and mild increase in pigmentation at the injection site. Nineteen cats were deceased at study close. The most common cause of death was melanoma (14 cats). Hematological and biochemical changes were observed in six cats, five of which had concurrent disease or treatments that likely caused or greatly contributed to the laboratory abnormalities found. Therefore, these adverse events were considered unlikely to be caused by the melanoma vaccine. One cat had transient grade 1 hypoalbuminemia, which was possibly caused by the vaccination but not thoroughly evaluated. Conclusions and relevance The canine melanoma DNA vaccine can be safely administered to cats, with minimal risk of adverse effects.

  10. The Danish Melanoma Database

    Directory of Open Access Journals (Sweden)

    Hölmich Lr

    2016-10-01

    Full Text Available Lisbet Rosenkrantz Hölmich,1 Siri Klausen,2 Eva Spaun,3 Grethe Schmidt,4 Dorte Gad,5 Inge Marie Svane,6,7 Henrik Schmidt,8 Henrik Frank Lorentzen,9 Else Helene Ibfelt10 1Department of Plastic Surgery, 2Department of Pathology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, 3Institute of Pathology, Aarhus University Hospital, Aarhus, 4Department of Plastic and Reconstructive Surgery, Breast Surgery and Burns, Rigshospitalet – Glostrup, University of Copenhagen, Copenhagen, 5Department of Plastic Surgery, Odense University Hospital, Odense, 6Center for Cancer Immune Therapy, Department of Hematology, 7Department of Oncology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, 8Department of Oncology, 9Department of Dermatology, Aarhus University Hospital, Aarhus, 10Registry Support Centre (East – Epidemiology and Biostatistics, Research Centre for Prevention and Health, Glostrup – Rigshospitalet, University of Copenhagen, Glostrup, Denmark Aim of database: The aim of the database is to monitor and improve the treatment and survival of melanoma patients.Study population: All Danish patients with cutaneous melanoma and in situ melanomas must be registered in the Danish Melanoma Database (DMD. In 2014, 2,525 patients with invasive melanoma and 780 with in situ tumors were registered. The coverage is currently 93% compared with the Danish Pathology Register.Main variables: The main variables include demographic, clinical, and pathological characteristics, including Breslow’s tumor thickness, ± ulceration, mitoses, and tumor–node–metastasis stage. Information about the date of diagnosis, treatment, type of surgery, including safety margins, results of lymphoscintigraphy in patients for whom this was indicated (tumors > T1a, results of sentinel node biopsy, pathological evaluation hereof, and follow-up information, including recurrence, nature, and treatment hereof is registered. In case of death, the cause and date

  11. Six versus fewer planned cycles of first-line platinum-based chemotherapy for non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Rossi, Antonio; Chiodini, Paolo; Sun, Jong-Mu

    2014-01-01

    BACKGROUND: Platinum-based chemotherapy is the standard first-line treatment for patients with advanced non-small-cell lung cancer. However, the optimum number of treatment cycles remains controversial. Therefore, we did a systematic review and meta-analysis of individual patient data to compare ...

  12. Pooled analysis of phase II trials evaluating weekly or conventional cisplatin as first-line therapy for advanced urothelial carcinoma

    DEFF Research Database (Denmark)

    Maughan, Benjamin L; Agarwal, Neeraj; Hussain, Syed A

    2013-01-01

    Weekly gemcitabine with GC every 3-4 weeks is considered conventional first-line chemotherapy for advanced urothelial carcinoma (UC). Weekly split-dose cisplatin with wGC might be less toxic and have similar activity, but has not been compared with GC. We pooled published phase II trials of GC...

  13. Incidence and predictors of severe anemia in Asian HIV-infected children using first-line antiretroviral therapy

    NARCIS (Netherlands)

    Bunupuradah, Torsak; Kariminia, Azar; Chan, Kwai-Cheng; Ramautarsing, Reshmie; Huy, Bui Vu; Han, Ning; Nallusamy, Revathy; Hansudewechakul, Rawiwan; Saphonn, Vonthanak; Sirisanthana, Virat; Chokephaibulkit, Kulkanya; Kurniati, Nia; Kumarasamy, Nagalingeswaran; Yusoff, Nik Khairulddin Nik; Razali, Kamarul; Fong, Siew Moy; Sohn, Annette H.; Lumbiganon, Pagakrong

    2013-01-01

    There are limited data on treatment-related anemia in Asian HIV-infected children. Data from Asian HIV-infected children aged <18 years on first-line highly active antiretroviral therapy (HAART) were used. Children who had pre-existing severe anemia at baseline were excluded. Anemia was graded using

  14. Treatment Options by Stage (Melanoma)

    Science.gov (United States)

    ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Funding for ... the skin far away from where it first started. Recurrent Melanoma Recurrent melanoma is cancer that has ...

  15. Intracerebral metastases from ocular melanoma.

    OpenAIRE

    Jones, D. R.; Scobie, I. N.; Sarkies, N. J.

    1988-01-01

    A blind painful eye may harbour an unsuspected malignant melanoma. We report a case of ocular melanoma that presented with confusion owing to direct extension via the optic nerve into the anterior cranial fossa.

  16. TAPIOCA MELANOMA OF THE IRIS

    NARCIS (Netherlands)

    DEKEIZER, RJW; OOSTERHUIS, JA; HOUTMAN, WA; DEWOLFFROUENDAAL, D

    Clinical identification of tapioca melanoma of the iris is important because its medical treatment may differ from that of other malignant iris melanomas. The characteristic iris nodules must be differentiated from granulomatous uveitis, metastases, and Lisch nodules (neurofibromatosis). We will

  17. Advanced Melanoma Facebook Live Event

    Science.gov (United States)

    In case you missed it, watch this recent Facebook Live event about the current state of research and treatment for advanced stage melanoma. To learn more, see our evidence-based information about skin cancer, including melanoma.

  18. Nanoscaled hydrated antimony (V oxide as a new approach to first-line antileishmanial drugs

    Directory of Open Access Journals (Sweden)

    Franco AMR

    2016-12-01

    Full Text Available Antonia MR Franco,1 Iryna Grafova,2 Fabiane V Soares,1,3 Gennaro Gentile,4 Claudia DC Wyrepkowski,1,3 Marcos A Bolson,5 Ézio Sargentini Jr,5 Cosimo Carfagna,4 Markku Leskelä,2 Andriy Grafov2 1Laboratory of Leishmaniasis and Chagas Disease, National Institute of Amazonian Research (INPA, Manaus, Amazonas, Brazil; 2Department of Chemistry, University of Helsinki, Helsinki, Finland; 3Multi-Institutional Post-Graduate Program in Biotechnology, Federal University of Amazonas, Manaus, Amazonas, Brazil; 4Institute for Polymers, Composites, and Biomaterials, National Research Council, Pozzuoli, Naples Province, Italy; 5Laboratory of Environmental Chemistry, National Institute of Amazonian Research (INPA, Manaus, Amazonas, Brazil Background: Coordination compounds of pentavalent antimony have been, and remain, the first-line drugs in leishmaniasis treatment for >70 years. Molecular forms of Sb (V complexes are commercialized as sodium stibogluconate (Pentostam® and meglumine antimoniate (MA (Glucantime®. Ever-increasing drug resistance in the parasites limits the use of antimonials, due to the low drug concentrations being administered against high parasitic counts. Sb5+ toxicity provokes severe side effects during treatment. To enhance therapeutic potency and to increase Sb (V concentration within the target cells, we decided to try a new active substance form, a hydrosol of Sb2O5⋅nH2O nanoparticles (NPs, instead of molecular drugs. Methodology/principal findings: Sb2O5⋅nH2O NPs were synthesized by controlled SbCl5 hydrolysis in a great excess of water. Sb2O5⋅nH2O phase formation was confirmed by X-ray diffraction. The surface of Sb (V NPs was treated with ligands with a high affinity for target cell membrane receptors. The mean particle size determined by dynamic light scattering and transmission electron microscopy was ~35–45 nm. In vitro tests demonstrated a 2.5–3 times higher antiparasitic activity of Sb (V nanohybrid hydrosols

  19. Metastatic melanoma after 23 years of primary ocular melanoma.

    LENUS (Irish Health Repository)

    Karde, Supriya Ramesh

    2016-11-23

    We describe a case of 52-year-old man who presented with an episode of tonic-clonic seizures. He had right ocular melanoma 23 years ago with subsequent enucleation which was the standard treatment at that time. CT scans of the brain and of the thorax-abdomen-pelvis revealed widespread metastatic lesions in the brain, lung and liver. Further investigations including bronchoscopy with cytopathology uncovered that the metastatic disease was a recurrence of ocular melanoma. He received palliative radiotherapy and died 6 months later. Ocular melanoma is often associated with fulminant metastatic disease after a period of dormancy. Thus, despite successful treatment of the localised disease at initial presentation, an effort is needed for optimal long-term follow-up plan in order to improve survival in case of recurrence.

  20. Antiestrogen therapy for breast cancer modifies the risk of subsequent cutaneous melanoma.

    Science.gov (United States)

    Huber, Caroline; Bouchardy, Christine; Schaffar, Robin; Neyroud-Caspar, Isabelle; Vlastos, Georges; Le Gal, Frédérique-Anne; Rapiti, Elisabetta; Benhamou, Simone

    2012-01-01

    Increased risk of secondary melanoma after breast cancer has been reported. Several lines of evidence suggest that elevated estrogen levels may be implicated in melanoma etiology. Accordingly, use of antiestrogens should be associated with decreased risk of melanoma. We compared melanoma incidence among a cohort of breast cancer patients with and without antiestrogen therapy, with data from the Geneva Cancer Registry. The cohort consisted of 7,360 women diagnosed with breast cancer between 1980 and 2005. About 54% of these patients received antiestrogens. All women were followed until December 2008. We compared cutaneous melanoma incidence rates among patients with and without antiestrogens with those expected in the general population by age and period standardized incidence ratios (SIR). A total of 34 women developed a melanoma during the follow-up period. Compared with the general population, the risk of melanoma was higher for patients who did not receive antiestrogens (SIR: 1.60, 95% CI: 1.08-2.12, P = 0.02). On the contrary, the risk was close to 1 (SIR: 0.98, 95% CI: 0.40-1.56, P = 0.57) for patients who received antiestrogen therapy. This study suggests that antiestrogen therapy modifies the risk of melanoma after breast cancer. Although our results are in agreement with the hypothesis that estrogens could play a role in melanoma occurrence, they need to be replicated in a larger study with data on potential confounders. . ©2011 AACR

  1. ORAL AMELANOTIC MELANOMA FEATURE ARTICLE

    African Journals Online (AJOL)

    hard palate (more than 40%) and the gingiva2. Melanomas arise from the uninhibited proliferation ... Malignant melanomas of the mucosal regions of the head and neck are extremely rare neoplasms accounting for less than 1% of .... head and neck region reported that amelanotic melanomas had a 20% survival at 3 years, ...

  2. Genetic Abnormalities in Uveal Melanoma

    NARCIS (Netherlands)

    N.C. Naus (Nicole)

    2001-01-01

    textabstractMelanocytic tumours are believed to arise from the neural crest-derived melanocytes. Five to twelve percent of all melanomas are located in the eye, making it, after the skin, the second most common site of melanomas (Egan et al., 1988; Chang et al., 1998). Uveal melanoma is the most

  3. Tumor markers cancer antigen 15.3, carcinoembryonic antigen, and tissue polypeptide antigen for monitoring metastatic breast cancer during first-line chemotherapy and follow-up

    DEFF Research Database (Denmark)

    Sölétormos, G; Nielsen, D; Schiøler, V

    1996-01-01

    progressive disease, the median positive lead time was 35 days during therapy and 76 days during follow-up. Tumor marker assessment may document that a therapy is effective and ought to be continued in spite of adverse toxic effects, and that a treatment is ineffective and should be stopped to prevent......We investigated whether model systems integrating stochastic variation into criteria for marker assessment could be used for monitoring metastatic breast cancer. A total of 3989 serum samples was obtained from 204 patients receiving first-line chemotherapy and from 112 of these patients during...... follow-up. Each sample was analyzed for cancer antigen 15.3, carcinoembryonic antigen, and tissue polypeptide antigen. The efficiency for identifying progression and nonprogression was 94% during therapy and 85% during follow-up, with no false-positive marker results for progressive disease. At clinical...

  4. PSA time to nadir as a prognostic factor of first-line docetaxel treatment in castration-resistant prostate cancer: evidence from patients in Northwestern China

    Directory of Open Access Journals (Sweden)

    Kai-Jie Wu

    2018-01-01

    Full Text Available Docetaxel-based chemotherapy remains the first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC in China; however, the prognostic factors associated with effects in these patients are still controversial. In this study, we retrospectively reviewed the data from 71 eligible Chinese patients who received docetaxel chemotherapy from 2009 to 2016 in our hospital and experienced a reduction of prostate-specific antigen (PSA level ≥50% during the treatment and investigated the potential role of time to nadir (TTN of PSA. TTN was defined as the time from start of chemotherapy to the nadir of PSA level during the treatment. Multivariable Cox regression models and Kaplan-Meier analysis were used to predict overall survival (OS. In these patients, the median of TTN was 17 weeks. Patients with TTN ≥17 weeks had a longer response time to chemotherapy compared to TTN 50% PSA remission.

  5. Malignant melanoma misdiagnosed as diabetic foot ulcer

    Science.gov (United States)

    Gao, Wei; Chen, Dawei; Ran, Xingwu

    2017-01-01

    Abstract Rationale: Acral lentiginous melanoma (AML) does not exhibit the classic signs of malignant melanoma. ALM is frequently misdiagnosed because of its unusual sites and atypical clinical morphologies, which lead to poor prognosis. Patient concerns: A female patient aged 78 years was presented to our center with two ulcers on her right foot. Diabetic foot ulcer was considered as the primary diagnosis. The ulcers failed to improve after 2 weeks’ therapy. Diagnoses: An incisional biopsy of the lesion revealed malignant melanoma. Interventions: The patient received wide excision, skin grafting as well as biotherapy. Outcomes: The lesion was healed and no other metastasis has been founded until now. Lessons: Clinicians must maintain a high level of suspicion in distinguishing malignant melanoma from other more benign skin lesions of the foot. The need for early biopsy of ulcer, even when clinical suspicion is low, can not be overemphasized. Only in this way can we reduce misdiagnosis rate and improve survival rate in patients with foot ulcer. PMID:28723771

  6. RAS testing of liquid biopsy correlates with the outcome of metastatic colorectal cancer patients treated with first-line FOLFIRI plus cetuximab in the CAPRI-GOIM trial.

    Science.gov (United States)

    Normanno, N; Esposito Abate, R; Lambiase, M; Forgione, L; Cardone, C; Iannaccone, A; Sacco, A; Rachiglio, A M; Martinelli, E; Rizzi, D; Pisconti, S; Biglietto, M; Bordonaro, R; Troiani, T; Latiano, T P; Giuliani, F; Leo, S; Rinaldi, A; Maiello, E; Ciardiello, F

    2018-01-01

    Liquid biopsy is an alternative to tissue for RAS testing in metastatic colorectal carcinoma (mCRC) patients. Little information is available on the predictive role of liquid biopsy RAS testing in patients treated with first-line anti-EGFR monoclonal antibody-based therapy. In the CAPRI-GOIM trial, 340 KRAS exon-2 wild-type mCRC patients received first-line cetuximab plus FOLFIRI. Tumor samples were retrospectively assessed by next generation sequencing (NGS). Baseline plasma samples were analyzed for KRAS and NRAS mutations using beads, emulsion, amplification, and magnetics digital PCR (BEAMing). Discordant cases were solved by droplet digital PCR (ddPCR) or deep-sequencing. A subgroup of 92 patients with available both NGS data on tumor samples and baseline plasma samples were included in this study. Both NGS analysis of tumor tissue and plasma testing with BEAMing identified RAS mutations in 33/92 patients (35.9%). However, 10 cases were RAS tissue mutant and plasma wild-type, and additional 10 cases were tissue wild-type and plasma mutant, resulting in a concordance rate of 78.3%. Analysis of plasma samples with ddPCR detected RAS mutations in 2/10 tissue mutant, plasma wild-type patients. In contrast, in all tissue wild-type and plasma mutant cases, ddPCR or deep-sequencing analysis of tumor tissue confirmed the presence of RAS mutations at allelic frequencies ranging between 0.15% and 1.15%. The median progression-free survival of RAS mutant and wild-type patients according to tissue (7.9 versus 12.6 months; P = 0.004) and liquid biopsy testing (7.8 versus 13.8 moths; P < 0.001) were comparable. Similar findings were observed for the median overall survival of RAS mutant and wild-type patients based on tissue (22.1 versus 35.8 months; P = 0.016) and plasma (19.9 versus 35.8 months; P = 0.013) analysis. This study indicates that RAS testing of liquid biopsy results in a similar outcome when compared with tissue testing in mCRC patients

  7. Targeted Therapy for Melanoma

    International Nuclear Information System (INIS)

    Quinn, Thomas; Moore, Herbert

    2016-01-01

    The research project, entitled ''Targeted Therapy for Melanoma,'' was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the 212Pb/203 Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg 11 )CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of 212 Pb labeled DOTA-Re(Arg 11 )CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter 212 Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  8. Targeted Therapy for Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Quinn, Thomas [Alphamed, Jackson, TN (United States); Moore, Herbert [Alphamed, Jackson, TN (United States)

    2016-12-05

    The research project, entitled ”Targeted Therapy for Melanoma,” was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the 212Pb/203Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg11)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of 212Pb labeled DOTA-Re(Arg11)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter 212Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  9. Trends in the incidence of malignant melanoma in Denmark 1978-2007. Incidence on the island of Bornholm compared with the whole country incidence in Denmark

    DEFF Research Database (Denmark)

    Drejøe, Jennifer Berg; Drzewiecki, Krzysztof Tadeusz; Klit, Anders

    2011-01-01

    In Denmark, malignant melanoma is among the most rapidly increasing cancer types. Malignant melanoma accounts for the majority of skin cancer-related deaths. Sunshine is the main cause of the increase seen in melanoma incidence. Within Denmark, Bornholm is the area that receives most sunshine...

  10. Malignant melanoma misdiagnosed as diabetic foot ulcer: A case report.

    Science.gov (United States)

    Gao, Wei; Chen, Dawei; Ran, Xingwu

    2017-07-01

    Acral lentiginous melanoma (AML) does not exhibit the classic signs of malignant melanoma. ALM is frequently misdiagnosed because of its unusual sites and atypical clinical morphologies, which lead to poor prognosis. A female patient aged 78 years was presented to our center with two ulcers on her right foot. Diabetic foot ulcer was considered as the primary diagnosis. The ulcers failed to improve after 2 weeks' therapy. An incisional biopsy of the lesion revealed malignant melanoma. The patient received wide excision, skin grafting as well as biotherapy. The lesion was healed and no other metastasis has been founded until now. Clinicians must maintain a high level of suspicion in distinguishing malignant melanoma from other more benign skin lesions of the foot. The need for early biopsy of ulcer, even when clinical suspicion is low, can not be overemphasized. Only in this way can we reduce misdiagnosis rate and improve survival rate in patients with foot ulcer.

  11. Chemoprevention of Melanoma

    Science.gov (United States)

    Madhunapantula, SubbaRao V.; Robertson, Gavin P.

    2013-01-01

    Despite advances in drug discovery programs and molecular approaches for identifying the drug targets, incidence and mortality rates due to melanoma continues to rise at an alarming rate. Existing preventive strategies generally involve mole screening followed by surgical removal of the benign nevi and abnormal moles. However, due to lack of effective programs for screening and disease recurrence after surgical resection there is a need for better chemopreventive agents. Although sunscreens have been used extensively for protecting from UV-induced skin cancer, results of correlative population based studies are controversial, requiring further authentication to conclusively confirm the chemoprotective efficacy of sunscreens. Certain studies suggest increased skin-cancer rates in sunscreen users. Therefore, effective chemopreventive agents for preventing melanoma are urgently required. This book-chapter, reviews the current understanding regarding melanoma chemoprevention and the various strategies used to accomplish this objective. PMID:22959032

  12. The Immunology of Melanoma.

    Science.gov (United States)

    Ko, Jennifer S

    2017-09-01

    The relatively high DNA mutational burden in melanoma allows for the creation of potentially "foreign," immune-stimulating neoantigens, and leads to its exceptional immunogenicity. Brisk tumor-infiltrating lymphocytes, a marker of immune editing, confer improved overall survival in melanoma, possibly due to reduced sentinel lymph node spread. Meanwhile, T-cell-stimulating drugs, so-called T-cell checkpoint inhibitors, which reverse peripheral tolerance-dependent tumor escape, have demonstrated unparalleled clinical success in metastatic melanoma. Markers to predict response to immunotherapy are currently imperfect, and the subject of intense research, which will guide the future of ancillary pathologic testing in this setting. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Meta-analysis of first-line therapies with maintenance regimens for advanced non-small-cell lung cancer (NSCLC) in molecularly and clinically selected populations.

    Science.gov (United States)

    Tan, Pui San; Bilger, Marcel; de Lima Lopes, Gilberto; Acharyya, Sanchalika; Haaland, Benjamin

    2017-08-01

    Evidence has suggested survival benefits of maintenance for advanced NSCLC patients not progressing after first-line chemotherapy. Additionally, particular first-line targeted therapies have shown survival improvements in selected populations. Optimal first-line and maintenance therapies remain unclear. Here, currently available evidence was synthesized to elucidate optimal first-line and maintenance therapy within patient groups. Literature was searched for randomized trials evaluating first-line and maintenance regimens in advanced NSCLC patients. Bayesian network meta-analysis was performed within molecularly and clinically selected groups. The primary outcome was combined clinically meaningful OS and PFS benefits. A total of 87 records on 56 trials evaluating first-line treatments with maintenance were included. Results showed combined clinically meaningful OS and PFS benefits with particular first-line with maintenance treatments, (1) first-line intercalated chemotherapy+erlotinib, maintenance erlotinib in patients with EGFR mutations, (2) first-line afatinib, maintenance afatinib in patients with EGFR deletion 19, (3) first-line chemotherapy + bevacizumab, maintenance bevacizumab in EGFR wild-type patients, (4) chemotherapy+conatumumab, maintenance conatumumab in patients with squamous histology, (5) chemotherapy+cetuximab, maintenance cetuximab or chemotherapy + necitumumab, maintenance necitumumab in EGFR FISH-positive patients with squamous histology, and (6) first-line chemotherapy+bevacizumab, maintenance bevacizumab or first-line sequential chemotherapy+gefitinib, maintenance gefitinib in patients clinically enriched for EGFR mutations with nonsquamous histology. No treatment showed combined clinically meaningful OS and PFS benefits in patients with EGFR L858R or nonsquamous histology. Particular first-line with maintenance treatments show meaningful OS and PFS benefits in patients selected by EGFR mutation or histology. Further research is needed

  14. Utility of chest X-ray and abdominal ultrasound for stage III cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Breitenbauch, M. T. W.; Holm, J.; Rødgaard, J. C.

    2015-01-01

    Background: Current Danish Melanoma Guidelines suggest that stage III cutaneous malignant melanoma receive chest X-ray and abdominal ultrasound to exclude lung and liver metastases. The aim of this study was to examine the sensitivity, specificity, and negative predictive value of chest X-ray and...

  15. Cost-effectiveness of First-line Chronic Lymphocytic Leukemia Treatments When Full-dose Fludarabine Is Unsuitable.

    Science.gov (United States)

    Soini, Erkki; Hautala, Anne; Poikonen, Eira; Becker, Ursula; Kyttälä, Mira; Martikainen, Janne

    2016-04-01

    The cost-effectiveness of first-line chronic lymphocytic leukemia treatments was assessed among patients unsuitable for full doses of fludarabine. The study's key outcome was the life-time incremental cost-effectiveness ratio (ICER) (euro/quality-adjusted life-year [QALY] gained) with an annual 3% discounting. A probabilistic Markov model with 3 health states (progression-free, progression, and death) was developed. Survival time was modeled based on age-matched clinical data by using appropriate survival distributions. Each health state was assigned an EuroQoL-5D-3L quality-of-life estimate and Finnish payer costs according to treatment received, and Binet stage of disease; severe adverse events and treatment inconvenience were also included. Six approaches considered the risk and value of key outcomes: cost-effectiveness efficiency frontiers; Bayesian treatment ranking (BTR) rated the lowest ICERs and best QALY gains; the cost-effectiveness acceptability frontier demonstrated optimal treatment; expected value of perfect information; and the cost-benefit assessment (CBA), a type of clinical value analysis, increased the clinical interpretation and appeal of modeled outcomes by including both relative and absolute (impact investment [benefit obtained with a fixed limited budget]) benefit assessments. The ICERs compared with chlorambucil varied from €29,334 with obinutuzumab + chlorambucil to €82,159 with ofatumumab + chlorambucil. Based on the BTR of ICERs versus chlorambucil, obinutuzumab + chlorambucil was the most cost-effective with 93% probability; rituximab + chlorambucil was the second most cost-effective (73%); and rituximab + bendamustine was the third most cost-effective (65%). The ICERs of obinutuzumab + chlorambucil were €20,038, €11,556, and €15,586 compared with rituximab + chlorambucil, rituximab + bendamustine, and ofatumumab + chlorambucil. Obinutuzumab + chlorambucil was the most cost-effective treatment, with 54% and 99% probability at

  16. Angiogenesis and Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Ribatti, Domenico, E-mail: ribatti@anatomia.uniba.it; Annese, Tiziana; Longo, Vito [Department of Human Anatomy and Histology, University of Bari Medical School, Piazza G. Cesare, 11, Policlinico 70124, Bari (Italy)

    2010-02-25

    Angiogenesis occurs in pathological conditions, such as tumors, where a specific critical point in tumor progression is the transition from the avascular to the vascular phase. Tumor angiogenesis depends mainly on the release by neoplastic cells of growth factors specific for endothelial cells, which are able to stimulate the growth of the host’s blood vessels. This article summarizes the literature concerning the relationship between angiogenesis and human melanoma progression. The recent applications of antiangiogenic agents which interfere with melanoma progression are also described.

  17. Shifting from quinine to artesunate as first-line treatment of severe malaria in children and adults: saving more lives.

    Science.gov (United States)

    Noubiap, Jean Jacques N

    2014-01-01

    Severe malaria kills more than a half million people each year. Based on high-quality evidence of the efficacy superiority of artesunate over quinine in adults and children with severe malaria, the World Health Organization guidelines have been revised. The WHO currently recommends injectable artesunate as the first-line treatment for severe malaria. Since this revision in April 2011, only a small number of countries affected by malaria have adopted and implemented the new policy. If this policy is implemented, an additional 195,000 lives would be saved each year in Africa. Thus, there is an urgent need to speed up access to injectable artesunate in malaria-endemic countries. This review presents a background for recommending artesunate as the first-line treatment of severe malaria in children and adults, and interventions that are recommended to accelerate access to injectable artesunate. Copyright © 2014 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  18. Predictors of occupational stress and well-being in First-Line Nurse Managers: A cross-sectional survey study.

    Science.gov (United States)

    Adriaenssens, Jef; Hamelink, Ambre; Bogaert, Peter Van

    2017-08-01

    First-line nurse managers have a pivotal role in the organization of health care but have to deal with significant job-related issues and problems in a changing and challenging health care environment. As their new roles are complex and often unclear, it might be expected that these professionals are at risk for occupational stress. The objective of this study is to analyze and describe relationships between job characteristics, and also interdisciplinary conflicts with physicians as potential predictors of occupational well-being (job satisfaction, psychosomatic distress, turnover intention, work engagement and burnout). this study had a cross-sectional design and used a web-based survey. This study was conducted in 2015 in 11 Belgian (Flemish) hospitals. All First-line nurse managers were eligible (N=481) and 318 respondents (66.1%) agreed to take part in the survey. A hierarchical regression analyses was applied to analyze relationships between predictors and outcomes. job demand and job control measures were predictive of all outcomes. Collaboration with doctors only predicted job satisfaction and turnover intention. Social support from management was predictive of turnover intention. Social support from colleague- first-line nurse managers was not predictive. Social support from the staff members (team) was however a strong predictor of all stress outcomes. Job demands, job control and social support of the team and management were all important predictors of occupational well-being in first-line nurse managers. All of these variables can be influenced by hospital management to improve the work conditions of this professional group in order to retain their workforce. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. The cost-effectiveness of radiofrequency catheter ablation as first-line treatment for paroxysmal atrial fibrillation

    DEFF Research Database (Denmark)

    Aronsson, Mattias; Walfridsson, Håkan; Janzon, Magnus

    2014-01-01

    , based on MANTRA-PAF (Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation) study data, was developed to study long-term effects and costs of RFA compared with AADs as first-line treatment. Positive clinical effects were found in the overall population, a gain...... in older patients is uncertain, and in most of these AADs should be attempted before RFA (MANTRA-PAF ClinicalTrials.gov number; NCT00133211)....

  20. Effective Selection: A Study of First-Line Supervisor Selection Processes in the Department of Homeland Security

    Science.gov (United States)

    2011-03-01

    first-line supervisor selection process in the government has four important tenets. Similar to the construction of an Egyptian pyramid , these...of all segments of society. B  My supervisor/team leader provides me with constructive suggestions to improve my job performance. B  Supervisors/team...me with constructive suggestions to improve my job performance. √ √ Supervisors/team leaders in my work unit support employee development. √ √ My

  1. Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study.

    Science.gov (United States)

    Murakami, Kazunari; Sakurai, Yuuichi; Shiino, Madoka; Funao, Nobuo; Nishimura, Akira; Asaka, Masahiro

    2016-09-01

    The objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter pylori eradication therapy. A randomised, double-blind, multicentre, parallel-group study was conducted to verify the non-inferiority of vonoprazan 20 mg to lansoprazole 30 mg as part of first-line triple therapy (with amoxicillin 750 mg and clarithromycin 200 or 400 mg) in H pylori-positive patients with gastric or duodenal ulcer history. The first 50 patients failing first-line therapy with good compliance also received second-line vonoprazan-based triple therapy (with amoxicillin 750 mg and metronidazole 250 mg) as an open-label treatment. Of the 650 subjects randomly allocated to either first-line triple therapy, 641 subjects completed first-line therapy and 50 subjects completed second-line therapy. The first-line eradication rate (primary end point) was 92.6% (95% CI 89.2% to 95.2%) with vonoprazan versus 75.9% (95% CI 70.9% to 80.5%) with lansoprazole, with the difference being 16.7% (95% CI 11.2% to 22.1%) in favour of vonoprazan, thus confirming the non-inferiority of vonoprazan (ppylori-positive patients with a history of gastric or duodenal ulcer. NCT01505127. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  2. Does first line antiretroviral therapy increase the prevalence of cardiovascular risk factors in Indian patients?: A cross sectional study.

    Science.gov (United States)

    Carey, R A B; Rupali, P; Abraham, O C; Kattula, D

    2013-01-01

    Antiretroviral therapy (ART) is associated with a myriad of metabolic complications which are potential cardiovascular risk factors. Early detection of these risk factors could help in alleviating morbidity and mortality in human immunodeficiency virus (HIV) infected patients on ART. To study the prevalence of cardiovascular risk factors in patients on a combination of nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) - the standard combination first line ART regimen used in tertiary referral center. The prevalence of cardiovascular risk factors in HIV infected subjects with stage 1t disease on standard first line ART for at least 1 year, HIV infected subjects with stage 1 disease and not on ART and HIV negative subjects was assessed. The study was a cross-sectional study design. Basic demographic data was collected and patients were examined for anthropometric data and blood was collected for analysis of blood glucose, serum lipids, and fasting insulin levels. Chi-square test was used to calculate significance. Statistical Package for Social Sciences (SPSS) software version 16.0 was used for data analysis. The prevalence of hypercholesterolemia and hypertriglyceridemia was higher in the patients on ART when compared to patients not on ART (PART and those not on ART. First line ART is associated with increased prevalence of dyslipidemia. Early detection and treatment of dyslipidemia should help in reducing the cardiovascular morbidity in patients on ART.

  3. Underreporting of side effects of standard first-line ART in the routine setting in Blantyre, Malawi.

    Science.gov (United States)

    Tapsfield, Julia; Mathews, Teena; Lungu, Molly; van Oosterhout, Joep J

    2011-12-01

    In the Malawi ART programme, 92% of 250,000 patients are using the standard first-line regime of stavudine-lamivudine-nevaripine. National ART reports indicate Blantyre, Malawi. We determined the prevalence of symptoms that are common side-effects, described discrepancies between symptoms that patients reported to us and those that had been recorded by attending staff as side-effects in the point-of-care electronic monitoring system, and studied factors associated with such discrepancies. Of 170 participants, 75 (44%) reported at least one symptom, most common were symptoms suggesting peripheral neuropathy (n=57) and lipodystrophy (n=16). Forty-six (66%) symptomatic patients said they reported symptoms to attending ART staff. Side-effects were recorded in the clinic database for just 4 patients. Toxicity recording was too low for meaningful analysis of factors associated with discrepancies between reporting and recording of side-effects. The prevalence of symptoms indicating characteristic side-effects of the standard first-line regimen was 39% based on interviews, and 2% in the electronic monitoring system. There was gross under-recording of side-effects in this setting, mainly due to not recording by ART staff. Pressure of work and insufficient perceived benefit of side-effect recording are suspected causes. Local and national ART reports do not reflect the true toxicity of the standard first line regimen.

  4. [Cerebral MR imaging of malignant melanoma].

    Science.gov (United States)

    Breckwoldt, M; Bendszus, M

    2015-02-01

    Melanoma is the third leading cancer entity to metastasize to the central nervous system (CNS) after lung and breast cancer. This is often an early event in the disease course and limits survival. Metastasis in the CNS is the cause of death in 10-40 % of melanoma patients and the incidence of brain metastasis is even higher (50-75 %). Cerebral metastases are commonly found in the subcortical white matter. The signal characteristics can vary substantially and may change over time due to hemorrhages or the accumulation of melanin and paramagnetic ions. It is not yet clear whether novel targeted therapies (e.g. immunotherapy and kinase inhibitors) alter imaging characteristics. Also immune-related side effects, such as hypophysitis (in approximately 5 % of patients receiving ipilimumab therapy) or granulomatous disease (neurosarcoid) can occur. Melanoma metastases are usually hyperdense in computed tomography (CT). In magnetic resonance imaging (MRI) T2-weighted (T2-w) fluid-attentuated inversion recovery (FLAIR) and T1-w sequences (with and without i.v. contrast) should be obtained. Coronal and axial imaging planes should be scanned to cross-correlate findings. Susceptibility-weighted imaging is a new sensitive method to detect melanoma metastases. Approximately 66 % of melanoma metastases show intratumoral susceptibility signals (ITSS). This sets them apart from other metastases (e.g. lung and breast cancer show less ITSSs, specificity approximately 81-96 %). Diffusion imaging plays no major role in melanoma brain imaging. Susceptibility-weighted imaging increases the sensitivity to detect metastases but lacks specificity. Differentiating metastases, microbleeding or calcification can be impossible. It is controversial how to interpret susceptibility signals without correlative signs on other sequences (differential diagnosis: metastasis, microbleeding and calcification). CNS metastases are common in melanoma. MRI screening starting in stage IIc should be

  5. Spotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives

    Directory of Open Access Journals (Sweden)

    Giroux Leprieur E

    2016-06-01

    Full Text Available Etienne Giroux Leprieur,1,2 Vincent Fallet,3,4 Jacques Cadranel,3,4 Marie Wislez3,4 1Respiratory Diseases and Thoracic Oncology Department, APHP-Ambroise Paré Hospital, Boulogne-Billancourt, France; 2EA4340 Laboratory, UVSQ, Paris-Saclay University, France; 3Respiratory Diseases Department, APHP – Tenon Hospital, Paris, France; 4Sorbonne University, GRC 04, UPMC Univ Paris 06, France Abstract: Around 4% of advanced non-small-cell lung cancers (NSCLCs have an ALK rearrangement at the time of diagnosis. This molecular feature is more frequent in young patients, with no/light smoking habit and with adenocarcinoma pathological subtype. Crizotinib is a tyrosine kinase inhibitor, targeting ALK, ROS1, RON, and MET. The preclinical efficacy results led to a fast-track clinical development. The US Food and Drug Administration (FDA approval was achieved after the Phase I clinical trial in 2011 in ALK-rearranged advanced NSCLC progressing after a first-line treatment. In 2013, the randomized Phase III trial PROFILE-1007 confirmed the efficacy of crizotinib in ALK-rearranged NSCLC, compared to cytotoxic chemotherapy, in second-line setting or more. In 2014, the PROFILE-1014 trial showed the superiority of crizotinib in the first-line setting compared to the pemetrexed platinum doublet chemotherapy. The response rate was 74%, and the progression-free survival was 10.9 months with crizotinib. Based on these results, crizotinib received approval from the FDA and European Medicines Agency for first-line treatment of ALK-rearranged NSCLC. The various molecular mechanisms at the time of the progression (ALK mutations or amplification, ALK-independent mechanisms encourage performing re-biopsy at the time of progression under crizotinib. The best treatment strategy at the progression (crizotinib continuation beyond progression, switch to second-generation tyrosine kinase inhibitors, or cytotoxic chemotherapy depends on the phenotype of the progression, the

  6. Printed educational messages fail to increase use of thiazides as first-line medication for hypertension in primary care: a cluster randomized controlled trial [ISRCTN72772651].

    Science.gov (United States)

    Zwarenstein, Merrick; Grimshaw, Jeremy M; Presseau, Justin; Francis, Jill J; Godin, Gaston; Johnston, Marie; Eccles, Martin P; Tetroe, Jacqueline; Shiller, Susan K; Croxford, Ruth; Kelsall, Diane; Paterson, J Michael; Austin, Peter C; Tu, Karen; Yun, Lingsong; Hux, Janet E

    2016-09-17

    Evidence on the effectiveness of printed educational messages in contributing to increasing evidence-based clinical practice is contradictory. Nonetheless, these messages flood physician offices, in an attempt to promote treatments that can reduce costs while improving patient outcomes. This study evaluated the ability of printed educational messages to promote the choice of thiazides as the first-line treatment for individuals newly diagnosed with hypertension, a practice supported by good evidence and included in guidelines, and one which could reduce costs to the health care system. The study uses a pragmatic, cluster randomized controlled trial (randomized by physician practice group). The setting involves all Ontario general/family practice physicians. Messages advising the use of thiazides as the first-line treatment of hypertension were mailed to each physician in conjunction with a widely read professional newsletter. Physicians were randomized to receive differing versions of printed educational messages: an "insert" (two-page evidence-based article) and/or one of two different versions of an "outsert" (short, directive message stapled to the outside of the newsletter). One outsert was developed without an explicit theory and one with messages developed targeting factors from the theory of planned behaviour or neither (newsletter only, with no mention of thiazides). The percentage of patients aged over 65 and newly diagnosed with hypertension who were prescribed a thiazide as the sole initial prescription medication. The effect of the intervention was estimated using a logistic regression model estimated using generalized estimating equation methods to account for the clustering of patients within physician practices. Four thousand five hundred four physicians (with 23,508 patients) were randomized, providing 97 % power to detect a 5 % absolute increase in prescription of thiazides. No intervention effect was detected. Thiazides were prescribed to 27.6

  7. Melanoma Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing melanoma cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  8. Congenital uveal melanoma?

    Science.gov (United States)

    Singh, Arun D; Schoenfield, Lynn A; Bastian, Boris C; Aziz, Hassan A; Marino, Meghan J; Biscotti, Charles V

    2016-01-01

    A 3-month-old infant with a white mother and Asian father presented with discoloration and prominence of the left eye since birth. Examination revealed a normal right eye. The left eye had hyperchromic heterochromia and an enlarged cornea (diameter, 13.0 mm) with intraocular pressure of 26 mm Hg. There were multiple areas of subconjunctival nodular pigmentation that extended posteriorly into the superior fornix. Fundus examination showed a large ciliochoroidal pigmented mass extending from 10:30 to 3:00 o'clock position involving the superior half of the choroid and adjacent ciliary body. The eye was enucleated, confirming the diagnosis of diffuse uveal melanoma with extraocular extension. Systemic surveillance (hepatic panel and ultrasonography of the liver) performed every 6 months for 5 years was has been negative for metastases. The tumor was investigated intensively for the panel of genes (BAP1, BRAF, NRAS12, NRAS61, GNAQ, Kit 9,11,13,17,18) implicated in pathogenesis of blue nevus, cutaneous melanoma, and mucosal melanomas with negative results. Moreover, germline BAP1 mutation could not be identified. This case possibly represents as yet unidentified uveal melanocytic proliferation rather than a true variant of uveal melanoma. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Interleukin-6 and melanoma

    DEFF Research Database (Denmark)

    Hoejberg, Lise; Bastholt, Lars; Schmidt, Henrik

    2012-01-01

    Interleukin-6 (IL-6) is a pleiotropic immunomodulatory cytokine produced by various types of cells, including melanoma cells. IL-6 plays a major role in the pathogenesis and development of malignancies. It promotes tumour growth by inhibition of apoptosis and induces tumour angiogenesis. IL-6...

  10. A cost-effectiveness and budget impact analysis of first-line fidaxomicin for patients with Clostridium difficile infection (CDI) in Germany.

    Science.gov (United States)

    Watt, Maureen; McCrea, Charles; Johal, Sukhvinder; Posnett, John; Nazir, Jameel

    2016-10-01

    Clostridium difficile infection (CDI) represents a significant economic healthcare burden, especially the cost of recurrent disease. Fidaxomicin produced significantly lower recurrence rates and higher sustained cure rates in clinical trials. We evaluated the cost-effectiveness and budget impact of fidaxomicin compared with vancomycin in Germany in the first-line treatment of patient subgroups with CDI at increased risk of recurrence. A semi-Markov model was used to compare the cost-effectiveness and budget impact of fidaxomicin vs. vancomycin from a payer perspective in Germany. The model cycle length was 10 days. The time horizon was 1 year. Model inputs were probability of clinical cure, 30-day probability of recurrence, and 30-day attributable mortality based on evidence from two randomized controlled trials comparing fidaxomicin and vancomycin in patients with CDI. Cost-effectiveness outcomes were cost per quality-adjusted life year gained, cost per bed-day saved, and cost per recurrence avoided. Despite higher drug acquisition costs, fidaxomicin was dominant in the cancer subgroup (less costly and more effective) and cost-effective in the other subgroups, with incremental cost-effectiveness ratios vs. vancomycin ranging from €26,900 to €44,500. Hospitalization costs of the first-line treatment of CDI with fidaxomicin vs. vancomycin were lower in every patient subgroup, resulting in budget impacts ranging from -€1325 (in patients ≥65 years) to -€2438 (in cancer patients). Reductions in the cost of treating recurrence with fidaxomicin ranged from -€574.32 per patient in those receiving concomitant antibiotics to -€1500.68 per patient in renally impaired patients. In patient subgroups with CDI at increased recurrence risk, fidaxomicin was cost-effective vs. vancomycin, and less costly and more effective in patients with cancer.

  11. Phase II study of cetuximab as first-line single-drug therapy in patients with unresectable squamous cell carcinoma of the skin.

    Science.gov (United States)

    Maubec, Eve; Petrow, Peter; Scheer-Senyarich, Isabelle; Duvillard, Pierre; Lacroix, Ludovic; Gelly, Julien; Certain, Agnès; Duval, Xavier; Crickx, Béatrice; Buffard, Valérie; Basset-Seguin, Nicole; Saez, Pierre; Duval-Modeste, Anne-Bénédicte; Adamski, Henri; Mansard, Sandrine; Grange, Florent; Dompmartin, Anne; Faivre, Sandrine; Mentré, France; Avril, Marie-Françoise

    2011-09-01

    To evaluate the efficacy and safety of cetuximab, a monoclonal antibody that inhibits the epidermal growth factor receptor (EGFR), as a first-line monotherapy in patients with unresectable squamous cell carcinoma of the skin (SCCS). Thirty-six patients received cetuximab (initial dose of 400 mg/m(2) followed by subsequent weekly doses of 250 mg/m(2)) for at least 6 weeks with a 48-week follow-up. The primary end point was the disease control rate (DCR) at 6 weeks (according to Response Evaluation Criteria in Solid Tumors [RECIST] criteria). Secondary end points included best response rate, overall survival, progression-free survival (PFS), and toxicity assessment. Association of treatment efficacy with RAS mutations or FcγR genotypes was investigated. Median age of the study population was 79 years. DCR at 6 weeks was obtained in 25 of 36 patients (69%; 95% CI, 52% to 84%) of the intention-to-treat population. The best responses were eight partial responses and two complete responses. There were no cetuximab-related deaths. There were three related serious adverse events: two grade 4 infusion reactions and one grade 3 interstitial pneumopathy. Grade 1 to 2 acne-like rash occurred in 78% of patients and was associated with prolonged PFS. One HRAS mutation was identified. Combined FcγRIIa-131H/H and/or FcγRIIIa-158V/V polymorphisms were not associated with the clinical outcomes. As a first-line treatment in patients with unresectable SCCS, cetuximab achieved 69% DCR. A randomized phase III trial is warranted to confirm that cetuximab may be considered as a therapeutic option especially in elderly patients. The low frequency of RAS mutations in SCCS makes SCCS tumors attractive for EGFR inhibition.

  12. A pilot study of first-line chemotherapy with 5-FU and Platinum in advanced and recurrent cancer of the cervix

    Directory of Open Access Journals (Sweden)

    Ghaemmaghami F

    2003-06-01

    Full Text Available This study was designed to assess the role of first-line chemotherapy with 5-FU and platinum in the treatment of advanced or recurrent cervical cancer, ten patients with advanced or recurrent cancer of the cervix, with no prior chemotherapy were entered in phase II trial, from Oct. 2000 to Nov. 2001. Eight patients were treated with cis-platinum (50 mg/m2 over 60 minutes in first day followed by 5-FU (1 g/m2 over 24 hours for 4 days and two patients with impaired renal function were treated with carboplatin (300 mg/m2 over 15 minutes in first day followed by 5-FU (1 g/m2 over 24 hours for 4 days every three weeks, until progression of disease or prohibitive toxicity had been observed. Median age was 52 years (range: 28-70 years. Ten patients received a total of 42 cycles of chemotherapy. The mean number of chemotherapy cycles was 4.2 (median 4, range: 3-7. Three patients had partial response (30%, CI, 1.7%-58.5%. Mean response duration was 198 days (range: 122-273 days. Four patients required red blood cell transfusions; three of them had grade II and one of them grade III nausea and vomiting Two had fever and neutropenia (one developed acute renal insufficiency, and there wee no treatment related mortalities. First-line chemotherapy with platinum and 5-FU for advanced recurrent cervical cancer is promising and deserves consideration for large phase III trials.

  13. Gemcitabine plus docetaxel as first-line chemotherapy in patients with advanced non-small cell lung cancer: a lung cancer Galician group phase II study.

    Science.gov (United States)

    Casal, Joaquín; Amenedo, Margarita; Mel, José Ramón; Antón, Luis Miguel; Rodríguez-López, Rubén; López-López, Rafael; González-Ageitos, Ana; Castellanos, Javier; Constenla, Manuel; Tisaire, José L

    2007-10-01

    Numerous phase II and III clinical trials have demonstrated a higher activity of combined gemcitabine plus docetaxel schedules against non-small cell lung cancer (NSCLC) than that of both agents in monotherapy. This phase II study evaluated a 3-week based schedule of docetaxel 85 mg/m(2) (1-h i.v. infusion, d8) combined with gemcitabine 1,000 mg/m(2) (30-min i.v. infusion; d1,8) as first-line chemotherapy for patients with advanced NSCLC. Forty-one patients with non-resectable, stage IIIB/IV, and bidimensionally measurable disease were enrolled. A total of 182 chemotherapy cycles (median 6, range 1-6) was administered to 40 patients during the study; one patient did not receive chemotherapy due to a protocol deviation. Two patients were not evaluable for treatment efficacy. The overall response rate found was 44% (95% CI, 29-59%): three patients (7%) had a complete response and 15 patients (37%) had a partial response (median duration of response = 4.0 months). With a median follow-up of 8.7 months, the median time to disease progression was 4.4 months and the median overall survival was 7.3 months. The combined gemcitabine plus docetaxel chemotherapy was well tolerated except for pulmonary toxicity. The main grade 3-4 hematological toxicity was neutropenia (28% of patients, 9% of cycles). Two cases of febrile neutropenia were reported. The main grade 3-4 non-hematological toxicity was pulmonary toxicity (23% of patients, 6% of cycles). Gemcitabine 1,000 mg/m(2) on days 1 and 8 in combination with docetaxel 85 mg/m(2) on day 8 given in 3-week cycles is an active and well-tolerated first-line chemotherapeutic regimen for advanced NSCLC.

  14. A Triple and Quadruple Therapy with Doxycycline and Bismuth for First-Line Treatment of Helicobacter pylori Infection: A Pilot Study.

    Science.gov (United States)

    Ciccaglione, Antonio Francesco; Cellini, Luigina; Grossi, Laurino; Manzoli, Lamberto; Marzio, Leonardo

    2015-10-01

    Tetracycline-containing triple therapy has been suggested as an alternative first-line therapy for H. pylori infection. To evaluate the effect of two dosages of doxycycline (DOX) associated with amoxicillin and esomeprazole with and without bismuth subcitrate as first-line treatment of H. pylori infection. Helicobacter pylori-positive patients underwent a 10-day therapy randomized into four groups: Group A received esomeprazole, amoxicillin, and DOX-100 mg b.i.d. (EAD-100), Group B a quadruple therapy with esomeprazole, amoxicillin, DOX-100 mg b.i.d. and bismuth subcitrate (EADB-100), Group C a triple therapy with esomeprazole, amoxicillin, and DOX-200 mg b.i.d. (EAD-200) and Group D a quadruple therapy with esomeprazole, amoxicillin, DOX-200 mg b.i.d., and bismuth subcitrate (EADB-200). Success was accessed by (13)C urea breath test 2 months after the end of treatment. The number of patients to be recruited for each group had to be at least 50 subjects. Treatment success of 80% or less was considered unacceptable. Stopping rules therefore were anytime six failures had occurred. In the EAD-100 group and in EAD-200 group, the recruitment was stopped at the 14th and 15th patient, respectively. Fifty-two patients entered in the EADB-100 group and 51 in the EADB-200 group. Intention to treat eradication was in EADB-100 group 46/52 (88.5%, 95% CI 76.6-95.6); in the EADB-200 group 47/51 (92.1%, 95% CI: 81.1-97.8) (n.s.). Side effects were absent. The adjunction of bismuth subcitrate to a triple therapy that includes esomeprazole, amoxicillin, and DOX in patients who are treated for the first time for the H. pylori infection potentiates the therapeutic effect. This regimen, however, deserves to be optimized in terms of duration and dose of DOX. © 2015 John Wiley & Sons Ltd.

  15. Melanoma risk prediction models

    Directory of Open Access Journals (Sweden)

    Nikolić Jelena

    2014-01-01

    Full Text Available Background/Aim. The lack of effective therapy for advanced stages of melanoma emphasizes the importance of preventive measures and screenings of population at risk. Identifying individuals at high risk should allow targeted screenings and follow-up involving those who would benefit most. The aim of this study was to identify most significant factors for melanoma prediction in our population and to create prognostic models for identification and differentiation of individuals at risk. Methods. This case-control study included 697 participants (341 patients and 356 controls that underwent extensive interview and skin examination in order to check risk factors for melanoma. Pairwise univariate statistical comparison was used for the coarse selection of the most significant risk factors. These factors were fed into logistic regression (LR and alternating decision trees (ADT prognostic models that were assessed for their usefulness in identification of patients at risk to develop melanoma. Validation of the LR model was done by Hosmer and Lemeshow test, whereas the ADT was validated by 10-fold cross-validation. The achieved sensitivity, specificity, accuracy and AUC for both models were calculated. The melanoma risk score (MRS based on the outcome of the LR model was presented. Results. The LR model showed that the following risk factors were associated with melanoma: sunbeds (OR = 4.018; 95% CI 1.724- 9.366 for those that sometimes used sunbeds, solar damage of the skin (OR = 8.274; 95% CI 2.661-25.730 for those with severe solar damage, hair color (OR = 3.222; 95% CI 1.984-5.231 for light brown/blond hair, the number of common naevi (over 100 naevi had OR = 3.57; 95% CI 1.427-8.931, the number of dysplastic naevi (from 1 to 10 dysplastic naevi OR was 2.672; 95% CI 1.572-4.540; for more than 10 naevi OR was 6.487; 95%; CI 1.993-21.119, Fitzpatricks phototype and the presence of congenital naevi. Red hair, phototype I and large congenital naevi were

  16. Melanoma of the clavicular region: multimodal treatment.

    Science.gov (United States)

    Lam, L; Krementz, E; McGinness, C; Godfrey, R

    2001-09-01

    Treatment for melanoma that has metastasized to the supraclavicular nodes should be intensive and use a multimodality approach. Retrospective analysis of clinical records. Six primary care centers, 2 of which were referral centers. Eighteen patients diagnosed as having a rare pattern of advanced melanoma metastatic to the clavicular region. Combined radiotherapy, chemotherapy, and thorough surgical excision of the affected nodal basins. Length of survival from time of diagnosis and treatment to time of follow-up. Median survival among the 18 patients was 28 months with a 22% survival rate at 5 years after diagnosis. Among patients who received radiotherapy to the clavicular node basin, mean length of survival was 88.7 months with a 50% 5-year survival rate compared with a mean length of survival of 33.8 months and an 8.3% 5-year survival rate in patients who did not receive radiotherapy (Pbasin and continued to be disease-free at 82 and 130 months. All long-term survivors had been treated with intra-arterial chemotherapy. In a series of patients with malignant melanoma metastatic to the clavicular lymph nodes, multimodality treatment using radiotherapy, chemotherapy, and thorough surgical excision of affected nodal basins provided an appreciable 5-year survival rate.

  17. RARE METASTASES OF MALIGNANT MELANOMA

    Directory of Open Access Journals (Sweden)

    Marija Trenkić-Božinović

    2014-09-01

    Full Text Available Melanomas are malignant neoplasms that originate from melanocytes. The most common are on the skin and mucous membranes. Choroidal melanomas are quite different from cutaneous melanomas with regard to presentation, metastases, and treatment. We report two cases of metastatic gastric malignant melanoma of the eye and skin, with reference to the literature. The first patient was a woman aged 23 years, who underwent gastrectomy 22 months after enucleation of the eye due to malignant choroid melanoma. The second patient was a man, 72 years old, who underwent surgery 28 months before because of malignant melanoma of the skin of the forehead. Paraffin sections, 4 μm thick were stained using a classic method, as well as immunohistochemical DAKO APAAP method, using a specific S - 100 antibody and Melan A antibodies. The stomach is considered a rare place for the development of metastases. Metastases in the stomach are often limited to the submucosal as well as the serousmuscular layer, as noted in one of our patients. Metastatic melanoma of the gastrointestinal tract should be suspected in any patient with a history of malignant melanoma and new gastrointestinal symptoms. Because of the similarity between certain common histopathological types of malignant melanoma, primarily achromatic, and types of primary cancers of the stomach, the following immunohistochemical studies are needed: Melan A and S - 100 protein ( markers of malignant melanoma , as well as mucins: MUC5AC, MUC2 and CDX2 ( markers of different types of primary gastric carcinoma.

  18. Multicenter pilot study of radiochemotherapy as first-line treatment for adults with medulloblastoma (NOA-07).

    Science.gov (United States)

    Beier, Dagmar; Proescholdt, Martin; Reinert, Christiane; Pietsch, Torsten; Jones, David T W; Pfister, Stefan M; Hattingen, Elke; Seidel, Clemens; Dirven, Linda; Luerding, Ralf; Reijneveld, Jaap; Warmuth-Metz, Monika; Bonsanto, Matteo; Bremer, Michael; Combs, Stephanie E; Rieken, Stefan; Herrlinger, Ulrich; Kuntze, Holger; Mayer-Steinacker, Regine; Moskopp, Dag; Schneider, Thomas; Beringer, Andreas; Schlegel, Uwe; Stummer, Walter; Welker, Helmut; Weyerbrock, Astrid; Paulsen, Frank; Rutkowski, Stefan; Weller, Michael; Wick, Wolfgang; Kortmann, Rolf-Dieter; Bogdahn, Ulrich; Hau, Peter

    2018-02-19

    Medulloblastoma in adult patients is rare, with 0.6 cases per million. Prognosis depends on clinical factors and medulloblastoma entity. No prospective data on the feasibility of radiochemotherapy exist. The German Neuro-Oncology Working Group (NOA) performed a prospective descriptive multicenter single-arm phase II trial to evaluate feasibility and toxicity of radio-polychemotherapy. The NOA-07 trial combined craniospinal irradiation with vincristine, followed by 8 cycles of cisplatin, lomustine, and vincristine. Adverse events, imaging and progression patterns, histological and genetic markers, health-related quality of life (HRQoL), and cognition were evaluated. Primary endpoint was the rate of toxicity-related treatment terminations after 4 chemotherapy cycles, and the toxicity profile. The feasibility goal was reached if at least 45% of patients received at least 4 cycles of maintenance chemotherapy. Thirty patients were evaluable. Each 50% showed classic and desmoplastic/nodular histology. Sixty-seven percent were classified into the sonic hedgehog (SHH) subgroup without TP53 alterations, 13% in wingless (WNT), and 17% in non-WNT/non-SHH. Four cycles of chemotherapy were feasible in the majority (n = 21; 70.0%). Hematological side effects and polyneuropathy were prevalent toxicities. During the active treatment period, HRQoL and verbal fluency improved significantly. The 3-year event-free survival rate was 66.6% at the time of databank lock. Radio-polychemotherapy did lead to considerable toxicity and a high amount of dose reductions throughout the first 4 chemotherapy cycles that may affect efficacy. Thus, we propose frequent patient surveillance using this regimen. Modifications of the regimen may increase feasibility of radio-polychemotherapy of adult patients with medulloblastoma. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  19. Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC

    Science.gov (United States)

    Besse, Benjamin; Charrier, Mélinda; Lapierre, Valérie; Dansin, Eric; Lantz, Olivier; Planchard, David; Le Chevalier, Thierry; Livartoski, Alain; Barlesi, Fabrice; Laplanche, Agnès; Ploix, Stéphanie; Vimond, Nadège; Peguillet, Isabelle; Théry, Clotilde; Lacroix, Ludovic; Zoernig, Inka; Dhodapkar, Kavita; Dhodapkar, Madhav; Viaud, Sophie; Soria, Jean-Charles; Reiners, Katrin S.; Pogge von Strandmann, Elke; Vély, Frédéric; Rusakiewicz, Sylvie; Eggermont, Alexander; Pitt, Jonathan M.; Zitvogel, Laurence; Chaput, Nathalie

    2016-01-01

    ABSTRACT Dendritic cell-derived exosomes (Dex) are small extracellular vesicles secreted by viable dendritic cells. In the two phase-I trials that we conducted using the first generation of Dex (IFN-γ-free) in end-stage cancer, we reported that Dex exerted natural killer (NK) cell effector functions in patients. A second generation of Dex (IFN-γ-Dex) was manufactured with the aim of boosting NK and T cell immune responses. We carried out a phase II clinical trial testing the clinical benefit of IFN-γ-Dex loaded with MHC class I- and class II-restricted cancer antigens as maintenance immunotherapy after induction chemotherapy in patients bearing inoperable non-small cell lung cancer (NSCLC) without tumor progression. The primary endpoint was to observe at least 50% of patients with progression-free survival (PFS) at 4 mo after chemotherapy cessation. Twenty-two patients received IFN-γ-Dex. One patient exhibited a grade three hepatotoxicity. The median time to progression was 2.2 mo and median overall survival (OS) was 15 mo. Seven patients (32%) experienced stabilization of >4 mo. The primary endpoint was not reached. An increase in NKp30-dependent NK cell functions were evidenced in a fraction of these NSCLC patients presenting with defective NKp30 expression. Importantly, MHC class II expression levels of the final IFN-γ-Dex product correlated with expression levels of the NKp30 ligand BAG6 on Dex, and with NKp30-dependent NK functions, the latter being associated with longer progression-free survival. This phase II trial confirmed the capacity of Dex to boost the NK cell arm of antitumor immunity in patients with advanced NSCLC. PMID:27141373

  20. [Therapeutic strategies and systemic treatment of brain melanoma metastases].

    Science.gov (United States)

    Durando, Xavier; Mansard, Sandrine; Daste, Amaury; Gimbergues, Pierre; Brocard, Laura; Magné, Nicolas; Thivat, Emilie

    2013-01-01

    Brain metastases affect 37% of patients suffering from metastatic melanoma, and their prognosis remains poor, with an overall survival lower than six months. At the moment, there is no standard therapeutic strategy for management of melanoma brain metastases. In some cases, having recourse to a systemic treatment is justified, for example, when brain metastases are combined with a progressive peripheral disease, or with unresecable brain lesions. In France, the use of fotemustine, which received the AMM approval, for metastatic melanoma treatment, is one of the treatments recommended in the case of brain metastases as this chemotherapy, that is active on the melanoma passes the blood-brain barrier. Temozolomide also shows some activity in the brain metastases treatment of melanoma that remains modest in monotherapy but seems interesting when it is combined with radiotherapy. The place of new drugs, in particular ipilimumab and vemurafenib, in the strategy of melanoma brain metastases treatment, still has to be defined and may improve the prognosis of these patients and their quality of life. The new targeted therapies, the widespread use of stereotactic radiosurgery and the improvement in neurosurgical operations would need a prospective clinical assessment, all the more so, in most of clinical studies, the presence of metastases is an exclusion criterion.

  1. Computed tomography and magnetic resonance imaging study of uveal melanoma

    International Nuclear Information System (INIS)

    Xian Junfang; Wang Zhenchang; Yan Fei

    1998-01-01

    Purpose: To study CT and MRI findings of uveal melanoma and detect the most appropriate MRI scanning sequences. Materials and methods: A series of MRI scanning sequences were performed in 15 cases, and CT was performed in 11 cases. MRI and CT findings were compared with pathologic, operative and clinical findings. Results: Of 11 cases receiving CT scanning, 9 displayed iso-density masses with respect to extraocular muscles. The other two tumors were too small to be demonstrated. Fourteen cases of melanoma showed characteristic MR appearances with hyperintense signal with respect to the vitreous on T 1 -weighted images and hypointense with respect to the vitreous on T 2 -weighted images. One case of iris melanoma only 3 mm in height was not demonstrated on T 1 -weighted images, but was displayed hypointense signal on T 2 -weighted images. Eleven cases associated with retinal detachment showed high intensity signal on T 1 - and T 2 -weighted images and could not be distinguished from melanoma. Postcontrast T 1 -weighted images with fat suppression technique were found to be the most helpful in detecting and delineating small melanomas less than 5 mm as well as distinguishing them from retinal detachment. Conclusion: MRI was superior to ultrasound or CT. Collaborative diagnosis including clinical, ultrasonographic, CT and MRI examinations is the best for ocular melanoma

  2. The predictive value of single nucleotide polymorphisms in the VEGF system to the efficacy of first-line treatment with bevacizumab plus chemotherapy in patients with metastatic colorectal cancer : Results from the Nordic ACT trial

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Christensen, René Depont; Andersen, Rikke Fredslund

    2012-01-01

    PURPOSE: Bevacizumab and chemotherapy is a common choice for first-line treatment of metastatic colorectal cancer (mCRC). So far, no predictive markers have been identified. The aim was to investigate the possible predictive value of single nucleotide polymorphisms (SNPs) in the vascular endothel......PURPOSE: Bevacizumab and chemotherapy is a common choice for first-line treatment of metastatic colorectal cancer (mCRC). So far, no predictive markers have been identified. The aim was to investigate the possible predictive value of single nucleotide polymorphisms (SNPs) in the vascular...... endothelial growth factor (VEGF) system in this setting. METHODS: Pre-treatment blood samples and response evaluations were available from 218 of the 249 included patients. All patients received bevacizumab and chemotherapy comprising fluorouracil and leucovorin or capecitabine combined with either...... marker for bevacizumab plus chemotherapy in patients with mCRC. Patients with the A allele appeared to have increased response rates. The results call for validation....

  3. Communication about melanoma and risk reduction after melanoma diagnosis.

    Science.gov (United States)

    Rodríguez, Vivian M; Berwick, Marianne; Hay, Jennifer L

    2017-12-01

    Melanoma patients are advised to perform regular risk-reduction practices, including sun protection as well as skin self-examinations (SSEs) and physician-led examinations. Melanoma-specific communication regarding family risk and screening may promote such behaviors. To this end, associations between patients' melanoma-specific communication and risk reduction were examined. Melanoma patients (N = 169) drawn from a population-based cancer registry reported their current risk-reduction practices, perceived risk of future melanoma, and communication with physicians and relatives about melanoma risk and screening. Patients were, on average, 56 years old and 6.7 years' post diagnosis; 51% were male, 93% reported "fair/very fair" skin color, 75% completed at least some college, and 22% reported a family history of melanoma. Patients reported varying levels of regular (always/nearly always) sun protection: sunscreen use (79%), shade seeking (60%), hat use (54%), and long-sleeve shirt use (30%). Only 28% performed thorough SSE regularly, whereas 92% reported undergoing physician-led skin examinations within the past year. Participants who were female, younger, and had a higher perceived risk of future melanoma were more likely to report past communication. In adjusted analyses, communication remained uniquely associated with increased sunscreen use and SSE. Encouraging melanoma patients to have a more active role in discussions concerning melanoma risk and screening with relatives and physicians alike may be a useful strategy to promote 2 key risk-reduction practices post melanoma diagnosis and treatment. Future research is needed to identify additional strategies to improve comprehensive risk reduction in long-term melanoma patients. Copyright © 2016 John Wiley & Sons, Ltd.

  4. Books Received

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. Books Received. Articles in Resonance – Journal of Science Education. Volume 1 Issue 1 January 1996 pp 118-118 Books Received. Books Received · More Details Fulltext PDF. Volume 1 Issue 2 February 1996 pp 120-120 Books Received. Books Received.

  5. Nomogram-based Prediction of Overall Survival in Patients with Metastatic Urothelial Carcinoma Receiving First-line Platinum-based Chemotherapy

    DEFF Research Database (Denmark)

    Necchi, Andrea; Sonpavde, Guru; Lo Vullo, Salvatore

    2017-01-01

    BACKGROUND: The available prognostic models for overall survival (OS) in patients with metastatic urothelial carcinoma (UC) have been derived from clinical trial populations of cisplatin-treated patients. OBJECTIVE: To develop a new model based on real-world patients. DESIGN, SETTING, AND PARTICI...

  6. Resin-based Yttrium-90 microspheres for unresectable and failed first-line chemotherapy intrahepatic cholangiocarcinoma: preliminary results.

    Science.gov (United States)

    Jia, Zhongzhi; Paz-Fumagalli, Ricardo; Frey, Gregory; Sella, David M; McKinney, J Mark; Wang, Weiping

    2017-03-01

    To evaluate the value of resin-based yttrium-90 ( 90 Y) radioembolization for unresectable and failed first-line chemotherapy (cisplatin plus gemcitabine) intrahepatic cholangiocarcinoma (ICC). From February 2006 to September 2015, a retrospective study was conducted of all patients who underwent resin-based 90 Y therapy for unresectable and failed first-line chemotherapy ICC. Tumor response was assessed using modified RECIST criteria; side effects were assessed using Common Terminology Criteria for Adverse Events version 4.03; survivals were calculated from the date of diagnosis of ICC, beginning of first-line chemotherapy and first 90 Y procedure, respectively; effects of factors on survival were analyzed by Cox regression model. Twenty-four patients (eight male and 16 female) were included in this study. Mean 5.6 ± 1.6 cycles of first-line chemotherapy were performed prior to 90 Y treatment. The mean delivered activity of 90 Y was 1.6 ± 0.4 GBq with a total of 27 treatments. Disease control rate was 81.8% at 3 months after 90 Y therapy, with partial response (n = 8, 36.4%), stable disease (n = 10, 45.5%) and progressive disease (n = 6, 18.2%). CA199 changes pre- and 1 month post-treatment were complete (n = 2), partial (n = 2), none (n = 5) and progression (n = 2), respectively. Side effects included fatigue (n = 21, 87.5%), anorexia (n = 19, 79.2%), nausea (n = 15, 62.5%), abdominal pain (n = 10, 58.3%), vomiting (n = 4, 16.7%) and fever (n = 3, 12.5%). Radiation-induced gastrointestinal ulcer was identified in one patient. The mean follow-up was 11.3 ± 6.6 months, and the median survivals from the time of diagnosis of ICC, beginning of first-line chemotherapy and first 90 Y procedure were 24.0, 16.0 and 9.0 months, respectively, and the 6-, 12-, 18-, 24- and 30-month survival after 90 Y therapy were 69.9, 32.6, 27.2, 20.4 and 20.4%, respectively. ECOG performance status (P = 0.002) and lymph node metastases (P = 0

  7. Risk Factors for Incident Diabetes in a Cohort Taking First-Line Nonnucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy.

    Science.gov (United States)

    Karamchand, Sumanth; Leisegang, Rory; Schomaker, Michael; Maartens, Gary; Walters, Lourens; Hislop, Michael; Dave, Joel A; Levitt, Naomi S; Cohen, Karen

    2016-03-01

    Efavirenz is the preferred nonnucleoside reverse transcriptase inhibitor (NNRTI) in first-line antiretroviral therapy (ART) regimens in low- and middle-income countries, where the prevalence of diabetes is increasing. Randomized control trials have shown mild increases in plasma glucose in participants in the efavirenz arms, but no association has been reported with overt diabetes. We explored the association between efavirenz exposure and incident diabetes in a large Southern African cohort commencing NNRTI-based first-line ART. Our cohort included HIV-infected adults starting NNRTI-based ART in a private sector HIV disease management program from January 2002 to December 2011. Incident diabetes was identified by the initiation of diabetes treatment. Patients with prevalent diabetes were excluded. We included 56,298 patients with 113,297 patient-years of follow-up (PYFU) on first-line ART. The crude incidence of diabetes was 13.24 per 1000 PYFU. Treatment with efavirenz rather than nevirapine was associated with increased risk of developing diabetes (hazard ratio 1.27 (95% confidence interval (CI): 1.10-1.46)) in a multivariate analysis adjusting for age, sex, body mass index, baseline CD4 count, viral load, NRTI backbone, and exposure to other diabetogenic medicines. Zidovudine and stavudine exposure were also associated with an increased risk of developing diabetes. We found that treatment with efavirenz, as well as stavudine and zidovudine, increased the risk of incident diabetes. Interventions to detect and prevent diabetes should be implemented in ART programs, and use of antiretrovirals with lower risk of metabolic complications should be encouraged.

  8. Biofeedback as a first-line treatment for overactive bladder syndrome refractory to standard urotherapy in children.

    Science.gov (United States)

    Ebiloglu, Turgay; Kaya, Engin; Köprü, Burak; Topuz, Bahadır; Irkilata, Hasan Cem; Kibar, Yusuf

    2016-10-01

    Overactive bladder syndrome (OAB) and dysfunctional voiding (DV) are subgroups of lower urinary tract dysfunction (LUTD). Standard urotherapy is the first-line treatment option of OAB in children. The aim was to investigate the use of biofeedback as a first-line treatment option in OAB refractory to standard urotherapy, and determine the factors affecting efficacy. Between 2005 and 2015, we retrospectively analyzed a total of 136 hospital records of children with OAB who had not previously used any anticholinergics and were refractory to standard urotherapy. Patients with urgency and/or urge incontinence and/or making holding maneuvers to suppress urgency were defined as having OAB symptoms, and resolution of these complaints was defined as successful biofeedback therapy. Seventy-three of 136 OAB patients' urgency recovered by biofeedback therapy with the success rate of 53% (p < 0.001). Sixty-two of 101 patients with holding maneuvers (success rate 61%) (p < 0.001), 70 of 101 patients with urgency incontinence (success rate 69%) (p < 0.001), 76 of 114 patients with daytime incontinence (success rate 66%) (p = 0.023), 87 of 97 patients with enuresis (success rate 89%) (p = 0.009), and 27 of 39 patients with dysuria (success rate 69%) (p = 0.007) recovered from their symptoms significantly. The mean lower urinary tract symptom score (LUTSS) was 16.38 and 8.18 before and after biofeedback therapies, respectively (p < 0.001) (Table). Patients without holding maneuvers (p = 0.045), daytime incontinence (p = 0.030), and enuresis (p = 0.045) had better recovery compared to the opposites. Biofeedback can be thought of as the first-line treatment option when standard urotherapy fails in children with OAB. Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  9. HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia

    Science.gov (United States)

    Jiamsakul, Awachana; Sungkanuparph, Somnuek; Law, Matthew; Kantor, Rami; Praparattanapan, Jutarat; Li, Patrick CK; Phanuphak, Praphan; Merati, Tuti; Ratanasuwan, Winai; Lee, Christopher KC; Ditangco, Rossana; Mustafa, Mahiran; Singtoroj, Thida; Kiertiburanakul, Sasisopin

    2014-01-01

    Introduction First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. Methods We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance – Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥2 TAMs; or M184V+≥1 TAM. Virological suppression was defined as viral load (VL) 2 years (OR=6.25, 95% CI [2.39–16.36], p<0.001). Among 87/105 patients with available VL at 12 months after switch to second-line ART, virological suppression was achieved in 85%. The median genotypic susceptibility score (GSS) for the second-line regimen was 2.00. Patients with ART adherence ≥95% were more likely to be virologically suppressed (OR=9.33, 95% CI (2.43–35.81), p=0.001). Measures of patient resistance to second-line ART, including the GSS, were not significantly associated with virological outcome. Conclusions Multi-NRTI RAMs at first-line failure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving virological response. This emphasizes the importance of continued adherence counselling well into second-line therapy. PMID:25141905

  10. Response to first line HAART using CD4 cell counts experience in a university hospital in Kingston.

    Science.gov (United States)

    Clarke, T R; Barrow, G; Thompson, D; Gibson, R; Barton, E N

    2010-07-01

    To assess the extent to which the current practice for first line therapy concurs with the recommended guidelines and to examine the response of treatment naïve patients to first line Highly Active Antiretroviral Therapy (HAART) at the University Hospital of the West Indies, using CD4 cell counts. Over a three-month period, a cross-sectional study design was instituted and data were collected on all patients on HAARTat the University Hospital of the West Indies (UHWI) outpatient HIV clinic. Information was collected by reviewing patient medical records using data collection sheets. The data obtained from the medical records included: age, gender date of diagnosis of HIV date at which HAART was commenced, CD4 cell counts prior to the commencement of antiretrovirals, the initial HAART regimes and subsequent CD4 cell counts. A total of 165 persons who met the criteria of being on HAART therapy were enrolled in the study The average time span between diagnosis of HIV and commencement of antiretroviral therapy was 1.92 years and the range for this was 0 to 12.29 years. The average CD4 count prior to initiation of HAART was 186 cells/mm3. The most common regime used at the UHWI for first line therapy was combivir and efavirenz, n = 78 (47.3%), followed by combivir and nevirapine, n = 29 (17.6%). The average difference between the initial CD4 count prior to the initiation of HAART and first repeated CD4 count was 102 cells/mm3. The mean time between the first and repeated CD4 cell counts was 376 days. The recommended guidelines were adhered to for the majority of patients initiated on antiretrovirals at the UHWI. The treatment outcomes achieved at the UHWI were similar to those achieved in developed countries. This gives substantial evidence in support of international efforts to make antiretroviral therapy available in developing countries.

  11. Gemcitabine and irinotecan as first-line therapy for carcinoma of unknown primary: results of a multicenter phase II trial.

    Directory of Open Access Journals (Sweden)

    Shernan G Holtan

    Full Text Available Metastatic carcinoma of unknown primary (CUP has a very poor prognosis, and no standard first-line therapy currently exists. Here, we report the results of a phase II study utilizing a combination of gemcitabine and irinotecan as first-line therapy. Treatment was with gemcitabine 1000 mg/m(2 and irinotecan 75 mg/m(2 weekly times four on a six week cycle (Cohort I. Due to excessive toxicity, the dose and schedule were modified as follows: gemcitabine 750 mg/m(2 and irinotecan 75 mg/m(2 given weekly times three on a four week cycle (Cohort II. The primary endpoint was the confirmed response rate (CR + PR. Secondary endpoints consisted of adverse events based upon the presence or absence of the UDP glucuronosyltransferase 1 family, polypeptide A1*28 (UGT1A1*28 polymorphism, time to progression, and overall survival. Thirty-one patients were enrolled with a median age of 63 (range: 38-94, and 26 patients were evaluable for efficacy. Significant toxicity was observed in Cohort 1, characterized by 50% (7/14 patients experiencing a grade 4+ adverse event, but not in cohort II. The confirmed response rate including patients from both cohorts was 12% (95% CI: 2-30%, which did not meet the criteria for continued enrollment. Overall median survival was 7.2 months (95% CI: 4.0 to 11.6 for the entire cohort but notably longer in cohort II than in cohort I (9.3 months (95% CI: 4.1 to 12.1 versus 4.0 months (95% CI: 2.2 to 15.6. Gemcitabine and irinotecan is not an active combination when used as first line therapy in patients with metastatic carcinoma of unknown primary. Efforts into developing novel diagnostic and therapeutic approaches remain important for improving the outlook for this heterogeneous group of patients.ClinicalTrials.gov NCT00066781.

  12. Rituximab for the first-line maintenance treatment of follicular non-Hodgkin's lymphoma : a NICE single technology appraisal.

    Science.gov (United States)

    Greenhalgh, Janette; Bagust, Adrian; Boland, Angela; Blundell, Michaela; Oyee, James; Beale, Sophie; Dundar, Yenal; Hockenhull, Juliet; Proudlove, Chris; Chu, Patrick

    2013-05-01

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of rituximab (RTX) [Roche] to submit evidence for the clinical and cost effectiveness of RTX as first-line maintenance treatment for patients with follicular non-Hodgkin's lymphoma (fNHL) whose disease has responded to induction therapy with RTX plus cytotoxic chemotherapy (R-CTX) in accordance with the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarizes the ERG's review of the evidence submitted by the manufacturer and provides a summary of the Appraisal Committee's (AC) decision. The clinical evidence was derived from a multi-centred, open-label, randomized phase III study (PRIMA) comparing first-line maintenance treatment with RTX with observation only in 1,018 patients with previously untreated advanced fNHL. Median time to event (MTE) for the primary endpoint of progression-free survival (PFS) in the RTX arm was not estimable due to data immaturity; median PFS in the observation arm was 48.36 months. A statistically significant benefit of RTX maintenance therapy for PFS was reported (hazard ratio [HR] 0.55, 95 % CI 0.44-0.68; p Markov methodology rather than patient simulations, the impact of patient age on the outcome and the projective PFS modelling. The ERG considered it impossible to draw firm conclusions regarding the clinical or cost effectiveness of the intervention as the dataset was as yet too immature. At a third meeting, the AC concluded that RTX could be recommended as first-line maintenance treatment for patients with fNHL whose disease has responded to induction R-CTX.

  13. Glass Microspheres 90Y Selective Internal Radiation Therapy and Chemotherapy as First-Line Treatment of Intrahepatic Cholangiocarcinoma.

    Science.gov (United States)

    Edeline, Julien; Du, Fanny Le; Rayar, Michel; Rolland, Yan; Beuzit, Luc; Boudjema, Karim; Rohou, Tanguy; Latournerie, Marianne; Campillo-Gimenez, Boris; Garin, Etienne; Boucher, Eveline

    2015-11-01

    Intrahepatic cholangiocarcinoma's incidence is increasing. We studied the efficacy of Y selective internal radiation therapy (SIRT) as first-line treatment, with chemotherapy, and compared with the results of chemotherapy alone. We retrospectively studied data from patients treated at our institution with glass microspheres SIRT for intrahepatic cholangiocarcinoma as part of first-line treatment in combination with chemotherapy. We compared results with those of similar patients treated in the ABC-02 study (a study in advanced biliary tract cancer that defined the current standard chemotherapy), assessed as not progressing after the first evaluation. We assessed progression-free survival (PFS) and overall survival (OS). Twenty-four patients were treated with SIRT. Chemotherapy was given concomitantly in 10 (42%), as induction before SIRT in 13 (54%) or after SIRT in 1 (4%). Grade 3 adverse events were reported in 1 (4%). Median PFS after SIRT was 10.3 months. Longer PFS was observed when chemotherapy was given concomitantly than when chemotherapy was given before SIRT, with respective median of 20.0 versus 8.8 months (P = 0.001). Median OS after SIRT was not reached. Eleven patients went to surgery (46%). Thirty-three patients in ABC-02 had locally advanced nonextrahepatic cholangiocarcinoma, not progressing after first evaluation. From the start of any treatment, the median PFS was 16.0 months in our cohort versus 11.3 months in ABC-02 (P = 0.25), whereas the median OS was significantly higher in our cohort, not reached versus 17.9 months, respectively (P = 0.026). Selective internal radiation therapy combined with concomitant chemotherapy seems a promising strategy as first-line treatment for unresectable intrahepatic cholangiocarcinoma.

  14. First-line lesional aspiration in acute stroke thrombectomy using a novel intermediate catheter: Initial experiences with the SOFIA.

    Science.gov (United States)

    Kabbasch, C; Möhlenbruch, M; Stampfl, S; Mpotsaris, A; Behme, D; Liebig, T

    2016-06-01

    Five randomized controlled trials (RCTs) on endovascular therapy (EVT) of stroke have proven a clinical benefit over conservative treatment or IV-thrombolysis alone. Lesional clot aspiration with a dedicated system can achieve revascularization without an additional retriever (a direct-aspiration first-pass technique, ADAPT), and the SOFIA has been shown to be both safe and efficacious in a multicentric retrospective study. We have evaluated a subset of these data acquired in two major stroke centers with regard to using the SOFIA for first-line lesional aspiration. Thirty patients with large-vessel occlusions treated with first-line lesional aspiration were identified. Procedural data, clot length, reperfusion success (mTICI), procedural timings, complications, and clinical status at admission, discharge and at 90 days were analyzed. The median baseline NIHSS was 16. IV thrombolysis was administered in 15/30 patients. Ninety-three percent of occlusions were in the anterior circulation. TICI ≥ 2b was achieved in 90% of multimodality treatments; lesional aspiration was successful in 67% within a median time of 20 minutes. The highest first-attempt success rate was in MCA occlusions (median time to recanalization 10 minutes). There were no device-related events. Symptomatic intracerebral hemorrhage (sICH) occurred in 10%, but never with sole lesional aspiration. Embolization to new territories was recorded in 1/30 (3%). Median discharge NIHSS was 7; 30% were mRS ≤ 2 at discharge and 43% at 90-day follow-up. Lesional aspiration with SOFIA is in line with published data. The SOFIA may be used as a first-line device, aiming at fast recanalization by sole aspiration with good safety and efficacy. If unsuccessful, it converts into part of a stent retriever-based multimodality treatment. © The Author(s) 2016.

  15. Risk factors for the development of non-response to first-line treatment for tuberculosis in southern Vietnam.

    Science.gov (United States)

    Keane, V P; de Klerk, N; Krieng, T; Hammond, G; Musk, A W

    1997-10-01

    Acquired resistance to standard chemotherapy for tuberculosis (TB) is an increasing problem worldwide. Vietnam has one of the highest incidences of TB and also has a large population of potential migrants to other countries. Since 1979 the International Organisation for Migration (IOM) has been running a supervised programme of TB treatment for intending migrants from Vietnam where few facilities for bacteriological culture and sensitivity testing exist. This study aimed to assess the most important factors for predicting non-response to first-line treatment as treatment starts and whether any further indicators occur during the course of treatment which may enable more accurate prediction of non-response. In all, 130 subjects failing to respond to first-line therapy (cases) between 1990 and 1995 were compared with 673 subjects who responded to therapy (controls) on various demographic and clinical characteristics using logistic regression to create a prognostic index. Variables analysed included the patient history of past TB treatment, weight, age, sex and radiological and bacteriological findings. All subjects also tested negative for HIV status. The chief markers of successful response were x-ray signs and degree of sputum smear positivity. These markers provided a prognostic index with an optimal cutoff providing about 70% sensitivity and 80% specificity. Incorporating further measures obtained through the first 3 months of treatment improved the sensitivity to 80%. While this study enabled prediction of the majority of subjects failing to respond to first-line therapy, other factors need to be assessed before recommendations for altering treatment regimens can be made. The prognostic index could be useful in assessing subjects for closer supervision.

  16. Pharmacokinetics of the First-Line Antituberculosis Drugs in Ghanaian Children with Tuberculosis with or without HIV Coinfection.

    Science.gov (United States)

    Antwi, Sampson; Yang, Hongmei; Enimil, Anthony; Sarfo, Anima M; Gillani, Fizza S; Ansong, Daniel; Dompreh, Albert; Orstin, Antoinette; Opoku, Theresa; Bosomtwe, Dennis; Wiesner, Lubbe; Norman, Jennifer; Peloquin, Charles A; Kwara, Awewura

    2017-02-01

    Although human immunodeficiency virus (HIV) coinfection is the most important risk factor for a poor antituberculosis (anti-TB) treatment response, its effect on the pharmacokinetics of the first-line drugs in children is understudied. This study examined the pharmacokinetics of the four first-line anti-TB drugs in children with TB with and without HIV coinfection. Ghanaian children with TB on isoniazid, rifampin, pyrazinamide, and ethambutol for at least 4 weeks had blood samples collected predose and at 1, 2, 4, and 8 hours postdose. Drug concentrations were determined by validated liquid chromatography-mass spectrometry methods and pharmacokinetic parameters calculated using noncompartmental analysis. The area under the concentration-time curve from 0 to 8 h (AUC 0-8 ), maximum concentration (C max ), and apparent oral clearance divided by bioavailability (CL/F) for each drug were compared between children with and without HIV coinfection. Of 113 participants, 59 (52.2%) had HIV coinfection. The baseline characteristics were similar except that the coinfected patients were more likely to have lower weight-for-age and height-for-age Z scores (P children than in those with TB alone. In the multivariate analysis, drug dose and HIV coinfection jointly influenced the apparent oral clearance and AUC 0-8 for rifampin, pyrazinamide, and ethambutol. Isoniazid pharmacokinetics were not different by HIV coinfection status. HIV coinfection was associated with lower plasma exposure of three of the four first-line anti-TB drugs in children. Whether TB/HIV-coinfected children need higher dosages of rifampin, pyrazinamide, and ethambutol requires further investigation. (This study has been registered at ClinicalTrials.gov under identifier NCT01687504.). Copyright © 2017 American Society for Microbiology.

  17. Noncutaneous malignant melanoma: a prognostic model from a retrospective multicenter study

    Directory of Open Access Journals (Sweden)

    Kim Jung Han

    2010-04-01

    Full Text Available Abstract Background We performed multicenter study to define clinical characteristics of noncutaneous melanomas and to establish prognostic factors patients who received curative resection. Methods Of the 141 patients who were diagnosed of non-cutaneous melanoma at 4 institutions in Korea between June 1992 and May 2005, 129 (91.5% satisfied the selection criteria. Results Of the 129 noncutaneous melanoma patients, 14 patients had ocular melanoma and 115 patients had mucosal melanoma. For mucosal melanoma, anorectum was the most common anatomic site (n = 39, 30.2% which was followed by nasal cavity (n = 30, 23.3%, genitourinary (n = 21, 16.3%, oral cavity (n = 14, 10.9%, upper gastrointestinal tract (n = 6, 4.7% and maxillary sinus (n = 5, 3.9% in the order of frequency. With the median 64.5 (range 4.3-213.0 months follow-up, the median overall survival were 24.4 months (95% CI 13.2-35.5 for all patients, and 34.6 (95% CI 24.5-44.7 months for curatively resected mucosal melanoma patients. Adverse prognostic factors of survival for 87 curatively resected mucosal melanoma patients were complete resection (R1 resection margin, and age > 50 years. For 14 ocular melanoma, Survival outcome was much better than mucosal melanoma with 73.3% of 2 year OS and 51.2 months of median OS (P = .04. Conclusion Prognosis differed according to primary sites of noncutaneous melanoma. Based on our study, noncutaneous melanoma patients should be treated differently to improve survival outcome.

  18. Melanoma Epidemiology and Public Health

    Science.gov (United States)

    Berwick, Marianne; Erdei, Esther; Hay, Jennifer

    2013-01-01

    Melanoma has presented a conundrum to physicians and prevention researchers. We should be able to reduce incidence and mortality rather easily because evolving melanoma lesions are observable on the surface of the skin. However, melanoma has not proved tractable. The incidence and mortality have risen in all developed countries during the past 50 years. However, mortality appears to be abating among younger cohorts even though the reason for this is not clear. PMID:19254665

  19. Melanoma and immunotherapy bridge 2015

    OpenAIRE

    Nanda, Vashisht G. Y.; Peng, Weiyi; Hwu, Patrick; Davies, Michael A.; Ciliberto, Gennaro; Fattore, Luigi; Malpicci, Debora; Aurisicchio, Luigi; Ascierto, Paolo Antonio; Croce, Carlo M.; Mancini, Rita; Spranger, Stefani; Gajewski, Thomas F.; Wang, Yangyang; Ferrone, Soldano

    2016-01-01

    Table of contents MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A. Davies K2 Non-mutational adaptive changes in melanoma cells exposed to BRAF and MEK inhibitors help the establishment of drug resistance Gennaro Ciliberto, Luigi Fattore, Debora Malpicci, Luigi Aurisicchio, Paolo Antonio Ascierto, Carlo M. Croce, Rita Mancin...

  20. Maintenance therapy following first-line chemotherapy in metastatic colorectal cancer: toxicity and efficacy-single-institution experience.

    Science.gov (United States)

    Fedyanin, Mikahil; Tryakin, Alexey; Vybarava, Anna; Chekini, Dzhennet; Pokataev, Ilya; Sekhina, Olga; Gordeev, Sergey; Aliev, Vechaslav; Tjulandin, Sergei

    2015-01-01

    A role of maintenance chemotherapy (mCT) in patients (pts) with metastatic colorectal cancer (mCRC) is still controversial. The purpose of this retrospective study was to investigate the toxicity and efficacy of mCT in pts with mCRC. There were 97/291 (33 %) pts with mCRC completed 18-20 weeks of first-line CT from 2007 to 2013 in our center. Then, pts who had no disease progression were non-randomly allocated to mCT with capecitabine ± bevacizumab (n = 35) or surveillance (n = 62). PFS was used as a primary endpoint and was calculated from the date of completion of first-line CT. Multivariate Cox stepwise regression analysis was performed to determine independent prognostic factors. Median follow-up time was 15 (range 5-60) months. Median PFS and OS were higher in pts with mCT: 7 versus 3 months (HR 0.5, 95 %CI 0.28-0.82, p = 0.007) and 29 vs 16 months (HR 0.6, 95 %CI 0.3-1.1, 0.04-Gehan-Breslow-Wilcoxon test). Following independent negative prognostic factors was significant on multivariate analysis: CEA level >2.5 ng/ml before start of first-line CT (p = 0.02), liver metastases (p = 0.03) and number of metastatic zones >2 (p = 0.008). MCT had an independent positive impact on PFS (HR 0.5, p = 0.003). MCT prolonged PFS in pts with at least one negative prognostic factors (7 vs. 3 months, p = 0.001, HR 0.38, 95 % CI 0.22-0.68). The mCT was most beneficial in pts with negative prognostic factors: CEA level >2.5 ng/ml before start of first-line CT and/or liver metastases and/or number of metastatic zones >2.

  1. A high molecular weight melanoma-associated antigen-specific chimeric antigen receptor redirects lymphocytes to target human melanomas.

    Science.gov (United States)

    Burns, William R; Zhao, Yangbing; Frankel, Timothy L; Hinrichs, Christian S; Zheng, Zhili; Xu, Hui; Feldman, Steven A; Ferrone, Soldano; Rosenberg, Steven A; Morgan, Richard A

    2010-04-15

    Immunotherapy, particularly the adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL), is a very promising therapy for metastatic melanoma. Some patients unable to receive TIL have been successfully treated with autologous peripheral blood lymphocytes (PBL), genetically modified to express human leukocyte antigen (HLA) class I antigen-restricted, melanoma antigen-reactive T-cell receptors; however, substantial numbers of patients remain ineligible due to the lack of expression of the restricting HLA class I allele. We sought to overcome this limitation by designing a non-MHC-restricted, chimeric antigen receptor (CAR) targeting the high molecular weight melanoma-associated antigen (HMW-MAA), which is highly expressed on more than 90% of human melanomas but has a restricted distribution in normal tissues. HMW-MAA-specific CARs containing an antigen recognition domain based on variations of the HMW-MAA-specific monoclonal antibody 225.28S and a T-cell activation domain based on combinations of CD28, 4-1BB, and CD3zeta activation motifs were constructed within a retroviral vector to allow stable gene transfer into cells and their progeny. Following optimization of the HMW-MAA-specific CAR for expression and function in human PBL, these gene-modified T cells secreted cytokines, were cytolytic, and proliferated in response to HMW-MAA-expressing cell lines. Furthermore, the receptor functioned in both CD4(+) and CD8(+) cells, was non-MHC restricted, and reacted against explanted human melanomas. To evaluate this HMW-MAA-specific CAR in patients with metastatic melanoma, we developed a clinical-grade retroviral packaging line. This may represent a novel means to treat the majority of patients with advanced melanoma, most notably those unable to receive current ACT therapies. (c)2010 AACR.

  2. Nodular amelanotic melanoma

    Directory of Open Access Journals (Sweden)

    Nalamwar Rashmi

    2010-01-01

    Full Text Available We report a case of 65-year-old male patient who presented with multiple erythematous papules coalescing to form a nodular mass over posterior aspect of right thigh of six months duration. His general and systemic examinations were within normal range except for right inguinal lymphadenopathy. Biopsy from the lesion was done, which showed diffuse infiltrate of nests of atypical melanocytes extending upto reticular dermis. Malignant cells were positive for S100 and human melanin black 45(HMB 45. Hence, a diagnosis of amelanotic melanoma (AM - Clarke level IV and TNM stage III was reached. MRI of involved leg showed fungating soft tissue mass in the posterolateral aspect of right thigh and metastatic right inguinal adenopathy. Fine needle aspiration cytology (FNAC from the right inguinal nodes confirmed metastasis of melanoma. The patient was referred to oncosurgery department for further management.

  3. Dermoscopy of difficult-to-diagnose Melanomas

    Directory of Open Access Journals (Sweden)

    Papageorgiou Chrysoula

    2016-09-01

    Full Text Available Dermoscopy is a non-invasive procedure that allows the evaluation of cutaneous lesions, and is considered to be a useful tool that improves the diagnostic accuracy of melanoma. Many dermoscopic criteria of melanoma have been established and several algorithms have been created for melanoma detection. However, the recognition of some melanomas remains challenging. Melanomas on specific body sites, melanomas in patients with multiple atypical moles, and nodular melanomas represent the most difficult-to-recognize melanoma subtypes, since they typically lack the “classic” melanoma-specific criteria. This paper provides an update on dermoscopy of difficult-to-diagnose melanomas by summarizing the newest data. Lastly, we highlight the importance of digital dermoscopy in the follow-up of melanocytic lesions for the detection of incipient melanomas while maintaining a low excision rate.

  4. GEMCYTABIN (CYTOGEM® AND CISPLATIN AS FIRST-LINE THERAPY FOR ADVANCED BLADDER CANCER: RESULTS OF A PROSPECTIVE OPEN-LABELED NON-COMPARATIVE NON-RANDOMIZED STUDY

    Directory of Open Access Journals (Sweden)

    V. B. Matveev

    2009-01-01

    Full Text Available Purpose.  The primary end-points of the study were overall response rate, progressive-free and overall survival in patients received Gemcytabin (Cytogem® and Cisplatin as first-line therapy for transitional-cell bladder cancer. Secondary end-points were toxicity and safty of the regimen. Material. From February 2005 to March 2007 25 patients with morphologically verified inoperable locally advanced and metastatic transitional-cell bladder cancer were recruited. Men-to-women ratio was 3:1. Median age of the patients was 66,5±6,8 years. All the patients received Cytogem® 1000 mg/m2 days 1, 8, 15, cisplatin 70 mg/m2 on day 2; every 28 days. No more than 6 cycles were allowed if the evidence of disease progression and unacceptable toxicity were not registered. Median follow-up was 36,2±12,1 months.  Results. Complete response was observed in 2 (8%, partial — in 11 (44%, stabilization — in 10 (40%, progression — in 2 (8% of 25 patients. Twelve- and 24-month overall survival was — 51,3% and 22,4% (median 13,4±3,5 (95% CI: 6,6—20,4 months, progressive- free survival — 26% and 13% respectively (median 8,8±1 (95% CI: 6,6—10,6 months. Toxicity was evaluated in 24 patients and occurred in all cases (grade I—II — 16 (67%, grade III—IV — 8 (33%. The main regimen-related toxicity was hematological (neutropenia — 16 (67% (grade I—II — 8 (33%, grade III—IV — 8 (33%, thrombocytopenia — 14 (58% (grade I—II — 10 (41,5%, grade III—IV — 4 (16,5%, anemia — 7 (29% (grade I—II — 5 (21%, grade III—IV — 2 (8%. Hematological toxicity was not associated with com- plications in any case. Non-hematological side-effects were nausea and vomiting in 21 (88% (grade I—II — 67%, grade III — 21%, alopecia — in 11 (44% patients. The regimen-related toxicity was considerable and reversible. No side-effect demanded blood transfusion, antibiotic and/or growth factors administration, and hospital admission.

  5. GEMCYTABIN (CYTOGEM® AND CISPLATIN AS FIRST-LINE THERAPY FOR ADVANCED BLADDER CANCER: RESULTS OF A PROSPECTIVE OPEN-LABELED NON-COMPARATIVE NON-RANDOMIZED STUDY

    Directory of Open Access Journals (Sweden)

    V. B. Matveev

    2014-08-01

    Full Text Available Purpose.  The primary end-points of the study were overall response rate, progressive-free and overall survival in patients received Gemcytabin (Cytogem® and Cisplatin as first-line therapy for transitional-cell bladder cancer. Secondary end-points were toxicity and safty of the regimen. Material. From February 2005 to March 2007 25 patients with morphologically verified inoperable locally advanced and metastatic transitional-cell bladder cancer were recruited. Men-to-women ratio was 3:1. Median age of the patients was 66,5±6,8 years. All the patients received Cytogem® 1000 mg/m2 days 1, 8, 15, cisplatin 70 mg/m2 on day 2; every 28 days. No more than 6 cycles were allowed if the evidence of disease progression and unacceptable toxicity were not registered. Median follow-up was 36,2±12,1 months.  Results. Complete response was observed in 2 (8%, partial — in 11 (44%, stabilization — in 10 (40%, progression — in 2 (8% of 25 patients. Twelve- and 24-month overall survival was — 51,3% and 22,4% (median 13,4±3,5 (95% CI: 6,6—20,4 months, progressive- free survival — 26% and 13% respectively (median 8,8±1 (95% CI: 6,6—10,6 months. Toxicity was evaluated in 24 patients and occurred in all cases (grade I—II — 16 (67%, grade III—IV — 8 (33%. The main regimen-related toxicity was hematological (neutropenia — 16 (67% (grade I—II — 8 (33%, grade III—IV — 8 (33%, thrombocytopenia — 14 (58% (grade I—II — 10 (41,5%, grade III—IV — 4 (16,5%, anemia — 7 (29% (grade I—II — 5 (21%, grade III—IV — 2 (8%. Hematological toxicity was not associated with com- plications in any case. Non-hematological side-effects were nausea and vomiting in 21 (88% (grade I—II — 67%, grade III — 21%, alopecia — in 11 (44% patients. The regimen-related toxicity was considerable and reversible. No side-effect demanded blood transfusion, antibiotic and/or growth factors administration, and hospital admission.

  6. Stent therapy for malignant superior vena cava syndrome: Should be first line therapy or simple adjunct to radiotherapy

    International Nuclear Information System (INIS)

    Chatziioannou, A.; Alexopoulos, Th.; Mourikis, D.; Dardoufas, K.; Katsenis, K.; Lazarou, S.; Koutoulidis, V.; Ladopoulos, Ch.; Vlachos, L.

    2003-01-01

    The goal of this paper is to present our experience with superior vena cava (SVC) stenting, as first line procedure for immediate relief, in patients with malignancy, and its potential influence in the subsequent radiotherapy (XRT). Over a 1-year period, 18 patients with SVC syndrome due to severe stenosis secondary to mediastinal malignancy were referred for stent insertion. A SVC score was used to measure treatment effectiveness. Stent insertion had been successful in 18/18 patients (technical success 100%). All patients experienced symptomatic relief within few hours of the procedure. There were no major complications. In all patients we were able to start radiotherapy (XRT) the next day, after stenting according to our new institutional protocol. All patients were able to comply with the XRT program, perfectly well. Conclusions: SVC stenting provides immediate significant relief of the very annoying SVC syndrome symptoms, thus facilitating excellent compliance of all the patients to the subsequently XRT protocols. We strongly recommend SVC stenting as first line procedure, in patients with SVC syndrome due to malignancy prior to radiotherapy

  7. Metabolic syndrome in patients on first-line antiretroviral therapy containing zidovudine or tenofovir in rural Lesotho, Southern Africa.

    Science.gov (United States)

    Labhardt, Niklaus Daniel; Müller, Urs Franz; Ringera, Isaac; Ehmer, Jochen; Motlatsi, Mokete M; Pfeiffer, Karolin; Hobbins, Michael A; Muhairwe, Josephine A; Muser, Juergen; Hatz, Christoph

    2017-06-01

    To assess the prevalence of metabolic syndrome (MetS) among patients in rural Lesotho who are taking first-line antiretroviral therapy (ART) containing either zidovudine or tenofovir disoproxil. Cross-sectional survey in 10 facilities in Lesotho among adult (≥16 years) patients on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART for ≥6 months. MetS was defined according to the International Diabetes Federation criteria. Among 1166 patients (65.8% female), 22.2% (95% CI: 19.3-25.3) of women and 6.3% (4.1-9.1) of men met the IDF definition of MetS (P < 0.001). In both sexes, there was no significant difference in MetS prevalence between NNRTIs. However, in women taking zidovudine as nucleoside reverse transcriptase inhibitor (NRTI), MetS prevalence was 27.9%, vs. 18.8% in those taking tenofovir. In the multivariate logistic regression allowing for socio-demographic and clinical covariates, ART containing zidovudine was associated with MetS in women (aOR 2.17 (1.46-3.22), P < 0.001) but not in men. In this study, taking ART containing zidovudine instead of tenofovir disoproxil was an independent predictor of MetS in women but not in men. This finding endorses WHO's recommendation of tenofovir as preferred NRTI. © 2017 John Wiley & Sons Ltd.

  8. CD4 cell count response to first-line combination ART in HIV-2+ patients compared with HIV-1+ patients

    DEFF Research Database (Denmark)

    Wittkop, Linda; Arsandaux, Julie; Trevino, Ana

    2017-01-01

    excluded. Evolution of CD4 cell count was studied using adjusted linear mixed models. Results: We included 185 HIV-2+ and 30321 HIV-1+ patients with median age of 46 years (IQR 36-52) and 37 years (IQR 31-44), respectively. Median observed pretreatment CD4 cell counts/mm3 were 203 (95% CI 100-290) in HIV-2......Background: CD4 cell recovery following first-line combination ART (cART) is poorer in HIV-2+ than in HIV-1+ patients. Only large comparisons may allow adjustments for demographic and pretreatment plasma viral load (pVL). Methods: ART-naive HIV+ adults from two European multicohort collaborations......, COHERE (HIV-1 alone) and ACHIeV2e (HIV-2 alone), were included, if they started first-line cART (without NNRTIs or fusion inhibitors) between 1997 and 2011. Patients without at least one CD4 cell count before start of cART, without a pretreatment pVL and with missing a priori-defined covariables were...

  9. High dose amoxicillin-based first line regimen is equivalent to sequential therapy in the eradication of H. pylori infection.

    Science.gov (United States)

    Franceschi, F; Ojetti, V; Gabrielli, M; Petruzziello, C; Tortora, A; Gasbarrini, G; Lopetuso, L R; Scaldaferri, F; Gasbarrini, A

    2016-01-01

    Helicobater (H.) pylori eradication rates with standard first-line triple therapy have declined to unacceptable levels. To date, amoxicillin-resistant H. pylori strains have rarely been detected. Whether increasing the dosage of amoxicillin in a standard 7 days eradicating regimen may enhance its efficacy is not known. The aim of this paper is to compare the efficacy of a 7 days high-dose amoxicillin based first-line regimen with sequential therapy. We have retrospectively analyzed data from 300 sex and age matched patients, who underwent 3 different therapeutic schemes: (1) standard LCA, lansoprazole 30 mg bid, clarithromycin 500 mg bid and amoxicillin 1000 mg bid for 7 days; (2) high dose LCA (HD-LCA), lansoprazole 30 mg bid, clarithromycin 500 mg bid and amoxicillin 1000 mg tid for 7 days; (3) sequential LACT, lansoprazole 30 mg bid plus amoxicillin 1000 mg bid for 5 days, followed by lansoprazole 30 mg bid, clarithromycin 500 mg bid and tinidazole 500 mg bid for 5 days. Eradication was confirmed by 13C-urea breath test. Compliance and occurrence of adverse effects were also assessed. Eradication rates were: 55% for LCA, 75% for HD-LCA and 73% for LACT. Eradication rates were higher in HD-LCA group compared to LCA (pamoxicillin based eradicating treatment is superior to standard triple therapy and equivalent to sequential therapy; compared to the latter, the shorter duration may represent an advantage.

  10. Case Reports of Idiopathic Thrombocytopenia Unresponsive to First-Line Therapies Treated With Traditional Herbal Medicines Based on Syndrome Differentiation.

    Science.gov (United States)

    Yang, Juno; Lee, Beom-Joon; Lee, Jun-Hwan

    The objective of our study is to present two cases showing the effects of traditional Korean herbal medicines based on traditional Korean medicine (TKM) for the treatment of immune thrombocytopenic purpura (ITP). One patient showed no response to treatment with steroids and an immunosuppressive agent. Moreover, liver toxicity and side effects of steroids were evident. However, after he ceased conventional treatment and started to take an herbal medicine, his liver function normalized and the steroid side effects resolved. Ultimately, he achieved complete remission. Another patient with ITP had sustained remission after steroid therapy in childhood, but extensive uterine bleeding and thrombocytopenia recurred when she was 16 years old. She was managed with steroids again for 2 years, but severe side effects occurred, and eventually she ceased taking steroids. She refused a splenectomy, and was then treated with a herbal medicine for 7 months, ultimately leading to sustained remission again. Many patients with resistance to first-line treatments tend to be reluctant to undergo a splenectomy, considered a standard second-line treatment. In conclusion, herbal medicines, based on TKM, may offer alternative treatments for persistent or chronic ITP that is resistant to existing first-line treatments. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Baseline and Trend of Lymphocyte-to-Monocyte Ratio as Prognostic Factors in Epidermal Growth Factor Receptor Mutant Non-Small Cell Lung Cancer Patients Treated with First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

    Directory of Open Access Journals (Sweden)

    Yu-Mu Chen

    Full Text Available Patients with early-stage lung cancer who have a high baseline lymphocyte-to-monocyte ratio (LMR have a favorable prognosis. However, the prognostic significance of LMR in patients with advanced-stage EGFR-mutant non-small cell lung cancer (NSCLC receiving first-line epidermal growth factor receptor (EGFR-tyrosine kinase inhibitors (TKIs has not been established. We conducted a retrospective analysis to investigate the influence of LMR on clinical outcomes including progression-free survival (PFS and overall survival (OS in EGFR-mutant patients with NSCLC.Of 1310 lung cancer patients diagnosed between January 2011 and October 2013, 253 patients receiving first-line EGFR-TKIs for EGFR-mutant NSCLC were included. The cut-off values for baseline and the 1-month-to-baseline ratio of LMR (MBR, determined by using receiver operating characteristic curves, were 3.29 and 0.63, respectively. Patients were divided into 3 prognostic groups: high LMR and MBR, high LMR or MBR, and low LMR and MBR.The mean patient age was 65.2 years, and 41% were men. The median PFS and OS were 10.3 and 22.0 months, respectively. The PFS in patients with high LMR and MBR, high LMR or MBR, and low LMR and MBR were 15.4, 7.1, and 2.0 months, respectively (p < 0.001, whereas the OS were 32.6, 13.7, and 5.1 months, respectively (p < 0.001.A combination of baseline and trend of LMR can be used to identify patients with a high mortality risk in EGFR-mutant NSCLC patients receiving first-line EGFR-TKIs.

  12. Circulating melanoma cells and survival in metastatic melanoma

    NARCIS (Netherlands)

    Rao, C.; Bui, T.; Connelly, M.; Doyle, G.; Karydis, I.; Middleton, M. R.; Clack, G.; Malone, M.; Coumans, F. A. W.; Terstappen, L. W. M. M.

    2011-01-01

    A validated assay for the enumeration of circulating melanoma cells (CMCs) may facilitate the development of more effective therapies for metastatic melanoma patients. In this study CD146(+) cells were immunomagnetically enriched from 7.5 ml of blood. Isolated cells were fluorescently stained with

  13. Proton beam radiotherapy of iris melanoma

    International Nuclear Information System (INIS)

    Damato, Bertil; Kacperek, Andrzej; Chopra, Mona; Sheen, Martin A.; Campbell, Ian R.; Errington, R. Douglas

    2005-01-01

    Purpose: To report on outcomes after proton beam radiotherapy of iris melanoma. Methods and Materials: Between 1993 and 2004, 88 patients with iris melanoma received proton beam radiotherapy, with 53.1 Gy in 4 fractions. Results: The patients had a mean age of 52 years and a median follow-up of 2.7 years. The tumors had a median diameter of 4.3 mm, involving more than 2 clock hours of iris in 32% of patients and more than 2 hours of angle in 27%. The ciliary body was involved in 20%. Cataract was present in 13 patients before treatment and subsequently developed in another 18. Cataract had a 4-year rate of 63% and by Cox analysis was related to age (p = 0.05), initial visual loss (p < 0.0001), iris involvement (p < 0.0001), and tumor thickness (p < 0.0001). Glaucoma was present before treatment in 13 patients and developed after treatment in another 3. Three eyes were enucleated, all because of recurrence, which had an actuarial 4-year rate of 3.3% (95% CI 0-8.0%). Conclusions: Proton beam radiotherapy of iris melanoma is well tolerated, the main problems being radiation-cataract, which was treatable, and preexisting glaucoma, which in several patients was difficult to control

  14. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial.

    Science.gov (United States)

    Maughan, Timothy S; Adams, Richard A; Smith, Christopher G; Meade, Angela M; Seymour, Matthew T; Wilson, Richard H; Idziaszczyk, Shelley; Harris, Rebecca; Fisher, David; Kenny, Sarah L; Kay, Edward; Mitchell, Jenna K; Madi, Ayman; Jasani, Bharat; James, Michelle D; Bridgewater, John; Kennedy, M John; Claes, Bart; Lambrechts, Diether; Kaplan, Richard; Cheadle, Jeremy P

    2011-06-18

    In the Medical Research Council (MRC) COIN trial, the epidermal growth factor receptor (EGFR)-targeted antibody cetuximab was added to standard chemotherapy in first-line treatment of advanced colorectal cancer with the aim of assessing effect on overall survival. In this randomised controlled trial, patients who were fit for but had not received previous chemotherapy for advanced colorectal cancer were randomly assigned to oxaliplatin and fluoropyrimidine chemotherapy (arm A), the same combination plus cetuximab (arm B), or intermittent chemotherapy (arm C). The choice of fluoropyrimidine therapy (capecitabine or infused fluouroracil plus leucovorin) was decided before randomisation. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and C is described in a companion paper. Here, we present the comparison of arm A and B, for which the primary outcome was overall survival in patients with KRAS wild-type tumours. Analysis was by intention to treat. Further analyses with respect to NRAS, BRAF, and EGFR status were done. The trial is registered, ISRCTN27286448. 1630 patients were randomly assigned to treatment groups (815 to standard therapy and 815 to addition of cetuximab). Tumour samples from 1316 (81%) patients were used for somatic molecular analyses; 565 (43%) had KRAS mutations. In patients with KRAS wild-type tumours (arm A, n=367; arm B, n=362), overall survival did not differ between treatment groups (median survival 17·9 months [IQR 10·3-29·2] in the control group vs 17·0 months [9·4-30·1] in the cetuximab group; HR 1·04, 95% CI 0·87-1·23, p=0·67). Similarly, there was no effect on progression-free survival (8·6 months [IQR 5·0-12·5] in the control group vs 8·6 months [5·1-13·8] in the cetuximab group; HR 0·96, 0·82-1·12, p=0·60). Overall response rate increased from 57% (n=209) with chemotherapy alone to 64% (n=232) with

  15. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    International Nuclear Information System (INIS)

    Ungerer, Christopher; Doberstein, Kai; Buerger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning; Boehm, Beate; Pfeilschifter, Josef; Dummer, Reinhard; Mihic-Probst, Daniela; Gutwein, Paul

    2010-01-01

    Research highlights: → Strong ADAM15 expression is found in normal melanocytes. → ADAM15 expression is significantly downregulated in patients with melanoma metastasis. → TGF-β can downregulate ADAM15 expression in melanoma cells. → Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. → Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-γ and TGF-β downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  16. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Ungerer, Christopher; Doberstein, Kai [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Buerger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning [Department of Dermatology, Clinic of the Goethe-University, Theodor-Stern-Kai, Frankfurt (Germany); Boehm, Beate [Division of Rheumatology, Goethe University, Frankfurt am Main (Germany); Pfeilschifter, Josef [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Dummer, Reinhard [Department of Pathology, Institute of Surgical Pathology, University Hospital, Zurich (Switzerland); Mihic-Probst, Daniela [Department of Dermatology, University Hospital Zurich (Switzerland); Gutwein, Paul, E-mail: p.gutwein@med.uni-frankfurt.de [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany)

    2010-10-22

    Research highlights: {yields} Strong ADAM15 expression is found in normal melanocytes. {yields} ADAM15 expression is significantly downregulated in patients with melanoma metastasis. {yields} TGF-{beta} can downregulate ADAM15 expression in melanoma cells. {yields} Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. {yields} Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-{gamma} and TGF-{beta} downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  17. Health-related quality of life in melanoma patients: Impact of melanoma-related limb lymphoedema.

    Science.gov (United States)

    Gjorup, Caroline A; Groenvold, Mogens; Hendel, Helle W; Dahlstroem, Karin; Drzewiecki, Krzysztof T; Klausen, Tobias W; Hölmich, Lisbet R

    2017-11-01

    To explore health-related quality of life (HRQoL) in recurrence-free melanoma patients, with a focus on the association between melanoma-related limb lymphoedema and HRQoL. HRQoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the breast cancer module (EORTC QLQ-BR23) subscales body image and future perspective, the Functional Assessment for Cancer Therapy-General subscale social/family well-being and the Hospital Anxiety and Depression Scale. Data were analysed using linear and ordinal logistic regression adjusting for age and gender. A total of 431 melanoma patients who had undergone wide local excision and axillary or inguinal sentinel lymph node biopsy (SLNB) and/or complete lymph node dissection (CLND) participated. No patients had had recurrence of the disease or had received adjuvant radiotherapy. The HRQoL scores improved with time after surgery. Melanoma-related limb lymphoedema was present in 109 patients (25%). Patients with lymphoedema had significantly worse HRQoL scores in the EORTC QLQ-C30 subscales global health status/quality of life, role and social functioning, fatigue, pain and financial difficulties, as well as in the QLQ-BR23 body image subscale. No associations were found between the limb affected (upper or lower limb), clinical stage of lymphoedema, duration of lymphoedema or type of surgery (SLNB or CLND) and HRQoL. We found an interaction with age and gender in the associations between lymphoedema and HRQoL: younger patients and women with lymphoedema had worse social functioning and women had significantly more impaired body image. The negative impact of melanoma-related limb lymphoedema on HRQoL emphasises the importance of developing strategies for increasing awareness and improving prevention and treatment of lymphoedema. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Treatment with Ipilimumab: A Case Report of Complete Response in a Metastatic Malignant Melanoma Patient

    Directory of Open Access Journals (Sweden)

    Alfredo Addeo

    2013-05-01

    Full Text Available Introduction: Over the past year, 3 agents have been approved for the treatment of melanoma by the Food and Drug Administration. These include pegylated interferon α-2b for stage III melanoma, vemurafenib for unresectable or metastatic melanoma with BRAF V600E mutation, and ipilimumab for unresectable or metastatic melanoma. Case Presentation: We present here the case of a 65-year-old Caucasian male diagnosed with advanced melanoma in April 2011 and treated with ipilimumab (Yervoy®, a monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4, as second-line treatment after progression with dacarbazine, for (wild-type BRAF metastatic melanoma. The patient was referred to us for several painful lumps on his right arm. A biopsy of one of them revealed melanoma. CT and PET scans did not show any other lesions or a primary site. The patient was started on first-line chemotherapy with dacarbazine 850 mg/m2 on day 1, every 3 weeks. After 3 cycles, the patient showed disease progression with an increase in size of the skin metastasis. Second-line treatment was started with ipilimumab 3 mg/kg on day 1, every 3 weeks. At the end of the treatment, after 4 cycles, we documented a complete clinical response with total resolution of the skin metastasis. At the time of writing this paper, our patient had finished his treatment more than 9 months earlier and is still in complete remission. Conclusion: This is a paradigmatic case where, despite extensive metastatic disease, treatment with ipilimumab has confirmed its efficacy. It is still an open question why only a minority of patients have such a remarkable response, and further trials are warranted to address this important question.

  19. Prognosis of mucous naso-sinus melanomas

    International Nuclear Information System (INIS)

    Thariat, J.; Poissonnet, G.; Dassonville, O.; Santini, J.; Castillo, L.; Iattes, L.; Bensadoun, R.J.; Castillo, L.

    2009-01-01

    Purpose: The mucous melanoma of superior aero-digestive tracts represents 1-2% of malignant melanomas, 5-10% of head and neck melanomas, and concerns particularly, the nasal cavities and naso-sinus cavities. The recurrences are frequent, often local ones, sometimes multifocal ones, the survival rate at five years is ≤ 30%. The Ballantyne classification distinguishes three stages: 1 localised tumors, 2 ganglions attack, 3 metastases. Are pejorative: a stage number 3 ( deep invasion, muscles, bones, cartilages) according to the Prasad classification (1: in situ or micro invasive, 2: invasion of the lamina propria), the achromia sub-type, a pseudo papillary or sarcoma, vascular emboli, necrosis. The recommendations rest on evidence level at 4. The complete excision is the rule and must be counterbalanced with the morbidity in case of orbital, dura-mater, frontal lobe, and infra temporal fossa. The adjuvant irradiation is debated.We evaluated the prognosis of mucous naso-sinus melanomas. Conclusion: The principal cause of death was the local failure. The Ballantyne classification does not take into account the extensions and overestimates the prognosis impact of ganglions invasion that is yet ≤10% ( and does not justify a radiotherapy in lack of adenopathy). It underestimates probably the impact of adjuvant radiotherapy. One should be able to distinguish the unfavourable stage 1 tumors (receiving eventually a radiotherapy) and these ones of very localised stage 1 for which it could be omitted. The fractionation and the optimal dose remain to be defined. The volume ≥100 ml and the irradiation by carbon ions seem promising in term of local control but the metastases stay a problem in the recent series. (N.C.)

  20. Ki67 expression in the primary tumor predicts for clinical benefit and time to progression on first-line endocrine therapy in estrogen receptor-positive metastatic breast cancer.

    Science.gov (United States)

    Delpech, Y; Wu, Y; Hess, K R; Hsu, L; Ayers, M; Natowicz, R; Coutant, C; Rouzier, R; Barranger, E; Hortobagyi, G N; Mauro, D; Pusztai, L

    2012-09-01

    We examined whether baseline Ki67 expression in estrogen receptor-positive (ER+) primary breast cancer correlates with clinical benefit and time to progression on first-line endocrine therapy and survival in metastatic disease. Ki67 values and outcome information were retrieved from a prospectively maintained clinical database and validated against the medical records; 241 patients with metastatic breast cancer were included--who had ER+ primary cancer with known Ki67 expression level--and received first-line endocrine therapy for metastatic disease. Patients were assigned to low (25 %) Ki67 expression groups. Kaplan-Meier survival curves were plotted and multivariate analysis was performed to assess association between clinical and immunohistochemical variables and outcome. The clinical benefit rates were 81, 65, and 55 % in the low (n = 32), intermediate (n = 103), and high (n = 106) Ki67 expression groups (P = 0.001). The median times to progression on first-line endocrine therapy were 20.3 (95 % CI, 17.5-38.5), 10.8 (95 % CI, 8.9-18.8), and 8 (95 % CI, 6.1-11.1) months, respectively (P = 0.0002). The median survival times after diagnosis of metastatic disease were also longer for the low/intermediate compared to the high Ki67 group, 52 versus 30 months (P Ki67 expression in the primary tumor remained an independent adverse prognostic factor in metastatic disease (P = 0.001). Low Ki67 expression in the primary tumor is associated with higher clinical benefit and longer time to progression on first-line endocrine therapy and longer survival after metastatic recurrence.

  1. Radioimmunotherapy for first-line and relapse treatment of aggressive B-cell non-Hodgkin lymphoma: an analysis of 215 patients registered in the international RIT-Network

    Energy Technology Data Exchange (ETDEWEB)

    Hohloch, Karin; Lankeit, H.K.; Truemper, L. [Georg August University, Hematology and Oncology, Goettingen (Germany); Zinzani, P.L. [University of Bologna, Institute of Hematology and Medical Oncology ' ' L. e A. Seragnoli' ' , Bologna (Italy); Scholz, C.W. [Charite, University Berlin, Hematology, Oncology and Tumor Immunology, Berlin (Germany); Lorsbach, M.; Windemuth-Kieselbach, C. [Alcedis GmbH, Giessen (Germany)

    2014-08-15

    Very few reliable clinical data about the use of radioimmunotherapy in aggressive B-cell lymphoma exist. Patients with aggressive B-cell lymphoma registered in the international RIT-Network were analysed with regard to prior treatment, response and side effects. The RIT-Network is a web-based registry that collects observational data from radioimmunotherapy-treated patients with malignant lymphoma across 13 countries. This analysis included 215 with aggressive B-cell lymphoma out of 232 patients registered in the RIT-Network. Histological subtypes were as follows: 190 diffuse large B-cell, 15 primary mediastinal, 9 anaplastic large cell, and 1 intravascular lymphoma. The median age of the patients was 62 years (range 17 - 88), with 27 % above the age of 70 years. Radioimmunotherapy was mainly used as consolidation after first-line or second-line chemotherapy (56.1 %), as part of third-line to eighth-line therapy for relapse (16.4 %), and in refractory disease (12.2 %). Grade IV neutropenia and thrombopenia and grade III anaemia were observed. The median time to recovery of blood count was 81 days (range 0 - 600 days). The overall response rate was 63.3 %. The complete response rate was 76.4 % in patients treated as part of first-line therapy, and 44.3 % in patients with relapse. Mean overall survival in first-line therapy patients was 32.7 months and 14.0 months in patients with relapse or refractory disease, respectively. Most patients with aggressive B-cell lymphoma in the RIT-Network received radioimmunotherapy as consolidation after first-line therapy with excellent complete remission and overall survival rates compared to published data. In relapsed aggressive B-cell lymphoma, radioimmunotherapy is a safe and feasible treatment leading to satisfactory response rates with acceptable toxicity. (orig.)

  2. Lymphatic invasion and the Shields index in predicting melanoma metastases.

    Science.gov (United States)

    Špirić, Zorica; Erić, Mirela; Eri, Živka

    2017-11-01

    Findings of the prognostic significance of lymphatic invasion are contradictory. To determine an as efficient cutaneous melanoma metastasis predictor as possible, Shields et al. created a new prognostic index. This study aimed to examine whether the lymphatic invasion analysis and the Shields index calculation can be used in predicting lymph node status in patients with cutaneous melanoma. Lymphatic invasion of 100 melanoma specimens was detected by dual immunohistochemistry staining for the lymphatic endothelial marker D2-40 and melanoma cell S-100 protein. The Shields index was calculated as a logarithm by multiplying the melanoma thickness, square of peritumoural lymphatic vessel density and the number "2" for the present lymphatic invasion. No statistically significant difference was observed between lymph node metastatic and nonmetastatic melanomas regarding the lymphatic invasion. Metastatic melanomas showed a significantly higher Shields index value than nonmetastatic melanomas (p = 0.00). Area under the receiver operator characteristic (ROC) curve (AUC) proved that the Shields index (AUC = 0.86, 95% confidence interval (CI) 0.79-0.93, p = 0.00) was the most accurate predictor of lymph node status, followed by the melanoma thickness (AUC = 0.76, 95% CI 0.67-0.86, p = 0.00) and American Joint Committee on Cancer (AJCC) staging (AUC = 0.75, 95% CI 0.66-0.85, p = 0.00), while lymphatic invasion was not successful in predicting (AUC = 0.56, 95% CI 0.45-0.67, p = 0.31). The Shields index achieved 81.3% sensitivity and 75% specificity (cut-off mean value). Our findings show that D2-40/S-100 immunohistochemical analysis of lymphatic invasion cannot be used for predicting the lymph node status, while the Shields index calculation predicts disease outcome more accurately than the melanoma thickness and AJCC staging. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights

  3. Pediatric Melanoma and Drug Development

    Directory of Open Access Journals (Sweden)

    Klaus Rose

    2018-03-01

    Full Text Available Importance—Pediatric melanoma occurs, albeit rarely. Should patients be treated by today’s medical standards, or be subjected to medically unnecessary clinical studies? Observations—We identified international, industry-sponsored pediatric melanoma studies triggered by regulatory demands in www.clinicaltrials.gov and further pediatric melanoma studies demanded by European Union pediatric investigation plans. We retrieved related regulatory documents from the internet. We analyzed these studies for rationale and medical beneficence on the basis of physiology, pediatric clinical pharmacology and rationale. Regulatory authorities define children by chronological age, not physiologically. Newborns’ organs are immature but they develop and mature rapidly. Separate proof of efficacy in underage patients is justified formally/regulatorily but lacks medical sense. Children—especially post-puberty—and adults vis-a-vis medications are physiologically very similar. Two adolescent melanoma studies were terminated in 2016 because of waning recruitment, while five studies in pediatric melanoma and other solid tumors, triggered by European Union pediatric investigation plans, continue recruiting worldwide. Conclusions and Relevance—Regulatory-demanded pediatric melanoma studies are medically superfluous. Melanoma patients of all ages should be treated with effective combination treatment. Babies need special attention. Children need dose-finding and pharmacokinetic studies but adolescents metabolize and respond to drugs similarly to adults. Institutional Review Boards/ethics committees should suspend ongoing questionable pediatric melanoma studies and reject newly submitted questionable studies.

  4. Histopathological findings concerning ocular melanomas.

    Science.gov (United States)

    Costache, Mariana; Pătraşcu, Oana Maria; Dumitru, Adrian; Costache, Diana; Voinea, Liliana Mary; Simionescu, Olga; Sajin, Maria

    2014-01-01

    Ocular melanoma is rare in clinical practice. In this study, we present three cases of ocular melanoma surgically removed in the Department of Ophthalmology of the Emergency University Hospital of Bucharest, Romania, and diagnosed in the Department of Pathology of the same hospital using conventional histopathological techniques and immunohistochemical tests.

  5. Angiogenic profile of uveal melanoma.

    NARCIS (Netherlands)

    Notting, I.C.; Missotten, G.S.; Sijmons, B.; Boonman, Z.F.; Keunen, J.E.E.; Pluijm, G. van der

    2006-01-01

    Uveal melanoma develops in one of the most capillary-rich tissues of the body and is disseminated hematogenously. Knowledge of the nature and the spatiotemporal expression of angiogenic factors in uveal melanoma is essential to the development of new treatment strategies, especially with regard to

  6. Clinical characteristics and management of melanoma families

    NARCIS (Netherlands)

    Rhee, Jasper Immanuel van der

    2013-01-01

    Being a member of a melanoma family is a major risk factor for cutaneous malignant melanoma. In this thesis clinical characteristics and management of melanoma families are discussed. In the first part of the thesis clinical and histological characteristics of melanoma (patients) from families with

  7. Immune Checkpoint Inhibitors for Treatment of Metastatic Melanoma of the Orbit and Ocular Adnexa.

    Science.gov (United States)

    Ford, Joshua; Thuro, Bradley A; Thakar, Sudip; Hwu, Wen-Jen; Richani, Karina; Esmaeli, Bita

    Programmed cell death 1 (PD-1) inhibitors are members of a new class of drugs known as immune checkpoint inhibitors and have proven efficacy in the treatment of metastatic melanoma. Herein, the authors report the use of nivolumab and pembrolizumab, 2 recently Food and Drug Administration-approved PD-1 inhibitors, in 3 patients: 1 with metastatic conjunctival melanoma and 2 with metastatic cutaneous melanoma and orbital involvement. The patients' metastatic disease responded well to drug treatment. As of this writing, 2 patients have completed therapy and remain disease free at least 1 year after treatment completion; the other patient is still receiving treatment, and his orbital disease is responding. The authors herein describe the use of PD-1 inhibitors as a new alternative in the treatment of metastatic melanoma to the orbit or metastatic ocular adnexal melanomas in these clinical settings.

  8. Melanoma Therapy via Peptide-Targeted a-Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Yubin; Hylarides, Mark; Fisher, Darrell R.; Shelton, Tiffani; Moore, Herbert A.; Wester, Dennis W.; Fritzberg, Alan R.; Winkelmann, Christopher T.; Hoffman, Timothy J.; Quinn, Thomas P.

    2005-08-01

    Malignant melanoma is the most lethal form of skin cancer. Current chemotherapy and external beam radiation therapy regimens are ineffective agents against melanoma, as shown by a 10-year survival rate for patients with disseminated disease of approximately 5% (reference?). In this study, the unique combination of a melanoma targeting peptide and an in vivo generated a-particle emitting radioisotope was investigated for its melanoma therapy potential. Alpha-radiation is densely ionizing and energy is locally absorbed, resulting in high concentrations of destructive free radicals and irreparable DNA double strand breaks. This high linear-energy-transfer overcomes radiation resistant tumor cells and oxygen-enhancement effects. The melanoma targeting peptide DOTA-Re(Arg11)CCMSH was radiolabeled with 212Pb, the parent of 212Bi, which decays via alpha and beta decay. Biodistribution and therapy studies were performed in the B16/F1 melanoma bearing C57 mouse flank tumor model. 212Pb[DOTA]-R e(Arg11)CCMSH exhibited rapid tumor uptake and extended retention coupled with rapid whole body disappearance. Radiation dose delivered to the tumor was estimated to be 61 cGy/uCi 212Pb administered. Treatment of melanoma-bearing mice with 50, 100 and 200 uCi of 212Pb[DOTA]-Re(Arg11)CCMSH extended mean survival of mice to 22, 28, and 49.8 days, respectively, compared to the 14.6 day mean survival of the placebo control group. Forty-five percent of the mice receiving 200 uCi survived the study disease-free.

  9. Comparative Aspects of Canine Melanoma

    Directory of Open Access Journals (Sweden)

    Adriana Tomoko Nishiya

    2016-02-01

    Full Text Available Melanomas are malignant neoplasms originating from melanocytes. They occur in most animal species, but the dog is considered the best animal model for the disease. Melanomas in dogs are most frequently found in the buccal cavity, but the skin, eyes, and digits are other common locations for these neoplasms. The aim of this review is to report etiological, epidemiological, pathological, and molecular aspects of melanomas in dogs. Furthermore, the particular biological behaviors of these tumors in the different body locations are shown. Insights into the therapeutic approaches are described. Surgery, chemotherapy, radiotherapy, immunotherapy, and the outcomes after these treatments are presented. New therapeutic perspectives are also depicted. All efforts are geared toward better characterization and control of malignant melanomas in dogs, for the benefit of these companion animals, and also in an attempt to benefit the treatment of human melanomas.

  10. Effect of ABO blood type on the outcomes of patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors.

    Science.gov (United States)

    Omae, Kenji; Fukuma, Shingo; Ikenoue, Tatsuyoshi; Kondo, Tsunenori; Takagi, Toshio; Ishihara, Hiroki; Tanabe, Kazunari; Fukuhara, Shunichi

    2017-09-01

    To assess the effect of blood type on survival outcomes and adverse events (AEs) in patients treated with tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). Patients who received TKIs as first-line therapy for mRCC between 2008 and 2015 at our hospital were included in the study (n = 136). Patients were divided into 2 groups based on their blood type as O and non-O. Survival outcomes and AEs were compared according to blood type. Cox regression models were used for univariate and multivariate survival analyses. Of the 136 patients, 34 (25%) and 102 (75%) had O and non-O blood types, respectively. Blood type O was associated with an increased number of disease sites. There were no differences between the 2 groups with respect to other baseline characteristics. The progression-free survival in patients with O and non-O blood types was 12.1 and 11.6 months, respectively; the overall survival was 34.4 and 24.8 months, respectively. On univariate and multivariate analyses, the ABO blood type was not a significant prognostic factor for progression-free survival or overall survival. Furthermore, the incidences of serious AEs were similar in the 2 blood groups. ABO blood type was not associated with survival outcomes or incidences of serious AEs in mRCC patients treated with TKIs. However, blood type O may be associated with an increased number of disease sites. Copyright © 2017. Published by Elsevier Inc.

  11. First-line treatment with bortezomib rapidly stimulates both osteoblast activity and bone matrix deposition in patients with multiple myeloma, and stimulates osteoblast proliferation and differentiation in vitro

    Science.gov (United States)

    Lund, Thomas; Søe, Kent; Abildgaard, Niels; Garnero, Patrick; Pedersen, Per T; Ormstrup, Tina; Delaissé, Jean-Marie; Plesner, Torben

    2010-01-01

    Objectives: The aim of the study was to investigate the effect of bortezomib on osteoblast proliferation and differentiation, as well as on bone matrix deposition for the first time in bisphosphonate-naïve, previously untreated patients with myeloma. Methods: Twenty newly diagnosed patients received four cycles of bortezomib treatment, initially as monotherapy and then combined with a glucocorticoid from cycle two to four. Bone remodeling markers were monitored closely during treatment. Furthermore, the effects of bortezomib and a glucocorticoid on immature and mature osteoblasts were also studied in vitro. Results: Treatment with bortezomib caused a significant increase in bone-specific alkaline phosphatase and pro-collagen type I N-terminal propeptide, a novel bone formation marker. The addition of a glucocorticoid resulted in a transient decrease in collagen deposition. In vitro bortezomib induced osteoblast proliferation and differentiation. Differentiation but not proliferation was inhibited by glucocorticoid treatment. Conclusions: Bortezomib used as first-line treatment significantly increased collagen deposition in patients with multiple myeloma and osteolytic lesions, but the addition of a glucocorticoid to the treatment transiently inhibited the positive effect of bortezomib, suggesting that bortezomib may result in better healing of osteolytic lesions when used without glucocorticoids in patients that have obtained remission with a previous therapy. The potential bone-healing properties of single-agent bortezomib are currently being explored in a clinical study in patients who have undergone high-dose therapy and autologous stem cell transplantation. PMID:20528908

  12. Does Type of Tumor Histology Impact Survival among Patients with Stage IIIB/IV Non-Small Cell Lung Cancer Treated with First-Line Doublet Chemotherapy?

    Science.gov (United States)

    Clements, Karen M.; Peltz, Gerson; Faries, Douglas E.; Lang, Kathleen; Nyambose, Joshua; Earle, Craig C.; Sugarman, Katherine P.; Taylor, Douglas C. A.; Thompson, David; Marciniak, Martin D.

    2010-01-01

    Chemotherapy regimens may have differential efficacy by histology in nonsmall cell lung cancer (NSCLC). We examined the impact of histology on survival of patients (N = 2,644) with stage IIIB/IV NSCLC who received first-line cisplatin/carboplatin plus gemcitabine (C/C+G) and cisplatin/carboplatin plus a taxane (C/C+T) identified retrospectively in the SEER cancer registry (1997–2002). Patients with squamous and nonsquamous cell carcinoma survived 8.5 months and 8.1 months, respectively (P = .018). No statistically significant difference was observed in survival between C/C+G and C/C+T in both histologies. Adjusting for clinical and demographic characteristics, the effect of treatment regimen on survival did not differ by histology (P for interaction = .257). There was no statistically significant difference in hazard of death by histology in both groups. These results contrast the predictive role of histology and improved survival outcomes observed for cisplatin-pemetrexed regimens in advanced nonsquamous NSCLC. PMID:22482053

  13. Does Type of Tumor Histology Impact Survival among Patients with Stage IIIB/IV Non-Small Cell Lung Cancer Treated with First-Line Doublet Chemotherapy?

    Directory of Open Access Journals (Sweden)

    Karen M. Clements

    2010-01-01

    Full Text Available Chemotherapy regimens may have differential efficacy by histology in nonsmall cell lung cancer (NSCLC. We examined the impact of histology on survival of patients (N=2,644 with stage IIIB/IV NSCLC who received first-line cisplatin/carboplatin plus gemcitabine (C/C+G and cisplatin/carboplatin plus a taxane (C/C+T identified retrospectively in the SEER cancer registry (1997–2002. Patients with squamous and nonsquamous cell carcinoma survived 8.5 months and 8.1 months, respectively (P=.018. No statistically significant difference was observed in survival between C/C+G and C/C+T in both histologies. Adjusting for clinical and demographic characteristics, the effect of treatment regimen on survival did not differ by histology (P for interaction =.257. There was no statistically significant difference in hazard of death by histology in both groups. These results contrast the predictive role of histology and improved survival outcomes observed for cisplatin-pemetrexed regimens in advanced nonsquamous NSCLC.

  14. Serum anti-BPAG1 auto-antibody is a novel marker for human melanoma.

    Directory of Open Access Journals (Sweden)

    Takashi Shimbo

    2010-05-01

    Full Text Available Malignant melanoma is one of the most aggressive types of tumor. Because malignant melanoma is difficult to treat once it has metastasized, early detection and treatment are essential. The search for reliable biomarkers of early-stage melanoma, therefore, has received much attention. By using a novel method of screening tumor antigens and their auto-antibodies, we identified bullous pemphigoid antigen 1 (BPAG1 as a melanoma antigen recognized by its auto-antibody. BPAG1 is an auto-antigen in the skin disease bullous pemphigoid (BP and anti-BPAG1 auto-antibodies are detectable in sera from BP patients and are used for BP diagnosis. However, BPAG1 has been viewed as predominantly a keratinocyte-associated protein and a relationship between BPAG1 expression and melanoma has not been previously reported. In the present study, we show that bpag1 is expressed in the mouse F10 melanoma cell line in vitro and F10 melanoma tumors in vivo and that BPAG1 is expressed in human melanoma cell lines (A375 and G361 and normal human melanocytes. Moreover, the levels of anti-BPAG1 auto-antibodies in the sera of melanoma patients were significantly higher than in the sera of healthy volunteers (p<0.01. Furthermore, anti-BPAG1 auto-antibodies were detected in melanoma patients at both early and advanced stages of disease. Here, we report anti-BPAG1 auto-antibodies as a promising marker for the diagnosis of melanoma, and we discuss the significance of the detection of such auto-antibodies in cancer biology and patients.

  15. Association between tumor tissue TIMP-1 levels and objective response to first-line chemotherapy in metastatic breast cancer

    DEFF Research Database (Denmark)

    Klintman, Marie; Würtz, Sidse Ørnbjerg; Christensen, Ib Jarle

    2010-01-01

    In a previous study from our laboratory, high tumor levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) have been associated with an adverse response to chemotherapy in metastatic breast cancer suggesting that TIMP-1, which is known to inhibit apoptosis, may be a new predictive marker...... in this disease. The purpose of this study was to investigate the association between TIMP-1 and objective response to chemotherapy in an independent patient population consisting of patients with metastatic breast cancer from Sweden and Denmark. TIMP-1 was measured using ELISA in 162 primary tumor extracts from...... patients who later developed metastatic breast cancer and these levels were related to the objective response to first-line chemotherapy. Increasing levels of TIMP-1 were associated with a decreasing probability of response to treatment, reaching borderline significance (OR = 1.59, 95% CI: 0.97-2.62, P = 0...

  16. FIRST LINE 5-FU-BASED CHEMOTHERAPY WITH/WITHOUT BEVACIZUMAB FOR METASTATIC COLORECTAL CANCER: TISSUE BIOMARKER CANDIDATES

    Directory of Open Access Journals (Sweden)

    Assia Konsoulova

    2016-03-01

    Full Text Available Purpose: Colorectal cancer is the second leading cause of cancer mortality in the USA. According to Bulgarian National Statistics Institute, 2370 colon and 1664 rectal cancer cases were diagnosed in 2012 with total number of patients 29995. Adding bevacizumab to chemotherapy in patients with metastatic disease improves progression-free survival (PFS but no predictive markers have been proven in the clinical practice. In our study we examined two tissue biomarkers that may correlate with response to bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer. Patients and Methods: 54 patients with metastatic colorectal cancer were assigned to first line 5-Fu-based chemotherapy with/without bevacizumab. The primary end point was PFS, with additional determination of response and toxicity. Paraffin-embedded samples from primary tumors were collected from all 54 patients. Expression levels of two tumor biomarkers VEGFR-2 and Neuropilin 1 (NP-1 were evaluated with immunohistochemistry. Results: The median PFS for the group treated with CT/Bev was 8.8 months, compared with 5.4 months for the group with chemotherapy alone (95% CI, log-rank test P =0.003. The corresponding overall response rates were 19.3% and 10.2% respectively (P < 0.05 for CT/Bev vs CT. Patients with low NP-1 had statistically significant prolongation of PFS as compared to those with high NP-1 (95% CI, log rank test p= 0.017. Patients with low NP-1 appeared to experience a larger bevacizumab treatment effect in terms of PFS (p=0,049,HR 0.333, 95% CI, 0.111 to 0.995 than patients with high NP-1. Conclusion: The addition of bevacizumab to 5-Fu based chemotherapy improves PFS for patients with metastatic colorectal cancer. Expression of tumor NP-1 is a potential biomarker candidate for prediction of clinical outcome in patients with metastatic colorectal cancer, treated with first line chemotherapy plus bevacizumab.

  17. Resistance to first-line anti-TB drugs is associated with reduced nitric oxide susceptibility in Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Jonna Idh

    Full Text Available The relative contribution of nitric oxide (NO to the killing of Mycobacterium tuberculosis in human tuberculosis (TB is controversial, although this has been firmly established in rodents. Studies have demonstrated that clinical strains of M. tuberculosis differ in susceptibility to NO, but how this correlates to drug susceptibility and clinical outcome is not known.In this study, 50 sputum smear- and culture-positive patients with pulmonary TB in Gondar, Ethiopia were included. Clinical parameters were recorded and drug susceptibility profile and spoligotyping patterns were investigated. NO susceptibility was studied by exposing the strains to the NO donor DETA/NO.Clinical isolates of M. tuberculosis showed a dose- and time-dependent response when exposed to NO. The most frequent spoligotypes found were CAS1-Delhi and T3_ETH in a total of nine known spoligotypes and four orphan patterns. There was a significant association between reduced susceptibility to NO (>10% survival after exposure to 1 mM DETA/NO and resistance against first-line anti-TB drugs, in particular isoniazid (INH. Patients infected with strains of M. tuberculosis with reduced susceptibility to NO showed no difference in cure rate or other clinical parameters but a tendency towards lower rate of weight gain after two months of treatment, independent of antibiotic resistance.There is a correlation between resistance to first-line anti-TB drugs and reduced NO susceptibility in clinical strains of M. tuberculosis. Further studies including the mechanisms of reduced NO susceptibility are warranted and could identify targets for new therapeutic interventions.

  18. First line treatment of advanced non-small-cell lung cancer – specific focus on albumin bound paclitaxel

    Directory of Open Access Journals (Sweden)

    Gupta N

    2013-12-01

    Full Text Available Neha Gupta, Hassan Hatoum, Grace K DyDepartment of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USAAbstract: Lung cancer is the leading cause of cancer mortality worldwide in both men and women. Non-small-cell lung cancer (NSCLC is the most common type of lung cancer, accounting for more than 80% of cases. Paclitaxel has a broad spectrum of activity against various malignancies, including NSCLC. Paclitaxel is poorly soluble in water and thus, until recently, its commercially available preparations contained a non-ionic solvent Cremophor EL®. Cremophor EL® improves the solubility of paclitaxel and allows its intravenous administration. However, certain side-effects associated with paclitaxel, such as hypersensitivity reactions, myelosuppression, and peripheral neuropathy, are known to be worsened by Cremophor®. Nanoparticle albumin-bound paclitaxel ([nab-paclitaxel] ABRAXANE® ABI-007 is a new generation formulation of paclitaxel that obviates the need for Cremophor®, resulting in a safer and faster infusion without requiring the use of premedications to avoid hypersensitivity. Albumin-binding receptor-mediated delivery and lack of sequestering Cremophor® micelles allow higher intratumoral concentration of pharmacologically active paclitaxel. Multiple clinical trials have demonstrated a superior tolerability profile of nab-paclitaxel in comparison to solvent-bound paclitaxel (sb-paclitaxel. A recent Phase III trial compared the effects of weekly nab-paclitaxel in combination with carboplatin versus sb-paclitaxel in combination with carboplatin given every 3 weeks for first line treatment of NSCLC. This trial highlights the weekly nab-paclitaxel combination as an alternate treatment option for NSCLC, with higher response rate in squamous cell NSCLC and longer survival in elderly patients. This review will focus on the properties of nab-paclitaxel and its use in the first line treatment of NSCLC.Keywords: ABI-007, Abraxane, nab

  19. [Cuadruple concomitant non-bismuth therapy vs. classical triple therapy as first line therapy for Helicobacter pylori infection].

    Science.gov (United States)

    Campillo, Ana; Ostiz, Miriam; Amorena, Edurne; Kutz, Marcos; La Iglesia, Matilde

    2016-09-02

    In a previous study we found that the classical triple therapy for Helicobacter pylori (H. pylori) had low efficacy (under 70%) in our area. After this finding, in mid 2012 quadruple concomitant therapy started to be prescribed in our hospital. The aim of the present study is to compare the efficacy of classical triple therapy and quadruple concomitant therapy without bismuth. Observational retrospective study of prescribed treatments between 1st January 2012 and 5th May 2014 and their efficacy. During the study period 510 patients were prescribed a first line therapy; in 179 cases (35,1%) the combination amoxiciline+clarithromicine+PPI was prescribed during 7-14 days, and 298 patients (58,4%) were treated with amoxicillin+clarithromycin+metronidazole+PPI for 10 days. The quadruple concomitant therapy had a higher efficacy than the classical triple therapy, both in an "intention to treat" (84.8% vs. 65.7%, P=.001) and "per protocol" (86.9% vs. 67.2%, P=.001) analysis. Triple therapy had a higher efficacy when it was prescribed for 10 days compared to 7 days (77.9% vs. 56.5%, P=.005 per "intention to treat" and 77.9% vs. 58.5%, P=.011 "per protocol"). When quadruple concomitant therapy was compared with classical triple therapy prescribed over 10 days no significant differences were found. In our setting, cuadruple concomitant therapy without bismuth has a high efficacy as first line therapy for H. pylori eradication, with much better results than classical triple therapy in the way that it is most widely prescribed (short courses of 7-day with a single dose of omeprazole). Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  20. Uterine Artery Embolization for Retained Products of Conception with Marked Vascularity: A Safe and Efficient First-Line Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Bazeries, Paul, E-mail: paul.bazeries@chu-angers.fr; Paisant-Thouveny, Francine; Yahya, Sultan; Bouvier, Antoine; Nedelcu, Cosmina [Centre Hospitalier Universitaire d’Angers, Département d’Imagerie Diagnostique et interventionnelle (France); Boussion, Francoise; Sentilhes, Loic [Centre Hospitalier Universitaire d’Angers, Département de Gynécologie et Obstétrique (France); Willoteaux, Serge; Aubé, Christophe [Centre Hospitalier Universitaire d’Angers, Département d’Imagerie Diagnostique et interventionnelle (France)

    2017-04-15

    ObjectiveTo report our clinical practice regarding a case series of retained products of conception (RPOC) with marked vascularity (MV) managed with selective uterine artery embolization (UAE) as first-line treatment.MethodsThis was a monocentric, retrospective study of 31 consecutive cases of RPOC with MV diagnosed by Doppler ultrasound in the context of postpartum/postabortal bleeding. The primary outcome was the absence of rebleeding following embolization.ResultsRPOC with MV occurred after abortion in 27 out of 31 patients (87%). The time elapsed between delivery/abortion and UAE ranged from 1 to 210 days (mean 55.7 ± 45 days). Primary clinical success was achieved in 23 women (74.2%) following a single embolization. In total, 27 out of 31 women (87%) had been exclusively managed by UAE with conservative success. Although procedural success was achieved in this number, six women had a further procedure to evacuate RPOC despite procedural success. Large uterine arteriovenous (AV) shunts associated with RPOC were observed in five cases (16.1%), among which two were successfully treated after a single UAE and one after two UAEs, while hysterectomy was performed in the last two cases despite two and three UAE procedures respectively. RPOC was histologically proven in ten cases (32.2%) including four out of five cases of uterine AV shunt.ConclusionRPOC with MV can present with large uterine AV shunt, particularly in case of late management. Uterine artery embolization is an effective and safe first-line treatment, and should be evaluated for this indication in larger prospective trials.

  1. FDG PET scan strategies and long-term outcomes after first-line therapy in Hodgkin's Disease

    Energy Technology Data Exchange (ETDEWEB)

    Poulou, Loukia S. [Department of Computed Tomography, ' Sotiria' General Hospital for Chest Diseases, Athens (Greece); Karianakis, George [Bone Marrow Transplantation Unit, ' Hygeia' Diagnostic and Therapeutic Centre, 4 Erythrou Stavrou Street, 151 23 Athens (Greece); Ziakas, Panayiotis D. [Bone Marrow Transplantation Unit, ' Hygeia' Diagnostic and Therapeutic Centre, 4 Erythrou Stavrou Street, 151 23 Athens (Greece)], E-mail: zpanos@otenet.gr

    2009-06-15

    Background: The use of positron emission tomography with fluoro-deoxy-glucose (FDG PET) in Hodgkin's disease (HD) is continuing to expand worldwide, with response assessment after completion of therapy being its most widely utilized application. A positive scan has been associated with high relapse rates and disease progression. Methods: A decision analysis was performed to determine the long-term impact of FDG PET restaging both with and without computed tomography (CT) in terms of the 5-year progression-free survival (5yrPFS). Outcomes and utilities were based on published data. The first strategy involved CT restaging after first-line therapy, with or without subsequent FDG PET, while Second strategy used FDG PET scan alone. All positive test required histological examination. Upon histological confirmation of active lymphoma, patients were considered candidates for autologous transplantation and long-term outcomes were retrieved. The expected clinical benefit of the two strategies was calculated and depicted, along with the mean costs. One-way and two-way sensitivity analyses were performed to ensure the validity of the results. Results: CT restaging plus FDG PET when residual mass is detected, results in a 2% benefit at 5yrPFS at baseline compared to FDG PET-alone restaging and remains positive for a wide range of probabilities. This strategy reduces the average cost by Euro 1863 per patient, including costs of biopsy and autologous transplantation. Conclusion: A more conservative approach that includes CT restaging after first-line therapy and FDG PET scan only on residual mass, is the preferred strategy in HD. Furthermore it appears to confer the maximal diagnostic yield along with a substantial reduction in the mean cost.

  2. Role of erlotinib in first-line and maintenance treatment of advanced non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Noemí Reguart

    2010-06-01

    Full Text Available Noemí Reguart1, Andrés Felipe Cardona2, Rafael Rosell31Medical Oncology Service, ICMHO, Hospital Clinic Barcelona, Barcelona, Spain; 2Clinical and Translational Oncology Group, Institute of Oncology, Fundación Santa Fe de Bogotá, Bogotá, D.C., Colombia; 3Medical Oncology Service, Catalan Institute of Oncology, ICO, Hospital Germans Trias i Pujol, Badalona, Barcelona, SpainAbstract: Erlotinib hydrochloride (Tarceva® is a member of a class of small molecule inhibitors that targets the tyrosine kinase domain of the epidermal growth factor receptor (EGFR, with anti-tumor activity in preclinical models. Erlotinib represents a new-generation of agents known as “targeted therapies” designed to act upon cancer cells by interfering with aberrant specific activated pathways needed for tumor growth, angiogenesis and cell survival. Since its approval in November 2004 for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC after the failure of at least one prior chemotherapy regimen and with a view to improving patients’ outcomes and prevent symptoms, the scientific community has evaluated the potential role of erlotinib in other scenarios such as in maintenance therapy and, in first-line setting for a selected population based on biological markers of response such as mutations of the EGFR. The convenient once-a-day pill administration and the good toxicity profile of erlotinib make it a reasonable candidate for testing in this context. This report provides a review of the role of erlotinib therapy in advanced NSCLC. It summarizes current data and perspectives of erlotinib in upfront treatment and maintenance for advanced NSCLC as well as looking at candidate biomarkers of response to these new targeted-agents.Keywords: erlotinib, tyrosine kinase inhibitors, first line, maintenance, non-small-cell lung cancer

  3. Capecitabine in combination with either cisplatin or weekly paclitaxel as a first-line treatment for metastatic esophageal squamous cell carcinoma: a randomized phase II study

    International Nuclear Information System (INIS)

    Lee, Su Jin; Kim, Sungmin; Kim, Moonjin; Lee, Jeeyun; Park, Yeon Hee; Im, Young-Hyuck; Park, Se Hoon

    2015-01-01

    The aim of this study was to assess the efficacy and safety of a combination regimen of capecitabine plus cisplatin (CC) or capecitabine plus paclitaxel (CP) as a first-line treatment in patients with metastatic esophageal squamous cell carcinoma. Patients with recurrent or metastatic esophageal squamous cell carcinoma were enrolled in this open-label, phase II, randomized trial. Patients were assigned to either the CC arm (days [D]1–14 capecitabine 1000 mg/m 2 twice daily + D1 cisplatin 75 mg/m 2 , every 3 weeks) or the CP arm (D1–14 capecitabine 1000 mg/m 2 twice daily + D1, 8 paclitaxel 80 mg/m 2 , every 3 weeks). The primary endpoint of the study was response rate and secondary endpoints were progression-free survival (PFS), overall survival (OS), toxicity and quality of life. A total of 94 patients were entered into this study between October 2008 and October 2012, 46 patients in the CC arm and 48 in the CP arm. Patients in both arms received a median of six cycles of treatment (range, 1–14) and the response rates were 57 and 58 % in the cisplatin and paclitaxel arm, respectively. With a median follow-up of 23 months, the median PFS was 5.1 months (95 % CI 4.0–6.2 months) in the cisplatin arm and 6.7 months (95 % CI 4.9–8.5 months) in the paclitaxel arm, whereas the median OS was 10.5 months (95 % CI 9.2–11.9 months) in the cisplatin arm and 13.2 months (95 % CI 9.4–17.0 months) in the paclitaxel arm. Patients in the cisplatin arm were more likely to experience neutropenia and thrombocytopenia, whereas patients in the paclitaxel arm had a higher frequency of neuropathy and alopecia. Quality of life was similar between treatment arms. Both CC and CP regimens were effective and well tolerated as a first-line treatment in patients with metastatic esophageal squamous cell carcinoma

  4. Interactive Tailored Website to Promote Sun Protection and Skin Self-Check Behaviors in Patients With Stage 0-III Melanoma

    Science.gov (United States)

    2017-11-15

    Stage 0 Skin Melanoma; Stage I Skin Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage II Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage III Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma

  5. Female Urethral Malignant Melanoma With Vesical Invasion: A Case Report

    Directory of Open Access Journals (Sweden)

    Alpaslan Akbas

    2010-02-01

    Full Text Available We report a 75-year-old female with a primary urethral malignant melanoma. A mass protruding from inside the urethra was detected on physical examination. Abdominopelvic magnetic resonance imaging revealed a mass extending from the urethra with dimensions of 4 × 2 cm, and periurethral heterogenous fatty planes consistent with infiltration. The histopathologic examination was consistent with HMB45(+ malignant melanoma. We performed cystourethrectomy and bilateral inguinal and pelvic lymphadenectomy in one session. The pathology report revealed primary malignant melanoma of the urethra invading the inferior bladder wall. The patient received no adjuvant therapy because of cardiopulmonary morbidities and the presence of multiple pulmonary metastases. The patient eventually died 13 months after surgery.

  6. Vinorelbine as first-line or second-line therapy for advanced breast cancer: a Phase I-II trial by the Danish Breast Cancer Co-operative Group

    DEFF Research Database (Denmark)

    Langkjer, S.T.; Ejlertsen, B.; Mouridsen, H.

    2008-01-01

    INTRODUCTION: This study was conducted to establish the maximum tolerated dose (MTD) of intravenous vinorelbine and on the determined dose to assess efficacy and safety in patients with metastatic breast cancer previously treated with epirubicin. PATIENTS AND METHODS: Patients had histologically...... proven breast cancer and had received a prior epirubicin based regimen either adjuvant or as first line therapy for advanced disease. Vinorelbine was administered intravenously day 1 and 8 in a 3 weeks' schedule. Subsequently 48 additional patients were treated at one dose-level below MTD. RESULTS: Fifty...

  7. Synchronous high-risk melanoma and lymphoid neoplasia.

    LENUS (Irish Health Repository)

    Cahill, R A

    2012-02-03

    Large population-based studies have shown a significant association between melanoma and lymphoid neoplasia, particularly non-Hodgkin\\'s lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), that is independent of any treatment received for the initial tumour. This study examines the presentation, diagnosis, treatment and progress of three patients who developed advanced melanoma concurrently with a lymphoid neoplasm (one NHL, two CLLs), in order to illustrate their association, discuss common aetiological factors and examine possible therapeutic options. As it is the melanoma rather than the lymphoid neoplasm that represents the bigger threat to overall survival, initial treatment should be targeted towards this cancer. However, because of the interplay between the diseases and the possible side-effects of the various treatments, the choice of adjuvant therapy requires careful consideration. Immunosuppression associated with chemotherapy may permit a more aggressive course for the melanoma, while locoregional radiotherapy is contraindicated following lymph node dissections. As immunotherapy is of benefit in the treatment of melanoma and has also been recently shown to be effective in the management of lymphoid neoplasia, we instituted interferon-alpha as adjuvant therapy for these patients, thereby utilizing a single agent to treat the dual pathologies. The three patients have now been followed-up for 6 months without evidence of disease recurrence or progression.

  8. Histological Types of Polypoid Cutaneous Melanoma II

    OpenAIRE

    Knežević, Fabijan; Duančić, Vjekoslav; Šitić, Sanda; Horvat-Knežević, Anica; Benković, Vesna; Ramić, Snježana; Kostović, Krešimir; Ramljak, Vesna; Velemir Vrdoljak, Danko; Stanec, Mladen; Božović, Angelina

    2007-01-01

    The aim of this study was to ascertain which histological types of melanoma can clinically and morphologically appear as polypoid melanomas. In 645 cases of primary cutaneous melanoma we have analyzed criteria for diagnosis of polypoid cutaneous melanoma and afterwards we have analyzed growth phase in each polypoid melanoma, histological type of atypical melanocytes, the number of epidermal ridges which are occupied by atypical melanocytes, and distribution according to age, sex a...

  9. Correlation of histologic regression in primary melanoma with sentinel node status.

    Science.gov (United States)

    Botella-Estrada, Rafael; Traves, Victor; Requena, Celia; Guillen-Barona, Carlos; Nagore, Eduardo

    2014-08-01

    The influence of regression on the status of the sentinel node (SN) is controversial. In many centers, the presence of regression in thin melanomas supports the performance of an SN biopsy. To identify whether regression in primary melanoma has any influence on SN involvement. Retrospective study of melanomas with a Breslow thickness greater than 0.75 mm and undergoing SN biopsy from January 1, 2003, through December 31, 2010, at Instituto Valenciano de Oncología, which receives melanoma patients from regional hospitals and dermatology practices. Only cases with paraffin blocks or histologic slides representative of the primary tumor and available for review were included in the study. Melanomas from 201 patients met these criteria and constitute the core of this study. Sentinel node biopsy in melanoma. Presence or absence of regression in the primary melanoma, type (early vs late), and extension were correlated with the presence or absence of metastasis in the SNs. In addition, the main clinical and histologic characteristics of the primary melanoma were correlated with the status of SN and the regression features. Regression was found in 52 melanomas (25.9%). Regression did not show a statistically significant association with SN status. When melanomas were subdivided by Breslow thickness into 4 groups, those with regression had a lower frequency of positive SNs in 3 of the 4 groups (≤1.00, 1.01-2.00, and >4.00 mm), although differences did not reach statistical significance in any group. We found no influence by type of regression or its extension on the SN status. Regression was found more frequently in thin melanomas (≤1.00 mm), melanomas located on an axial site, and superficial spreading or lentigo maligna melanoma types (P = .02, P < .001, and P = .03, respectively). Regression of the primary melanoma is not associated with a higher proportion of positive SNs. These data do not support the practice of performing SN biopsy in thin melanomas

  10. Preventing Melanoma PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2015-06-02

    This 60 second public service announcement is based on the June 2015 CDC Vital Signs report. Skin cancer is the most common form of cancer in the U.S. In 2011, there were more than 65,000 cases of melanoma, the most deadly form of skin cancer. Learn how everyone can help prevent skin cancer.  Created: 6/2/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 6/2/2015.

  11. Dermoscopy of melanoma and non-melanoma skin cancer.

    Science.gov (United States)

    Babino, G; Lallas, A; Longo, C; Moscarella, E; Alfano, R; Argenziano, G

    2015-10-01

    Skin cancer is a major health problem because of its high incidence in white populations, as well as its related potential morbidity and mortality. Dermoscopy is a noninvasive tool that allows the identification of specific morphological features in different skin tumors, improving significantly the early diagnosis of melanoma and non-melanoma skin cancer (NMSC). This tool has also gained increased interest in the management of NMSC therapy and in the post-treatment follow-up. In this article, we provide a review of the dermoscopic patterns and criteria for the diagnosis of melanoma and NMSC described until now in the literature.

  12. A prospective study of XELIRI plus bevacizumab as a first-line therapy in Japanese patients with unresectable or recurrent colorectal cancer (KSCC1101).

    Science.gov (United States)

    Ando, Koji; Emi, Yasunori; Suenaga, Toyokuni; Hamanoue, Masahiro; Maekawa, Soichiro; Sakamoto, Yasuo; Kai, Seiichiro; Satake, Hironaga; Shimose, Takayuki; Shimokawa, Mototsugu; Saeki, Hiroshi; Oki, Eiji; Sakai, Kenji; Akagi, Yoshito; Baba, Hideo; Maehara, Yoshihiko

    2017-10-01

    This study was designed to evaluate the efficacy and toxicity of XELIRI plus bevacizumab for the treatment of Japanese patients with unresectable or recurrent colorectal cancer (CRC). This was a multicenter, single-arm, open-label prospective study. The major inclusion criteria were previously untreated unresectable or recurrent CRC, presence of measurable lesions, ≥20 years of age, Eastern Cooperative Oncology Group performance status 0 or 1, and adequate organ function. Patients received bevacizumab (7.5 mg/kg on day 1) and XELIRI (irinotecan 200 mg/m 2 on day 1 plus capecitabine 800 mg/m 2 b.i.d. on days 1-14) every 3 weeks. The primary endpoint was the objective tumor response rate. A total of 36 patients were enrolled in this study from July 2011 to September 2012. One patient did not fulfill the eligibility criteria and one patient withdrew their consent before the start of the treatment protocol. The confirmed objective response rate was 58.8% (95% CI 35.1-70.2%). The median progression-free survival was 9.6 months (95% CI 5.1-11.1 months) and the median overall survival was 23.1 months (95% CI 11.3-36.7 months). The grade ≥3 adverse events that were frequently encountered in this study were neutropenia (31.4%), leukopenia (22.9%), diarrhea (22.9%), anemia (20.0%), anorexia (20.0%) and febrile neutropenia (17.2%). The frequency of grade 3/4 adverse events, such as neutropenia and leukopenia, was much higher in patients with a UGT1A1 polymorphism. A first-line therapy comprising XELIRI plus bevacizumab yielded a promising response rate. However, careful attention should be given to adverse clinical events in Japanese patients receiving treatment with unresectable or recurrent CRC.

  13. Clinical Impact of the Number of Treatment Cycles in First-Line Docetaxel for Patients With Metastatic Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Kongsted, Per; Svane, Inge Marie; Lindberg, Henriette; Sengeløv, Lisa

    2017-04-01

    We investigated the impact of the number of docetaxel cycles administered in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line chemotherapy. Charts from 421 consecutive patients who initiated standard treatment with docetaxel-based chemotherapy (75 mg/m 2 every 3 weeks) between 2007 and 2013 were reviewed. Patients who received patients were divided into 2 groups on the basis of whether or not ≥ 9 cycles of docetaxel were administered (n = 108 and 184, respectively). Reasons for treatment discontinuation and postdocetaxel treatments were registered. Prostate-specific antigen (PSA) responses were defined as a confirmed ≥ 50% decrease in baseline PSA levels. Overall survival (OS) was calculated from start of therapy using the Kaplan-Meier method. Cox proportional hazards were calculated to estimate the effect of clinical variables on OS. OS was longer in patients treated with ≥ 9 cycles of docetaxel (21.9 months vs. 17.2 months; P patients treated with ≥ 9 cycles of docetaxel when only patients ending docetaxel because of toxicity or treatment conclusion (22.3 vs. 19.4 months; P = .048, log rank) or patients who achieved a PSA response (22.3 vs. 18.7 months; P = .012, log rank) were evaluated. mCRPC-related prognostic factors and patients who received ≥ 1 subsequent line of therapy post-docetaxel were well balanced. On the basis of our retrospective findings, a superior OS was found in patients treated with ≥ 9 cycles of docetaxel when adjusting for known prognostic factors. Dose reductions might increase the number of docetaxel cycles administered. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. PSA time to nadir as a prognostic factor of first-line docetaxel treatment in castration-resistant prostate cancer: evidence from patients in Northwestern China.

    Science.gov (United States)

    Wu, Kai-Jie; Pei, Xin-Qi; Tian, Ge; Wu, Da-Peng; Fan, Jin-Hai; Jiang, Yu-Mei; He, Da-Lin

    2018-01-01

    Docetaxel-based chemotherapy remains the first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) in China; however, the prognostic factors associated with effects in these patients are still controversial. In this study, we retrospectively reviewed the data from 71 eligible Chinese patients who received docetaxel chemotherapy from 2009 to 2016 in our hospital and experienced a reduction of prostate-specific antigen (PSA) level ≥50% during the treatment and investigated the potential role of time to nadir (TTN) of PSA. TTN was defined as the time from start of chemotherapy to the nadir of PSA level during the treatment. Multivariable Cox regression models and Kaplan-Meier analysis were used to predict overall survival (OS). In these patients, the median of TTN was 17 weeks. Patients with TTN ≥17 weeks had a longer response time to chemotherapy compared to TTN PSA progression in patients with TTN ≥17 weeks was 11.44 weeks compared to 5.63 weeks when TTN was PSA level at the diagnosis of cancer (HR: 4.337, 95% CI: 1.616-11.645, P = 0.004), duration of initial androgen deprivation therapy (HR: 2.982, 95% CI: 1.104-8.045, P = 0.031), neutrophil-to-lymphocyte ratio (HR: 3.963, 95% CI: 1.380-11.384, P = 0.011), and total PSA response (Class 1 [PSA remains an important prognostic marker in predicting therapeutic outcome in Chinese population who receive chemotherapy for mCRPC and have >50% PSA remission.

  15. The benefit of a remotely monitored implantable loop recorder as a first line investigation in unexplained syncope: the EaSyAS II trial.

    Science.gov (United States)

    Sulke, Neil; Sugihara, Conn; Hong, Paul; Patel, Nik; Freemantle, Nick

    2016-06-01

    This prospective randomized controlled study evaluated the first-line use of a novel remotely monitored implantable loop recorder (ILR) in the initial investigation of unexplained syncope, and compared this to conventional therapy and a dedicated Syncope Clinic (SC). A total of 246 patients (mean age 70.3 years) were randomly allocated to conventional management, SC alone, ILR alone, or SC + ILR. Median follow-up was 20 months (IQR 15-25 months). Time to electrocardiogram (ECG) diagnosis was significantly shorter with ILR alone vs. conventional [hazard ratio (HR) 35.5, P = 0.0004] and with SC vs. conventional (HR 25.6, P = 0.002). Seventy-four per cent of first syncopal events documented in the SC groups occurred during provocative tilt testing. Twenty-two per cent of patients who received an ILR were found to have a bradycardia indication for permanent pacing, compared with 3% of patients who did not. Overall, more investigative tests were undertaken in the conventional group than in any other. Only patients who received an ILR had a significant increase in time to second syncope (P = 0.02), suggesting successful diagnosis and management of treatable causes of syncope. Implantable loop recorder monitoring achieved a more rapid diagnosis in unexplained syncope than usual care. Conventional management of syncope failed to achieve an ECG diagnosis despite a large number of investigative tests. Syncope Clinic and provocative tilt testing delivered a rapid ECG diagnosis, but did not prevent recurrent syncope. Implantable loop recorders offered rapid diagnosis, increased the likelihood of syncope being reported, demonstrated a high rate of intermittent bradycardia requiring pacing, and reduced recurrent syncope. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  16. Optimal duration of a first-line palliative chemotherapy in disseminated colorectal cancer – a review of the literature from a developing country perspective

    OpenAIRE

    Wojciech Rogowski; Violetta Sulżyc-Bielicka

    2016-01-01

    We still do not know whether the presently used protocol of the first-line palliative treatment of disseminated colorectal cancer (FOLFOX/FOLFIRI protocol) allows maximization of therapeutic response and minimization of side effects. No-one has verified whether continuation of the first-line chemotherapy despite the lack of progression is reflected by improved prognosis or significant risk of toxicity. This issue is of vital importance in the case of developing countries where targeted therap...

  17. Cerebral metastases from malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, G. (Royal Prince Alfred Hospital, Sydney (Australia). Department of Radiation Oncology Royal Prince Alfred Hospital, Sydney (Australia). Sydney Melanoma Unit); Firth, I. (Royal Prince Alfred Hospital, Sydney (Australia). Department of Medical Oncology); Coates, A. (Royal Prince Alfred Hospital, Sydney (Australia). Department of Radiation Oncology Royal Prince Alfred Hospital, Sydney (Australia). Sydney Melanoma Unit)

    1993-03-01

    A retrospective study was undertaken of factors affecting survival in 129 patients with cerebral metastases from malignant melanoma referred to the Department of Radiation Oncology from June '82-January '90. Their ages ranged from 19-83 years and the time interval form diagnosis of the primary tumour to development of cerebral metastases ranged from 1 month-17 years. Cerebral metastases were apparently solitary in 59 (46%) and multiple in 70 (54%) patients. Craniotomy with resection of tumour was performed in 49 patients, of whom 24 had a solitary cerebral metastasis as the only evidence of disease Most patients (94%) received radiotherapy-course. Median survival of the whole group after detection of cerebral metastases was 5 months (range <1-87+). Univariate analysis indicated that a solitary cerebral metastasis, absence of extracranial disease and tumour resection predicted improved survival, but only surgical intervention was of independent prognostic significance in a multivariate analysis. The effect of cranial irradiation on survival could not be assessed, but the dose of radiation did not influence survival. Of the 10 patients who survived for more than 2 years, 8 had total resection of a solitary cerebral metastasis. (author). 25 refs., 3 figs., 3 tabs.

  18. Cost-utility of First-line Disease-modifying Treatments for Relapsing-Remitting Multiple Sclerosis.

    Science.gov (United States)

    Soini, Erkki; Joutseno, Jaana; Sumelahti, Marja-Liisa

    2017-03-01

    This study evaluated the cost-effectiveness of first-line treatments of relapsing-remitting multiple sclerosis (RRMS) (dimethyl fumarate [DMF] 240 mg PO BID, teriflunomide 14 mg once daily, glatiramer acetate 20 mg SC once daily, interferon [IFN]-β1a 44 µg TIW, IFN-β1b 250 µg EOD, and IFN-β1a 30 µg IM QW) and best supportive care (BSC) in the health care payer setting in Finland. The primary outcome was the modeled incremental cost-effectiveness ratio (ICER; €/quality-adjusted life-year [QALY] gained, 3%/y discounting). Markov cohort modeling with a 15-year time horizon was employed. During each 1-year modeling cycle, patients either maintained the Expanded Disability Status Scale (EDSS) score or experienced progression, developed secondary progressive MS (SPMS) or showed EDSS progression in SPMS, experienced relapse with/without hospitalization, experienced an adverse event (AE), or died. Patients׳ characteristics, RRMS progression probabilities, and standardized mortality ratios were derived from a registry of patients with MS in Finland. A mixed-treatment comparison (MTC) informed the treatment effects. Finnish EuroQol Five-Dimensional Questionnaire, Three-Level Version quality-of-life and direct-cost estimates associated with EDSS scores, relapses, and AEs were applied. Four approaches were used to assess the outcomes: cost-effectiveness plane and efficiency frontiers (relative value of efficient treatments); cost-effectiveness acceptability frontier, which demonstrated optimal treatment to maximize net benefit; Bayesian treatment ranking (BTR); and an impact investment assessment (IIA; a cost-benefit assessment), which increased the clinical interpretation and appeal of modeled outcomes in terms of absolute benefit gained with fixed drug-related budget. Robustness of results was tested extensively with sensitivity analyses. Based on the modeled results, teriflunomide was less costly, with greater QALYs, versus glatiramer acetate and the IFNs

  19. A novel tandem mass spectrometry method for first-line screening of mainly beta-thalassemia from dried blood spots.

    Science.gov (United States)

    Yu, Chaowen; Huang, Shuodan; Wang, Ming; Zhang, Juan; Liu, Hao; Yuan, Zhaojian; Wang, Xingbin; He, Xiaoyan; Wang, Jie; Zou, Lin

    2017-02-10

    Traditional methods for thalassemia screening are time-consuming and easily affected by cell hemolysis or hemoglobin degradation in stored blood samples. Tandem mass spectrometry (MS/MS) proved to be an effective technology for sickle cell disorders (SCD) screening. Here, we developed a novel MS/MS method for β-thalassemia screening from dried blood spots (DBS). Stable isotopic-labeled peptides were used as internal standards for quantification and calculation of the α:β-globin ratios. We used the α:β-globin ratio cutoffs to differentiate between normal individuals and patients with thalassemia. About 781 patients and 300 normal individuals were analyzed. The α:β-globin ratios showed significant difference between normal and β-thalassemia patients (Pthalassemia mutation. In the parallel study, all cases screened for suspected thalassemia from six hundred DBS samples by using this MS/MS method were successfully confirmed by genotyping. The intra-assay and inter-assay CVs of the ratios ranged from 2.4% to 3.9% and 4.7% to 7.1%, and there was no significant sample carryover or matrix effect for this MS/MS method. Combined with SCD screening, this MS/MS method could be used as a first-line screening assay for both structural and expression abnormalities of human hemoglobin. Traditional methods for thalassemia screening were depending on the structural integrity of tetramers and could be affected by hemolysis and degradation of whole blood samples, especially when stored. We used proteospecific peptides produced by the tryptic digestion of each globin to evaluate the production ratio between α- and β-globin chains, which turned out to be quite stable even when stored for more than two months. Though most of the peptides were specific to α-globin or β-globin, we only chose four most informative peptides and its stable isotopic-labeled peptides as internal standards for analysis, which could obtain a high accuracy. Currently, we are the first to address the

  20. The Effects of First-Line Anti-Tuberculosis Drugs on the Actions of Vitamin D in Human Macrophages.

    Science.gov (United States)

    Chesdachai, Supavit; Zughaier, Susu M; Hao, Li; Kempker, Russell R; Blumberg, Henry M; Ziegler, Thomas R; Tangpricha, Vin

    2016-12-01

    Tuberculosis (TB) is a major global health problem. Patients with TB have a high rate of vitamin D deficiency, both at diagnosis and during the course of treatment with anti-tuberculosis drugs. Although data on the efficacy of vitamin D supplementation on Mycobacterium tuberculosis (Mtb) clearance is uncertain from randomized controlled trials (RCTs), vitamin D enhances the expression of the anti-microbial peptide human cathelicidin (hCAP18) in cultured macrophages in vitro. One possible explanation for the mixed (primarily negative) results of RCTs examining vitamin D treatment in TB infection is that anti-TB drugs given to enrolled subjects may impact actions of vitamin D to enhance cathelicidin in macrophages. To address this hypothesis, human macrophage-like monocytic (THP-1) cells were treated with varying doses of first-line anti-tuberculosis drugs in the presence of the active form of vitamin D, 1N1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ). The expression of hCAP18 was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). 1,25(OH) 2 D 3 strongly induced expression of hCAP18 mRNA in THP-1 cells (fold-change from control). The combination of the standard 4-drug TB therapy (isoniazid, rifampicin, pyrazinamide and ethambutol) in the cultured THP-1 cells demonstrated a significant decrease of hCAP18 mRNA at the dosage of 10 ug/mL. In 31 subjects with newly diagnosed drug-sensitive TB randomized to either high-dose vitamin D 3 (1.2 million IU over 8 weeks, n=13) versus placebo (n=18), there was no change from baseline to week 8 in hCAP18 mRNA levels in peripheral blood mononuclear cells or in plasma concentrations of LL-37, the protein product of hCAP18.These data suggest that first-line anti-TB drugs may alter the vitamin D-dependent increase in hCAP18 and LL-37 human macrophages.

  1. High-dose dual therapy is superior to standard first-line or rescue therapy for Helicobacter pylori infection.

    Science.gov (United States)

    Yang, Jyh-Chin; Lin, Chun-Jung; Wang, Hong-Long; Chen, Jin-De; Kao, John Y; Shun, Chia-Tung; Lu, Chien-Wei; Lin, Bor-Ru; Shieh, Ming-Jium; Chang, Ming-Chu; Chang, Yu-Ting; Wei, Shu-Chen; Lin, Lin-Chih; Yeh, Wen-Chun; Kuo, Jen-Shin; Tung, Chien-Chih; Leong, Yew-Loong; Wang, Teh-Hong; Wong, Jau-Min

    2015-05-01

    The efficacy of treatment of Helicobacter pylori infection has decreased steadily because of increasing resistance to clarithromycin, metronidazole, and levofloxacin. Resistance to amoxicillin is generally low, and high intragastric pH increases the efficacy of amoxicillin, so we investigated whether a combination of a high-dose proton pump inhibitor and amoxicillin (dual therapy) was more effective than standard first-line or rescue therapies in eradicating H pylori. We performed a large-scale multihospital trial to compare the efficacy of a high-dose dual therapy (HDDT) with that of standard therapies in treatment-naive (n = 450) or treatment-experienced (n = 168) patients with H pylori infection. Treatment-naive patients were randomly assigned to groups given HDDT (rabeprazole 20 mg and amoxicillin 750 mg, 4 times/day for 14 days, group A1), sequential therapy for 10 days (group B1), or clarithromycin-containing triple therapy for 7 days (group C1). Treatment-experienced patients were randomly assigned to groups given HDDT for 14 days (group A2), sequential therapy for 10 days (B2), or levofloxacin-containing triple therapy for 7 days (C2). H pylori infection was detected by using the (13)C-urea breath test. We evaluated factors associated with treatment outcomes. In the intention-to-treat analysis, H pylori was eradicated in 95.3% of patients in group A1 (95% confidence interval [CI], 91.9%-98.8%), 85.3% in B1 (95% CI, 79.6%-91.1%), and 80.7% in group C1 (95% CI, 74.3%-87.1%). Infection was eradicated in 89.3% of patients in group A2 (95% CI, 80.9%-97.6%), 51.8% in group B2 (95% CI, 38.3%-65.3%), and 78.6% (95% CI, 67.5%-89.7%) in group C2. The efficacy of HDDT was significantly higher than that of currently recommended regimens, irrespective of CYP2C19 genotype. Bacterial resistance to drugs was associated with treatment failure. There were no significant differences between groups in adverse events or patient adherence. HDDT is superior to standard regimens

  2. Longitudinal Analysis of Adherence to First-Line Antiretroviral Therapy: Evidence of Treatment Sustainability from an Indian HIV Cohort.

    Science.gov (United States)

    Shet, Anita; Kumarasamy, N; Poongulali, Selvamuthu; Shastri, Suresh; Kumar, Dodderi Sunil; Rewari, Bharath B; Arumugam, Karthika; Antony, Jimmy; De Costa, Ayesha; D'Souza, George

    2016-01-01

    Given the chronic nature of HIV infection and the need for life-long antiretroviral therapy (ART), maintaining long-term optimal adherence is an important strategy for maximizing treatment success. In order to understand better the dynamic nature of adherence behaviors in India where complex cultural and logistic features prevail, we assessed the patterns, trajectories and time-dependent predictors of adherence levels in relation to virological failure among individuals initiating first-line ART in India. Between July 2010 and August 2013, eligible ART-naïve HIV-infected individuals newly initiating first-line ART within the national program at three sites in southern India were enrolled and monitored for two years. ART included zidovudine/stavudine/tenofovir plus lamivudine plus nevirapine/efavirenz. Patients were assessed using clinical, laboratory and adherence parameters. Every three months, medication adherence was measured using pill count, and a structured questionnaire on adherence barriers was administered. Optimal adherence was defined as mean adherence ≥95%. Statistical analysis was performed using a bivariate and a multivariate model of all identified covariates. Adherence trends and determinants were modeled as rate ratios using generalized estimating equation analysis in a Poisson distribution. A total of 599 eligible ART-naïve patients participated in the study, and contributed a total of 921 person-years of observation time. Women constituted 43% and mean CD4 count prior to initiating ART was 192 cells/mm3. Overall mean adherence among all patients was 95.4%. The proportion of patients optimally adherent was 75.6%. Predictors of optimal adherence included older age (≥40 years), high school-level education and beyond, lower drug toxicity-related ART interruption, full disclosure, sense of satisfaction with one's own health and patient's perception of having good access to health-care services. Adherence was inversely proportional to virological

  3. Melanoma Surveillance in the US: The Economic Burden of Melanoma

    Centers for Disease Control (CDC) Podcasts

    2011-10-19

    This podcast accompanies the publication of a series of articles on melanoma surveillance in the United States, available in the November supplement edition of the Journal of the American Academy of Dermatology. Dr. Gery Guy, from the CDC’s Division of Cancer Prevention and Control, discusses the economic burden of melanoma.  Created: 10/19/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/19/2011.

  4. Superficial melanomas of oral mucous membranes.

    Science.gov (United States)

    Regezi, J A; Hayward, J R; Pickens, T N

    1978-05-01

    In accordance with microscopic and clinical criteria established for superficial melanomas of the skin (superficial spreading melanoma, lentigo maligna melanoma, acral-lentiginous melanoma), three oral lesions have been evaluated. The literature on oral melanomas has also been reviewed, with special attention given to those cases that had pre-existing melanosis. One patient with a diagnosis of superficial spreading melanoma eventually died of his untreated lesion 11 years after its first appearance. Two patients had lesions diagnosed as acral-lentiginous melanoma (a group which also includes volar and subungual melanomas) that exhibited aggressive, recurrent behavior. These lesions had microsocpic features similar to lentigo maligna melanoma but did not behave in a manner consistent with that diagnosis. Electron microscopic study of one acral-lentiginous melanoma demonstrated malenosomes and premelanosomes that were like those seen in normal melanocytes and nevus cells. The superficial or radial growth phase of many oral melanomas has apparently gone unrecognized. Melanosis has been reported to be a common feature of invasive oral melanomas but has not generally been related to the natural history of these lesions. Oral lesions with a prolonged intra-epithelial or radial growth phase would be expected to have a better prognosis than nodular melanomas, but meaningful survival data are not available because of the infrequency with which oral melanomas have been subclassified.

  5. Primary dermal melanoma: a West Australian cohort.

    Science.gov (United States)

    Teow, James; Chin, Olivia; Hanikeri, Mark; Wood, Benjamin A

    2015-09-01

    The objectives of this study were to identify a subgroup of patients with putative primary dermal melanoma after thorough multidisciplinary clinical and histological evaluation, and to describe the clinical, histological and selected molecular features of these lesions. The records of the Western Australian Melanoma Advisory Service were searched for potential cases of primary dermal melanoma. The clinical and histological features were reviewed, immunohistochemical assessment was performed and clinical outcomes recorded. Eighteen cases of putative primary dermal melanoma with available clinical data were identified. Two of 12 cases in which further histological sections could be obtained were excluded because of the presence of findings suggesting an epidermal origin on these further sections. In one additional case, such origin could not be histologically excluded. Median follow-up period for the remaining cases was 68 months. Confirmed primary dermal melanoma accounts for 0.87% of cases of melanoma referred to a subspecialist melanoma advisory service. These cases show significant histological overlap with dermal/subcutaneous metastases of melanoma, but display a relatively good prognosis, with a 5-year survival of 87.5%. Our results support the recognition of a distinct group of melanoma that mimics metastatic melanoma, but is associated with a relatively favourable outcome. The group of putative primary dermal melanoma is likely to be heterogenous, including cases of primary nodular melanoma in which epidermal connection has not been identified, metastatic melanoma with an occult primary lesion and true primary dermal melanoma. © 2015 Royal Australasian College of Surgeons.

  6. Melanoma of the skin in the Danish Cancer Registry and the Danish Melanoma Database

    DEFF Research Database (Denmark)

    Pedersen, Sidsel Arnspang; Schmidt, Sigrun Alba Johannesdottir; Klausen, Siri

    2018-01-01

    BACKGROUND: The nationwide Danish Cancer Registry and the Danish Melanoma Database both record data on melanoma for purposes of monitoring, quality assurance and research. However, the data quality of the Cancer Registry and the Melanoma Database has not been formally evaluated. METHODS: We...... estimated the positive predictive value (PPV) of melanoma diagnosis for random samples of 200 patients from the Cancer Registry (n=200) and the Melanoma Database (n=200) during 2004-2014, using the Danish Pathology Registry as 'gold-standard' reference. We further validated tumor characteristics...... in the Cancer Registry and the Melanoma Database. Additionally, we estimated the PPV of in situ melanoma diagnoses in the Melanoma Database, and the sensitivity of melanoma diagnoses in 2004-2014. RESULTS: The PPVs of melanoma in the Cancer Registry and the Melanoma Database were 97% (95% CI, 94-99) and 100...

  7. High accuracy of family history of melanoma in Danish melanoma cases

    DEFF Research Database (Denmark)

    Wadt, Karin A W; Drzewiecki, Krzysztof T; Gerdes, Anne-Marie

    2015-01-01

    The incidence of melanoma in Denmark has immensely increased over the last 10 years making Denmark a high risk country for melanoma. In the last two decades multiple public campaigns have sought to increase the awareness of melanoma. Family history of melanoma is a known major risk factor...... but previous studies have shown that self-reported family history of melanoma is highly inaccurate. These studies are 15 years old and we wanted to examine if a higher awareness of melanoma has increased the accuracy of self-reported family history of melanoma. We examined the family history of 181 melanoma...... probands who reported 199 cases of melanoma in relatives, of which 135 cases where in first degree relatives. We confirmed the diagnosis of melanoma in 77% of all relatives, and in 83% of first degree relatives. In 181 probands we validated the negative family history of melanoma in 748 first degree...

  8. Is First-Line Vancomycin Still the Best Option to Treat Staphylococcus Health Care-Associated Meningitis?

    Science.gov (United States)

    Mounier, Roman; Lobo, David; Hulin, Anne; Nebbad, Biba; Cook, Fabrice; Dhonneur, Gilles

    2017-03-01

    Cerebrospinal fluid (CSF) penetration of vancomycin through the blood-brain barrier is poor but important inflammation improved it. Hence, vancomycin is recommended for the treatment of community meningitis. However, what about mild inflammatory health care-associated meningitis? The aim of this study was to evaluate the impact of vancomycin diffusion on CSF in Staphylococcus epidermidis health care-associated meningitis. This was a retrospective study of all consecutive patients with S. epidermidis CSF shunt-associated infection, which was treated by continuous intravenous vancomycin after standard of care (60 mg/kg/d after a loading dose of 15 mg/kg). Patient outcome, CSF protein level, and vancomycin concentration in CSF and serum were assessed. We report 6 consecutives cases. Clinical and biologic manifestations were of mild intensity. Meningeal permeability was moderately altered with low CSF protein levels. Despite appropriate vancomycin dosage resulting in high serum concentrations, CSF remained below the S. epidermidis minimal inhibitory concentration. We propose to reassess vancomycin use as first-line therapy when meningeal inflammation is mild-to-moderate in favor of antibiotics, which have a better CSF penetration. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Cost analysis of biologic drugs in rheumatoid arthritis first line treatment after methotrexate failure according to patients' body weight.

    Science.gov (United States)

    Román Ivorra, José Andrés; Ivorra, José; Monte-Boquet, Emilio; Canal, Cristina; Oyagüez, Itziar; Gómez-Barrera, Manuel

    2016-01-01

    The objective was to assess the influence of patients' weight in the cost of rheumatoid arthritis treatment with biologic drugs used in first line after non-adequate response to methotrexate. Pharmaceutical and administration costs were calculated in two scenarios: non-optimization and optimization of intravenous (IV) vials. The retrospective analysis of 66 patients from a Spanish 1,000 beds-hospital Rheumatology Clinic Service was used to obtain posology and weight data. The study time horizon was two years. Costs were expressed in 2013 euros. For an average 69kg-weighted patient the lowest cost corresponded to abatacept subcutaneous (SC ABA) (€21,028.09) in the scenario without IV vials optimization and infliximab (IFX) (€20,779.29) with optimization. Considering patients' weight in the scenario without IV vials optimization infliximab (IFX) was the least expensive drug in patients ranged 45-49kg, IV ABA in 50-59kg and SC ABA in patients over 60kg. With IV vials optimization IFX was the least expensive drug in patients under 69kg and SC ABA over 70kg. Assuming comparable effectiveness of biological drugs, patient's weight is a variable to consider, potentials savings could reach €20,000 in two years. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  10. Course of murine tuberculosis and response to first-line therapy depends on route of infection and inoculum size.

    Science.gov (United States)

    de Steenwinkel, J E M; ten Kate, M T; de Knegt, G J; Verbrugh, H A; van Belkum, A; Hernandez-Pando, R; Bakker-Woudenberg, I A J M

    2011-11-01

    In the search for new anti-tuberculosis drugs, numerous potential drugs are being screened in vitro. In animal models, promising new anti-tuberculosis drugs are assessed in terms of toxic side effects and comparative therapeutic efficacy. Mice are frequently used and experimental infections are established in different ways. To investigate to what extent the route of Mycobacterium tuberculosis inoculation is a determinant in the pathogenesis of tuberculosis (TB) and the therapeutic outcome. Results will contribute to insight into the translational value of TB models used for preclinical studies. TB in mice was established through intratracheal or intravenous mycobacterial inoculation. The efficacy of a 26-week treatment regimen was evaluated, including assessment of relapse of infection 13 weeks post-treatment. It was shown that the course of TB and the therapeutic response, in terms of histopathological characteristics and mycobacterial load, in lungs and extra- pulmonary organs is substantially different and dependent on the route of infection applied and the inoculum size used. When evaluating the comparative therapeutic potential of novel anti-tuberculosis drugs or drug treatment schedules investigated in different studies, it should be noted that the route of infection applied and the inoculum size used influence the course of murine TB and the therapeutic response to the standard first- line anti-tuberculosis drug regimen.

  11. An assessment of the efficacy of first-line Helicobacter pylori-eradication therapy based on clarithromycin susceptibility.

    Science.gov (United States)

    Miyaki, Akira; Yamaguchi, Kentaro; Ida, Arika; Miyauchi, Tatsuomi

    2016-09-01

    In recent years, the efficacy of standard triple therapy comprising proton pump inhibitor, clarithromycin (CAM), and amoxicillin, for the eradication of Helicobacter pylori (H. pylori) infection has reduced owing to the increasing CAM resistance of H. pylori. In this study, we evaluated the effectiveness of first-line H. pylori-eradication therapy on the basis of CAM sensitivity. We enrolled 447 patients who were diagnosed with H. pylori infection from January 2011 to July 2014 and examined the antimicrobial resistance. In total, 260 patients without a history of H. pylori eradication therapy were treated with CAM- or metronidazole (MNZ)-based eradication therapy on the basis of the treatment period and CAM sensitivity of H. pylori. Between January 2011 and June 2013, patients were treated with CAM-based empirical therapy. Between July 2013 and July 2014, patients with CAM-sensitive strains were treated with CAM-based eradication therapy, and those with CAM-resistant strains were treated with MNZ-based therapy. The overall rate of resistance to CAM was 29.8%. The eradication rates of the empirical therapy and CAM-sensitivity-based therapy were 76.5% and 93.0%, respectively (Ppylori-infected patients.

  12. Non small-cell lung cancer and treatment options after tyrosine kinase inhibitors failure in the first line

    International Nuclear Information System (INIS)

    Chowaniecova, G.

    2014-01-01

    Introduction: Advanced non-small cell lung cancer with present epidermal growth factor receptor (EGFR) sensitising mutation is standardly treated with tyrosine kinase inhibitors (TKI). During treatment a resistance to TKI develops, disease progresses. We differ primary and secondary resistance. The most effective treatment after TKI failure is not definitively proven. Standard chemotherapy is usually introduced, eventually it is possible to use other TKI in the next lines. Case: The author presents a case of 60-year old patient with lung adenocarcinoma with EGFR sensitising mutation, where primary resistance to TKI was observed. Chemotherapy after progression was introduced. Planned therapy with afatnib was not carried out due to deterioration of patient´s condition. Conclusion: Presented case of EGFR mutation-positive patient represents an example of not very frequent primary resistance to TKI. Mechanisms of primary resistance are not well understood. Treatment after first line TKI failure in non-small cell lung cancer with EGFR mutation represents a challenge for medical research. (author)

  13. Short term outcomes of topiramate monotherapy as a first-line treatment in newly diagnosed West syndrome.

    Science.gov (United States)

    Lee, Gyu Min; Lee, Kyung Suk; Lee, Eun Hye; Chung, Sajun

    2011-09-01

    To investigate the efficacy of topiramate monotherapy in West syndrome prospectively. The study population included 28 patients (15 male and 13 female children aged 2 to 18 months) diagnosed with West syndrome. After a 2-week baseline period for documentation of the frequency of spasms, topiramate was initiated at 2 mg/kg/day. The dose was increased by 2 mg/kg every week to a maximum of 12 mg/kg/day. Clinical assessment was based on the parents' report and a neurological examination every 2 weeks for the first 2 months of treatment. The baseline electroencephalograms (EEGs) were compared with the post-treatment EEGs at 2 weeks and 1 month. West syndrome was considered to be cryptogenic in 7 of the 28 patients and symptomatic in 21 patients. After treatment, 11 patients (39%) became spasm-free, 6 (21%) had more than 50% spasmsreduction, 3 (11%) showed less than 50% reduction, and 8 (29%) did not respond. The effective daily dose for achieving more than 50% reduction in spasm frequency, including becoming spasm-free, was found to be 5.8±1.1 mg/kg/day. Nine patients (32%) showed complete disappearance of spasms and hypsarrhythmia, and 11 (39%) showed improved EEG results. Despite adverse events (4 instances of irritability, 3 of drowsiness, and 1 of decreased feeding), no patients discontinued the medication. Topiramate monotherapy seems to be effective and well tolerated as a first line therapy for West syndrome and is not associated with serious adverse effects.

  14. Podoplanin Expression in Canine Melanoma.

    Science.gov (United States)

    Ogasawara, Satoshi; Honma, Ryusuke; Kaneko, Mika K; Fujii, Yuki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

    2016-12-01

    A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistry. Of interest, PMab-38 stained the lymphatic endothelial cells and cancer-associated fibroblasts in melanoma tissues, although it did not stain any lymphatic endothelial cells in normal tissues. PMab-38 could be useful for uncovering the function of PDPN in canine melanomas.

  15. Economic impact of healthcare resource utilisation patterns among patients diagnosed with advanced melanoma in the United Kingdom, Italy, and France: results from a retrospective, longitudinal survey (MELODY study).

    Science.gov (United States)

    Johnston, K; Levy, A R; Lorigan, P; Maio, M; Lebbe, C; Middleton, M; Testori, A; Bédane, C; Konto, C; Dueymes, A; Sbarigia, U; van Baardewijk, M

    2012-09-01

    To describe patterns of healthcare resource utilisation and associated costs for patients with advanced melanoma in the United Kingdom (UK), Italy, and France. For patients receiving systemic treatment, or supportive care, data describing hospitalisations, hospice care, and outpatient visits were retrieved retrospectively from advanced disease diagnosis as part of a multicountry observational study. Costs were estimated by multiplying utilisation level by unit cost. In an exploratory analysis, costs were compared between individuals who died within one year of initiating first-line treatment (short-term survivors) and those with ≥ 1 year follow-up (long-term survivors). Hospitalisation costs were highest in France (€6262 per-person compared with €3225 in the UK and €2486 in Italy), reflecting higher rates of hospitalisation. In contrast, outpatient costs were highest in the UK (€782 per-person, compared with €115 in France and €72 in Italy), reflecting the highest rate and frequency of outpatient visits and the highest cost per visit. Hospitalisation rates were consistently higher during supportive care compared with systemic therapy. Roughly one-third of patients entered clinical trials and were not included in the analysis. In exploratory analysis, total costs were generally higher for long-term survivors, but monthly per-patient costs were generally lower for long-term survivors, consistent with a hypothesis that resource utilisation and costs do not necessarily increase proportionally with extended survival. Total costs associated with resource utilisation for advanced melanoma patients varied across countries. Overall cost differences were due to differences in frequency and intensity of utilisation patterns and variation in unit costs of health resources. Copyright © 2012. Published by Elsevier Ltd.

  16. Podoplanin Expression in Canine Melanoma

    OpenAIRE

    Ogasawara, Satoshi; Honma, Ryusuke; Kaneko, Mika K.; Fujii, Yuki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

    2016-01-01

    A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistr...

  17. Case studies of skin melanoma

    Directory of Open Access Journals (Sweden)

    A. V. Kozlova

    2015-01-01

    Full Text Available Skin melanoma is a malignant tumor originating in the cells of the melanocytic system, which is characterized by an aggressive clinical course, significant metastatic potential and unfavorable prognosis. These features of the tumor stipulate the need to improve measures to optimize early diagnosis of tumors. The article presents cases of pigmented skin melanoma to demonstrate the variability of clinical manifestations of this tumor requiring dermatologist skills in the differential diagnostics of neoplasms.

  18. [Choroidal melanoma - evolution and prognosis].

    Science.gov (United States)

    Chiruţa, Daria; Stan, Cristina

    2014-01-01

    Choroidal melanoma is the most common primary intraocular malignant tumor. We present the case of a 62 year old patient who was diagnosed with intraocular tumor in his right eye, for about three years. Regarding the fact that the patient refused any kind of treatment during this period, we just had the opportunity to monitor this case. Finally, the diagnosis was choroidal melanoma, confirmed by the histopathological exam.

  19. Umbilicus reconstruction after melanoma excision

    Directory of Open Access Journals (Sweden)

    Miguel Costa-Silva

    2017-01-01

    Full Text Available An 81-year-old woman was admitted with a nodular cutaneous melanoma of the abdominal wall involving the umbilicus. After performing wide excision with 2 cm margin of the melanoma, umbilical reconstruction and defect closure were planned. After careful consideration, we decided to use an island pedicle flap which allowed closure of the defect and reconstruction of the umbilicus.

  20. An ANOCEF genomic and transcriptomic microarray study of the response to radiotherapy or to alkylating first-line chemotherapy in glioblastoma patients

    Directory of Open Access Journals (Sweden)

    Ducray François

    2010-09-01

    Full Text Available Abstract Background The molecular characteristics associated with the response to treatment in glioblastomas (GBMs remain largely unknown. We performed a retrospective study to assess the genomic characteristics associated with the response of GBMs to either first-line chemotherapy or radiation therapy. The gene expression (n = 56 and genomic profiles (n = 67 of responders and non-responders to first-line chemotherapy or radiation therapy alone were compared on Affymetrix Plus 2 gene expression arrays and BAC CGH arrays. Results According to Verhaak et al.'s classification system, mesenchymal GBMs were more likely to respond to radiotherapy than to first-line chemotherapy, whereas classical GBMs were more likely to respond to first-line chemotherapy than to radiotherapy. In patients treated with radiation therapy alone, the response was associated with differential expression of microenvironment-associated genes; the expression of hypoxia-related genes was associated with short-term progression-free survival ( 10 months. Consistently, infiltration of the tumor by both CD3 and CD68 cells was significantly more frequent in responders to radiotherapy than in non-responders. In patients treated with first-line chemotherapy, the expression of stem-cell genes was associated with resistance to chemotherapy, and there was a significant association between response to treatment and p16 locus deletions. Consistently, in an independent data set of patients treated with either radiotherapy alone or with both radiotherapy and adjuvant chemotherapy, we found that patients with the p16 deletion benefited from adjuvant chemotherapy regardless of their MGMT promoter methylation status, whereas in patients without the p16 deletion, this benefit was only observed in patients with a methylated MGMT promoter. Conclusion Differential expression of microenvironment genes and p16 locus deletion are associated with responses to radiation therapy and to first-line

  1. Systematic review of psychosocial outcomes for patients with advanced melanoma.

    Science.gov (United States)

    Dunn, Jeff; Watson, Maggie; Aitken, Joanne F; Hyde, Melissa K

    2017-11-01

    New advanced melanoma therapies are associated with improved survival; however, quality of survivorship, particularly psychosocial outcomes, for patients overall and those treated with newer therapies is unclear. Synthesize qualitative and quantitative evidence about psychosocial outcomes for advanced (stage III/IV) melanoma patients. Five databases were searched (01/01/1980 to 31/01/2016). Inclusion criteria were as follows: advanced melanoma patients or sub-group analysis; assessed psychosocial outcomes; and English language. Fifty-two studies met review criteria (4 qualitative, 48 quantitative). Trials comprise mostly medical not psychosocial interventions, with psychosocial outcomes assessed within broader quality of life measures. Patients receiving chemotherapy or IFN-alpha showed decreased emotional and social function and increased distress. Five trials of newer therapies appeared to show improvements in emotional and social function. Descriptive studies suggest that patients with advanced, versus localized disease, had decreased emotional and social function and increased distress. Contributors to distress were largely unexplored, and no clear framework described coping/adjustment trajectories. Patients with advanced versus localized disease had more supportive care needs, particularly amount, quality, and timing of melanoma-related information, communication with and emotional support from clinicians. Limitations included: lack of theoretical underpinnings guiding study design; inconsistent measurement approaches; small sample sizes; non-representative sampling; and cross-sectional design. Quality trial evidence is needed to clarify the impact of treatment innovations for advanced melanoma on patients' psychosocial well-being. Survivorship research and subsequent translation of that knowledge into programs and services currently lags behind gains in the medical treatment of advanced melanoma, a troubling circumstance that requires immediate and focused

  2. External Validation of the Liverpool Uveal Melanoma Prognosticator Online.

    Science.gov (United States)

    DeParis, Sarah W; Taktak, Azzam; Eleuteri, Antonio; Enanoria, Wayne; Heimann, Heinrich; Coupland, Sarah E; Damato, Bertil

    2016-11-01

    To validate the Liverpool Uveal Melanoma Prognosticator Online (LUMPO) in a cohort of patients treated at the University of California-San Francisco (UCSF). A retrospective chart review was performed of 390 patients treated between 2002 and 2007 for choroidal melanoma at UCSF. Similar patients (n = 1175) treated at the Liverpool Ocular Oncology Centre (LOOC) were included in the study. The data were analyzed using the model previously developed for LUMPO, an online prognostication tool combining multiple prognostic factors. Main outcome measures included all-cause mortality and melanoma-specific mortality. Reliability of the survival estimates in each group of patients was indicated by the C-indices of discrimination and Hosmer-Lemeshow test. Patients treated at UCSF tended to be younger with thicker tumors, and were more likely to receive proton beam radiotherapy as primary treatment compared to patients at LOOC. There were no significance differences with respect to ciliary body involvement, melanoma cytomorphology, and mitotic counts between the two groups. Death occurred in 140/390 (35%) patients from UCSF and 409/1175 (34%) patients from LOOC, with no difference in overall mortality by Kaplan-Meier analysis (log rank test, P = 0.503). For all-cause mortality and melanoma-specific mortality, the C-index of discrimination and Hosmer-Lemeshow test at 5 years after treatment indicated good discrimination performance of the model, with no statistically significant difference between observed and predicted survival. Despite differences between the two cohorts, external validation in patients treated at UCSF indicates that LUMPO estimated the all-cause and melanoma-specific mortality well.

  3. Efficacy of chemotherapy after first-line gefitinib therapy in EGFR mutation-positive advanced non-small cell lung cancer-data from a randomized Phase III study comparing gefitinib with carboplatin plus paclitaxel (NEJ002).

    Science.gov (United States)

    Miyauchi, Eisaku; Inoue, Akira; Kobayashi, Kunihiko; Maemondo, Makoto; Sugawara, Shunichi; Oizumi, Satoshi; Isobe, Hiroshi; Gemma, Akihiko; Saijo, Yasuo; Yoshizawa, Hirohisa; Hagiwara, Koichi; Nukiwa, Toshihiro

    2015-07-01

    Epidermal growth factor receptor tyrosine kinase inhibitors are effective as first-line therapy for advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutations. However, it is unknown whether second-line platinum-based chemotherapy after epidermal growth factor receptor tyrosine kinase inhibitor therapy could lead to better outcomes. We evaluated the efficacy of second-line platinum-based chemotherapy after gefitinib for advanced non-small cell lung cancers harboring epidermal growth factor receptor mutations (the NEJ002 study). Seventy-one non-small cell lung cancers, treated with gefitinib as first-line therapy and then receiving platinum-based chemotherapy as second-line therapy were evaluated in NEJ002. Patients were evaluated for antitumor response to second-line chemotherapy by computed tomography according to the criteria of the Response Evaluation Criteria in Solid Tumors group (version 1.0). Of the 71 patients receiving platinum-based chemotherapy after first-line gefitinib, a partial response was documented in 25.4% (18/71), stable disease in 43.7% (31/71) and progression of disease in 21.1% (15/71). The objective response and disease control rates were 25.4% (18/71) and 69% (49/71), respectively. There was no significant difference between first- and second-line chemotherapy in objective response and disease control rates for advanced non-small cell lung cancer harboring activating epidermal growth factor receptor mutations. In the analysis of epidermal growth factor receptor mutation types, the objective responses of deletions in exon 19 and a point mutation in exon 21 (L858R) were 27.3% (9/33) and 28.1% (9/32), respectively, but these differences between objective response rates were not significant. The efficacy of second-line platinum-based chemotherapy followed at progression by gefitinib was similar to first-line platinum-based chemotherapy, and epidermal growth factor receptor mutation types did not influence

  4. Clinical characteristics, management and survival in young adults diagnosed with malignant melanoma: A population-based cohort study.

    Science.gov (United States)

    Plym, Anna; Ullenhag, Gustav J; Breivald, Mats; Lambe, Mats; Berglund, Anders

    2014-05-01

    Few studies to date have described the clinical features of malignant melanoma in young adulthood. Also, little is known about patterns of care in young patients. We examined and compared clinical characteristics, management and survival between young adult (15-39 years) and older adult melanoma patients in Central Sweden. Patients diagnosed with invasive malignant melanoma between 1997 and 2011 were identified in the Regional Quality Register of Cutaneous Malignant Melanoma in Central Sweden, a population-based register covering a source population of about two million. Data on clinical characteristics, management and survival were retrieved and compared according to age at diagnosis. Of 5915 patients included in the study, 584 (9.9%) were between 15 and 39 years of age at diagnosis. Compared with older patients, young adult patients were more likely to be female, with higher proportions of thin, non-ulcerated melanomas, superficial spreading melanoma and melanomas located on the lower extremity. Young adults had shorter waiting times for surgical procedures and a higher proportion received surgical treatment according to guidelines. Overall, young patients had better relative survival than older patients. Age-related survival differences varied by stage of disease at diagnosis, and were most prominent in stage II disease. The observed differences in clinical characteristics, management and survival between young adult and older melanoma patients call for an improved understanding of not only disease etiology but also factors driving management decisions. A better understanding of these differences may help improve care and prognosis for melanoma patients of all ages.

  5. Nestin expression in primary and metastatic uveal melanoma - possible biomarker for high-risk uveal melanoma.

    Science.gov (United States)

    Djirackor, Luna; Shakir, Dilem; Kalirai, Helen; Petrovski, Goran; Coupland, Sarah E

    2018-01-16

    Nestin, a member of the intermediate filament protein family, has been described as a putative cancer stem cell marker (CSC) in uveal melanoma and poor prognostic factor in a variety of tumours, including cutaneous melanoma. In this study, we examined the expression of nestin in primary (PUM) and metastatic uveal melanoma (MUM) samples, and correlated the findings with histological, clinical and survival data. Nestin expression was assessed by immunohistochemistry in 141 PUM and 26 MUM samples; 11 PUM cases were matched with their corresponding metastases. The percentage of tumour cells expressing nestin was scored by three independent observers. Statistical analysis of all data was performed with SPSS. Nestin expression was identified in both the cytoplasm and membrane of UM cells. Increased expression of nestin in PUM samples was associated with known poor prognostic parameters, including epithelioid cell morphology (p < 0.001), closed loops (p = 0.001), higher mitotic count (p < 0.001), monosomy 3 (p = 0.007) and chromosome 8q gain (p < 0.001). Primary uveal melanoma (PUM) with nestin expression levels above a cut-off value of 10% [as determined by receiver operating characteristic (ROC) analysis] was associated with a significantly reduced survival time (Log-rank, p = 0.002). In MUM, a higher percentage of nestin-positive tumour cells combined with poor prognostic markers in the PUM led to a shorter survival time following the development of metastases. In conclusion, increased nestin expression in PUM is a predictor of a tumour phenotype associated with metastatic progression and reduced survival time at onset of metastasis. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  6. Induction with Infliximab and a Plant-Based Diet as First-Line (IPF) Therapy for Crohn Disease: A Single-Group Trial.

    Science.gov (United States)

    Chiba, Mitsuro; Tsuji, Tsuyotoshi; Nakane, Kunio; Tsuda, Satoko; Ishii, Hajime; Ohno, Hideo; Watanabe, Kenta; Ito, Mai; Komatsu, Masafumi; Sugawara, Takeshi

    2017-01-01

    Approximately 30% of patients with Crohn disease (CD) are unresponsive to biologics. No previous study has focused on a plant-based diet in an induction phase of CD treatment. To investigate the remission rate of infliximab combined with a plant-based diet as first-line (IPF) therapy for CD. This was a prospective single-group trial conducted at tertiary hospitals. Subjects included consecutive adults with a new diagnosis (n = 26), children with a new diagnosis (n = 11), and relapsing adults (n = 9) with CD who were naïve to treatment with biologics. Patients were admitted and administered a standard induction therapy with infliximab (5 mg/kg; 3 infusions at 0, 2, and 6 weeks). Additionally, they received a lacto-ovo-semivegetarian diet. The primary end point was remission, defined as the disappearance of active CD symptoms at week 6. Secondary end points were Crohn Disease Activity Index (CDAI) score, C-reactive protein (CRP) concentration, and mucosal healing. Two adults with a new diagnosis were withdrawn from the treatment protocol because of intestinal obstruction. The remission rates by the intention-to-treat and per-protocol analyses were 96% (44/46) and 100% (44/44), respectively. Mean CDAI score (314) on admission decreased to 63 at week 6 (p < 0.0001). Mean CRP level on admission (5.3 mg/dL) decreased to 0.2 (p < 0.0001). Mucosal healing was achieved in 46% (19/41) of cases. IPF therapy can induce remission in most patients with CD who are naïve to biologics regardless of age or whether they have a new diagnosis or relapse.

  7. Randomized Trial Comparing Esomeprazole and Rabeprazole in First-line Eradication Therapy for Helicobacter pylori Infection based on the Serum Levels of Pepsinogens.

    Science.gov (United States)

    Shimoyama, Tadashi; Chinda, Daisuke; Sawada, Yoshihiko; Komai, Kazuo; Chiba, Hironobu; Saito, Yoshiharu; Sasaki, Yoshio; Matsuzaka, Masashi; Fukuda, Shinsaku

    2017-01-01

    Objective CYP2C19 metabolic activity influences the efficacy of Helicobacter pylori eradication therapies comprising PPIs. Rabeprazole (RPZ) and esomeprazole (EPZ) are PPIs not extensively metabolized by CYP2C19. The aim of this study was to elucidate whether or not first-line triple therapies using RPZ or EPZ are equally effective in Japanese patients with different CYP2C19 genotypes. Methods Two-hundred patients infected with H. pylori were randomized to receive one of the following regimens: amoxicillin (750 mg), clarithromycin (200 mg), and either esomeprazole (20 mg) (EAC group) or rabeprazole (10 mg) (RAC group), twice a day for one week. The CYP2C19 polymorphisms were determined by polymerase chain reaction and the serum level of pepsinogens was measured. Results The eradication rates of the EAC and RAC regimens were 79.8% (95% confidential interval: 71.7-89.0%) and 74.7% (66.0-83.4%), respectively, in a per protocol (PP) analysis (p=0.488). The eradication rates of the EAC and RAC regimens were not significantly different between patients with the homo EM genotype (p=0.999) or hetero IM or PM genotypes (p=0.286). A lower PG I/II ratio was associated with lower eradication rates (p=0.025). Conclusion Although the eradication rate was less than 80%, the EAC and RAC regimens were equally effective in each CYP2C19 genotype group. The PG I/II ratio was associated with the results of EAC and RAC therapy in this series of patients.

  8. Efficacy of plasma vascular endothelial growth factor in monitoring first-line chemotherapy in patients with advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Mohan Anant

    2009-12-01

    Full Text Available Abstract Background Along with the development of new cancer therapeutics, more effective tools for the estimation of response to therapy and prediction of disease progression are required for the better management of inoperable cancer patients. Methods We studied 134 newly diagnosed and primarily untreated advanced non-small cell lung cancer patients and 100 controls. Forty two patients received platinum-based chemotherapy. Plasma VEGF levels were quantified in all samples at baseline and also before second and third chemotherapy cycle in 42 patients and correlated with response to therapy as assessed by computed tomography after the third chemotherapy cycle. Results We observed that, patients who went into remission had significantly lower baseline VEGF levels before second and third cycles of chemotherapy when compared with patients with no change and progression. Plasma VEGF levels showed a greater decrease from cycle 1 to 2 and from cycle 1 to 3 in patients who showed remission in comparison to those with no change or progression. Plasma VEGF levels before the second cycle detected poor response to therapy with a sensitivity and specificity of 76.9% and 75.0%, respectively (area under the ROC curve = 0.724. Early prediction of disease progression was achieved with a sensitivity and specificity of 71.4% for plasma VEGF before cycle 2 (area under the ROC curve = 0.805. The kinetics of VEGF form cycle 1 to 2 and cycle 1 to 3 also gave significant information for predicting disease progression as well as insufficient therapy response. Conclusion Monitoring of plasma VEGF levels during the course of first-line chemotherapy could identify patients who are likely to have insufficient response to therapy and disease progression at an early stage. This may help in individualizing treatment and could lead to better management of the advanced stage lung cancer.

  9. Melanoma and intravascular coagulation disseminated fulminant

    International Nuclear Information System (INIS)

    Aponte, Diego; Garzon, Javier; Burgos, Erick; Abenoza, Lina; Cardona, Andres Felipe; Ramos, Pedro; Reveiz, Ludovic

    2005-01-01

    Clinical discoveries, imaginological and pathological of a 54 year-old woman, with pruritus, ulceration and bled intermittent in dorsal nevus, located in the region left sub-scapular. The biopsy demonstrated the presence of malign melanoma. Two months after having carried out the procedure the reappearance of the tumoral lesion it was documented on the same area by what was practiced wide local resection; the report was compatible with recidivate melanoma, later on (four weeks after the second surgical intervention), she noticed the presence of conglomerate left axillary ganglion of quick growth for metastatic melanoma. To the moment of the initial evaluation, it founded a mass axillary left, of 10 x 6 cm, associated to local swelling and to slight functional limitation for the active and passive mobility of the extremity. It decided to carry out new surgical resection that demonstrated persistence tumoral in the deep borders and commitment in 1 of 9 ganglions for metastasis, associated to reaction inflammatory chronicle. It began treatment adjuvant with interferon alpha 2b with appropriate tolerance and poor answer. In June of the same year it presented progressive dyspnoea, for what decided to suspend the immune-therapy and to begin dacarbacina with palliative intention, also, she received radiotherapy on the left axilla and temozolamida. In March of 2004, it entered to the service of urgencies to present scheme of 8 days of evolution characterized by the presence of progressive asymmetric edema of the left inferior member, associated to functional limitation for the march, with pain during the bipedestation and appearance of multiple lesions nodular hyper-pigmented in the previous thorax and in the face

  10. Lean from the First-line Managers’ Perspective – Assuredness about the Effects of Lean as a Driving Force for Sustainable Change

    Directory of Open Access Journals (Sweden)

    Kahm Therese

    2017-06-01

    Full Text Available The purpose of this article is to present the results from a survey concerning first-line managers’ assuredness about the effects of Lean after two years of Lean application in a Swedish healthcare organization. The purpose is also to reflect about assuredness as a driving force for sustainable change. Questionnaires were sent to all first-line managers in a healthcare organization in order to investigate how these managers consider their role, ability and conditions to create change according to Lean. One of the questions included 17 statements about how assured these managers were about the effects of Lean. The results from this question will be presented in this paper. The study showed that the majority of the first-line managers in this particular healthcare organization were assured that developmental work supported by Lean contributes to a higher patient focus, supports first-line managers with useful tools and methods, contributes to the development of an improvement culture and that the Lean concept in general is a support in improvement work. The question can either be used separately or as a part of an entire questionnaire in healthcare organizations. Asking first-line managers about their assuredness about the effects of Lean on a regular basis is one way to follow the Lean process from their perspective. The survey question might encourage discussions about the process of Lean and hopefully contribute to a greater understanding about the importance of assuredness and about the desired effects when applying Lean.

  11. Quadruple-first line drug resistance in Mycobacterium tuberculosis in Vietnam: What can we learn from genes?

    Science.gov (United States)

    Nguyen, Huy Quang; Nguyen, Nhung Viet; Contamin, Lucie; Tran, Thanh Hoa Thi; Vu, Thuong Thi; Nguyen, Hung Van; Nguyen, Ngoc Lan Thi; Nguyen, Son Thai; Dang, Anh Duc; Bañuls, Anne-Laure; Nguyen, Van Anh Thi

    2017-06-01

    In Vietnam, a country with high tuberculosis (137/100.000 population) and multidrug-resistant (MDR)-TB burdens (7.8/100.000 population), little is known about the molecular signatures of drug resistance in general and more particularly of second line drug (SLD) resistance. This study is specifically focused on Mycobacterium tuberculosis isolates resistant to four first-line drugs (FLDs) that make TB much more difficult to treat. The aim is to determine the proportion of SLD resistance in these quadruple drug resistant isolates and the genetic determinants linked to drug resistance to better understand the genetic processes leading to quadruple and extremely drug resistance (XDR). 91 quadruple (rifampicin, isoniazid, ethambutol and streptomycin) FLD resistant and 55 susceptible isolates were included. Spoligotyping and 24-locus MIRU-VNTR techniques were performed and 9 genes and promoters linked to FLD and SLD resistance were sequenced. SLD susceptibility testing was carried out on a subsample of isolates. High proportion of quadruple-FLD resistant isolates was resistant to fluoroquinolones (27%) and second-line injectable drugs (30.2%) by drug susceptibility testing. The sequencing revealed high mutation diversity with prevailing mutations at positions katG315, inhA-15, rpoB531, embB306, rrs1401, rpsL43 and gyrA94. The sensitivity and specificity were high for most drug resistances (>86%), but the sensitivity was lower for injectable drug resistances (resistance. Nevertheless, particular mutation patterns linked to high-level resistance and low fitness costs seem to be favored. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Predictors of early mortality after rabbit antithymocyte globulin as first-line treatment in severe aplastic anemia.

    Science.gov (United States)

    Atta, Elias H; Lima, Carlos B L; Dias, Danielle S P; Clé, Diego V; Bonduel, Mariana M; Sciuccati, Gabriela B; Medeiros, Larissa A; Oliveira, Michel M; Salvino, Marco A; Garanito, Marlene P; Blum Fonseca, Patricia B; Saad, Sara Teresinha O; Calado, Rodrigo T; Scheinberg, Phillip

    2017-11-01

    Despite being recommended as first-line immunosuppressive therapy in severe aplastic anemia (SAA), horse antithymocyte globulin (ATG) is still unavailable in many countries outside the USA. Rabbit ATG is more lymphocytoxic than horse ATG, and this might result in a higher incidence of severe infections and early mortality. This study was designed to identify the risk factors for early mortality and overall survival (OS) after rabbit ATG in patients with SAA. We retrospectively reviewed 185 patients with SAA who underwent rabbit ATG and cyclosporine. The incidence of death in 3 months following rabbit ATG therapy was 15.1% (28/185). Early mortality was mainly related to infectious complications, despite adequate antibiotic and/or antifungal treatment. Age > 35 years (odds ratio [OR] 5.06, P = 0.001) and baseline absolute neutrophil count (ANC) ≤ 0.1 × 10 9 /L (OR 7.64, P mortality after immunosuppressive therapy with this agent. Hematological response at 6 months was observed in only 29.7% of all patients. OS at 1 year after rabbit ATG was 75.3%; and age > 35 years (OR 1.88, P = 0.03), baseline ANC ≤ 0.1 × 10 9 /L (OR 2.65, P mortality. Alternative strategies are needed for the treatment of SAA patients in countries were horse ATG is unavailable, particularly for those at high risk for early mortality after rabbit ATG due to a higher age and very low pre-treatment neutrophil count.

  13. First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Shu Yong-Qian

    2010-09-01

    Full Text Available Abstract Background Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK inhibitor of epidermal growth factor receptor (EGFR, displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC in Chinese population are not sufficient. Purpose To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC, a study of single agent treatment with gefitinib in Chinese patients was conducted. Methods 45 patients with advanced NSCLC were treated with gefitinib (250 mg daily until the disease progression or intolerable toxicity. Results Among the 45 patients, 15 patients achieved partial response (PR, 17 patients experienced stable disease (SD, and 13 patients developed progression disease (PD. None of the patients achieved complete response (CR. The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively. The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively. In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively. Conclusions Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.

  14. Semi-quantitative analysis of salivary gland scintigraphy in Sjögren's syndrome diagnosis: a first-line tool.

    Science.gov (United States)

    Angusti, Tiziana; Pilati, Emanuela; Parente, Antonella; Carignola, Renato; Manfredi, Matteo; Cauda, Simona; Pizzigati, Elena; Dubreuil, Julien; Giammarile, Francesco; Podio, Valerio; Skanjeti, Andrea

    2017-09-01

    The aim of this study was the assessment of semi-quantified salivary gland dynamic scintigraphy (SGdS) parameters independently and in an integrated way in order to predict primary Sjögren's syndrome (pSS). Forty-six consecutive patients (41 females; age 61 ± 11 years) with sicca syndrome were studied by SGdS after injection of 200 MBq of pertechnetate. In sixteen patients, pSS was diagnosed, according to American-European Consensus Group criteria (AECGc). Semi-quantitative parameters (uptake (UP) and excretion fraction (EF)) were obtained for each gland. ROC curves were used to determine the best cut-off value. The area under the curve (AUC) was used to estimate the accuracy of each semi-quantitative analysis. To assess the correlation between scintigraphic results and disease severity, semi-quantitative parameters were plotted versus Sjögren's syndrome disease activity index (ESSDAI). A nomogram was built to perform an integrated evaluation of all the scintigraphic semi-quantitative data. Both UP and EF of salivary glands were significantly lower in pSS patients compared to those in non-pSS (p quantitative parameters and ESSDAI. The proposed nomogram accuracy was 87%. SGdS is an accurate and reproducible tool for the diagnosis of pSS. ESSDAI was not shown to be correlated with SGdS data. SGdS should be the first-line imaging technique in patients with suspected pSS.

  15. Current problems in the first-line treatment of metastatic breast cancer: focus on the role of docetaxel

    Directory of Open Access Journals (Sweden)

    Filippo Montemurro

    2010-09-01

    Full Text Available Metastatic breast cancer is a very heterogeneous disease, both from a clinical and a biological point of view. Despite being still incurable, the expanding therapeutic repertoire has determined a progressive increase in median survival. We describe the clinical course of a 67-year-old woman with a locally advanced, hormone-receptor positive breast cancer with synchronous liver metastases. Single-agent docetaxel at the dose of 100 mg/m2 for 8 cycles determined a pathological complete remission in the breast and a near complete remission of liver metastases. After more than 4 years from diagnosis, the patient is alive and without signs of tumour progression. Based on this clinical case, we discuss management issues like the choice of the initial treatment, the use of monochemotherapy vs polychemotherapy, the worth of surgery of the primary tumour in patients with stage IV disease, and the issue of maintenance endocrine therapy. Furthermore, we reviewed the pivotal role of docetaxel in the management of advanced breast cancer. Whether monochemotherapy or polychemotherapy is felt to be an adequate choice in the clinical practice, docetaxel qualifies as one of the most active and manageable agents. Single agent activity ranging from 20-48% in terms of response rate has been reported in several clinical trials in patients treated in various clinical settings. Docetaxel-based combinations with other cytotoxic agents have become established in the first line treatment both in patients with anthracycline-resistant and anthracycline-sensitive metastatic breast cancer. Finally, docetaxel has been shown to be an optimal companion drug for biologically targeted agents like trastuzumab or bevacizumab, resulting in further treatment options.

  16. HLA genotyping as first-line screening tool for coeliac disease in children with juvenile idiopathic arthritis.

    Science.gov (United States)

    Skrabl-Baumgartner, Andrea; Christine Hauer, Almuthe; Erwa, Wolfgang; Jahnel, Jörg

    2017-07-01

    Coeliac disease (CD) and juvenile idiopathic arthritis (JIA) often coexist. This association warrants assessment for CD in patients with JIA. We evaluated the clinical relevance and cost-effectiveness of human leucocyte antigen (HLA) genotyping in first-line screening for development of CD in children with JIA. 95 patients with JIA were screened for CD using CD-specific antibodies. In case of positivity, a small intestinal biopsy was performed to confirm diagnosis. In addition, HLA genotyping was performed. 110 age-matched and sex-matched Caucasian children from the same geographical area served as controls. CD was diagnosed in 4 of 95 patients with JIA (4.2%), a rate significantly higher compared with controls (pHLA-DQ2.5 genotype: one was homozygote, the remainder heterozygote. Twenty-two patients are, judging by their HLA genotypes, at risk of developing CD and require repeated serological screening. None of the 69 patients without HLA-DQ2/DQ8 genotypes had CD-specific antibodies. Screening with HLA genotyping becomes cheaper than screening without after the second determination. In our cohort of patients with JIA, lack of HLA-DQ2/DQ8 genotypes identified a majority not at risk of CD in whom repeated serological testing is unnecessary. Genotyping is nowadays the most efficient and cost-effective way to screen for CD risk in JIA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  17. Short term outcomes of topiramate monotherapy as a first-line treatment in newly diagnosed West syndrome

    Directory of Open Access Journals (Sweden)

    Gyu Min Lee

    2011-09-01

    Full Text Available Purpose : To investigate the efficacy of topiramate monotherapy in West syndrome prospectively. Methods : The study population included 28 patients (15 male and 13 female children aged 2 to 18 months diagnosed with West syndrome. After a 2-week baseline period for documentation of the frequency of spasms, topiramate was initiated at 2 mg/kg/day. The dose was increased by 2 mg/kg every week to a maximum of 12 mg/ kg/day. Clinical assessment was based on the parents’ report and a neurological examination every 2 weeks for the first 2 months of treatment. The baseline electroencephalograms (EEGs were compared with the post-treatment EEGs at 2 weeks and 1 month. Results : West syndrome was considered to be cryptogenic in 7 of the 28 patients and symptomatic in 21 patients. After treatment, 11 patients (39% became spasm-free, 6 (21% had more than 50% spasmsreduction, 3 (11% showed less than 50% reduction, and 8 (29% did not respond. The effective daily dose for achieving more than 50% reduction in spasm frequency, including becoming spasm-free, was found to be 5.8±1.1 mg/kg/day. Nine patients (32% showed complete disappearance of spasms and hypsarrhythmia, and 11 (39% showed improved EEG results. Despite adverse events (4 instances of irritability, 3 of drowsiness, and 1 of decreased feeding, no patients discontinued the medication. Conclusion : Topiramate monotherapy seems to be effective and well tolerated as a first line therapy for West syndrome and is not associated with serious adverse effects.

  18. Multicenter phase II study of capecitabine plus cisplatin as first-line therapy for human epidermal growth factor receptor 2-negative advanced gastric cancer: Yokohama Clinical Oncology Group Study YCOG1107.

    Science.gov (United States)

    Sato, Kei; Kunisaki, Chikara; Kosaka, Takashi; Takagawa, Ryo; Takahashi, Masazumi; Izumisawa, Yusuke; Miyamoto, Hiroshi; Sato, Sho; Tanaka, Yusaku; Yamaguchi, Naotaka; Kimura, Jun; Ono, Hidetaka A; Makino, Hirochika; Akiyama, Hirotoshi; Endo, Itaru

    2017-11-01

    S-1 plus cisplatin therapy is the recommended standard first-line regimen for human epidermal growth factor receptor 2 (HER-2)-negative advanced unresectable or recurrent gastric cancer (AGC) in the Japanese Gastric Cancer Treatment Guidelines. By contrast, capecitabine plus cisplatin (XP) therapy has been second-line therapy for these patients. This prospective study aimed to evaluate the efficacy and safety of XP as a first-line regimen for HER2-negative patients with AGC. In this multicenter, open-label, phase II study, patients received cisplatin (80 mg/m 2 i.v. day 1) plus capecitabine (1000 mg/m 2 orally, twice daily, days 1-14) at 3 week intervals until disease progression or non-continuation for various reasons. The primary endpoint was overall response rate; secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity profiles. Thirty-six patients with HER2-negative AGC were enrolled in this study. Of these, 16 patients with evaluable lesions were assessable for efficacy and 36 were assessable for toxicity. One patient achieved a complete response and five partial responses. The overall response rate was 37.5% [95% confidence interval (CI) 13.7-61.2%] calculated on an intention-to-treat basis. The median PFS and median OS were 5.2 months (95% CI 4.2-6.2 months) and 16.9 months (95% CI 5.8-27.9 months), respectively. Treatment-related adverse events were generally mild; the most common grade 3/4 adverse event was neutropenia (27.8%), followed by anorexia (19.4%), leucopenia (16.7%), anemia (16.7%), and nausea (13.9%). XP as first-line therapy is effective and well tolerated by patients with HER2-negative AGC.

  19. High-dose chemotherapy and auto-SCT for relapsed and refractory Hodgkin's lymphoma patients refractory to first-line salvage chemotherapy but responsive to second-line salvage chemotherapy.

    Science.gov (United States)

    Rauf, Muhammad Shahzad; Maghfoor, Irfan; Elhassan, Tusneem Ahmed M; Akhtar, Saad

    2015-01-01

    Relapsed or primary refractory Hodgkin's lymphoma (HL) patients refractory to first-line salvage chemotherapy (first salvage) and unable to undergo high-dose chemotherapy (HDC) and autologous stem cell transplant (auto-SCT) have very poor outcome. Some patients are offered second-line salvage chemotherapy (second salvage), if they are responsive and may receive HDC auto-SCT. We identified 31 patients (18 males, 13 females) from 1996-2012 who received second salvage prior to auto-SCT. Median age at auto-SCT is 22 years. Patients were grouped as (1) relapsed-refractory (Rel:Ref): patients with prior complete response (CR) and on relapse found refractory to first salvage and received second salvage and (2) refractory-refractory (Ref:Ref): patients refractory to both primary treatment and first salvage and received second salvage. Median follow-up is 63 months (18-170). Disease status after second salvage prior to HDC was CR 16 %, partial response (PR) 71 % and stable disease 13 %. After HDC auto-SCT, CR:PR: progressive disease was observed in 18 (58 %): four (12 %): nine (29 %) patients, respectively. Five-year overall survival (OS) for whole group is 57 % (Rel:Ref vs. Ref:Ref, 73 % vs. 48 %, p = 0.48). Progression-free survival (PFS) for whole group is 52 % (Rel:Ref vs. Ref:Ref, 73 % vs. 40 % respectively, p = 0.11). Second-line salvage is a valid approach with no long-term side effects for those HL patients who do not respond to first-line salvage chemotherapy and they can be candidate of HDC and stem cell transplant with a high ORR, the PFS and OS in relapse-refractory and refractory-refractory group of patients.

  20. Ubiquitination in melanoma pathogenesis and treatment.

    Science.gov (United States)

    Ma, Jinyuan; Guo, Weinan; Li, Chunying

    2017-06-01

    Melanoma is one of the most aggressive skin cancers with fiercely increasing incidence and mortality. Since the progressive understanding of the mutational landscape and immunologic pathogenic factors in melanoma, the targeted therapy and immunotherapy have been recently established and gained unprecedented improvements for melanoma treatment. However, the prognosis of melanoma patients remains unoptimistic mainly due to the resistance and nonresponse to current available drugs. Ubiquitination is a posttranslational modification which plays crucial roles in diverse cellular biological activities and participates in the pathogenesis of various cancers, including melanoma. Through the regulation of multiple tumor promoters and suppressors, ubiquitination is emerging as the key contributor and therefore a potential therapeutic target for melanoma. Herein, we summarize the current understanding of ubiquitination in melanoma, from mechanistic insights to clinical progress, and discuss the prospect of ubiquitination modification in melanoma treatment. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  1. The role of nitric oxide in melanoma.

    Science.gov (United States)

    Yarlagadda, Keerthi; Hassani, John; Foote, Isaac P; Markowitz, Joseph

    2017-12-01

    Nitric oxide (NO) is a small gaseous signaling molecule that mediates its effects in melanoma through free radical formation and enzymatic processes. Investigations have demonstrated multiple roles for NO in melanoma pathology via immune surveillance, apoptosis, angiogenesis, melanogenesis, and on the melanoma cell itself. In general, elevated levels of NO prognosticate a poor outcome for melanoma patients. However, there are processes where the relative concentration of NO in different environments may also serve to limit melanoma proliferation. This review serves to outline the roles of NO in melanoma development and proliferation. As demonstrated by multiple in vivo murine models and observations from human tissue, NO may promote melanoma formation and proliferation through its interaction via inhibitory immune cells, inhibition of apoptosis, stimulation of pro-tumorigenic cytokines, activation of tumor associated macrophages, alteration of angiogenic processes, and stimulation of melanoma formation itself. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Tool to Distinguish Moles from Melanoma

    Science.gov (United States)

    “Moles to Melanoma: Recognizing the ABCDE Features” presents photos that show changes in individual pigmented lesions over time, and describes the different appearances of moles, dysplastic nevi, and melanomas.

  3. Data Set for Pathology Reporting of Cutaneous Invasive Melanoma

    Science.gov (United States)

    Judge, Meagan J.; Evans, Alan; Frishberg, David P.; Prieto, Victor G.; Thompson, John F.; Trotter, Martin J.; Walsh, Maureen Y.; Walsh, Noreen M.G.; Ellis, David W.

    2013-01-01

    An accurate and complete pathology report is critical for the optimal management of cutaneous melanoma patients. Protocols for the pathologic reporting of melanoma have been independently developed by the Royal College of Pathologists of Australasia (RCPA), Royal College of Pathologists (United Kingdom) (RCPath), and College of American Pathologists (CAP). In this study, data sets, checklists, and structured reporting protocols for pathologic examination and reporting of cutaneous melanoma were analyzed by an international panel of melanoma pathologists and clinicians with the aim of developing a common, internationally agreed upon, evidence-based data set. The International Collaboration on Cancer Reporting cutaneous melanoma expert review panel analyzed the existing RCPA, RCPath, and CAP data sets to develop a protocol containing “required” (mandatory/core) and “recommended” (nonmandatory/noncore) elements. Required elements were defined as those that had agreed evidentiary support at National Health and Medical Research Council level III-2 level of evidence or above and that were unanimously agreed upon by the review panel to be essential for the clinical management, staging, or assessment of the prognosis of melanoma or fundamental for pathologic diagnosis. Recommended elements were those considered to be clinically important and recommended for good practice but with lesser degrees of supportive evidence. Sixteen core/required data elements for cutaneous melanoma pathology reports were defined (with an additional 4 core/required elements for specimens received with lymph nodes). Eighteen additional data elements with a lesser level of evidentiary support were included in the recommended data set. Consensus response values (permitted responses) were formulated for each data item. Development and agreement of this evidence-based protocol at an international level was accomplished in a timely and efficient manner, and the processes described herein may

  4. Books Received

    Indian Academy of Sciences (India)

    Books Received. Challenge and Thrill of Pre-College. Mathematics. V Krishnamurthy et al. New Age International. 1996, Rs.220. Mathematics for Science. S M Uppal and H M Humphreys. New Age International. 1996, Rs.17S. Physics for Engineers. M R Srinivasan. New Age Publications. 1996. Statement about ownership ...

  5. Unexplained developmental delay/learning disability: guidelines for best practice protocol for first line assessment and genetic/metabolic/radiological investigations.

    Science.gov (United States)

    O'Byrne, J J; Lynch, S A; Treacy, E P; King, M D; Betts, D R; Mayne, P D; Sharif, F

    2016-02-01

    Investigation of patients, particularly children, with unexplained global developmental delay (GDD)/learning disability (LD) has been challenging due to a lack of clear guidance from specialised centres. Limited knowledge of rare diseases and a poor understanding of the purpose or limitations of appropriate investigations have been some of the principal reasons for this difficulty. A guideline development group was formed to recommend on appropriate, first line metabolic, genetic and radiological investigations for children and adults with unexplained GDD/ID. A comprehensive literature search was conducted, evaluated and reviewed by the guideline committee and a best practice protocol for first line assessment and genetic, metabolic and radiological investigations was decided upon after considering diagnostic yield, practicality, treatability and costs. It is hoped that these recommendations will become national guidelines for the first line metabolic, genetic and radiological investigation of patients presenting with unexplained GDD/ID.

  6. Large melanoma metastases to the gastrointestinal tract.

    OpenAIRE

    Silverman, J M; Hamlin, J A

    1989-01-01

    It is well known that malignant melanoma can metastasize widely. Although these metastases in the gastrointestinal tract usually appear as small 'bull's-eye' or 'target' lesions, there are a few reports of relatively large melanoma metastases. We report five cases of large melanoma lesions metastatic to the alimentary canal. We also emphasise the consideration of a thorough gastrointestinal tract evaluation in patients with malignant melanoma especially if they are symptomatic.

  7. Unusual presentations of melanoma: melanoma of unknown primary site, melanoma arising in childhood, and melanoma arising in the eye and on mucosal surfaces.

    Science.gov (United States)

    Sondak, Vernon K; Messina, Jane L

    2014-10-01

    Most melanomas present as primary tumors on the skin surface in adults; however, melanomas also arise in the eye and on the mucosal surfaces or present as apparently metastatic disease without any known history of a cutaneous primary. Melanoma is also being diagnosed during childhood more frequently than ever. Surgeons need to be aware of and understand these unusual presentations of melanoma to optimally manage their patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Cross-market cost-effectiveness analysis of erlotinib as first-line maintenance treatment for patients with stable non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Vergnenègre A

    2012-01-01

    Full Text Available Alain Vergnenègre1, Joshua A Ray2, Christos Chouaid3, Francesco Grossi4, Helge G Bischoff5, David F Heigener6, Stefan Walzer21Department of Pneumology, Hôpital du Cluzeau, Limoges, France; 2Global Health Economics and Strategic Pricing, F Hoffmann-La Roche Ltd, Basel, Switzerland; 3Respiratory Service, Hôpital Saint Antoine, Paris, France; 4Lung Cancer Unit, National Institute for Cancer Research, Genoa, Italy; 5Thoracic Oncology, Onkologie Thoraxklinik Heidelberg, Heidelberg, Germany; 6Department of Thoracic Oncology, Krankenhaus Großhansdorf, Großhansdorf, GermanyBackground: Platinum-doublet, first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC is limited to 4–6 cycles. An alternative strategy used to prolong the duration of first-line treatment and extend survival in metastatic NSCLC is first-line maintenance therapy. Erlotinib was approved for first-line maintenance in a stable disease population following results from a randomized, controlled Phase III trial comparing erlotinib with best supportive care. We aimed to estimate the incremental cost-effectiveness of erlotinib 150 mg/day versus best supportive care when used as first-line maintenance therapy for patients with locally advanced or metastatic NSCLC and stable disease.Methods: An economic decision model was developed using patient-level data for progression-free survival and overall survival from the SATURN (SequentiAl Tarceva in UnResectable NSCLC study. An area under the curve model was developed; all patients entered the model in the progression-free survival health state and, after each month, moved to progression or death. A time horizon of 5 years was used. The model was conducted from the perspective of national health care payers in France, Germany, and Italy. Probabilistic sensitivity analyses were performed.Results: Treatment with erlotinib in first-line maintenance resulted in a mean life expectancy of 1.39 years in all countries

  9. Pregnancy and early-stage melanoma

    NARCIS (Netherlands)

    Daryanani, D; Plukker, JT; De Hullu, JA; Kuiper, H; Nap, RE; Hoekstra, HJ

    2003-01-01

    BACKGROUND. Cutaneous melanomas are aggressive tumors with an unpredictable biologic behavior. It has been suggested that women who present with melanoma during pregnancy have a worse prognosis due to more aggressive behavior of the melanoma. The objective of the current study was to evaluate the

  10. Clinicopathological and molecular aspects of cutaneous Melanoma

    NARCIS (Netherlands)

    Bogenrieder, T.

    2009-01-01

    Clinicopathological and molecular aspects of cutaneous melanoma. Melanoma arises form the transformation of neural crest-derived melanocytes, the pigment cells of the skin, which reside in the basal layer of the epidermis. Melanoma is the deadliest form of skin cancer and one of the most aggressive

  11. Genetic prognostic factors in uveal melanoma

    NARCIS (Netherlands)

    Maat, Willem

    2012-01-01

    Uveal melanoma (UM) is the most common malignancy of the eye in adults and it is the second most common form of melanoma after cutaneous melanoma (CM). The identification of patients who have a high risk of developing metastases would allow the possibility of providing adjuvant therapies to prevent

  12. Melanoma continues to rise throughout the world

    African Journals Online (AJOL)

    Review Article: Melanoma continues to rise throughout the world. 530 ... of melanoma. The radiation in the ultraviolet B range is said to be the critical component. Generally, worldwide, the incidence of melanoma in white people4,5 correlates inversely with .... lymphocytes, mitotic rate, regression, angiolymphatic invasion ...

  13. Decreased tumor-infiltrating lymphocytes in nodular melanomas compared with matched superficial spreading melanomas.

    Science.gov (United States)

    Lin, Richard L; Wang, Thomas J; Joyce, Cara J; Mihm, Martin C; Murphy, George F; Lian, Christine G; Lin, Jennifer Y

    2016-10-01

    Melanoma causes over 9000 deaths annually in the USA. Among its subtypes, nodular melanoma leads to a disproportionate number of fatalities compared with superficial spreading melanoma, the most common subtype. Recent breakthroughs in melanoma research have indicated a strong connection between melanoma virulence and the immune system. We hypothesize that the aggression of nodular melanoma may, in part, be because of decreased recognition by the immune system, as represented by a decreased presence of tumor-infiltrating lymphocytes (TILs), compared with its superficial spreading counterpart. Indeed, TILs on a primary melanoma have been used as a marker for immune response and have prognostic value for survival and sentinel lymph node status. After matching melanoma cases by age, sex, and Breslow thickness, we found significantly fewer TILs in nodular melanomas than in superficial spreading melanomas. This association was prominent in thin (≤2 mm) melanomas and was no longer significant in thick (>2 mm) melanomas. In addition, this difference in TILs was only present in men and not in women. Our finding suggests that nodular melanomas are more frequently associated with absent TILs, providing an avenue for further investigation into differences in immunogenicity of the primary melanoma and whether they underlie the unique virulence of nodular melanoma.

  14. Rituximab for the first-line treatment of stage III/IV follicular non-Hodgkin's lymphoma.

    Science.gov (United States)

    Dundar, Y; Bagust, A; Hounsome, J; McLeod, C; Boland, A; Davis, H; Walley, T; Dickson, R

    2009-06-01

    This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of rituximab for the first-line treatment of stage III/IV follicular non-Hodgkin's lymphoma (FNHL) based upon the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The manufacturer's scope restricts the intervention to rituximab in combination with CVP (cyclophosphamide, vincristine and prednisolone) (R-CVP); the only comparator used was CVP alone. The evidence from the one included randomised controlled trial (RCT) suggests that the addition of rituximab to a CVP chemotherapy regimen has a positive effect on the outcomes of time to treatment failure, disease progression, overall tumour response, duration of response and time to new lymphoma treatment in patients with stage III/IV FNHL compared with CVP alone. Adverse events were comparable between the two arms. This study was confirmed as the only relevant RCT. The economic analyses provided by the manufacturer were modelled using a three-state Markov model with with the health states being defined as progression-free survival (PFS), progressed (in which patients have relapsed) and death (which is an absorbing state). The model generated results for a cohort of patients with an initial age of 53 and makes no distinction between men and women. The model is basic in design, with several serious design flaws and key parameter values that are probably incompatible. Attempting to rectify the identified errors and limitations of the model did not increase the incremental cost-effectiveness ratio (ICER) above 30,000 pounds. Although the cost-effectiveness results obtained appear to be compelling in support of R-CVP compared with CVP for the trial population the results may not be so convincing for a more representative population. The results of the ERG analysis on the impact of age suggest that ICERs increase

  15. Cost-effectiveness analysis of pharmaceutical treatment options in the first-line management of major depressive disorder in Belgium.

    Science.gov (United States)

    Annemans, Lieven; Brignone, Mélanie; Druais, Sylvain; De Pauw, Ann; Gauthier, Aline; Demyttenaere, Koen

    2014-05-01

    The objective of this study was to assess the cost effectiveness of commonly used antidepressants as first-line treatment of major depressive disorder (MDD) in Belgium. The model structure was based on a decision tree developed by the Swedish TLV (Tandvårds- och läkemedelsförmånsverket) and adapted to the Belgium healthcare setting, using primary local data on the patterns of treatment and following KCE [Federal Knowledge Center (Federaal Kenniscentrum voor de Gezondheidszorg)] recommendations. Comparators were escitalopram, citalopram, fluoxetine, paroxetine, sertraline, duloxetine, venlafaxine, and mirtazapine. In the model, patients not achieving remission or relapsing after remission on the assessed treatment moved to a second therapeutic step (titration, switch, add-on, or transfer to a specialist). In case of failure in the second step or following a suicide attempt, patients were assumed to be referred to secondary care. The time horizon was 1 year and the analysis was conducted from the National Institute for Health and Disability Insurance (NIHDI; national health insurance) and societal perspectives. Remission rates were obtained from the TLV network meta-analysis and risk of relapse, efficacy following therapeutic change, risk of suicide attempts and related death, utilities, costs (2012), and resources were derived from the published literature and expert opinion. The effect of uncertainty in model parameters was estimated through scenario analyses and a probabilistic sensitivity analysis (PSA). In the base-case analysis, escitalopram was identified as the optimal strategy: it dominated all other treatments except venlafaxine from the NIHDI perspective, against which it was cost effective with an incremental cost-effectiveness ratio of 6,352 per quality-adjusted life-year (QALY). Escitalopram also dominated all other treatments from the societal perspective. At a threshold of 30,000 per QALY and from the NIHDI perspective, the PSA showed that the

  16. Randomized Clinical Trial: Esomeprazole, Bismuth, Levofloxacin, and Amoxicillin or Cefuroxime as First-Line Eradication Regimens for Helicobacter pylori Infection.

    Science.gov (United States)

    Fu, Wei; Song, Zhiqiang; Zhou, Liya; Xue, Yan; Ding, Yu; Suo, Baojun; Tian, Xueli; Wang, Li

    2017-06-01

    The eradication of Helicobacter pylori infection remains a challenge, especially in the patients unsuitable to take penicillin. Cephalosporin has the potential to replace amoxicillin for H. pylori eradication. To compare the effectiveness, safety, and compliance of amoxicillin- and cefuroxime-containing quadruple regimens in treatment-naïve patients. In this open-label randomized control study, 400 patients with H. pylori infection were divided into amoxicillin-containing (esomeprazole 20 mg twice/day, amoxicillin 1000 mg twice/day, levofloxacin 500 mg once/day, and bismuth 220 mg twice/day for 14 days) or cefuroxime-containing (esomeprazole 20 mg twice/day, cefuroxime 500 mg twice/day, levofloxacin 500 mg once/day, and bismuth 220 mg twice/day for 14 days) quadruple therapy groups. The safety and compliance were assessed 1-3 days after eradication. Urea breath test was performed 8-12 weeks after eradication to determine treatment outcome. The baseline data including antibiotic resistance were well matched between the two groups. The eradication rates between amoxicillin- and cefuroxime-containing quadruple therapy groups were not significantly different [intention-to-treat analysis: 83.5% (95% confidence interval 78.3-88.7%) vs. 81.0% (75.5-86.5%), P = 0.513; modified intention-to-treat analysis: 90.3% (86.0-94.6%) vs. 88.5% (83.9-93.2%), P = 0.586; per-protocol analysis: 91.6% (87.5-95.7%) vs. 89.8% (85.3-94.3%), P = 0.560]. The incidence of adverse effects (18.4 vs. 20.1%, P = 0.678) and compliance (94.7 vs. 94.2%, P = 0.813) were also similar. Variate analyses showed that antibiotic resistance and poor compliance were the independent risk factors for eradication failure. Esomeprazole, bismuth, levofloxacin, and amoxicillin or cefuroxime achieved similar and relatively satisfactory cure rates, safety, and compliance in first-line H. pylori eradication. Cefuroxime may be a good alternative medicine for eradication instead of amoxicillin for

  17. Binimetinib for the treatment of NRAS-mutant melanoma.

    Science.gov (United States)

    Queirolo, Paola; Spagnolo, Francesco

    2017-11-01

    Activating NRAS mutations occur in approximately 15-20% of melanomas and are the second most common oncogenic driver mutation in this disease, after BRAF mutations. There is an unmet medical need for new targeted therapy opportunities in metastatic patients whose tumors harbor an NRAS mutation. Binimetinib, a mitogen-activated protein kinase kinase (MEK) inhibitor, has shown clinical activity in this group of patients. Areas covered: The purpose of this paper was to review the safety, activity and efficacy of the MEK inhibitor binimetinib for the treatment of NRAS-mutant melanoma, as well as to discuss future therapeutic perspectives such as multiple pathways, targeted therapy, and combinations with immunotherapy. Expert commentary: Only a modest progression-free survival (PFS) benefit was observed in NRAS-mutated patients who received binimetinib compared with dacarbazine in a randomized phase 3 clinical trial, with no improvement in overall survival. Nevertheless, binimetinib represents another promising treatment option for advanced melanoma and the first molecularly targeted therapy for the NRAS-mutant population. Binimetinib may also have a role in treating NRAS-mutated melanoma patients after failure of immunotherapy.

  18. Primary gastric melanoma: case report of a rare malignancy

    Directory of Open Access Journals (Sweden)

    Alexander Augustyn

    2015-03-01

    Full Text Available We report the case of a 64-year-old white male who presented to his primary care physician with complaints of fatigue. Physical exam was unremarkable and laboratory studies revealed profound anemia, for which the patient received a transfusion. Esophagogastroduodenoscopy revealed a bleeding mass in the proximal stomach that was histologically determined to be malignant melanoma, with immunohistochemical staining demonstrating positivity for SOX10, S100, MART-1, and HMG-45. After an extensive dermatological exam no other primary lesion was identified. Whole body positron emission tomography (18-FDG-PET/CT demonstrated pathologic uptake only in the area of the proximal stomach. For this reason, primary gastric melanoma was suspected in this patient. The patient underwent subtotal gastrectomy with mass excision followed by Roux-en-Y reconstruction. Very few cases of primary gastric melanoma have been reported. We report this case and present diagnostic criteria for primary non-cutaneous melanoma and discuss potential non-surgical therapies.

  19. Ipilimumab in advanced melanoma: reports of long-lasting responses.

    Science.gov (United States)

    Farolfi, Alberto; Ridolfi, Laura; Guidoboni, Massimo; Nicoletti, Stefania Vittoria Luisa; Piciucchi, Sara; Valmorri, Linda; Costantini, Matteo; Scarpi, Emanuela; Amadori, Dino; Ridolfi, Ruggero

    2012-06-01

    Patients with metastatic melanoma have a poor prognosis; the results of chemotherapy remain unsatisfactory. Ipilimumab, an anticytotoxic T lymphocyte-associated antigen-4 antibody, has shown promising results in several clinical trials. In this report, advanced melanoma patients receiving ipilimumab were scored according to novel immune-related response criteria (irRC) in an attempt to capture additional response patterns and to avoid premature treatment cessation. Thirty-six heavily pretreated metastatic melanoma patients recieved ipilimumab within five international clinical trials at our Institution from May 2006 to August 2008. Disease progression was defined as an increase in tumor burden by at least 25% compared with the nadir, irrespective of any initial increase in baseline lesions or the appearance of new lesions. We report unusually long-lasting responses in patients treated with ipilimumab 10 mg/kg. An overall response was observed in six out of 30 patients (20%), a complete response in three (10%), and disease control in 11 (37%), which seemed to be of a long duration (median of 16 months; complete response 36+, 34+, and 41+ months). All irRC patterns seemed to be strongly associated with an improvement in overall survival. Interestingly, we found a correlation between the presence of a grade 3/4 immune-related adverse event and responses, time to progression, and overall survival. Ipilimumab therapy resulted in clinically meaningful responses in advanced melanoma patients, supporting the need for further irRC validation.

  20. Common Genetic Risk for Melanoma Encourages Preventive Behavior Change

    Directory of Open Access Journals (Sweden)

    Lori Diseati

    2015-02-01

    Full Text Available There is currently great interest in using genetic risk estimates for common disease in personalized healthcare. Here we assess melanoma risk-related preventive behavioral change in the context of the Coriell Personalized Medicine Collaborative (CPMC. As part of on-going reporting activities within the project, participants received a personalized risk assessment including information related to their own self-reported family history of melanoma and a genetic risk variant showing a moderate effect size (1.7, 3.0 respectively for heterozygous and homozygous individuals. Participants who opted to view their report were sent an optional outcome survey assessing risk perception and behavioral change in the months that followed. Participants that report family history risk, genetic risk, or both risk factors for melanoma were significantly more likely to increase skin cancer preventive behaviors when compared to participants with neither risk factor (ORs = 2.04, 2.79, 4.06 and p-values = 0.02, 2.86 × 10−5, 4.67 × 10−5, respectively, and we found the relationship between risk information and behavior to be partially mediated by anxiety. Genomic risk assessments appear to encourage positive behavioral change in a manner that is complementary to family history risk information and therefore may represent a useful addition to standard of care for melanoma prevention.

  1. Emerging targeted therapies for melanoma.

    Science.gov (United States)

    Johnson, Douglas B; Pollack, Megan H; Sosman, Jeffrey A

    2016-06-01

    Melanoma is an aggressive cutaneous malignancy associated with poor response to traditional therapies. Recent regulatory approval for immune checkpoint inhibitors and agents targeting mutated BRAF has led to a tremendous expansion of effective treatment options for patients with advanced melanoma. Unfortunately, primary or acquired resistance develops in most patients, highlighting the need for additional therapies. Numerous genetic and other molecular features of this disease may provide effective targets for therapy development. This article reviews available melanoma treatments, including immune and molecularly-targeted therapies. We then discuss agents in development, with a focus on targeted (rather than immune) therapies. In particular, we discuss agents that block mitogen-activated protein kinase (MAPK) signaling, as well as other emerging approaches such as antibody-drug conjugates, cell-cycle targeting, and novel genetically-informed clinical trials. Despite the incredible advances in melanoma therapeutics over the last several years, a clear need to develop more effective therapies remains. Molecularly-targeted therapy approaches will likely remain a cornerstone of melanoma treatment in parallel to immune therapy strategies.

  2. Current systemic therapies for melanoma.

    Science.gov (United States)

    Palathinkal, Darren M; Sharma, Timmie R; Koon, Henry B; Bordeaux, Jeremy S

    2014-09-01

    Systemic agents are used in melanoma for adjuvant therapy and to treat metastatic disease. Currently, interferon-α is the only agent approved for adjuvant therapy. Six drugs are FDA approved for metastatic disease: dacarbazine, interleukin-2 (IL-2), vemurafenib, ipilimumab, dabrafenib, and trametinib. Vemurafenib and ipilimumab were approved in 2011, whereas dabrafenib and trametinib were approved in 2013. This review will update the practicing dermatologist on the differences in efficacy, adverse events, and cost of systemic therapies available for the treatment of melanoma. This article is a review of the current literature on systemic therapies for advanced melanoma. Key search words included "advanced melanoma," "systemic therapy," and "adjuvant therapy" with particular focus on the past 20 years. Before 2011, dacarbazine and IL-2 were the only FDA approved therapies for metastatic melanoma, and IFN-α is the only approved agent for adjuvant therapy. The new agents vemurafenib, ipilimumab, dabrafenib, and trametinib are the first to have improved overall survival in Phase III studies in comparison with other systemic therapies. Despite new developments, there remains a significant need for better therapies with improved long-term efficacy and decreased toxicity.

  3. Other targeted drugs in melanoma.

    Science.gov (United States)

    González-Cao, María; Rodón, Jordi; Karachaliou, Niki; Sánchez, Jesús; Santarpia, Mariacarmela; Viteri, Santiago; Pilotto, Sara; Teixidó, Cristina; Riso, Aldo; Rosell, Rafael

    2015-10-01

    Targeted therapy drugs are developed against specific molecular alterations on cancer cells. Because they are "targeted" to the tumor, these therapies are more effective and better tolerated than conventional therapies such as chemotherapy. In the last decade, great advances have been made in understanding of melanoma biology and identification of molecular mechanisms involved in malignant transformation of cells. The identification of oncogenic mutated kinases involved in this process provides an opportunity for development of new target therapies. The dependence of melanoma on BRAF-mutant kinase has provided an opportunity for development of mutation-specific inhibitors with high activity and excellent tolerance that are now being used in clinical practice. This marked a new era in the treatment of metastatic melanoma and much research is now ongoing to identify other "druggable" kinases and transduction signaling networking. It is expected that in the near future the spectrum of target drugs for melanoma treatment will increase. Herein, we review the most relevant potential novel drugs for melanoma treatment based on preclinical data and the results of early clinical trials.

  4. Real-World Treatment Patterns, Survival, and Prediction of CNS Progression in ALK-Positive Non-Small-Cell Lung Cancer Patients Treated with First-Line Crizotinib in Latin America Oncology Practices.

    Science.gov (United States)

    Martín, Claudio; Cardona, Andrés F; Zatarain-Barrón, Zyanya Lucia; Ruiz-Patiño, Alejandro; Castillo, Omar; Oblitas, George; Corrales, Luis; Lupinacci, Lorena; Pérez, María Angelina; Rojas, Leonardo; González, Lisde; Chirinos, Luis; Ortíz, Carlos; Lema, Mauricio; Vargas, Carlos; Puparelli, Carmen; Carranza, Hernán; Otero, Jorge; Arrieta, Oscar

    2018-03-06

    This study describes the real-world characteristics, treatment sequencing, and outcomes among Hispanic patients with locally advanced/metastatic ALK-positive non-small-cell lung cancer (NSCLC) treated with crizotinib. A retrospective patient review was conducted for several centers in Latin America. Clinicians identified ALK-positive NSCLC patients who received crizotinib and reported their clinical characteristics, treatments, and survival. Overall survival and progression-free survival (PFS) were described. A Random Forest Tree (RFT) model was constructed to predict brain progression. A total of 73 patients were included; median age at diagnosis was 58 years, 60.3% were female, and 93.2% had adenocarcinoma. Eighty-nine percent of patients were never smokers/former smokers, 71.1% had ≥2 sites of metastasis, and 20.5% had brain metastases at diagnosis. The median PFS on first-line crizotinib was 7.07 months (95% CI 3.77-12.37) and the overall response rate was 52%. Of those who discontinued crizotinib, 55.9% progressed in the central nervous system (CNS). The RFT model reached a sensitivity of 100% and a specificity of 88% for prediction of CNS progression. The overall response rate and the PFS observed in Hispanic patients with ALK-positive NSCLC treated with first-line crizotinib were similar to those in previous reports. An RFT model is helpful in predicting CNS progression and can help clinicians tailor treatments in a resource-limited practice. © 2018 S. Karger AG, Basel.

  5. Melanoma stem cells in experimental melanoma are killed by radioimmunotherapy

    International Nuclear Information System (INIS)

    Jandl, Thomas; Revskaya, Ekaterina; Jiang, Zewei; Harris, Matthew; Dorokhova, Olena; Tsukrov, Dina; Casadevall, Arturo; Dadachova, Ekaterina

    2013-01-01

    Introduction: In spite of recently approved B-RAF inhibitors and immunomodulating antibodies, metastatic melanoma has poor prognosis and novel treatments are needed. Melanoma stem cells (MSC) have been implicated in the resistance of this tumor to chemotherapy. Recently we demonstrated in a Phase I clinical trial in patients with metastatic melanoma that radioimmunotherapy (RIT) with 188-Rhenium( 188 Re)-6D2 antibody to melanin was a safe and effective modality. Here we investigated the interaction of MSC with RIT as a possible mechanism for RIT efficacy. Methods: Mice bearing A2058 melanoma xenografts were treated with either 1.5 mCi 188 Re-6D2 antibody, saline, unlabeled 6D2 antibody or 188 Re-labeled non-specific IgM. Results: On Day 28 post-treatment the tumor size in the RIT group was 4-times less than in controls (P < 0.001). The tumors were analyzed by immunohistochemistry and FACS for two MSC markers — chemoresistance mediator ABCB5 and H3K4 demethylase JARID1B. There were no significant differences between RIT and control groups in percentage of ABCB5 or JARID1B-positive cells in the tumor population. Our results demonstrate that unlike chemotherapy, which kills tumor cells but leaves behind MSC leading to recurrence, RIT kills MSC at the same rate as the rest of tumor cells. Conclusions: These results have two main implications for melanoma treatment and possibly other cancers. First, the susceptibility of ABCB5 + and JARID1B + cells to RIT in melanoma might be indicative of their susceptibility to antibody-targeted radiation in other cancers where they are present as well. Second, specifically targeting cancer stem cells with radiolabeled antibodies to ABCB5 or JARID1B might help to completely eradicate cancer stem cells in various cancers

  6. A novel approach for the detection and genetic analysis of live melanoma circulating tumor cells.

    Directory of Open Access Journals (Sweden)

    Melody J Xu

    Full Text Available Circulating tumor cell (CTC detection and genetic analysis may complement currently available disease assessments in patients with melanoma to improve risk stratification and monitoring. We therefore sought to establish the feasibility of a telomerase-based assay for detecting and isolating live melanoma CTCs.The telomerase-based CTC assay utilizes an adenoviral vector that, in the presence of elevated human telomerase activity, drives the amplification of green fluorescent protein. Tumor cells are then identified via an image processing system. The protocol was tested on melanoma cells in culture or spiked into control blood, and on samples from patients with metastatic melanoma. Genetic analysis of the isolated melanoma CTCs was then performed for BRAF mutation status.The adenoviral vector was effective for all melanoma cell lines tested with sensitivity of 88.7% (95%CI 85.6-90.4% and specificity of 99.9% (95%CI 99.8-99.9%. In a pilot trial of patients with metastatic disease, CTCs were identified in 9 of 10 patients, with a mean of 6.0 CTCs/mL. At a cutoff of 1.1 CTCs/mL, the telomerase-based assay exhibits test performance of 90.0% sensitivity and 91.7% specificity. BRAF mutation analysis of melanoma cells isolated from culture or spiked control blood, or from pilot patient samples was found to match the known BRAF mutation status of the cell lines and primary tumors.To our knowledge, this is the first report of a telomerase-based assay effective for detecting and isolating live melanoma CTCs. These promising findings support further studies, including towards integrating into the management of patients with melanoma receiving multimodality therapy.

  7. High accuracy of family history of melanoma in Danish melanoma cases.

    Science.gov (United States)

    Wadt, Karin A W; Drzewiecki, Krzysztof T; Gerdes, Anne-Marie

    2015-12-01

    The incidence of melanoma in Denmark has immensely increased over the last 10 years making Denmark a high risk country for melanoma. In the last two decades multiple public campaigns have sought to increase the awareness of melanoma. Family history of melanoma is a known major risk factor but previous studies have shown that self-reported family history of melanoma is highly inaccurate. These studies are 15 years old and we wanted to examine if a higher awareness of melanoma has increased the accuracy of self-reported family history of melanoma. We examined the family history of 181 melanoma probands who reported 199 cases of melanoma in relatives, of which 135 cases where in first degree relatives. We confirmed the diagnosis of melanoma in 77% of all relatives, and in 83% of first degree relatives. In 181 probands we validated the negative family history of melanoma in 748 first degree relatives and found only 1 case of melanoma which was not reported in a 3 case melanoma family. Melanoma patients in Denmark report family history of melanoma in first and second degree relatives with a high level of accuracy with a true positive predictive value between 77 and 87%. In 99% of probands reporting a negative family history of melanoma in first degree relatives this information is correct. In clinical practice we recommend that melanoma diagnosis in relatives should be verified if possible, but even unverified reported melanoma cases in relatives should be included in the indication of genetic testing and assessment of melanoma risk in the family.

  8. Pulse-mediated chemotherapy enhances local control and survival in a spontaneous canine model of primary mucosal melanoma.

    Science.gov (United States)

    Spugnini, Enrico P; Dragonetti, Emanuele; Vincenzi, Bruno; Onori, Nicoletta; Citro, Gennaro; Baldi, Alfonso

    2006-02-01

    Mucosal melanomas account for 1% of all malignant melanomas in humans. Treatment options include surgery, chemotherapy, immunotherapy and radiation therapy; however, local recurrence and distant dissemination are still frequent. We treated locally aggressive spontaneous canine oral melanomas that, because of their advanced stage, were not treatable with conventional strategies. A cohort of 10 dogs with oral melanoma was enrolled over a 4-year period. The dogs received two sessions of local bleomycin, followed by the application of trains of biphasic pulses. The treatment was well tolerated and resulted in an overall response rate of 80% with 50% long-term control. Of interest, only one of the dogs died of metastatic disease, and four of the long-term survivors showed a vitiligo-like discoloration at the site of treatment, potentially suggesting a recruitment of the immune system by the therapy. Further studies are needed to characterize this approach and to determine its suitability for head and neck mucosal melanoma.

  9. Real-time supervised detection of pink areas in dermoscopic images of melanoma: importance of color shades, texture and location.

    Science.gov (United States)

    Kaur, R; Albano, P P; Cole, J G; Hagerty, J; LeAnder, R W; Moss, R H; Stoecker, W V

    2015-11-01

    Early detection of malignant melanoma is an important public health challenge. In the USA, dermatologists are seeing more melanomas at an early stage, before classic melanoma features have become apparent. Pink color is a feature of these early melanomas. If rapid and accurate automatic detection of pink color in these melanomas could be accomplished, there could be significant public health benefits. Detection of three shades of pink (light pink, dark pink, and orange pink) was accomplished using color analysis techniques in five color planes (red, green, blue, hue, and saturation). Color shade analysis was performed using a logistic regression model trained with an image set of 60 dermoscopic images of melanoma that contained pink areas. Detected pink shade areas were further analyzed with regard to the location within the lesion, average color parameters over the detected areas, and histogram texture features. Logistic regression analysis of a separate set of 128 melanomas and 128 benign images resulted in up to 87.9% accuracy in discriminating melanoma from benign lesions measured using area under the receiver operating characteristic curve. The accuracy in this model decreased when parameters for individual shades, texture, or shade location within the lesion were omitted. Texture, color, and lesion location analysis applied to multiple shades of pink can assist in melanoma detection. When any of these three details: color location, shade analysis, or texture analysis were omitted from the model, accuracy in separating melanoma from benign lesions was lowered. Separation of colors into shades and further details that enhance the characterization of these color shades are needed for optimal discrimination of melanoma from benign lesions. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Clear cells in acral melanoma.

    Science.gov (United States)

    Schmuth, M; Spötl, L; Zelger, B; Weinlich, G; Zelger, B

    2001-01-01

    Acral melanoma may present clinically and histologically with atypical features causing a delay in proper diagnosis. The aim of the present study was to assess the frequency of a histological variant with clear cell changes. Clinical information, hematoxylin & eosin stained paraffin sections and immunohistochemical staining profiles were reviewed in 49 cases of acral melanoma. Twenty-one (43%) specimens contained tumor cells with clear cell changes in focal areas, whereas in 7 (14%) specimens clear cells were the major tumor constituting cells. The tumor thickness ranged from melanoma in situ to 14 mm. Immunohistochemistry demonstrated weak staining for S100 and HMB45 as well as strong positivity for Melan A and NK1C3. Recognition of clear cell features is important since differential diagnosis includes a variety of other clear cell malignancies, among them metastasis from renal cell carcinoma, clear cell sarcoma and hidradenocarcinoma.

  11. Familial skin cancer syndromes: Increased melanoma risk.

    Science.gov (United States)

    Ransohoff, Katherine J; Jaju, Prajakta D; Jaju, Prajaka D; Tang, Jean Y; Carbone, Michele; Leachman, Sancy; Sarin, Kavita Y

    2016-03-01

    Phenotypic traits, such as red hair and freckling, increase melanoma risk by 2- to 3-fold. In addition, approximately 10% of melanomas are caused by inherited germline mutations that increase melanoma risk from 4- to >1000-fold. This review highlights the key genes responsible for inherited melanoma, with an emphasis on when a patient should undergo genetic testing. Many genetic syndromes associated with increased melanoma risk are also associated with an increased risk of other cancers. Identification of these high-risk patients is essential for preventive behavior reinforcement, genetic counseling, and ensuring other required cancer screenings. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  12. Melanoma: oncogenic drivers and the immune system.

    Science.gov (United States)

    Karachaliou, Niki; Pilotto, Sara; Teixidó, Cristina; Viteri, Santiago; González-Cao, María; Riso, Aldo; Morales-Espinosa, Daniela; Molina, Miguel Angel; Chaib, Imane; Santarpia, Mariacarmela; Richardet, Eduardo; Bria, Emilio; Rosell, Rafael

    2015-10-01

    Advances and in-depth understanding of the biology of melanoma over the past 30 years have contributed to a change in the consideration of melanoma as one of the most therapy-resistant malignancies. The finding that oncogenic BRAF mutations drive tumor growth in up to 50% of melanomas led to a molecular therapy revolution for unresectable and metastatic disease. Moving beyond BRAF, inactivation of immune regulatory checkpoints that limit T cell responses to melanoma has provided targets for cancer immunotherapy. In this review, we discuss the molecular biology of melanoma and we focus on the recent advances of molecularly targeted and immunotherapeutic approaches.

  13. Treatment of multicentric or cranial mediastinal high-grade T-cell lymphoma in dogs with a first-line CCNU-L(-chlorambucil)-CHOP protocol

    NARCIS (Netherlands)

    Ossowska, M.; Teske, E.; Beirens-Van Kuijk, L.; Zandvliet, Maurice; De Vos, J. P.

    2016-01-01

    This retrospective study determined disease free survival (DFS) and progression free survival (PFS) in chemo-naïve dogs with multicentric or cranial mediastinal high-grade T-cell lymphoma, treated with a first-line CCNU-L(-chlorambucil)-CHOP protocol. Of thirteen dogs with multicentric lymphoma,

  14. Effect of first line cancer treatment on the ovarian reserve and follicular density in girls under the age of 18 years

    DEFF Research Database (Denmark)

    El Issaoui, Meryam; Giorgione, Veronica; Mamsen, Linn Salto

    2016-01-01

    OBJECTIVE: To study the impact of first-line antineoplastic treatment on ovarian reserve in young girls returning for ovarian tissue cryopreservation (OTC) in connection with a relapse. DESIGN: Retrospective case-control study. SETTING: University hospitals. PATIENT(S): Sixty-three girls under...

  15. Prolonged first-line PEG-asparaginase treatment in pediatric acute lymphoblastic leukemia in the NOPHO ALL2008 protocol-Pharmacokinetics and antibody formation

    DEFF Research Database (Denmark)

    Tram Henriksen, Louise; Gottschalk Højfeldt, Sofie; Schmiegelow, Kjeld

    2017-01-01

    BACKGROUND: As pegylated asparaginase is becoming the preferred first-line asparaginase preparation in the chemotherapy regimens of childhood acute lymphoblastic leukemia (ALL), there is a need to evaluate this treatment. METHODS: The aim of this study was to evaluate the pharmacokinetics...

  16. Patterns of HIV-1 Drug Resistance After First-Line Antiretroviral Therapy (ART) Failure in 6 Sub-Saharan African Countries: Implications for Second-Line ART Strategies

    NARCIS (Netherlands)

    Hamers, Raph L.; Sigaloff, Kim C. E.; Wensing, Annemarie M.; Wallis, Carole L.; Kityo, Cissy; Siwale, Margaret; Mandaliya, Kishor; Ive, Prudence; Botes, Mariette E.; Wellington, Maureen; Osibogun, Akin; Stevens, Wendy S.; Rinke de Wit, Tobias F.; Schuurman, Rob; Siwale, M.; Njovu, C.; Labib, M.; Menke, J.; Botes, M. E.; Conradie, F.; Ive, P.; Sanne, I.; Wallis, C. L.; Letsoalo, E.; Stevens, W. S.; Hardman, M.; Wellington, M.; Luthy, R.; Mandaliya, K.; Abdallah, S.; Jao, I.; Dolan, M.; Namayanja, G.; Nakatudde, L.; Nankya, I.; Kiconco, M.; Abwola, M.; Mugyenyi, P.; Osibogun, A.; Akanmu, S.; Schuurman, R.; Wensing, A. M.; Straatsma, E.; Wit, F. W.; Dekker, J.; van Vugt, M.; Lange, J. M.

    2012-01-01

    Background. Human immunodeficiency virus type 1 (HIV-1) drug resistance may limit the benefits of antiretroviral therapy (ART). This cohort study examined patterns of drug-resistance mutations (DRMs) in individuals with virological failure on first-line ART at 13 clinical sites in 6 African

  17. Lenalidomide maintenance after first-line therapy for high-risk chronic lymphocytic leukaemia (CLLM1): final results from a randomised, double-blind, phase 3 study

    NARCIS (Netherlands)

    Fink, Anna Maria; Bahlo, Jasmin; Robrecht, Sandra; Al-Sawaf, Othman; Aldaoud, Ali; Hebart, Holger; Jentsch-Ullrich, Kathleen; Dörfel, Steffen; Fischer, Kirsten; Wendtner, Clemens-Martin; Nösslinger, Thomas; Ghia, Paolo; Bosch, Francesc; Kater, Arnon P.; Döhner, Hartmut; Kneba, Michael; Kreuzer, Karl-Anton; Tausch, Eugen; Stilgenbauer, Stephan; Ritgen, Matthias; Böttcher, Sebastian; Eichhorst, Barbara; Hallek, Michael

    2017-01-01

    Background The combined use of genetic markers and detectable minimal residual disease identifies patients with chronic lymphocytic leukaemia with poor outcome after first-line chemoimmunotherapy. We aimed to assess lenalidomide maintenance therapy in these high-risk patients. Methods In this

  18. First-line sunitinib versus pazopanib in metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

    DEFF Research Database (Denmark)

    Ruiz-Morales, Jose Manuel; Swierkowski, Marcin; Wells, J Connor

    2016-01-01

    BACKGROUND: Sunitinib (SU) and pazopanib (PZ) are standards of care for first-line treatment of metastatic renal cell carcinoma (mRCC). However, how the efficacy of these drugs translates into effectiveness on a population-based level is unknown. PATIENTS AND METHODS: We used the International m...

  19. Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome: a prospective randomized multinational study

    NARCIS (Netherlands)

    Homburg, R.R.; Hendriks, M.L.; König, T.E.; Anderson, R.A.; Balen, A.H.; Brincat, M.; Child, T.; Davies, M.; D'Hooghe, T.; Martinez, A; Rajkhowa, M.; Rueda-Saenz, R.; Hompes, P.G.A.; Lambalk, C.B.

    2012-01-01

    BACKGROUND: Clomifene citrate (CC) is accepted as the first-line method for ovulation induction (OI) in patients with polycystic ovary syndrome (PCOS) associated with infertility owing to anovulation. Low-dose FSH has been reserved for women failing to conceive with CC. In this RCT, we tested the

  20. Costs of managing adverse events in the treatment of first-line metastatic renal cell carcinoma: Bevacizumab in combination with interferon-α2a compared with sunitinib

    NARCIS (Netherlands)

    G.H.J. Mickisch; M. Gore (Martin); B. Escudier (B.); G. Procopio (G.); S. Walzer (S.); M.J.C. Nuijten (Mark)

    2010-01-01

    textabstractBackground: Bevacizumab plus interferon-α2a (IFN) prolongs progression-free survival to>10 months, which is comparable with sunitinib as first-line treatment of metastatic renal cell carcinoma (RCC). The two regimens have different tolerability profiles; therefore, costs for managing

  1. Safety and efficacy of vinorelbine in combination with pertuzumab and trastuzumab for first-line treatment of patients with HER2-positive locally advanced or metastatic breast cancer

    DEFF Research Database (Denmark)

    Perez, Edith A; López-Vega, José Manuel; Petit, Thierry

    2016-01-01

    BACKGROUND: Pertuzumab, trastuzumab, and docetaxel is standard of care for first-line treatment of HER2-positive metastatic breast cancer (MBC). However, alternative chemotherapy partners are required to align with patient/physician preferences and to increase treatment flexibility. We report...

  2. Systematic review and meta-analysis on the prognostic value of complete remission status at FDG-PET in Hodgkin lymphoma after completion of first-line therapy

    NARCIS (Netherlands)

    Adams, Hugo J A; Nievelstein, Rutger A J; Kwee, Thomas C.

    This study aimed to systematically review and meta-analyze the prognostic value of complete remission status at 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in Hodgkin lymphoma after completion of first-line therapy. A systematic literature search was performed in the MEDLINE

  3. Long-term use of first-line highly active antiretroviral therapy is not associated with carotid artery stiffness in human immunodeficiency virus-positive patients

    Directory of Open Access Journals (Sweden)

    Haohui Zhu

    2014-09-01

    Conclusion: The first-line highly active antiretroviral therapy currently used in China is not associated with carotid artery stiffness in human immunodeficiency virus-positive patients with good highly active antiretroviral therapy compliance. Human immunodeficiency virus may play a role in the development of atherosclerosis.

  4. Short communication: high rates of thymidine analogue mutations and dual-class resistance among HIV-infected Ugandan children failing first-line antiretroviral therapy

    NARCIS (Netherlands)

    Sigaloff, Kim C. E.; Kayiwa, Joshua; Musiime, Victor; Calis, Job C. J.; Kaudha, Elizabeth; Mukuye, Andrew; Matama, Christine; Nankya, Immaculate; Nakatudde, Lillian; Dekker, John T.; Hamers, Raph L.; Mugyenyi, Peter; Rinke de Wit, Tobias F.; Kityo, Cissy

    2013-01-01

    HIV-infected children are at high risk of acquiring drug-resistant viruses, which is of particular concern in settings where antiretroviral drug options are limited. We aimed to assess resistance patterns and predict viral drug susceptibility among children with first-line antiretroviral therapy

  5. Choroidal melanoma in a dog.

    Science.gov (United States)

    Miwa, Yasutsugu; Matsunaga, Satoru; Kato, Kumiko; Ogawa, Hiroyuki; Nakayama, Hiroyuki; Tsujimoto, Saori; Sasaki, Nobuo

    2005-08-01

    A 7-year-old intact female golden Retriever was referred for evaluation of an intraorbital mass of the left eye. Based on ophthalmoscopy, ultrasonography and magnetic resonance imaging (MRI), the tentative diagnosis was made as an intraocular neoplasia, especially choroidal melanoma. The orbital exenteration of the affected eye was performed. The mass was histologically diagnosed as malignant choroidal melanoma. No signs of recurrence and metastasis were detected by thoracic radiographs, blood examinations and MR images, and the dog was clinically healthy for 23 months after operation.

  6. Oral mucosal melanoma: A case report

    Directory of Open Access Journals (Sweden)

    Ramlal Gantala

    2017-01-01

    Full Text Available Malignant melanoma is most deadly of all primary skin cancers. Over 90% of melanomas occur on the skin. Half of such melanomas occur in the oral cavity, followed by nasal cavity (44% and sinuses (8%. In the oral cavity, the most frequent sites of occurrence are hard palate and maxillary gingiva. Mucosal melanomas represent a diagnostic challenge than the more common cutaneous melanomas because oral melanomas demonstrate significant heterogeneity in morphological features, developmental process, and biological behaviour. This case report highlights an exophytic, lobulated oral malignant melanoma involving maxillary gingiva and is presented to reemphasize the fact that any pigmented lesion in the oral cavity should be examined with suspicion; proper investigation should be carried out to rule out any untoward experiences later.

  7. Rituximab plus chemotherapy as first-line treatment in Chinese patients with diffuse large B-cell lymphoma in routine practice: a prospective, multicentre, non-interventional study

    International Nuclear Information System (INIS)

    Wu, Jianqiu; Song, Yongping; Su, Liping; Xu, Li; Chen, Tingchao

    2016-01-01

    The efficacy and safety of rituximab-based chemotherapy (R-chemo), the standard regimen for patients with diffuse large B-cell lymphoma (DLBCL), which is more common in Asia than in Western countries, are well confirmed in randomized controlled trials (RCTs). However, the safety and effectiveness of R-chemo in patients who are largely excluded from RCTs have not been well characterized. This real-world study investigated the safety and effectiveness of R-chemo as first-line treatment in Chinese patients with DLBCL. Treatment-naive DLBCL patients who were CD20 positive and eligible to receive R-chemo were enrolled with no specific exclusion criteria. Data collected at baseline included age, gender, disease stage, international prognostic index (IPI), B symptoms, extranodal involvement, performance status, and medical history. In the present study, data on safety, treatment effectiveness, and HBV infection management were collected 120 days after the last R-chemo administration. Overall, R-chemo was well tolerated. The safety profile of R-chemo in patients with a history of heart or liver disease was well described without any additional unexpected safety concerns. The overall response rate (ORR) in the Chinese patients from this study was 94.2 % (complete response [CR], 55.0 %; CR unconfirmed [CRu] 18.2 %; and partial response [PR], 20.9 %). Compared to patients with no history of disease, the CR and PR rates of patients with a history of heart or liver disease were lower and higher, respectively; this tendency could be in part explained by treatment interruptions in patients with heart or liver diseases. HBsAg positivity and a maximum tumor diameter of ≥7.5 cm negatively correlated with CR + CRu, whereas age and HBsAg positivity negatively correlated with CR. This study further validated the safety and effectiveness of R-chemo in Chinese patients with DLBCL. Patients with a history of heart or liver disease may further benefit from R-chemo if preventive measures

  8. Survival after failure of first-line chemotherapy in advanced gastric cancer patients: differences between Japan and the rest of the world.

    Science.gov (United States)

    Takashima, Atsuo; Iizumi, Sakura; Boku, Narikazu

    2017-07-01

    In this review, we focus on post-progression survival after first-line chemotherapy of advanced gastric cancer, and particularly the differences between Japan and the rest of the world. We reviewed 15 recent phase III trials of which 4 were solely recruited from Japanese and 11 from rest of the world. The patient characteristics age, performance status, previous gastrectomy and the number of metastatic sites were similar in Japan and rest of the world. However, the diffuse histological type was more common in Japan. While overall survival was longer in Japan (10.5-14.1 vs. 7.9-12.2 months), progression-free survival tended to be shorter in Japan (3.6-6.0 vs. 3.1-7.4 months). Post-progression survival calculated as the difference between median overall survival and progression-free survival was clearly longer in Japan (6.9-8.6 vs. 2.4-6.2 months). The proportion of patients receiving second-line chemotherapy (%2nd-CX) was quite different in Japan and rest of the world (69-85% vs. 11-59%). Correlations between %2nd-CX and post-progression survival were strong (Spearman's rank correlation coefficient; ρ = 0.86, P < 0.001). Correlations between %2nd-CX and ratio of post-progression survival to total overall survival were also strong (ρ = 0.84, P < 0.001). Because a survival benefit of second-CX was documented in several phase III trials, it can be concluded that higher %2nd-CX partly contributed to extended post-progression survival. However, considering that second-CX increased survival only by ~1.5 months at median, other factors such as third-line chemotherapy may have some influences to prolonged post-progression survival. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. USE OF A COMBINATION OF АVASTIN AND LOW-DOSE INTERFERON- α IN THE FIRST-LINE TREATMENT OF METASTATIC RENAL-CELL CANCER

    Directory of Open Access Journals (Sweden)

    A. S. Kalpinsky

    2013-01-01

    Full Text Available Background. The registered AVOREN Phase III trial demonstrated the efficacy of a combination of bevacizumab and interferon-α (IFN-α as first-line targeted therapy in patients with metastatic renal-cell cancer (mRCC. The median progression-free survival (PFS was significantly higher in the bevacizumab + IFN-α group, amounting to 10.2 months versus 5.4 months in the IFN-α group (p < 0.0001. The most common grade 3 and 4 side effects in the AVOREN study included the adverse events due to IFN-α use; this initiated a prospective multicenter BEVLiN (Bevacizumab and Low-Dose Interferon Phase II trial in 2008 to evaluate the efficacy and tolerability of a combination of bevacizumab and low-dose IFN-α in patients with mRCC to diminish the toxicity of treatment.Subjects and methods. The trial enrolled 146 patients having good and moderate prognosis according to the MSKCC scale. The patients received Avastin 10 mg/kg every 2 weeks and IFN-α 3,000,000 IU thrice weekly. The historical control group was taken from the AVOREN trial as a control group. The main purposes of the trial were to evaluate the tolerability of treatment (the frequency of adverse events due to IFN-α use, grade 3 or more toxicity and PFS. The additional goals were to estimate overall survival (OS, objective response rates, and the incidence of any adverse events of grade 3–4 toxicity.Results. The median follow-up was 29.4 months (range 1.5–35.4 months. The rate of objective responses was 28.8 % (95 % confidence interval (CI 21.4–37.1. The median PFS was 15.3 months (95 % CI 11.7–18.0 and PFS was 58.2 and 28.9 % at 12 and 24 months of treatment, respectively. The median OS was 30.7 months (95 % CI 25.7 was unachieved. In the IFN-α group, all grades of adverse reactions and their grade 3 or more were recorded in 53.4 and 10.3 % of the patients, respectively. The adverse events that were a reason for IFN-α discontinuation were recorded in 24.0 % of the patients

  10. In-depth characterization of microRNA transcriptome in melanoma.

    Directory of Open Access Journals (Sweden)

    James Kozubek

    Full Text Available The full repertoire of human microRNAs (miRNAs that could distinguish common (benign nevi from cutaneous (malignant melanomas remains to be established. In an effort to gain further insight into the role of miRNAs in melanoma, we applied Illumina next-generation sequencing (NGS platform to carry out an in-depth analysis of miRNA transcriptome in biopsies of nevi, thick primary (>4.0 mm and metastatic melanomas with matched normal skin in parallel to melanocytes and melanoma cell lines (both primary and metastatic (n=28. From this data representing 698 known miRNAs, we defined a set of top-40 list, which properly classified normal from cancer; also confirming 23 (58% previously discovered miRNAs while introducing an additional 17 (42% known and top-15 putative novel candidate miRNAs deregulated during melanoma progression. Surprisingly, the miRNA signature distinguishing specimens of melanoma from nevus was significantly different than that of melanoma cell lines from melanocytes. Among the top list, miR-203, miR-204-5p, miR-205-5p, miR-211-5p, miR-23b-3p, miR-26a-5p and miR-26b-5p were decreased in melanomas vs. nevi. In a validation cohort (n=101, we verified the NGS results by qRT-PCR and showed that receiver-operating characteristic curves for miR-211-5p expression accurately discriminated invasive melanoma (AUC=0.933, melanoma in situ (AUC=0.933 and dysplastic (atypical nevi (AUC=0.951 from common nevi. Target prediction analysis of co-transcribed miRNAs showed a cooperative regulation of key elements in the MAPK signaling pathway. Furthermore, we found extensive sequence variations (isomiRs and other non-coding small RNAs revealing a complex melanoma transcriptome. Deep-sequencing small RNAs directly from clinically defined specimens provides a robust strategy to improve melanoma diagnostics.

  11. Targeted treatment and immunotherapy in leptomeningeal metastases from melanoma.

    Science.gov (United States)

    Geukes Foppen, M H; Brandsma, D; Blank, C U; van Thienen, J V; Haanen, J B; Boogerd, W

    2016-06-01

    Historically leptomeningeal metastases (LM) from melanoma have a poor prognosis, with a median survival of only 2 months despite treatment. Targeted therapy and immune checkpoint inhibitors are promising new treatment options in advanced melanoma. We sought to determine the impact of targeted therapy and immunotherapy on the outcome of melanoma patients with LM and to evaluate the influence of prognostic factors. We analyzed a series of 39 consecutive patients diagnosed with LM from melanoma between May 2010 and March 2015 treated at the Netherlands Cancer Institute. Thirty-four of these patients also had brain metastases (BM). Statistical analyses assessed the influence of clinical and biological characteristics on survival. Median overall survival of the entire cohort was 6.9 weeks (95% confidence interval 0.9-12.8). Due to a poor performance status or rapidly progressive disease, 14 patients received no treatment. Median overall survival of untreated patients after the diagnosis of LM was 2.9 versus 16.9 weeks for treated patients (P treatment was given, whereas 2 patients are in ongoing remission for 26 weeks (following dabrafenib) and 235 weeks (following WBRT and ipilimumab). Elevated serum lactate dehydrogenase and S100B at diagnosis of LM were associated with shorter survival. LM from melanoma still has an extremely poor prognosis. As observed in extracranial metastatic disease, new treatment modalities such as systemic targeted therapy and immune checkpoint inhibitors seem to increase overall survival in LM, and may result in long-term remission. These new treatment options should be considered in patients with LM. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  12. Association of Delays in Surgery for Melanoma With Insurance Type.

    Science.gov (United States)

    Adamson, Adewole S; Zhou, Lei; Baggett, Christopher D; Thomas, Nancy E; Meyer, Anne-Marie

    2017-11-01

    Timely receipt of treatment for cancer is an important aspect of health care quality. It is unknown how delays of surgery for melanoma vary by insurance type. To analyze factors associated with delays between diagnosis and surgery for melanoma in patients with Medicare, Medicaid, or private insurance. Retrospective cohort study of patients who received a diagnosis of melanoma between 2004 and 2011 in North Carolina using data from the North Carolina Cancer Registry linked to administrative claims from Medicare, Medicaid, and private insurance. Inclusion criteria were incident patients with a diagnosis of melanoma stage 0 to III and with continuous insurance enrollment from at least 1 month prior to the month of diagnosis to 12 months after diagnosis of melanoma. Surgical delay, defined as definitive surgical excision occurring more than 6 weeks after melanoma diagnosis. Generalized linear models with log link, Poisson distributions, and robust standard errors were used to estimate adjusted risk ratios (RRs) to model risk of delay in definitive surgery. A total of 7629 patients were included (4210 [55%] female; mean [SD] age, 64 [15] years), 48% (n = 3631) Medicare, 48% (n = 3667) privately insured, and 4% (n = 331) Medicaid patients. Privately insured patients were least likely to experience a delay in definitive surgery, followed by Medicare and Medicaid patients (519 [14%], 609 [17%], and 79 [24%], respectively; P insurance (RR, 1.36; 95% CI, 1.09-1.70). Delays were more likely in nonwhite patients (RR, 1.38; 95% CI, 1.02-1.87). Surgical delays were less likely if the physician performing the surgery (RR, 0.82; 95% CI, 0.72-0.93) or the diagnosing clinician (RR, 0.81; 95% CI, 0.71-0.93) was a dermatologist as compared with a nondermatologist. Surgical treatment delays were common but were less prevalent in patients diagnosed or surgically treated by a dermatologist. Medicaid patients experienced the most surgical delays. A reduction in delays in

  13. Selective Internal Radiation Therapy (SIRT) with yttrium-90 resin microspheres plus standard systemic chemotherapy regimen of FOLFOX versus FOLFOX alone as first-line treatment of non-resectable liver metastases from colorectal cancer: the SIRFLOX study.

    Science.gov (United States)

    Gibbs, Peter; Gebski, Val; Van Buskirk, Mark; Thurston, Kenneth; Cade, David N; Van Hazel, Guy A

    2014-12-01

    In colorectal cancer (CRC), unresectable liver metastases are linked to poor prognosis. Systemic chemotherapy with regimens such as FOLFOX (combination of infusional 5-fluorouracil, leucovorin and oxaliplatin) is the standard first-line treatment. The SIRFLOX trial was designed to assess the efficacy and safety of combining FOLFOX-based chemotherapy with Selective Internal Radiation Therapy (SIRT or radioembolisation) using yttrium-90 resin microspheres (SIR-SpheresR; Sirtex Medical Limited, North Sydney, Australia). SIRFLOX is a randomised, multicentre trial of mFOLFOX6 chemotherapy+/-SIRT as first-line treatment of patients with liver-only or liver-predominant metastatic CRC (mCRC). The trial aims to recruit adult chemotherapy-naive patients with proven liver metastases with or without limited extra-hepatic disease, a life expectancy of >=3 months and a WHO performance status of 0-1. Patients will be randomised to receive either mFOLFOX6 or SIRT+mFOLFOX6 (with a reduced dose of oxaliplatin in cycles 1-3 following SIRT). Patients in both arms can receive bevacizumab at investigator discretion. Protocol chemotherapy will continue until there is unacceptable toxicity, evidence of tumour progression, complete surgical resection or ablation of cancerous lesions, or the patient requests an end to treatment. The primary endpoint of the SIRFLOX trial is progression-free survival (PFS). Secondary endpoints include: PFS in the liver; tumour response rate (liver and any site); site of tumour progression; health-related quality of life; toxicity and safety; liver resection rate; and overall survival. Assuming an increase in the median PFS from 9.4 months to 12.5 months with the addition of SIRT to mFOLFOX6, recruiting >=450 patients will be sufficient for 80% power and 95% confidence. The SIRFLOX trial will establish the potential role of SIRT+standard systemic chemotherapy in the first-line management of mCRC with non-resectable liver metastases. SIRFLOX Clinical

  14. Real-world first-line treatment and overall survival in non-small cell lung cancer without known EGFR mutations or ALK rearrangements in US community oncology setting.

    Directory of Open Access Journals (Sweden)

    Amy P Abernethy

    Full Text Available To establish a baseline for care and overall survival (OS based upon contemporary first-line treatments prescribed in the era before the introduction of immune checkpoint inhibitors, for people with metastatic non-small cell lung cancer (NSCLC without common actionable mutations.Using a nationally representative electronic health record data from the Flatiron dataset which included 162 practices from different regions in US, we identified patients (≥18 years old newly diagnosed with stage IV NSCLC initiating first-line anticancer therapy (November 2012- January 2015, with follow-up through July 2015. Patients with documented epidermal growth factor receptor (EGFR or anaplastic lymphoma kinase (ALK translocation were excluded. Anti-cancer drug therapy and overall survival were described overall, and by histology.A total of 2,014 patients with stage IV NSCLC without known EGFR or ALK genomic tumor aberrations initiated systemic anticancer therapy, 22% with squamous and 78% with nonsquamous histology. Their mean (SD age was 67 (10 years, 55% were male, and 87% had a smoking history. In nonsquamous NSCLC, carboplatin plus pemetrexed either without (25.7% or with bevacizumab (16% were the most common regimens; 26.6% of nonsquamous patients receiving induction therapy also received continuation maintenance therapy. In squamous NSCLC, carboplatin plus paclitaxel (37.6% or nab-paclitaxel (21.1% were the most commonly used regimens. Overall median OS was 9.7 months (95% CI: 9.1, 10.3, 8.5 months (95% CI: 7.4, 10.0 for squamous, and 10.0 months (95% CI: 9.4, 10.8 for nonsquamous NSCLC.The results provide context for evaluating the effect of shifting treatment patterns of NSCLC treatments on patient outcomes, and for community oncology benchmarking initiatives.

  15. Impact of immunotherapy among patients with melanoma brain metastases managed with radiotherapy.

    Science.gov (United States)

    Stokes, William A; Binder, David C; Jones, Bernard L; Oweida, Ayman J; Liu, Arthur K; Rusthoven, Chad G; Karam, Sana D

    2017-12-15

    Patients with melanoma brain metastases (MBM) have been excluded from trials evaluating immunotherapy in melanoma. As such, immunotherapy's role in MBM is poorly understood, particularly in combination with radiotherapy. The National Cancer Database was queried for patients with MBM receiving brain radiotherapy. They were classified according to immunotherapy receipt. Multivariate Cox regression was performed to identify factors associated with survival. Among 1287 patients, 185 received immunotherapy. Factors associated with improved survival included younger age, academic facility, lower extracranial disease burden, stereotactic radiotherapy, chemotherapy, and immunotherapy. Adding immunotherapy to radiotherapy for MBM is associated with improved survival. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Fever and the use of paracetamol during IL-2-based immunotherapy in metastatic melanoma

    DEFF Research Database (Denmark)

    Køstner, Anne Helene; Ellegaard, Mai-Britt Bjørklund; Christensen, Ib Jarle

    2015-01-01

    effective antitumor immune response. The purpose of this retrospective study was to examine the potential role of the IL-2-induced fever in melanoma patients treated with or without paracetamol in two consecutive cohorts. One hundred and seventy-nine patients with metastatic melanoma treated with a modified...... decrescendo regimen of IL-2 and Interferon (IFN) between 2004 and 2010 were retrospectively studied. 87 patients treated before 2007 received paracetamol as part of the treatment schedule, and 92 patients treated after 2007 did not receive paracetamol routinely. Body temperature was analyzed as dichotomized...

  17. Cutavirus in Cutaneous Malignant Melanoma

    DEFF Research Database (Denmark)

    Mollerup, Sarah; Fridholm, Helena; Vinner, Lasse

    2017-01-01

    A novel human protoparvovirus related to human bufavirus and preliminarily named cutavirus has been discovered. We detected cutavirus in a sample of cutaneous malignant melanoma by using viral enrichment and high-throughput sequencing. The role of cutaviruses in cutaneous cancers remains...

  18. Prognostic stratification of ulcerated melanoma

    DEFF Research Database (Denmark)

    Bønnelykke-Behrndtz, Marie L; Schmidt, Henrik; Christensen, Ib J

    2014-01-01

    OBJECTIVES: For patients with melanoma, ulceration is an important prognostic marker and interestingly also a predictive marker for the response of adjuvant interferon. A consensual definition and accurate assessment of ulceration are therefore crucial for proper staging and clinical management. We...

  19. Stages of Intraocular (Uveal) Melanoma

    Science.gov (United States)

    ... or tans poorly. Blue or green or other light-colored eyes. Older age. Being white. Signs of intraocular melanoma include blurred vision ... to treat small tumors. This is also called light coagulation. ... are being tested in clinical trials. Information about clinical trials ...

  20. Prognostic Factors in Uveal Melanoma

    NARCIS (Netherlands)

    E. Kiliç (Emine)

    2006-01-01

    textabstractUveal melanoma is the most common intra-ocular tumour in the western world with an annual incidence of seven per million. Approximately 50% of the patients treated by enucleation dye eventually due to metastatic disease. Besides enucleation there are nowadays more conservative treatment

  1. Transarterial chemoembolization of liver metastases in patients with uveal melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Huppert, P.E., E-mail: huppert@klinikum-darmstadt.d [Department of Diagnostic and Interventional Radiology, Klinikum Darmstadt, Darmstadt (Germany); Fierlbeck, G., E-mail: gerhard.fierlbeck@med.uni-tuebingen.d [Department of Dermatology, University of Tuebingen, Liebermeisterstrasse 25, D-72076 Tuebingen (Germany); Pereira, P., E-mail: philippe.pereira@slk-kliniken.d [Department of Diagnostic Radiology, University of Tuebingen, Hoppe-Seyler-Strasse 3, D-72076 Tuebingen (Germany); Schanz, S., E-mail: stefan.schanz@med.uni-tuebingen.d [Department of Dermatology, University of Tuebingen, Liebermeisterstrasse 25, D-72076 Tuebingen (Germany); Duda, S.H., E-mail: stephan.duda@t-online.d [Department of Diagnostic Radiology, University of Tuebingen, Hoppe-Seyler-Strasse 3, D-72076 Tuebingen (Germany); Wietholtz, H., E-mail: hubertus.wietholtz@klinikum-darmstadt.d [Department of Internal Medicine II, Klinikum Darmstadt, Darmstadt (Germany); Rozeik, C., E-mail: rozeik.christoph@klinloe.d [Department of Diagnostic and Interventional Radiology, Klinikum Darmstadt, Darmstadt (Germany); Claussen, C.D., E-mail: claus.claussen@med.uni-tuebingen.d [Department of Diagnostic Radiology, University of Tuebingen, Hoppe-Seyler-Strasse 3, D-72076 Tuebingen (Germany)

    2010-06-15

    Summary: Metastases from uveal melanoma are often confined to the liver. Palliative hepatic chemoembolization has been considered to be a reasonable treatment approach. We enrolled 14 patients with hepatic metastases from uveal melanoma into a pilot trial of transarterial chemoembolization (TACE). All patients received additional systemic immuno-chemotherapy or best supportive care. In 31 procedures 100 mg/m{sup 2} of cisplatine was continuously infused by means of a power injector preceding embolization by manual injection of polyvinyl alcohol particles. In three procedures cisplatine was replaced by 200 mg/m{sup 2} carboplatine because of increased serum creatinine levels. Tumor response was evaluated using RECIST criteria. Fourteen patients received 34 TACE's (mean: 2.4 treatments). Eight patients (57%) achieved partial response (PR), four patients (29%) had stable disease and two patients (14%) tumor progression. Median time to progression was 8.5 months (5-35 months). Median survival after first TACE was 14.5 months in responders compared to 10 months in non-responders (p = 0.18, not significant) and 11.5 months (3-69 months) in all patients. In seven patients with metastases occupying less than 25% of liver volume median survival was 17 months compared to 11 months in seven patients with tumor involvement of more than 25% (p = 0.02) with partial response rate of 86% and 29%, respectively. TACE of liver metastases from uveal melanoma is well tolerated and may prolong survival in patients with limited tumor extension.

  2. Trabeculectomy in patients with uveal melanoma after proton beam therapy.

    Science.gov (United States)

    Riechardt, Aline I; Cordini, Dino; Rehak, Matus; Hager, Annette; Seibel, Ira; Böker, Alexander; Gundlach, Enken; Heufelder, Jens; Joussen, Antonia M

    2016-07-01

    Retrospective evaluation of intraocular pressure, use of topical and systemic anti-glaucoma medication, secondary complications, local tumor control and survival in patients treated with trabeculectomy for the regulation of the intraocular pressure (IOP) after proton beam therapy for uveal melanoma. In this retrospective clinical case series we evaluated the follow-up of 15 patients receiving a trabeculectomy as surgical treatment if the IOP could not be lowered adequately by medications or laser surgery. All patients had received proton beam therapy for uveal melanoma at the Helmholtz-Zentrum Berlin between 1998 and 2010. The median IOP decreased significantly from 35 mmHg ± 8.8 before TE to 16 mmHg ± 8.2 (=52.3 %) six months after TE (Wilcoxon-Mann-Whitney-U Test, p<0.01). None of the patients needed any glaucoma medication six months after trabeculectomy. Two patients developed local recurrence during follow-up, which were independent of the trabeculectomy. One patient had to be enucleated due to intractable pain and suspected remaining tumor activity. One patient died due to metastasis. Trabeculectomy is an option in intractable glaucoma in patients with uveal melanoma after proton beam therapy in single cases. Secondary interventions are common. Inoculation metastases are possible. Secure local tumor control must be a prerequisite for filtrating operations.

  3. Pediatric melanoma: incidence, treatment, and prognosis

    Directory of Open Access Journals (Sweden)

    Saiyed FK

    2017-04-01

    Full Text Available Faiez K Saiyed,1 Emma C Hamilton,1 Mary T Austin,1,2 1Department of Pediatric Surgery, McGovern Medical School, 2Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: The purpose of this review is to outline recent advancements in diagnosis, treatment, and prevention of pediatric melanoma. Despite the recent decline in incidence, it continues to be the deadliest form of skin cancer in children and adolescents. Pediatric melanoma presents differently from adult melanoma; thus, the traditional asymmetry, border irregularity, color variegation, diameter >6 mm, and evolution (ABCDE criteria have been modified to include features unique to pediatric melanoma (amelanotic, bleeding/bump, color uniformity, de novo/any diameter, evolution of mole. Surgical and medical management of pediatric melanoma continues to derive guidelines from adult melanoma treatment. However, more drug trials are being conducted to determine the specific impact of drug combinations on pediatric patients. Alongside medical and surgical treatment, prevention is a central component of battling the incidence, as ultraviolet (UV-related mutations play a central role in the vast majority of pediatric melanoma cases. Aggressive prevention measures targeting sun safety and tanning bed usage have shown positive sun-safety behavior trends, as well as the potential to decrease melanomas that manifest later in life. As research into the field of pediatric melanoma continues to expand, a prevention paradigm needs to continue on a community-wide level. Keywords: melanoma, pediatric, adolescent, childhood

  4. RAGE-aptamer Attenuates the Growth and Liver Metastasis of Malignant Melanoma in Nude Mice.

    Science.gov (United States)

    Nakamura, Nobutaka; Matsui, Takanori; Ishibashi, Yuji; Sotokawauchi, Ami; Fukami, Kei; Higashimoto, Yuichiro; Yamagishi, Sho-Ichi

    2017-11-06

    Epidemiological studies have suggested the link between cumulative diabetic exposure and cancer. Interaction of advanced glycation end products (AGEs) with their receptor (RAGE) may contribute to the phenomenon. We examined here the effects of DNA aptamer raised against RAGE (RAGE-aptamer) on growth and liver metastasis of G361 melanoma in nude mice. Malignant melanoma cells were intradermally injected into the upper flank region of nude mice, which received continuous administration of RAGE-aptamer (38.4 pmol/day/g body weight) or vehicle intraperitoneally by an osmotic pump up to 42 days. RAGE-aptamer significantly reduced levels of 8-hydroxy-2'-deoxy-guanosine, AGEs, RAGE, proliferating nuclear antigen, cyclin D1, vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), and CD31 and Mac-3, respective markers of endothelial cells and macrophages in tumors of nude mice and suppressed the proliferation and liver metastasis of malignant melanoma. Furthermore, RAGE-aptamer attenuated the AGE-induced oxidative stress generation, proliferation, and VEGF and MCP-1 gene expression in both G361 melanoma cells and endothelial cells. The present findings suggest that RAGE-aptamer could attenuate melanoma growth and liver metastasis in nude mice by suppressing the tumor angiogenesis and macrophage infiltration via inhibition of the AGE-RAGE system. RAGE-aptamer may be a novel therapeutic tool for the treatment of malignant melanoma.

  5. Guideline on the Management of Melanoma | Board | South African ...

    African Journals Online (AJOL)

    Validation. Melanoma management involves many medical specialties. Guidelines should therefore be developed through a multidisciplinary consensus. The Melanoma Advisory Board consists of a forum of dermatologists, oncologists, plastic surgeons and pathologists. Guideline sponsor. The meetings of the Melanoma ...

  6. Mucosal malignant melanoma - a clinical, oncological, pathological and genetic survey

    DEFF Research Database (Denmark)

    Mikkelsen, Lauge H; Larsen, Ann-Cathrine; von Buchwald, Christian

    2016-01-01

    Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral...... cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma...... is the treatment of choice. The prognosis is poor, with the 5-year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma)....

  7. Risk factors for second primary melanoma among Dutch patients with melanoma

    NARCIS (Netherlands)

    Schuurman, M.S.; Waal, A.C. de; Thijs, E.J.M.; Rossum, M.M. van; Kiemeney, L.A.L.M.; Aben, K.K.H.

    2017-01-01

    BACKGROUND: Patients with melanoma are at increased risk of developing subsequent primary melanomas. Knowledge about risk factors for these subsequent primaries is scarce. More evidence may help clinicians in tailoring surveillance schedules by selecting patients who could benefit from intensified

  8. Risk Factors for Melanoma Among Survivors of Non-Hodgkin Lymphoma

    Science.gov (United States)

    Lam, Clara J.K.; Curtis, Rochelle E.; Dores, Graça M.; Engels, Eric A.; Caporaso, Neil E.; Polliack, Aaron; Warren, Joan L.; Young, Heather A.; Levine, Paul H.; Elmi, Angelo F.; Fraumeni, Joseph F.; Tucker, Margaret A.; Morton, Lindsay M.

    2015-01-01

    Purpose Previous studies have reported that survivors of non-Hodgkin lymphoma (NHL) have an increased risk of developing cutaneous melanoma; however, risks associated with specific treatments and immune-related risk factors have not been quantified. Patients and Methods We evaluated second melanoma risk among 44,870 1-year survivors of first primary NHL diagnosed at age 66 to 83 years from 1992 to 2009 and included in the Surveillance, Epidemiology, and End Results-Medicare database. Information on NHL treatments, autoimmune diseases, and infections was derived from Medicare claims. Results A total of 202 second melanoma cases occurred among survivors of NHL, including 91 after chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 111 after other NHL subtypes (cumulative incidence by age 85 years: CLL/SLL, 1.37%; other NHL subtypes, 0.78%). Melanoma risk after CLL/SLL was significantly increased among patients who received infused fludarabine-containing chemotherapy with or without rituximab (n = 18: hazard ratio [HR], 1.92; 95% CI, 1.09 to 3.40; n = 10: HR, 2.92; 95% CI, 1.42 to 6.01, respectively). Significantly elevated risks also were associated with T-cell activating autoimmune diseases diagnosed before CLL/SLL (n = 36: HR, 2.27; 95% CI, 1.34 to 3.84) or after CLL/SLL (n = 49: HR, 2.92; 95% CI, 1.66 to 5.12). In contrast, among patients with other NHL subtypes, melanoma risk was not associated with specific treatments or with T-cell/B-cell immune conditions. Generally, infections were not associated with melanoma risk, except for urinary tract infections (CLL/SLL), localized scleroderma, pneumonia, and gastrohepatic infections (other NHLs). Conclusion Our findings suggest immune perturbation may contribute to the development of melanoma after CLL/SLL. Increased vigilance is warranted among survivors of NHL to maximize opportunities for early detection of melanoma. PMID:26240221

  9. Efficacy and safety of endocrine monotherapy as first-line treatment for hormone-sensitive advanced breast cancer: A network meta-analysis.

    Science.gov (United States)

    Zhang, Jingwen; Huang, Yanhong; Wang, Changyi; He, Yuanfang; Zheng, Shukai; Wu, Kusheng

    2017-08-01

    Endocrine therapy was recommended as the preferred first-line treatment for hormone receptor-positive (HR+, i.e., ER+ and/or PgR+), human epidermal growth factor receptor-2-negative (HER2-) postmenopausal advanced breast cancer (ABC), but which endocrine monotherapy is optimal lacks consensus. We aimed to identify the optimal endocrine monotherapy with a network meta-analysis. We performed a network meta-analysis for a comprehensive analysis of 6 first-line endocrine monotherapies (letrozole, anastrozole, exemestane, tamoxifen, fulvestrant 250 mg and 500 mg) for HR+ HER2- metastatic or locally advanced breast cancer in postmenopausal patients. The main outcomes were objective response rate (ORR), time to progression (TTP), and progression-free survival (PFS). Secondary outcomes were adverse events. We identified 27 articles of 8 randomized controlled trials including 3492 patients in the network meta-analysis. For ORR, the treatments ranked in descending order of effectiveness were letrozole > exemestane > anastrozole > fulvestrant 500 mg > tamoxifen > fulvestrant 250 mg. For TTP/PFS, the order was fulvestrant 500 mg > letrozole > anastrozole > exemestane > tamoxifen > fulvestrant 250 mg. We directly compared adverse events and found that tamoxifen produced more hot flash events than fulvestrant 250 mg. Fulvestrant 500 mg and letrozole might be optimal first-line endocrine monotherapy choices for HR+ HER2- ABC because of efficacious ORR and TTP/PFS, with a favorable tolerability profile. However, direct comparisons among endocrine monotherapies in the first-line therapy setting are still required to robustly demonstrate any differences among these endocrine agents. Clinical choices should also depend on the specific disease situation and duration of endocrine therapy.

  10. Irinotecan, Continuous 5-Fluorouracil, and Low dose of Leucovorin (modified FOLFIRI) as First Line of Therapy in Recurrent or Metastatic Colorectal Cancer

    OpenAIRE

    Lee, Myung-Ah; Byun, Jae-Ho; Shim, Byoung-Young; Woo, In-Sook; Kang, Jin-Hyung; Hong, Young Seon; Lee, Kyung Shik; Choi, Myung Gyu; Chang, Suk Kyun; Oh, Seong Taek; Choi, Sung Il; Lee, Doo Suk

    2005-01-01

    Background Irinotecan, in combination with 5-fluorouracil (5-FU) and a high dose of leucovorin (LV), known as FOLFIRI regimen, has shown activity in recurrent or metastatic colorectal cancer. Therefore, we evaluated the efficacy and safety of irinotecan, 5-FU and a low dose of LV (modified FOLFIRI) as a first line of therapy for patients with relapsed or metastatic colorectal cancer. Methods Between January 2002 and October 2004, 44 patients with histologically confirmed recurrent or metastat...

  11. Phase II study of ipilimumab in adolescents with unresectable stage III or IV malignant melanoma

    DEFF Research Database (Denmark)

    Geoerger, Birgit; Bergeron, Christophe; Gore, Lia

    2017-01-01

    BACKGROUND: Ipilimumab is approved for the treatment of advanced melanoma in adults; however, little information on the efficacy and safety of ipilimumab in younger patients is available. METHODS: Patients aged 12 to ... malignant melanoma received ipilimumab 3 or 10 mg/kg every 3 weeks. Primary end-points were 1-year overall survival and safety. RESULTS: Over a period of 3.5 years, 12 patients received ipilimumab at either 3 mg/kg (n = 4) or 10 mg/kg (n = 8). The median number of ipilimumab doses was four for 3 mg....... There was one grade 3/4 immune-mediated adverse reaction with 3 mg/kg and five with 10 mg/kg. There were no treatment-related deaths. The study was stopped due to slow accrual. CONCLUSIONS: At >1 year follow-up, ipilimumab demonstrated activity in melanoma patients aged 12 to safety...

  12. Metastatic melanoma masquerading as a furuncle

    Directory of Open Access Journals (Sweden)

    Imran Aslam

    2017-10-01

    Full Text Available Melanoma metastasizes to the skin in about 10-17% of patients. Although there are reports of metastatic melanoma masquerading as panniculitis and erysipelas, it is very uncommon for it to present as an inflammatory skin lesion. When malignant melanoma cells invade the superficial dermal lymphatic vessels it can result in erythema, edema and induration of the overlying skin. This presentation can be problematic for clinicians if they do not suspect melanoma and choose not to biopsy the lesion. We report a case of an elderly man with a history of invasive melanoma who presented with a furuncle-like lesion that was found to be in-transit metastatic melanoma.

  13. Molecular insights into melanoma brain metastases.

    Science.gov (United States)

    Westphal, Dana; Glitza Oliva, Isabella C; Niessner, Heike

    2017-06-01

    Substantial proportions of patients with metastatic melanoma develop brain metastases during the course of their disease, often resulting in significant morbidity and death. Despite recent advances with BRAF/MEK and immune-checkpoint inhibitors in the treatment of patients who have melanoma with extracerebral metastases, patients who have melanoma brain metastases still have poor overall survival, highlighting the need for further therapy options. A deeper understanding of the molecular pathways involved in the development of melanoma brain metastases is required to develop more brain-specific therapies. Here, the authors summarize the currently known preclinical data and describe steps involved in the development of melanoma brain metastases. Only by knowing the molecular background is it possible to design new therapeutic agents that can be used to improve the outcome of patients with melanoma brain metastases. Cancer 2017;123:2163-75. © 2017 American Cancer Society. © 2017 American Cancer Society.

  14. Subcutaneous immunoglobulin as first-line therapy in treatment-naive patients with chronic inflammatory demyelinating polyneuropathy

    DEFF Research Database (Denmark)

    Markvardsen, L. H.; Sindrup, S. H.; Christiansen, I.

    2017-01-01

    Background and purpose: Subcutaneous immunoglobulin (SCIG) is effective as maintenance treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). We investigated whether multiple subcutaneous infusions are as effective as conventional therapy with intravenous loading doses in treatment...... treatment arm and followed for a further 10 weeks. All participants were evaluated at weeks 0, 2, 5 and 10 during both therapies. Primary outcome was combined isokinetic muscle strength (cIKS). Secondary outcomes were disability, clinical evaluation of muscle strength and the performance of various function...... tests. Results: All participants received both therapies, 14 completing the protocol. Overall, cIKS increased by 7.4 ± 14.5% (P = 0.0003) during SCIG and by 6.9 ± 16.8% (P = 0.002) during IVIG, the effect being similar (P = 0.80). Improvement of cIKS peaked 2 weeks after IVIG and 5 weeks after SCIG...

  15. Psychometric testing of the Leadership and Management Inventory: a tool to measure the skills and abilities of first-line nurse managers.

    Science.gov (United States)

    Skytt, Bernice; Carlsson, Marianne; Ljunggren, Birgitta; Engström, Maria

    2008-10-01

    To estimate the validity and reliability of the Leadership and Management Inventory, a tool to measure the skills and abilities of first-line nurse managers. The decision to develop an inventory reflects the need for an instrument that can measure the various skills and abilities first-line nurse managers should possess. Factor analysis was conducted and internal consistency initially estimated on data from 149 registered nurses; a second sample of 197 health care personnel was used to test these results. Principal component analysis of the first sample resulted in a preferred three-factor solution that explained 65.8% of the variance; Cronbach's alpha coefficient varied between 0.90 and 0.95. Analysis of the second sample also resulted in a three-factor solution that explained 64.2% of the variance; Cronbach's alpha coefficient varied from 0.88 to 0.96. For both samples, the factors were labelled 'interpersonal skills and group management', 'achievement orientation' and 'overall organizational view and political savvy'. Results indicate that estimates of validity and reliability for the Leadership and Management Inventory can be considered acceptable. The Leadership and Management Inventory can be used when first-line nurse managers' leadership and management skills and abilities are to be measured.

  16. Epidermal Growth Factor-like Domain 7 Predicts Response to First-Line Chemotherapy and Bevacizumab in Patients with Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Nielsen, Boye Schnack; Sørensen, Flemming Brandt

    2014-01-01

    The number of approved antiangiogenic drugs is constantly growing and emphasizes the need for predictive biomarkers. The aim of this study was to analyze the predictive value of epidermal growth factor-like domain 7 (EGFL7) and microRNA-126 (miR126) to first-line chemotherapy combined with bevaci......The number of approved antiangiogenic drugs is constantly growing and emphasizes the need for predictive biomarkers. The aim of this study was to analyze the predictive value of epidermal growth factor-like domain 7 (EGFL7) and microRNA-126 (miR126) to first-line chemotherapy combined...... in responding patients of 4 [95% confidence interval (CI), 4-6] compared with 8.5 (95% CI, 7-11) in nonresponders, P = 0.0008. This difference translated into a borderline significant difference in PFS (P = 0.06). Furthermore, a significant relationship between high EGFL7 VA and KRAS mutation was detected (P...... = 0.049). The results showed no significant relationship between the miR126 VA and the clinical endpoints. Our study suggests a predictive value of EGFL7 in regard to first-line chemotherapy and bevacizumab in patients with mCRC and supports the mechanism of a dual blocking of the vascular endothelial...

  17. Addition of bevacizumab to first-line chemotherapy in advanced colorectal cancer: a systematic review and meta-analysis, with emphasis on chemotherapy subgroups

    Directory of Open Access Journals (Sweden)

    Macedo Ligia

    2012-03-01

    Full Text Available Abstract Background Bevacizumab has an important role in first-line treatment of metastatic colorectal cancer. However, clinical trials studying its effect have involved distinct chemotherapy regimens with divergent results. The aim of this meta-analysis is to gather current data and evaluate not only the efficacy of bevacizumab, but also the impact of divergent backbone regimens. Methods A wide search of randomized clinical trials using bevacizumab in first-line metastatic colorectal cancer was performed in Embase, MEDLINE, LILACS and Cochrane databases. Meeting presentations and abstracts were also investigated. The resulting data were examined and included in the meta-analysis according to the type of regimen. Results Six trials, totaling 3060 patients, were analyzed. There was an advantage to using bevacizumab for overall survival (OS and progression-free survival (PFS (HR = 0.84; CI: 0.77-0.91; P Conclusions Bevacizumab has efficacy in first-line treatment of advanced colorectal cancer, but the current data are insufficient to support efficacy in all regimens, especially infusional fluorouracil regimens, like FOLFIRI and FOLFOX.

  18. Preliminary study of the effects of an educational workshop on therapeutic use of music and aesthetic experience with music in first-line nurses.

    Science.gov (United States)

    Lai, Hui-Ling

    2011-11-01

    The purpose of this study was to assess the effects of an educational workshop on knowledge of and attitude toward therapeutic use of music and aesthetic experiences with music among first-line nurses. A one-group pre-test/post-test design was used. Forty-six first-line nurses, aged 21-56 years, were recruited from seven different hospitals. Questionnaires were used to assess the nurses' knowledge of and attitude toward therapeutic use of music and aesthetic experience with music before and after the workshop, and 3 months after the workshop. The workshop comprised three sessions; the nurses participated in 8h of instruction the first week and 4h, the second week covering analytical music appreciation, music staves comprehension, theory and practice of music therapy, and evidence-based music intervention. Educational workshop significantly improved knowledge of and attitudes toward therapeutic use of music and music aesthetic experiences (pmusic aesthetic experiences between nurse with and without music backgrounds differed significantly (p=0.01). The workshop enhanced the knowledge of and attitude toward therapeutic use of music and aesthetic experiences with music among first-line nurses. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. A Critical Review of the Current Evidence for Measuring Drug Concentrations of First-Line Agents Used to Treat Tuberculosis in Children.

    Science.gov (United States)

    Wilby, Kyle John; Shabana, Sara; Ensom, Mary H H; Marra, Fawziah

    2016-01-01

    Tuberculosis is a leading cause of infectious disease-related morbidity and mortality worldwide. Additionally, treatment is complex with most patients requiring combination therapy of first-line agents for multiple months. Children are especially at risk from the medications used to treat tuberculosis and therefore interventions to optimize both efficacy and safety are needed. Protocols exist for therapeutic drug monitoring in tuberculosis patients yet there is a gap in knowledge regarding the extent of any benefits achieved, especially in children. This review aims to summarize and evaluate literature reporting outcomes related to the measurement of drug concentrations of first-line agents used to treat tuberculosis (rifampin, isoniazid, pyrazinamide, ethambutol) in children. Findings showed a lack of strong evidence to support therapeutic drug monitoring in children with tuberculosis. Standard weight-based dosing of first-line agents does not commonly achieve target concentrations yet the effect on clinical outcomes remains unclear. As such, therapeutic drug monitoring should not be recommended currently as a widespread practice for all children with tuberculosis. However, future research should assess any benefit in special populations such as those with relapsing or recurrent disease, or those presenting with adverse drug reactions.

  20. Melanoma-specific marker expression in skin biopsy tissues as a tool to facilitate melanoma diagnosis.

    Science.gov (United States)

    Alexandrescu, Doru T; Kauffman, C Lisa; Jatkoe, Timothy A; Hartmann, Dan P; Vener, Tatiana; Wang, Haiying; Derecho, Carlo; Rajpurohit, Yashoda; Wang, Yixin; Palma, John F

    2010-07-01

    Diagnosis of cutaneous melanoma requires accurate differentiation of true malignant tumors from highly atypical lesions, which lack the capacity to develop uncontrolled proliferation and to metastasize. We used melanoma markers from previous work to differentiate benign and atypical lesions from melanoma using paraffin-embedded tissue. This critical step in diagnosis generates the most uncertainty and discrepancy between dermatopathologists. A total of 193 biopsy tissues were selected: 47 melanomas, 48 benign nevi, and 98 atypical/suspicious, including 48 atypical nevi and 50 melanomas as later assigned by expert dermatopathologists. Performance for SILV, GDF15, and L1CAM normalized to TYR in unequivocal melanoma versus benign nevi resulted in an area under the curve (AUC) of 0.94, 0.67, and 0.5, respectively. SILV also differentiated atypical cases classified as melanoma from atypical nevi with an AUC=0.74. Furthermore, SILV showed a significant difference between suspicious melanoma and each suspicious atypia group: melanoma versus severe atypia and melanoma versus moderate atypia had P-values of 0.0077 and 0.0009, respectively. SILV showed clear discrimination between melanoma and benign unequivocal cases as well as between different atypia subgroups in the group of suspicious samples. The role and potential utility of this molecular assay as an adjunct to the morphological diagnosis of melanoma are discussed.

  1. Residual neurotoxicity in ovarian cancer patients in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: The Multicenter Italian Trial in Ovarian cancer (MITO-4) retrospective study

    International Nuclear Information System (INIS)

    Pignata, Sandro; Manzione, Luigi; Cartenì, Giacomo; Nardi, Mario; Danese, Saverio; Valerio, Maria Rosaria; Matteis, Andrea de; Massidda, Bruno; Gasparini, Giampietro; Di Maio, Massimo; Pisano, Carmela; De Placido, Sabino; Perrone, Francesco; Biamonte, Rosalbino; Scambia, Giovanni; Di Vagno, Giovanni; Colucci, Giuseppe; Febbraro, Antonio; Marinaccio, Marco; Vernaglia Lombardi, Alessandra

    2006-01-01

    Carboplatin/paclitaxel is the chemotherapy of choice for advanced ovarian cancer, both in first line and in platinum-sensitive recurrence. Although a significant proportion of patients have some neurotoxicity during treatment, the long-term outcome of chemotherapy-induced neuropathy has been scantly studied. We retrospectively assessed the prevalence of residual neuropathy in a cohort of patients in clinical remission after first-line carboplatin/paclitaxel for advanced ovarian cancer. 120 patients have been included in this study (101 participating in a multicentre phase III trial evaluating the efficacy of consolidation treatment with topotecan, and 19 treated at the National Cancer Institute of Naples after the end of the trial). All patients received carboplatin (AUC 5) plus paclitaxel (175 mg/m 2 ) every 3 weeks for 6 cycles, completing treatment between 1998 and 2003. Data were collected between May and September 2004. Residual sensory and motor neurotoxicity were coded according to the National Cancer Institute – Common Toxicity Criteria. 55 patients (46%) did not experience any grade of neurological toxicity during chemotherapy and of these none had signs of neuropathy during follow-up. The other 65 patients (54%) had chemotherapy-induced neurotoxicity during treatment and follow-up data are available for 60 of them. Fourteen out of 60 patients (23%) referred residual neuropathy at the most recent follow-up visit, after a median follow up of 18 months (range, 7–58 months): 12 patients had grade 1 and 2 patients grade 2 peripheral sensory neuropathy; 3 patients also had grade 1 motor neuropathy. The remaining 46/60 patients (77%) had no residual neuropathy at the moment of interview: recovery from neurotoxicity had occurred in the first 2 months after the end of chemotherapy in 22 (37%), between 2 and 6 months in 15 (25%), or after more than 6 months in 9 patients (15%). Considering all 120 treated patients, there was a 15% probability of persistent

  2. Residual neurotoxicity in ovarian cancer patients in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: The Multicenter Italian Trial in Ovarian cancer (MITO-4 retrospective study

    Directory of Open Access Journals (Sweden)

    Danese Saverio

    2006-01-01

    Full Text Available Abstract Background Carboplatin/paclitaxel is the chemotherapy of choice for advanced ovarian cancer, both in first line and in platinum-sensitive recurrence. Although a significant proportion of patients have some neurotoxicity during treatment, the long-term outcome of chemotherapy-induced neuropathy has been scantly studied. We retrospectively assessed the prevalence of residual neuropathy in a cohort of patients in clinical remission after first-line carboplatin/paclitaxel for advanced ovarian cancer. Methods 120 patients have been included in this study (101 participating in a multicentre phase III trial evaluating the efficacy of consolidation treatment with topotecan, and 19 treated at the National Cancer Institute of Naples after the end of the trial. All patients received carboplatin (AUC 5 plus paclitaxel (175 mg/m2 every 3 weeks for 6 cycles, completing treatment between 1998 and 2003. Data were collected between May and September 2004. Residual sensory and motor neurotoxicity were coded according to the National Cancer Institute – Common Toxicity Criteria. Results 55 patients (46% did not experience any grade of neurological toxicity during chemotherapy and of these none had signs of neuropathy during follow-up. The other 65 patients (54% had chemotherapy-induced neurotoxicity during treatment and follow-up data are available for 60 of them. Fourteen out of 60 patients (23% referred residual neuropathy at the most recent follow-up visit, after a median follow up of 18 months (range, 7–58 months: 12 patients had grade 1 and 2 patients grade 2 peripheral sensory neuropathy; 3 patients also had grade 1 motor neuropathy. The remaining 46/60 patients (77% had no residual neuropathy at the moment of interview: recovery from neurotoxicity had occurred in the first 2 months after the end of chemotherapy in 22 (37%, between 2 and 6 months in 15 (25%, or after more than 6 months in 9 patients (15%. Considering all 120 treated patients

  3. A phase II study of nanoparticle albumin-bound paclitaxel plus carboplatin as the first-line therapy in elderly patients with previously untreated advanced non-small cell lung cancer.

    Science.gov (United States)

    Okuma, Yusuke; Hosomi, Yukio; Takahashi, Satoshi; Nakahara, Yoshiro; Watanabe, Kageaki; Nagamata, Makoto; Takagi, Yusuke; Mikura, Shinichiro

    2016-08-01

    The objective of this clinical trial was to explore the efficacy and tolerability of first-line chemotherapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel), a novel agent that uses a drug delivery system, plus carboplatin, in elderly Japanese patients with advanced non-small cell lung cancer (NSCLC). In this phase II, single-arm, open-label, single-institutional study, we aimed to enroll 37 elderly patients, aged more than 70 years, with advanced NSCLC of performance status 0 or 1. The patients received each cycle of first-line therapy consisting of 100 mg/m(2) nab-paclitaxel intravenously administered on days 1, 8, and 15 of each 21-day cycle, plus carboplatin area under curve 6 on day 1 of each 21-day cycle, for up to six cycles. The primary end point was determining the objective response rate, and secondary endpoints were progression-free survival, overall survival, and safety. The study was interrupted early because of two treatment-related deaths and 1 life-threatening severe adverse event; therefore, only 10 patients (median age, 77 years; range 71-82 years) were enrolled. The primary end point of the objective response was 50 % for the 10 patients analyzed. Progression-free survival was 4.48 months [95 % confidence interval (CI) 0.36-6.44], and overall survival was 7.89 months (95 % CI 0.36-26.88). Common treatment-related adverse events higher than grade 2 included decreased neutrophil counts, anemia, decreased albumin, anorexia, and peripheral neuropathy. Regarding severe adverse events, two patients had febrile neutropenia and lung infection. Two patients died, and one patient had febrile neutropenia with intubation during the first cycle. The Data and Safety Monitoring Committee therefore recommended interruption of patient enrollment. Nab-paclitaxel plus carboplatin, without dose reduction, is indicated to be toxic and intolerable as first-line chemotherapy in elderly Japanese patients with advanced NSCLC. Care must be taken when

  4. Melanoma of unknown origin: a case series.

    LENUS (Irish Health Repository)

    Kelly, J

    2010-12-01

    The natural history of metastatic melanoma involving lymph nodes, in the absence of a known primary site (cutaneous, ocular or mucosal) has, to date, been poorly defined; and the optimal management of this rare subtype of disease is therefore unclear. Melanomas of unknown primary site (MUP) are estimated to comprise between 3.7 and 6% of all melanomas (Anbari et al. in Cancer 79:1861-1821, 1997).

  5. Melanoma epidemiology, prognosis and trends in Latvia.

    Science.gov (United States)

    Azarjana, K; Ozola, A; Ruklisa, D; Cema, I; Rivosh, A; Azaryan, A; Pjanova, D

    2013-11-01

    Melanoma incidence and mortality rates are increasing worldwide within the white population. Clinical and histological factors have been usually used for the prognosis and assessment of the risk for melanoma. The aim of the study was to describe the clinical and histopathological features of the cutaneous melanoma (CM) in the Latvian population, to test the association between melanoma features and patient survival, and to assess the time trends for melanoma incidence. We undertook a descriptive, retrospective analysis of archive data of 984 melanoma patients treated at the largest oncological hospital of Latvia, Riga East University Hospital Latvian Oncology Centre (LOC), between 1998 and 2008. Cox proportional hazards model was used to analyse patient survival and autoregressive models were applied to detect trends in melanoma incidence over time for various categories of melanoma. The study showed a significant ascending trend in melanoma incidence in Latvia during the time period from 1998 to 2008 (ß = 1.83, 95% CI = 1.15-2.91, P = 0.011). Nodular melanoma was the most common tumour subtype with a frequency of 39.2%. Ulceration was present in 45.2% of melanomas. The mean Breslow thickness was 6.0 mm (6.8 mm) and no significant decline in median Breslow thickness was observed during the study period (P = 0.609). A better overall prognosis was detected for females in comparison with males (HR = 1.49; 95% CI = 1.22-1.81; P Latvia with the majority of melanomas diagnosed at late stages with poor prognosis for survival. © 2012 The Authors Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

  6. Giant hanging melanoma of the eyelid skin