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Sample records for second-line salvage treatment

  1. Second-line salvage treatment of AIDS-associated Pneumocystis jirovecii pneumonia: a case series and systematic review

    DEFF Research Database (Denmark)

    Benfield, T.; Atzori, C.; Miller, R.F.

    2008-01-01

    BACKGROUND: Limited clinical data exist to guide the choice of second-line salvage treatment for AIDS-associated Pneumocystis jirovecii pneumonia (PCP). METHODS: We did a systematic search of MEDLINE for all randomized and observational studies of PCP treatment published up to August 2007...... and included individual treatment data of AIDS-associated PCP from a tricenter study. We calculated pooled estimates of reported outcome of second-line treatment using averaged odds ratios (ORs). RESULTS: Twenty-nine studies with sufficient detail of second-line treatment and outcome, including data from 82...... individual cases from the tricenter study, yielded a total of 468 PCP second-line treatment episodes. Response rates to second-line treatment were comparable for trimethoprim-sulfamethoxazole (TMP-SMX; 68%) and clindamycin-primaquine (73%) (OR for response = 2.1 [95% confidence interval (CI): 1.1 to 3...

  2. 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.

  3. Addition of rapamycin and hydroxychloroquine to metronomic chemotherapy as a second line treatment results in high salvage rates for refractory metastatic solid tumors: a pilot safety and effectiveness analysis in a small patient cohort.

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    Chi, Kwan-Hwa; Ko, Hui-Ling; Yang, Kai-Lin; Lee, Cheng-Yen; Chi, Mau-Shin; Kao, Shang-Jyh

    2015-06-30

    Autophagy is an important oncotarget that can be modulated during anti-cancer therapy. Enhancing autophagy using chemotherapy and rapamycin (Rapa) treatment and then inhibiting it using hydroxychloroquine (HCQ) could synergistically improve therapy outcome in cancer patients. It is still unclear whether addition of Rapa and HCQ to chemotherapy could be used for reversing drug resistance. Twenty-five stage IV cancer patients were identified. They had no clinical response to first-line metronomic chemotherapy; the patients were salvaged by adding an autophagy inducer (Rapa, 2 mg/day) and an autophagosome inhibitor (HCQ, 400 mg/day) to their current metronomic chemotherapy for at least 3 months. Patients included 4 prostate, 4 bladder, 4 lung, 4 breast, 2 colon, and 3 head and neck cancer patients as well as 4 sarcoma patients. Chemotherapy was administered for a total of 137 months. The median duration of chemotherapy cycles per patient was 4 months (95% confidence interval, 3-7 months). The overall response rate to this treatment was of 40%, with an 84% disease control rate. The most frequent and clinically significant toxicities were myelotoxicities. Grade ≥3 leucopenia occurred in 6 patients (24%), grade ≥3 thrombocytopenia in 8 (32%), and anemia in 3 (12%). None of them developed febrile neutropenia. Non-hematologic toxicities were fatigue (total 32%, with 1 patient developing grade 3 fatigue), diarrhea (total 20%, 1 patient developed grade 3 fatigue), reversible grade 3 cardiotoxicity (1 patient), and grade V liver toxicity from hepatitis B reactivation (1 patient). Our results of Rapa, HCQ and chemotherapy triplet combination suggest autophagy is a promising oncotarget and warrants further investigation in phase II studies.

  4. Delays in switching patients onto second-line antiretroviral treatment ...

    African Journals Online (AJOL)

    Background: South Africa has one of the largest antiretroviral treatment (ART) programmes globally. In addition to increasing access to ART, it is important that the health system also focuses on the appropriate management of patients who fail first-line ART. Delays in switching patients onto second-line ART can adversely ...

  5. Reemergence of Splenectomy for ITP Second-line Treatment?

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    Chater, Charbel; Terriou, Louis; Duhamel, Alain; Launay, David; Chambon, Jean P; Pruvot, François R; Rogosnitzky, Moshe; Zerbib, Philippe

    2016-11-01

    Corticosteroids are still the standard first-line treatment for immune thrombocytopenic purpura (ITP). As second-line therapy, splenectomy and Rituximab are both recommended. The aim of our study was to compare the efficacy of Rituximab to splenectomy in persistent or chronic ITP patients. Between January 1999 and March 2015, we retrospectively selected all consecutive patients who underwent an ITP second-line treatment: Rituximab or splenectomy. The distinction between open (OS) and laparoscopic splenectomy (LS) was analyzed. Primary outcome was composite: hospitalization for bleeding and/or thrombocytopenia and death from hemorrhage or infection. Secondary outcomes were based on response (R) and complete response (CR) rates as defined by the American Society of Hematology. Ninety-six patients were included: 30 patients received Rituximab, 37 underwent OS, and 29 underwent LS. The follow-up was 30, 60, and 120 months in Rituximab, LS, and OS groups, respectively. At 30 month, the primary outcome-free survival rate was higher in splenectomy groups (84% for OS, 86% for LS) than Rituximab group (47%) (P = 0.0002). Similarly, at 30 month, R and CR rates were higher for OS (86.5% and 75.7%, respectively) and LS groups (93.1% and 89.7%) than Rituximab (46.7% and 30%) (P = 0.0001). Moreover, R rates remained elevated at 60 month for OS and LS groups (83.7% and 89.6% respectively) and 78.4% at 120 month for OS group. We observed that splenectomy for ITP second-line treatment was more effective than Rituximab regarding maintenance of R, CR, and overall response rates. OS and LS had similar efficacy.

  6. Symptom burden & quality of life among patients receiving second-line treatment of metastatic colorectal cancer

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    Walker Mark S

    2012-06-01

    Full Text Available Abstract Background Bevacizumab (B and cetuximab (C are both approved for use in the treatment of metastatic colorectal cancer (mCRC in the second-line. We examined patient reported symptom burden during second-line treatment of mCRC. Methods Adult mCRC patients treated in the second-line setting with a regimen that included B, C, or chemotherapy only (O and who had completed ≥ 1 Patient Care Monitor (PCM surveys as part of routine clinical care were drawn from the ACORN Data Warehouse. Primary endpoints were rash, dry skin, itching, nail changes, nausea, vomiting, fatigue, burning in hands/feet, and diarrhea. Linear mixed models examined change in PCM scores across B, C and O (B = reference. Results 182 patients were enrolled (B: n = 106, C: n = 38, O: n = 38. Patients were 51% female, 67% Caucasian, with mean age of 62.0 (SD = 12.6. Groups did not differ on demographic or clinical characteristics. The most common second-line regimens were FOLFIRI ± B or C (23.1% and FOLFOX ± B or C (22.5%. Results showed baseline scores to be strongly predictive of second-line symptoms across all PCM items (all p’s  Conclusions Patients receiving second-line treatment for mCRC with B report less symptom burden, especially dermatologic, compared to patients treated with C.

  7. Capecitabine and oxaliplatin as second-line treatment in patients with carcinoma of unknown primary site

    DEFF Research Database (Denmark)

    Møller, Anne Kirstine Hundahl; Pedersen, Karen Damgaard; Abildgaard, Julie Rafn

    2010-01-01

    tumours may be overrepresented. These patients could be candidates for GI tract-directed therapy. We here report the results obtained with oxaliplatin and capecitabine as second-line therapy in 25 recurrent/refractory CUP patients following first-line treatment with paclitaxel, cisplatin and gemcitabine.......Treatment of patients with carcinoma of unknown primary site (CUP) remains a challenge, and no effective second-line treatment has been identified. In CUP patients who are non-responsive or relapse early after first-line platinum/taxane-based regimens, it is likely that gastrointestinal (GI) tract...

  8. Metastatic melanoma: results of 'classical' second-line treatment with cytotoxic chemotherapies.

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    Perrin, Christophe; Pracht, Marc; Talour, Karen; Adamski, Henri; Cumin, Isabelle; Porneuf, Marc; Talarmin, Marie; Mesbah, Habiba; Audrain, Odile; Moignet, Aline; Lefeuvre-Plesse, Claudia; Lesimple, Thierry

    2014-10-01

    Metastatic melanoma is one of the most aggressive tumours, with a median survival that does not exceed 12 months. None of the cytotoxic first-line therapies have shown survival benefit in randomised clinical trials. To describe clinical benefit of second-line cytotoxic chemotherapy in the second line of treatment for metastatic melanoma. In a retrospective study, we analyse the outcome of patients with metastatic melanoma who had received two lines or more of cytotoxic treatments in four French dermato-oncology departments between 1999 and 2009. We describe the outcomes for 109 patients. Most of these patients received dacarbazine for the first line of chemotherapy and fotemustine for the second line of chemotherapy (67.0 and 64.2%, respectively). A clinical benefit was observed in 24.1% of the patients and overall survival was 4.1 months after the second-line treatment. At least 23.8% of patients suffered from grade 3 or 4 toxicities. The presence of more than two sites of metastasis and an M1c staging according to the AJCC classification represented negative predictive factors of clinical benefit. This study shows the modest benefit of a second line of cytotoxic chemotherapy in a nonselected population. If eligible, these patients should be proposed for ongoing clinical trials or for targeted therapies.

  9. Efficacy and Safety of Capecitabine, Irinotecan, Gemcitabine, and Bevacizumab as Second-Line Treatment in Advanced Biliary Tract Cancer

    DEFF Research Database (Denmark)

    Larsen, Finn Ole; Markussen, Alice; Diness, Laura V

    2018-01-01

    , there are no phase III trials supporting second-line treatment, and the phase II trials with chemotherapy do not show any clear benefit. In this study, we investigated the effect of adding bevacizumab to chemotherapy in second-line treatment. METHODS: From November 2013 to January 2016, 50 patients with advanced...

  10. Advanced colorectal cancer, refractory to infusional fluorouracil treatment: efficacy of second line fluorouracil in combination with a different biochemical modulation

    NARCIS (Netherlands)

    van Halteren, H. K.; Wagener, D. J.; Vreugdenhil, G.; Punt, C. J.

    1997-01-01

    Currently there is no standard second line treatment for patients with advanced colorectal cancer (ACC). Previous reports have demonstrated that some patients may benefit from second line infusional 5-fluorouracil (5-FU) after failing 5-FU bolus treatment. We retrospectively studied the efficacy and

  11. Second line drug susceptibility testing to inform the treatment of rifampin-resistant tuberculosis: a quantitative perspective

    Directory of Open Access Journals (Sweden)

    Emily A. Kendall

    2017-03-01

    Full Text Available Treatment failure and resistance amplification are common among patients with rifampin-resistant tuberculosis (TB. Drug susceptibility testing (DST for second-line drugs is recommended for these patients, but logistical difficulties have impeded widespread implementation of second-line DST in many settings. To provide a quantitative perspective on the decision to scale up second-line DST, we synthesize literature on the prevalence of second-line drug resistance, the expected clinical and epidemiologic benefits of using second-line DST to ensure that patients with rifampin-resistant TB receive effective regimens, and the costs of implementing (or not implementing second-line DST for all individuals diagnosed with rifampin-resistant TB. We conclude that, in most settings, second-line DST could substantially improve treatment outcomes for patients with rifampin-resistant TB, reduce transmission of drug-resistant TB, prevent amplification of drug resistance, and be affordable or even cost-saving. Given the large investment made in each patient treated for rifampin-resistant TB, these payoffs would come at relatively small incremental cost. These anticipated benefits likely justify addressing the real challenges faced in implementing second-line DST in most high-burden settings.

  12. Metronomic capecitabine as second-line treatment for hepatocellular carcinoma after sorafenib discontinuation.

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    Trevisani, Franco; Brandi, Giovanni; Garuti, Francesca; Barbera, Maria Aurelia; Tortora, Raffaella; Casadei Gardini, Andrea; Granito, Alessandro; Tovoli, Francesco; De Lorenzo, Stefania; Inghilesi, Andrea Lorenzo; Foschi, Francesco Giuseppe; Bernardi, Mauro; Marra, Fabio; Sacco, Rodolfo; Di Costanzo, Giovan Giuseppe

    2018-02-01

    Metronomic capecitabine (MC) is a well-tolerated systemic treatment showing promising results in one retrospective study, as second-line therapy after sorafenib failure, in patients with hepatocellular carcinoma (HCC). 117 patients undergoing MC were compared to 112 patients, eligible for this treatment, but undergoing best supportive care (BSC) after sorafenib discontinuation for toxicity or HCC progression. The two groups were compared for demographic and clinical features. A multivariate regression analysis was conducted to detect independent prognostic factors. To balance confounding factors between the two groups, a propensity score model based on independent prognosticators (performance status, neoplastic thrombosis, causes of sorafenib discontinuation and pre-sorafenib treatment) was performed. Patients undergoing MC showed better performance status, lower tumor burden, lower prevalence of portal vein thrombosis, and better cancer stage. Median (95% CI) post-sorafenib survival (PSS) was longer in MC than in BSC patients [9.5 (7.5-11.6) vs 5.0 (4.2-5.7) months (p < 0.001)]. Neoplastic thrombosis, cause of sorafenib discontinuation, pre-sorafenib treatment and MC were independent prognosticators. The benefit of capecitabine was confirmed in patients after matching with propensity score [PSS: 9.9 (6.8-12.9) vs. 5.8 (4.8-6.8) months, (p = 0.001)]. MC lowered the mortality risk by about 40%. MC achieved better results in patients who stopped sorafenib for adverse events than in those who progressed during it [PSS: 17.3 (10.5-24.1) vs. 7.8 (5.2-10.1) months, (p = 0.035)]. Treatment toxicity was low and easily manageable with dose modulation. MC may be an efficient and safe second-line systemic therapy for HCC patients who discontinued sorafenib for toxicity or tumor progression.

  13. Operative shortening of the sling as a second-line treatment after TVT failure

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    Matuszewski, Marcin; Michajłowski, Jerzy; Krajka, Kazimierz

    2011-01-01

    Introduction Stress urinary incontinence (SUI) is defined as an involuntary loss of urine during physical exertion, sneezing, coughing, laughing, or other activities that put pressure on the bladder. In some cases, recurrent or persistent SUI after sling operations may be caused by too loose placement of the sling. In the current study, we describe our method of shortening of the sling as a second-line treatment of tension-free vaginal tape (TVT) failure. Materials and methods Four women, aged 46-61, after initial TVT operation were treated for persistent SUI. The severity of SUI was estimated by: physical examinations, cough tests, 24-h pad tests, and King's Health Questionnaire. The shortening procedure, based on excising the fragment of tape and suturing it back, was performed in all patients. Results All cases achieved a good result, which was defined as restoration of full continence. No complications occurred. The 12-month follow-up showed no side-effects. The postoperative control tests: the cough and 24-h pad tests were negative in all women. The general health perceptions increased after the shortening procedure by a mean value 44.25%. The incontinence impact decreased by a mean value 44.6%. In all patients, role and physical limitations significantly decreased (by 88.5% and 80.5%, respectively). The negative emotions connected with SUI significantly decreased after the second procedure. Conclusions The operative shortening of the implanted sling is a simple, cheap, and effective method of second-line treatment in cases of TVT failure and may be offered to the majority of patients with insufficient urethral support after the first procedure. PMID:24578885

  14. Hypothyroidism during second-line treatment of multidrug-resistant tuberculosis: a prospective study.

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    Bares, R; Khalid, N; Daniel, H; Dittmann, H; Reimold, M; Gallwitz, B; Schmotzer, C

    2016-07-01

    Hypothyroidism is an adverse effect of certain anti-tuberculosis drugs. This is a prospective study of the frequency and possible pathomechanisms associated with hypothyroidism due to second-line treatment of multidrug-resistant tuberculosis. Fifty human immunodeficiency virus negative patients and 20 controls were included. All participants underwent ultrasonography of the thyroid and measurement of thyroid stimulating hormone (TSH). TSH levels were checked every 3 months. If hypothyroidism was present, T3, T4 and thyroid peroxidase autoantibodies were measured, and imaging extended to scintigraphy and repeated ultrasonography. Before treatment, 7 patients (14%) and 1 control (5%) were hypothyreotic. During the first 6 months of treatment, TSH levels increased in 41 patients (82%), 39 (78%) had values above the normal range and 19 (38%) had overt hypothyroidism. As none of the patients had signs of autoimmune thyroiditis, interaction with anti-tuberculosis drugs was assumed to be the cause of hypothyroidism. Nine patients died during treatment, all of whom had developed hypothyroidism. In seven, the metabolic situation at their death was known, and they had become euthyreotic following levothyroxine substitution. TSH levels should be checked before initiating anti-tuberculosis treatment and after 3 and 6 months to start timely replacement of levothyroxine. Further studies are needed to elucidate the exact pathomechanism involved in hypothyroidism and whether hypothyroidism can be used as predictor of treatment failure.

  15. Second-line treatments: moving towards an opportunity to improve survival in advanced gastric cancer?

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    Salati, Massimiliano; Di Emidio, Katia; Tarantino, Vittoria; Cascinu, Stefano

    2017-01-01

    Gastric cancer is the third leading cause of cancer-related death globally with approximately 723 000 deaths every year. Most patients present with advanced unresectable or metastatic disease, only amenable to palliative systemic treatment and a median survival uncommonly exceeding 12 months. Over the last years, the efficacy of chemotherapy combination has plateaued and the introduction of the anti-human epidermal growth factor receptor 2 trastuzumab has resulted in a limited survival gain in the upfront setting. After this positive experience, first-line treatment with new targeted therapies failed to improve the outcome of advanced gastric cancer. On the contrary, second-line options, including monochemotherapy with taxanes or irinotecan and the anti-vascular endothelial growth factor receptor 2 ramucirumab, either alone or combined with paclitaxel, opened new therapeutic rooms for an ever-increasing number of patients who maintain an acceptable performance status across multiple lines. This article provides an updated overview on the current management of advanced gastric cancer and discusses how the different treatment options available may be best combined to favourably impact the outcome of patients following the logic of a treatment strategy.

  16. Comparison of Efficacy and Safety of Different Therapeutic Regimens as 
Second-line Treatment for Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Zhihua LI

    2015-05-01

    Full Text Available Background and objective Small-cell lung cancer (SCLC is an aggressive disease for which the mainstay of treatment is cytotoxic chemotherapy. Despite good initial responses most patients will relapse or progress after the first-line therapy. The evidence of a benefit from second-line chemotherapy is limited in patients with relapsed/advanced SCLC. Some drugs are recommended by guidelines, but more regimens are formulated based on experience in clinical. So we conducted this retrospective study in order to compare the efficacy and safety of different second-line treatment regimens. Methods We totally analyzed 309 patients received second-line treatment in our retrospective study. 157 patients received best supportive care (BSC, and the rest 152 patients received second-line chemotherapy. The Kaplan-Meier method survival curves and Log-rank test were used to analysis the differences among different groups. The endpoints were objective response rate (ORR, disease control rate (DCR, progression-free survival (PFS, and overall survival (OS. Results Patients administered second-line chemotherapy lived significantly longer, with a total OS from first-line therapy of 11.5 mo compared to 6.0 mo in patients with best supportive care alone (P<0.001, and the ORR, DCR, PFS and OS of the former (including the sensitive disease and resistance/refractory disease patients were obviously better than that of the latter. The ORR and DCR of the patients who received second-line chemotherapy is 39.5% and 59.2%, respectively. The median PFS and OS from second-line chemotherapy were 3.3 mo and 5.3 mo. The patients who received second-line chemotherapy were divided by types of second-line regimens. The sensitive disease patients were from group A (VP-16-based rechallenge and group B1 (CPT-11-based regimen. The ORR of the two groups were 48.6% and 35.3%, and the DCR were 68.6% and 58.8%, respectively. There was no statistically significant difference (P=0.264; P=0

  17. Treatment Failure in HIV-Infected Children on Second-line Protease Inhibitor-Based Antiretroviral Therapy.

    Science.gov (United States)

    Suaysod, Rapeepan; Ngo-Giang-Huong, Nicole; Salvadori, Nicolas; Cressey, Tim R; Kanjanavanit, Suparat; Techakunakorn, Pornchai; Krikajornkitti, Sawitree; Srirojana, Sakulrat; Laomanit, Laddawan; Chalermpantmetagul, Suwalai; Lallemant, Marc; Le Cœur, Sophie; McIntosh, Kenneth; Traisathit, Patrinee; Jourdain, Gonzague

    2015-07-01

    Human immunodeficiency virus (HIV)-infected children failing second-line antiretroviral therapy (ART) have no access to third-line antiretroviral drugs in many resource-limited settings. It is important to identify risk factors for second-line regimen failure. HIV-infected children initiating protease inhibitor (PI)-containing second-line ART within the Program for HIV Prevention and Treatment observational cohort study in Thailand between 2002 and 2010 were included. Treatment failure was defined as confirmed HIV type 1 RNA load >400 copies/mL after at least 6 months on second-line regimen or death. Adherence was assessed by drug plasma levels and patient self-report. Cox proportional hazards regression analyses were used to identify risk factors for failure. A total of 111 children started a PI-based second-line regimen, including 59 girls (53%). Median first-line ART duration was 1.9 years (interquartile range [IQR], 1.4-3.3 years), and median age at second-line initiation was 10.7 years (IQR, 6.3-13.4 years). Fifty-four children (49%) experienced virologic failure, and 2 (2%) died. The risk of treatment failure 24 months after second-line initiation was 41%. In multivariate analyses, failure was independently associated with exposure to first-line ART for >2 years (adjusted hazard ratio [aHR], 1.8; P = .03), age >13 years (aHR, 2.9; P < .001), body mass index-for-age z score < -2 standard deviations at second-line initiation (aHR, 2.8; P = .03), and undetectable drug levels within 6 months following second-line initiation (aHR, 4.5; P < .001). Children with longer exposure to first-line ART, entry to adolescence, underweight, and/or undetectable drug levels were at higher risk of failing second-line ART and thus should be closely monitored. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Metronomic capecitabine as second-line treatment in hepatocellular carcinoma after sorafenib failure.

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    Granito, Alessandro; Marinelli, Sara; Terzi, Eleonora; Piscaglia, Fabio; Renzulli, Matteo; Venerandi, Laura; Benevento, Francesca; Bolondi, Luigi

    2015-06-01

    No standard second-line treatments are available for hepatocellular carcinoma patients who fail sorafenib therapy. We assessed the safety and efficacy of metronomic capecitabine after first-line sorafenib failure. Retrospective analysis of consecutive hepatocellular carcinoma patients receiving metronomic capecitabine between January 2012 and November 2014. The primary end-point was safety, secondary end-point was efficacy, including time-to-progression and overall survival. Twenty-six patients (80% Child-Pugh A, 80% Barcelona Clinic Liver Cancer stage C) received metronomic capecitabine (500 mg/bid). Median treatment duration was 3.2 months (range 0.6-31). Fourteen (53%) patients experienced at least one adverse event. The most frequent drug-related adverse events were bilirubin elevation (23%), fatigue (15%), anaemia (11%), lymphoedema (11%), and hand-foot syndrome (7.6%). Treatment was interrupted in 19 (73%) for disease progression, in 4 (15%) for liver deterioration, and in 1 (3.8%) for adverse event. Disease control was achieved in 6 (23%) patients. Median time-to-progression was 4 months (95% confidence interval 3.2-4.7). Median overall survival was 8 months (95% confidence interval 3.7-12.3). Metronomic capecitabine was well tolerated in hepatocellular carcinoma patients who had been treated with sorafenib. Preliminary data show potential anti-tumour activity with long-lasting disease control in a subgroup of patients that warrants further evaluation in a phase III study. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  19. Systematic review, meta-analysis, and meta-regression: Successful second-line treatment for Helicobacter pylori.

    Science.gov (United States)

    Muñoz, Neus; Sánchez-Delgado, Jordi; Baylina, Mireia; Puig, Ignasi; López-Góngora, Sheila; Suarez, David; Calvet, Xavier

    2018-06-01

    Multiple Helicobacter pylori second-line schedules have been described as potentially useful. It remains unclear, however, which are the best combinations, and which features of second-line treatments are related to better cure rates. The aim of this study was to determine that second-line treatments achieved excellent (>90%) cure rates by performing a systematic review and when possible a meta-analysis. A meta-regression was planned to determine the characteristics of treatments achieving excellent cure rates. A systematic review for studies evaluating second-line Helicobacter pylori treatment was carried out in multiple databases. A formal meta-analysis was performed when an adequate number of comparative studies was found, using RevMan5.3. A meta-regression for evaluating factors predicting cure rates >90% was performed using Stata Statistical Software. The systematic review identified 115 eligible studies, including 203 evaluable treatment arms. The results were extremely heterogeneous, with 61 treatment arms (30%) achieving optimal (>90%) cure rates. The meta-analysis favored quadruple therapies over triple (83.2% vs 76.1%, OR: 0.59:0.38-0.93; P = .02) and 14-day quadruple treatments over 7-day treatments (91.2% vs 81.5%, OR; 95% CI: 0.42:0.24-0.73; P = .002), although the differences were significant only in the per-protocol analysis. The meta-regression did not find any particular characteristics of the studies to be associated with excellent cure rates. Second-line Helicobacter pylori treatments achieving>90% cure rates are extremely heterogeneous. Quadruple therapy and 14-day treatments seem better than triple therapies and 7-day ones. No single characteristic of the treatments was related to excellent cure rates. Future approaches suitable for infectious diseases-thus considering antibiotic resistances-are needed to design rescue treatments that consistently achieve excellent cure rates. © 2018 John Wiley & Sons Ltd.

  20. Voriconazole salvage treatment of invasive candidiasis.

    NARCIS (Netherlands)

    Ostrosky-Zeichner, L.; Oude Lashof, A.M.L.; Kullberg, B.J.; Rex, J.H.

    2003-01-01

    Data on the salvage treatment of invasive candidiasis with voriconazole in 52 patients intolerant of other antifungal agents or with infection refractory to other antifungal agents were analyzed. Patients had received a mean of two previous antifungal agents (range, 1-4 agents), and 83% had received

  1. A budget-impact and cost-effectiveness model for second-line treatment of major depression.

    Science.gov (United States)

    Malone, Daniel C

    2007-07-01

    Depressed patients who initially fail to achieve remission when placed on a selective serotonin reuptake inhibitor (SSRI) may require a second treatment. The purpose of this study was to evaluate the effectiveness, cost, cost-effectiveness, and budget impact of second-line pharmacologic treatment for major depressive disorder (MDD). A cost-effectiveness analysis was conducted to evaluate second-line therapies (citalopram, escitalopram, fluoxetine, paroxetine, paroxetine controlled release [CR], sertraline, and venlafaxine extended release [XR]) for the treatment of depression. Effectiveness data were obtained from published clinical studies. The primary outcome was remission defined as a score of 7 or less on the Hamilton Rating Scale for Depression (HAM-D) or a score of 10 or less on the montgomery-Asberg Depression Rating Scale (MADRS) depression rating scales. The wholesale acquisition cost (WAC) for medications and medical treatment costs for depression were included. The perspective was derived from a managed care organization (MCO) with 500,000 members, a 1.9% annual incidence of depression, and treatment duration of 6 months. Assumptions included: second-line treatment is not as effective as first-line treatment, WAC price reflects MCO costs, and side effects were identical. Sensitivity analyses were conducted to determine variables that influenced the results. Second-line remission rates were 20.4% for venlafaxine XR, 16.9% for sertraline, 16.4% for escitalopram, 15.1% for generic SSRIs (weighted average), and 13.6% for paroxetine CR. Pharmacy costs ranged from $163 for generic SSRIs to $319 for venlafaxine SR. Total cost per patient achieving remission was $14,275 for venlafaxine SR, followed by $16,100 for escitalopram. The incremental cost-effectiveness ratio (ICER) for venlafaxine SR compared with generic SSRIs was $2,073 per patient achieving remission, followed by escitalopram with an ICER of $3,566. The model was most sensitive to other therapies

  2. Continued efficacy of sulfadoxine-pyrimethamine as second line treatment for malaria in children in Guinea-Bissau

    DEFF Research Database (Denmark)

    Kofoed, Poul-Erik; Rodrigues, Amabelia; Aaby, Peter

    2006-01-01

    BACKGROUND: Sulfadoxine-pyrimethamine (S/P) is widely used for treatment of failures following the first line treatment for malaria in Africa. In Guinea-Bissau, it has been recommended as second line therapy by the National Malaria Programme since 1996. In order to monitor any change of the in vivo...... sensitivity, the efficacy of S/P was studied immediately before the introduction of the drug and 6-9 years later. METHODS: Children participating in clinical in vivo studies were given S/P if having late clinical treatment failure following the treatment with quinine, chloroquine, or amodiaquine...

  3. Epirubicin plus paclitaxel regimen as second-line treatment of patients with small-cell lung cancer.

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    Pasello, Giulia; Carli, Paolo; Canova, Fabio; Bonanno, Laura; Polo, Valentina; Zago, Giulia; Urso, Loredana; Conte, Pierfranco; Favaretto, Adolfo

    2015-04-01

    Most patients with small cell lung cancer (SCLC) experience relapse within one year after first-line treatment. The aim of this study was to describe activity and safety of second-line with epirubicin at 70 mg/m(2) followed by paclitaxel at 135 mg/m(2) on day 1 every three weeks for a maximum of six cycles. This is a retrospective review of all patients with SCLC evaluated for second-line treatment between 2003 and 2013 at our Institution. Sixty-eight patients received the study regimen of epirubicin with paclitaxel. We observed partial response in 19 (30%), stable disease in 22 (34%) and total early failure rate in 23 (36%) patients. Median progression free and overall survival were 21.8 and 26.5 weeks, respectively. Haematological toxicities were as follows: grade 3-4 leukopenia and neutropenia in 18 (31%) and 30 (22%) of patients, respectively; grade 3 anaemia and grade 4 thrombocytopenia were reported in 2 (3%) and 5 (9%) of patients, respectively. Epirubicin with paclitaxel is an active and tolerable second-line regimen in patients with SCLC. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  4. Pharmacoeconomic analysis of the use of first- and second-line drugs in the treatment of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    V. R. Mkrtchyan

    2015-01-01

    Full Text Available Objective: to make a pharmacoeconomic comparison of the administration of first- and second-line drugs in the treatment of multiple sclerosis through cost, cost-effectiveness, and budget impact analyses using the 2015 state prices.Material and methods. A pharmacoeconomic analysis was carried out on the basis of the data available in the literature on trials of the effects of the drugs on the rates of exacerbations and disability. On calculating, the authors took into account the current standards for the out- and inpatient management of patients with this nosological entity in accordance with the compulsory health insurance (CHI program; prices for state drug purchases in March 2015; prices for medical services in compliance with the CHI standards in Moscow in 2015; the average sizes of minimum wage, salary, and disability grants with consideration for a discount rate of 3%. The cost-effectiveness and budget impact analyses were performed for intramuscular interferon (INF-β1a (avonex, 30 μg, subcutaneous INF-β1a (rebif, 44 μg, subcutaneous INF-β1b (ronbetal, 8,000,000 IU, subcutaneous INF-β1b (betaferon, 9,600,000 IU, subcutaneous glatiramer acetate (copaxone, 20 mg, intravenous natalizumab (tyzabri, 300 mg, and oral fingolimod (gilenya, 0.5 mg.Results and discussion. The second-line drug tyzabri outperforms the first-line agents for cost-effectiveness. The first-line drugs betaferon and copaxone is slightly exceeded in this indicator by tyzabri; the other both first- and second-line agents compared are all the more inferior in this indicator. The budget impact analysis has shown that the cost of the second-line drugs was higher than that of the first-line ones.

  5. Phase II study of biweekly cetuximab in combination with irinotecan as second-line treatment in patients with platinum-resistant gastro-oesophageal cancer

    DEFF Research Database (Denmark)

    Schønnemann, K R; Yilmaz, Mette Karen; Bjerregaard, J K

    2012-01-01

    The purpose of this phase II trial was to evaluate the efficacy and safety of cetuximab and irinotecan as second-line treatment in patients with gastro-oesophageal adenocarcinoma.......The purpose of this phase II trial was to evaluate the efficacy and safety of cetuximab and irinotecan as second-line treatment in patients with gastro-oesophageal adenocarcinoma....

  6. Characterization of HIV-1 antiretroviral drug resistance after second-line treatment failure in Mali, a limited-resources setting

    Science.gov (United States)

    Maiga, Almoustapha Issiaka; Fofana, Djeneba Bocar; Cisse, Mamadou; Diallo, Fodié; Maiga, Moussa Youssoufa; Traore, Hamar Alassane; Maiga, Issouf Alassane; Sylla, Aliou; Fofana, Dionke; Taiwo, Babafemi; Murphy, Robert; Katlama, Christine; Tounkara, Anatole; Calvez, Vincent; Marcelin, Anne-Geneviève

    2012-01-01

    Objectives We describe the outcomes of second-line drug resistance profiles and predict the efficacy of drugs for third-line therapy in patients monitored without the benefit of plasma HIV-1 RNA viral load (VL) or resistance testing. Methods We recruited 106 HIV-1-infected patients after second-line treatment failure in Mali. VL was determined by the Abbott RealTime system and the resistance by the ViroSeq HIV-1 genotyping system. The resistance testing was interpreted using the latest version of the Stanford algorithm. Results Among the 106 patients, 93 had isolates successfully sequenced. The median age, VL and CD4 cells were respectively 35 years, 72 000 copies/mL and 146 cells/mm3. Patients were exposed to a median of 4 years of treatment and to six antiretrovirals. We found 20% of wild-type viruses. Resistance to etravirine was noted in 38%, to lopinavir in 25% and to darunavir in 12%. The duration of prior nucleos(t)ide reverse transcriptase inhibitor exposure was associated with resistance to abacavir (P < 0.0001) and tenofovir (P = 0.0001), and duration of prior protease inhibitor treatment with resistance to lopinavir (P < 0.0001) and darunavir (P = 0.06). Conclusion Long duration of therapy prior to failure was associated with high levels of resistance and is directly related to limited access to VL monitoring and delayed switches to second-line treatment, precluding efficacy of drugs for third-line therapy. This study underlines the need for governments and public health organizations to recommend the use of VL monitoring and also the availability of darunavir and raltegravir for third-line therapies in the context of limited-resource settings. PMID:22888273

  7. Qualitative study of patients’ decision-making when accepting second-line treatment after failure of first-line chemotherapy

    Science.gov (United States)

    Roch, Benoît; Roth, Caroline; Mérel, Jean-Pierre

    2018-01-01

    Objective Treatment failures in advanced lung cancer are frequent events affecting patients during or after first-line chemotherapy. International guidelines recommend second-line chemotherapy. However, around one half of patients who experience disease progression enter a systemic second-line therapy. In the herein qualitative study, we investigated patients' thoughts and attitudes determining the decision to undergo a second-line chemotherapy. Methods Thirty-three purposively selected patients who recently accepted second-line or palliative chemotherapy were invited to participate in this survey consisting of semi-structured in-depth interviews. Grounded theory was applied to investigate participants’ perceptions of the context that have surrounded their decision to undergo palliative chemotherapy. Results For most patients, tumor burden and reduced quality of life in relation with lung cancer itself were major drivers of the decision-making process. There was a balance between two different attitudes: making a decision to undergo a new line of chemotherapy or starting a psychological process in order to accept end of life. Choosing between these two attitudes allowed the patient to keep the matter of palliative care at a distance. Even in case of low chance of success, many patients who worried about their life partner's future would accept a new chemotherapy line. Some patients experienced ambivalent thoughts regarding social network, particularly about their family as daily function impairment required an increased need for relative's support. The initial "Worrying about others" thoughts left place to in an increasing self-need of care as those provided by relatives; this phenomenon might increase patients' self- perception of being a burden for others. Confidence previously established with formal caregiver support was another major decision driver: some patients with sustained confidence in their medical staff may have privileged this formal support rather

  8. Second-Line Treatment Options in Non-Small-Cell Lung Cancer: Report From an International Experts Panel Meeting of the Italian Association of Thoracic Oncology

    NARCIS (Netherlands)

    Gridelli, Cesare; Baas, Paul; Barlesi, Fabrice; Ciardiello, Fortunato; Crinò, Lucio; Felip, Enriqueta; Gadgeel, Shirish; Papadimitrakopoulou, Vali; Paz-Ares, Luis; Planchard, David; Perol, Maurice; Hanna, Nasser; Sgambato, Assunta; Casaluce, Francesca; de Marinis, Filippo

    2017-01-01

    Non-small-cell lung cancer (NSCLC) patients inevitably progress to first-line therapy and further active treatments are warranted. In the past few years, new second-line therapies, beyond chemotherapy agents, have become available in clinical practice. To date, several options for the second-line

  9. Clinical potential of nintedanib for the second-line treatment of advanced non-small-cell lung cancer: current evidence

    Directory of Open Access Journals (Sweden)

    Rothschild SI

    2014-09-01

    Full Text Available Sacha I Rothschild Department of Internal Medicine, Medical Oncology, University Hospital Basel, Basel, Switzerland Abstract: The therapeutic landscape in non-small-cell lung cancer (NSCLC is changing. The description of molecular alterations leading to NSCLC carcinogenesis and progression (so-called oncogenic driver mutations and the development of targeted agents interfering with the tumor-promoting intracellular signaling pathways have improved the outcome for many patients with advanced/metastatic NSCLC. However, many patients with stage IV NSCLC do not have one of the targetable predictive biomarkers, and are therefore in need of classical chemotherapy. This especially applies to squamous cell cancer. A platinum-based doublet chemotherapy is the standard of care for patients with stage IV NSCLC. As second-line therapies, docetaxel, pemetrexed, and the EGFR tyrosine-kinase inhibitor erlotinib have demonstrated benefit in Phase III randomized trials. Recently, the addition of the angiokinase inhibitor nintedanib to docetaxel has proven efficacious, and is a new treatment option in the second-line setting. Preclinical and clinical data of nintedanib for the treatment of lung cancer patients are reviewed here. Keywords: nintedanib, lung cancer, angiokinase inhibitor, VEGFR, PDGF, FGFR

  10. Cost minimisation analysis of fingolimod vs natalizumab as a second line of treatment for relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Crespo, C; Izquierdo, G; García-Ruiz, A; Granell, M; Brosa, M

    2014-05-01

    At present, there is a lack of economic assessments of second-line treatments for relapsing-recurring multiple sclerosis. The aim of this study was to compare the efficiency between fingolimod and natalizumab in Spain. A cost minimisation analysis model was developed for a 2-year horizon. The same relapse rate was applied to both treatment arms and the cost of resources was calculated using Spain's stipulated rates for 2012 in euros. The analysis was conducted from the perspective of Spain's national health system and an annual discount rate of 3% was applied to future costs. A sensitivity analysis was performed to validate the robustness of the model. Indirect comparison of fingolimod with natalizumab revealed no significant differences (hazard ratio between 0.82 and 1.07). The total direct cost, considering a 2-year analytical horizon, a 7.5% discount stipulated by Royal Decree, and a mean annual relapse rate of 0.22, was € 40914.72 for fingolimod and € 45890.53 for natalizumab. Of the total direct costs that were analysed, the maximum cost savings derived from prescribing fingolimod prescription was € 4363.63, corresponding to lower administration and treatment maintenance costs. Based on the sensitivity analysis performed, fingolimod use was associated with average savings of 11% (range 3.1%-18.7%). Fingolimod is more efficient than natalizumab as a second-line treatment option for relapsing-remitting multiple sclerosis and it generates savings for the Spanish national health system. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  11. Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa.

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    Julie H Levison

    Full Text Available We investigated the prevalence of wild-type virus (no major drug resistance and drug resistance mutations at second-line antiretroviral treatment (ART failure in a large HIV treatment program in South Africa.HIV-infected patients ≥ 15 years of age who had failed protease inhibitor (PI-based second-line ART (2 consecutive HIV RNA tests >1000 copies/ml on lopinavir/ritonavir, didanosine, and zidovudine were identified retrospectively. Patients with virologic failure were continued on second-line ART. Genotypic testing for drug resistance was performed on frozen plasma samples obtained closest to and after the date of laboratory confirmed second-line ART failure. Of 322 HIV-infected patients on second-line ART, 43 were adults with confirmed virologic failure, and 33 had available plasma for viral sequencing. HIV-1 RNA subtype C predominated (n = 32, 97%. Mean duration on ART (SD prior to initiation of second-line ART was 23 (17 months, and time from second-line ART initiation to failure was 10 (9 months. Plasma samples were obtained 7(9 months from confirmed failure. At second-line failure, 22 patients (67% had wild-type virus. There was no major resistance to PIs found. Eleven of 33 patients had a second plasma sample taken 8 (5.5 months after the first. Median HIV-1 RNA and the genotypic resistance profile were unchanged.Most patients who failed second-line ART had wild-type virus. We did not observe evolution of resistance despite continuation of PI-based ART after failure. Interventions that successfully improve adherence could allow patients to continue to benefit from second-line ART therapy even after initial failure.

  12. Initial Results of Image-Guided Percutaneous Ablation as Second-Line Treatment for Symptomatic Vascular Anomalies

    International Nuclear Information System (INIS)

    Thompson, Scott M.; Callstrom, Matthew R.; McKusick, Michael A.; Woodrum, David A.

    2015-01-01

    PurposeThe purpose of this study was to determine the feasibility, safety, and early effectiveness of percutaneous image-guided ablation as second-line treatment for symptomatic soft-tissue vascular anomalies (VA).Materials and MethodsAn IRB-approved retrospective review was undertaken of all patients who underwent percutaneous image-guided ablation as second-line therapy for treatment of symptomatic soft-tissue VA during the period from 1/1/2008 to 5/20/2014. US/CT- or MRI-guided and monitored cryoablation or MRI-guided and monitored laser ablation was performed. Clinical follow-up began at one-month post-ablation.ResultsEight patients with nine torso or lower extremity VA were treated with US/CT (N = 4) or MRI-guided (N = 2) cryoablation or MRI-guided laser ablation (N = 5) for moderate to severe pain (N = 7) or diffuse bleeding secondary to hemangioma–thrombocytopenia syndrome (N = 1). The median maximal diameter was 9.0 cm (6.5–11.1 cm) and 2.5 cm (2.3–5.3 cm) for VA undergoing cryoablation and laser ablation, respectively. Seven VA were ablated in one session, one VA initially treated with MRI-guided cryoablation for severe pain was re-treated with MRI-guided laser ablation due to persistent moderate pain, and one VA was treated in a planned two-stage session due to large VA size. At an average follow-up of 19.8 months (range 2–62 months), 7 of 7 patients with painful VA reported symptomatic pain relief. There was no recurrence of bleeding at five-year post-ablation in the patient with hemangioma–thrombocytopenia syndrome. There were two minor complications and no major complications.ConclusionImage-guided percutaneous ablation is a feasible, safe, and effective second-line treatment option for symptomatic VA

  13. Initial Results of Image-Guided Percutaneous Ablation as Second-Line Treatment for Symptomatic Vascular Anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Scott M., E-mail: Thompson.scott@mayo.edu [Mayo Clinic, Mayo Graduate School, Mayo Medical School and the Mayo Clinic Medical Scientist Training Program, College of Medicine (United States); Callstrom, Matthew R., E-mail: callstrom.matthew@mayo.edu; McKusick, Michael A., E-mail: mckusick.michael@mayo.edu; Woodrum, David A., E-mail: woodrum.david@mayo.edu [Mayo Clinic, Department of Radiology, College of Medicine (United States)

    2015-10-15

    PurposeThe purpose of this study was to determine the feasibility, safety, and early effectiveness of percutaneous image-guided ablation as second-line treatment for symptomatic soft-tissue vascular anomalies (VA).Materials and MethodsAn IRB-approved retrospective review was undertaken of all patients who underwent percutaneous image-guided ablation as second-line therapy for treatment of symptomatic soft-tissue VA during the period from 1/1/2008 to 5/20/2014. US/CT- or MRI-guided and monitored cryoablation or MRI-guided and monitored laser ablation was performed. Clinical follow-up began at one-month post-ablation.ResultsEight patients with nine torso or lower extremity VA were treated with US/CT (N = 4) or MRI-guided (N = 2) cryoablation or MRI-guided laser ablation (N = 5) for moderate to severe pain (N = 7) or diffuse bleeding secondary to hemangioma–thrombocytopenia syndrome (N = 1). The median maximal diameter was 9.0 cm (6.5–11.1 cm) and 2.5 cm (2.3–5.3 cm) for VA undergoing cryoablation and laser ablation, respectively. Seven VA were ablated in one session, one VA initially treated with MRI-guided cryoablation for severe pain was re-treated with MRI-guided laser ablation due to persistent moderate pain, and one VA was treated in a planned two-stage session due to large VA size. At an average follow-up of 19.8 months (range 2–62 months), 7 of 7 patients with painful VA reported symptomatic pain relief. There was no recurrence of bleeding at five-year post-ablation in the patient with hemangioma–thrombocytopenia syndrome. There were two minor complications and no major complications.ConclusionImage-guided percutaneous ablation is a feasible, safe, and effective second-line treatment option for symptomatic VA.

  14. Chemotherapy or targeted therapy as second-line treatment of advanced gastric cancer. A systematic review and meta-analysis of published studies.

    Science.gov (United States)

    Iacovelli, Roberto; Pietrantonio, Filippo; Farcomeni, Alessio; Maggi, Claudia; Palazzo, Antonella; Ricchini, Francesca; de Braud, Filippo; Di Bartolomeo, Maria

    2014-01-01

    Chemotherapy is a cornerstone in treatments of gastric cancer, but despite its benefit, less than 60% of patients receive salvage therapy in clinical practice. We performed a systematic review and meta-analysis based on trial data on the role of second-line treatment of advanced gastric cancer. MEDLINE/PubMed and Cochrane Library were searched for randomized phase III trials that compared active therapy to best supportive care in advanced gastric cancer. Data extraction was conducted according to the PRISMA statement. Summary HR for OS was calculated using a hierarchical Bayesian model and subgroup analysis was performed based on baseline Eastern Cooperative Oncology Group Performance Status (ECOG) performance status (0 vs. 1 or more). A total of 1,407 patients were evaluable for efficacy, 908 were treated in the experimental arms, with chemotherapy (231 pts) or with targeted therapies (677 pts). The risk of death was decreased by 18% (HR = 0.82; 95% CI, 0.79-0.85; posterior probability HR≥1: Chemotherapy and ramucirumab were able to decrease this risk by 27% and 22%, respectively. No differences were found between chemotherapy and ramucirumab. In patients with ECOG = 0 a greater benefit was found for chemotherapy with a reduction of the risk of death by 43% and no benefits were found for ramucirumab or everolimus. In patients with ECOG = 1 or more a significant reduction of the risk of death by 32% was reported in patients treated with ramucirumab, even if no significant difference was reported between chemotherapy and ramucirumab. This analysis reports that active and available therapies are able to prolong survival in patients with advanced gastric cancer with a different outcome based on initial patient's performance status. New trials based on a better patient stratification are awaited.

  15. Effect of therapy switch on time to second-line antiretroviral treatment failure in HIV-infected patients.

    Science.gov (United States)

    Häggblom, Amanda; Santacatterina, Michele; Neogi, Ujjwal; Gisslen, Magnus; Hejdeman, Bo; Flamholc, Leo; Sönnerborg, Anders

    2017-01-01

    Switch from first line antiretroviral therapy (ART) to second-line ART is common in clinical practice. However, there is limited knowledge of to which extent different reason for therapy switch are associated with differences in long-term consequences and sustainability of the second line ART. Data from 869 patients with 14601 clinical visits between 1999-2014 were derived from the national cohort database. Reason for therapy switch and viral load (VL) levels at first-line ART failure were compared with regard to outcome of second line ART. Using the Laplace regression model we analyzed the median, 10th, 20th, 30th and 40th percentile of time to viral failure (VF). Most patients (n = 495; 57.0%) switched from first-line to second-line ART without VF. Patients switching due to detectable VL with (n = 124; 14.2%) or without drug resistance mutations (DRM) (n = 250; 28.8%) experienced VF to their second line regimen sooner (median time, years: 3.43 (95% CI 2.90-3.96) and 3.20 (95% 2.65-3.75), respectively) compared with those who switched without VF (4.53 years). Furthermore level of VL at first-line ART failure had a significant impact on failure of second-line ART starting after 2.5 years of second-line ART. In the context of life-long therapy, a median time on second line ART of 4.53 years for these patients is short. To prolong time on second-line ART, further studies are needed on the reasons for therapy changes. Additionally patients with a high VL at first-line VF should be more frequently monitored the period after the therapy switch.

  16. Effect of therapy switch on time to second-line antiretroviral treatment failure in HIV-infected patients.

    Directory of Open Access Journals (Sweden)

    Amanda Häggblom

    Full Text Available Switch from first line antiretroviral therapy (ART to second-line ART is common in clinical practice. However, there is limited knowledge of to which extent different reason for therapy switch are associated with differences in long-term consequences and sustainability of the second line ART.Data from 869 patients with 14601 clinical visits between 1999-2014 were derived from the national cohort database. Reason for therapy switch and viral load (VL levels at first-line ART failure were compared with regard to outcome of second line ART. Using the Laplace regression model we analyzed the median, 10th, 20th, 30th and 40th percentile of time to viral failure (VF.Most patients (n = 495; 57.0% switched from first-line to second-line ART without VF. Patients switching due to detectable VL with (n = 124; 14.2% or without drug resistance mutations (DRM (n = 250; 28.8% experienced VF to their second line regimen sooner (median time, years: 3.43 (95% CI 2.90-3.96 and 3.20 (95% 2.65-3.75, respectively compared with those who switched without VF (4.53 years. Furthermore level of VL at first-line ART failure had a significant impact on failure of second-line ART starting after 2.5 years of second-line ART.In the context of life-long therapy, a median time on second line ART of 4.53 years for these patients is short. To prolong time on second-line ART, further studies are needed on the reasons for therapy changes. Additionally patients with a high VL at first-line VF should be more frequently monitored the period after the therapy switch.

  17. Limb salvage treatment vs. amputation in sarcoma

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    Motamedi M

    1993-05-01

    Full Text Available Many years ago the treatment of sarcoma was radiotherapy up to 2000-4000 rad. This treatment was very complicated, due to producing neoplasm after radiotherapy. By this method of treatment of osteosarcoma, the rate of survival became about 20% (two years. The second method of treatment was chemotherapy for a period of 2-5 weeks that amputation was performed afterwards. By chemotherapy, the rate of being alive reached up to 25-27% (five years. Right now, the best treatment for sarcoma is limb salvage. In our report, the chance of being alive in chondrosarcoma was about four years. This was nearly the same as that of the other institutes in the world especially in America, Europe, and Japan. The rate of recurrence was also more than that from different parts of the world. The survival rate in osteosarcomatic patients was about two years less for males the females, and it was more in tall people than short ones. The survival rate of the patients with giant cell tumor was more than osteosarcoma up to five years, and it has no recurrence or metastasis

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

    Directory of Open Access Journals (Sweden)

    Trojan J

    2016-09-01

    Full Text Available Jörg Trojan, Oliver Waidmann Medizinische Klinik 1, Universitätsklinikum Frankfurt, Germany Abstract: Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC. In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months. Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1 blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC. Keywords: hepatocellular carcinoma, receptor tyrosine kinase inhibitor, sorafenib, regorafenib, lenvatinib, tivantinib, cabozantinib, ramucirumab, immunotherapy, anti-CTLA-4, anti-PD-1, oncolytic virus

  19. Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer

    DEFF Research Database (Denmark)

    Joensuu, H; Holli, K; Heikkinen, M

    1998-01-01

    PURPOSE: We report results of a randomized prospective study that compared single agents of low toxicity given both as the first-line and second-line chemotherapy with combination chemotherapy in advanced breast cancer with distant metastases. PATIENTS AND METHODS: Patients in the single-agent arm...... (n = 153) received weekly epirubicin (E) 20 mg/m2 until progression or until the cumulative dose of 1,000 mg/m2, followed by mitomycin (M) 8 mg/m2 every 4 weeks, and those in the combination chemotherapy arm (n = 150) were first given cyclophosphamide 500 mg/m2, E 60 mg/m2, and fluorouracil 500 mg/m2...... younger than 50. RESULTS: An objective response (complete [CR] or partial [PR]) was obtained in 55%, 48%, 16%, and 7% of patients treated with CEF, E, M, and MV, respectively. A response to CEF tended to last longer than a response to E (median, 12 v 10.5 months; P = .07). Treatment-related toxicity...

  20. Prices of second-line antiretroviral treatment for middle-income countries inside versus outside sub-Saharan Africa.

    Science.gov (United States)

    Simmons, Bryony; Hill, Andrew; Ford, Nathan; Ruxrungtham, Kiat; Ananworanich, Jintanat

    2014-01-01

    Antiretrovirals are available at low prices in sub-Saharan Africa, but these prices may not be consistently available for middle-income countries in other regions with large HIV epidemics. Over 30% of HIV infected people live in countries outside sub-Saharan Africa. Several key antiretrovirals are still on patent, with generic production restricted. We assessed price variations for key antiretroviral drugs inside versus outside sub-Saharan Africa. HIV drug prices used in national programmes (2010-2014) were extracted from the WHO Global Price Reporting Mechanism database for all reporting middle-income countries as classified by the World Bank. Treatment costs (branded and generic) were compared for countries inside sub-Saharan Africa versus those outside. Five key second-line antiretrovirals were analysed: abacavir, atazanavir, darunavir, lopinavir/ritonavir, raltegravir. Prices of branded antiretrovirals were significantly higher outside sub-Saharan Africa (psub-Saharan Africa versus $4689 (IQR $4075-5717) in non-African middle-income countries, an increase of 541%. However, when supplied by generic companies, most antiretrovirals were similarly priced between countries in sub-Saharan Africa and other regions. Pharmaceutical companies are selling antiretrovirals to non-African middle-income countries at prices 74-541% higher than African countries with similar gross national incomes. However, generic companies are selling most of these drugs at similar prices across regions. Mechanisms to ensure fair pricing for patented antiretrovirals across both African and non-African middle-income countries need to be improved, to ensure sustainable treatment access.

  1. Effectiveness of carboplatin and paclitaxel as first- and second-line treatment in 61 patients with metastatic melanoma.

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    Annette Pflugfelder

    Full Text Available BACKGROUND: Patients with metastatic melanoma have a very unfavorable prognosis with few therapeutic options. Based on previous promising experiences within a clinical trial involving carboplatin and paclitaxel a series of advanced metastatic melanoma patients were treated with this combination. METHODS: Data of all patients with cutaneous metastatic melanoma treated with carboplatin and paclitaxel (CP at our institution between October 2005 and December 2007 were retrospectively evaluated. For all patients a once-every-3-weeks dose-intensified regimen was used. Overall and progression free survival were calculated using the method of Kaplan and Meier. Tumour response was evaluated according to RECIST criteria. RESULTS: 61 patients with cutaneous metastatic melanoma were treated with CP. 20 patients (85% M1c received CP as first-line treatment, 41 patients (90.2% M1c had received at least one prior systemic therapy for metastatic disease. Main toxicities were myelosuppression, fatigue and peripheral neuropathy. Partial responses were noted in 4.9% of patients, stable disease in 23% of patients. No complete response was observed. Median progression free survival was 10 weeks. Median overall survival was 31 weeks. Response, progression-free and overall survival were equivalent in first- and second-line patients. 60 patients of 61 died after a median follow up of 7 months. Median overall survival differed for patients with controlled disease (PR+SD (49 weeks compared to patients with progressive disease (18 weeks. CONCLUSIONS: Among patients with metastatic melanoma a subgroup achieved disease control under CP therapy which may be associated with a survival benefit. This potential advantage has to be weighed against considerable toxicity. Since response rates and survival were not improved in previously untreated patients compared to pretreated patients, CP should thus not be applied as first-line treatment.

  2. Second-line therapy in diffuse large B-cell lymphoma (DLBCL): treatment patterns and outcomes in older patients receiving outpatient chemotherapy.

    Science.gov (United States)

    Danese, Mark D; Griffiths, Robert I; Gleeson, Michelle L; Dalvi, Tapashi; Li, Jingyi; Mikhael, Joseph R; Deeter, Robert; Dreyling, Martin

    2017-05-01

    Using SEER-Medicare linked data we identified elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) between January 2000 and December 2007 who received second-line outpatient chemotherapy for relapsed or refractory disease. Second-line regimens were classified into three mutually exclusive groups: aggressive, conventional, and palliative. Of the 632 (426 relapsed, 206 refractory) patients in the cohort, 27.8% received aggressive second-line therapy, 39.1% received conventional therapy, and 33.1% received palliative therapy. There were no differences in survival by type of therapy received, either for relapsed or refractory patients, although the patient risk profile differed significantly. However, duration of remission, male gender, and anemia at diagnosis were important predictors in relapsed patients, and male gender, B-symptoms, comorbidity burden, and poverty status were important predictors in refractory patients. Survival in elderly patients receiving second-line therapy remains poor, and the 24-month cost of all care exceeds $97,000. Patients would benefit from improved treatment options.

  3. First and second line drug resistance among treatment naïve pulmonary tuberculosis patients in a district under Revised National Tuberculosis Control Programme (RNTCP in New Delhi

    Directory of Open Access Journals (Sweden)

    Vithal Prasad Myneedu

    2015-12-01

    Full Text Available There is limited information of level of drug resistance to first-line and second line anti-tuberculosis agents in treatment naïve pulmonary tuberculosis (PTB patients from the Indian region. Therefore, the present prospective study was conducted to determine the antimicrobial susceptibility to first-line and second line anti-TB drug resistance in such patients. Sputum samples from consecutive treatment naïve PTB cases registered in Lala Ram Sarup (LRS district, under RNTCP containing 12 Directly Observed Treatment Centre’s (DOTS, were enrolled using cluster sampling technology. A total of 453 samples were received from July 2011 to June 2012. All samples were cultured on solid medium followed by drug susceptibility to first and second line anti-tubercular drugs as per RNTCP guidelines. Primary multi-drug resistance (MDR was found to be 18/453; (4.0%. Extensively drug resistance (XDR was found in one strain (0.2%, which was found to be resistant to other antibiotics. Data of drug resistant tuberculosis among treatment naïve TB patients are lacking in India. The presence of XDR-TB and high MDR-TB in small population studied, calls for conducting systematic multi-centric surveillance across the country.

  4. Quality of Life in Second-Line Treatment of Metastatic Castration-Resistant Prostate Cancer Using Cabazitaxel or Other Therapies After Previous Docetaxel Chemotherapy: Swiss Observational Treatment Registry.

    Science.gov (United States)

    Stenner, Frank; Rothschild, Sacha I; Betticher, Daniel; Caspar, Clemens; Morant, Rudolf; Popescu, Razvan; Rauch, Daniel; Huber, Urs; Zenhäusern, Reinhard; Rentsch, Cyrill; Cathomas, Richard

    2017-08-24

    The aim was to evaluate quality of life (QoL), pain, and fatigue in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with different regimens after first-line docetaxel, as well as disease progression. Patients with mCRPC having received first-line chemotherapy with docetaxel were eligible. Second-line treatment choice was at the discretion of the local investigator. All patients had regular assessments of QoL with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, of fatigue with the Brief Fatigue Inventory, and of pain with the McGill Pain Questionnaire-Short Form. The primary end point was QoL maintenance defined as having a maximum decrease in 2 functional domains of the FACT-P. One hundred thirty-eight patients were included in 36 oncology centers across Switzerland. QoL analysis was available for all patients (59 who received cabazitaxel; 79 who received other therapy [OT] including 75 who received abiraterone). No significant differences for any of the end points were found between groups. A numerically higher number of patients had QoL maintenance with OT (25 of 79 patients, 32%) compared with cabazitaxel (8 of 59 patients, 14%). QoL improvement was found in 20% of patients (12 of 59) who received cabazitaxel and 24% (19 of 79) who received OT. Mean FACT-P score did not change in a clinically relevant manner over time in either group. Pain was present in 70% of patients (96 of 138), and a pain response to treatment was noted in 22% (13 of 59) who received cabazitaxel and 29% (23 of 79) who received OT. A similar but minor improvement of fatigue was noted in both groups. Some degree of QoL decrease was seen in most patients regardless of second-line treatment. No significant differences in QoL parameters between cabazitaxel or other second line treatments were found. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Efficacy and safety of sequential versus quadruple therapy as second-line treatment for helicobacter pylori infection-A randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Daniela Munteanu

    Full Text Available Quadruple therapy is recommended as second-line treatment for Helicobacter pylori eradication failure. However, high cost, multiple side effects, and low adherence rates are major drawbacks to its routine use. Our aim was to compare the efficacy and safety of sequential versus quadruple regimens as second line treatment for persistent Helicobacter pylori infection.Prospective, randomized, open label trial was conducted at a large academic, tertiary care center in Israel. Patients who previously failed a standard triple treatment eradication course were randomly assigned (1:1 to receive a 10-day sequential therapy course, or a 14-day quadruple regimen. Compliance and adverse events were evaluated by telephone questionnaires. The primary endpoint for analysis was the rate of Helicobacter pylori eradication as defined by either a negative 13C-urea breath-test, or stool antigen test, 4-16 weeks after treatment assessed under the non-inferiority hypothesis. The trial was terminated prematurely due to low recruitment rates. See S1 Checklist for CONSORT checklist.One hundred and one patients were randomized. Per modified intention-to-treat analysis, eradication rate was 49% in the sequential versus 42.5% in the quadruple regimen group (p-value for non-inferiority 0.02. Forty-two (84.0% versus 33 (64.7% patients completed treatment in the sequential and quadruple groups respectively (p 0.027. Gastrointestinal side effects were more common in the quadruple regimen group.Sequential treatment when used as a second line regimen, was non-inferior to the standard of care quadruple regimen in achieving Helicobacter pylori eradication, and was associated with better compliance and fewer adverse effects. Both treatment protocols failed to show an adequate eradication rate in the population of Southern Israel.ClinicalTrials.gov NCT01481844.

  6. Second-line therapy with levofloxacin after failure of treatment to eradicate helicobacter pylori infection: time trends in a Spanish Multicenter Study of 1000 patients.

    Science.gov (United States)

    Gisbert, Javier P; Pérez-Aisa, Angeles; Bermejo, Fernando; Castro-Fernández, Manuel; Almela, Pedro; Barrio, Jesús; Cosme, Angel; Modolell, Inés; Bory, Felipe; Fernández-Bermejo, Miguel; Rodrigo, Luis; Ortuño, Jesús; Sánchez-Pobre, Pilar; Khorrami, Sam; Franco, Alejandro; Tomas, Albert; Guerra, Iván; Lamas, Eloisa; Ponce, Julio; Calvet, Xavier

    2013-02-01

    Second-line bismuth-containing quadruple therapy is complex and frequently induces adverse effects. A triple rescue regimen containing levofloxacin is a potential alternative; however, resistance to quinolones is rapidly increasing. To evaluate the efficacy and tolerability of a second-line triple-regimen-containing levofloxacin in patients whose Helicobacter pylori eradication treatment failed and to assess whether the efficacy of the regimen decreases with time. Prospective multicenter study. In whom treatment with a regimen comprising a proton-pump inhibitor, clarithromycin, and amoxicillin had failed. Levofloxacin (500 mg bid), amoxicillin (1 g bid), and omeprazole (20 mg bid) for 10 days. Eradication was confirmed using the C-urea breath test 4 to 8 weeks after therapy. Compliance/tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. The study sample comprised 1000 consecutive patients (mean age, 49 ± 15 y, 42% men, 33% peptic ulcer) of whom 97% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 75.1% (95% confidence interval, 72%-78%) and 73.8% (95% confidence interval, 71%-77%). Efficacy (intention-to-treat) was 76% in the year 2006, 68% in 2007, 70% in 2008, 76% in 2009, 74% in 2010, and 81% in 2011. In the multivariate analysis, none of the studied variables (including diagnosis and year of treatment) were associated with success of eradication. Adverse effects were reported in 20% of patients, most commonly nausea (7.9%), metallic taste (3.9%), myalgia (3.1%), and abdominal pain (2.9%). Ten-day levofloxacin-containing therapy is an encouraging second-line strategy, providing a safe and simple alternative to quadruple therapy in patients whose previous standard triple therapy has failed. The efficacy of this regimen remains stable with time.

  7. [Eyeball salvage treatment or enucleation for advanced retinoblastoma].

    Science.gov (United States)

    Qian, J; Xue, K

    2016-10-11

    The management of retinoblastoma (RB) has dramatically changed over the past two decades. The introduction of chemotherapy has transformed treatment algorithms completely. Chemotherapy is currently used as a first line approach for children with RB and can be delivered by intravenous, intra-arterial and intravitreal routes. However, there still remains some controversy on the treatment of advanced RB, especially in eyeball salvage. This article described domestic and international approaches to eyeball salvage treatment. We would like to further discuss our opinion on the management of advanced RB based on our clinical experience for attracting more clinical concern on this issue. Many factors should be considered when choosing the appropriate conservative therapy. The choice of eyeball salvage treatment not only depends upon the tumor staging and laterality but also upon compliance and economic factors. Doctors and parents should not blindly pursue eye saving. However, there are still cases where enucleation is definitely the treatment of choice. (Chin J Ophthalmol, 2016, 52: 728-732) .

  8. Helicobacter pylori second-line rescue therapy with levofloxacin- and bismuth-containing quadruple therapy, after failure of standard triple or non-bismuth quadruple treatments.

    Science.gov (United States)

    Gisbert, J P; Romano, M; Gravina, A G; Solís-Muñoz, P; Bermejo, F; Molina-Infante, J; Castro-Fernández, M; Ortuño, J; Lucendo, A J; Herranz, M; Modolell, I; Del Castillo, F; Gómez, J; Barrio, J; Velayos, B; Gómez, B; Domínguez, J L; Miranda, A; Martorano, M; Algaba, A; Pabón, M; Angueira, T; Fernández-Salazar, L; Federico, A; Marín, A C; McNicholl, A G

    2015-04-01

    The most commonly used second-line Helicobacter pylori eradication regimens are bismuth-containing quadruple therapy and levofloxacin-containing triple therapy, both offering suboptimal results. Combining bismuth and levofloxacin may enhance the efficacy of rescue eradication regimens. To evaluate the efficacy and tolerability of a second-line quadruple regimen containing levofloxacin and bismuth in patients whose previous H. pylori eradication treatment failed. This was a prospective multicenter study including patients in whom a standard triple therapy (PPI-clarithromycin-amoxicillin) or a non-bismuth quadruple therapy (PPI-clarithromycin-amoxicillin-metronidazole, either sequential or concomitant) had failed. Esomeprazole (40 mg b.d.), amoxicillin (1 g b.d.), levofloxacin (500 mg o.d.) and bismuth (240 mg b.d.) was prescribed for 14 days. Eradication was confirmed by (13) C-urea breath test. Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by questionnaires. 200 patients were included consecutively (mean age 47 years, 67% women, 13% ulcer). Previous failed therapy included: standard clarithromycin triple therapy (131 patients), sequential (32) and concomitant (37). A total of 96% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 91.1% (95%CI = 87-95%) and 90% (95%CI = 86-94%). Cure rates were similar regardless of previous (failed) treatment or country of origin. Adverse effects were reported in 46% of patients, most commonly nausea (17%) and diarrhoea (16%); 3% were intense but none was serious. Fourteen-day bismuth- and levofloxacin-containing quadruple therapy is an effective (≥90% cure rate), simple and safe second-line strategy in patients whose previous standard triple or non-bismuth quadruple (sequential or concomitant) therapies have failed. © 2015 John Wiley & Sons Ltd.

  9. Disease-related mortality exceeds treatment-related mortality in patients with chronic myeloid leukemia on second-line or later therapy.

    Science.gov (United States)

    Pearson, Edward; McGarry, Lisa; Gala, Smeet; Nieset, Christopher; Nanavaty, Merena; Mwamburi, Mkaya; Levy, Yair

    2016-04-01

    Treatment of newly-diagnosed patients with chronic-phase chronic myeloid leukemia (CP-CML) with tyrosine kinase inhibitors (TKIs) results in near-normal life expectancy. However, CP-CML patients resistant to initial TKIs face a poorer prognosis and significantly higher CML-related mortality. We conducted a systematic literature review to evaluate the specific causes of deaths (diseases progression versus drug-related) in CP-CML patients receiving second- or third-line therapy. We identified eight studies based on our criteria that reported causes of death. Overall, 5% of second-line and 10% of third-line patients died during the study follow-up period. For second-line, (7 studies, n=1926), mortality was attributed to disease progression for 41% of deaths, 2% to treatment-related causes, 3% were treatment-unrelated, and 50% were unspecified adverse events (AEs), not likely related to study drug. In third-line, (2 studies, n=144), 71% deaths were attributed to disease progression, 7% treatment-related AEs, 14% treatment-unrelated and 7% unspecified AEs. Annual death rates for second- and third-line therapy were significantly higher than for general population in similar age group. Our findings suggest death attributed to disease progression is approximately 10 times that due to treatment-related AEs in patients with CP-CML receiving second- or third-line therapy. Therefore, the potential benefits of effective treatment for these patients with the currently available TKIs outweigh the risks of treatment-induced AEs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8)

    DEFF Research Database (Denmark)

    Soria, Jean-Charles; Felip, Enriqueta; Cobo, Manuel

    2015-01-01

    BACKGROUND: There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced...... squamous cell carcinoma of the lung. METHODS: We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum...... be an additional option for the treatment of patients with squamous cell carcinoma of the lung. FUNDING: Boehringer Ingelheim....

  11. Angiographic Embolization of a Postpartum Vulvovaginal Hematoma in a Patient with Situs Inversus Totalis: An Effective Second-Line Treatment

    Directory of Open Access Journals (Sweden)

    Elias M. Dahdouh

    2013-01-01

    Full Text Available Situs inversus totalis is a rare congenital anomaly where asymmetrical positioning of internal organs may affect the surgical and radiological management of certain conditions. Vulvovaginal hematoma is a life-threatening complication of vaginal delivery whose primary treatment usually consists of incision and drainage of the hematoma and ligation of the responsible vessels, followed by wound packing. Failure of these measures to control the bleeding was previously considered as an indication for laparotomy to perform bilateral hypogastric artery ligation and, if needed, a hysterectomy. Relative to major abdominal surgery, selective percutaneous angiographic embolization offers considerable advantages and significant less morbidity. Indeed, angiographic embolization is routinely used as a measure to control refractory pelvic bleeding, though the literature and experience in women with situs inversus totalis are scarce. In this paper, we report a case of postpartum vulvovaginal hematoma in a patient with situs inversus, refractory to conventional treatment, where arteriographic embolization was successfully used to control the bleeding. The management of this obstetrical complication and the use of this minimally invasive technique are also reviewed. To the best of our knowledge, this is the first report in the literature describing the feasibility of this technique in a patient with situs inversus totalis.

  12. Second-line treatment of recurrent HNSCC: tumor debulking in combination with high-dose-rate brachytherapy and a simultaneous cetuximab-paclitaxel protocol

    International Nuclear Information System (INIS)

    Ritter, M.; Teudt, I. U.; Meyer, J. E.; Schröder, U.; Kovács, G.; Wollenberg, B.

    2016-01-01

    After the failure of first-line treatment, the clinical prognosis in head and neck cancer (HNSCC) deteriorates. Effective therapeutic strategies are limited due to the toxicity of previous treatments and the diminished tolerance of surrounding normal tissue. This study demonstrates a promising second-line regimen, with function preserving surgical tumor debulking, followed by a combination of postoperative interstitial brachytherapy and a simultaneous protocol of cetuximab and taxol. From January 2006 to May 2013, 197 patients with HNSCC were treated with brachytherapy at the University Hospital Schleswig-Holstein Campus Lübeck, including 94 patients due to recurrent cancer. Within these, 18 patients were referred to our clinic because of early progressive disease following first- or second-line treatment failure. They received the new palliative regimen. A matched-pair analysis including recurrent tumor stage, status of resection margins, tissue invasion and previous therapy was performed to evaluate this treatment retrospectively. Overall survival (OS), disease-free survival (DFS), functional outcome and treatment toxicity was analyzed on the basis of medical records and follow-up data. DFS and OS of the study group were 8.7 and 14.8 months. Whereas, DFS and OS of the control group, treated only by function preserving tumor debulking and brachytherapy, was 3.9 and 6.1 months respectively. This demonstrates a positive trend through the additional use of the cetuximab-taxane protocol. Furthermore, no increase of therapy induced toxicities was displayed. Pre-treated patients with a further relapse benefit from the ‘cetuximab-taxane recurrency scheme’. It seems to be a valuable complement to interdisciplinary and multimodal tumor therapy, which improves OS and results in acceptable toxicity. The online version of this article (doi:10.1186/s13014-016-0583-0) contains supplementary material, which is available to authorized users

  13. Second-line rescue triple therapy with levofloxacin after failure of non-bismuth quadruple "sequential" or "concomitant" treatment to eradicate H. pylori infection.

    Science.gov (United States)

    Gisbert, Javier P; Molina-Infante, Javier; Marin, Alicia C; Vinagre, Gemma; Barrio, Jesus; McNicholl, Adrian Gerald

    2013-06-01

    Non-bismuth quadruple "sequential" and "concomitant" regimens, including a proton pump inhibitor (PPI), amoxicillin, clarithromycin and a nitroimidazole, are increasingly used as first-line treatments for Helicobacter pylori infection. Eradication with rescue regimens may be challenging after failure of key antibiotics such as clarithromycin and nitroimidazoles. To evaluate the efficacy and tolerability of a second-line levofloxacin-containing triple regimen (PPI-amoxicillin-levofloxacin) in the eradication of H. pylori after non-bismuth quadruple-containing treatment failure. prospective multicenter study. in whom a non-bismuth quadruple regimen, administered either sequentially (PPI + amoxicillin for 5 days followed by PPI + clarithromycin + metronidazole for 5 more days) or concomitantly (PPI + amoxicillin + clarithromycin + metronidazole for 10 days) had previously failed. levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.) and PPI (standard dose b.i.d.) for 10 days. eradication was confirmed with (13)C-urea breath test 4-8 weeks after therapy. Compliance and tolerance: compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. 100 consecutive patients were included (mean age 50 years, 62% females, 12% peptic ulcer and 88% dyspepsia): 37 after "sequential", and 63 after "concomitant" treatment failure. All patients took all medications correctly. Overall, per-protocol and intention-to-treat H. pylori eradication rates were 75.5% (95% CI 66-85%) and 74% (65-83%). Respective intention-to-treat cure rates for "sequential" and "concomitant" failure regimens were 74.4% and 71.4%, respectively. Adverse effects were reported in six (6%) patients; all of them were mild. Ten-day levofloxacin-containing triple therapy constitutes an encouraging second-line strategy in patients with previous non-bismuth quadruple "sequential" or "concomitant" treatment failure.

  14. The effect of PD-L1 testing on the cost-effectiveness and economic impact of immune checkpoint inhibitors for the second-line treatment of NSCLC.

    Science.gov (United States)

    Aguiar, P N; Perry, L A; Penny-Dimri, J; Babiker, H; Tadokoro, H; de Mello, R A; Lopes, G L

    2017-09-01

    Immune checkpoint inhibitors improve outcomes compared with chemotherapy in lung cancer. Tumor PD-L1 receptor expression is being studied as a predictive biomarker. The objective of this study was to assess the cost-effectiveness and economic impact of second-line treatment with nivolumab, pembrolizumab, and atezolizumab with and without the use of PD-L1 testing for patient selection. We developed a decision-analytic model to determine the cost-effectiveness of PD-L1 assessment and second-line immunotherapy versus docetaxel. The model used outcomes data from randomized clinical trials (RCTs) and drug acquisition costs from the United States. Thereafter, we used epidemiologic data to estimate the economic impact of the treatment. We included four RCTs (2 with nivolumab, 1 with pembrolizumab, and 1 with atezolizumab). The incremental quality-adjusted life year (QALY) for nivolumab was 0.417 among squamous tumors and 0.287 among non-squamous tumors and the incremental cost-effectiveness ratio (ICER) were $155 605 and $187 685, respectively. The QALY gain in the base case for atezolizumab was 0.354 and the ICER was $215 802. Compared with treating all patients, the selection of patients by PD-L1 expression improved incremental QALY by up to 183% and decreased the ICER by up to 65%. Pembrolizumab was studied only in patients whose tumors expressed PD-L1. The QALY gain was 0.346 and the ICER was $98 421. Patient selection also reduced the budget impact of immunotherapy. The use of PD-L1 expression as a biomarker increases cost-effectiveness of immunotherapy but also diminishes the number of potential life-years saved. © The Author 2017. 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.

  15. Second-Line Therapy for Advanced NSCLC.

    Science.gov (United States)

    Weiss, Jared M; Stinchcombe, Thomas E

    2013-01-01

    Most patients with lung cancer have non-small cell lung cancer (NSCLC) subtype and have advanced disease at the time of diagnosis. Improvements in both first-line and subsequent therapies are allowing longer survival and enhanced quality of life for these patients. The median overall survival observed in many second-line trials is approximately 9 months, and many patients receive further therapy after second-line therapy. The cytotoxic agents pemetrexed and docetaxel and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib are standard second-line therapies. For patients with EGFR mutation, a TKI is the favored second-line therapy if not already used in first-line therapy. For patients without the EGFR mutation, TKIs are an option, but many oncologists favor cytotoxic therapy. The inhibitor of the EML4/ALK fusion protein, crizotinib, has recently become a standard second-line treatment for patients with the gene rearrangement and has promise for patients with the ROS1 rearrangement.

  16. Survival effect of first- and second-line treatments for patients with primary glioblastoma: a cohort study from a prospective registry, 1997–2010

    Science.gov (United States)

    Nava, Francesca; Tramacere, Irene; Fittipaldo, Andrea; Bruzzone, Maria Grazia; DiMeco, Francesco; Fariselli, Laura; Finocchiaro, Gaetano; Pollo, Bianca; Salmaggi, Andrea; Silvani, Antonio; Farinotti, Mariangela; Filippini, Graziella

    2014-01-01

    Background Prospective follow-up studies of large cohorts of patients with glioblastoma (GBM) are needed to assess the effectiveness of conventional treatments in clinical practice. We report GBM survival data from the Brain Cancer Register of the Fondazione Istituto Neurologico Carlo Besta (INCB) in Milan, Italy, which collected longitudinal data for all consecutive patients with GBM from 1997 to 2010. Methods Survival data were obtained from 764 patients (aged>16 years) with histologically confirmed primary GBM who were diagnosed and treated over a 7-year period (2004–2010) with follow-up to April 2012 (cohort II). Equivalent data from 490 GBM patients diagnosed and treated over the preceding 7 years (1997–2003) with follow-up to April 2005 (cohort I) were available for comparison. Progression-free survival (PFS) was available from 361 and 219 patients actively followed up at INCB in cohorts II and I, respectively. Results Survival probabilities were 54% at 1 year, 21% at 2 years, and 11% at 3 years, respectively, in cohort II compared with 47%, 11%, and 5%, respectively, in cohort I. PFS was 22% and 12% at 1 year in cohorts II and I. Better survival and PFS in cohort II was significantly associated with introduction of the Stupp protocol into clinical practice, with adjusted hazard ratios (HRs) of 0.78 for survival and 0.73 for PFS, or a 22% relative decrease in the risk of death and a 27% relative decrease in the risk of recurrence. After recurrence, reoperation was performed in one-fifth of cohort I and in one-third of cohort II but was not effective (HR, 1.05 in cohort I and 1.02 in cohort II). Second-line chemotherapy, mainly consisting of nitrosourea-based chemotherapy, temozolomide, mitoxantrone, fotemustine, and bevacizumab, improved survival in both cohorts (HR, 0.57 in cohort I and 0.74 in cohort II). Radiosurgery was also effective (HR, 0.52 in cohort II). Conclusions We found a significant increase in overall survival, PFS, and survival after

  17. Survival effect of first- and second-line treatments for patients with primary glioblastoma: a cohort study from a prospective registry, 1997-2010.

    Science.gov (United States)

    Nava, Francesca; Tramacere, Irene; Fittipaldo, Andrea; Bruzzone, Maria Grazia; Dimeco, Francesco; Fariselli, Laura; Finocchiaro, Gaetano; Pollo, Bianca; Salmaggi, Andrea; Silvani, Antonio; Farinotti, Mariangela; Filippini, Graziella

    2014-05-01

    Prospective follow-up studies of large cohorts of patients with glioblastoma (GBM) are needed to assess the effectiveness of conventional treatments in clinical practice. We report GBM survival data from the Brain Cancer Register of the Fondazione Istituto Neurologico Carlo Besta (INCB) in Milan, Italy, which collected longitudinal data for all consecutive patients with GBM from 1997 to 2010. Survival data were obtained from 764 patients (aged>16 years) with histologically confirmed primary GBM who were diagnosed and treated over a 7-year period (2004-2010) with follow-up to April 2012 (cohort II). Equivalent data from 490 GBM patients diagnosed and treated over the preceding 7 years (1997-2003) with follow-up to April 2005 (cohort I) were available for comparison. Progression-free survival (PFS) was available from 361 and 219 patients actively followed up at INCB in cohorts II and I, respectively. Survival probabilities were 54% at 1 year, 21% at 2 years, and 11% at 3 years, respectively, in cohort II compared with 47%, 11%, and 5%, respectively, in cohort I. PFS was 22% and 12% at 1 year in cohorts II and I. Better survival and PFS in cohort II was significantly associated with introduction of the Stupp protocol into clinical practice, with adjusted hazard ratios (HRs) of 0.78 for survival and 0.73 for PFS, or a 22% relative decrease in the risk of death and a 27% relative decrease in the risk of recurrence. After recurrence, reoperation was performed in one-fifth of cohort I and in one-third of cohort II but was not effective (HR, 1.05 in cohort I and 1.02 in cohort II). Second-line chemotherapy, mainly consisting of nitrosourea-based chemotherapy, temozolomide, mitoxantrone, fotemustine, and bevacizumab, improved survival in both cohorts (HR, 0.57 in cohort I and 0.74 in cohort II). Radiosurgery was also effective (HR, 0.52 in cohort II). We found a significant increase in overall survival, PFS, and survival after recurrence after 2004, likely due to

  18. Cost-effectiveness of sunitinib as second-line treatment for gastrointestinal stromal tumor in the People’s Republic of China

    Directory of Open Access Journals (Sweden)

    Li J

    2017-01-01

    Full Text Available Jian Li,1 Hong Ye Ren,2 Juanjuan Zhang,2 Peng Dong,2 Yan Wang,3 Andrea L Stevens,3 Yi Han,3 Min Huang4 1Laboratory of Carcinogenesis and Translational Research for the Ministry of National Education, Department of GI Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute, 2Pfizer Inc., Beijing, People’s Republic of China; 3WG Consulting, New York, NY, USA; 4School of Pharmacy, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China Objective: To evaluate the cost-effectiveness of sunitinib as a second-line treatment in patients with advanced gastrointestinal stromal tumors that no longer respond to imatinib 400 mg/d, compared with imatinib 600 mg/d, 800 mg/d, or best supportive care (BSC in the People’s Republic of China. Methods: This study was conducted from the government payer’s perspective with a time horizon of 5 years. Three health states were considered: progression-free survival, disease progression survival, and death, with a cycle length of 6 weeks. Probabilities of disease progression and death were estimated based on survival functions using exponential distribution and progression survival data in the clinical trials. Drug costs were based on drug retail prices and the patient assistance program in the People’s Republic of China, and adverse event management costs were based on published data and/or expert opinion. Uncertainties for parameters in the study were addressed through one-way deterministic and probabilistic sensitivity analysis. Results: When sunitinib was compared with imatinib 600 mg/d and BSC, the incremental cost-effectiveness ratio was RMB75,715 with RMB121,080 per quality-adjusted life-year (QALY gained. Sunitinib demonstrated lower costs and higher QALYs than imatinib 800 mg/d. In the probabilistic sensitivity analysis, the willingness-to-pay per QALY gained was set to be three times the per capita gross domestic product of the People’s Republic of

  19. Biomodulation with sequential intravenous IFN-alpha2b and 5-fluorouracil as second-line treatment in patients with advanced colorectal cancer.

    Science.gov (United States)

    Pérez, J E; Lacava, J A; Domínguez, M E; Rodríguez, R; Barbieri, M R; Romero Acuña, L A; Romero Acuña, J M; Langhi, M J; Amato, S; Marrone, N; Ortiz, E H; Leone, B A; Vallejo, C T; Machiavelli, M R; Romero, A O

    1998-08-01

    A phase II trial was carried out by the Grupo Oncologico Cooperativo del Sur (G.O.C.S.) to assess the efficacy and toxicity of a biochemical modulation of 5-fluorouracil (5-FU) by i.v. pretreatment with interferon (IFN)-alpha2b in patients with advanced colorectal carcinoma refractory to previous therapy with 5-FU modulated by methotrexate (MTX) or leucovorin (LV) or both. Between January 1993 and October 1995, 34 patients were entered on the study. The treatment was IFN-alpha2b 5 x 10(6)/m2 IU in a 1-h i.v. infusion, followed immediately by 5-FU 600 mg/m2 i.v. bolus injection. Courses were repeated weekly until observation of progressive disease or severe toxicity. One patient could not be assessed for response. Objective regression was observed in 2 of 33 patients (6%, 95% confidence interval, 0%-14%). No patient achieved a complete response. Two patients had partial responses (6%). No change was recorded in 14 patients (41%), and progressive disease occurred in 17 (52%). The median time to treatment failure was 3 months, and the median survival was 5 months. Toxicity was within acceptable limits. The main side effects were mucositis and diarrhea. Four episodes of grade 2 stomatitis were observed, causing dosage modifications. The most frequent toxic effects attributable to IFN-alpha2b were mild fatigue and fever. In conclusion, second-line therapy with i.v. IFN-alpha2b preceding 5-FU has shown an interesting profile of activity in a patient population with clearly unfavorable characteristics. From this perspective, further appropriately designed studies are needed to identify the greatest potential of IFN-alpha2b as a modulator of 5-FU.

  20. Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral and Second Line Anti-TB Treatment in Mumbai, India

    Science.gov (United States)

    Isaakidis, Petros; Varghese, Bhanumati; Mansoor, Homa; Cox, Helen S.; Ladomirska, Joanna; Saranchuk, Peter; Da Silva, Esdras; Khan, Samsuddin; Paryani, Roma; Udwadia, Zarir; Migliori, Giovanni Battista; Sotgiu, Giovanni; Reid, Tony

    2012-01-01

    in the urgently needed rapid scale-up of antiretroviral therapy and second-line anti-TB treatment. PMID:22792406

  1. Meta-analysis of published efficacy and safety data for docetaxel in second-line treatment of patients with advanced non-small-cell lung cancer.

    Science.gov (United States)

    Stroh, Mark; Green, Michelle; Cha, Edward; Zhang, Nancy; Wada, Russ; Jin, Jin

    2016-03-01

    To gain a better understanding of the impact of dose and other prognostic factors on safety and efficacy of docetaxel in second-line non-small-cell lung cancer patients. A model-based meta-analysis (MBMA) of a published docetaxel monotherapy data in 6085 second-line non-small-cell lung cancer patients from 46 trials was conducted. The logit of grade 3/4 neutropenia incidence was a linear function of dose, with a 5% increase in the odds of neutropenia per mg/m(2) increase in dose [odds ratio (OR) 1.05, 95% confidence interval (CI) 1.04-1.06], and a Japanese study effect (OR 17.1, 95% CI 6.05-48.4). The logit of overall response rate (ORR) was a linear function of cumulative dose (0.4% increase in the odds of response per mg/m(2) increase; OR 1.004, 95% CI 1.001-1.008) and median population age (OR 1.08 per year, 95% CI 1.02-1.15). A Japanese study effect was identified for overall survival (OS) in addition to prognostic factors identified by a previous meta-analysis. This current MBMA identified docetaxel dose-response relationships for both neutropenia and ORR, an effect of age on ORR, and Japanese study effects on both neutropenia and OS.

  2. Pre-treatment prediction of chemoresistance in second-line chemotherapy of ovarian carcinoma: value of serological tumor marker determination (tetranectin, YKL-40, CASA, CA 125)

    DEFF Research Database (Denmark)

    Grønlund, B; Høgdall, E V S; Christensen, Ib Jarle

    2006-01-01

    for the biochemical tumor markers tetranectin, YKL-40, CASA (cancer-associated serum antigen), and CA 125. The serum tumor marker levels at time of relapse were correlated with response status at landmark time after 4 cycles of second-line chemotherapy. Univariate and multivariate logistic regression analyses...... (OR 1.8; 95% CI: 1.0-3.3; p=0.045), and CASA (OR 1.8; 95% CI: 1.2-2.7; p=0.007) had predictive value for second-line chemoresistance, whereas serum CA 125 had no predictive value. In a multivariate logistic regression analysis, serum tetranectin and CASA both had independent predictive value...... for chemoresistance. The combined determination of tetranectin and CASA had a specificity of 90% with 33% sensitivity for the prediction of chemoresistance (area under the receiver operating characteristic curve = 0.78; 95% CI: 0.66-0.91; p=0.001). CONCLUSION: Low serum levels of tetranectin, or high serum levels...

  3. The use of anthracycline at first-line compared to alkylating agents or nucleoside analogs improves the outcome of salvage treatments after relapse in follicular lymphoma The REFOLL study by the Fondazione Italiana Linfomi.

    Science.gov (United States)

    Rossi, Giuseppe; Marcheselli, Luigi; Dondi, Alessandra; Bottelli, Chiara; Tucci, Alessandra; Luminari, Stefano; Arcaini, Luca; Merli, Michele; Pulsoni, Alessandro; Boccomini, Carola; Puccini, Benedetta; Micheletti, Moira; Martinelli, Giovanni; Rossi, Andrea; Zilioli, Vittorio Ruggero; Bozzoli, Valentina; Balzarotti, Monica; Bolis, Silvia; Cabras, Maria Giuseppina; Federico, Massimo

    2015-01-01

    Follicular lymphoma (FL) patients experience multiple remissions and relapses and commonly receive multiple treatment lines. A crucial question is whether anthracyclines should be used at first-line or whether they would be better "reserved" for relapse and whether FL outcome can be optimized by definite sequences of treatments. Randomized trials can be hardly designed to address this question. In this retrospective multi-institutional study, time-to-next-treatment after first relapse was analyzed in 510 patients who had received either alkylating agents- or anthracycline- or nucleoside analogs-based chemotherapy with/without rituximab at first-line and different second-line therapies. After a median of 42 months, median time-to-next-treatment after relapse was 41 months (CI95%:34-47 months). After adjustment for covariates, first-line anthracycline-based chemotherapy with/without rituximab was associated with better time-to-next-treatment after any salvage than alkylating agents-based chemotherapy with/without rituximab or nucleoside analogs-based chemotherapy with/without rituximab (HR:0.74, P = 0.027). The addition of rituximab to first-line chemotherapy had no significant impact (HR:1.22, P = 0.140). Autologs stem cell transplantation performed better than any other salvage treatment (HR:0.53, P < 0.001). First-line anthracycline-based chemotherapy significantly improved time-to-next-treatment even in patients receiving salvage autologs stem cell transplantation (P = 0.041). This study supports the concept that in FL previous treatments significantly impact on the outcome of subsequent therapies. The outcome of second-line treatments, either with salvage chemoimmunotherapy or with autologs stem cell transplantation, was better when an anthracycline-containing regimen was used at first-line. © 2014 Wiley Periodicals, Inc.

  4. A comparison of individualized treatment guided by VeriStrat with standard of care treatment strategies in patients receiving second-line treatment for advanced non-small cell lung cancer: A cost-utility analysis.

    Science.gov (United States)

    Nelson, Richard E; Stenehjem, David; Akerley, Wallace

    2013-12-01

    Two therapies are appropriate as 2nd-line treatment of non-small cell lung cancer (NSCLC) patients: chemotherapy and epidermal growth factor receptor (EGFR) inhibitor therapy. VeriStrat, a serum proteomic test, can be used to guide treatment decisions for NSCLC patients. The test classifies patients as likely to benefit from either of these two treatment options. The objective of this research was to model the anticipated survival and cost-effectiveness of four different treatment strategies: chemotherapy for all patients (C-all), EGFR inhibitor for all (E-all), a performance status guided selection strategy (PS-guided), and a strategy guided by VeriStrat test results (V-guided). We developed a Markov model with the perspective of the U.S. health care system. Model inputs were taken from published literature for the base-case analysis. One-way and probabilistic sensitivity analyses were performed. The C-all treatment strategy showed the best overall survival outcome (10.1 months), followed by V-guided (9.6 months), PS-guided (9.2 months), and E-all (8.2 months) strategies. The incremental cost-effectiveness ratio (ICER) of a V-guided treatment strategy was $91,111 (vs. E-all) and $8462 (vs. PS-guided) per quality-adjusted life year (QALY). The ICER for C-all compared to V-guided was $105,616. This cost-utility analysis indicates that a treatment strategy guided by the VeriStrat test in patients receiving second-line therapy for NSCLC may experience an overall survival benefit at an incremental cost-effectiveness ratio that is reasonable when compared with other practices, including cancer treatments, generally covered in the U.S. health care system. However, treating all patients with chemotherapy yielded the greatest expected survival. Copyright © 2013. Published by Elsevier Ireland Ltd.

  5. External and internal hemipelvectomy for sarcomas of the pelvic girdle : consequences of limb-salvage treatment

    NARCIS (Netherlands)

    Ham, SJ; Veth, RPH; van Horn, [No Value; Eisma, WH; Hoekstra, HJ; Schraffordt Koops, H.

    1997-01-01

    The outcome of different Limb-saving treatment modalities for pelvic girdle sarcoma is controversial. The oncological and functional results after 11 external and 10 internal hemipelvectomies and the consequences of limb-salvage treatment were studied in 21 consecutive patients with primary bone (19

  6. Second-line Treatment of Stage III/IV Non-Small-Cell Lung Cancer (NSCLC with pemetrexed in routine clinical practice: Evaluation of performance status and health-related quality of life

    Directory of Open Access Journals (Sweden)

    Schuette Wolfgang

    2012-01-01

    Full Text Available Abstract Background Second-line treatment of advanced non-small-cell lung cancer (NSCLC improves overall survival. There is a lack of data regarding the impact on patients' overall health condition. This prospective, non-interventional study evaluated performance status (PS and health-related quality of life (HR-QoL during second-line pemetrexed treatment in routine clinical practice. Methods Stage III/IV NSCLC patients who initiated second-line pemetrexed (standard vitamin and dexamethasone supplementation were observed for a maximum of 9 treatment cycles. The primary objective was to evaluate the proportion of patients achieving improvement of Karnofsky Index (KI of ≥ 10% (absolute or maintaining KI ≥ 80% after the second treatment cycle ("KI benefit response". HR-QoL was self-rated using the EuroQoL-5D questionnaire (EQ-5D. Factors potentially associated with KI benefit response were evaluated using logistic regression models. Results Of 521 eligible patients (73.5% Stage IV, median age 66.3 yrs, 36.1% ≥ 70 yrs, 62.0% with KI ≥ 80%, 471 (90.4% completed at least 2 treatment cycles. 58.0% (95%CI 53.6%;62.2% achieved KI benefit response after the second cycle. Patients with baseline KI ≥ 80%, no Grade 3/4 toxicities during the first 2 cycles, or combination regimen as prior first-line therapy were more likely to achieve a KI benefit response. EQ-5D scores improved over time. Grade 3/4 toxicities were reported in 23.8% of patients (mainly fatigue/asthenia 15.9%, neutropenia 8.7%. Conclusions In this large prospective, non-interventional study of second-line pemetrexed treatment in patients with advanced NSCLC, including 36% elderly patients ( ≥ 70 years, physician-rated PS and self-rated HR-QoL were maintained or improved in the majority of patients. Trial registration Registered on ClinicalTrials.gov (NCT00540241 on October 4, 2007

  7. Multidisciplinary ''limb salvage'' treatment of soft tissue and skeletal sarcomas

    International Nuclear Information System (INIS)

    Weisenburger, T.H.; Eilber, F.R.; Grant, T.T.; Morton, D.L.; Mirra, J.J.; Steinberg, M.; Rickles, D.

    1984-01-01

    The goal of treating primary bone and soft tissue tumors, as with most other malignancies, is to control the disease locally and systematically while preserving as much function as possible. For soft tissue sarcomas the results following radical excision and post-operative radiation therapy with preservation of the limb have equaled the control rates of amputation. However, local recurrence rates of approximately 25-30% are reported for high-grade lesions of the proximal lower extremity. Amputations provides excellent local control for osteosarcoma but the functional results may be less than optimal. In an attempt to achieve limb salvage for these tumors, a multidisciplinary protocol was developed using intra-arterial doxorubicin, pre-operative radiation therapy and limb-sparing radical wide excision followed by post-operative chemotherapy for presumed micro-metastatic disease

  8. Failure pattern and salvage treatment after radical treatment of head and neck cancer

    DEFF Research Database (Denmark)

    Pagh, Anja; Grau, Cai; Overgaard, Jens

    2016-01-01

    Purpose The aim of the study was to test the hypothesis that head and neck cancer (HNC) patients benefit from specialized follow-up (FU), as this strategy ensures timely detection of relapses for successful salvage treatment. This was done by evaluation of the pattern of failure, the temporal...... recordings of recurrent disease in 567 patients with primary tumors of the larynx, pharynx, oral cavity, nasal cavity, paranasal sinuses and salivary glands. A review of medical records was performed in order to update and supplement the database. Results Failures of the 567 patients were primarily in T...

  9. Efficacy of bendamustine and rituximab as first salvage treatment in chronic lymphocytic leukemia and indirect comparison with ibrutinib: a GIMEMA, ERIC and UK CLL FORUM study.

    Science.gov (United States)

    Cuneo, Antonio; Follows, George; Rigolin, Gian Matteo; Piciocchi, Alfonso; Tedeschi, Alessandra; Trentin, Livio; Medina Perez, Angeles; Coscia, Marta; Laurenti, Luca; Musuraca, Gerardo; Farina, Lucia; Rivas Delgado, Alfredo; Orlandi, Ester Maria; Galieni, Piero; Mauro, Francesca Romana; Visco, Carlo; Amendola, Angela; Billio, Atto; Marasca, Roberto; Chiarenza, Annalisa; Meneghini, Vittorio; Ilariucci, Fiorella; Marchetti, Monia; Molica, Stefano; Re, Francesca; Gaidano, Gianluca; Gonzalez, Marcos; Forconi, Francesco; Ciolli, Stefania; Cortelezzi, Agostino; Montillo, Marco; Smolej, Lukas; Schuh, Anna; Eyre, Toby A; Kennedy, Ben; Bowles, Kris M; Vignetti, Marco; de la Serna, Javier; Moreno, Carol; Foà, Robin; Ghia, Paolo

    2018-04-19

    We performed an observational study on the efficacy of bendamustine and rituximab as first salvage regimen in chronic lymphocytic leukemia. In an intention-to-treat analysis including 237 patients, the median progression free survival was 25 months. The presence of del(17p), unmutated IGHV and advanced stage were associated with a shorter progression free survival at multivariate analysis. The median time-to-next treatment was 31.3 months. Front-line treatment with a chemoimmunotherapy regimen was the only predictive factor for a shorter time to next treatment at multivariate analysis. The median overall survival was 74.5 months. Advanced Binet stage (i.e. III-IV or C) and resistant disease were the only parameters significantly associated with a shorter OS. Grade 3-5 infections were recorded in 6.3% of patients. A matched-adjusted indirect comparison with ibrutinib given second-line within named patient programs in the United Kingdom and in Italy was carried out with overall survival as objective endpoint. When restricting the analysis to patients with intact 17p who had received chemoimmunotherapy in first line, the overall survival did not differ between patients treated with ibrutinib (63% alive at 36 months) and patients treated with BR (74.4% alive at 36 months). BR is an efficacious first salvage regimen in chronic lymphocytic leukemia in a real-life population, including the elderly and unfit patients. BR and ibrutinib may be equally effective in terms of overall survival when used as first salvage treatment in patients without 17p deletion. ClinicalTrials.gov identifier: NCT02491398. Copyright © 2018, Ferrata Storti Foundation.

  10. Fotemustine as second-line treatment for recurrent or progressive glioblastoma after concomitant and/or adjuvant temozolomide: a phase II trial of Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).

    Science.gov (United States)

    Brandes, Alba A; Tosoni, A; Franceschi, E; Blatt, V; Santoro, A; Faedi, M; Amistà, P; Gardiman, M; Labianca, R; Bianchini, C; Ermani, M; Reni, M

    2009-09-01

    Standardized salvage treatment has not yet proved effective in glioblastoma multiforme (GBM) patients who receive prior standard radiotherapy plus concomitant and adjuvant temozolomide. Patients with progressive GBM after radiotherapy plus concomitant and/or adjuvant temozolomide received three-weekly doses (100-75 mg m(2)) of fotemustine followed, after a 5-week rest, by fotemustine (100 mg m(2)) every 3 weeks for nitrosourea activity. Moreover, this is the first study to evaluate correlation between MGMT promoter status and outcome of fotemustine for relapsing GBM previously treated with radiotherapy and temozolomide.

  11. Elucidation of salvage laryngectomy pathologic and clinical variables to guide further treatment intensification investigation.

    Science.gov (United States)

    Scharpf, Joseph; Ward, Matthew; Adelstein, David; Koyfman, Shlomo; Li, Mingsi

    2018-04-01

    There are limited treatment options beyond surgical salvage for patients who fail nonoperative treatment for laryngeal squamous cell carcinoma. In this study, we examine the failure patterns after surgical salvage and the potential pathologic and clinical prognostic variables that might guide further postoperative intensification investigation. Retrospective analysis at a tertiary academic referral center. From an institutional review board-approved institutional head and neck cancer registry, a consecutive series of 147 patients who underwent salvage laryngectomy for squamous cell cancer recurrence or persistence after radiotherapy with or without chemotherapy between May 1995 and May 2016 were identified. Variables potentially associated with oncologic outcome after surgical salvage were then collected and retrospectively evaluated. The projected 2-year locoregional failure rate was 21.8% (95% confidence interval [CI], 14.6%-29.0%]), and the overall survival 65% (95% CI, 57.5%-74.3%) for the entire cohort after salvage laryngectomy. On multivariable analysis, sarcomatoid/spindle cell pathology (hazard ratio [HR], 3.147; 95% CI, 1.181-8.386; P = 0.022), lymphovascular space invasion (LVSI) (positive vs. negative; HR, 2.31; 95% CI, 1.21-4.42; P = 0.011), and advanced initial American Joint Committee on Cancer 7th Edition grouped stage (stages III-IVB vs. stages I-II; HR, 1.64; 95% CI, 1.04-2.6; P = 0.035) were found to be independently associated with inferior disease-free survival. No other clinical or pathologic variables predicted failure. Salvage laryngectomy after nonoperative treatment failure results in successful locoregional control rates and survival in the majority of patients failing initial therapy. This should temper enthusiasm for routine treatment intensification with postoperative re-irradiation and/or other systemic treatments for the vast majority of patients. Sarcomatoid pathology, LVSI, and an advanced initial stage are associated with inferior

  12. Treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy for prostate cancer

    International Nuclear Information System (INIS)

    Wadasaki, Koichi; Kaneyasu, Yuko; Kenjo, Masahiro; Matsuura, Kanji; Murakami, Yuji; Hashimoto, Yasutoshi; Ito, Katsuhide; Kiriu, Hiroshi; Ito, Atsushi

    2007-01-01

    The indications for and the efficacy of radiation therapy after radical operation for patients with prostate cancer are not clear. We analyzed the treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy. Between September 1997 and November 2004, 57 patients received adjuvant radiotherapy or salvage radiotherapy after radical prostatectomy. Fifteen patients received radiation therapy because of positive margins and/or extracapsular invasion in surgical specimens (adjuvant group). Forty-two patients received radiation therapy because of rising prostate-specific antigen (PSA) during follow-up (salvage group). Radiation therapy was delivered to the fossa of the prostate±seminal vesicles by a three-dimensional (3-D) conformal technique to a total dose of 60-66 Gy (median, 60 Gy). Biochemical control was defined as the maintenance of a PSA level of less than 0.2 ng/ml. The median follow-up period after radiation therapy was 33 months (range, 12-98 months). Three-year biochemical control rates were 87% for the adjuvant group and 61% for the salvage group. For patients in the salvage group treated without hormone therapy, the preradiation PSA value was the most significant factor for the biochemical control rate. The 3-year biochemical control rate was 93% in patients whose preradiation PSA was 0.5 ng/ml or less and 29% in patients whose preradiation PSA was more than 0.5 ng/ml. No severe adverse effects (equal to or more than grade 3) were seen in treated patients. Radiation therapy after radical prostatectomy seemed to be effective for adjuvant therapy and for salvage therapy in patients with a preradiation PSA of 0.5 ng/ml or less. Also, radiation to the fossa of the prostate±seminal vesicles, to a total dose of 60-66 Gy, using a three-dimensional (3-D) conformal technique, seemed to be safe. (author)

  13. Ilfeld abduction orthosis is an effective second-line treatment after failure of Pavlik harness for infants with developmental dysplasia of the hip.

    Science.gov (United States)

    Sankar, Wudbhav N; Nduaguba, Afamefuna; Flynn, John M

    2015-02-18

    Closed reduction and spica casting is the most commonly recommended choice for infants with developmental dysplasia of the hip (DDH) for whom Pavlik harness treatment has failed, but it requires general anesthesia in addition to the challenges of spica cast care. The purposes of this study were to evaluate the effectiveness of Ilfeld bracing for infants for whom Pavlik harness treatment is unsuccessful and to compare these results with those for a similar cohort of patients directly undergoing closed reduction and spica casting. We reviewed the cases of a consecutive series of children with DDH who had failure of Pavlik harness treatment and were subsequently managed with Ilfeld bracing (the BR cohort) and compared this cohort with a similar historical group of infants who had failure of Pavlik harness treatment but had standard closed reduction and spica casting (the CR cohort). The cohorts were compared with respect to clinical and ultrasonographic data at the time of Pavlik discontinuation. At one year, the hip stability and acetabular index were assessed; the presence of osteonecrosis was graded according to the criteria described by Salter et al. Twenty-eight hips (nineteen infants) made up the BR cohort and twenty-two hips (sixteen infants) made up the CR cohort. Ultrasonographic indices (including the alpha angle and the percentage of femoral head coverage) were comparable between the two cohorts (p=0.66 and 0.19, respectively). Following treatment, a stable reduction was achieved in twenty-three (82%) of twenty-eight hips in the BR cohort compared with twenty (91%) of twenty-two hips in the CR cohort. At one year, acetabular indices were similar between both cohorts (mean and standard deviation, 27°±6° for the BR cohort versus 27°±5° for the CR cohort; p=0.62); however, osteonecrosis developed in three hips in the CR cohort compared with none in the BR cohort. In our series of infants with DDH for whom Pavlik harness treatment had failed, Ilfeld

  14. Influence of [18F] fluorodeoxyglucose positron emission tomography on salvage treatment decision making for locally persistent nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Zheng Xiaojang; Chen Longhua; Wang Quanshi; Wu Fubing

    2006-01-01

    Purpose: The purpose of this study was to evaluate the role of [ 18 F] fluorodeoxyglucose positron emission tomography (FDG-PET) in influencing salvage treatment decision making for locally persistent nasopharyngeal carcinoma (NPC). Methods and Materials: A total of 33 NPC patients with histologic persistence at nasopharynx 1 to 6 weeks after a full course of radiotherapy underwent both computed tomography (CT) and FDG-PET/CT simulation at the same treatment position. The salvage treatment decisions, with regard to the decision to offer salvage treatment and the definition of gross tumor volume (GTV), were made before knowledge of the FDG-PET findings. Subsequently the salvage treatment decisions were made again based on the FDG-PET findings and compared with the pre-FDG-PET decisions. Results: All 33 patients were referred for salvage treatment in the pre-FDG-PET decision. After knowledge of the FDG-PET results, the decision to offer salvage treatment was withdrawn in 4 of 33 patients (12.1%), as no abnormal uptake of FDG was found at nasopharynx. Spontaneous remission was observed in repeat biopsies and no local recurrence was found in these 4 cases. For the remaining 29 patients, GTV based on FDG-PET was smaller than GTV based on CT in 24 (82.8%) cases and was greater in 5 (17.2%) cases, respectively. The target volume had to be significantly modified in 9 of 29 patients (31%), as GTV based on FDG-PET images failed to be enclosed by the treated volume in the salvage treatment plan performed based on GTV based on CT simulation images. Conclusion: Use of FDG-PET was found to influence the salvage treatment decision making for locally persistent NPC by identifying patients who were not likely to benefit from additional treatment and by improving accuracy of GTV definition in salvage treatment planning

  15. Iodine-125 brachytherapy as upfront and salvage treatment for brain metastases. A comparative analysis

    Energy Technology Data Exchange (ETDEWEB)

    Romagna, Alexander; Schwartz, Christoph; Tonn, Joerg-Christian; Kreth, Friedrich-Wilhelm [Ludwig-Maximilians-University, Department of Neurosurgery, Munich (Germany); Egensperger, Rupert [Ludwig-Maximilians-University, Center for Neuropathology and Prion Research, Munich (Germany); Watson, Juliana; Belka, Claus; Nachbichler, Silke Birgit [Ludwig-Maximilians-University, Department of Radiation-Oncology, Munich (Germany)

    2016-11-15

    Outcome and toxicity profiles of salvage stereotactic ablative radiation strategies for recurrent pre-irradiated brain metastases are poorly defined. This study compared risk-benefit profiles of upfront and salvage iodine-125 brachytherapy (SBT) for small brain metastases. As the applied SBT treatment algorithm required histologic proof of metastatic brain disease in all patients, we additionally aimed to elucidate the value of biopsy before SBT. Patients with small untreated (n = 20) or pre-irradiated (n =28) suspected metastases intended for upfront or salvage SBT, respectively, were consecutively included. Temporary iodine-125 implants were used (median reference dose: 50 Gy, median dose rate: 15 cGy/h). Cumulative biologically effective doses (BED) were calculated and used for risk assessment. Treatment toxicity was classified according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria. Upfront SBT was initiated in 20 patients and salvage SBT in 23. In 5 patients, salvage SBT was withheld because of proven radiation-induced lesions. Treatment groups exhibited similar epidemiologic data except for tumor size (which was slightly smaller in the salvage group). One-year local/distant tumor control rates after upfront and salvage SBT were similar (94 %/65 % vs. 87 %/57 %, p = 0.45, respectively). Grade I/II toxicity was suffered by 2 patients after salvage SBT (cumulative BED: 192.1 Gy{sub 3} and 249.6 Gy{sub 3}). No toxicity-related risk factors were identified. SBT combines diagnostic yield with effective treatment in selected patients. The low toxicity rate in the salvage group points to protective radiobiologic characteristics of continuous low-dose rate irradiation. Upfront and salvage SBT are similarly effective and safe. Histologic reevaluation should be reconsidered after previous radiotherapy to avoid under- or overtreatment. (orig.) [German] Daten zu Risiko und Effizienz ablativer

  16. Everolimus plus exemestane versus bevacizumab-based chemotherapy for second-line treatment of hormone receptor-positive metastatic breast cancer in Greece: An economic evaluation study.

    Science.gov (United States)

    Kourlaba, Georgia; Rapti, Vasiliki; Alexopoulos, Athanasios; Relakis, John; Koumakis, Georgios; Chatzikou, Magdalini; Maniadakis, Nikos; Georgoulias, Vassilis

    2015-08-05

    The objective of our study was to conduct a cost-effectiveness (CE) study of combined everolimus (EVE) and exemestane (EXE) versus the common clinical practice in Greece for the treatment of postmenopausal women with HR+/HER2- advanced breast cancer (BC) progressing on nonsteroidal aromatase inhibitors (NSAI). The combinations of bevacizumab (BEV) plus paclitaxel (PACL) and BEV plus capecitabine (CAPE) were selected as comparators. A Markov model, consisting of three health states, was used to describe disease progression and evaluate the CE of the comparators from a third-party payer perspective over a lifetime horizon. Efficacy and safety data as well as utility values considered in the model were extracted from the relevant randomized Phase III clinical trials and other published studies. Direct medical costs referring to the year 2014 were incorporated in the model. A probabilistic sensitivity analysis was conducted to account for uncertainty and variation in the parameters of the model. Primary outcomes were patient survival (life-years), quality-adjusted life years (QALYs), total direct costs and incremental cost-effectiveness ratios (ICER). The discounted quality-adjusted survival of patients treated with EVE plus EXE was greater by 0.035 and 0.004 QALYs, compared to BEV plus PACL and BEV plus CAPE, respectively. EVE plus EXE was the least costly treatment in terms of drug acquisition, administration, and concomitant medications. The total lifetime cost per patient was estimated at €55,022, €67,980, and €62,822 for EVE plus EXE, BEV plus PACL, and BEV plus CAPE, respectively. The probabilistic analysis confirmed the deterministic results. Our results suggest that EVE plus EXE may be a dominant alternative relative to BEV plus PACL and BEV plus CAPE for the treatment of HR+/HER2- advanced BC patients failing initial therapy with NSAIs.

  17. Nintedanib in combination with docetaxel for second-line treatment of advanced non-small-cell lung cancer; GENESIS-SEFH drug evaluation report

    Directory of Open Access Journals (Sweden)

    María Espinosa Bosch

    2016-07-01

    Full Text Available Nintedanib is a triple angiokinase inhibitor that has been approved by the European Agency Medicines (EMA in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent non small cell lung cancer (NSCLC of adenocarcinoma tumour histology, after first-line chemotherapy. In LUME-Lung 1 clinical trial, the combination of nintedanib plus docetaxel vs. placebo plus docetaxel improved progression free survival (PFS in NSCLC patients, and improved overall survival in the population of adenocarcinoma patients, particularly in those with progression within 9 months after first line treatment initiation, median 10.9 months ( [95% CI 8.5–12.6] vs. 7.9 months [6.7–9.1]; HR 0.75 [95% CI 0.60–0.92], p=0.0073. The toxicity profile of the combination included a higher incidence of neutropenia, gastro-intestinal (GI disorders, and liver enzyme elevations; however, this did not cause a detrimental effect on patient quality of life. According to data from the clinical trial mentioned, the addition of nintedanib to docetaxel would lead to an estimated incremental cost-effectiveness ratio (ICER per year of life with PFS in the overall population of 134,274.47 € (notified price. In the adenocarcinoma population per each life of year gained (LYG, the ICER of adding nintedanib to docetaxel would be 40,886.14 €; while by implementing a sensitivity analysis with a 25% discount in the drug price, the cost per LYG would be 32,364.05 €, and would place it close to the threshold of cost-effectiveness usually considered acceptable in our setting. In view of efficacy and safety results the proposed positioning is to recommend its inclusion in the Hospital Formulary only for adult patients with metastatic or locally recurrent NSCLC with adenocarcinoma histology after first line chemotherapy, with progression < 9 months from the initiation of first line treatment, taking into account the inclusion and

  18. The Additional Costs per Month of Progression-Free Survival and Overall Survival: An Economic Model Comparing Everolimus with Cabozantinib, Nivolumab, and Axitinib for Second-Line Treatment of Metastatic Renal Cell Carcinoma.

    Science.gov (United States)

    Swallow, Elyse; Messali, Andrew; Ghate, Sameer; McDonald, Evangeline; Duchesneau, Emilie; Perez, Jose Ricardo

    2018-04-01

    When considering optimal second-line treatments for metastatic renal cell carcinoma (mRCC), clinicians and payers seek to understand the relative clinical benefits and costs of treatment. To use an economic model to compare the additional cost per month of overall survival (OS) and of progression-free survival (PFS) for cabozantinib, nivolumab, and axitinib with everolimus for the second-line treatment of mRCC from a third-party U.S. payer perspective. The model evaluated mean OS and PFS and costs associated with drug acquisition/administration; adverse event (AE) treatment; monitoring; and postprogression (third-line treatment, monitoring, and end-of-life costs) over 1- and 2-year horizons. Efficacy, safety, and treatment duration inputs were estimated from regimens' pivotal clinical trials; for everolimus, results were weighted across trials. Mean 1- and 2-year OS and mean 1-year PFS were estimated using regimens' reported OS and PFS Kaplan-Meier curves. Dosing and administration inputs were consistent with approved prescribing information and the clinical trials used to estimate efficacy and safety inputs. Cost inputs came from published literature and public data. Additional cost per additional month of OS or PFS was calculated using the ratio of the cost difference per treated patient and the corresponding difference in mean OS or PFS between everolimus and each comparator. One-way sensitivity analyses were conducted by varying efficacy and cost inputs. Compared with everolimus, cabozantinib, nivolumab, and axitinib were associated with 1.6, 0.3, and 0.5 additional months of PFS, respectively, over 1 year. Cabozantinib and nivolumab were associated with additional months of OS compared with everolimus (1 year: 0.7 and 0.8 months; 2 years: 1.6 and 2.3 months; respectively); axitinib was associated with fewer months (1 year: -0.2 months; 2 years: -0.7 months). The additional costs of treatment with cabozantinib, nivolumab, or axitinib versus everolimus over 1

  19. Amputations for extremity soft tissue sarcoma in an era of limb salvage treatment : Local control and survival

    NARCIS (Netherlands)

    Stevenson, Marc G; Musters, Annelie H; Geertzen, Jan H B; van Leeuwen, Barbara L; Hoekstra, Harald J; Been, Lukas B

    2018-01-01

    BACKGROUND: Despite multimodality limb salvage treatment (LST) for locally advanced extremity soft tissue sarcoma (ESTS), some patients still need an amputation. Indications for amputation and oncological outcome for these patients are described. METHODS: Between 1996 and 2016, all patients who

  20. Long-Term Outcomes After High-Dose Postprostatectomy Salvage Radiation Treatment

    International Nuclear Information System (INIS)

    Goenka, Anuj; Magsanoc, Juan Martin; Pei Xin; Schechter, Michael; Kollmeier, Marisa; Cox, Brett; Scardino, Peter T.; Eastham, James A.; Zelefsky, Michael J.

    2012-01-01

    Purpose: To review the impact of high–dose radiotherapy (RT) in the postprostatectomy salvage setting on long-term biochemical control and distant metastases–free survival, and to identify clinical and pathologic predictors of outcomes. Methods and Materials: During 1988–2007, 285 consecutive patients were treated with salvage RT (SRT) after radical prostatectomy. All patients were treated with either three-dimensional conformal RT or intensity-modulated RT. Two hundred seventy patients (95%) were treated to a dose ≥66 Gy, of whom 205 (72%) received doses ≥70 Gy. Eighty-seven patients (31%) received androgen-deprivation therapy as a component of their salvage treatment. All clinical and pathologic records were reviewed to identify treatment risk factors and response. Results: The median follow-up time after SRT was 60 months. Seven-year actuarial prostate-specific antigen (PSA) relapse-free survival and distant metastases–free survival were 37% and 77%, respectively. Independent predictors of biochemical recurrence were vascular invasion (p 0.4 ng/mL (p < 0.01), androgen-deprivation therapy (p = 0.03), Gleason score ≥7 (p = 0.02), and seminal vesicle involvement (p = 0.05). Salvage RT dose ≥70 Gy was not associated with improvement in biochemical control. A doubling time <3 months was the only independent predictor of metastatic disease (p < 0.01). There was a trend suggesting benefit of SRT dose ≥70 Gy in preventing clinical local failure in patients with radiographically visible local disease at time of SRT (7 years: 90% vs. 79.1%, p = 0.07). Conclusion: Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in patients with greater burden of disease at time of SRT as reflected by

  1. Long-Term Outcomes After High-Dose Postprostatectomy Salvage Radiation Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Goenka, Anuj; Magsanoc, Juan Martin; Pei Xin; Schechter, Michael; Kollmeier, Marisa; Cox, Brett [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Scardino, Peter T.; Eastham, James A. [Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Zelefsky, Michael J., E-mail: zelefskm@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2012-09-01

    Purpose: To review the impact of high-dose radiotherapy (RT) in the postprostatectomy salvage setting on long-term biochemical control and distant metastases-free survival, and to identify clinical and pathologic predictors of outcomes. Methods and Materials: During 1988-2007, 285 consecutive patients were treated with salvage RT (SRT) after radical prostatectomy. All patients were treated with either three-dimensional conformal RT or intensity-modulated RT. Two hundred seventy patients (95%) were treated to a dose {>=}66 Gy, of whom 205 (72%) received doses {>=}70 Gy. Eighty-seven patients (31%) received androgen-deprivation therapy as a component of their salvage treatment. All clinical and pathologic records were reviewed to identify treatment risk factors and response. Results: The median follow-up time after SRT was 60 months. Seven-year actuarial prostate-specific antigen (PSA) relapse-free survival and distant metastases-free survival were 37% and 77%, respectively. Independent predictors of biochemical recurrence were vascular invasion (p < 0.01), negative surgical margins (p < 0.01), presalvage PSA level >0.4 ng/mL (p < 0.01), androgen-deprivation therapy (p = 0.03), Gleason score {>=}7 (p = 0.02), and seminal vesicle involvement (p = 0.05). Salvage RT dose {>=}70 Gy was not associated with improvement in biochemical control. A doubling time <3 months was the only independent predictor of metastatic disease (p < 0.01). There was a trend suggesting benefit of SRT dose {>=}70 Gy in preventing clinical local failure in patients with radiographically visible local disease at time of SRT (7 years: 90% vs. 79.1%, p = 0.07). Conclusion: Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in

  2. Potential health gains for patients with metastatic renal cell carcinoma in daily clinical practice: A real-world cost-effectiveness analysis of sequential first- and second-line treatments.

    Directory of Open Access Journals (Sweden)

    S De Groot

    Full Text Available Randomised controlled trials have shown that targeted therapies like sunitinib are effective in metastatic renal cell carcinoma (mRCC. Little is known about the current use of these therapies, and their associated costs and effects in daily clinical practice. We estimated the real-world cost-effectiveness of different treatment strategies comprising one or more sequentially administered drugs.Analyses were performed using patient-level data from a Dutch population-based registry including patients diagnosed with primary mRCC from January 2008 to December 2010 (i.e., treated between 2008 and 2013. The full disease course of these patients was estimated using a patient-level simulation model based on regression analyses of the registry data. A healthcare sector perspective was adopted; total costs included healthcare costs related to mRCC. Cost-effectiveness was expressed in cost per life-year and cost per quality-adjusted life-year (QALY gained. Probabilistic sensitivity analysis was conducted to estimate the overall uncertainty surrounding cost-effectiveness.In current daily practice, 54% (336/621 of all patients was treated with targeted therapies. Most patients (84%; 282/336 received sunitinib as first-line therapy. Of the patients receiving first-line therapy, 30% (101/336 also received second-line therapy; the majority was treated with everolimus (40%, 40/101 or sorafenib (28%, 28/101. Current treatment practice (including patients not receiving targeted therapy led to 0.807 QALYs; mean costs were €58,912. This resulted in an additional €105,011 per QALY gained compared to not using targeted therapy at all. Forty-six percent of all patients received no targeted therapy; of these patients, 24% (69/285 was eligible for sunitinib. If these patients were treated with first-line sunitinib, mean QALYs would improve by 0.062-0.076 (where the range reflects the choice of second-line therapy. This improvement is completely driven by the health

  3. Proposed salvage treatment strategy for biochemical failure after radical prostatectomy in patients with prostate cancer: a retrospective study

    International Nuclear Information System (INIS)

    Miyake, Makito; Tanaka, Nobumichi; Asakawa, Isao; Morizawa, Yosuke; Anai, Satoshi; Torimoto, Kazumasa; Aoki, Katsuya; Yoneda, Tatsuo; Hasegawa, Masatoshi; Konishi, Noboru; Fujimoto, Kiyohide

    2014-01-01

    Treatment options for patients with recurrent disease after radical prostatectomy include salvage radiotherapy of the prostatic bed and/or androgen deprivation therapy. To establish an effective treatment strategy for recurrent disease after radical prostatectomy, we retrospectively analyzed the outcome of salvage radiation monotherapy in such cases. Data from 61 men who had undergone salvage radiation monotherapy for biochemical recurrent disease after radical prostatectomy were retrospectively reviewed. In all patients, salvage radiotherapy consisted of iraradiation to the prostatic bed (70 Gy) using three-dimensional conformal radiotherapy techniques. Treatment outcome was analyzed to identify predictive factors of salvage radiotherapy. The biochemical recurrence-free survival after salvage radiation monotherapy at 2 and 5 years was 55% and 38%, respectively. Cox proportional regression models revealed that the independent predictive factors for biochemical recurrence were Gleason Score ≥ 8, negative surgical margin, and PSA velocity ≥ 0.38 ng/mL/year. Negative surgical margin and PSA velocity ≥ 0.8 ng/mL/year were significantly associated with poor response in the serum PSA levels after salvage radiotherapy. Based on our findings, we propose a treatment strategy for biochemical recurrent disease after radical prostatectomy. Patients with Gleason score ≤ 7, positive surgical margin, and PSA velocity < 0.38 ng/mL/year are categorized the most favorable group, so that eradication by salvage radiation monotherapy could be expected. Other patients could be divided to two groups depending on surgical margin status and PSA velocity: 1) patients who might require combination of SRT and short-term androgen deprivation therapy and 2) patients who should be treated by androgen deprivation monotherapy

  4. Salvage robotic radical prostatectomy

    Directory of Open Access Journals (Sweden)

    Samuel D Kaffenberger

    2014-01-01

    Full Text Available Failure of non-surgical primary treatment for localized prostate cancer is a common occurrence, with rates of disease recurrence ranging from 20% to 60%. In a large proportion of patients, disease recurrence is clinically localized and therefore potentially curable. Unfortunately, due to the complex and potentially morbid nature of salvage treatment, radical salvage surgery is uncommonly performed. In an attempt to decrease the morbidity of salvage therapy without sacrificing oncologic efficacy, a number of experienced centers have utilized robotic assistance to perform minimally invasive salvage radical prostatectomy. Herein, we critically evaluate the existing literature on salvage robotic radical prostatectomy with a focus on patient selection, perioperative complications and functional and early oncologic outcomes. These results are compared with contemporary and historical open salvage radical prostatectomy series and supplemented with insights we have gained from our experience with salvage robotic radical prostatectomy. The body of evidence by which conclusions regarding the efficacy and safety of robotic salvage radical prostatectomy can be drawn comprises fewer than 200 patients with limited follow-up. Preliminary results are promising and some outcomes have been favorable when compared with contemporary open salvage prostatectomy series. Advantages of the robotic platform in the performance of salvage radical prostatectomy include decreased blood loss, short length of stay and improved visualization. Greater experience is required to confirm the long-term oncologic efficacy and functional outcomes as well as the generalizability of results achieved at experienced centers.

  5. Salvage treatment after r-interferon α-2a in advanced neuroendocrine tumors

    International Nuclear Information System (INIS)

    Zilembo, N.; Buzzoni, R.; Bajetta, E.; Di Bartolomeo, M.; De Braud, F.; Castellani, R.; Maffioli, L.; Celio, L.; Villa, E.; Lorusso, V.; Fosser, V.; Buzzi, F.

    1993-01-01

    The use of interferon (IFN) in neuroendocrine advanced tumors has achieved control of hormonal symptoms but low objective tumor response rate. In patients resistant to, or failing on, IFN a second line treatment may be required. Seventeen patients having received recombinant IFN α-2a as last treatment entered the study. There were 12 carcinoids, 3 medullary thyroid carcinomas, one Merkel cell carcinoma, and one neuroendocrine pancreatic tumor. Two different treatments were used: one radiometabolic therapy with metaiodobenzylguanidine (MIBG) in 3 patients with high MIBG uptake and one polychemotherapy regimen, including streptozotocin 500 mg/m 2 intravenously days 1, 2, 3 and epirubicin 75 mg/m 2 intravenously day 1, in the remaining 14 patients. Stable disease with relief of symptoms and tumor marker reduction was obtained in two patients receiving MIGB therapy, whereas the third patient had progressive disease. In the chemotherapy group only one partial response was obtained and neither tumor marker reduction nor subjective improvement were seen. Our second-line treatment was not especially effective but may be considered for rapidly progressive and/or symptomatic disease. The radiometabolic therapy appears promising in symptomatic patients with small tumor burden whereas our chemotherapy regimen appears ineffective. (orig.)

  6. Preliminary Experience in Treatment of Papillary and Macular Retinoblastoma: Evaluation of Local Control and Local Complications After Treatment With Linear Accelerator-Based Stereotactic Radiotherapy With Micromultileaf Collimator as Second-Line or Salvage Treatment After Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Pica, Alessia, E-mail: Alessia.Pica@chuv.ch [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland); Moeckli, Raphael [University Institute for Radiation Physics, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland); Balmer, Aubin [Department of Radiation Oncology, Jules Gonin Eye Hospital, Lausanne (Switzerland); Beck-Popovic, Maja [Unit of Pediatric Oncology, University of Lausanne, Lausanne (Switzerland); Chollet-Rivier, Madeleine [Department of Anesthesiology, University of Lausanne, Lausanne (Switzerland); Do, Huu-Phuoc [University Institute for Radiation Physics, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland); Weber, Damien C. [Department of Radiation Oncology, Geneva University Hospital, University of Geneva, Geneva (Switzerland); Munier, Francis L. [Department of Radiation Oncology, Jules Gonin Eye Hospital, Lausanne (Switzerland)

    2011-12-01

    Purpose: To determine the local control and complication rates for children with papillary and/or macular retinoblastoma progressing after chemotherapy and undergoing stereotactic radiotherapy (SRT) with a micromultileaf collimator. Methods and Materials: Between 2004 and 2008, 11 children (15 eyes) with macular and/or papillary retinoblastoma were treated with SRT. The mean age was 19 months (range, 2-111). Of the 15 eyes, 7, 6, and 2 were classified as International Classification of Intraocular Retinoblastoma Group B, C, and E, respectively. The delivered dose of SRT was 50.4 Gy in 28 fractions using a dedicated micromultileaf collimator linear accelerator. Results: The median follow-up was 20 months (range, 13-39). Local control was achieved in 13 eyes (87%). The actuarial 1- and 2-year local control rates were both 82%. SRT was well tolerated. Late adverse events were reported in 4 patients. Of the 4 patients, 2 had developed focal microangiopathy 20 months after SRT; 1 had developed a transient recurrence of retinal detachment; and 1 had developed bilateral cataracts. No optic neuropathy was observed. Conclusions: Linear accelerator-based SRT for papillary and/or macular retinoblastoma in children resulted in excellent tumor control rates with acceptable toxicity. Additional research regarding SRT and its intrinsic organ-at-risk sparing capability is justified in the framework of prospective trials.

  7. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    Energy Technology Data Exchange (ETDEWEB)

    Selle, F.; Gligorov, J. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France); Richard, S.; Khalil, A. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Alexandre, I. [Medical Oncology Department, Hospital Centre of Bligny, Briis-sous-Forges (France); Avenin, D.; Provent, S.; Soares, D.G. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Lotz, J.P. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France)

    2014-11-04

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

  8. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    International Nuclear Information System (INIS)

    Selle, F.; Gligorov, J.; Richard, S.; Khalil, A.; Alexandre, I.; Avenin, D.; Provent, S.; Soares, D.G.; Lotz, J.P.

    2014-01-01

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis

  9. Second Line of Defense Spares Program Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, Dale L.; Muller, George; Mercier, Theresa M.; Brigantic, Robert T.; Perkins, Casey J.; Cooley, Scott K.

    2012-11-20

    The Office of the Second Line of Defense (SLD) is part of the Department of Energy‘s (DOE) National Nuclear Security Administration (NNSA). The SLD Program accomplishes its critical global security mission by forming cooperative relationships with partner countries to install passive radiation detection systems that augment traditional inspection and law enforcement measures by alerting border officials to the presence of special nuclear or other radiological materials in cross-border traffic. An important tenet of the program is to work collaboratively with these countries to establish the necessary processes, procedures, infrastructure and conditions that will enable them to fully assume the financial and technical responsibilities for operating the equipment. As the number of operational deployments grows, the SLD Program faces an increasingly complex logistics process to promote the timely and efficient supply of spare parts.

  10. A Phase II Study of Weekly Docetaxel as Second-Line Chemotherapy in Patients With Metastatic Urothelial Carcinoma.

    Science.gov (United States)

    Kim, Young Saing; Lee, Soon Il; Park, Se Hoon; Park, Silvia; Hwang, In Gyu; Lee, Sang-Cheol; Sun, Jong-Mu; Lee, Jeeyun; Lim, Ho Yeong

    2016-02-01

    The present multicenter phase II study evaluated the efficacy and safety of weekly docetaxel as second-line chemotherapy for metastatic urothelial carcinoma. Weekly docetaxel was well tolerated but demonstrated modest activity, with a response rate of 6%, a median progression-free survival (PFS) of 1.4 months, and a median overall survival (OS) of 8.3 months. The dichotomy between PFS and OS was likely associated with subsequent platinum-based chemotherapy received by 58% of the patients. Docetaxel is commonly used for second-line therapy for metastatic urothelial carcinoma (UC). However, myelosuppression is a substantial concern when the traditional 3-week docetaxel cycle is used. The present multicenter phase II study evaluated the efficacy and safety of weekly docetaxel as second-line chemotherapy for metastatic UC. Patients with progression after previous platinum-based chemotherapy for advanced or metastatic disease were treated with docetaxel 30 mg/m(2) on days 1 and 8 every 21 days. The primary endpoint was the response rate. The study enrolled 31 patients. Their median age was 64 years (range, 40-79 years). An Eastern Cooperative Oncology Group performance status of 1, liver metastasis, and a hemoglobin level chemotherapy had been administered for metastatic disease in 29 patients (94%). Although fatigue (13%) and anorexia (6%) were the most frequently observed grade 3 to 4 toxicities, the safety profiles were generally mild and manageable. Two patients (6%) achieved an objective response, which was maintained for 3.0 to 7.8 months. Eight patients experienced disease stabilization (disease control rate, 32%). The median progression-free survival (PFS) and overall survival (OS) were 1.4 months (95% confidence interval [CI], 1.3-1.6) and 8.3 months (95% CI, 5.9-10.6), respectively. A relatively long OS was associated with further salvage platinum-based chemotherapy (n = 18, 58%) showing an encouraging activity (response rate, 44%; median PFS, 4.0 months

  11. Second Line of Defense Spares Program

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, Dale L.; Holmes, Aimee E.; Muller, George; Mercier, Theresa M.; Brigantic, Robert T.; Perkins, Casey J.; Cooley, Scott K.; Thorsen, Darlene E.

    2012-11-20

    During Fiscal Year 2012, a team from the Pacific Northwest National Laboratory (PNNL) conducted an assessment and analysis of the Second Line of Defense (SLD) Sustainability spare parts program. Spare parts management touches many aspects of the SLD Sustainability Program including contracting and integration of Local Maintenance Providers (LMP), equipment vendors, analyses and metrics on program performance, system state of health, and maintenance practices. Standardized spares management will provide better data for decisions during site transition phase and will facilitate transition to host country sustainability ownership. The effort was coordinated with related SLD Sustainability Program initiatives, including a configuration items baselining initiative, a metrics initiative, and a maintenance initiative. The spares study has also led to pilot programs for sourcing alternatives that include regional intermediate inventories and partnering agreements that leverage existing supply chains. Many partners from the SLD Sustainability program contributed to and were consulted in the course of the study. This document provides a description of the findings, recommendations, and implemented solutions that have resulted from the study.

  12. "Salvage microbiology": detection of bacteria directly from clinical specimens following initiation of antimicrobial treatment.

    Directory of Open Access Journals (Sweden)

    John J Farrell

    Full Text Available PCR coupled with electrospray ionization mass spectrometry (ESI-MS is a diagnostic approach that has demonstrated the capacity to detect pathogenic organisms from culture negative clinical samples after antibiotic treatment has been initiated. [1] We describe the application of PCR/ESI-MS for detection of bacteria in original patient specimens that were obtained after administration of antibiotic treatment in an open investigation analysis.We prospectively identified cases of suspected bacterial infection in which cultures were not obtained until after the initiation of antimicrobial treatment. PCR/ESI-MS was performed on 76 clinical specimens that were submitted for conventional microbiology testing from 47 patients receiving antimicrobial treatment.In our series, 72% (55/76 of cultures obtained following initiation of antimicrobial treatment were non-diagnostic (45 negative cultures; and 10 respiratory specimens with normal flora (5, yeast (4, or coagulase-negative staphylococcus (1. PCR/ESR-MS detected organisms in 83% (39/47 of cases and 76% (58/76 of the specimens. Bacterial pathogens were detected by PCR/ESI-MS in 60% (27/45 of the specimens in which cultures were negative. Notably, in two cases of relapse of prosthetic knee infections in patients on chronic suppressive antibiotics, the previous organism was not recovered in tissue cultures taken during extraction of the infected knee prostheses, but was detected by PCR/ESI-MS.Molecular methods that rely on nucleic acid amplification may offer a unique advantage in the detection of pathogens collected after initiation of antimicrobial treatment and may provide an opportunity to target antimicrobial therapy and "salvage" both individual treatment regimens as well as, in select cases, institutional antimicrobial stewardship efforts.

  13. Extracorporeal membrane oxygenation (ECMO as salvage treatment for pulmonary Echinococcus granulosus infection with acute cyst rupture

    Directory of Open Access Journals (Sweden)

    Sören L. Becker

    2017-11-01

    Full Text Available Extracorporeal membrane oxygenation (ECMO has been used successfully for the treatment of patients with respiratory failure due to severe infections. Although rare, parasites can also cause severe pulmonary disease. Tapeworms of the genus Echinococcus give rise to the development of cystic structures in the liver, lungs, and other organs. Acute cyst rupture leads to potentially life-threatening infection, and affected patients may deteriorate rapidly. The case of a young woman from Bulgaria who was admitted to hospital with severe dyspnoea, progressive chest pain, and haemoptysis is described. Computed tomography of the chest was pathognomonic for cystic echinococcosis with acute cyst rupture. Following deterioration on mechanical ventilation, she was cannulated for veno-venous ECMO. The patient’s condition improved considerably, and she was weaned successfully from ECMO and mechanical ventilation. Following lobectomy of the affected left lower lobe, the patient was discharged home in good condition. This appears to be the first report of the successful use of ECMO as salvage treatment for a severe manifestation of a helminthic disease. Due to recent migration to Western Europe, the number of patients presenting with respiratory failure due to pulmonary echinococcosis with cyst rupture is likely to increase. Keywords: Extracorporeal membrane oxygenation (ECMO, Infection, Echinococcosis, Echinococcus granulosus, Hydatid disease, Infection

  14. Salvage treatment for local or local-regional recurrence after initial breast conservation treatment with radiation for ductal carcinoma in situ

    NARCIS (Netherlands)

    Solin, Lawrence J.; Fourquet, Alain; Vicini, Frank A.; Taylor, Marie; Haffty, Bruce; Strom, Eric A.; Wai, Elaine; Pierce, Lori J.; Marks, Lawrence B.; Bartelink, Harry; Campana, Francois; McNeese, Marsha D.; Jhingran, Anuja; Olivotto, Ivo A.; Bijker, Nina; Hwang, Wei-Ting

    2005-01-01

    The present study evaluated the outcome of salvage treatment for women with local or local-regional recurrence after initial breast conservation treatment with radiation for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast. The study cohort consisted of

  15. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer.

    Science.gov (United States)

    Pérol, Maurice; Chouaid, Christos; Pérol, David; Barlési, Fabrice; Gervais, Radj; Westeel, Virginie; Crequit, Jacky; Léna, Hervé; Vergnenègre, Alain; Zalcman, Gérard; Monnet, Isabelle; Le Caer, Hervé; Fournel, Pierre; Falchero, Lionel; Poudenx, Michel; Vaylet, Fabien; Ségura-Ferlay, Céline; Devouassoux-Shisheboran, Mojgan; Taron, Miquel; Milleron, Bernard

    2012-10-01

    This phase III study investigated whether continuation maintenance with gemcitabine or switch maintenance with erlotinib improves clinical outcome compared with observation in patients with advanced non-small-cell lung cancer (NSCLC) whose disease was controlled after cisplatin-gemcitabine induction chemotherapy. Four hundred sixty-four patients with stage IIIB/IV NSCLC without tumor progression after four cycles of cisplatin-gemcitabine were randomly assigned to observation or to gemcitabine (1,250 mg/m(2) days 1 and 8 of a 3-week cycle) or daily erlotinib (150 mg/day) study arms. On disease progression, patients in all three arms received pemetrexed (500 mg/m(2) once every 21 days) as predefined second-line therapy. The primary end point was progression-free survival (PFS). PFS was significantly prolonged by gemcitabine (median, 3.8 v 1.9 months; hazard ratio [HR], 0.56; 95% CI, 0.44 to 0.72; log-rank P benefit was consistent across all clinical subgroups. Both maintenance strategies resulted in a nonsignificant improvement in overall survival (OS); patients who received second-line pemetrexed or with a performance status of 0 appeared to derive greater benefit. Exploratory analysis showed that magnitude of response to induction chemotherapy may affect the OS benefit as a result of gemcitabine maintenance. Maintenance gemcitabine and erlotinib were well tolerated with no unexpected adverse events. Gemcitabine continuation maintenance or erlotinib switch maintenance significantly reduces disease progression in patients with advanced NSCLC treated with cisplatin-gemcitabine as first-line chemotherapy. Response to induction chemotherapy may affect OS only for continuation maintenance.

  16. Bipolar hip arthroplasty as salvage treatment for loosening of the acetabular cup with significant bone defects

    Directory of Open Access Journals (Sweden)

    Ghanem, Mohamed

    2016-04-01

    Full Text Available Introduction: Revision arthroplasty of the hip is becoming increasingly important in recent years. Early primary arthroplasty and longer life expectancy of the patients increases the number of revision surgery. Revision surgery of hip arthroplasty is major surgery for the patients, especially the elderly, with significant risks concerning the general condition of the patient. The aim of this work is to evaluate the outcome of bipolar hip arthroplasty as a salvage procedure for treatment of loosening of the acetabular cup with significant acetabular bone defects after total hip replacement (THR in multi-morbid patients.Patients and methods: During the period from January 1 2007 to December 31 2011 19 revision hip surgeries were performed in , in which the loosened acetabular cup was replaced by a bipolar head. The examined patient group consisted exclusively of female patients with an average of 75 years. The predominant diagnosis was “aseptic loosening” (84.2%. All patients in our study were multi-morbid. We decided to resort to bipolar hip arthroplasty due to the compromised general condition of patients and the major acetabular bone defects, which were confirmed intraoperatively. The postoperative follow-up ranged from 0.5 to 67 months (average 19.1 months. Results: Evaluation of the modified Harris Hip Score showed an overall improvement of the function of the hip joint after surgery of approximately 45%.Surgery was less time consuming and thus adequate for patients with significantly poor general health condition. We noticed different complications in a significant amount of patients (68.4%. The most common complication encountered was the proximal migration of the bipolar head.The rate of revision following the use of bipolar hip arthroplasty in revision surgery of the hip in our patients was high (21%. Despite the high number of complications reported in our study, we have noticed significant improvement of hip joint function as well

  17. Salvage Treatment With Hypofractionated Radiotherapy in Patients With Recurrent Small Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Bae, Sun Hyun; Park, Hee Chul; Lim, Do Hoon; Lee, Jung Ae; Gwak, Geum Yeon; Choi, Moon Seok; Lee, Joon Hyoek; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul

    2012-01-01

    Purpose: To investigate the rates of tumor response and local control in patients with recurrent small hepatocellular carcinoma (HCC) treated with hypofractionated radiotherapy (RT) as a salvage treatment and to evaluate treatment-related toxicities. Methods and Materials: Between 2006 and 2009, a total of 20 patients with recurrent small HCC were treated with hypofractionated RT after the failure of previous treatment. The eligibility criteria for hypofractionated RT were as follows: 1) HCC less than 5 cm, 2) HCC not adjacent to critical organs, 3) HCC without portal vein tumor thrombosis, and 4) less than 15% of normal liver volume that would be irradiated with 50% of prescribed dose. The RT dose was 50 Gy in 10 fractions. The tumor response was determined by CT scans performed 3 months after the end of RT. Results: The median follow-up period after RT was 22 months. The overall survival rates at 1 and 2 years were 100% and 87.9%, respectively. Complete response (CR) was achieved in seven of 20 lesions (35%) evaluated by CT scans performed 3 months after the end of RT. In-field local control was achieved in 85% of patients. Fourteen patients (70%) developed intra-hepatic metastases. Six patients developed grade 1 nausea or anorexia during RT, and two patients had progression of ascites after RT. There was no grade 3 or greater treatment-related toxicities. Conclusions: The current study showed a favorable outcome with respect to hypofractionated RT for small HCC. Partial liver irradiation with 50 Gy in 10 fractions is considered tolerable without severe complications.

  18. Salvage Treatment With Hypofractionated Radiotherapy in Patients With Recurrent Small Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Sun Hyun [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Park, Hee Chul, E-mail: rophc@skku.edu [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lim, Do Hoon; Lee, Jung Ae [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Gwak, Geum Yeon; Choi, Moon Seok; Lee, Joon Hyoek; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul [Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-03-15

    Purpose: To investigate the rates of tumor response and local control in patients with recurrent small hepatocellular carcinoma (HCC) treated with hypofractionated radiotherapy (RT) as a salvage treatment and to evaluate treatment-related toxicities. Methods and Materials: Between 2006 and 2009, a total of 20 patients with recurrent small HCC were treated with hypofractionated RT after the failure of previous treatment. The eligibility criteria for hypofractionated RT were as follows: 1) HCC less than 5 cm, 2) HCC not adjacent to critical organs, 3) HCC without portal vein tumor thrombosis, and 4) less than 15% of normal liver volume that would be irradiated with 50% of prescribed dose. The RT dose was 50 Gy in 10 fractions. The tumor response was determined by CT scans performed 3 months after the end of RT. Results: The median follow-up period after RT was 22 months. The overall survival rates at 1 and 2 years were 100% and 87.9%, respectively. Complete response (CR) was achieved in seven of 20 lesions (35%) evaluated by CT scans performed 3 months after the end of RT. In-field local control was achieved in 85% of patients. Fourteen patients (70%) developed intra-hepatic metastases. Six patients developed grade 1 nausea or anorexia during RT, and two patients had progression of ascites after RT. There was no grade 3 or greater treatment-related toxicities. Conclusions: The current study showed a favorable outcome with respect to hypofractionated RT for small HCC. Partial liver irradiation with 50 Gy in 10 fractions is considered tolerable without severe complications.

  19. Survival predictors for second-line chemotherapy in Caucasian patients with metastatic gastric cancer

    OpenAIRE

    Bohanes, Pierre; Courvoisier, Delphine; Perneger, Thomas; Morel, Philippe; Huber, Olivier; Roth, Arnaud

    2011-01-01

    There are very limited data suggesting a benefit for second-line chemotherapy in advanced gastric cancer. Therefore, the number of patients who receive further treatment after failure of first-line chemotherapy varies considerably, ranging from 14% to 75%. In the absence of a demonstrated survival benefit of second-line chemotherapy, appropriate selection of patients based on survival predictors is essential. However, no clinico-pathologic parameters are currently widely adopted in clinical p...

  20. Non-Hodgkin's lymphoma - Part II: Management of primary extranodal lymphomas, generalized disease and salvage treatment

    International Nuclear Information System (INIS)

    Gospodarowicz, Mary K.; Sutcliffe, Simon B.

    1996-01-01

    Objective: To review the approach to the diagnosis, classification, assessment, treatment and continuing management of patients with primary extranodal non-Hodgkin's lymphoma, and the management of generalized disease with the emphasis on the current role of salvage treatment with high dose chemotherapy and stem cell/bone marrow support strategies. Non-Hodgkin's lymphoma may involve any part of the body. Many lymphomas, such as MALT, angiocentric T-cell, etc., commonly present in extranodal sites. Lymphomas presenting in the GI tract, and head and neck, are most common with the single most common site being the stomach. Gastric lymphoma is associated with Helicobacter pylorii and is most common in areas endemic for Helicobacter pylorii infection. Recent advances in the understanding of the etiology of gastric MALT, thyroid, and intestinal lymphomas present new opportunities for the application of novel therapeutic approaches e.g. antibiotic therapy for Helicobacter pylori and early stage IPSID. Lymphomas presenting in the orbit, thyroid, breast, bone, extradural and skin are of interest because of the importance of expert RT in securing local control. Primary brain lymphomas present a particular challenge to the radiation oncologist. Although localized, primary brain lymphomas are extremely difficult to control. Rare sites of extranodal lymphoma include testis, female genital tract, and lung. Extranodal lymphomas are often localized and cure with RT or CMT is possible. They represent a assorted group of diseases with diverse presentations, prognosis, sensitivity to RT and expected outcome. They are of particular importance to radiation oncologists as they require special attention to patterns of spread and treatment planning. The principles of management of primary extranodal lymphoma, however, follow those applicable to localized nodal presentations. Although primary extranodal lymphomas are highly curable, a proportion of patients will fail with disseminated

  1. Effectiveness of tipranavir versus darunavir as a salvage therapy in HIV-1 treatment-experienced patients.

    Science.gov (United States)

    Domínguez-Hermosillo, Juan Carlos; Mata-Marin, José Antonio; Herrera-González, Norma Estela; Chávez-García, Marcelino; Huerta-García, Gloria; Nuñez-Rodríguez, Nohemí; García-Gámez, José Gerardo; Jiménez-Romero, Anai; Gaytán-Martínez, Jesús Enrique

    2016-09-30

    Although both tipranavir (TPV) and darunavir (DRV) represent important options for the management of patients with multi-protease inhibitor (PI)-resistant human immunodeficiency virus (HIV), currently there are no studies comparing the effectiveness and safety of these two drugs in the Mexican population. The aim of this study was to compare the effectiveness of TPV versus DRV as a salvage therapy in HIV-1 treatment-experienced patients. This was a comparative, prospective, cohort study. Patients with HIV and triple-class drug resistance evaluated at the Hospital de Infectología "La Raza", National Medical Center, were included. All patients had the protease and retrotranscriptase genotype; resistance mutation interpretation was done using the Stanford database. A total of 35 HIV-1 triple-class drug-resistant patients were analyzed. All of them received tenofovir and raltegravir, 22 received darunavir/ritonavir (DRV/r), and 13 received tipranavir/ritonavir (TPV/r) therapies. The median baseline RNA HIV-1 viral load and CD4+ cell count were 4.34 log (interquartile range [IQR], 4.15-4.72) and 267 cells/mm3 (IQR, 177-320) for the DRV/r group, and 4.14 log (IQR, 3.51-4.85) and 445 cells/mm3 (IQR, 252-558) for the TPV/r group. At week 24 of treatment, 91% of patients receiving DRV/r and 100% of patients receiving TPV/r had an RNA HIV-1 viral load HIV-1 patients who were highly experienced in antiretroviral therapy.

  2. A randomized, double-blind, phase III study comparing two doses of erlotinib for second-line treatment of current smokers with advanced non-small-cell lung cancer (CurrentS).

    Science.gov (United States)

    Smit, Egbert F; Wu, Yi-Long; Gervais, Radj; Zhou, Caicun; Felip, Enriqueta; Feng, Jifeng; Guclu, Salih Zeki; Hoiczyk, Mathias; Dorokhova, Elena; Freudensprung, Ulrich; Grange, Susan; Perez-Moreno, Pablo Diego; Mitchell, Lada; Reck, Martin

    2016-09-01

    Active smokers with non-small-cell lung cancer (NSCLC) have increased erlotinib metabolism versus non-smoking patients, which reduces exposure. Therefore, an increased erlotinib dose may be beneficial. The CurrentS study (NCT01183858) assessed efficacy and safety of 300mg erlotinib (E300) as second-line therapy in current smokers with locally advanced or metastatic NSCLC versus the standard 150mg dose (E150). Patients with stage IIIB/IV NSCLC (current smokers who failed first-line platinum-based chemotherapy) were randomized to receive E150 or E300 until progression/death/unacceptable toxicity. progression-free survival (PFS). Secondary endpoints: overall survival (OS), disease control rate and safety. A total of 342 patients were screened; the intent-to-treat population comprised 159 E300 patients and 154 E150 patients. Median PFS was 7.0 versus 6.9 weeks with E300 versus E150, respectively (unstratified hazard ratio [HR]=1.05, 95% confidence interval [CI]: 0.83-1.33; unstratified log-rank P=0.671). Median OS was 6.8 months in both arms (unstratified HR=1.03, 95% CI: 0.80-1.32; unstratified log-rank P=0.846). Overall, 89.2% (E300 arm) and 84.4% (E150 arm) experienced ≥1 adverse event (AE) of any grade (44.3% and 37%, respectively, experienced grade ≥3 AEs); AEs of special interest were reported in 67.7% and 47.4% of patients, respectively. E300 resulted in higher mean plasma concentrations versus E150, however, this did not improve efficacy. Despite the difference in erlotinib exposure, there was no evidence of an incremental efficacy benefit of a higher erlotinib dose versus the standard dose in this population of highly active smokers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Effect of post-fire salvage logging treatments on micobiological properties of two different soils in the Povince of Alicante.

    Science.gov (United States)

    Arcenegui, Victoria

    2017-04-01

    It is well known that the natural wildfire regime in Mediterranean forests is greatly disturbed by human activities. Fire can induce temporal or permanent changes in the soil (see Certini, 2005) and can retard or compromise the recovery of the ecosystem afterwards. Changes in soil properties and the impact on soil functions depend mainly on the severity of the fires (Neary et al., 1999) and type of soil and weather during and after burning (Robichaud & Hungerford, 2000). Post-fire management can have an additional impact on the ecosystem; in some cases, even more severe than the fire. Post-fire salvage logging treatments are very frequently but its ecological impact is uncertain. Mainly because there are so many variables at play. A research has been done in "Sierra de Mariola Natural Park" in Alcoi (M) and ''Cabo de San Antonio'' in Javea (J), both in the Province of Alicante (E Spain). A big forest fire (>500 has) occurred in July 2012 and in September 2014 respectively. After fire, salvage logging (SL) treatment were done. In the first area (M), with a soil classified as Typic Xerorthent, extraction of the burned wood using heavy machinery was applied. In contrast, in the second area (J), a Rhodoxeralf soil, not heavy machinery was used. Plots for monitoring this effect were installed in both areas and in a similar nearby area where no treatment was done, and then used as control (C) for comparison. Soil samplings were done immediately after treatment and 4 years and two years in M site and J site respectively. We examined the effect of salvage logging on basal soil respiration (BSR), and microbial biomass carbon (Cmic). Our results showed that in site M four years after the treatment, the plots without treatment showed a much better improvement for the properties monitored. And not differences were found in site J after two years of monitoring. The impact of salvage logging was different depending on the soil type and the way to do the treatment.

  4. Systemic Chemotherapy as Salvage Treatment for Locally Advanced Rectal Cancer Patients Who Fail to Respond to Standard Neoadjuvant Chemoradiotherapy.

    Science.gov (United States)

    Sclafani, Francesco; Brown, Gina; Cunningham, David; Rao, Sheela; Tekkis, Paris; Tait, Diana; Morano, Federica; Baratelli, Chiara; Kalaitzaki, Eleftheria; Rasheed, Shahnawaz; Watkins, David; Starling, Naureen; Wotherspoon, Andrew; Chau, Ian

    2017-06-01

    The potential of chemotherapy as salvage treatment after failure of neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC) has never been explored. We conducted a single-center, retrospective analysis to address this question. Patients with newly diagnosed LARC who were inoperable or candidates for extensive (i.e., beyond total mesorectal excision [TME]) surgery after long-course chemoradiotherapy and who received salvage chemotherapy were included. The primary objective was to estimate the proportion of patients who became suitable for TME after chemotherapy. Forty-five patients were eligible (39 candidates for extensive surgery and 6 unresectable). Previous radiotherapy was given concurrently with chemotherapy in 43 cases (median dose: 54.0 Gy). Oxaliplatin- and irinotecan-based salvage chemotherapy was administered in 40 (88.9%) and 5 (11.1%) cases, respectively. Eight patients (17.8%) became suitable for TME after chemotherapy, 10 (22.2%) ultimately underwent TME with clear margins, and 2 (4.4%) were managed with a watch and wait approach. Additionally, 13 patients had extensive surgery with curative intent. Three-year progression-free survival and 5-year overall survival in the entire population were 30.0% (95% confidence interval [CI]: 15.0-46.0) and 44.0% (95% CI: 26.0-61.0), respectively. For the curatively resected and "watch and wait" patients, these figures were 52.0% (95% CI: 27.0-73.0) and 67.0% (95% CI: 40.0-84.0), respectively. Systemic chemotherapy may be an effective salvage strategy for LARC patients who fail to respond to chemoradiotherapy and are inoperable or candidates for beyond TME surgery. According to our study, one out of five patients may become resectable or be spared from an extensive surgery after systemic chemotherapy. High-quality evidence to inform the optimal management of rectal cancer patients who are inoperable or candidates for beyond total mesorectal excision surgery following standard chemoradiotherapy is

  5. Perceived adherence barriers among patients failing second-line ...

    African Journals Online (AJOL)

    Perceived adherence barriers among patients failing second-line antiretroviral therapy in Khayelitsha, South Africa. W Barnett, G Patten, B Kerschberger, K Conradie, DB Garone, G van Cutsem, CJ Colvin ...

  6. Health-related quality of life after salvage high-intensity focused ultrasound (HIFU) treatment for locally radiorecurrent prostate cancer

    International Nuclear Information System (INIS)

    Berge, V.; Baco, E.; Dahl, A.A.; Karlsen, S.J.

    2011-01-01

    The objective of this study was to evaluate health-related quality of life (HRQOL) after salvage high-intensity focused ultrasound (HIFU) for locally radiorecurrent prostate cancer (PCa). Since June 2006 we have treated 61 patients consecutively by salvage HIFU. All patients were offered the University of California, Los Angeles Prostate Cancer Index (UCLA-PCI) questionnaire at baseline and at follow-up. Scores ranged from 0 (worst) to 100 (best). Clinically significant changes were defined as a minimum difference of 10 points between the baseline score and the score at follow-up. Fifty-seven patients (93%) had evaluable data at baseline, compared with 46 (75%) after treatment. The mean time lapse between HIFU treatment and questionnaire response was 17.5 months (range 6-29 months). The mean score for urinary function decreased from 79.7±12.1 prior to HIFU to 67.4±17.8 after HIFU (P<0.001). The mean score for sexual function decreased from 32.1±24.1 prior to HIFU to 17.2±17.0 after HIFU (P<0.001). There were no significant effects on bowel function. There was a significant reduction in the mean score for Physical HRQOL, but the mean score for Mental HRQOL was did not change significantly. Treatment of localized radiorecurrent PCa by salvage HIFU is associated with clinically significant reductions in urinary and sexual function domains after a mean follow-up of 17.5 months. (author)

  7. Single-Stage Treatment of Osteomyelitis for Digital Salvage by Using an Antibiotic-Eluting, Methylmethacrylate Joint-Spanning Spacer.

    Science.gov (United States)

    Aimé, Victoria L; Kidwell, John T; Webb, Leland H

    2017-06-01

    Osteomyelitis of the digit is a challenging problem that can result in amputation. We describe 13 cases of osteomyelitis involving bones of the hand managed with a novel technique. We reviewed records of 12 patients (13 digits) who had joint-spanning, antibiotic-eluting (tobramycin or vancomycin), methylmethacrylate spacers placed as definitive, single-stage treatment for digital osteomyelitis. The primary outcome was digit salvage. Secondary outcomes were infection eradication (no recurrence at 3 months) and spacer removal. Patients were followed up until the infection resolved (ie, no cutaneous signs of infection, including pain, erythema, or swelling). At a mean of 24 months, 10 of 13 infections had successful one-stage treatment. One patient required a second operation to revise a soft tissue flap but the spacer remained in place. Two spacers were removed because of malalignment. An antibiotic-eluting methylmethacrylate spacer is an innovative treatment for digital osteomyelitis. In 12 consecutive patients (13 digits), we successfully salvaged the digit. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  8. LHRH analogue as a depot preparation (Zoladex) in the treatment of advanced carcinoma of the prostate followed by orchiectomy as a second line therapy--a phase II study

    DEFF Research Database (Denmark)

    Iversen, P; Rose, C; Stage, J G

    1989-01-01

    in 68% of the patients. During treatment, serum testosterone was in the castrate range in all patients except five. Possible explanations for this escape phenomenon are discussed. No toxicity was observed and treatment was well tolerated in all patients. Thirty-two patients underwent bilateral...

  9. Long-term results of salvage radiotherapy for the treatment of recurrent cervical carcinoma after prior surgery

    International Nuclear Information System (INIS)

    Haasbeek, Cornelis J.A.; Uitterhoeve, Apollonia L.J.; Velden, Jacobus van der; Gonzalez, Dionisio Gonzalez; Stalpers, Lukas J.A.

    2008-01-01

    Abstarct: Background and purpose: Tumor recurrence after surgery for cervical carcinoma is associated with high fatality and morbidity, forming a major therapeutic challenge. This paper presents our experience with treatment of this patient group by salvage radiotherapy with curative intent. Materials and methods: Thirty-five patients with a pelvic recurrence after hysterectomy received high-dose radiotherapy. A retrospective analysis of long-term outcome and prognostic factors was performed. Results: After a median follow-up period of 12.1 years, actuarial 2-,5- and 10-year overall survival rates were 66%, 43% and 33%; disease-free survival rates were 62%, 45% and 41%, respectively. Pelvic control rates at 2-,5- and 10-years were 77%, 69% and 62%. Unfavorable prognostic factors on univariate analysis for survival were: recurrence extending to the pelvic wall versus central recurrence, early recurrence after surgery, external boost versus brachytherapy boost, low total dose and high age. Only a brachytherapy boost and a long interval between surgery and recurrence were significant on multivariate analysis. Severe complications (≥grade 3) were seen in 6 patients (17%; actuarial after 5 years, 21%). Conclusions: Salvage radiotherapy for recurrent cervical carcinoma following surgery may result in 40-50% long-term disease-free survival and an acceptable risk of severe treatment complications, even in patient with recurrences extending to the pelvic wall

  10. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1)

    DEFF Research Database (Denmark)

    Machiels, Jean-Pascal H; Haddad, Robert I; Fayette, Jérôme

    2015-01-01

    BACKGROUND: Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (HNSCC) progressing after first-line platinum regimens have a poor prognosis and few treatment options. Afatinib, an irreversible ERBB family blocker, has shown efficacy in a phase 2 study in this setting......%]), and neutropenia (1 [... provide important new insights into the treatment of this patient population and support further investigations with irreversible ERBB family blockers in HNSCC. FUNDING: Boehringer Ingelheim....

  11. Rill erosion in burned and salvage logged western montane forests: Effects of logging equipment type, traffic level, and slash treatment

    Science.gov (United States)

    Wagenbrenner, J. W.; Robichaud, P. R.; Brown, R. E.

    2016-10-01

    Following wildfires, forest managers often consider salvage logging burned trees to recover monetary value of timber, reduce fuel loads, or to meet other objectives. Relatively little is known about the cumulative hydrologic effects of wildfire and subsequent timber harvest using logging equipment. We used controlled rill experiments in logged and unlogged (control) forests burned at high severity in northern Montana, eastern Washington, and southern British Columbia to quantify rill overland flow and sediment production rates (fluxes) after ground-based salvage logging. We tested different types of logging equipment-feller-bunchers, tracked and wheeled skidders, and wheeled forwarders-as well as traffic levels and the addition of slash to skid trails as a best management practice. Rill experiments were done at each location in the first year after the fire and repeated in subsequent years. Logging was completed in the first or second post-fire year. We found that ground-based logging using heavy equipment compacted soil, reduced soil water repellency, and reduced vegetation cover. Vegetation recovery rates were slower in most logged areas than the controls. Runoff rates were higher in the skidder and forwarder plots than their respective controls in the Montana and Washington sites in the year that logging occurred, and the difference in runoff between the skidder and control plots at the British Columbia site was nearly significant (p = 0.089). Most of the significant increases in runoff in the logged plots persisted for subsequent years. The type of skidder, the addition of slash, and the amount of forwarder traffic did not significantly affect the runoff rates. Across the three sites, rill sediment fluxes were 5-1900% greater in logged plots than the controls in the year of logging, and the increases were significant for all logging treatments except the low use forwarder trails. There was no difference in the first-year sediment fluxes between the feller

  12. Absolute lymphocyte count predicts response to rituximab-containing salvage treatment for relapsed/refractory B-cell non-Hodgkin's lymphoma with prior rituximab exposure

    Directory of Open Access Journals (Sweden)

    Man-Hsin Hung

    2013-04-01

    Conclusion: Our study results show that for patients with relapsed/refractory B-cell NHL, rituximab-containing salvage treatment is feasible and generally tolerable. A high ALC-R value was significantly associated with a better response to this treatment.

  13. Second-line systemic therapy for metastatic colorectal cancer.

    Science.gov (United States)

    Mocellin, Simone; Baretta, Zora; Roqué I Figuls, Marta; Solà, Ivan; Martin-Richard, Marta; Hallum, Sara; Bonfill Cosp, Xavier

    2017-01-27

    The therapeutic management of people with metastatic colorectal cancer (CRC) who did not respond to first-line treatment represents a formidable challenge. To determine the efficacy and toxicity of second-line systemic therapy in people with metastatic CRC. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 4), Ovid MEDLINE (1950 to May 2016), Ovid MEDLINE In-process & Other Non-Indexed Citations (1946 to May 2016) and Ovid Embase (1974 to May 2016). There were no language or date of publication restrictions. Randomized controlled trials (RCTs) assessing the efficacy (survival, tumour response) and toxicity (incidence of severe adverse effects (SAEs)) of second-line systemic therapy (single or combined treatment with any anticancer drug, at any dose and number of cycles) in people with metastatic CRC that progressed, recurred or did not respond to first-line systemic therapy. Authors performed a descriptive analysis of each included RCT in terms of primary (survival) and secondary (tumour response, toxicity) endpoints. In the light of the variety of drug regimens tested in the included trials, we could carry out meta-analysis considering classes of (rather than single) anticancer regimens; to this aim, we applied the random-effects model to pool the data. We used hazard ratios (HRs) and risk ratios (RRs) to describe the strength of the association for survival (overall (OS) and progression-free survival (PFS)) and dichotomous (overall response rate (ORR) and SAE rate) data, respectively, with 95% confidence intervals (CI). Thirty-four RCTs (enrolling 13,787 participants) fulfilled the eligibility criteria. Available evidence enabled us to address multiple clinical issues regarding the survival effects of second-line systemic therapy of people with metastatic CRC.1. Chemotherapy (irinotecan) was more effective than best supportive care (HR for OS: 0.58, 95% CI 0.43 to 0.80; 1 RCT; moderate-quality evidence); 2

  14. Salvage treatment for childhood ependymoma after surgery only: Pitfalls of omitting 'at once' adjuvant treatment

    International Nuclear Information System (INIS)

    Massimino, Maura; Giangaspero, Felice; Garre, Maria Luisa; Genitori, Lorenzo; Perilongo, Giorgio; Collini, Paola; Riva, Daria; Valentini, Laura; Scarzello, Giovanni; Poggi, Geraldina; Spreafico, Filippo; Peretta, Paola; Mascarin, Maurizio; Modena, Piergiorgio; Sozzi, Gabriella; Bedini, Nice; Biassoni, Veronica; Urgesi, Alessandro; Balestrini, Maria Rosa; Finocchiaro, Gaetano; Sandri, Alessandro; Gandola, Lorenza

    2006-01-01

    Purpose: To discuss the results obtained by giving adjuvant treatment for childhood ependymoma (EPD) at relapse after complete surgery only. Methods and Materials: Between 1993 and 2002, 63 children older than 3 years old entered the first Italian Association for Pediatric Hematology and Oncology protocol for EPD (group A), and another 14 patients were referred after relapsing after more tumor excisions only (group B). Prognostic factors were homogeneously matched in the two groups. We report on the outcome of group B. Results: Mean time to first local progression in group B had been 14 months. Tumors originated in the posterior fossa (PF) in 10 children and were supratentorial (ST) in 4; 11 had first been completely excised (NED) and 3 had residual disease (ED). Diagnoses were classic EPD in 9 patients, anaplastic in 5. Eight children were referred NED and 6 ED after two or more operations, 5 had cranial nerve palsy, 1 had recurrent meningitis, and 2 had persistent hydrocephalus. All received radiotherapy (RT) to tumor bed and 5 also had pre-RT chemotherapy. Six of 14 patients (6/10 with PF tumors) had a further relapse a mean 6 months after the last surgery; 4 of 6 died: progression-free survival and overall survival at 4 years after referral were 54.4% and 77%, respectively. Considering only PF tumors and setting time 0 as at the last surgery for group B, progression-free survival and overall survival were 32% and 50% for group B and 52% (p < 0.20)/70% (p < 0.29) for the 46 patients in group A with PF tumors. Local control was 32% in group B and 70.5% in group A (p = 0.02). Conclusions: Relapsers after surgery only, especially if with PF-EPD, do worse than those treated after first diagnosis; subsequent surgery for tumor relapse has severe neurologic sequelae

  15. Resistance to fluoroquinolones and second-line injectable drugs: impact on multidrug-resistant TB outcomes

    NARCIS (Netherlands)

    Falzon, Dennis; Gandhi, Neel; Migliori, Giovanni B.; Sotgiu, Giovanni; Cox, Helen S.; Holtz, Timothy H.; Hollm-Delgado, Maria-Graciela; Keshavjee, Salmaan; Deriemer, Kathryn; Centis, Rosella; D'Ambrosio, Lia; Lange, Christoph G.; Bauer, Melissa; Menzies, Dick; Ahuja, S. D.; Ashkin, D.; Avendaño, M.; Banerjee, R.; Bauer, M.; Becerra, M. C.; Benedetti, A.; Burgos, M.; Centis, R.; Chan, E. D.; Chiang, C. Y.; Cobelens, F.; Cox, H.; D'Ambrosio, L.; de Lange, W. C. M.; DeRiemer, K.; Enarson, D.; Falzon, D.; Flanagan, K. L.; Flood, J.; Gandhi, N.; Garcia-Garcia, M. L.; Granich, R. M.; Hollm-Delgado, M. G.; Holtz, T. H.; Hopewell, P.; Iseman, M. D.; Jarlsberg, L. G.; Keshavjee, S.; Kim, H. R.; Koh, W. J.; Lancaster, J. L.; Lange, C.; Leimane, V.; Leung, C. C.; Li, J.

    2013-01-01

    A meta-analysis for response to treatment was undertaken using individual data of multidrug-resistant tuberculosis (MDR-TB) (resistance to isoniazid and rifampicin) patients from 26 centres. The analysis assessed the impact of additional resistance to fluoroquinolones and/or second-line injectable

  16. Effectiveness and tolerability of second-line treatment with vildagliptin versus other oral drugs for type 2 diabetes in a real-world setting in the Middle East: results from the EDGE study.

    Science.gov (United States)

    Saab, Charles; Al-Saber, Feryal A; Haddad, Jihad; Jallo, Mahir Khalil; Steitieh, Habib; Bader, Giovanni; Ibrahim, Mohamed

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is a chronic progressive disease that requires treatment intensification with antihyperglycemic agents due to progressive deterioration of β-cell function. A large observational study of 45,868 patients with T2DM across 27 countries (EDGE) assessed the effectiveness and safety of vildagliptin as add-on to other oral antidiabetic drugs (OADs) versus other comparator OAD combinations. Here, we present results from the Middle East countries (Bahrain, Jordan, Kuwait, Lebanon, Oman, Palestine, and the United Arab Emirates). Patients inadequately controlled with OAD monotherapy were eligible after the add-on treatment was chosen by the physician based on clinical judgment and patient need. Patients were assigned to either vildagliptin or comparator OADs (sulfonylureas, thiazolidinediones, glinides, α-glucosidase inhibitors, or metformin, except incretin-based therapies) based on the add-on therapy. The primary endpoint was the proportion of patients achieving a glycated hemoglobin (HbA1c) reduction of >0.3% without peripheral edema, hypoglycemia, discontinuation due to a gastrointestinal event, or weight gain≥5%. One of the secondary endpoints was the proportion of patients achieving HbA1cvildagliptin and 2,267 received other OADs. Overall, the mean (±standard deviation) age at baseline was 52.1±10.2 years, mean HbA1c was 8.5%±1.3%, and mean T2DM duration was 4.2±4.0 years. The proportion of patients achieving the primary (76.1% versus 61.6%, Pvildagliptin than with the comparator OADs. The unadjusted odds ratios for the primary and secondary endpoints were 1.98 (95% confidence interval 1.75-2.25) and 2.8 (95% confidence interval 2.5-3.2), respectively, in favor of vildagliptin. Vildagliptin achieved a numerically greater reduction in HbA1c (1.7%) from baseline versus comparator OADs (1.4%). The overall incidence of adverse events was comparable between studied cohorts. In real life, treatment with vildagliptin was associated with

  17. Title of the paper goes here second line

    Indian Academy of Sciences (India)

    %%Please download if these packages are not included %%in your local TeX distribution %%txfonts,balance,textcase,float %% \\begin{document} %%paper title %%For line breaks, \\\\ can be used within title \\title{Title of the paper goes here\\\\ second line} %%author names are separated by comma (,) %%use \\and before ...

  18. Title of the paper goes here second line

    Indian Academy of Sciences (India)

    Title of the paper goes here second line. AUTHOR11, AUTHOR21 and AUTHOR32,*. 1 Department of P, University X. 2 Department of Q, University Z. Abstract. Abstract text goes here. Abstract text goes here. Abstract text goes here. Abstract text goes here. Abstract text goes here. Abstract text goes here. Abstract text goes ...

  19. Perceived adherence barriers among patients failing second-line ...

    African Journals Online (AJOL)

    1 School of Public Health and Family Medicine, University of Cape Town, South Africa ... To examine factors affecting adherence to second-line ART from the perspective of clinic staff and .... because she did not realise her VL would go up.

  20. Effectiveness and tolerability of second-line treatment with vildagliptin versus other oral drugs for type 2 diabetes in a real-world setting in the Middle East: results from the EDGE study

    Directory of Open Access Journals (Sweden)

    Saab C

    2015-02-01

    Full Text Available Charles Saab,1 Feryal A Al-Saber,2 Jihad Haddad,3 Mahir Khalil Jallo,4 Habib Steitieh,5 Giovanni Bader,6 Mohamed Ibrahim,7 1Department of Endocrinology and Metabolism, Sacre Coeur University Hospital, Baabda, Lebanon; 2Endocrine Department, Bahrain Defence Force Hospital, Rifaa, Bahrain; 3Division of Endocrinology Department of Internal Medicine, Prince Hamaza Hospital, Amman, Jordan; 4Department of Internal Medicine, Gulf Medical University, Ajman, United Arab Emirates; 5New Mowasat Hospital, Safat, Kuwait; 6Novartis Pharma AG, Basel, Switzerland; 7Novartis Pharma Services AG, Dubai, United Arab Emirates Background: Type 2 diabetes mellitus (T2DM is a chronic progressive disease that requires treatment intensification with antihyperglycemic agents due to progressive deterioration of β-cell function. A large observational study of 45,868 patients with T2DM across 27 countries (EDGE assessed the effectiveness and safety of vildagliptin as add-on to other oral antidiabetic drugs (OADs versus other comparator OAD combinations. Here, we present results from the Middle East countries (Bahrain, Jordan, Kuwait, Lebanon, Oman, Palestine, and the United Arab Emirates. Methods: Patients inadequately controlled with OAD monotherapy were eligible after the add-on treatment was chosen by the physician based on clinical judgment and patient need. Patients were assigned to either vildagliptin or comparator OADs (sulfonylureas, thiazolidinediones, glinides, α-glucosidase inhibitors, or metformin, except incretin-based therapies based on the add-on therapy. The primary endpoint was the proportion of patients achieving a glycated hemoglobin (HbA1c reduction of >0.3% without peripheral edema, hypoglycemia, discontinuation due to a gastrointestinal event, or weight gain ≥5%. One of the secondary endpoints was the proportion of patients achieving HbA1c <7% without hypoglycemia or weight gain. Change in HbA1c from baseline to study endpoint and safety were also

  1. Experience with second line drugs in frequently relapsing and steroid dependent childhood nephrotic syndrome in a large Saudi center

    Directory of Open Access Journals (Sweden)

    Khalid Alsaran, M.D.

    2017-06-01

    Conclusion: All the second line drugs in our study were equally effective. However, we recommend that the initial treatment of FR/SD nephrotic syndrome should be chosen with the least toxic yet equally efficacious drug Levamisole.

  2. Serum anti-Mullerian hormone levels after ovarian drilling for the second-line treatment of polycystic ovary syndrome: a pilot-randomized study comparing laparoscopy and transvaginal hydrolaparoscopy.

    Science.gov (United States)

    Giampaolino, Pierluigi; Morra, Ilaria; Della Corte, Luigi; Sparice, Stefania; Di Carlo, Costantino; Nappi, Carmine; Bifulco, Giuseppe

    2017-01-01

    Aim of the study was to asses and compare serum anti-Mullerian harmone (AMH) levels after laparoscopic ovarian drilling (LOD) and transvaginal hydrolaparoscopy (THL) ovarian drilling in clomifene citrate (CC)-resistant polycystic ovary syndrome (PCOS) patients; secondary outcome was to evaluate postoperative pain to estimate the acceptability of procedures. A total of 246 patients with CC-resistant PCOS were randomized into two groups: 123 underwent LOD and 123 underwent THL ovarian drilling. AMH serum levels were evaluated before and after the procedure; moreover, women were asked to rate pain on a visual analog scale (VAS) from 0 (no pain, perfectly acceptable) to 10 (unbearable pain, completely unacceptable). In both groups, postoperative serum AMH levels were significantly reduced compared to preoperative levels (6.06 ± 1.18 and 5.84 ± 1.16 versus 5.00 ± 1.29 and 4.83 ± 1.10; p ovarian drilling in comparison to THL (3.26 ± 1.1 versus 1.11 ± 0.5; p ovarian drilling is comparable to the LOD in terms of reduction in AMH, but it is preferred by patients in terms of acceptability. These results could support to use of THL ovarian drilling in the treatment of patients with CC- resistant PCOS.

  3. Proton Therapy as Salvage Treatment for Local Relapse of Prostate Cancer Following Cryosurgery or High-Intensity Focused Ultrasound

    International Nuclear Information System (INIS)

    Holtzman, Adam L.; Hoppe, Bradford S.; Letter, Haley P.; Bryant, Curtis; Nichols, Romaine C.; Henderson, Randal H.; Mendenhall, William M.; Morris, Christopher G.; Williams, Christopher R.; Li, Zuofeng; Mendenhall, Nancy P.

    2016-01-01

    Purpose: Local recurrence of prostate cancer after cryosurgery (CS) and high-intensity focused ultrasound (HIFU) is an emerging problem for which optimal management is unknown. Proton therapy (PT) may offer advantages over other local therapeutic options. This article reviews a single institution's experience using PT for salvage of local recurrent disease after HIFU or CS. Methods and Materials: We reviewed the medical records of 21 consecutive patients treated with salvage PT following a local recurrence of prostate cancer after CS (n=12) or HIFU (n=9) between January 2007 and July 2014. Patients were treated to a median dose of 74 Gy(relative biological effectiveness [RBE]; range: 74-82 Gy[RBE]) and 8 patients received androgen deprivation therapy with radiation therapy. Patients were evaluated for quality of life (QOL) by using the Expanded Prostate Index Composite questionnaire and toxicity by using Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment, every 6 months for 2 years after treatment, and then annually. Results: Median follow-up was 37 months (range: 6-95 months). The 3-year biochemical progression-free survival (bPFS) rate was 77%. The 3-year grade 3 toxicity rate was 17%; however, 2 of these patients had pre-existing grade 3 GU toxicities from their HIFU/CRYO prior to PT. At 1 year, bowel summary, urinary incontinence, and urinary obstructive QOL scores declined, but only the bowel QOL score at 12 months met the minimally important difference threshold. Conclusions: PT achieved a high rate of bPFS with acceptable toxicity and minimal changes in QOL scores compared with baseline pre-PT functions. Although most patients have done fairly well, the study size is small, follow-up is short, and early results suggest that outcomes with PT for salvage after HIFU or CS failure are inferior to outcomes with PT given in the de novo setting with respect to disease control, toxicity, and QOL.

  4. Proton Therapy as Salvage Treatment for Local Relapse of Prostate Cancer Following Cryosurgery or High-Intensity Focused Ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Holtzman, Adam L. [University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida (United States); Hoppe, Bradford S., E-mail: bhoppe@floridaproton.org [University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida (United States); Letter, Haley P.; Bryant, Curtis; Nichols, Romaine C.; Henderson, Randal H.; Mendenhall, William M.; Morris, Christopher G. [University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida (United States); Williams, Christopher R. [Department of Surgery, University of Florida College of Medicine, Jacksonville, Florida (United States); Li, Zuofeng; Mendenhall, Nancy P. [University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida (United States)

    2016-05-01

    Purpose: Local recurrence of prostate cancer after cryosurgery (CS) and high-intensity focused ultrasound (HIFU) is an emerging problem for which optimal management is unknown. Proton therapy (PT) may offer advantages over other local therapeutic options. This article reviews a single institution's experience using PT for salvage of local recurrent disease after HIFU or CS. Methods and Materials: We reviewed the medical records of 21 consecutive patients treated with salvage PT following a local recurrence of prostate cancer after CS (n=12) or HIFU (n=9) between January 2007 and July 2014. Patients were treated to a median dose of 74 Gy(relative biological effectiveness [RBE]; range: 74-82 Gy[RBE]) and 8 patients received androgen deprivation therapy with radiation therapy. Patients were evaluated for quality of life (QOL) by using the Expanded Prostate Index Composite questionnaire and toxicity by using Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment, every 6 months for 2 years after treatment, and then annually. Results: Median follow-up was 37 months (range: 6-95 months). The 3-year biochemical progression-free survival (bPFS) rate was 77%. The 3-year grade 3 toxicity rate was 17%; however, 2 of these patients had pre-existing grade 3 GU toxicities from their HIFU/CRYO prior to PT. At 1 year, bowel summary, urinary incontinence, and urinary obstructive QOL scores declined, but only the bowel QOL score at 12 months met the minimally important difference threshold. Conclusions: PT achieved a high rate of bPFS with acceptable toxicity and minimal changes in QOL scores compared with baseline pre-PT functions. Although most patients have done fairly well, the study size is small, follow-up is short, and early results suggest that outcomes with PT for salvage after HIFU or CS failure are inferior to outcomes with PT given in the de novo setting with respect to disease control, toxicity, and QOL.

  5. Second-line failure and first experience with third-line antiretroviral therapy in Mumbai, India

    Directory of Open Access Journals (Sweden)

    Samsuddin Khan

    2014-07-01

    Full Text Available Background: There are limited data on the failure of second-line antiretroviral therapy (ART and the use of third-line ART in people living with HIV in resource-limited settings. Since 2011, the Médecins Sans Frontières (MSF HIV/tuberculosis programme in Mumbai, India, has been providing third-line ART to patients in care. Objective: To describe the experiences and programmatic challenges during management of suspected second-line ART failure and third-line ART therapy for patients living with HIV, including the use of HIV viral load (VL testing. Design: This was a retrospective, observational cohort study of patients with suspected second-line ART treatment failure, who were followed for at least 12 months between January 2011 and March 2014. Results: A total of 47 patients with suspected second-line failure met the inclusion criteria during the study period. Twenty-nine of them (62% responded to enhanced adherence support, had a subsequent undetectable VL after a median duration of 3 months and remained on second-line ART. The other 18 patients had to be initiated on a third-line ART regimen, which consisted of darunavir–ritonavir, raltegravir, and one or more appropriate nucleoside or nucleotide reverse transcriptase inhibitors, based on the results of HIV genotype testing. Of the 13 patients for whom follow-up VL results were available, 11 achieved virological suppression after a median duration of 3 months on third-line ART (interquartile range: 2.5–3.0. No serious treatment-related adverse events were recorded. Conclusions: With intensive counselling and adherence support in those suspected of failing second-line ART, unnecessary switching to more expensive third-line ART can be averted in the majority of cases. However, there is an increasing need for access to third-line ART medications such as darunavir and raltegravir, for which national ART programmes should be prepared. The cost of such medications and inadequate access to VL

  6. TEXTILE SALVAGE

    CERN Multimedia

    Relations with the Host States Service

    2002-01-01

    Readers are reminded that Geneva's agency for salvaging used clothing, other textiles and old shoes (Coordination d'oeuvres d'entraide pour la récupération de vêtements, textiles et chaussures usagés dans le canton de Genève) has a container in the car park outside CERN's Meyrin site. In 2001, 1000 tonnes of such items were collected in the Canton of Geneva (as compared with 840 tonnes in 2000), of which 4460 kg came from the container outside the Meyrin site. The operation's organisers (Caritas, Centre Social Protestant, the Geneva Section of the Swiss Red Cross, Terre des Hommes, the Geneva branch of Terre des Hommes Suisse and Emmaüs, Geneva) would like to thank all those who have donated clothing or otherwise supported their campaign. Relations with the Host States Service Tel. 72848 http://www.cern.ch/relations/

  7. Treatment and Prognosis of Isolated Local Relapse after Stereotactic Body Radiotherapy for Clinical Stage I Non-Small-Cell Lung Cancer: Importance of Salvage Surgery.

    Science.gov (United States)

    Hamaji, Masatsugu; Chen, Fengshi; Matsuo, Yukinori; Ueki, Nami; Hiraoka, Masahiro; Date, Hiroshi

    2015-11-01

    Many efforts have been made to detect local relapse (LR) in the follow-up after stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer (NSCLC) although limited data are available on its treatment and prognosis. We aimed to characterize treatment options and clarify long-term outcomes of isolated LR after SBRT for patients with clinical stage I NSCLC. We reviewed our institutional database in search of patients with isolated LR after SBRT for clinical stage I NSCLC at our institution between 1999 and 2013. Patient characteristics were compared with Mann-Whitney U test, χ2 test, or Fisher's exact test as appropriate. Survival outcomes were estimated with Kaplan-Meier method. Potential prognostic factors were investigated using Cox proportional hazard model. Of 308 patients undergoing SBRT for clinical stage I NSCLC, 49 patients were identified to have isolated LR. Twelve patients underwent salvage surgery, none underwent radiotherapy, and eight patients received chemotherapy, whereas 29 patients received best supportive care. No patient characteristic except operability was significantly related with patient selection for LR treatments. Five-year overall survival (OS) rate of the whole cohort was 47.9% from SBRT and 25.7% from LR. Salvage surgery was associated with improved OS after LR (p = 0.014), and 5-year OS for patients undergoing salvage surgery was 79.5% from LR. It was confirmed that our patient selection for salvage surgery for isolated LR was associated with favorable survival outcomes. Operability based on multidisciplinary conferences, rather than measurable patient characteristics, is essential for appropriate patient selection for salvage surgery.

  8. Boosted protease inhibitor monotherapy versus boosted protease inhibitor plus lamivudine dual therapy as second-line maintenance treatment for HIV-1-infected patients in sub-Saharan Africa (ANRS12 286/MOBIDIP): a multicentre, randomised, parallel, open-label, superiority trial.

    Science.gov (United States)

    Ciaffi, Laura; Koulla-Shiro, Sinata; Sawadogo, Adrien Bruno; Ndour, Cheik Tidiane; Eymard-Duvernay, Sabrina; Mbouyap, Pretty Rosereine; Ayangma, Liliane; Zoungrana, Jacques; Gueye, Ndeye Fatou Ngom; Diallo, Mohamadou; Izard, Suzanne; Bado, Guillaume; Kane, Coumba Toure; Aghokeng, Avelin Fobang; Peeters, Martine; Girard, Pierre Marie; Le Moing, Vincent; Reynes, Jacques; Delaporte, Eric

    2017-09-01

    Despite satisfactory efficacy of WHO-recommended second-line antiretroviral treatment for patients with HIV in low-income countries, the need for simplified, low-cost, and less-toxic maintenance strategies remains high. We compared boosted protease inhibitor monotherapy with dual therapy with boosted protease inhibitor plus lamivudine in patients on second-line antiretrovial therapy (ART). We did a multicentre, randomised, parallel, open-label, superiority, trial in the HIV services of five hospitals in sub-Saharan Africa (Yaoundé, Cameroon; Dakar, Senegal; and Bobo Dioulasso, Burkina Faso). We recruited patients from the long-term, post-trial cohort of the ANRS 12169/2LADY study that compared the efficacy of three second-line combinations based on boosted protease inhibitors. Participants for our study were HIV-1 infected with multiple mutations including M184V, at first-line failure, aged 18 years and older, on boosted protease inhibitor plus two nucleoside reverse transcriptase inhibitors (NRTI) for at least 48 weeks with at least 48 weeks follow-up in the 2LADY trial, with two viral load measurements of less than 200 copies per mL in the previous 6 months, CD4 counts of more than 100 cells per μL, adherence of at least 90%, and no change to ART in the past 3 months. We randomly assigned participants (1:1) to receive either monotherapy with their boosted protease inhibitor (once-daily darunavir 800 mg [two 400 mg tablets] boosted with ritonavir 100 mg [one tablet] or coformulation of lopinavir 200 mg with ritonavir 50 mg [two tablets taken twice per day]) or to boosted protease inhibitor plus once-daily lamivudine 300 mg (one 300 mg tablet or two 150 mg tablets). Computer-generated randomisation was stratified by study site and viral load at screening (treatment allocation was not masked from clinicians or patients]. Patients had follow-up visits at weeks 4 and 12, and every 3 months until 96 weeks; if viral load exceeded 500 copies per mL at any visit, NRTI

  9. Salvage Treatment for Recurrent Intracranial Germinoma After Reduced-Volume Radiotherapy: A Single-Institution Experience and Review of the Literature

    International Nuclear Information System (INIS)

    Hu, Yu-Wen; Huang, Pin-I; Wong, Tai-Tong; Ho, Donald Ming-Tak; Chang, Kai-Ping; Guo, Wan-Yuo; Chang, Feng-Chi; Shiau, Cheng-Yin; Liang, Muh-Lii; Lee, Yi-Yen

    2012-01-01

    Purpose: Intracranial germinomas (IGs) are highly curable with radiotherapy (RT). However, recurrence still occurs, especially when limited-field RT is applied, and the optimal salvage therapy remains controversial. Methods and Materials: Between January 1989 and December 2010, 14 patients with clinically or pathologically diagnosed recurrent IGs after RT were reviewed at our institution. Of these, 11 received focal-field RT, and the other 3 received whole-brain irradiation, whole-ventricle irradiation, and Gamma Knife radiosurgery as the respective first course of RT. In addition, we identified from the literature 88 patients with recurrent IGs after reduced-volume RT, in whom the details of salvage therapy were recorded. Results: The median time to recurrence was 30.3 months (range, 3.8–134.9 months). One patient did not receive further treatment and was lost during follow-up. Of the patients, 7 underwent salvage with craniospinal irradiation (CSI) plus chemotherapy (CT), 4 with CSI alone, 1 with whole-brain irradiation plus CT, and 1 with Gamma Knife radiosurgery. The median follow-up time was 105.1 months (range, 24.2–180.9 months). Three patients died without evidence of disease progression: two from second malignancies and one from unknown cause. The others remained disease free. The 3-year survival rate after recurrence was 83.3%. A total of 102 patients from our study and the literature review were analyzed to determine the factors affecting prognosis and outcomes. After recurrence, the 5-year survival rates were 71% and 92.9% for all patients and for those receiving salvage CSI, respectively. Univariate analysis showed that initial RT volume, initial RT dose, initial CT, and salvage RT type were significant prognostic predictors of survival. On multivariable analysis, salvage CSI was the most significant factor (p = 0.03). Conclusions: Protracted follow-up is recommended because late recurrence is not uncommon. CSI with or without CT is an effective

  10. Exeresis and Brachytherapy as Salvage Treatment for Local Recurrence After Conservative Treatment for Breast Cancer: Results of a Ten-Year Pilot Study

    International Nuclear Information System (INIS)

    Guix, Benjamin; Lejarcegui, Jose Antonio; Tello, Jose Ignacio; Zanon, Gabriel; Henriquez, Ivan; Finestres, Fernando; Martinez, Antonio; Fernandez-Ibiza, Jaume; Quinzanos, Luis; Palombo, Pau; Encinas, Xavier; Guix, Ines

    2010-01-01

    Purpose: To analyze the long-term results of a pilot study assessing excision and brachytherapy as salvage treatment for local recurrence after conservative treatment of breast cancer. Methods and Materials: Between December 1990 and March 2001, 36 patients with breast-only recurrence less than 3 cm in diameter after conservative treatment for Stage I or II breast carcinoma were treated with local excision followed by high-dose rate brachytherapy implants (30 Gy in 12 fractions over a period of 5 days). No patient was lost to follow-up. Special attention was paid to local, regional, or distant recurrences; survival; cosmesis; and early and late side effects. Results: All patients completed treatment. During follow-up (range, 1-13 years), 8 patients presented metastases (2 regional and 6 distant) as their first site of failure, 1 had a differed local recurrence, and 1 died of the disease. Actuarial results at 10 years were as follows: local control, 89.4%; disease-free survival, 64.4%; and survival, 96.7%. Cosmetic results were satisfactory in 90.4%. No patient had Grade 3 or 4 early or late complications. Of the 11 patients followed up for at least 10 years, all but 1 still had their breast in place at the 10-year stage. Conclusions: High-dose rate brachytherapy is a safe, effective treatment for small-size, low-risk local recurrence after local excision in conservatively treated patients. The dose of 30 Gy of high-dose rate brachytherapy (12 fractions over a period of 5 days twice daily) was well tolerated. The excellent results support the use of breast preservation as salvage treatment in selected patients with local recurrence after conservative treatment for breast cancer.

  11. Clinical outcomes of gamma knife radiosurgery in the salvage treatment of patients with recurrent high-grade glioma.

    Science.gov (United States)

    Elaimy, Ameer L; Mackay, Alexander R; Lamoreaux, Wayne T; Demakas, John J; Fairbanks, Robert K; Cooke, Barton S; Lamm, Andrew F; Lee, Christopher M

    2013-12-01

    Previously published randomized evidence did not report a survival advantage for patients diagnosed with grade IV glioma who were treated with stereotactic radiosurgery followed by external beam radiation therapy and chemotherapy when compared to patients treated with external beam radiation therapy and chemotherapy alone. In recent years, gamma knife radiosurgery has become increasingly popular as a salvage treatment modality for patients diagnosed with recurrent high-grade glioma. The purpose of this article is to review the efficacy of gamma knife radiosurgery for patients who suffer from this malignancy. Retrospective, prospective, and randomized clinical studies published between the years 2000 and 2012 analyzing gamma knife radiosurgery for patients with high-grade glioma were reviewed. After assessing patient age, Karnofsky performance status, tumor histology, and extent of resection, gamma knife radiosurgery is a viable, minimally invasive treatment option for patients diagnosed with recurrent high-grade glioma. The available prospective and retrospective evidence suggests that gamma knife radiosurgery provides patients with a high local tumor control rate and a median survival after tumor recurrence ranging from 13 to 26 months. Gamma knife radiosurgery followed by chemotherapy for recurrent high-grade glioma may provide select patients with increased levels of survival. However, further investigation into this matter is needed due to the limited number of published reports. Additional clinical research is also needed to analyze the efficacy and radiation-related toxicities of fractionated gamma knife radiosurgery due to its potential to limit treatment-associated morbidity. Gamma knife radiosurgery is a safe and effective treatment option for select patients diagnosed with recurrent high-grade glioma. Although treatment outcomes have improved, further evidence in the form of phase III randomized trials is needed to assess the durability of treating

  12. Radiation therapy alone is not successful as salvage treatment for locally recurrent prostate cancer after radical prostatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Oas, Lute G; Zagars, Gunar K; Pollack, Alan

    1995-07-01

    Purpose/Objectives: To evaluate radiotherapy (XRT) as potential salvage treatment for patients with locally recurrent prostate cancer after redical prostatectomy (RP). Materials and Methods: Twenty-four consecutive patients with adenocarcinoma of the prostate who received definitive XRT between 1987 and 1993 for biopsy-proven (n=18) or for prostate-specific antigen (PSA) - producing (n=6) recurrent disease following RP were evaluated. No patient had clinically or radiographically evident distant disease. Biopsies of suspicious nodules or ultrasound findings in the prostatic fossa were positive in 18 and negative in 3. Three patients had no focal abnormalities and had no biopsy. The time between RP and XRT varied from 6 to 277 months (mean 52 months). XRT doses to the prostatic fossa ranged from 60 to 70 Gy (median, 66 Gy). Outcome was analyzed relative to local control, metastatic disease and PSA status. Persistently undetectable PSA was required to define freedom from disease. Results: Pre-XRT PSA levels ranged from 0.7 to 26.8 ng/ml (mean 7.3 ng/ml, median 2.5 ng/ml). Although PSA fell post-XRT in all but 3 patients and 10 (52%) achieved undetectable levels, the outcome at a median follow-up of 42 months (range 13-90 months) was poor, with 15 patients (63%) developing persistent/progressive disease. The patterns of progression in these 15 were: local 3, metastatic 3, persistent PSA 9. All patients whose PSA was persistently detectable developed a rising PSA profile. The actuarial incidence of freedom from disease at 1, 2, 3 and 4 years was 75%, 43%, 36% and 27% respectively. The only factor correlating to outcome was the pre-XRT PSA level. The 9 patients who remain free of disease had a mean PSA level of 3.6 ng/ml compared to a mean level of 9.6 ng/ml among the 15 who failed (p<0.01). All patients with a pre-XRT level >2.5 ng/ml developed disease relapse, whereas the 4-year freedom from disease in those with levels {<=}2.5 ng/ml was 52%. Eleven of the 15 patients

  13. Predicting for activity of second-line trastuzumab-based therapy in her2-positive advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Rottenfusser Andrea

    2009-10-01

    Full Text Available Abstract Background In Her2-positive advanced breast cancer, the upfront use of trastuzumab is well established. Upon progression on first-line therapy, patients may be switched to lapatinib. Others however remain candidates for continued antibody treatment (treatment beyond progression. Here, we aimed to identify factors predicting for activity of second-line trastuzumab-based therapy. Methods Ninety-seven patients treated with > 1 line of trastuzumab-containing therapy were available for this analysis. Her2-status was determined by immunohistochemistry and re-analyzed by FISH if a score of 2+ was gained. Time to progression (TTP on second-line therapy was defined as primary study endpoint. TTP and overall survival (OS were estimated using the Kaplan-Meier product limit method. Multivariate analyses (Cox proportional hazards model, multinomial logistic regression were applied in order to identify factors associated with TTP, response, OS, and incidence of brain metastases. p values Results Median TTP on second-line trastuzumab-based therapy was 7 months (95% CI 5.74-8.26, and 8 months (95% CI 6.25-9.74 on first-line, respectively (n.s.. In the multivariate models, none of the clinical or histopthological features could reliably predict for activity of second-line trastuzumab-based treatment. OS was 43 months suggesting improved survival in patients treated with trastuzumab in multiple-lines. A significant deterioration of cardiac function was observed in three patients; 40.2% developed brain metastases while on second-line trastuzumab or thereafter. Conclusion Trastuzumab beyond progression showed considerable activity. None of the variables investigated correlated with activity of second-line therapy. In order to predict for activity of second-line trastuzumab, it appears necessary to evaluate factors known to confer trastuzumab-resistance.

  14. Splenectomy vs. rituximab as a second-line therapy in immune thrombocytopenic purpura: a single center experience.

    Science.gov (United States)

    Al Askar, Ahmed S; Shaheen, Naila A; Al Zahrani, Mohsen; Al Otaibi, Mohammed G; Al Qahtani, Bader S; Ahmed, Faris; Al Zughaibi, Mohand; Kamran, Ismat; Mendoza, May Anne; Khan, Altaf

    2018-01-01

    Immune thrombocytopenic purpura (ITP) is a common hematological disease treated primarily by corticosteroids. The aim of the present study was to compare response rate between patients, underwent splenectomy vs. rituximab as second-line therapy. Adult patients diagnosed with ITP who did not respond to corticosteroids or relapsed during the period 1990-2014 were included in a quasi-experimental study. Categorical variables were compared using Fisher exact test. Response to treatment was compared using logistic regression. Data were analyzed using SAS V9.2. One-hundred and forty-three patients with ITP were identified through medical records. Of 62 patients treated, 30 (48.38%) required second-line therapy. 19 (63%) patients received rituximab, and 11 (37%) underwent splenectomy. Platelets at diagnosis were not different between study groups (p = 0.062). Splenectomy group patients were younger (p = 0.011). Response to second-line therapy showed no significant difference between two groups (OR 2.03, 95% CI (0.21-22.09), p = 0.549). Results did not show a statistically significant difference in platelet counts over time between treatment groups (p = 0.101). When used exclusively as a second-line therapy for steroid-refractory ITP, the response rate was not statistically different between rituximab and splenectomy. However, further large studies are needed to assess the response rates for these treatment modalities as a second-line therapy.

  15. Timber salvage economics

    Science.gov (United States)

    Jeffrey P. Prestemon; Thomas P. Holmes

    2008-01-01

    Timber salvage is commonly done following natural disturbances, to recover some value from damaged forests. Decision making about salvage, however, is affected by ownership objectives, the nature of the damage agent, site factors, and the strength of the local timber market. For profit-maximizing landowners, salvage decisions must balance the cost of harvesting...

  16. Enhanced Morbidity of Pectoralis Major Myocutaneous Flap Used for Salvage after Previously Failed Oncological Treatment and Unsuccessful Reconstructive Head and Neck Surgery

    Directory of Open Access Journals (Sweden)

    Christiana Maria Ribeiro Salles Vanni

    2012-01-01

    Full Text Available Introduction. The reconstruction of complex cervicofacial defects arising from surgical treatment for cancer is a real challenge for head and neck surgeons, especially in salvage reconstruction surgery and/or failed previous reconstruction. The pectoralis major myocutaneous flap (PMMF has been widely used in these specific situations due to its reliability and low rate of failure or complications. Objectives. Identify factors that determine complications and influence the final outcome of the reconstructions with PMMF in salvage cancer surgery or in salvage reconstruction. Methods. A cross-sectional study design was used to evaluate a sample including 17 surgical patients treated over a period of ten years that met the inclusion criteria. Results. Reconstruction was successful in 13 cases (76.5%, with two cases of partial flap loss and no case of total loss. Complications occurred in 13 cases (76.5% and were specifically related to the flap in nine instances (52.9%. An association was identified between the development of major complications and reconstruction of the hypopharynx (=0.013 as well as in patients submitted to surgery in association with radiation therapy as a previous cancer treatment (=0.002. The former condition is also associated with major reconstruction failure (=0.018. An even lower incidence of major complications was noted in patients under the age of 53 (=0.044. Conclusion. Older patients, with hypopharyngeal defects and submitted to previous surgery plus radiation therapy, presented a higher risk of complications and reconstruction failure with PMMF.

  17. Effect of combined treatment with salvage radiotherapy plus androgen suppression on quality of life in patients with recurrent prostate cancer after radical prostatectomy

    International Nuclear Information System (INIS)

    Pearce, Andrew; Choo, Richard; Danjoux, Cyril; Morton, Gerard; Loblaw, D. Andrew; Szumacher, Ewa; Cheung, Patrick; Deboer, Gerrit; Chander, Sarat

    2006-01-01

    Purpose: To examine the effect of salvage radiotherapy (RT) plus 2-year androgen suppression (AS) on quality of life (QOL). Methods and Materials: A total of 74 patients with biopsy-proven local recurrence or PSA relapse after radical prostatectomy were treated with salvage RT plus 2-year AS, as per a phase II study. Quality of life was prospectively assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-Item Version 3.0 with the added prostate cancer-specific module at baseline and predefined follow-up visits. Results: Patients experienced a significant increase in bowel dysfunction (23%) by the end of RT (p < 0.0001). This bowel dysfunction improved after RT but remained slightly elevated (5-10%) throughout the 2-year AS period. This extent of residual bowel dysfunction would be considered of minimal clinical importance. A similar, but less pronounced, pattern of change did occur for urinary dysfunction. Erectile function showed no change during RT, but had an abrupt decline (10%) with initiation of AS that was of moderate clinical significance (p < 0.01). None of the other QOL domains demonstrated a persistent, significant change from baseline that would be considered of major clinical significance. Conclusion: The combined treatment with salvage RT plus 2-year AS had relatively minor long-term effects on QOL

  18. Pulsed dose rate (PDR) brachytherapy as salvage treatment of locally advanced or recurrent gynecologic cancer

    DEFF Research Database (Denmark)

    Jensen, P T; Roed, H; Engelholm, S A

    1998-01-01

    PURPOSE: Pulsed dose rate (PDR) brachytherapy is a new treatment option permitting dose distribution optimization in interstitial implants. It possesses the advantage of equipment simplification and radiation protection to the staff, compared to the manually afterloading technique. This study pre...

  19. Airway necrosis after salvage esophagectomy

    International Nuclear Information System (INIS)

    Tanaka, Norimitsu; Hokamura, Nobukazu; Tachimori, Yuji

    2010-01-01

    Salvage esophagectomy is the sole curative intent treatment for patients with persistent or recurrent locoregional disease after definitive chemoradiotherapy (CRT) for esophageal carcinoma. However, salvage esophagectomy is a very high-risk operation, and airway necrosis is a fatal complication. Between 1997 and 2007, 49 patients with thoracic esophageal cancer underwent salvage esophagectomy after definitive CRT. We retrospectively compared patients with and without airway necrosis, and investigated operative procedures related to airway necrosis. Airway necrosis occurred in five patients (10.2%), of four patients (80%) died during their hospitalization. Airway necrosis seemed to be closely related to operative procedures, such as resection of bronchial artery and cervical and subcarinal lymph node dissection. Bronchogastric fistula following necrosis of gastric conduit occured in 2 patients reconstructed through posterior mediastinal route. Airway necrosis is a highly lethal complication after salvage esophagectomy. It is important in salvage esophagectomy to take airway blood supply into consideration sufficiently and to reconstruct through retrosternal route to prevent bronchogastric fistula. (author)

  20. Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Popat, Sanjay; Mellemgaard, Anders; Fahrbach, Kyle

    2015-01-01

    BACKGROUND: Nintedanib plus docetaxel has proven an overall survival benefit over docetaxel monotherapy in second-line treatment of non-small-cell lung cancer of adenocarcinoma histology in the LUME-Lung 1 pivotal trial. No published trials have previously compared nintedanib plus docetaxel...... with advanced non-small-cell lung cancer of adenocarcinoma histology, results suggest that nintedanib plus docetaxel offers clinical benefit compared with docetaxel alone, when used as second-line treatment, and suggests that this combination may also add clinical benefit compared with erlotinib in this patient...

  1. Role of salvage esophagectomy after definitive chemoradiotherapy

    International Nuclear Information System (INIS)

    Tachimori, Yuji

    2009-01-01

    Chemoradiotherapy has become a popular definitive therapy among many patients and oncologists for potentially resectable esophageal carcinoma. Although the complete response rates are high and short-term survival is favorable after chemoradiotherapy, persistent or recurrent locoregional disease is quite frequent. Salvage surgery is the sole curative intent treatment option for this course. As experience with definitive chemoradiotherapy grows, the number of salvage surgeries may increase. Selected articles about salvage esophagectomy after definitive chemoradiotherapy for esophageal carcinoma are reviewed. The number of salvage surgeries was significantly lower than the number of expected candidates. To identify candidates for salvage surgery, patients undergoing definitive chemoradiotherapy should be followed up carefully. Salvage esophagectomy is difficult when dissecting fibrotic masses from irradiated tissues. Patients who underwent salvage esophagectomy had increased morbidity and mortality. Pulmonary complications such as pneumonia and acute respiratory distress syndrome were common. The anastomotic leak rate was significantly increased because of the effects of the radiation administered to the tissues used as conduits. The most significant factor associated with long-term survival appeared to be complete resection. However, precise evaluation of resectability before operation was difficult. Nevertheless, increased morbidity and mortality will be acceptable in exchange for potential long-term survival after salvage esophagectomy. Such treatment should be considered for carefully selected patients at specialized centers. (author)

  2. Cost effectiveness of regorafenib as second-line therapy for patients with advanced hepatocellular carcinoma.

    Science.gov (United States)

    Parikh, Neehar D; Singal, Amit G; Hutton, David W

    2017-10-01

    Regorafenib, a multikinase inhibitor, has demonstrated prolonged survival by 2.8 months as a second-line agent in patients with hepatocellular carcinoma (HCC) who progress on sorafenib therapy. The objective of the current study was to examine the cost effectiveness of regorafenib for the treatment of HCC. The authors constructed a Markov simulation model of patients with unresectable HCC and Child-Pugh A cirrhosis who received treatment with regorafenib versus best supportive care. Model inputs for regorafenib effectiveness and rates of adverse events in patients with HCC were based on published clinical trial data and literature review. Quality-adjusted life years (QALYs) were calculated along with the incremental cost-effectiveness ratio (ICER) of regorafenib therapy. One-way sensitivity analyses also were conducted simultaneously on all model parameters and on various Monte-Carlo simulation parameters, and the regorafenib cost threshold at which cost effectiveness would be achieved was determined. Regorafenib provided an increase of 0.18 QALYs at a cost of $47,112. The ICER for regorafenib, compared with best supportive care, was $224,362. In 1-way sensitivity analyses, there were no scenarios in which regorafenib was cost effective. In cost threshold analysis, regorafenib would have to be priced at or below $67 per pill to be cost effective at an ICER of $100,000. Regorafenib is not cost effective as a second-line agent in the treatment of HCC, with a marginal increase in QALYs at a high cost. Lowering the cost of regorafenib or improving the selection of patients who can achieve maximal survival benefit would improve its value as a second-line treatment option for patients with HCC. Cancer 2017;123:3725-3731. © 2017 American Cancer Society. © 2017 American Cancer Society.

  3. Successful salvage treatment of native valve Enterococcus faecalis infective endocarditis with telavancin: two case reports.

    Science.gov (United States)

    Thompson, Mickala M; Hassoun, Ali

    2017-07-01

    Infective endocarditis (IE) one-year mortality rates approach 40%. Here, we report two native valve Enterococcus faecalis IE cases in patients successfully treated with telavancin. An 88-year-old with mitral valve endocarditis and a penicillin allergy, initially treated with intravenous vancomycin, was switched to telavancin. A 69-year-old, who previously received amoxicillin and intravenous vancomycin for presumed enterococcal bacteraemia, was diagnosed with dual valve endocarditis for which he received telavancin. Both received six weeks of telavancin. Neither had telavancin-related adverse events, evidence of infection at six months, nor required telavancin dosing adjustments. Documented use of novel treatments for serious enterococcal infections is needed.

  4. Rill erosion in burned and salvage logged western montane forests: Effects of logging equipment type, traffic level, and slash treatment

    Science.gov (United States)

    J. W. Wagenbrenner; P. R. Robichaud; R. E. Brown

    2016-01-01

    Following wildfires, forest managers often consider salvage logging burned trees to recover monetary value of timber, reduce fuel loads, or to meet other objectives. Relatively little is known about the cumulative hydrologic effects of wildfire and subsequent timber harvest using logging equipment. We used controlled rill experiments in logged and unlogged (control)...

  5. Percutaneous radiofrequency ablation (RFA) or robotic radiosurgery (RRS) for salvage treatment of colorectal liver metastases

    Energy Technology Data Exchange (ETDEWEB)

    Stintzing, Sebastian; Hendrich, Saskia; Heinemann, Volker [Dept. of Medical Oncology and Comprehensive Cancer Center, Klinikum Grosshadern, LMU, Munich (Germany)], E-mail: sebastian.stintzing@med.uni-muenchen.de; Grothe, Alexander; Trumm, Christoph G. [Dept. of Clinical Radiology, Univ. Hospital Grosshadern, LMU Munich, Munich (Germany); Hoffmann, Ralf-Thorsten [Dept. and Policlinics of Diagnostic Radiology, Universitaetsklinikum Carl Gustav Carus Dresden (Germany); Rentsch, Markus [Dept. of Surgery, Univ. Hospital Grosshadern, LMU Munich, Munich (Germany); Fuerweger, Christoph; Muacevic, Alexander [European Cyberknife Center Munich, Munich (Germany)

    2013-06-15

    Background. Stereotactic radiation therapy is an evolving modality to treat otherwise unresectable liver metastases. In this analysis, two local therapies: 1) single session robotic radiosurgery (RRS) and 2) percutaneous radiofrequency ablation (RFA) were compared in a total of 60 heavily pretreated colorectal cancer patients. Methods. Thirty patients with a total of 35 colorectal liver metastases not qualifying for surgery that were treated in curative intent with RRS were prospectively followed. To compare efficacy of both treatment modalities, patients treated with RFA during the same period of time were matched according to number and size of the treated lesions. Local tumor control, local disease free survival (DFS), and freedom from distant recurrence (FFDR) were analyzed for effi cacy. Treatment-related side effects were recorded for comparison. Results. The median diameter of the treated lesions was 33 mm (7-53 mm). Baseline characteristics did not differ significantly between the groups. One- and two-year local control rates showed no signifi cant difference but favored RRS (85% vs. 65% and 80% vs. 61%, respectively). A signifi cantly longer local DFS of patients treated with RRS compared to RFA (34.4 months vs. 6.0 months; p 0.001) was found. Both, median FFDR (11.4 months for RRS vs. 7.1 months for RFA p=0.25) and the recurrence rate (67% for RRS and 63% for RFA, p>0.99) were comparable. Conclusion. Single session RRS is a safe and effective method to treat colorectal liver metastases. In this analysis, a trend towards longer DFS was seen in patients treated with RRS when compared to RFA.

  6. Percutaneous radiofrequency ablation (RFA) or robotic radiosurgery (RRS) for salvage treatment of colorectal liver metastases

    International Nuclear Information System (INIS)

    Stintzing, Sebastian; Hendrich, Saskia; Heinemann, Volker; Grothe, Alexander; Trumm, Christoph G.; Hoffmann, Ralf-Thorsten; Rentsch, Markus; Fuerweger, Christoph; Muacevic, Alexander

    2013-01-01

    Background. Stereotactic radiation therapy is an evolving modality to treat otherwise unresectable liver metastases. In this analysis, two local therapies: 1) single session robotic radiosurgery (RRS) and 2) percutaneous radiofrequency ablation (RFA) were compared in a total of 60 heavily pretreated colorectal cancer patients. Methods. Thirty patients with a total of 35 colorectal liver metastases not qualifying for surgery that were treated in curative intent with RRS were prospectively followed. To compare efficacy of both treatment modalities, patients treated with RFA during the same period of time were matched according to number and size of the treated lesions. Local tumor control, local disease free survival (DFS), and freedom from distant recurrence (FFDR) were analyzed for effi cacy. Treatment-related side effects were recorded for comparison. Results. The median diameter of the treated lesions was 33 mm (7-53 mm). Baseline characteristics did not differ significantly between the groups. One- and two-year local control rates showed no signifi cant difference but favored RRS (85% vs. 65% and 80% vs. 61%, respectively). A signifi cantly longer local DFS of patients treated with RRS compared to RFA (34.4 months vs. 6.0 months; p 0.001) was found. Both, median FFDR (11.4 months for RRS vs. 7.1 months for RFA p=0.25) and the recurrence rate (67% for RRS and 63% for RFA, p>0.99) were comparable. Conclusion. Single session RRS is a safe and effective method to treat colorectal liver metastases. In this analysis, a trend towards longer DFS was seen in patients treated with RRS when compared to RFA

  7. Serum PSA Evaluations during salvage radiotherapy for post-prostatectomy biochemical failures as prognosticators for treatment outcomes

    International Nuclear Information System (INIS)

    Do, Tri; Dave, Giatri; Parker, Robert; Kagan, A. Robert

    2001-01-01

    Introduction: Serum prostate specific antigen (PSA) levels have proved to be sensitive markers for the diagnosis of prostate cancer. In addition, PSA levels are useful for detecting and monitoring prostate cancer progression after radiotherapy. Serum PSA evaluations during radiotherapy, however, have not been well documented. In this study, we investigate the prognostic value of PSA evaluations during salvage radiotherapy for prostatectomy failures. Methods: Forty-one patients with biochemical failures after prostatectomy treated with salvage radiotherapy consented to have their serum PSA levels evaluated at 30 Gy and 45 Gy of irradiation. All 41 patients had negative metastatic workup and pathologically uninvolved pelvic lymph nodes at the time of referral for salvage radiotherapy. Radiation therapy was delivered with 10-25 MV photons, with doses of 59.4-66.6 Gy. No patients received hormonal ablation therapy before irradiation. Results: The mean follow-up for all patients was 30.9 months. At last follow-up, 28/41 patients (68.3%) were free from biochemical failure, with 20 of 41 patients (48.8%) expressing undetectable PSA levels. Serum PSA evaluations at 30 Gy did not significantly predict for either biochemical (p=0.0917) or clinical (p=0.106) disease-free outcome. However, serum PSA evaluations at 45 Gy significantly predicted for both biochemical (p=0.0043) and clinical (p=0.0244) disease-free outcomes, with PSA elevations at 45 Gy significantly associated with poor outcomes. On univariate analysis of prognosticators for biochemical failures, the following were significant: an elevation in serum PSA levels at 45 Gy, detectable serum PSA immediately after prostatectomy, Gleason score 7-10, and serum PSA level >1 ng/ml before salvage radiotherapy. Conclusion: Evaluation of serum PSA level at 45 Gy of salvage radiotherapy for biochemical relapses after prostatectomy may serve as a significant prognosticator for both biochemical and clinical disease-free outcomes

  8. Phase 1 Trial of Everolimus and Radiation Therapy for Salvage Treatment of Biochemical Recurrence in Prostate Cancer Patients Following Prostatectomy

    International Nuclear Information System (INIS)

    Narayan, Vivek; Vapiwala, Neha; Mick, Rosemarie; Subramanian, Pearl; Christodouleas, John P.; Bekelman, Justin E.; Deville, Curtiland; Rajendran, Ramji; Haas, Naomi B.

    2017-01-01

    Purpose: In up to half of patients treated with salvage radiation therapy (SRT) for rising prostate-specific antigen levels, a second biochemical recurrence ultimately develops. Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin pathway can lead to tumor hypoxia and radioresistance. Everolimus is a mammalian target of rapamycin inhibitor with both antitumor and radiosensitizing effects. Methods and Materials: We performed a phase 1 study using a modified 3 + 3 dose-escalation design to evaluate the safety and tolerability of everolimus in combination with standard SRT for the treatment of biochemical recurrence following prostatectomy. After a 2-week run-in period of everolimus daily therapy, patients received prostate bed irradiation with daily cone beam computed tomography localization in 37 fractions of 1.8 Gy each (total dose, 66.6 Gy). Patients were monitored for both acute (≤90 days) and chronic (>90 days) treatment-related toxicities. Results: Eighteen patients received everolimus at dose levels of 5 mg (n=6), 7.5 mg (n=6), or 10 mg (n=6) daily in conjunction with SRT. No dose-limiting toxicities were observed. Common acute treatment-related toxicities included grade 1 or 2 mucositis (55.6%), grade 1 or 2 fatigue (38.9%), grade 1 or 2 rash (61.1%), and grade 1 urinary symptoms (61.1%). A grade 3 acute toxicity occurred in 4 patients (22.2%) (n=1 for rash, anemia, lymphopenia, and neutropenia), and no patients had a chronic toxicity of grade 3 or greater. After a median follow-up time of 17.8 months (range, 1.2-46.0 months), an undetectable prostate-specific antigen nadir was achieved in 9 patients (56.3%) and a second biochemical recurrence developed in 5 patients (31.3%). Conclusions: Everolimus at a dose of ≤10 mg daily appears to be safe and tolerable in combination with fractionated post-prostatectomy radiation therapy.

  9. Phase 1 Trial of Everolimus and Radiation Therapy for Salvage Treatment of Biochemical Recurrence in Prostate Cancer Patients Following Prostatectomy.

    Science.gov (United States)

    Narayan, Vivek; Vapiwala, Neha; Mick, Rosemarie; Subramanian, Pearl; Christodouleas, John P; Bekelman, Justin E; Deville, Curtiland; Rajendran, Ramji; Haas, Naomi B

    2017-02-01

    In up to half of patients treated with salvage radiation therapy (SRT) for rising prostate-specific antigen levels, a second biochemical recurrence ultimately develops. Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin pathway can lead to tumor hypoxia and radioresistance. Everolimus is a mammalian target of rapamycin inhibitor with both antitumor and radiosensitizing effects. We performed a phase 1 study using a modified 3 + 3 dose-escalation design to evaluate the safety and tolerability of everolimus in combination with standard SRT for the treatment of biochemical recurrence following prostatectomy. After a 2-week run-in period of everolimus daily therapy, patients received prostate bed irradiation with daily cone beam computed tomography localization in 37 fractions of 1.8 Gy each (total dose, 66.6 Gy). Patients were monitored for both acute (≤90 days) and chronic (>90 days) treatment-related toxicities. Eighteen patients received everolimus at dose levels of 5 mg (n=6), 7.5 mg (n=6), or 10 mg (n=6) daily in conjunction with SRT. No dose-limiting toxicities were observed. Common acute treatment-related toxicities included grade 1 or 2 mucositis (55.6%), grade 1 or 2 fatigue (38.9%), grade 1 or 2 rash (61.1%), and grade 1 urinary symptoms (61.1%). A grade 3 acute toxicity occurred in 4 patients (22.2%) (n=1 for rash, anemia, lymphopenia, and neutropenia), and no patients had a chronic toxicity of grade 3 or greater. After a median follow-up time of 17.8 months (range, 1.2-46.0 months), an undetectable prostate-specific antigen nadir was achieved in 9 patients (56.3%) and a second biochemical recurrence developed in 5 patients (31.3%). Everolimus at a dose of ≤10 mg daily appears to be safe and tolerable in combination with fractionated post-prostatectomy radiation therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Phase 1 Trial of Everolimus and Radiation Therapy for Salvage Treatment of Biochemical Recurrence in Prostate Cancer Patients Following Prostatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Narayan, Vivek [Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Vapiwala, Neha [Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Mick, Rosemarie [Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Subramanian, Pearl [Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Christodouleas, John P.; Bekelman, Justin E.; Deville, Curtiland; Rajendran, Ramji [Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Haas, Naomi B., E-mail: naomi.haas@uphs.upenn.edu [Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2017-02-01

    Purpose: In up to half of patients treated with salvage radiation therapy (SRT) for rising prostate-specific antigen levels, a second biochemical recurrence ultimately develops. Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin pathway can lead to tumor hypoxia and radioresistance. Everolimus is a mammalian target of rapamycin inhibitor with both antitumor and radiosensitizing effects. Methods and Materials: We performed a phase 1 study using a modified 3 + 3 dose-escalation design to evaluate the safety and tolerability of everolimus in combination with standard SRT for the treatment of biochemical recurrence following prostatectomy. After a 2-week run-in period of everolimus daily therapy, patients received prostate bed irradiation with daily cone beam computed tomography localization in 37 fractions of 1.8 Gy each (total dose, 66.6 Gy). Patients were monitored for both acute (≤90 days) and chronic (>90 days) treatment-related toxicities. Results: Eighteen patients received everolimus at dose levels of 5 mg (n=6), 7.5 mg (n=6), or 10 mg (n=6) daily in conjunction with SRT. No dose-limiting toxicities were observed. Common acute treatment-related toxicities included grade 1 or 2 mucositis (55.6%), grade 1 or 2 fatigue (38.9%), grade 1 or 2 rash (61.1%), and grade 1 urinary symptoms (61.1%). A grade 3 acute toxicity occurred in 4 patients (22.2%) (n=1 for rash, anemia, lymphopenia, and neutropenia), and no patients had a chronic toxicity of grade 3 or greater. After a median follow-up time of 17.8 months (range, 1.2-46.0 months), an undetectable prostate-specific antigen nadir was achieved in 9 patients (56.3%) and a second biochemical recurrence developed in 5 patients (31.3%). Conclusions: Everolimus at a dose of ≤10 mg daily appears to be safe and tolerable in combination with fractionated post-prostatectomy radiation therapy.

  11. Cost-Effectiveness Analysis of Second-Line Chemotherapy Agents for Advanced Gastric Cancer.

    Science.gov (United States)

    Lam, Simon W; Wai, Maya; Lau, Jessica E; McNamara, Michael; Earl, Marc; Udeh, Belinda

    2017-01-01

    Gastric cancer is the fifth most common malignancy and second leading cause of cancer-related mortality. Chemotherapy options for patients who fail first-line treatment are limited. Thus the objective of this study was to assess the cost-effectiveness of second-line treatment options for patients with advanced or metastatic gastric cancer. Cost-effectiveness analysis using a Markov model to compare the cost-effectiveness of six possible second-line treatment options for patients with advanced gastric cancer who have failed previous chemotherapy: irinotecan, docetaxel, paclitaxel, ramucirumab, paclitaxel plus ramucirumab, and palliative care. The model was performed from a third-party payer's perspective to compare lifetime costs and health benefits associated with studied second-line therapies. Costs included only relevant direct medical costs. The model assumed chemotherapy cycle lengths of 30 days and a maximum number of 24 cycles. Systematic review of literature was performed to identify clinical data sources and utility and cost data. Quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. The primary outcome measure for this analysis was the ICER between different therapies, where the incremental cost was divided by the number of QALYs saved. The ICER was compared with a willingness-to-pay (WTP) threshold that was set at $50,000/QALY gained, and an exploratory analysis using $160,000/QALY gained was also used. The model's robustness was tested by using 1-way sensitivity analyses and a 10,000 Monte Carlo simulation probabilistic sensitivity analysis (PSA). Irinotecan had the lowest lifetime cost and was associated with a QALY gain of 0.35 year. Docetaxel, ramucirumab alone, and palliative care were dominated strategies. Paclitaxel and the combination of paclitaxel plus ramucirumab led to higher QALYs gained, at an incremental cost of $86,815 and $1,056,125 per QALY gained, respectively. Based on our prespecified

  12. Second-line combination therapies in nonsmall cell lung cancer without known driver mutations

    Directory of Open Access Journals (Sweden)

    Maria-Virginia Bluthgen

    2015-12-01

    Full Text Available In advanced nonsmall cell lung cancer (NSCLC patients, platinum-based combination chemotherapy is standard treatment in the first-line setting; however, the large majority of patients ultimately progress. For more than a decade, single-agent therapy with docetaxel, pemetrexed or erlotinib has been the standard of care after failure with platinum salts, showing some benefit over best supportive care. Nonetheless, prognosis remains poor and new second-line strategies are urgently needed. Combinations of cytotoxic agents, including rechallenge with platinum salts, do not offer clear benefit over single-agent therapy for the majority of patients. In patients without a known tumoural oncogenic driver mutation, regimens based on combinations of targeted agents have shown promising results; however, a clear role in therapeutic management is yet to be established. Some success has been reported in recent research combining a cytotoxic agent with targeted therapies. In this review, we summarise published data for the various strategies evaluated over the past decade in second-line treatment of NSCLC patients without a known driver mutation. We focus on combination treatments and consider future perspectives, including the need to identify predictive markers to support personalised therapeutic strategies.

  13. Low lopinavir plasma or hair concentrations explain second-line protease inhibitor failures in a resource-limited setting

    NARCIS (Netherlands)

    van Zyl, Gert Uves; van Mens, Thijs E.; McIlleron, Helen; Zeier, Michele; Nachega, Jean B.; Decloedt, Eric; Malavazzi, Carolina; Smith, Peter; Huang, Yong; van der Merwe, Lize; Gandhi, Monica; Maartens, Gary

    2011-01-01

    In resource-limited settings, many patients, with no prior protease inhibitor (PI) treatment on a second-line, high genetic barrier, ritonavir-boosted PI-containing regimen have virologic failure. We conducted a cross-sectional survey to investigate the aetiology of virologic failure in 2 public

  14. Perceived adherence barriers among patients failing second-line antiretroviral therapy in Khayelitsha, South Africa

    Directory of Open Access Journals (Sweden)

    W Barnett

    2013-11-01

    Full Text Available Background. The recent scale-up of antiretroviral therapy (ART coverage in resource-limited settings has greatly improved access to treatment. However, increasing numbers of patients are failing first- and second-line ART. Objective. To examine factors affecting adherence to second-line ART from the perspective of clinic staff and patients, assessing both individual and structural perceived barriers. Methods. Research was conducted at a large primary care tuberculosis (TB/HIV clinic in Khayelitsha, a peri-urban township in Cape Town, South Africa. Participants were drawn from a Médecins Sans Frontières-run programme to support patients failing second-line ART. A qualitative research approach was used, combining multiple methodologies including key informant interviews with staff (n=11, in-depth interviews with patients (n=10 and a Photovoice workshop (n=11. Responses and photographs were coded by content; data were transformed into variables and analysed accordingly. Results. Staff identified drinking, non-disclosure, not using condoms and pill fatigue as barriers to ART adherence, while patients identified side-effects, not using condoms and a lack of understanding concerning medication timing. With respect to service delivery, staff identified a need for continued counselling and educational support following ART initiation. Patients were concerned about missing medical records and poor staff attitudes in the clinic. Conclusion. These findings identify discrepancies between provider and patient perceptions of barriers to, and facilitators of adherence, as well as of service delivery solutions. This highlights the need for on-going counselling and education following ART initiation, improved quality of counselling, and improved methods to identify and address specific barriers concerning medication adherence.

  15. Early antiretroviral therapy and potent second-line drugs could decrease HIV incidence of drug resistance.

    Science.gov (United States)

    Shen, Mingwang; Xiao, Yanni; Rong, Libin; Meyers, Lauren Ancel; Bellan, Steven E

    2017-06-28

    Early initiation of antiretroviral therapy (ART) reduces the risk of drug-sensitive HIV transmission but may increase the transmission of drug-resistant HIV. We used a mathematical model to estimate the long-term population-level benefits of ART and determine the scenarios under which earlier ART (treatment at 1 year post-infection, on average) could decrease simultaneously both total and drug-resistant HIV incidence (new infections). We constructed an infection-age-structured mathematical model that tracked the transmission rates over the course of infection and modelled the patients' life expectancy as a function of ART initiation timing. We fitted this model to the annual AIDS incidence and death data directly, and to resistance data and demographic data indirectly among men who have sex with men (MSM) in San Francisco. Using counterfactual scenarios, we assessed the impact on total and drug-resistant HIV incidence of ART initiation timing, frequency of acquired drug resistance, and second-line drug effectiveness (defined as the combination of resistance monitoring, biomedical drug efficacy and adherence). Earlier ART initiation could decrease the number of both total and drug-resistant HIV incidence when second-line drug effectiveness is sufficiently high (greater than 80%), but increase the proportion of new infections that are drug resistant. Thus, resistance may paradoxically appear to be increasing while actually decreasing. © 2017 The Author(s).

  16. Cabazitaxel as second-line or third-line therapy in patients with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Kongsted, Per; Svane, Inge M; Lindberg, Henriette

    2016-01-01

    To compare treatment outcomes in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel (CA) as second-line or third-line therapy in the everyday clinical setting. Charts from 94 patients treated with CA as second-line (n=28) or third-line therapy (n=66) were...... evaluated. Common Terminology Criteria for Adverse Events were used to register grade 3-4 nonhematological toxicity during treatment with CA. Baseline metastatic castration-resistant prostate cancer-related prognostic factors, duration of therapy, and maximum prostate-specific antigen (PSA) percentage...... change were registered during treatment with CA and previous/subsequent novel androgen receptor targeting therapies. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. A median of 6 versus 5 treatment cycles was administered in patients treated...

  17. Susceptibility tests to second line drugs and re-treatment of tuberculosis: Revisiting Early Experiences Las pruebas de sensibilidad a drogas de segunda línea y el re-tratamiento de la tuberculosis: Visión retrospectiva de tres estudios

    Directory of Open Access Journals (Sweden)

    Isabel N. De Kantor

    2007-06-01

    Full Text Available The value of susceptibility tests in guiding antituberculous therapy with second-line drugs remains controversial. We reanalyzed three reports regarding the relationship between in vitro susceptibility of Mycobacterium tuberculosis and the clinical outcome of in-patients treated with these drugs at the Muñiz Hospital, Buenos Aires, during the sixties. These patients had been irregularly treated with a standard regimen consisting of isoniazid, streptomycin and PAS; they developed resistance to at least the first two drugs and persisted culture-positive. Susceptibility testing to ethionamide, cycloserine and kanamycin were performed by the proportion method on Löwenstein Jensen medium. Some level of resistance was detected among isolates from patients not previously treated with these drugs, that could be due to cross resistance with previously administered first line structural analogs. However, the studies evidenced significant association between resistance to ethionamide and cycloserine and prior treatment with these drugs. Increased resistanceto all three drugs was detected within the first three months of treatment. In vitro resistance to ethionamide emerged earlier and was the most frequent followed by resistance to cycloserine and kanamycin. The low frequency of resistance to kanamycin could be related to the low dosage of this drug used at that time. Simultaneous resistance to the three agents, but not to two or one drug, appeared to be a marker of treatment failure. An apparent reversion of drug resistance was observed in near 6% of patients, for whom susceptibility tests were repeated on subsequent isolates, indicating this percentage of inconsistency in reproducibility of test results.La correlación entre resultados de pruebas de sensibilidad a drogas antituberculosas de segunda línea y evolución de los pacientes en tratamiento, aún es discutida. Se reanalizan aquí tres estudios realizados en la década del 60, sobre la relaci

  18. Paclitaxel with Cisplatin as Salvage Treatment for Patients with Previously Treated Advanced Transitional Cell Carcinoma of the Urothelial Tract

    Directory of Open Access Journals (Sweden)

    Ji Eun Uhm

    2007-01-01

    Full Text Available BACKGROUND: This study was performed to evaluate the safety and efficacy of paclitaxel with cisplatin as salvage therapy in patients previously treated with gemcitabine and cisplatin (G/C for advanced transitional cell carcinoma (TCC of the urothelial tract. METHODS: Twenty-eight patients with metastatic or locally advanced TCC who had received prior G/C chemotherapy were enrolled. All patients received paclitaxel (175 mg/m2 and cisplatin (60 mg/m2 every 3 weeks for eight cycles or until disease progression. RESULTS: The median age was 61 years (range, 43–83 years, and the median Eastern Cooperative Oncology Group performance status was 1 (range, 0–2. The overall response rate was 36% [95% confidence interval (95% CI = 18–54], with three complete responses and seven partial responses. The median time to progression was 6.2 months (95% CI = 3.9–8.5, and the median overall survival was 10.3 months (95% CI = 6.1–14.1. The most common Grade 3/4 nonhematologic and hematologic toxicities were emesis (10 of 28 patients; 36% and neutropenia (5 of 110 cycles; 5%. CONCLUSIONS: Salvage chemotherapy with paclitaxel and cisplatin displayed promising results with tolerable toxicity profiles in patients with metastatic or locally advanced TCC who had been pretreated with G/C.

  19. Neither high-dose nor low-dose brachytherapy increases flap morbidity in salvage treatment of recurrent head and neck cancer

    Directory of Open Access Journals (Sweden)

    Peter W. Henderson

    2016-08-01

    Full Text Available Purpose: While brachytherapy is often used concurrently with flap reconstruction following surgical ablation for head and neck cancer, it remains unclear whether it increases morbidity in the particularly high risk subset of patients undergoing salvage treatment for recurrent head and neck cancer (RH&NC. Material and methods : A retrospective chart review was undertaken that evaluated patients with RH&NC who underwent flap coverage after surgical re-resection and concomitant brachytherapy. The primary endpoint was flap viability, and the secondary endpoints were flap and recipient site complications. Results : In the 23 subjects included in series, flap viability and skin graft take was 100%. Overall recipient site complication rate was 34.8%, high-dose radiation (HDR group 50%, and low-dose radiation (LDR group 29.4%. There was no statistically significant difference between these groups. Conclusions : In patients who undergo flap reconstruction and immediate postoperative radiotherapy following salvage procedures for RH&NC, flap coverage of defects in combination with brachytherapy remains a safe and effective means of providing stable soft tissue coverage.

  20. Efficacy and feasibility of ambulatory treatment-based monthly nedaplatin plus S-1 in definitive or salvage concurrent chemoradiotherapy for early, advanced, and relapsed esophageal cancer

    International Nuclear Information System (INIS)

    Yamashita, Hideomi; Haga, Akihiro; Takenaka, Ryousuke; Kiritoshi, Tomoki; Okuma, Kae; Ohtomo, Kuni; Nakagawa, Keiichi

    2016-01-01

    Standard chemoradiotherapy (CRT) using cisplatin (CDDP) and 5-fluorouracil (5-FU) is an optional treatment for patients with stage II-III esophageal cancer. However, there are some demerits in this regimen because CDDP administration requires a large transfusion volume and 5-FU must be continuously infused over 24 h. Therefore, hospitalization is unavoidable. We collected retrospectively the data of definitive CRT with nedaplatin and S-1 as carried out in our institution. Patients with early and advanced esophageal cancer and relapsed esophageal cancer after radical surgery were included. Nedaplatin 80 mg/m 2 was given on days 1 and 29, and S-1 80 mg/m 2 on days 1-14 and 29-42. No prophylactic treatment with granulocyte colony stimulating factor was administered. Patients received two courses of concurrent radiotherapy of more than 50 Gy with or without two additional courses as adjuvant therapy every 4 weeks. Between August 2011 and June 2015, 89 patients (age range, 44–86 years; K-PS 90–100, 81 %; squamous cell carcinoma histology, 97 %; definitive/salvage CRT, 75/25 %) were collected. Twenty-one (24 %) patients completed four cycles, and 94 % received two or more cycles. Grade 4 leukopenia, thrombocytopenia, and anemia occurred in 12, 7, and 10 % of the patients, respectively. Five patients developed febrile neutropenia. Grade 3 non-hematological toxicity included infection in 12 %, mucositis/esophagitis in 3 %, kidney in 3 %, and fatigue in 3 %. Sixty-four patients (72 %) received the prescribed full dose and full cycles of chemotherapy. A complete response was achieved in 76 patients (85 %). The 3-year overall survival rate was 54.4 % in definitive CRT and 39.8 % in salvage CRT, respectively. Sixty-two subjects (70 %) received treatment as outpatients. Nedaplatin and S-1 in combination with radiotherapy is feasible, and toxicity is tolerable. This treatment method has the potential to shorten hospitalization without impairing the efficacy of CRT

  1. Efficacy and feasibility of ambulatory treatment-based monthly nedaplatin plus S-1 in definitive or salvage concurrent chemoradiotherapy for early, advanced, and relapsed esophageal cancer.

    Science.gov (United States)

    Yamashita, Hideomi; Haga, Akihiro; Takenaka, Ryousuke; Kiritoshi, Tomoki; Okuma, Kae; Ohtomo, Kuni; Nakagawa, Keiichi

    2016-01-19

    Standard chemoradiotherapy (CRT) using cisplatin (CDDP) and 5-fluorouracil (5-FU) is an optional treatment for patients with stage II-III esophageal cancer. However, there are some demerits in this regimen because CDDP administration requires a large transfusion volume and 5-FU must be continuously infused over 24 h. Therefore, hospitalization is unavoidable. We collected retrospectively the data of definitive CRT with nedaplatin and S-1 as carried out in our institution. Patients with early and advanced esophageal cancer and relapsed esophageal cancer after radical surgery were included. Nedaplatin 80 mg/m(2) was given on days 1 and 29, and S-1 80 mg/m(2) on days 1-14 and 29-42. No prophylactic treatment with granulocyte colony stimulating factor was administered. Patients received two courses of concurrent radiotherapy of more than 50 Gy with or without two additional courses as adjuvant therapy every 4 weeks. Between August 2011 and June 2015, 89 patients (age range, 44-86 years; K-PS 90-100, 81 %; squamous cell carcinoma histology, 97 %; definitive/salvage CRT, 75/25 %) were collected. Twenty-one (24 %) patients completed four cycles, and 94 % received two or more cycles. Grade 4 leukopenia, thrombocytopenia, and anemia occurred in 12, 7, and 10 % of the patients, respectively. Five patients developed febrile neutropenia. Grade 3 non-hematological toxicity included infection in 12 %, mucositis/esophagitis in 3 %, kidney in 3 %, and fatigue in 3 %. Sixty-four patients (72 %) received the prescribed full dose and full cycles of chemotherapy. A complete response was achieved in 76 patients (85 %). The 3-year overall survival rate was 54.4 % in definitive CRT and 39.8 % in salvage CRT, respectively. Sixty-two subjects (70 %) received treatment as outpatients. Nedaplatin and S-1 in combination with radiotherapy is feasible, and toxicity is tolerable. This treatment method has the potential to shorten hospitalization without impairing the efficacy of CRT.

  2. Body composition and metabolic outcomes after 96 weeks of treatment with ritonavir-boosted lopinavir plus either nucleoside or nucleotide reverse transcriptase inhibitors or raltegravir in patients with HIV with virological failure of a standard first-line antiretroviral therapy regimen: a substudy of the randomised, open-label, non-inferiority SECOND-LINE study.

    Science.gov (United States)

    Boyd, Mark A; Amin, Janaki; Mallon, Patrick W G; Kumarasamy, Nagalingeswaran; Lombaard, Johan; Wood, Robin; Chetchotisakd, Ploenchan; Phanuphak, Praphan; Mohapi, Lerato; Azwa, Iskandar; Belloso, Waldo H; Molina, Jean-Michel; Hoy, Jennifer; Moore, Cecilia L; Emery, Sean; Cooper, David A

    2017-01-01

    Lipoatrophy is one of the most feared complications associated with the use of nucleoside or nucleotide reverse transcriptase inhibitors (N[t]RTIs). We aimed to assess soft-tissue changes in participants with HIV who had virological failure of a first-line antiretroviral (ART) regimen containing a non-nucleoside reverse transcriptase inhibitor plus two N(t)RTIs and were randomly assigned to receive a second-line regimen containing a boosted protease inhibitor given with either N(t)RTIs or raltegravir. Of the 37 sites that participated in the randomised, open-label, non-inferiority SECOND-LINE study, eight sites from five countries (Argentina, India, Malaysia, South Africa, and Thailand) participated in the body composition substudy. All sites had a dual energy x-ray absorptiometry (DXA) scanner and all participants enrolled in SECOND-LINE were eligible for inclusion in the substudy. Participants were randomly assigned (1:1), via a computer-generated allocation schedule, to receive either ritonavir-boosted lopinavir plus raltegravir (raltegravir group) or ritonavir-boosted lopinavir plus two or three N(t)RTIs (N[t]RTI group). Randomisation was stratified by site and screening HIV-1 RNA. Participants and investigators were not masked to group assignment, but allocation was concealed until after interventions were assigned. DXA scans were done at weeks 0, 48, and 96. The primary endpoint was mean percentage and absolute change in peripheral limb fat from baseline to week 96. We did intention-to-treat analyses of available data. This substudy is registered with ClinicalTrials.gov, number NCT01513122. Between Aug 1, 2010, and July 10, 2011, we recruited 211 participants into the substudy. The intention-to-treat population comprised 102 participants in the N(t)RTI group and 108 participants in the raltegravir group, of whom 91 and 105 participants, respectively, reached 96 weeks. Mean percentage change in limb fat from baseline to week 96 was 16·8% (SD 32·6) in the N

  3. The need for second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030: a mathematical modelling study.

    Science.gov (United States)

    Estill, Janne; Ford, Nathan; Salazar-Vizcaya, Luisa; Haas, Andreas D; Blaser, Nello; Habiyambere, Vincent; Keiser, Olivia

    2016-03-01

    The number of patients in need of second-line antiretroviral drugs is increasing in sub-Saharan Africa. We aimed to project the need of second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030. We developed a simulation model for HIV and applied it to each sub-Saharan African country. We used the WHO country intelligence database to estimate the number of adult patients receiving antiretroviral therapy from 2005 to 2014. We fitted the number of adult patients receiving antiretroviral therapy to observed estimates, and predicted first-line and second-line needs between 2015 and 2030. We present results for sub-Saharan Africa, and eight selected countries. We present 18 scenarios, combining the availability of viral load monitoring, speed of antiretroviral scale-up, and rates of retention and switching to second-line. HIV transmission was not included. Depending on the scenario, 8·7-25·6 million people are expected to receive antiretroviral therapy in 2020, of whom 0·5-3·0 million will be receiving second-line antiretroviral therapy. The proportion of patients on treatment receiving second-line therapy was highest (15·6%) in the scenario with perfect retention and immediate switching, no further scale-up, and universal routine viral load monitoring. In 2030, the estimated range of patients receiving antiretroviral therapy will remain constant, but the number of patients receiving second-line antiretroviral therapy will increase to 0·8-4·6 million (6·6-19·6%). The need for second-line antiretroviral therapy was two to three times higher if routine viral load monitoring was implemented throughout the region, compared with a scenario of no further viral load monitoring scale-up. For each monitoring strategy, the future proportion of patients receiving second-line antiretroviral therapy differed only minimally between countries. Donors and countries in sub-Saharan Africa should prepare for a substantial increase in the need for second-line

  4. Viable tumor in salvage neck dissections in head and neck cancer : Relation with initial treatment, change of lymph node size and human papillomavirus

    NARCIS (Netherlands)

    van den Bovenkamp, Karlijn; Dorgelo, Bart; Noordhuis, Maartje G; van der Laan, Bernard F A M; van der Vegt, Bert; Bijl, Hendrik P; Roodenburg, Jan L; van Dijk, Boukje A C; Oosting, Sjoukje F; Schuuring, Ed M D; Langendijk, Johannes A; Halmos, Gyorgy B; Plaat, Boudewijn E C

    Objectives: To identify predictive factors for the presence of viable tumor and outcome in head and neck cancer patients who undergo therapeutic salvage neck dissections. Materials and Methods: Retrospective analysis of 76 salvage neck dissections after radiotherapy alone (n = 22), radiotherapy in

  5. In chronic myeloid leukemia patients on second-line tyrosine kinase inhibitor therapy, deep sequencing of BCR-ABL1 at the time of warning may allow sensitive detection of emerging drug-resistant mutants.

    Science.gov (United States)

    Soverini, Simona; De Benedittis, Caterina; Castagnetti, Fausto; Gugliotta, Gabriele; Mancini, Manuela; Bavaro, Luana; Machova Polakova, Katerina; Linhartova, Jana; Iurlo, Alessandra; Russo, Domenico; Pane, Fabrizio; Saglio, Giuseppe; Rosti, Gianantonio; Cavo, Michele; Baccarani, Michele; Martinelli, Giovanni

    2016-08-02

    Imatinib-resistant chronic myeloid leukemia (CML) patients receiving second-line tyrosine kinase inhibitor (TKI) therapy with dasatinib or nilotinib have a higher risk of disease relapse and progression and not infrequently BCR-ABL1 kinase domain (KD) mutations are implicated in therapeutic failure. In this setting, earlier detection of emerging BCR-ABL1 KD mutations would offer greater chances of efficacy for subsequent salvage therapy and limit the biological consequences of full BCR-ABL1 kinase reactivation. Taking advantage of an already set up and validated next-generation deep amplicon sequencing (DS) assay, we aimed to assess whether DS may allow a larger window of detection of emerging BCR-ABL1 KD mutants predicting for an impending relapse. a total of 125 longitudinal samples from 51 CML patients who had acquired dasatinib- or nilotinib-resistant mutations during second-line therapy were analyzed by DS from the time of failure and mutation detection by conventional sequencing backwards. BCR-ABL1/ABL1%(IS) transcript levels were used to define whether the patient had 'optimal response', 'warning' or 'failure' at the time of first mutation detection by DS. DS was able to backtrack dasatinib- or nilotinib-resistant mutations to the previous sample(s) in 23/51 (45 %) pts. Median mutation burden at the time of first detection by DS was 5.5 % (range, 1.5-17.5 %); median interval between detection by DS and detection by conventional sequencing was 3 months (range, 1-9 months). In 5 cases, the mutations were detectable at baseline. In the remaining cases, response level at the time mutations were first detected by DS could be defined as 'Warning' (according to the 2013 ELN definitions of response to 2nd-line therapy) in 13 cases, as 'Optimal response' in one case, as 'Failure' in 4 cases. No dasatinib- or nilotinib-resistant mutations were detected by DS in 15 randomly selected patients with 'warning' at various timepoints, that later turned into optimal

  6. Malignant bone tumors and limb-salvage surgery in children

    International Nuclear Information System (INIS)

    Meyer, James S.; Mackenzie, William

    2004-01-01

    Limb-salvage surgery plays a major role in the management of children with malignant bone tumors. This article provides background on the clinical presentation and imaging evaluation of children with malignant bone tumors and describes various limb-salvage procedures used in the treatment of these children. (orig.)

  7. Use of anti-retroviral therapy in tuberculosis patients on second-line anti-TB regimens: a systematic review.

    Directory of Open Access Journals (Sweden)

    Matthew Arentz

    Full Text Available Use of antiretroviral therapy (ART during treatment of drug susceptible tuberculosis (TB improves survival. However, data from HIV infected individuals with drug resistant TB are lacking. Second line TB drugs when combined with ART may increase drug interactions and lead to higher rates of toxicity and greater noncompliance. This systematic review sought to determine the benefit of ART in the setting of second line drug therapy for drug resistant TB.We included individual patient data from studies that evaluated treatment of drug-resistant tuberculosis in HIV-1 infected individuals published between January 1980 and December of 2009. We evaluated the effect of ART on treatment outcomes, time to smear and culture conversion, and adverse events.Ten observational studies, including data from 217 subjects, were analyzed. Patients using ART during TB treatment had increased likelihood of cure (hazard ratio (HR 3.4, 95% CI 1.6-7.4 and decreased likelihood of death (HR 0.4, 95% CI 0.3-0.6 during treatment for drug resistant TB. These associations remained significant in patients with a CD4 less than 200 cells/mm(3 and less than 50 cells/mm(3, and when correcting for drug resistance pattern.We identified only observational studies from which individual patient data could be drawn. Limitations in study design, and heterogeneity in a number of the outcomes of interest had the potential to introduce bias.While there are insufficient data to determine if ART use increases adverse drug interactions when used with second line TB drugs, ART use during treatment of drug resistant TB appears to improve cure rates and decrease risk of death. All individuals with HIV appear to benefit from ART use during treatment for TB.

  8. Prognostic and predictive factors in patients with advanced penile cancer receiving salvage (2nd or later line systemic treatment: a retrospective, multi-center study

    Directory of Open Access Journals (Sweden)

    Carlo Buonerba

    2016-12-01

    Full Text Available AbstractIntroduction & objectives: Metastatic penile squamous cell carcinoma (PSCC is associated with dismal outcomes with median overall survival (OS of 6-12 months in the first-line and <6 months in the salvage setting. Given the rarity of this disease, randomized trials are difficult. Prognostic risk models may assist in rational drug development by comparing observed outcomes in nonrandomized phase II studies and retrospective data versus predicted outcomes based on baseline prognostic factors in the context of historically used agents. In this retrospective study, we constructed a prognostic model in the salvage setting of PSCC patients receiving second or later line systemic treatment, and also explored differences in outcomes based on type of treatment.Materials & methods: We performed a chart review to identify patients with locally advanced unresectable or metastatic PSCC who received second or later line systemic treatment in centers from North America and Europe. The primary outcome was OS from initiation of treatment, with secondary outcomes being progression-free survival (PFS and response rate (RR. OS was estimated using the Kaplan-Meier method. Cox proportional hazards regression was used to identify prognostic factors for outcomes using univariable and multivariable models. Results: Sixty-five patients were eligible. Seventeen of 63 evaluable patients had a response (27.0%, 95% confidence interval [CI]=16.6% to 39.7% and median OS and PFS were 20 (95% CI=20 to 21 and 12 (95% CI =12, 16 weeks, respectively. Visceral metastasis (VM and hemoglobin (Hb ≤10 gm/dl were consistently significant poor prognostic factors for both OS and PFS, and Hb was also prognostic for response. The 28 patients with neither risk factor had a median OS (95% CI of 24 (20-40 weeks and 1-year (95% CI OS of 13.7% (4.4-42.7%, while the 37 patients with 1 or 2 risk factors had median OS (95% CI of 20 (16-20 weeks and 1-year (95% CI OS of 6.7% (1

  9. Hemibody irradiation. An effective second-line therapy in drug-resistance multiple myeloma

    International Nuclear Information System (INIS)

    Singer, C.R.; Tobias, J.S.; Giles, F.; Rudd, G.N.; Blackman, G.M.; Richards, J.D.

    1989-01-01

    The authors report the results of treatment of 41 patients with melphalan-resistant multiple myeloma using single half-body irradiation (HBI) or double half-body irradiation (DHBI). Patients were grouped using prognostic classification reported by the Medical Research Council. Patients in group I and II showed the best response to therapy with reduction in serum of urinary paraprotein and improvement in symptoms, most notably a marked reduction in bone pain. In these groups five patients have survived over 2 years after therapy. The therapeutic response appeared better in those patients who received DHBI as opposed to those whom treated with single HBI. Patients in group III did not achieve prolonged survival but effective relief of bone pain was a consistent finding in these patients also. Thus HBI represents an alternative to combination chemotherapy as second-line treatment of patients with melphalan-resistant multiple myeloma. A comparative study of HBI versus combination chemotherapy is now indicated to establish which therapeutic approach is most effective

  10. Local recurrence risk after previous salvage mastectomy.

    Science.gov (United States)

    Tanabe, M; Iwase, T; Okumura, Y; Yoshida, A; Masuda, N; Nakatsukasa, K; Shien, T; Tanaka, S; Komoike, Y; Taguchi, T; Arima, N; Nishimura, R; Inaji, H; Ishitobi, M

    2016-07-01

    Breast-conserving surgery is a standard treatment for early breast cancer. For ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery, salvage mastectomy is the current standard surgical procedure. However, it is not rare for patients with IBTR who have received salvage mastectomy to develop local recurrence. In this study, we examined the risk factors of local recurrence after salvage mastectomy for IBTR. A total of 118 consecutive patients who had histologically confirmed IBTR without distant metastases and underwent salvage mastectomy without irradiation for IBTR between 1989 and 2008 were included from eight institutions in Japan. The risk factors of local recurrence were assessed. The median follow-up period from salvage mastectomy for IBTR was 4.6 years. Patients with pN2 or higher on diagnosis of the primary tumor showed significantly poorer local recurrence-free survival than those with pN0 or pN1 at primary tumor (p mastectomy for IBTR. Further research and validation studies are needed. (UMIN-CTR number UMIN000008136). Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Comparison of Second-Line Quadruple Therapies with or without Bismuth for Helicobacter pylori Infection

    Directory of Open Access Journals (Sweden)

    Guang-Hong Jheng

    2015-01-01

    Full Text Available The bismuth-based quadruple regimen has been applied in Helicobacter pylori rescue therapy worldwide. The non-bismuth-based quadruple therapy or “concomitant therapy” is an alternative option in first-line eradication but has not been used in second-line therapy. Discovering a valid regimen for rescue therapy in bismuth-unavailable countries is important. We conducted a randomized controlled trial to compare the efficacies of the standard quadruple therapy and a modified concomitant regimen. One hundred and twenty-four patients were randomly assigned into two groups: RBTM (rabeprozole 20 mg bid., bismuth subcitrate 120 mg qid, tetracycline 500 mg qid, and metronidazole 250 mg qid and RATM (rabeprozole 20 mg bid., amoxicillin 1 g bid., tetracycline 500 mg qid, and metronidazole 250 mg qid for 10 days. The eradication rate of the RBTM and RATM regimen was 92.1% and 90.2%, respectively, in intention-to-treat analysis. Patients in both groups had good compliance (~96%. The overall incidence of adverse events was higher in the RATM group (42.6% versus 22.2%, P=0.02, but only seven patients (11.5% experienced grades 2-3 events. In conclusion, both regimens had good efficacy, compliance, and acceptable side effects. The 10-day RATM treatment could be an alternative rescue therapy in bismuth-unavailable countries.

  12. Advances in imaging and in non-surgical salvage treatments after radiorecurrence in prostate cancer: what does the oncologist, radiotherapist and radiologist need to know?

    Energy Technology Data Exchange (ETDEWEB)

    Gravina, Giovanni Luca [University of L' Aquila, Medical School, Laboratory of Radiobiology, Division of Radiation Oncology, Department of Experimental Medicine, L' Aquila (Italy); S. Salvatore Hospital, Division of Radiation Oncology, L' Aquila (Italy); University of L' Aquila, Medical School, Department of Experimental Medicine, Laboratory of Radiobiology, L' Aquila (Italy); University of Rome ' ' La Sapienza' ' , Department of Experimental Medicine, Rome (Italy); Tombolini, Vincenzo [University of Rome ' ' La Sapienza' ' , Spencer-Lorillard Foundation (V.T.), Department of Radiological Sciences, Division of Radiotherapy, Rome (Italy); Di Staso, Mario; Franzese, Pietro; Bonfili, Pierluigi; Di Nicola, Leda [S. Salvatore Hospital, Division of Radiation Oncology, L' Aquila (Italy); Gennarelli, Antonio; Masciocchi, Carlo [University of L' Aquila, S. Salvatore Hospital, Department of Radiology, L' Aquila (Italy); Di Cesare, Ernesto di [University of L' Aquila, Medical School, Laboratory of Radiobiology, Division of Radiation Oncology, Department of Experimental Medicine, L' Aquila (Italy); S. Salvatore Hospital, Division of Radiation Oncology, L' Aquila (Italy); University of L' Aquila, Medical School, Department of Experimental Medicine, Laboratory of Radiobiology, L' Aquila (Italy)

    2012-12-15

    In this article the state of art the of prostate cancer (Pca) imaging and non-surgical salvage treatments (STs) is surveyed in order to explore the impact of imaging findings on the identification of radiorecurrent Pca after external beam radiotherapy (EBRT). A computerised search was performed to identify all relevant studies in Medline up to 2012. Additional articles were extracted based on recommendations from an expert panel of authors. Definitive EBRT for Pca is increasingly used as treatment. After radiorecurrent Pca, non-surgical STs are emerging and shifting from investigational status to more established therapeutic options. Therefore, several scientific societies have published guidelines including clinical and imaging recommendations, even if the timing, efficacy and long-term toxicity of these STs have to be established. In some measure, accurately delineating the location and the extent of cancer is critical in selecting target lesions and in identifying patients who are candidates for STs. However, there is increasing awareness that anatomical approaches based on measurements of tumour size have substantial limitations, especially for tumours of unknown activity that persist or recur following irradiation To date, the main focus for innovations in imaging is the combination of excellence in anatomical resolution with specific biological correlates that depict metabolic processes and hallmarks at the tumour level. The emergence of new molecular markers could favour the development of methods that directly determine their presence, thereby improving tumour detection. (orig.)

  13. Advances in imaging and in non-surgical salvage treatments after radiorecurrence in prostate cancer: what does the oncologist, radiotherapist and radiologist need to know?

    International Nuclear Information System (INIS)

    Gravina, Giovanni Luca; Tombolini, Vincenzo; Di Staso, Mario; Franzese, Pietro; Bonfili, Pierluigi; Di Nicola, Leda; Gennarelli, Antonio; Masciocchi, Carlo; Di Cesare, Ernesto di

    2012-01-01

    In this article the state of art the of prostate cancer (Pca) imaging and non-surgical salvage treatments (STs) is surveyed in order to explore the impact of imaging findings on the identification of radiorecurrent Pca after external beam radiotherapy (EBRT). A computerised search was performed to identify all relevant studies in Medline up to 2012. Additional articles were extracted based on recommendations from an expert panel of authors. Definitive EBRT for Pca is increasingly used as treatment. After radiorecurrent Pca, non-surgical STs are emerging and shifting from investigational status to more established therapeutic options. Therefore, several scientific societies have published guidelines including clinical and imaging recommendations, even if the timing, efficacy and long-term toxicity of these STs have to be established. In some measure, accurately delineating the location and the extent of cancer is critical in selecting target lesions and in identifying patients who are candidates for STs. However, there is increasing awareness that anatomical approaches based on measurements of tumour size have substantial limitations, especially for tumours of unknown activity that persist or recur following irradiation To date, the main focus for innovations in imaging is the combination of excellence in anatomical resolution with specific biological correlates that depict metabolic processes and hallmarks at the tumour level. The emergence of new molecular markers could favour the development of methods that directly determine their presence, thereby improving tumour detection. (orig.)

  14. Second-line afatinib administration in an elderly patient with squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hohenforst-Schmidt W

    2017-03-01

    Full Text Available Wolfgang Hohenforst-Schmidt,1 Paul Zarogoulidis,2 Michael Steinheimer,1 Naim Benhassen,3 Chrysanthi Sardeli,4 Nikos Stalikas,2 Melpomeni Toitou,2 Haidong Huang5 1Sana Clinic Group Franken, Department of Cardiology/Pulmonology/Intensive Care/Nephrology, “Hof” Clinics, University of Erlangen, Hof, Germany; 2Pulmonary Department – Oncology Unit, “G Papanikolaou” General Hospital, Thessaloniki, Greece; 3Medical Clinic I, “Fuerth” Hospital, University of Erlangen, Fuerth, Germany; 4Department of Pharmacology & Clinical Pharmacology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; 5Department of Respiratory and Critical Care Medicine, Changhai Hospital/First Affiliated Hospital of the Secondary Military Medical University, Shanghai, China Introduction: The majority of cases of lung cancer are still diagnosed at a late stage. At this stage, palliative therapeutic options including nonspecific cytotoxic drugs, targeted therapy, or immunotherapy can be utilized. In 2016, immunotherapy was approved in Europe for squamous cell carcinoma and adenocarcinoma. Moreover, afatinib was also approved as second-line therapy for squamous cell carcinoma. Case report: This article presents a case of a 76-year-old male with squamous cell carcinoma who received nab-paclitaxel as first-line therapy, and his treatment was switched to the tyrosine kinase inhibitor afatinib (40 mg after disease progression with left lung atelectasis. After receiving afatinib for only 28 days, the atelectasis resolved. No adverse effects were observed from the afatinib therapy. Discussion: In this case, afatinib 40 mg proved to be an effective alternative treatment for an elderly patient. Treatment choice should be based on the performance status of the patient, cost-effectiveness, and drug treatment guidelines. Keywords: lung cancer, EGFR, afatinib

  15. First- and Second-Line Targeted Systemic Therapy in Hepatocellular Carcinoma—An Update on Patient Selection and Response Evaluation

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    Johann von Felden

    2016-11-01

    Full Text Available Advanced hepatocellular carcinoma (HCC with vascular invasion and/or extrahepatic spread and preserved liver function, according to stage C of the Barcelona Clinic Liver Cancer (BCLC classification, has a dismal prognosis. The multi-targeted tyrosine-kinase receptor inhibitor (TKI sorafenib is the only proven active substance in systemic HCC therapy for first-line treatment. In this review, we summarize current aspects in patient selection and management of side effects, and provide an update on response evaluation during first-line sorafenib therapy. Since second-line treatment options have been improved with the successful completion of the RESORCE trial, demonstrating a survival benefit for second-line treatment with the TKI regorafenib, response monitoring during first-line therapy will be critical to deliver optimal systemic therapy in HCC. To this regard, specific side effects, in particular worsening of arterial hypertension and diarrhea, might suggest treatment response during first-line sorafenib therapy; however, clear predictive clinical markers, as well as laboratory test or serum markers, are not established. Assessment of radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST is helpful to identify patients who do not benefit from sorafenib treatment.

  16. Clinical study of salvage surgery after concurrent chemoradiotherapy

    International Nuclear Information System (INIS)

    Shimane, Toshikazu; Nakamura, Taisuke; Shimotatara, Yuko

    2013-01-01

    As the use of concurrent chemoradiotherapy (CCRT) is becoming more widespread, with numerous facilities performing it to maintain function and form, the number of cases requiring salvage surgery is also increasing. We investigated the postoperative prognosis of patients who experienced complications during salvage surgery after CCRT. Subjects were 27 patients who underwent salvage surgery following CCRT at our department during the 7-year period between January 2005 and December 2011. We selected all cases of salvage surgery, comprising neck dissections, total laryngectomies, partial laryngectomies, esophageal resections, and reconstructive surgeries, for analysis. The results were favorable, with a complication rate during salvage surgery after CCRT of 14.8% and a survival rate of 77.8%. Although it is difficult to compare these complications and outcome findings with available reports on salvage surgery without CCRT, it is believed complications can arise in approximately half of the cases. Thus, surgeons should be cognizant of the potential for serious complications, which are sometimes unexpected. Different from our findings, the prognosis following salvage surgery is generally not thought to be favorable and therefore care should be taken to detect recurrence and provide treatment early in salvage surgery cases. (author)

  17. Limb salvage surgery.

    Science.gov (United States)

    Kadam, Dinesh

    2013-05-01

    The threat of lower limb loss is seen commonly in severe crush injury, cancer ablation, diabetes, peripheral vascular disease and neuropathy. The primary goal of limb salvage is to restore and maintain stability and ambulation. Reconstructive strategies differ in each condition such as: Meticulous debridement and early coverage in trauma, replacing lost functional units in cancer ablation, improving vascularity in ischaemic leg and providing stable walking surface for trophic ulcer. The decision to salvage the critically injured limb is multifactorial and should be individualised along with laid down definitive indications. Early cover remains the standard of care, delayed wound coverage not necessarily affect the final outcome. Limb salvage is more cost-effective than amputations in a long run. Limb salvage is the choice of procedure over amputation in 95% of limb sarcoma without affecting the survival. Compound flaps with different tissue components, skeletal reconstruction; tendon transfer/reconstruction helps to restore function. Adjuvant radiation alters tissue characters and calls for modification in reconstructive plan. Neuropathic ulcers are wide and deep often complicated by osteomyelitis. Free flap reconstruction aids in faster healing and provides superior surface for offloading. Diabetic wounds are primarily due to neuropathy and leads to six-fold increase in ulcerations. Control of infections, aggressive debridement and vascular cover are the mainstay of management. Endovascular procedures are gaining importance and have reduced extent of surgery and increased amputation free survival period. Though the standard approach remains utilising best option in the reconstruction ladder, the recent trend shows running down the ladder of reconstruction with newer reliable local flaps and negative wound pressure therapy.

  18. Limb salvage surgery

    Directory of Open Access Journals (Sweden)

    Dinesh Kadam

    2013-01-01

    Full Text Available The threat of lower limb loss is seen commonly in severe crush injury, cancer ablation, diabetes, peripheral vascular disease and neuropathy. The primary goal of limb salvage is to restore and maintain stability and ambulation. Reconstructive strategies differ in each condition such as: Meticulous debridement and early coverage in trauma, replacing lost functional units in cancer ablation, improving vascularity in ischaemic leg and providing stable walking surface for trophic ulcer. The decision to salvage the critically injured limb is multifactorial and should be individualised along with laid down definitive indications. Early cover remains the standard of care, delayed wound coverage not necessarily affect the final outcome. Limb salvage is more cost-effective than amputations in a long run. Limb salvage is the choice of procedure over amputation in 95% of limb sarcoma without affecting the survival. Compound flaps with different tissue components, skeletal reconstruction; tendon transfer/reconstruction helps to restore function. Adjuvant radiation alters tissue characters and calls for modification in reconstructive plan. Neuropathic ulcers are wide and deep often complicated by osteomyelitis. Free flap reconstruction aids in faster healing and provides superior surface for offloading. Diabetic wounds are primarily due to neuropathy and leads to six-fold increase in ulcerations. Control of infections, aggressive debridement and vascular cover are the mainstay of management. Endovascular procedures are gaining importance and have reduced extent of surgery and increased amputation free survival period. Though the standard approach remains utilising best option in the reconstruction ladder, the recent trend shows running down the ladder of reconstruction with newer reliable local flaps and negative wound pressure therapy.

  19. Phase II trial of second-line erlotinib and digoxin for nonsmall cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    Fadi Kayali

    2011-02-01

    Full Text Available Fadi Kayali, Muhamad A Janjua, Damian A Laber, Donald Miller, Goetz H KloeckerUniversity of Louisville, James Graham Brown Cancer Center, Louisville, KY, USABackground: In vitro digoxin sensitizes cancer cells to the induction of apoptosis by chemotherapy. Inhibition of the Na/K-ATPase enzyme by ouabain disturbs the intracellular ion composition of cancer cells, altering cellular homeostasis. This suggests that inhibition of the Na/K pump results in cellular sensitization of malignant but not benign cells to the induction of apoptosis. Epidemiologic studies have also shown beneficial effects of digitalis in breast cancer incidence. At ASCO (American Society of Clinical Oncology 2007 our group presented a Phase II study showing encouraging results by adding digoxin to biochemotherapy for melanoma. Erlotinib is one of the standard second-line treatments for nonsmall cell lung cancer (NSCLC, with a response rate (RR of 10%. This study's hypothesis was that adding digoxin to erlotinib will improve the RR and time to progression (TTP in NSCLC.Methods: Patients with progressive disease (PD after chemotherapy were enrolled if they had an ECOG (Eastern Cooperative Oncology Group score from 0 to 2 and good organ function. Daily erlotinib 150 mg and digoxin 0.25 mg were taken by mouth. The digoxin dose was adjusted to keep levels between 1 and 2 ng/mL. Computed tomography scans were done every 6 weeks. Treatment continued until PD or significant toxicity occurred.Results: Patient accrual lasted from March 2006 until August 2008 and was stopped early at the time of interim analysis. Twenty-eight patients were enrolled, and 24 who completed at least 6 weeks of therapy are presented here. All patients had unresectable NSCLC stage III/IV at diagnosis. Median age was 61 (34–78, 14 were female, 17 had prior radiation (not involving the target lesions, 23 had one prior chemotherapy, and one subject had two. Only one patient was a never-smoker. Histologies were

  20. Tuberculosis drug issues: prices, fixed-dose combination products and second-line drugs.

    Science.gov (United States)

    Laing, R O; McGoldrick, K M

    2000-12-01

    Access to tuberculosis drugs depends on multiple factors. Selection of a standard list of TB drugs to procure is the first step. This paper reviews the advantages and disadvantages of procuring and using fixed-dose combination (FDC) products for both the intensive and continuation phases of treatment. The major advantages are to prevent the emergence of resistance, to simplify logistic management and to reduce costs. The major disadvantage is the need for the manufacturers to assure the quality of these FDCs by bioavailability testing. The paper reports on the inclusion of second-line TB drugs in the 1999 WHO Essential Drug List (EDL). The need to ensure that these drugs are used within established DOTS-Plus programs is stressed. The price of TB drugs is determined by many factors, including producer prices, local taxes and duties as well as mark-ups and fees. TB drug prices for both the public and private sectors from industrialized and developing countries are reported. Price trends over time are also reported. The key findings of this study are that TB drug prices have generally declined in developing countries while they have increased in developed countries, both for the public and private sectors. Prices vary between countries, with the US paying as much as 95 times the price paid in a specific developing country. The prices of public sector first-line TB drugs vary little between countries, although differences do exist due to the procurement methods used. The price of tuberculin, a diagnostic agent, has increased dramatically in the US, with substantial inter-country variations in price. The paper suggests that further research is necessary to identify the reasons for the price disparities and changes over time, and suggests methods which can be used by National Tuberculosis Programme managers to ensure availability of quality assured TB drugs at low prices.

  1. Effects of salvage logging and pile-and-burn on fuel loading, potential fire behaviour, fuel consumption and emissions

    Science.gov (United States)

    Morris C. Johnson; Jessica E. Halofsky; David L. Peterson

    2013-01-01

    We used a combination of field measurements and simulation modelling to quantify the effects of salvage logging, and a combination of salvage logging and pile-and-burn fuel surface fuel treatment (treatment combination), on fuel loadings, fire behaviour, fuel consumption and pollutant emissions at three points in time: post-windstorm (before salvage logging), post-...

  2. Association Between Proton Pump Inhibitors and Metronomic Capecitabine as Salvage Treatment for Patients With Advanced Gastrointestinal Tumors: A Randomized Phase II Trial.

    Science.gov (United States)

    Marchetti, Paolo; Milano, Annalisa; D'Antonio, Chiara; Romiti, Adriana; Falcone, Rosa; Roberto, Michela; Fais, Stefano

    2016-12-01

    The acidification of extracellular compartment represents a conceivable mechanism of drug resistance in malignant cells. In addition, it has been reported to drive proliferation and promote invasion and metastasis. Experimental evidence has shown that proton pump inhibitors can counteract tumor acidification and restore sensitivity to anticancer drugs. Moreover, early clinical data have supported the role of proton pump inhibitors in anticancer treatments. Metronomic capecitabine has demonstrated beneficial effects as salvage chemotherapy for heavily pretreated or frail patients with gastrointestinal cancer. The present study (EudraCT Number: 2013-001096-20) was aimed at investigating the activity and safety of high-dose rabeprazole in combination with metronomic capecitabine in patients with advanced gastrointestinal cancer refractory to standard treatment. A total of 66 patients will be randomized 1:1 to receive capecitabine 1500 mg/daily, continuously with or without rabeprazole 1.5 mg/kg twice a day, 3 days a week until disease progression, undue toxicity, or withdrawal of informed consent. The primary endpoint is progression-free survival. The secondary endpoints are clinical benefit, which reflects the proportion of patients with complete response, partial response, and stable disease, and overall survival. Progression-free and overall survival will be evaluated using a log-rank test to determine the effect of rabeprazole independently at the 2-sided α-level of 0.05. Other assessments will include the frequency and severity of adverse events and changes in laboratory parameters to measure the safety, and the pharmacokinetics of capecitabine. The results are expected in 2016. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Second Line of Defense Virtual Private Network Guidance for Deployed and New CAS Systems

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Surya V.; Thronas, Aaron I.

    2010-01-01

    This paper discusses the importance of remote access via virtual private network (VPN) for the Second Line of Defense (SLD) Central Alarm System (CAS) sites, the requirements for maintaining secure channels while using VPN and implementation requirements for current and future sites.

  4. PREDICTORS OF OVERALL SURVIVAL IN PATIENTS WITH RECURRENT NON-SEMINOMATOUS GERMINAL TESTICULAR TUMORS ON CURRENT SECOND-LINE CHEMOTHERAPY

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2010-01-01

    Full Text Available Objective: to define predictors that influence longevity in patients with recurrent non-seminomatous germinal testicular tumors (NGTT on standard second-line chemotherapy (CT including cisplatin and iphosphamide. Statistical analysis was performed using the statistical packages Graph Pad Prism 4.00 for Windows and SPSS 15.0 for Windows. Subjects and methods. Case history data were analyzed in 693 patients with disseminated NGTT who had received current CT and followed up at the Department of Clinical Pharmacology and CT, N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences. The median follow-up was 32 (range 3-215 months. The disease progressed in 181 (26% patients. Detailed information was available on the nature of second-line CT in only 138 patients. Half (71 (51.7% of the 138 patients had second-line CT including iphosphamide. Uni- and multivariate analyses were made to identify predictors that influence longevity in patients with recurrent NGTT on standard secondline CT including cisplatin and iphosphamide. Results. Five-year overall survival (OS was 32% (95% confidence interval 25-41%. The multivariate analysis showed the morphological pattern of a primary tumor (a yolk sac tumor component, a pre-induction CT lactate dehydrogenase (LDH level of ?d1.5 units of the upper normal range, progression during induction CT, and a pre-second-line CT LDH level of ?d 1000 U/l to be negative predictors. According to the number of negative factors, the patients were classified into 3 groups: 1 good prognosis [n = 10 (14% of the 71 patients], 100% 3-year OS; 2 intermediate prognosis (one negative factor [n = 33 (46.5% of the 71 patients], 50.2% 3-year OS; 3 poor prognosis (?d 2 negative factors, 6.7% 3-year OS. Conclusion. Standard iphosphamide-containing therapy enables all patients to be treated in the good prognosis group of those with recurrent NGTT. That fails to achieve such striking results in the intermediate and

  5. Treatment Outcomes from 68Ga-PSMA PET/CT-Informed Salvage Radiation Treatment in Men with Rising PSA After Radical Prostatectomy: Prognostic Value of a Negative PSMA PET.

    Science.gov (United States)

    Emmett, Louise; van Leeuwen, Pim J; Nandurkar, Rohan; Scheltema, Matthijs J; Cusick, Thomas; Hruby, George; Kneebone, Andrew; Eade, Thomas; Fogarty, Gerald; Jagavkar, Raj; Nguyen, Quoc; Ho, Bao; Joshua, Anthony M; Stricker, Phillip

    2017-12-01

    68 Ga-PSMA (prostate-specific membrane antigen) PET/CT is increasingly used in men with prostate-specific antigen (PSA) failure after radical prostatectomy (RP) to triage those who will benefit from salvage radiation treatment (SRT). This study examines the value of PSMA-informed SRT in improving treatment outcomes in the context of biochemical failure after RP. Methods: We analyzed men with rising PSA after RP with PSA readings between 0.05 and 1.0 ng/mL, considered eligible for SRT at the time of PSMA. For each patient, clinical and pathologic features as well as scan results, including site of PSMA-positive disease, number of lesions, and a certainty score, were documented. Subsequent management, including SRT, and most recent PSA were recorded using medical records. Treatment response was defined as both PSA ≤ 0.1 ng/mL and >50% reduction in PSA. Multivariate logistic regression analysis was performed for association of clinical variables and treatment response to SRT. Results: One hundred sixty-four men were included. PSMA was positive in 62% ( n = 102/164): 38 of 102 in the prostatic fossa, 41 of 102 in pelvic nodes, and 23 of 102 distantly. Twenty-four patients received androgen-deprivation therapy (ADT) and were excluded for outcomes analysis. In total, 99 of 146 received SRT with a median follow-up after radiation treatment of 10.5 mo (interquartile range, 6-14 mo). Overall treatment response after SRT was 72% ( n = 71/99). Forty-five percent ( n = 27/60) of patients with a negative PSMA underwent SRT whereas 55% (33/60) did not. In men with a negative PSMA who received SRT, 85% ( n = 23/27) demonstrated a treatment response, compared with a further PSA increase in 65% (22/34) in those not treated. In 36 of 99 patients with disease confined to the prostate fossa on PSMA, 81% ( n = 29/36) responded to SRT. In total, 26 of 99 men had nodal disease on PSMA, of whom 61% ( n = 16/26) had treatment response after SRT. On multivariate logistic regression

  6. Pharmacokinetics of Second-Line Antituberculosis Drugs after Multiple Administrations in Healthy Volunteers.

    Science.gov (United States)

    Park, Sang-In; Oh, Jaeseong; Jang, Kyungho; Yoon, Jangsoo; Moon, Seol Ju; Park, Jong Sun; Lee, Jae Ho; Song, Junghan; Jang, In-Jin; Yu, Kyung-Sang; Chung, Jae-Yong

    2015-08-01

    Therapeutic drug monitoring (TDM) of second-line antituberculosis drugs would allow for optimal individualized dosage adjustments and improve drug safety and therapeutic outcomes. To evaluate the pharmacokinetic (PK) characteristics of clinically relevant, multidrug treatment regimens and to improve the feasibility of TDM, we conducted an open-label, multiple-dosing study with 16 healthy subjects who were divided into two groups. Cycloserine (250 mg), p-aminosalicylic acid (PAS) (5.28 g), and prothionamide (250 mg) twice daily and pyrazinamide (1,500 mg) once daily were administered to both groups. Additionally, levofloxacin (750 mg) and streptomycin (1 g) once daily were administered to group 1 and moxifloxacin (400 mg) and kanamycin (1 g) once daily were administered to group 2. Blood samples for PK analysis were collected up to 24 h following the 5 days of drug administration. The PK parameters, including the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve during a dosing interval at steady state (AUCτ), were evaluated. The correlations between the PK parameters and the concentrations at each time point were analyzed. The mean Cmax and AUCτ, respectively, for each drug were as follows: cycloserine, 24.9 mg/liter and 242.3 mg · h/liter; PAS, 65.9 mg/liter and 326.5 mg · h/liter; prothionamide, 5.3 mg/liter and 22.1 mg · h/liter; levofloxacin, 6.6 mg/liter and 64.4 mg · h/liter; moxifloxacin, 4.7 mg/liter and 54.2 mg · h/liter; streptomycin, 42.0 mg/liter and 196.7 mg · h/liter; kanamycin, 34.5 mg/liter and 153.5 mg · h/liter. The results indicated that sampling at 1, 2.5, and 6 h postdosing is needed for TDM when all seven drugs are administered concomitantly. This study indicates that PK characteristics must be considered when prescribing optimal treatments for patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT02128308.). Copyright © 2015, American Society for

  7. Use of flow-diverting stents as salvage treatment following failed stent-assisted embolization of intracranial aneurysms.

    Science.gov (United States)

    Heiferman, Daniel M; Billingsley, Joshua T; Kasliwal, Manish K; Johnson, Andrew K; Keigher, Kiffon M; Frudit, Michel E; Moftakhar, Roham; Lopes, Demetrius K

    2016-07-01

    Flow-diverting stents, including the Pipeline embolization device (PED) and Silk, have been beneficial in the treatment of aneurysms previously unable to be approached via endovascular techniques. Recurrent aneurysms for which stent-assisted embolization has failed are a therapeutic challenge, given the existing intraluminal construct with continued blood flow into the aneurysm. We report our experience using flow-diverting stents in the repair of 25 aneurysms for which stent-assisted embolization had failed. Nineteen (76%) of these aneurysms at the 12-month follow-up showed improved Raymond class occlusion, with 38% being completely occluded, and all aneurysms demonstrated decreased filling. One patient developed a moderate permanent neurologic deficit. Appropriate stent sizing, proximal and distal construct coverage, and preventing flow diverter deployment between the previously deployed stent struts are important considerations to ensure wall apposition and prevention of endoleak. Flow diverters are shown to be a reasonable option for treating previously stented recurrent cerebral aneurysms. 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/

  8. [Comparison of the Efficacy and Safety of Icotinib with Standard Second-line 
Chemotherapy in Previously Treated Advanced Non-small Cell Lung Cancer].

    Science.gov (United States)

    Yao, Shuyang; Qian, Kun; Wang, Ruotian; Li, Yuanbo; Zhang, Yi

    2015-06-01

    This study compared the efficacy and safety of icotinib with standard second-line chemotherapy (single-agent docetaxel or pemetrexed) in previously treated advanced non-small cell lung cancer (NSCLC). Thirty-two consecutive patients treated with icotinib and 33 consecutive patients treated with standard second-line chemotherapy in Xuanwu Hospital from January 2012 to July 2013 were enrolled in our retrospective research. The Response Evaluation Criteria in Solid Tumors were used to evaluate the tumor responses, and the progression-free survival (PFS) was evaluated by Kaplan-Meier method. Icotinib was comparable with standard second-line chemotherapy for advanced NSCLC in terms of overall response rate (ORR) (28.1% vs 18.2%, P=0.341), disease control rate (DFS)(43.8% vs 45.5%, P=0.890), and PFS (4.3 months vs 3.8 months, P=0.506). In the icotinib group, the ORR of epidermal growth factor receptor (EGFR) mutant was significantly higher than that of EGFR unknown or wild type (P=0.017). In multivariate analysis, age, gender, histology, and the optimum first-line treatment response were dependent prognostic factors based on the PFS of the icotinib group. The incidence of adverse events was significantly fewer in the icotinib group than in the chemotherapy group (P=0.001). Compared with the standard second-line chemotherapy, icotinib is active in the treatment of advanced NSCLC patients, especially with EGFR unknown in the second line, with an acceptable adverse event profile.

  9. Comparison of the Efficacy and Safety of Icotinib with Standard Second-line 
Chemotherapy in Previously Treated Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Shuyang YAO

    2015-06-01

    Full Text Available Background and objective This study compared the efficacy and safety of icotinib with standard second-line chemotherapy (single-agent docetaxel or pemetrexed in previously treated advanced non-small cell lung cancer (NSCLC. Methods Thirty-two consecutive patients treated with icotinib and 33 consecutive patients treated with standard second-line chemotherapy in Xuanwu Hospital from January 2012 to July 2013 were enrolled in our retrospective research. The Response Evaluation Criteria in Solid Tumors were used to evaluate the tumor responses, and the progression-free survival (PFS was evaluated by Kaplan-Meier method. Results Icotinib was comparable with standard second-line chemotherapy for advanced NSCLC in terms of overall response rate (ORR (28.1% vs 18.2%, P=0.341, disease control rate (DFS(43.8% vs 45.5%, P=0.890, and PFS (4.3 months vs 3.8 months, P=0.506. In the icotinib group, the ORR of epidermal growth factor receptor (EGFR mutant was significantly higher than that of EGFR unknown or wild type (P=0.017. In multivariate analysis, age, gender, histology, and the optimum first-line treatment response were dependent prognostic factors based on the PFS of the icotinib group. The incidence of adverse events was significantly fewer in the icotinib group than in the chemotherapy group (P=0.001. Conclusion Compared with the standard second-line chemotherapy, icotinib is active in the treatment of advanced NSCLC patients, especially with EGFR unknown in the second line, with an acceptable adverse event profile.

  10. Second-Line Hormonal Therapy for Men With Chemotherapy-Naïve, Castration-Resistant Prostate Cancer: American Society of Clinical Oncology Provisional Clinical Opinion.

    Science.gov (United States)

    Virgo, Katherine S; Basch, Ethan; Loblaw, D Andrew; Oliver, Thomas K; Rumble, R Bryan; Carducci, Michael A; Nordquist, Luke; Taplin, Mary-Ellen; Winquist, Eric; Singer, Eric A

    2017-06-10

    Purpose ASCO provisional clinical opinions (PCOs) offer direction to the ASCO membership after publication or presentation of potential practice-changing data. This PCO addresses second-line hormonal therapy for chemotherapy-naïve men with castration-resistant prostate cancer (CRPC) who range from being asymptomatic with only biochemical evidence of CRPC to having documented metastases but minimal symptoms. Clinical Context The treatment goal for CRPC is palliation. Despite resistance to initial androgen deprivation therapy, most men respond to second-line hormonal therapies. However, guidelines have neither addressed second-line hormonal therapy for nonmetastatic CRPC nor provided specific guidance with regard to the chemotherapy-naïve population. Recent Data Six phase III randomized controlled trials and expert consensus opinion inform this PCO. Provisional Clinical Opinion For men with CRPC, a castrate state should be maintained indefinitely. Second-line hormonal therapy (eg, antiandrogens, CYP17 inhibitors) may be considered in patients with nonmetastatic CRPC at high risk for metastatic disease (rapid prostate-specific antigen doubling time or velocity) but otherwise is not suggested. In patients with radiographic evidence of metastases and minimal symptoms, enzalutamide or abiraterone plus prednisone should be offered after discussion with patients about potential harms, benefits, costs, and patient preferences. Radium-223 and sipuleucel-T also are options. No evidence provides guidance about the optimal order of hormonal therapies for CRPC beyond second-line treatment. Prostate-specific antigen testing every 4 to 6 months is reasonable for men without metastases. Routine radiographic restaging generally is not suggested but can be considered for patients at risk for metastases or who exhibit symptoms or other evidence of progression. Additional information is available at www.asco.org/genitourinary-cancer-guidelines and www.asco.org/guidelineswiki .

  11. Who will bear the torch tomorrow? Charismatic leadership and second-line leaders in development NGOs

    OpenAIRE

    M. Shameem Siddiqi

    2001-01-01

    Competent leadership has always been considered vital in every organisation and there has been considerable research on mainstream leadership issues in the corporate sector and in politics.1 But there has been very little research on leadership issues in the emerging sector of development NGOs. The issue of second-line leadership development2 is an important one not only for the NGOs themselves but also for the aid industry, the poor and vulnerable people for whom they work and for society as...

  12. TDF and quantitative ultrasound bone quality in African patients on second line ART, ANRS 12169 2LADY sub-study.

    Science.gov (United States)

    Kabore, Firmin Nongodo; Eymard-Duvernay, Sabrina; Zoungrana, Jacques; Badiou, Stéphanie; Bado, Guillaume; Héma, Arsène; Diouf, Assane; Delaporte, Eric; Koulla-Shiro, Sinata; Ciaffi, Laura; Cournil, Amandine

    2017-01-01

    Bone demineralization, which leads to osteoporosis and increased fracture risk, is a common metabolic disorder in HIV-infected individuals. In this study, we aimed to assess the change in bone quality using quantitative ultrasound (QUS) over 96 weeks of follow-up after initiation of second-line treatment, and to identify factors associated with change in bone quality. In a randomized trial (ANRS 12169), TDF and PI-naïve participants failing standard first-line treatment, from Burkina Faso, Cameroon, and Senegal were randomized to receive either TDF/FTC/LPVr, ABC/ddI/LPVr or TDF/FTC/DRVr. Their bone quality was assessed using calcaneal QUS at baseline and every 24 weeks until week 96. Stiffness index (SI) was used to measure bone quality. Out of 228 participants, 168 (74%) were women. At baseline, median age was 37 years (IQR: 33-46 years) and median T-CD4 count was 199 cells/μl (IQR: 113-319 cells/μl). The median duration of first-line antiretroviral treatment (ART) was 52 months (IQR: 36-72 months) and the median baseline SI was 101 (IQR: 87-116). In multivariable analysis, factors associated with baseline SI were sex (β = -10.8 [-18.1,-3.5] for women), age (β = -8.7 [-12.4,-5.1] per 10 years), body mass index (BMI) (β = +0.8 [0.1,1.5] per unit of BMI), and study site (β = +12.8 [6.5,19.1] for Cameroon). After 96 weeks of second-line therapy, a reduction of 7.1% in mean SI was observed, as compared with baseline. Factors associated with SI during the follow-up were similar to those found at baseline. Exposure to TDF was not associated with a greater loss of bone quality over time. Bone quality decreased after second-line ART initiation in African patients independently of TDF exposure. Factors associated with bone quality include age, sex, baseline BMI, study site, and duration of follow-up.

  13. Clinical Benefit of Second-Line Palliative Chemotherapy in Advanced Soft-Tissue Sarcoma

    Directory of Open Access Journals (Sweden)

    Anna Minchom

    2010-01-01

    Full Text Available Background. This paper aimed to assess the utility of second-line chemotherapy in patients with advanced soft-tissue sarcoma. Materials and Methods. A retrospective search of a prospectively maintained database identified patients treated between 1991 and 2005. Patients with gastrointestinal stromal tumours, small round cell tumours, and Ewing's sarcoma were excluded. Response was assessed using WHO and RECIST. Patients who achieved stable disease for 6 months or more were classified as having disease control. Results. Three hundred and seventy-nine patients received second-line chemotherapy. Eighty-six (22.7% achieved disease control. Median duration of response was 11 months (95% CI: 9–13. On multivariate analysis, pathological subtype, absence of lung metastases, and the use of combination chemotherapy were independent predictors of disease control. Twenty-eight (16.1% patients who failed to respond to first-line therapy achieved disease control. Eight (2.1% patients had sufficient downstaging to enable complete surgical resection. Progression-free survival was 23% at 6 months. Median overall survival was 8 months (95% CI: 7–10 months. On multivariate analysis, synovial histology and absence of lung metastases were associated with improved survival. Conclusion. Second-line chemotherapy can provide clinical benefit in over 20% of soft-tissue sarcoma patients.

  14. Second-Line Intraperitoneal Chemotherapy for Recurrent Epithelial Ovarian, Tubal and Peritoneal Cancer: A Propensity Score-Matching Study.

    Science.gov (United States)

    Lu, Chien-Hsing; Chang, Yen-Hou; Lee, Wai-Hou; Chang, Yi; Peng, Chia-Wen; Chuang, Chi-Mu

    2016-01-01

    The superiority of frontline intraperitoneal (IP) over intravenous (IV) chemotherapy is well established in the treatment of epithelial ovarian cancer. However, the role of IP chemotherapy in the second-line setting has rarely been investigated. Consecutive patients diagnosed with recurrent epithelial, tubal and peritoneal cancers between January 2000 and December 2012 were recruited using a propensity score-matching technique to adjust relevant risk factors. In total, 310 patients were included in the final analysis (94 for platinum-refractory/resistant disease and 216 for platinum-sensitive disease). IP chemotherapy demonstrated significantly longer median progression-free survival than IV chemotherapy (4.9 vs. 2.4 months, p chemotherapy confers longer progression-free survival than IV chemotherapy. Large-scale clinical trials should be conducted to validate the true efficacy. © 2016 S. Karger AG, Basel.

  15. 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....

  16. Original Article Did salvage ICE chemotherapy improve the outcome in primary resistant/relapsing stage Ill/TV neuroblastoma

    International Nuclear Information System (INIS)

    Abdel Rahman, M.; Zekri, W.Z.K.; Moussa, E.A.M.; El Debawy, E.; Mostafa, N.E.; Yones, A.; Ezzat, S.; Rayan, A.

    2011-01-01

    Neuroblastoma is the most common extracranial and deadly solid tumor in children. It accounts for 15% of the deaths from cancer in the pediatric age group. Approximately half of the newly diagnosed children are at h igh risk o f treatment failure. The aim of this study is to evaluate the response rate of salvage chemotherapy by the ICE (Ifosfamide, Carboplatin, and Etoposide) regimen when administered to previously treated primary refractory or progressive high risk neuroblastoma patients. Patients and methods: Sixty-six patients from the National Cancer Institute (NCI), Cairo University and the Children Cancer Hospital Egypt (CCHE) received salvage chemotherapy (ICE) either due to primary resistance in 51/66 (77.2%) or due to disease progression on primary chemotherapy in 15/66 (22.8%). Results: They were 40 males (60.6%) and 26 females (39.4%). Patients' age ranged between 3 months and 12.5 years. The most common tumor site was suprarenal, followed by retroperitoneal mass. Two patients (3%)'died from chemotherapy toxicity during ICE administration. Evaluation of tumor response in the remaining 64 patients showed the following: CR/PR in 24 patients (36.5%), SD in 11 patients (16.6%), and PD in 29 patients (43.9%). Fourteen patients (21.2%) were considered eligible for auto BMT, while 50/64 patients (78.8%) failed this second line (salvage) chemotherapy and had palliative lines of therapy. By the end of the study (May 2010), 47/66 (71.2%) of the patients were still alive, while 19/66 (28.8%) were dead. Two out of 14 patients (14.2%) who underwent HSCT died from post transplantation disease progression, while 12/14 (85.8%) were in CCR. Conclusion: Chemotherapy by ICE for primary resistant or progressive stage III/IV NB seems well tolerated. With a 36.6% response rate, 18% CCR, and 3% treatment mortality rate, it could be considered a good salvage therapy in the category of patients who are condemned for palliation

  17. "To look at death another way": Black teenage males' perspectives on second-lines and regular funerals in New Orleans.

    Science.gov (United States)

    Bordere, Tashel C

    The purpose of this study was to describe how Black adolescent males understand "second-line" (musical processions) and "regular"/traditional funeral rituals in New Orleans following the violent deaths of significant persons in their lives. In-depth interviews were conducted with 10 Black males between the ages of 12 and 15 using descriptive phenomenology methodology. Findings revealed that these participants understood death as a cause for celebration, remembrance, and unity related to their experiences with the second-line ritual. Three elements of the life world of Black teenage males were descriptive of second lines, including: a) observed locations of second lines; b) dancing to good music; and c) observed messages conveyed through t-shirts. Participants provided gender-based descriptions of perceived spoken and unspoken rights in grieving at the two distinct rituals. Related to their second-line experience, the teens reflect on ways in which they wish to have their deaths ritualized.

  18. A Bayesian network meta-analysis on second-line systemic therapy in advanced gastric cancer.

    Science.gov (United States)

    Zhu, Xiaofu; Ko, Yoo-Joung; Berry, Scott; Shah, Keya; Lee, Esther; Chan, Kelvin

    2017-07-01

    It is unclear which regimen is the most efficacious among the available therapies for advanced gastric cancer in the second-line setting. We performed a network meta-analysis to determine their relative benefits. We conducted a systematic review of randomized controlled trials (RCTs) through the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases and American Society of Clinical Oncology abstracts up to June 2014 to identify phase III RCTs on advanced gastric cancer in the second-line setting. Overall survival (OS) data were the primary outcome of interest. Hazard ratios (HRs) were extracted from the publications on the basis of reported values or were extracted from survival curves by established methods. A Bayesian network meta-analysis was performed with WinBUGS to compare all regimens simultaneously. Eight RCTs (2439 patients) were identified and contained extractable data for quantitative analysis. Network meta-analysis showed that paclitaxel plus ramucirumab was superior to single-agent ramucirumab [OS HR 0.51, 95 % credible region (CR) 0.30-0.86], paclitaxel (OS HR 0.81, 95 % CR 0.68-0.96), docetaxel (OS HR 0.56, 95 % CR 0.33-0.94), and irinotecan (OS HR 0.71, 95 % CR 0.52-0.99). Paclitaxel plus ramucirumab also had an 89 % probability of being the best regimen among all these regimens. Single-agent ramucirumab, paclitaxel, docetaxel, and irinotecan were comparable to each other with respect to OS and were superior to best supportive care. This is the first network meta-analysis to compare all second-line regimens reported in phase III gastric cancer trials. The results suggest the paclitaxel plus ramucirumab combination is the most effective therapy and should be the reference regimen for future comparative trials.

  19. Cyclophosphamide-hydroxycamptothecin as second-line chemotherapy for advanced Ewing's sarcoma: experience of a single institution.

    Science.gov (United States)

    Han, Kun; Sun, Yuanjue; Zhang, Jianjun; He, Aina; Zheng, Shui'er; Shen, Zan; Yao, Yang

    2014-06-01

    To investigate the feasibility and efficacy of cyclophosphamide (CTX)-hydroxycamptothecin (HCPT) as second-line chemotherapy on advanced Ewing's sarcoma. From April 2009 to November 2010, 27 patients with advanced Ewing's sarcoma who had progressive disease after the first-line chemotherapy regimen of vincristine, dactinomycin and cyclophosphamide and ifosfamide and etoposide were retrospectively reviewed in this analysis. CTX was given (0.6 g/m(2), i.v. push day 1) and HCPT (6 mg/m(2), i.v. drip days 1-5) as second-line chemotherapy every 3 weeks. The primary end-point was overall response rate, the secondary end-point included progression-free, overall survival, disease control rate and toxicities. A total of 134 cycles were given, median four cycles per patient (range 2-6). Overall response rate was 30% and disease control rate was 82%, with two complete response (8%), six partial remission (22%) and 14 stable disease (52%). The median time to progression and overall survival time were 7 months (95% CI 3-10) and 11 months (95% CI 5-18), respectively. Major severe toxicities (grade 3 and 4) were: nausea/vomiting (17%), alopecia (17%); leukopenia (27%) in total cycles. Mild toxicities (grade 1 or 2) were leukopenia (73%), nausea/vomiting (83%), hepatic lesion (14%) and anemia (44%). A CTX-HCPT regimen can control disease progression effectively and the side effects can be tolerable for Chinese advanced Ewing's sarcoma patients. Further assessment is necessary to confirm the safety and efficacy of this treatment. © 2012 Wiley Publishing Asia Pty Ltd.

  20. Systemic treatment in EGFR-ALK NSCLC patients: second line therapy and beyond

    International Nuclear Information System (INIS)

    Karachaliou, Niki; Rosell, Rafael

    2014-01-01

    Lung cancer is the most frequently diagnosed cancer and a leading cause of cancer mortality worldwide, with adenocarcinoma being the most common histological subtype. Deeper understanding of the pathobiology of non-small cell lung cancer (NSCLC) has led to the development of small molecules that target genetic mutations known to play critical roles in progression to metastatic disease and to influence response to targeted therapies. The principle goal of precision medicine is to define those patient populations most likely to respond to targeted therapies. However, the cancer genome landscape is composed of relatively few “mountains” [representing the most commonly mutated genes like KRAS, epidermal growth factor (EGFR), and anaplastic lymphoma kinase (ALK)] and a vast number of “hills” (representing low frequency but potentially actionable mutations). Low-frequency lesions that affect a druggable gene product allow a relatively small population of cancer patients for targeted therapy to be selected

  1. First and second line mechanisms of cadmium detoxification in the lichen photobiont Trebouxia impressa (Chlorophyta)

    International Nuclear Information System (INIS)

    Sanita di Toppi, L.; Pawlik-Skowronska, B.; Vurro, E.; Vattuone, Z.; Kalinowska, R.; Restivo, F.M.; Musetti, R.; Skowronski, T.

    2008-01-01

    'First line' defence mechanisms, such as phytochelatin biosynthesis, and 'second line' mechanisms, such as stress protein induction, were investigated in cadmium-exposed cells of Trebouxia impressa Ahmadjian, a green microalgal species that is a common photobiont of the lichen Physcia adscendens (Fr.) H. Olivier. When T. impressa cells were exposed to 0, 9 and 18 μM Cd for 6, 18 and 48 h, glutathione and phytochelatins efficiently protected the cells against Cd damage. By contrast, the highest Cd concentration (36 μM) at the longest exposure-time (48 h) caused marked drops in glutathione and phytochelatin content, several types of ultrastructural damage, and decreases in cell density and total chlorophyll concentration. In this case, induction of stress proteins was observed, but only long after the induction of phytochelatins. Thus, stress proteins could represent a 'second line' mechanism to counteract Cd stress, activated when there is a decline in the 'first line' mechanism of Cd detoxification given by phytochelatins. - Trebouxia impressa photobionts protect themselves against cadmium stress by means of phytochelatins and stress proteins

  2. First and second line mechanisms of cadmium detoxification in the lichen photobiont Trebouxia impressa (Chlorophyta)

    Energy Technology Data Exchange (ETDEWEB)

    Sanita di Toppi, L. [Dipartimento di Biologia Evolutiva e Funzionale, viale G.P. Usberti 11/A, Universita di Parma, 43100 Parma (Italy)], E-mail: luigi.sanitaditoppi@unipr.it; Pawlik-Skowronska, B. [Centre for Ecological Research, Polish Academy of Sciences, Experimental Station, Niecala 18/3, 20080 Lublin (Poland); Vurro, E. [Dipartimento di Biologia Evolutiva e Funzionale, viale G.P. Usberti 11/A, Universita di Parma, 43100 Parma (Italy); Vattuone, Z. [Dipartimento di Biologia Evolutiva e Funzionale, viale G.P. Usberti 11/A, Universita di Parma, 43100 Parma (Italy); Centre for Ecological Research, Polish Academy of Sciences, Experimental Station, Niecala 18/3, 20080 Lublin (Poland); Kalinowska, R. [Centre for Ecological Research, Polish Academy of Sciences, Experimental Station, Niecala 18/3, 20080 Lublin (Poland); Restivo, F.M. [Dipartimento di Genetica, Biologia dei Microrganismi, Antropologia, Evoluzione, viale G.P. Usberti 11/A, Universita di Parma, 43100 Parma (Italy); Musetti, R. [Dipartimento di Biologia Applicata alla Difesa delle Piante, via delle Scienze 208, Universita di Udine, 33100 Udine (Italy); Skowronski, T. [Centre for Ecological Research, Polish Academy of Sciences, Experimental Station, Niecala 18/3, 20080 Lublin (Poland)

    2008-01-15

    'First line' defence mechanisms, such as phytochelatin biosynthesis, and 'second line' mechanisms, such as stress protein induction, were investigated in cadmium-exposed cells of Trebouxia impressa Ahmadjian, a green microalgal species that is a common photobiont of the lichen Physcia adscendens (Fr.) H. Olivier. When T. impressa cells were exposed to 0, 9 and 18 {mu}M Cd for 6, 18 and 48 h, glutathione and phytochelatins efficiently protected the cells against Cd damage. By contrast, the highest Cd concentration (36 {mu}M) at the longest exposure-time (48 h) caused marked drops in glutathione and phytochelatin content, several types of ultrastructural damage, and decreases in cell density and total chlorophyll concentration. In this case, induction of stress proteins was observed, but only long after the induction of phytochelatins. Thus, stress proteins could represent a 'second line' mechanism to counteract Cd stress, activated when there is a decline in the 'first line' mechanism of Cd detoxification given by phytochelatins. - Trebouxia impressa photobionts protect themselves against cadmium stress by means of phytochelatins and stress proteins.

  3. Evaluation of MGIT 960 System for the Second-Line Drugs Susceptibility Testing of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Hyejin Kim

    2013-01-01

    Full Text Available Many laboratories validate DST of the second-line drugs by BACTEC MGIT 960 system. The objective of this study is to evaluate the critical concentration and perform DST for the 2nd line drugs. We evaluated 193 clinical strains of M. tuberculosis isolated from patients in South Korea. Testing the critical concentration of six second-line drugs was performed by MGIT 960 and compared with L-J proportion method. The critical concentration was determined to establish the most one that gave the difference between drug resistance and susceptibility in MGIT960 system. Good agreement of the following concentrations was found: Concordance was 95% for 0.5 μg/mL of moxifloxacin; 93.6%, 1.0 μg/mL of levofloxacin; 97.5%, 2.5 μg/mL of kanamycin; 90.6%, 2.5 μg/mL of capreomycin; 86.2%, 5.0 μg/mL of ethionamide; and 90.8%, 2.0 μg/mL of ρ-aminosalicylic acid. The critical concentrations of the four drugs, moxifloxacin, levofloxacin, kanamycin, and capreomycin, were concordant and reliable for testing 2nd line drug resistance. Further study of ethionamide and ρ-aminosalicylic acid is required.

  4. Ifosfamide, mesna and epirubicin as second-line chemotherapy in advanced breast cancer.

    Science.gov (United States)

    Kiraz, S; Baltali, E; Güler, N; Barista, I; Benekli, M; Celik, I; Güllü, I H; Kars, A; Tekuzman, G; Firat, D

    1996-08-01

    The ifosfamide, mesna and epirubicin (IMEpi) combination is administered to 16 patients having advanced metastatic breast carcinoma as second-line chemotherapy. We observed complete response in 6%, partial response in 44% (total overall response rate of 50%), stable disease in 12% and progressive disease in the remaining 38% of the patients. The median remission duration in responders was calculated to be 9.6 months. IMEpi regimen had a tolerable toxicity profile including alopecia, nausea and vomiting, microscopic hematuria, leukopenia and neurotoxicity in which serious complications necessitating discontinuation of the chemotherapy were not encountered. It might be concluded that IMEpi chemotherapy combination is an effective alternative among schedules in the management of patients with stage IV breast carcinoma without serious side effects.

  5. Second Line of Defense Megaports Initiative Operational Testing and Evaluation Plan Colon Container Terminal (CCT) Panama

    Energy Technology Data Exchange (ETDEWEB)

    Newhouse, Robert N.

    2010-01-01

    Report on the Operational Testing and Evaluation to validate and baseline an operable system that meets the Second Line of Defense (SLD) mission requirements. An SLD system is defined as the detection technology and associated equipment, the system operators from the host country, the standard operating procedures (SOPs), and other elements such as training and maintenance which support long-term system sustainment. To this end, the activities conducted during the OT&E phase must demonstrate that the Megaports System can be operated effectively in real-time by Panama Direccion General de Aduanas (DGA Panama Customs) personnel to the standards of the U.S. Department of Energy/National Nuclear Security Administration (DOE/NNSA).

  6. Aflibercept as a second-line therapy in metastatic colorectal cancer: A limited Indian experience

    Directory of Open Access Journals (Sweden)

    Govind Babu

    2016-01-01

    Full Text Available Introduction: Aflibercept in combination with FOLFIRI has been shown to improve overall survival in the pivotal VELOUR study. Aflibercept has not yet been marketed in India. Sanofi has made available this drug for Indian patients under a program called Named Patient Access Program (NPP. We present a limited clinical experience with the use of aflibercept at our center. Materials and Methods: We analyzed the data of the patients who received aflibercept under NPP. Aflibercept was given in combination with FOLFIRI as second-line for patients who progressed on oxaliplatin based therapy. Aflibercept was given at 4 mg/kg intravenous (IV every 15 days. Chemotoxicities were assessed as per CTCAE. Response evaluation was done every four cycles. Results: Five patients were enrolled. The median age was 34 years. The median number of aflibercept cycles administered was 12. Common grade 2/3 toxicities were mucositis, diarrhea, neutropenia thrombocytopenia, and hypertension seen in three (60%, three (60%, two (40%, two (40%, and one patient respectively. After four cycles, the response was assessed as: One complete remission (CR, three partial remissions (PR, and one progressive disease (PD. Three patients completed 12 cycles of chemotherapy and aflibercept. At the end of 12 cycles, one patient still in CR and two patients were in PR. Four patients were alive till date. Conclusion: As we had very less number of patients, it was very difficult to compare it with VELOUR data. It is one of option as second-line in metastatic colorectal cancer (mCRC who progressed on oxaliplatin chemotherapy. Mucositis, diarrhea, and hematological toxicity were the most common toxicity in our patient.

  7. Prevalence of resistance to second-line tuberculosis drug among multidrug-resistant tuberculosis patients in Viet Nam, 2011.

    Science.gov (United States)

    Nguyen, Hoa Binh; Nguyen, Nhung Viet; Tran, Huong Thi Giang; Nguyen, Hai Viet; Bui, Quyen Thi Tu

    2016-01-01

    Extensively drug-resistant tuberculosis (XDR-TB) represents an emerging public health problem worldwide. According to the World Health Organization, an estimated 9.7% of multidrug-resistant TB (MDR-TB) cases are defined as XDR-TB globally. The objective of this study was to determine the prevalence of drug resistance to second-line TB drugs among MDR-TB cases detected in the Fourth National Anti-Tuberculosis Drug Resistance Survey in Viet Nam. Eighty clusters of TB cases were selected using a probability-proportion-to-size approach. To identify MDR-TB cases, drug susceptibility testing (DST) was performed for the four major first-line TB drugs. DST of second-line drugs (ofloxacin, amikacin, kanamycin, capreomycin) was performed on isolates from MDR-TB cases to identify pre-XDR and XDR cases. A total of 1629 smear-positive TB cases were eligible for culture and DST. Of those, DST results for first-line drugs were available for 1312 cases, and 91 (6.9%) had MDR-TB. Second-line DST results were available for 84 of these cases. Of those, 15 cases (17.9%) had ofloxacin resistance and 6.0% were resistant to kanamycin and capreomycin. Five MDR-TB cases (6.0%) met the criteria of XDR-TB. This survey provides the first estimates of the proportion of XDR-TB among MDR-TB cases in Viet Nam and provides important information for local policies regarding second-line DST. Local policies and programmes that are geared towards TB prevention, early diagnosis and treatment with effective regimens are of high importance.

  8. Forest structure following tornado damage and salvage logging in northern Maine, USA

    Science.gov (United States)

    Shawn Fraver; Kevin J. Dodds; Laura S. Kenefic; Rick Morrill; Robert S. Seymour; Eben Sypitkowski

    2017-01-01

    Understanding forest structural changes resulting from postdisturbance management practices such as salvage logging is critical for predicting forest recovery and developing appropriate management strategies. In 2013, a tornado and subsequent salvage operations in northern Maine, USA, created three conditions (i.e., treatments) with contrasting forest structure:...

  9. Mitigating Hillslope Erosion After Post-fire Salvage Logging Operations

    Science.gov (United States)

    Robichaud, P. R.; Bone, E. D.; Brown, R. E.

    2017-12-01

    In the past decades, wildfires around the world have continued to increase in size, severity, and cost. Major concerns after wildfires are the increased runoff and erosion due to loss of the protective forest floor layer, loss of water storage, and creation of water repellent soil conditions. Salvage logging is often a post-fire forest management action to recoup the economic loss of the burned timber, yet concerns arise on the impacts of this activity on water quality. Recently, several studies have been conducted to determine the effect of salvage logging on hillslope erosion. Logging skid trails have been cited as being the cause of high erosion during and after salvage operations. We investigated the impacts of adding operational logging slash to skid trails to reduce hillslope erosion after salvage operations on the 2015 North Star Fire, Washington. We implemented well-designed rapid response approach to compare slash treatment effectiveness by monitoring sediment yield and runoff response from hillslopes with a concentrated flow (rill) experiment. Various runoff amounts are incrementally added to 4 m hillslope plots with and without slash treatments. Our initial results suggest that adding logging slash increased ground cover significantly which contributed to an order of magnitude decrease in hillslope erosion. Integrating erosion mitigation strategies into salvage logging operations should be commonplace when hillslope erosion is a concern.

  10. Second-line chemotherapy of disseminated malignant melanoma with cystemustine at 60 mg/m2: a phase II trial.

    Science.gov (United States)

    Thivat, Emilie; Durando, Xavier; D'Incan, Michel; Cure, Hervé; Mouret-Reynier, Marie-Ange; Madelmont, Jean-Claude; Souteyrand, Pierre; Chollet, Philippe

    2005-10-01

    Nitrosoureas possess some anti-tumor activity as a single agent in metastatic melanoma (MM). In a phase II trial, we evaluated the anti-tumor effects of cystemustine chemotherapy, a new nitrosourea, as a second-line treatment. Patients were required to have histologic evidence of disseminated MM and had failed in first-line chemotherapy. Treatment comprised cystemustine given at a dose of 60 mg/m every 2 weeks by a 15-min infusion. From February 1997 to September 1999, 22 patients (median age 66 years) were enrolled and were assessable. Two complete responses, one partial response, three stable diseases and 16 progressions were observed, giving an overall response rate of 13.6%. Median duration of response was 10 months (range 4-63). Median survival of responders and non-responders was 11 and 4 months, respectively. However, hematological toxicity, particularly thrombopenia, was a limiting factor for one-third of patients. We conclude that cystemustine at 60 mg/m is active in patients who progressed after one line of chemotherapy in advanced disease, and offers the possibility of complete responses and long durations of these responses.

  11. 25 CFR 700.99 - Salvage value.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Salvage value. 700.99 Section 700.99 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.99 Salvage value. Salvage value means the probable sale price of an...

  12. SINGLE AGENT DOCETAXEL AS SECOND- LINE CHEMOTHERAPY FOR PRETREATED PATIENTS WITH RECURRENT NON- SMALL CELL LUNG CANCER

    Directory of Open Access Journals (Sweden)

    Deyan N. Davidov

    2013-04-01

    Full Text Available Objective: Single agent Docetaxel is a standard therapy for patients with non- small cell lung cancer after the failure of platinum- containing regimens. The aim of this study was to explore the efficacy and safety of Docetaxel monotherapy as second- line chemotherapy in pretreated patient with inoperable non- small cell lung cancer. Methods: From January 2005 to May 2008 thirty- six consecutive patients with locally advanced or metastatic morphologically proven stage IIIB/ IV non- small cell lung cancer entered the study after failure of previous platinum- based regimens. Treatment schedule consist of Docetaxel 75 mg/m2 administered every three weeks with repetition after 21 days with Dexamethasone premedication. Results: Overall response rate, median time to progression and median survival was 16,6 %, 4,5 months and 5,6 months respectively. The main hematological toxicity was neutropenia. Conclusions: That data suggest that single agent Docetaxel remain reasonable choices for the chemotherapy in pretreated patients with non- small cell lung cancer.

  13. Clinical outcomes following salvage Gamma Knife radiosurgery for recurrent glioblastoma

    Science.gov (United States)

    Larson, Erik W; Peterson, Halloran E; Lamoreaux, Wayne T; MacKay, Alexander R; Fairbanks, Robert K; Call, Jason A; Carlson, Jonathan D; Ling, Benjamin C; Demakas, John J; Cooke, Barton S; Lee, Christopher M

    2014-01-01

    Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor with a survival prognosis of 14-16 mo for the highest functioning patients. Despite aggressive, multimodal upfront therapies, the majority of GBMs will recur in approximately six months. Salvage therapy options for recurrent GBM (rGBM) are an area of intense research. This study compares recent survival and quality of life outcomes following Gamma Knife radiosurgery (GKRS) salvage therapy. Following a PubMed search for studies using GKRS as salvage therapy for malignant gliomas, nine articles from 2005 to July 2013 were identified which evaluated rGBM treatment. In this review, we compare Overall survival following diagnosis, Overall survival following salvage treatment, Progression-free survival, Time to recurrence, Local tumor control, and adverse radiation effects. This report discusses results for rGBM patient populations alone, not for mixed populations with other tumor histology grades. All nine studies reported median overall survival rates (from diagnosis, range: 16.7-33.2 mo; from salvage, range: 9-17.9 mo). Three studies identified median progression-free survival (range: 4.6-14.9 mo). Two showed median time to recurrence of GBM. Two discussed local tumor control. Six studies reported adverse radiation effects (range: 0%-46% of patients). The greatest survival advantages were seen in patients who received GKRS salvage along with other treatments, like resection or bevacizumab, suggesting that appropriately tailored multimodal therapy should be considered with each rGBM patient. However, there needs to be a randomized clinical trial to test GKRS for rGBM before the possibility of selection bias can be dismissed. PMID:24829861

  14. Cost-Effectiveness of Saxagliptin versus Acarbose as Second-Line Therapy in Type 2 Diabetes in China.

    Science.gov (United States)

    Gu, Shuyan; Zeng, Yuhang; Yu, Demin; Hu, Xiaoqian; Dong, Hengjin

    2016-01-01

    This study assessed the long-term cost-effectiveness of saxagliptin+metformin (SAXA+MET) versus acarbose+metformin (ACAR+MET) in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on MET alone. Systematic literature reviews were performed to identify studies directly comparing SAXA+MET versus ACAR+MET, and to obtain diabetes-related events costs which were modified by hospital surveys. A Cardiff Diabetes Model was used to estimate the long-term economic and health treatment consequences in patients with T2DM. Costs (2014 Chinese yuan) were calculated from the payer's perspective and estimated over a patient's lifetime. SAXA+MET predicted lower incidences of most cardiovascular events, hypoglycemia events and fatal events, and decreased total costs compared with ACAR+MET. For an individual patient, the quality-adjusted life-years (QALYs) gained with SAXA+MET was 0.48 more than ACAR+MET at a cost saving of ¥18,736, which resulted in a cost saving of ¥38,640 per QALY gained for SAXA+MET versus ACAR+MET. Results were robust across various univariate and probabilistic sensitivity analyses. SAXA+MET is a cost-effective treatment alternative compared with ACAR+MET for patients with T2DM in China, with a little QALYs gain and lower costs. SAXA is an effective, well-tolerated drug with a low incidence of adverse events and ease of administration; it is anticipated to be an effective second-line therapy for T2DM treatment.

  15. LONG-TERM RESULTS OF TARGET THERAPY WITH FIRST AND * SECOND-LINE TYROSINE KINASE INHIBITORS IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA

    Directory of Open Access Journals (Sweden)

    L. L. Vysotskaya

    2015-01-01

    Full Text Available Aim: To assess long-term efficacy of firstand second-line tyrosine kinase inhibitors in non-selected patients with chronic myeloid leukemia in a real-life clinical setting.Materials and methods: The assessment is based on long-term results of a prospective single center comparative clinical trial that was based on non-selected groups of 116 patients with various stages of chronic myeloid leukemia being treated with a first generation tyrosine kinase inhibitor imatinib, and of 44 patients being treated with a second generation tyrosine kinase inhibitor nilotinib. We analyzed all-cause mortality, progression-free survival from April 2005 to April 2013, with a median of the follow-up of 128 months.Results: In 116 patients with chronic myeloid leukemia treated with imatinib, the Kaplan-Meier survival estimate was 120 months. In 44 patients at an early chronic phase, 5-year overall survival and progression-free survival was 93.2% and 8-year overall and progression-free survival was 79.5%. In 44 patients at a late chronic stage, 5-year overall and progression-free survival was 95.5%, 8-year overall and progression-free survival, 72.7%. In 28 patients at acceleration phase, 5-years overall survival was 78.6% and 8-year overall survival, 46%. Median of overall survival in patients treated with nilotinib was not reached. During 78.6 months of combination treatment with cytotoxic agents, tyrosine kinase inhibitors of the first (imatinib and second line (nilotinib, overall survival was 100%.Conclusion: In clinical practice, inclusion of patients with chronic myeloid leukemia and imatinib resistance (disease relapse or imatinib intolerance into the treatment program with frontline therapy with general cytotoxic agents and thereafter with firstand second-line tyrosine kinase inhibitors significantly improves overall survival.

  16. On the use of dental ceramics as a possible second-line approach to accident irradiation dosimetry

    International Nuclear Information System (INIS)

    Davies, J.E.

    1979-01-01

    Recent development in dental ceramic production has resulted in natural or depleted uranium, used for over half a century to mimic the fluorescence of natural teeth, being substituted in such ceramics by non-radioactive fluorescent materials. This creates the possibility of using dental ceramics incorporating the latter as second-line dosimeters in cases of accidental irradiation. This pilot study shows the feasbility of such an approach using both thermally stimulated exoelectron and thermoluminescent techniques. In conclusion, it is considered that it would be of interest to continue this investigation of dental ceramic materials as second-line accident dosimeters

  17. Efficacy of S-1 plus nedaplatin compared to standard second-line chemotherapy in EGFR-negative lung adenocarcinoma after failure of first-line chemotherapy.

    Science.gov (United States)

    Tang, Yu; Wang, Wei; Teng, Xiu-Zhi; Shi, Lin

    2014-09-01

    For patients with advanced non-small cell lung adenocarcinoma that fail to respond to first-line chemotherapy and that do not involve epidermal growth factor receptor (EGFR) mutations, previous empirical analysis showed that a single second-line chemotherapy agent may be inadequate for the control of further tumor development. This study examines the combination of S-1 drugs and nedaplatin that has no cross-resistance to first-line treatments; 179 cases of IIIb-IV stage non-small-cell lung adenocarcinoma that failed to respond to first-line chemotherapy were included, and these subjects did not have mutated EGFRs. In the present study, S-1 plus nedaplatin chemotherapy was better than standard second-line chemotherapy options in the treatment of advanced lung adenocarcinoma that did not involve EGFR mutations and that failed to respond to first-line chemotherapy. Additionally, the combination of S-1 and nedaplatin seemed to be well tolerated, making this chemotherapy technique a potentially strong candidate for the treatment of advanced non-small-cell lung adenocarcinoma.

  18. Use of antibiotic beads to salvage infected breast implants.

    Science.gov (United States)

    Sherif, Rami D; Ingargiola, Michael; Sanati-Mehrizy, Paymon; Torina, Philip J; Harmaty, Marco A

    2017-10-01

    When an implant becomes infected, implant salvage is often performed where the implant is removed, capsulectomy is performed, and a new implant is inserted. The patient is discharged with a PICC line and 6-8 weeks of intravenous (IV) antibiotics. This method has variable success and subjects the patient to long-term systemic antibiotics. In the 1960s, the use of antibiotic-impregnated beads for the treatment of chronic osteomyelitis was described. These beads deliver antibiotic directly to the site of the infection, thereby eliminating the complications of systemic IV antibiotics. This study aimed to present a case series illustrating the use of STIMULAN calcium sulfate beads loaded with vancomycin and tobramycin to increase the rate of salvage of the infected implant and forgo IV antibiotics. A retrospective analysis was performed of patients who were treated at Mount Sinai Hospital for implant infection with salvage and antibiotic beads. Twelve patients were identified, 10 of whom had breast cancer. Comorbidities included hypertension, smoking, and immunocompromised status. Infections were noted anywhere from 5 days to 8 years postoperatively. Salvage was successful in 9 out of the 12 infected implants using antibiotic bead therapy without home IV antibiotics. The use of antibiotic beads is promising for salvaging infected breast implants without IV antibiotics. Seventy-five percent of the implants were successfully salvaged. Of the three patients who had unsalvageable implants, one was infected with antibiotic-resistant Rhodococcus that was refractory to bead therapy and one was noncompliant with postoperative instructions. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  19. Re-irradiation after salvage mastectomy for local recurrence after a conservative treatment: a retrospective analysis of twenty patients (Nancy: 1988-2001)

    International Nuclear Information System (INIS)

    Racadot, S.; Marchal, C.; Charra-Brunaud, C.; Peiffert, D.; Bey, P.; Verhaeghe, J.L.

    2003-01-01

    Purpose. - To retrospectively assess the efficacy of post-mastectomy re-irradiation for local relapse of breast cancer. Patients and methods. - Twenty patients, initially treated by conservative surgery and radiotherapy (50 Gy in 25 fractions over 5 weeks) were treated from 1998 to 2001 for a local relapse by salvage mastectomy and re-irradiation (either electron or photon beams). Mean age was 53 years (31-71). Reasons for re-irradiation were that the local relapses were inflammatory (4 pts), multifocal (5 pts), cutaneous (5 pts), involved the nipple (3 pts) or because the surgical margins (either muscle or skin) were involved (3 pts). The median dose of re-irradiation was 45 Gy (33-65) in 15 fractions over 33 days. Mean follow-up was 48 months (5-97). Results. - Fifteen patients remained free of a second local recurrence and 10 were still alive, without metastasis. Neither the dose of re-irradiation nor the irradiated surfaces were prognostic factors of local control (P = 0.877 and P = 0.424). Five patients developed radiation-induced pneumonitis without functional respiratory impairment. The incidence of pneumonitis seemed to be related to the biological dose of re-irradiation (P = 0.037). Other late complications occurred such as pigmentation changes (12 pts), telangiectasia (8 pts), chondritis (2 pts), parietal fibrosis (7 pts), rib fractures (4 pts), severe pain (11 pts) and lymphedema (2 pts). The increase in biological equivalent dose was highly statistically linked with the occurrence of disabling pain (P = 0.0123). Conclusion. - Parietal re-irradiation achieves good and lasting local control with an acceptable rate of acute complications but with a risk of disabling late sequelae such as severe pain. (author)

  20. Second-line chemotherapy with dacarbazine and fotemustine in nitrosourea-pretreated patients with recurrent glioblastoma multiforme.

    Science.gov (United States)

    Fazeny-Dörner, Barbara; Veitl, Mario; Wenzel, Catharina; Piribauer, Maria; Rössler, Karl; Dieckmann, Karin; Ungersböck, Karl; Marosi, Christine

    2003-07-01

    The aim of this study was to assess the efficacy and toxicity of a combination of dacarbazine (D) and fotemustine (F) administered to a homogenous group of patients with recurrent or progressive glioblastoma multiforme (GBM). Thirty-one patients with computed tomography or magnetic resonance imaging scan evidence of recurrent or progressive GBM after first-line chemotherapy with nitrosoureas as well as radiation therapy were given a combination of D (200 mg/m2) and F (100 mg/m2). At 30 min after termination of D administration, F was given over 60 min. Treatment was performed in an outpatient setting every 21 days. A total of 140 cycles (range 1-12 cycles; median 4 cycles) was administered. One partial response (3%) lasting for 11 weeks was observed. Sixteen (52%) patients reached stable disease lasting between 7 and 94 weeks. Median survival from start of the D/F combination was 45 (range 10-150) weeks. Median time to progression was 17 (3-101) weeks for all patients. Major toxicity was myelosuppression resulting in exclusion from study in seven (23%) patients [due to thrombocytopenia common toxicity criteria (CTC) grade 2 persisting longer than 3 weeks in three patients, due to thrombocytopenia CTC grade >/=3 in three and due to leukopenia CTC grade 3 in one patient]. No other toxicity than alopecia occurred. We conclude that the D/F combination is a well-tolerated second-line regimen and can be administered in a complete outpatient setting. D/F shows efficacy even in nitrosourea-pretreated patients and justifies further investigation.

  1. U.S. second line of defense: preventing nuclear smuggling across Russia's borders

    International Nuclear Information System (INIS)

    Ball, D. Y.

    1998-01-01

    Preventing the theft of weapons-usable highly enriched uranium and plutonium in Russia is one of the central security concerns facing the US today. The dissolution of the highly centralized USSR and the resulting societal crisis has endangered Russia's ability to protect its more than 200 metric tons of plutonium and 1000 tons of highly enriched uranium (roughly 8 kg Pu or 25 kg HEU is sufficient to make a bomb). Producing this fissile material is the most difficult and expensive part of nuclear weapons production and the US must make every effort to ensure that fissile material (and nuclear-related technologies) does not reach the hands of terrorist groups, rogue states or other potential proliferators. In response to this concern, the US has undertaken a number of initiatives in partnership with Russia and other FSU states to prevent the theft of fissile material. The Material Protection, Control and Accounting Program (MPC and A) was begun in 1993 to prevent the theft of nuclear materials from Russian civilian complexes, that is facilities not under control of the Ministry of Defense, which is largely responsible for possession and oversight of nuclear weapons. The MPC and A program is considered the first line of defense against theft of nuclear material because its goal is to prevent theft of material at production and storage facilities. This year the Department of Energy (DOE) initiated a new program called the Second Line of Defense (SLD), the goal of which is to assist Russia in preventing the smuggling of nuclear material and weapons at its borders, either by land, sea or air. The SLD program represents an important phase in the overall effort to ensure the security of nuclear material and weapons in Russia. However, as the US engages Russian customs officials in this important project, Americans should keep in mind that providing equipment--even indigenous equipment--is insufficient by itself; material aid must be accompanied by rigorous inspection and

  2. Biweekly cetuximab and irinotecan as second-line therapy in patients with gastro-esophageal cancer previously treated with platinum

    DEFF Research Database (Denmark)

    Schoennemann, Katrine R; Bjerregaard, Jon K; Hansen, Tine P

    2011-01-01

    toxicities were: diarrhea (8%), fatigue (10%), neutropenia (16%), and febrile neutropenia (2%). CONCLUSION: Cetiri every two weeks is a convenient and well-tolerated second-line regimen in GEC patients. A promising effect was seen in patients with PS 0-1 and in patients who developed a rash....

  3. Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer of adenocarcinoma histology

    DEFF Research Database (Denmark)

    Popat, Sanjay; Mellemgaard, Anders; Reck, Martin

    2017-01-01

    PATIENTS & METHODS: We provide an update to a network meta-analysis evaluating the relative efficacy of nintedanib + docetaxel versus other second-line agents in adenocarcinoma histology non-small-cell lung cancer. RESULTS: Overall similarity of nintedanib + docetaxel versus ramucirumab + docetaxel...

  4. A phase I/II trial to evaluate the safety, feasibility and activity of salvage therapy consisting of the mTOR inhibitor Temsirolimus added to standard therapy of Rituximab and DHAP for the treatment of patients with relapsed or refractory diffuse large cell B-Cell lymphoma – the STORM trial

    International Nuclear Information System (INIS)

    Witzens-Harig, Mathias; Memmer, Marie Luise; Dreyling, Martin; Hess, Georg

    2013-01-01

    The current standard treatment of patients with relapsed or refractory diffuse large cell B-Cell lymphoma (DLBCL) primarily consists of intensified salvage therapy and, if the disease is chemo-sensitive, high dose therapy followed with autologous stem cell transplantation. In the rituximab era however, this treatment approach has shown only limited benefit. In particular, patients relapsing after rituximab-containing primary treatment have an adverse prognosis, especially if this occurs within the first year after therapy or if the disease is primarily refractory. Therefore there is an ultimate need for improved salvage treatment approaches. The STORM study is a prospective, multicentre phase I/II study to evaluate the safety, feasibility and activity of salvage therapy consisting of the mTOR inhibitor temsirolimus added to the standard therapy rituximab and DHAP for the treatment of patients with relapsed or refractory DLBCL. The primary objective of the phase I of the trial is to establish the maximum tolerated dose (MTD) of temsirolimus in combination with rituximab and DHAP. The secondary objective is to demonstrate that stem cells can be mobilized during this regimen in patients scheduled to proceed to high dose therapy. In phase II, the previously established maximum tolerated dose of temsirolimus will be used. The primary objective is to evaluate the overall response rate (ORR) in patients with relapsed DLBCL. The secondary objective is to evaluate progression free survival (PFS), overall survival (OS) and toxicity. The study will be accompanied by an analysis of lymphoma subtypes determined by gene expression analysis (GEP). The STORM trial evaluates the safety, feasibility and activity of salvage therapy consisting of the mTOR inhibitor temsirolimus added to standard therapy of rituximab and DHAP for the treatment of patients with relapsed or refractory DLBCL. It also might identify predictive markers for this treatment modality. ClinicalTrials.gov http

  5. Comparable Efficacy of Abatacept Used as First-line or Second-line Biological Agent for Severe Juvenile Idiopathic Arthritis-related Uveitis.

    Science.gov (United States)

    Birolo, Carolina; Zannin, Maria Elisabetta; Arsenyeva, Svetlana; Cimaz, Rolando; Miserocchi, Elisabetta; Dubko, Margarita; Deslandre, Chantal Job; Falcini, Fernanda; Alessio, Maria; La Torre, Francesco; Denisova, Ekaterina; Martini, Giorgia; Nikishina, Irina; Zulian, Francesco

    2016-11-01

    Abatacept (ABA) has recently been proposed as second-line treatment in patients with juvenile idiopathic arthritis (JIA)-associated uveitis refractory to anti-tumor necrosis factor-α (anti-TNF) agents, but little is known about its efficacy as a first-line approach. The aim of the present study was to compare the safety and efficacy of ABA as a first-line biological agent (ABA-1) with that of ABA as a second-line treatment after 1 or more anti-TNF agents (ABA-2), in patients with severe JIA-related uveitis. In this multicenter study, we collected data on patients with severe JIA-related uveitis treated with ABA as a first-line or second-line biological agent. Changes in frequency of uveitis flares/year and ocular complications before and after ABA treatment, clinical remission, and side effects were recorded. Thirty-five patients with a mean age of 10.8 years were treated with ABA for a mean period of 19.6 months. In 4 patients, ABA administration was discontinued, owing to inefficacy on arthritis in 3 cases and allergic reaction in 1. Thirty-one patients, 14 in the ABA-1 group and 17 in the ABA-2 group, completed the 12-month followup period; of these, 17 (54.8%) had clinical remission. The mean frequency of uveitis flares decreased from 4.1 to 1.2 in the ABA-1 group (p = 0.002) and from 3.7 to 1.2 in the ABA-2 group (p = 0.004). Preexisting ocular complications improved or remained stable in all but 5 patients, all in the ABA-2 group. No significant difference was found between the efficacy of the 2 treatment modalities. ABA confirmed its good safety profile. ABA, used as first-line biological treatment or after 1 or more anti-TNF agents, induces a comparable improvement in severe refractory JIA-related uveitis.

  6. Decision aids for second-line palliative chemotherapy: a randomised phase II multicentre trial

    NARCIS (Netherlands)

    Oostendorp, L.J.M.; Ottevanger, P.B.; Donders, A.R.T.; Wouw, A.J. van de; Schoenaker, I.J.; Smilde, T.J.; Graaf, W.T.A. van der; Stalmeier, P.F.M.

    2017-01-01

    BACKGROUND: There is increasing recognition of the delicate balance between the modest benefits of palliative chemotherapy and the burden of treatment. Decision aids (DAs) can potentially help patients with advanced cancer with these difficult treatment decisions, but providing detailed information

  7. Primary tumor site is a useful predictor of cetuximab efficacy in the third-line or salvage treatment of KRAS wild-type (exon 2 non-mutant) metastatic colorectal cancer: a nationwide cohort study

    International Nuclear Information System (INIS)

    Chen, Kuo-Hsing; Shao, Yu-Yun; Chen, Ho-Min; Lin, Yu-Lin; Lin, Zhong-Zhe; Lai, Mei-Shu; Cheng, Ann-Lii; Yeh, Kun-Huei

    2016-01-01

    Previous studies have shown left-sided colorectal cancer (LCRC) and right-sided colorectal cancer (RCRC) exhibit different molecular and clinicopathological features. We explored the association between the primary tumor site and cetuximab efficacy in KRAS wild-type colorectal cancer (CRC). This study enrolled a cohort of patients, who had received cetuximab treatment after two or more lines of chemotherapy for KRAS wild-type (exon 2 nonmutant) metastatic CRC, from the databases of Taiwan Cancer Registry (2004–2010) and National Health Insurance (2004–2011). Survival data were obtained from the National Death Registry. Time to treatment discontinuation (TTD) and overall survival (OS) after the start of cetuximab treatment were compared between patients with LCRC (splenic flexure to rectum) and RCRC (cecum to hepatic flexure). A total of 969 CRC patients were enrolled. Among them, 765 (78.9 %) and 136 (14.0 %) patients had LCRC and RCRC, respectively. Patients with LCRC, compared to patients with RCRC, had longer TTD (median, 4.59 vs. 2.75 months, P = .0005) and OS (median, 12.62 vs. 8.07 months, P < .0001) after the start of cetuximab treatment. Multivariate analysis revealed a right-sided primary tumor site was an independent predictor of shorter TTD (adjusted hazard ratio [HR] = 1.32, using the LCRC group as a reference, 95 % confidence interval: 1.08–1.61, P = .0072) and OS (adjusted HR = 1.45, 95 % CI: 1.18–1.78, P = .0003). Our findings demonstrate that a left-sided primary tumor site is a useful predictor of improved cetuximab efficacy in the third-line or salvage treatment of KRAS wild-type (exon 2 nonmutant) metastatic CRC

  8. Second line of defense program overview LA-UR-00-5161

    International Nuclear Information System (INIS)

    Knepper, P.L.; Martin, D.D.W.

    2001-01-01

    Full text: The illicit trafficking of nuclear material is a major concern for non-proliferation and global stability. The nuclear Material Protection, Control and Accounting (MPC and A) program provides the first line of defense in protecting nuclear materials within Russia by upgrading safeguards and security measures at Russian nuclear facilities. Second Line of Defense (SLD) is a cooperative program between the Russian Federation State Customs Committee (RF SCC) and the United States Department of Energy (US DOE) to minimize illicit trafficking of restricted nuclear materials through Russian border control points. This partnership was solidified with the signing of a protocol between DOE and the RF SCC in June 1998. The relationship will soon be formalized in a Memorandum of Understanding that will outline the working relationships and commitments to successful implementation of the SLD Program. The Russians first acknowledged the threat of nuclear smuggling at a Nuclear Safety Summit in Moscow in April 1996. Nikolai Kravehenko, head of the Regional Information and Technical Customs Department of the RF SCC, subsequently stated in a July 1998 interview, 'In order to stop trafficking and illegal shipment to other countries we [also] have to tighten security at the facilities and equip our borders with reliable technology.' At the September 1998 U.S.-Russia Presidential Summit, the then Chairman of the RF SCC, Valery Draganov, highlighted the illicit trafficking challenge confronting Russia and requested U.S. assistance. Since 1991, a myriad of cases associated with the diversion and recovery of nuclear materials appear to be linked to the FSU. In the majority of cases, the material's origin was attributed to Russia. With more than 20,000 km of border contiguous to fourteen other countries, and more than 350 customs and border sites, addressing the threat posed by nuclear smuggling in Russia is not only an urgent but also an expansive problem requiring joint U

  9. Postoperative Prostate-Specific Antigen Velocity Independently Predicts for Failure of Salvage Radiotherapy After Prostatectomy

    International Nuclear Information System (INIS)

    King, Christopher R.; Presti, Joseph C.; Brooks, James D.; Gill, Harcharan; Spiotto, Michael T.

    2008-01-01

    Purpose: Identification of patients most likely to benefit from salvage radiotherapy (RT) using postoperative (postop) prostate-specific antigen (PSA) kinetics. Methods and Materials: From 1984 to 2004, 81 patients who fit the following criteria formed the study population: undetectable PSA after radical prostatectomy (RP); pathologically negative nodes; biochemical relapse defined as a persistently detectable PSA; salvage RT; and two or more postop PSAs available before salvage RT. Salvage RT included the whole pelvic nodes in 55 patients and 4 months of total androgen suppression in 56 patients. The median follow-up was >5 years. All relapses were defined as a persistently detectable PSA. Kaplan-Meier and Cox proportional hazards multivariable analysis were performed for all clinical, pathological, and treatment factors predicting for biochemical relapse-free survival (bRFS). Results: There were 37 biochemical relapses observed after salvage RT. The 5-year bRFS after salvage RT for patients with postop prostate-specific antigen velocity ≤1 vs. >1 ng/ml/yr was 59% vs. 29%, p = 0.002. In multivariate analysis, only postop PSAV (p = 0.0036), pre-RT PSA level ≤1 (p = 0.037) and interval-to-relapse >10 months (p = 0.012) remained significant, whereas pelvic RT, hormone therapy, and RT dose showed a trend (p = ∼0.06). PSAV, but not prostate-specific antigen doubling time, predicted successful salvage RT, suggesting an association of zero-order kinetics with locally recurrent disease. Conclusions: Postoperative PSA velocity independently predicts for the failure of salvage RT and can be considered in addition to high-risk features when selecting patients in need of systemic therapy following biochemical failure after RP. For well-selected patients, salvage RT can achieve high cure rates

  10. Salvage image guided radiation therapy to the prostate after cryotherapy failure

    Directory of Open Access Journals (Sweden)

    Austin B. Hopper, BS

    2018-01-01

    Conclusions: High-dose IG-IMRT results in high rates of salvage and extremely low rates of serious late toxicity for patients with locally recurrent prostate cancer after cryotherapy. Although the results are encouraging, given the small number of patients in this and other series, we remain cautious with regard to this treatment and believe the use of salvage radiation therapy after cryotherapy warrants further study.

  11. SGLT2 inhibitors or GLP-1 receptor agonists as second-line therapy in type 2 diabetes: patient selection and perspectives.

    Science.gov (United States)

    Gurgle, Holly E; White, Karen; McAdam-Marx, Carrie

    2016-01-01

    Controversy exists regarding the selection of second-line therapy for patients with type 2 diabetes mellitus (T2DM) who are unable to achieve glycemic control with metformin therapy alone. Newer pharmacologic treatments for T2DM include glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors. Both the classes of medication are efficacious, exhibit positive effects on weight, and are associated with minimal risk of hypoglycemia. The purpose of this review is to compare the clinical trial and real-world effectiveness data of glucagon-like peptide-1 receptor agonists versus sodium-glucose cotransporter 2 inhibitors related to A1c reduction, weight loss, cost-effectiveness, cardiovascular outcomes, and safety in patients with T2DM. This review summarizes comparative evidence for providers who are determining which of the two classes may be the most appropriate for a specific patient.

  12. Extensively and Pre-Extensively Drug Resistant Tuberculosis in Clinical Isolates of Multi-Drug Resistant Tuberculosis Using Classical Second Line Drugs (Levofloxacin and Amikacin)

    International Nuclear Information System (INIS)

    Mirza, I. A.; Khan, F. A.; Khan, K. A.; Satti, L.; Ghafoor, T.; Fayyaz, M.

    2015-01-01

    Objective:To find out the frequency of Extensively Drug Resistant (XDR) and pre-XDR tuberculosis in clinical isolates of Multi-Drug Resistant (MDR) Tuberculosis (TB) by determining the susceptibilities against Levofloxacin and Amikacin (classical second line antituberculosis drugs). Study Design: A descriptive cross-sectional study. Place and Duration of Study: Microbiology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from September 2011 to August 2013. Methodology: Amikacin (AK) and Levofloxacin (LEVO) were obtained in chemically pure form from Sigma (Taufkirchen, Germany). The breakpoint concentration used for AK was 1.0 micro g/ml and for LEVO 2.0 micro g/ml. Mycobacterial Growth Indicator Tube (MGIT) 960 system was used to carry out drug susceptibility testing as per recommended protocol. Results: A total of 3 MDR-TB isolates (3 percentage) turned out to be XDR-TB based upon simultaneous resistance to injectable second line antituberculosis drug AK and one of the fluoro-quinolones (LEVO). A total of 24 MDR-TB isolates (24 percentage) were found to be pre-XDR based upon resistance to LEVO alone. Treatment status record of patients with XDR and pre-XDRTB isolates revealed that majority of patients had received fluoroquinolones (FQs) during the course of treatment. Conclusion: XDR-TB has started to emerge in MDR-TB isolates in our set up. The worrying sign is the high frequency of pre-XDR tuberculosis. Urgent steps need to be taken to stem the tide of pre-XDR-TB in our population. It is thus recommended to develop facilities to carry out drug susceptibility testing to monitor the status of pre-XDR and XDR-TB in our population. (author)

  13. Cetuximab as second-line therapy in patients with metastatic esophageal adenocarcinoma: A phase II Southwest Oncology Group Study (S0415)

    Science.gov (United States)

    Gold, Philip J.; Goldman, Bryan; Iqbal, Syma; Leichman, Lawrence P.; Zhang, Wu; Lenz, Heinz-Josef; Blanke, Charles D.

    2010-01-01

    Introduction Esophageal adenocarcinomas commonly express the Epidermal Growth Factor Receptor (EGFR). This trial assessed the six month overall survival probability in metastatic esophageal cancer patients treated with cetuximab as second line therapy. Methods This was a multicenter, open-label phase II study of single agent cetuximab for metastatic esophageal adenocarcinoma patients who failed one prior chemotherapy regimen. Adequate organ function and Zubrod performance status of 0-2 were required. Patients received cetuximab 400mg/m2 IV on week one, and 250 mg/m2 IV weekly thereafter. The primary objective was to determine 6 month overall survival. Secondary endpoints included progression-free survival, response rate, and toxicity. Tumor tissue was collected for correlative studies. Results Sixty-three patients were registered, with 8 ineligible or never treated. Fifty-five eligible patients (male=49, female=6; median age=61.2 years [range 30.7-88.5]) were enrolled. Twenty patients survived > 6 months for a 6-month overall survival rate of 36% (95% CI: 24%, 50%). The median overall survival was 4.0 months (95% CI: 3.2, 5.9). Median progression-free survival was 1.8 months (95% CI: 1.7, 1.9). One partial response and 2 unconfirmed partial responses were observed. Two patients experienced grade 4 fatigue. There was one treatment-related death due to pneumonitis. Germline polymorphisms of EGFR, EGF, IL-8, COX-2, VEGF, CCND1, NRP1 and Kras mutational status were not associated with response or survival. Conclusions The 6-month overall survival rate of 36% observed on this study failed to meet the primary survival objective. Thus, cetuximab alone cannot be recommended in the second-line treatment of metastatic esophageal cancer. PMID:20631636

  14. Trial-Based Cost-Utility Analysis of Icotinib versus Gefitinib as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer in China.

    Science.gov (United States)

    Zhang, Chunxiang; Zhang, Hongmei; Shi, Jinning; Wang, Dong; Zhang, Xiuwei; Yang, Jian; Zhai, Qizhi; Ma, Aixia

    2016-01-01

    Our objective is to compare the cost-utility of icotinib and gefitinib for the second-line treatment of advanced non-small cell lung cancer (NSCLC) from the perspective of the Chinese healthcare system. Model technology was applied to assess the data of randomized clinical trials and the direct medical costs from the perspective of the Chinese healthcare system. Five-year quality-adjusted life years (QALYs) and incremental cost-utility ratios (ICURs) were calculated. One-way and probabilistic sensitivity analyses (PSA) were performed. Our model suggested that the median progression-free survival (PFS) was 4.2 months in the icotinib group and 3.5 months in the gefitinib group while they were 4.6 months and 3.4 months, respectively, in the trials. The 5-year QALYs was 0.279 in the icotinib group and 0.269 in the gefitinib group, and the according medical costs were $10662.82 and $13127.57. The ICUR/QALY of icotinib versus gefitinib presented negative in this study. The most sensitive parameter to the ICUR was utility of PFS, ranging from $-1,259,991.25 to $-182,296.61; accordingly the icotinib treatment consistently represented a dominant cost-utility strategy. The icotinib strategy, as a second-line therapy for advanced NSCLC patients in China, is the preferred strategy relative to gefitinib because of the dominant cost-utility. In addition, icotinib shows a good curative effect and safety, resulting in a strong demand for the Chinese market.

  15. Trial-Based Cost-Utility Analysis of Icotinib versus Gefitinib as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer in China.

    Directory of Open Access Journals (Sweden)

    Chunxiang Zhang

    Full Text Available Our objective is to compare the cost-utility of icotinib and gefitinib for the second-line treatment of advanced non-small cell lung cancer (NSCLC from the perspective of the Chinese healthcare system.Model technology was applied to assess the data of randomized clinical trials and the direct medical costs from the perspective of the Chinese healthcare system. Five-year quality-adjusted life years (QALYs and incremental cost-utility ratios (ICURs were calculated. One-way and probabilistic sensitivity analyses (PSA were performed.Our model suggested that the median progression-free survival (PFS was 4.2 months in the icotinib group and 3.5 months in the gefitinib group while they were 4.6 months and 3.4 months, respectively, in the trials. The 5-year QALYs was 0.279 in the icotinib group and 0.269 in the gefitinib group, and the according medical costs were $10662.82 and $13127.57. The ICUR/QALY of icotinib versus gefitinib presented negative in this study. The most sensitive parameter to the ICUR was utility of PFS, ranging from $-1,259,991.25 to $-182,296.61; accordingly the icotinib treatment consistently represented a dominant cost-utility strategy.The icotinib strategy, as a second-line therapy for advanced NSCLC patients in China, is the preferred strategy relative to gefitinib because of the dominant cost-utility. In addition, icotinib shows a good curative effect and safety, resulting in a strong demand for the Chinese market.

  16. Cost Effectiveness Analysis of Different Management Strategies between Best Supportive Care and Second-line Chemotherapy for Platinum-resistant or Refractory Ovarian Cancer.

    Science.gov (United States)

    Luealon, Phanida; Khempech, Nipon; Vasuratna, Apichai; Hanvoravongchai, Piya; Havanond, Piyalamporn

    2016-01-01

    There is no standard treatment for patients with platinum-resistant or refractory epithelial ovarian cancer. Single agent chemotherapies have evidence of more efficacy and less toxicity than combination therapy. Most are very expensive, with appreciable toxicity and minimal survival. Since it is difficult to make comparison between outcomes, economic analysis of single-agent chemotherapy regimens and best supportive care may help to make decisions about an appropriate management for the affected patients. To evaluate the cost effectiveness of second-line chemotherapy compared with best supportive care for patients with platinum-resistant or refractory epithelial ovarian cancer. A Markov model was used to estimate the effectiveness and total costs associated with treatments. The hypothetical patient population comprised women aged 55 with platinum-resistant or refractory epithelial ovarian cancer. Four types of alternative treatment options were evaluated: 1) gemcitabine followed by BSC; 2) pegylated liposomal doxorubicin (PLD) followed by BSC; 3) gemcitabine followed by topotecan; and 4) PLD followed by topotecan. Baseline comparator of alternative treatments was BSC. Time horizon of the analysis was 2 years. Health care provider perspective and 3% discount rate were used to determine the costs of medical treatment in this study. Quality-adjusted life-years (QALY) were used to measure the treatment effectiveness. Treatment effectiveness data were derived from the literature. Costs were calculated from unit cost treatment of epithelial ovarian cancer patients at various stages of disease in King Chulalongkorn Memorial Hospital (KCMH) in the year 2011. Parameter uncertainty was tested in probabilistic sensitivity analysis by using Monte Carlo simulation. One-way sensitivity analysis was used to explore each variable's impact on the uncertainty of the results. Approximated life expectancy of best supportive care was 0.182 years and its total cost was 26,862 Baht. All

  17. Salvage surgery for local failure of oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Omura, Ken; Harada, Hiroyuki; Shimamoto, Hiroaki

    2003-01-01

    Local failure rates following treatment for squamous cell carcinoma of the oral cavity have been reported to be in the range of 25%-48%. This study investigated the pattern of failure for squamous cell carcinoma (SCC) of the oral cavity and evaluated salvage surgery for local recurrent disease. The tumor files of 549 patients undergoing treatment for SCC of the oral cavity between 1980 and 2000 at Chiba Cancer Center Hospital were reviewed. Of 549 patients, 289 were initially treated with radiation therapy for their primary tumor, and 260 with surgery, either with or without radiation therapy. One hundred and sixty-one patients developed failures, yielding a failure rate of 29.3%. The site of recurrent tumor was local in 72 (13.1%) patients, regional in 89 (16.2%) patients, and distant in 5 (0.9%) patients. Local failure developed in 49 (17.0%) patients with radiation therapy and in 23 (8.8%) patients with surgery. Out of these 72 patients with local failure, 41 (56.9%) patients had salvage surgery for their disease. Twenty-five (73.5%) of the 34 patients initially treated with radiation therapy were salvaged with surgery, and 4 (57.1%) of the 7 patients initially treated with surgery were cured with further surgery. For the treatment of patients with local failure, the disease should be diagnosed more carefully than untreated disease. The disease that has recurred after radiation therapy may be more likely to be salvaged by surgery, however, the disease that has developed after surgery may have a limited indication for re-surgery. (author)

  18. Improved darunavir genotypic mutation score predicting treatment response for patients infected with HIRaben-1 subtype B and non-subtype B receiving a salvage regimen

    NARCIS (Netherlands)

    De Luca, Andrea; Flandre, Philippe; Dunn, David; Zazzi, Maurizio; Wensing, Annemarie; Santoro, Maria Mercedes; Günthard, Huldrych F.; Wittkop, Linda; Kordossis, Theodoros; Garcia, Federico; Castagna, Antonella; Cozzi-Lepri, Alessandro; Churchill, Duncan; De Wit, Stéphane; Brockmeyer, Norbert H.; Imaz, Arkaitz; Mussini, Cristina; Obel, Niels; Perno, Carlo Federico; Roca, Bernardino; Reiss, Peter; Schülter, Eugen; Torti, Carlo; van Sighem, Ard; Zangerle, Robert; Descamps, Diane; Mocroft, Amanda; Kirk, Ole; Sabin, Caroline; De Wit, Stéphane; Casabona, Jordi; Miró, Jose M.; Touloumi, Giota; Garrido, Myriam; Teira, Ramon; Wit, Ferdinand; Warszawski, Josiane; Meyer, Laurence; Dabis, François; Krause, Murielle Mary; Ghosn, Jade; Leport, Catherine; Prins, Maria; Bucher, Heiner; Gibb, Diana; Fätkenheuer, Gerd; del Amo, Julia; Thorne, Claire; Stephan, Christoph; Pérez-Hoyos, Santiago; Hamouda, Osamah; Bartmeyer, Barbara; Chkhartishvili, Nikoloz; Noguera-Julian, Antoni; Antinori, Andrea; d'Arminio Monforte, Antonella; Prieto, Luis; Conejo, Pablo Rojo; Soriano-Arandes, Antoni; Battegay, Manuel; Kouyos, Roger; Tookey, Pat; Konopnick, Deborah; Goetghebuer, Tessa; Sönnerborg, Anders; Haerry, David; de Wit, Stéphane; Costagliola, Dominique; Raben, Dorthe; Chêne, Geneviève; Ceccherini-Silberstein, Francesca; Günthard, Huldrych; Judd, Ali; Barger, Diana; Schwimmer, Christine; Termote, Monique; Campbell, Maria; Frederiksen, Casper M.; Friis-Møller, Nina; Kjaer, Jesper; Brandt, Rikke Salbøl; Berenguer, Juan; Bohlius, Julia; Bouteloup, Vincent; Davies, Mary Anne; Dorrucci, Maria; Egger, Matthias; Furrer, Hansjakob; Guiguet, Marguerite; Grabar, Sophie; Lambotte, Olivier; Leroy, Valériane; Lodi, Sara; Matheron, Sophie; Monge, Susana; Nakagawa, Fumiyo; Paredes, Roger; Phillips, Andrew; Puoti, Massimo; Schomaker, Michael; Smit, Colette; Sterne, Jonathan; Thiebaut, Rodolphe; van der Valk, Marc; Wyss, Natasha; Aubert, V.; Battegay, M.; Bernasconi, E.; Böni, J.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Dollenmaier, G.; Egger, M.; Elzi, L.; Fehr, J.; Fellay, J.; Furrer, H.; Fux, C. A.; Gorgievski, M.; Günthard, H.; Haerry, D.; Hasse, B.; Hirsch, H. H.; Hoffmann, M.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Klimkait, T.; Kouyos, R.; Kovari, H.; Ledergerber, B.; Martinetti, G.; Martinez de Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Nicca, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schöni-Affolter, F.; Schmid, P.; Schüpbach, J.; Speck, R.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Yerly, S.

    2016-01-01

    Objectives: The objective of this studywas to improve the prediction of the impact of HIV-1 protease mutations in different viral subtypes on virological response to darunavir. Methods: Darunavir-containing treatment change episodes (TCEs) in patients previously failing PIs were selected from large

  19. A MULTICENTRE STUDY OF ASSESSING THE EFFECTIVENESS OF SALVAGING LYMPHADENECTOMY IN PATIENTS WITH PROSTATE CANCER WITH DISEASE PROGRESSION AFTER THE RADICAL TREATMENT

    Directory of Open Access Journals (Sweden)

    B. Y. Alekseev

    2016-01-01

    Full Text Available Prostate cancer (PC is one of the most urgent problems of modern oncourology because of the continuing high incidence of this pathology. The main methods of radical treatment of patients with localized and locally advanced prostate cancer are radical prostatectomy (RP and radiotherapy – remote (RRT or brachytherapy.  However, the frequency of biochemical markers of disease progression after curative treatment is high and reaches up to 27–53%. It is extremely important to find the tumor lesion that leads to the increase of the marker. The  palliative hormone therapy (PHT was the only accepted method in patients with occurrence of distant metastases in recent time. However, a significant number of patients relapse marker may be associated with the so-called oligo-metastatic disease progression, in which the number of detected metastatic lesions is minimal. As the results of the research, the use of surgical or radiological treatment in selected patients of this cohort can significantly increase the length of time prior to the appointment of HT, and in some cases completely abandon its holding.Purpose. To evaluate the results of the saving pelvic lymphadenectomy in patients with prostate cancer with disease progression after radical therapies.Patients and methods. The article summarizes the results of surgical treatment of patients who have undergone life-saving lymphadenectomy about oligo-nodal metastatic progression of prostate cancer after treatment in 3 centers – P. Hertsen MORI, the branch of NMRRC; N. Petrov Research Institute of Oncology and Russian scientific center of radiology and surgical technologies. In this multicenter study they evaluated the immediate and remote results of surgical treatment of 57 patients.Results. The results performed the high efficiency of the method of the saving pelvic lymphadenectomy in patients with prostate cancer with disease progression after radical treatment. So, response to therapy and reduction

  20. Modified endoscopic medial maxillectomy for zygomatic implant salvage.

    Science.gov (United States)

    Schwartz, Joseph S; Tajudeen, Bobby A; Adappa, Nithin D; Palmer, James N

    2016-01-01

    Odontogenic chronic rhinosinusitis (CRS) is an epidemiologically important disease process due, in part, to the increasingly commonplace use of dental restorative procedures such as zygomatic implantation. Traditional management of this clinical entity typically entails extraction of the infected hardware via an open or endoscopic approach. We describe a novel management strategy of odontogenic CRS following bilateral zygomatic implantation for oral rehabilitation that we surgically salvaged via a modified endoscopic medial maxillectomy. We describe the presentation and management of a case of metachronous development of bilateral CRS subsequent to zygomatic implantation. The patient's postoperative course was characterized by marked endoscopic, radiologic, and symptomatic improvement as measured by the 22-item Sino-Nasal Outcome Test. We describe a novel treatment strategy for the management of odontogenic sinusitis resulting from erroneous zygomatic implant placement. Modified endoscopic medial maxillectomy in this clinical context facilitates mucosal normalization of the affected sinus, while permitting preservation of oral function through salvage of the displaced implant.

  1. Peripheral Sympathectomy for Raynaud's Phenomenon: A Salvage Procedure

    Directory of Open Access Journals (Sweden)

    Wen-Her Wang

    2006-10-01

    Full Text Available We retrospectively reviewed the effectiveness of peripheral sympathectomy for severe Raynaud's phenomenon. In this study, a total of 14 digits from six patients with chronic digital ischemic change were included. All patients had pain, ulcer, or gangrenous change in the affected digits and were unresponsive to pharmacologic or other nonsurgical therapies. In all cases, angiography showed multifocal arterial lesions, so microvascular reconstruction was unfeasible. Peripheral sympathectomy was performed as a salvage procedure to prevent digit amputation. The results were analyzed according to reduction of pain, healing of ulcers, and prevention of amputation. In 12 of the 14 digits, the ulcers healed and amputation was avoided. In the other two digits, the ulcers improved and progressive gangrene was limited. As a salvage procedure for Raynaud's phenomenon recalcitrant to conservative treatment, peripheral sympathectomy improves perfusion to ischemic digits and enables amputation to be avoided.

  2. Implant breast reconstruction after salvage mastectomy in previously irradiated patients.

    Science.gov (United States)

    Persichetti, Paolo; Cagli, Barbara; Simone, Pierfranco; Cogliandro, Annalisa; Fortunato, Lucio; Altomare, Vittorio; Trodella, Lucio

    2009-04-01

    The most common surgical approach in case of local tumor recurrence after quadrantectomy and radiotherapy is salvage mastectomy. Breast reconstruction is the subsequent phase of the treatment and the plastic surgeon has to operate on previously irradiated and manipulated tissues. The medical literature highlights that breast reconstruction with tissue expanders is not a pursuable option, considering previous radiotherapy a contraindication. The purpose of this retrospective study is to evaluate the influence of previous radiotherapy on 2-stage breast reconstruction (tissue expander/implant). Only patients with analogous timing of radiation therapy and the same demolitive and reconstructive procedures were recruited. The results of this study prove that, after salvage mastectomy in previously irradiated patients, implant reconstruction is still possible. Further comparative studies are, of course, advisable to draw any conclusion on the possibility to perform implant reconstruction in previously irradiated patients.

  3. Second Line of Defense, Port of Buenos Aires and Exolgan Container Terminal Operational Testing and Evaluation Plan, Buenos Aires, Argentina

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, Bryan W.

    2012-08-23

    The Office of the Second Line of Defense (SLD) Megaports project team for Argentina will conduct operational testing and evaluation (OT&E) at Exolgan Container Terminal at the Port of Dock Sud from July 16-20, 2012; and at the Port of Buenos Aires from September 3-7, 2012. SLD is installing radiation detection equipment to screen export, import, and transshipment containers at these locations. The purpose of OT&E is to validate and baseline an operable system that meets the SLD mission and to ensure the system continues to perform as expected in an operational environment with Argentina Customs effectively adjudicating alarms.

  4. Adjuvant radiotherapy after salvage lymph node dissection because of nodal relapse of prostate cancer versus salvage lymph node dissection only

    International Nuclear Information System (INIS)

    Rischke, Hans Christian; Schultze-Seemann, Wolfgang; Kroenig, Malte; Schlager, Daniel; Jilg, Cordula Annette; Wieser, Gesche; Drendel, Vanessa; Stegmaier, Petra; Henne, Karl; Volegova-Neher, Natalia; Grosu, Anca-Ligia; Krauss, Tobias; Kirste, Simon

    2015-01-01

    Nodal pelvic/retroperitoneal recurrent prostate cancer (PCa) after primary therapy can be treated with salvage lymph node dissection (salvage-LND) in order to delay disease progression and offer cure for a subset of patients. Whether adjuvant radiotherapy (ART) in affected regions improves the outcome by elimination of residual tumour burden remains unclear. A total of 93 patients with exclusively nodal PCa relapse underwent choline-positron-emission tomography-computed-tomography-directed pelvic/retroperitoneal salvage-LND; 46 patients had surgery only and 47 patients received ART in regions with proven lymph node metastases. In case of subsequent prostate specific antigen (PSA) progression, different imaging modalities were performed to confirm next relapse within or outside the treated region (TR). Mean follow-up was 3.2 years. Lymphatic tumour burden was balanced between the two groups. Additional ART resulted in delayed relapse within TR (5-year relapse-free rate 70.7 %) versus surgery only (5-year relapse-free rate 26.3 %, p < 0.0001). In both treatment arms, time to next relapse outside the TR was almost equal (median 27 months versus 29.6 months, p = 0.359). With respect to the detection of the first new lesion, regardless if present within or outside the TR, 5 years after the treatment 34.3 % of patients in the group with additional ART were free of relapse, versus 15.4 % in the surgery only group (p = 0.0122). ART had no influence on the extent of PSA reduction at latest follow-up compared to treatment with surgery only. ART after salvage-LND provides stable local control in TR and results in overall significant improved next-relapse-free survival, compared to patients who received surgery only in case of nodal PCa-relapse. (orig.) [de

  5. Metastatic Urothelial Carcinoma with Glandular Differentiation That Confirmed the Response by Autopsy Specimen to Second-Line mFOLFOX6 (Fluorouracil, Oxaliplatin, and Leucovorin plus Bevacizumab Chemotherapy

    Directory of Open Access Journals (Sweden)

    Taku Naiki

    2017-11-01

    Full Text Available The prognostic significance of glandular differentiation in urothelial carcinoma (UC is controversial, and thus far there is no established treatment strategy against metastasis of glandular component. We describe here a case of metastatic UC with glandular differentiation that had histological disappearance of adenocarcinoma components at autopsy after sequential chemotherapy with S-1 and cisplatin (CDDP and with mFOLFOX6 (fluorouracil, oxaliplatin, and leucovorin plus bevacizumab (mFOLFOX6+Bev. A 62-year-old Asian male was diagnosed with invasive UC with glandular differentiation (T2N0M0 by radical cystectomy and ileal conduit, and careful follow-up observation was made. Eight years after radical operation, peritoneal metastases occurred, and a biopsy specimen using colon fiber revealed high-grade adenocarcinomas with an immunohistochemical profile that included positivity for cytokeratin 7 (CK7 and negativity for cytokeratin 20 (CK20 and uroplakin, which was identical to the radical cystectomy specimen. Thus, he received combination chemotherapy consisting of S-1 and CDDP; however, the peritoneal metastasis worsened after 2 cycles. Therefore, second-line mFOLFOX6+Bev chemotherapy was performed for a total of 5 courses. In spite of this, the patient died, and the final diagnosis by autopsy was multiple metastases of infiltrating pure UC to the lung, bone, and peritoneum. Interestingly, there were no pathological findings of adenocarcinoma, and the immunohistochemical profile of the metastatic lesions was identical to that of the previous specimens from the bladder and colon. This suggests that sequential chemotherapy of S-1 and CDDP and second-line mFOLFOX6+Bev might be a feasible option in metastatic UC with glandular differentiation.

  6. Where to Turn for Second-Line Cytoreduction After Hydroxyurea in Polycythemia Vera?

    Science.gov (United States)

    Nazha, Aziz; Gerds, Aaron T

    2016-04-01

    The goals of therapy in patients with polycythemia vera (PV) are to improve disease-related symptoms, prevent the incidence or recurrence of thrombosis, and possibly delay or prevent the transformation into myelofibrosis or acute myeloid leukemia (AML). Cytoreductive therapies have been used in older patients and those with a history of thrombosis to achieve these goals. Hydroxyurea (HU) remains the first-line cytoreductive choice; however, up to one in four patients treated with HU over time will develop resistance or intolerance to HU. More importantly, patients who fail HU have a 5.6-fold increase in mortality and a 6.8-fold increase risk of transformation to myelofibrosis or AML; therefore, alternative therapies are needed for these patients. Interferon-α has been used in PV and has shown significant activity in achieving hematologic responses and decreasing JAK2 V617F mutation allele burden. JAK inhibition has also been investigated and recently garnered regulatory approval for this indication. In this review, we will discuss the current treatment options that are available for patients after HU and the novel therapies that are currently under investigation. The outcomes of PV patients who fail or who are intolerant of hydroxyurea are poor. Although pegylated interferon can be considered in younger patients, currently, ruxolitinib is the only U.S. Food and Drug Administration-approved agent in this setting, representing a viable option, leading to hematocrit control and a reduction in spleen size and constitutional symptoms. Although a small number of patients will achieve a molecular response with continuous treatment, the implications of such response on the clinical outcomes are still unknown. Patients whose disease is not adequately controlled with ruxolitinib, or who lose their response, can be treated with low-dose busulfan or pipobroman; however, they should be encouraged to participate in trials with novel therapies. ©AlphaMed Press.

  7. Radiotherapy salvage for Hodgkin's disease after chemotherapy failure

    Energy Technology Data Exchange (ETDEWEB)

    Wirth, A; Corry, J; Liew, K H

    1995-07-01

    Purpose/Objective: The precise role of salvage radiotherapy (RT) following chemotherapy (CT) failure in patients with Hodgkin's disease (HD) remains undefined. The aims of this study are: (1) to assess the pattern of failure, failure-free and overall survival, in patients who receive salvage RT for HD after CT failure; and (2) to identify patient subsets most suitable for this treatment approach. Materials and Methods: A review of patients treated between 1978 and 1992 at the Peter MacCallum Cancer Institute identified 52 patients with relapsed/refractory HD following CT who received RT with curative intent. Eligibility for this study required either biopsy confirmation of relapse/residual disease, or else clear clinical or radiological disease progression. Patient characteristics at diagnosis: median age 26, with 32% > 40 years old; M/ F 31/21; stage I-4, II-16, III-25, IV-7. Initial CT was MOPP- 31 patients, ABVD-1, both-16. A median 6 cycles of CT was given per regimen. Prior to salvage RT, 26/52 patients had received both MOPP and ABVD, either as sequential regimens, or as alternating or hybrid protocols. The response to initial CT was: CR-30, PR/SD-18, PD-4. Duration of initial CR was < 12 months in 8/30 patients. Salvage treatment consisted of radiotherapy to all known areas of disease. Doses ranged from 3600-4000 cGy. Results: Twenty three patients (45%) achieved CR. With a median follow-up of 70 months (range 4.8-166), actuarial median failure free survival (FFS) and overall survival (OS) are 22 months and 83 months respectively. Actuarial 5 year FFS and OS are 26% and 57% respectively. Patients with CR duration > 12 months following initial CT, only one CT regimen prior to salvage RT, and anatomically limited relapse had a significantly longer FFS. These factors, and age < 40 were associated with significantly longer OS. Only 6% of patients failed solely in the irradiated volume as first site of relapse, with the total in-field relapse of 30%. Sixty

  8. Improved darunavir genotypic mutation score predicting treatment response for patients infected with HIV-1 subtype B and non-subtype B receiving a salvage regimen

    DEFF Research Database (Denmark)

    De Luca, Andrea; Flandre, Philippe; Dunn, David

    2016-01-01

    OBJECTIVES: The objective of this study was to improve the prediction of the impact of HIV-1 protease mutations in different viral subtypes on virological response to darunavir. METHODS: Darunavir-containing treatment change episodes (TCEs) in patients previously failing PIs were selected from...... was derived based on best subset least squares estimation with mutational weights corresponding to regression coefficients. Virological outcome prediction accuracy was compared with that from existing genotypic resistance interpretation systems (GISs) (ANRS 2013, Rega 9.1.0 and HIVdb 7.0). RESULTS: TCEs were...

  9. Allogeneic Hematopoietic Stem Cell Transplantation Is an Effective Salvage Therapy for Patients with Chronic Myeloid Leukemia Presenting with Advanced Disease or Failing Treatment with Tyrosine Kinase Inhibitors.

    Science.gov (United States)

    Nair, Anish P; Barnett, Michael J; Broady, Raewyn C; Hogge, Donna E; Song, Kevin W; Toze, Cynthia L; Nantel, Stephen H; Power, Maryse M; Sutherland, Heather J; Nevill, Thomas J; Abou Mourad, Yasser; Narayanan, Sujaatha; Gerrie, Alina S; Forrest, Donna L

    2015-08-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only known curative therapy for chronic myeloid leukemia (CML); however, it is rarely utilized given the excellent long-term results with tyrosine kinase inhibitor (TKI) treatment. The purpose of this study is to examine HSCT outcomes for patients with CML who failed TKI therapy or presented in advanced phase and to identify predictors of survival, relapse, and nonrelapse mortality (NRM). Fifty-one patients with CML underwent HSCT for advanced disease at diagnosis (n = 15), TKI resistance as defined by the European LeukemiaNet guidelines (n = 30), TKI intolerance (n = 2), or physician preference (n = 4). At a median follow-up of 71.9 months, the 8-year overall survival (OS), event-free survival (EFS), relapse, and NRM were 68%, 46%, 41%, and 23%, respectively. In univariate analysis, predictors of OS included first chronic phase (CP1) disease status at HSCT (P = .0005), European Society for Blood and Marrow Transplantation score 1 to 4 (P = .04), and complete molecular response (CMR) to HSCT (P treatment to optimize transplantation outcomes. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  10. Should total hip arthroplasty be performed acutely in the treatment of acetabular fractures in elderly or used as a salvage procedure only?

    Directory of Open Access Journals (Sweden)

    Katharine Hamlin

    2017-01-01

    Full Text Available Background: Total hip arthroplasty (THA is now an increasingly common procedure for people sustaining acetabular fractures. The incidence of acetabular fractures among the elderly population is increasing, and contemporary treatment aims to avoid the risks of prolonged incumbency associated with poor bone stock for fixation or inability to comply with limited weightbearing in this patient group. The concept of acute hip arthroplasty as a treatment for acetabular fracture is, therefore, becoming more topical and relevant. Our systematic review investigates whether THAs for acetabular fractures should be performed acutely, with a short delay, or as a late procedure for posttraumatic osteoarthritis (PTOA if it develops. Materials and Methods: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed when undertaking this systematic review. Detailed searches were performed on three different databases, using keywords, such as “acetabular fracture,” “acetabular trauma,” “total hip arthroplasty,” “hip arthroplasty,” and “hip prosthesis.” Studies from 1975 to September 2016 were included in the study. All studies included in the review were independently critically appraised by two of the authors. Results: Forty three studies were included in this review. Only two of them actually compared acute and delayed THAs for acetabular fractures with the rest focusing on one or the other. Results were comparable between acute and late THAs in terms of aseptic loosening, operative time, blood loss, Harris Hip Score, and ability to mobilize postoperatively without aid. Complication rates, however, were much higher in the acute group. Conclusion: Evidence based on this topic is scarce and therefore we have to be cautious about drawing a definitive conclusion. The findings of this systematic review do suggest, however, that acute THAs should be considered in elderly patients, where fixation is not possible, or

  11. Nivolumab as salvage treatment in a patient with HIV-related relapsed/refractory Hodgkin lymphoma and liver failure with encephalopathy.

    Science.gov (United States)

    Sandoval-Sus, Jose D; Mogollon-Duffo, Francis; Patel, Ankita; Visweshwar, Nathan; Laber, Damian A; Kim, Richard; Jagal, Michael V

    2017-01-01

    We report the first case to our knowledge of a patient with relapsed/refractory classical hodgkin lymphoma and liver failure with encephalopathy along with human immunodeficiency virus/acquired immunodeficiency syndrome infection, successfully treated with nivolumab without major side effects and encouraging prolonged disease control. In December 2015, at the time of the patient's progression from his Hodgkin lymphoma after fourth line treatment, he developed persistent fevers, abdominal distension, jaundice and worsening of his liver function tests. Magnetic resonance imaging of abdomen/pelvis demonstrated hepatomegaly with innumerable new liver lesions, splenomegaly with multiple splenic nodules and several new mediastinal, intraperitoneal and retroperitoneal lymphadenopathy. In accordance with the patient's wishes before admission, and after agreement with the family, nivolumab (3 mg/kg every 2 weeks) was given. Of note, antiretroviral therapy was on hold due to liver function tests, his viral load was undectable and cluster of differentiation 4 counts were 103/uL at the time of nivolumab administration. One week after the first dose of nivolumab both his hepatic encephalopathy and constitutional symptoms started to improve, and after 2 doses, (January 2016) his LFTs were almost back to normal. After 5 months of nivolumab treatment (10 doses), restaging (computerized tomography scans of neck, chest, abdomen, pelvis) done on May 2016 showed resolution of hepatosplenomegaly with two residual small hepatic lesions, heterogeneous spleen with no splenic lesions, and stable non-enlarged retroperitoneal lymph nodes without intraabdominal lymphadenopathy; consistent with partial response. We report a case of a patient with human immunodeficiency virus/acquired immunodeficiency syndrome -related relapsed/refractory classical Hodgkin lymphoma and acute liver failure with encephalopathy successfully treated with nivolumab after failing all standard therapeutic options

  12. Salvage HIFU after radiotherapy and salvage radiotherapy after HIFU in locally recurrent prostate cancer: Retrospective analysis of morbidity

    International Nuclear Information System (INIS)

    Lee, J.-W.; Hannoun-Leviac, J.-M.; Chevallier, D.; Rouscoff, Y.; Durand, M.; Amiel, J.; Gal, J.; Natale, R.; Chand, M.-E.; Raffaelli, C.; Ambrosetti, D.

    2012-01-01

    To evaluate the toxicity of therapeutic sequences High Intensity Focused Ultrasound (HIFU)-salvage radiotherapy (HIFU-RT) or radiotherapy-salvage HIFU (RT-HIFU) in case of locally recurrent prostate cancer. Nineteen patients had a local recurrence of prostate cancer. Among them, 10 patients were treated by HIFU-RT and 9 patients by RT- HIFU (4 by external beam radiotherapy [EBR] and 5 by brachytherapy [BRACHY]). Urinary side effects were assessed using CTCAE v4. At the time of the initial management, the median age was 66.5 years (53 72), the median PSA was 10.8 ng/mL (3.4 50) and the median initial Gleason score was 6.3 (5 8). Median follow-up after salvage treatment was 46.3 months (2 108). Thirty percent of the patients in the HIFU-RT group and 33.3 % of the patients in the RT-HIFU group, all belonging to the sub-group BRACHY-HIFU, had urinary complication greater than or equal to grade 2. Among all the patients, only 1 had grade 1 gastrointestinal toxicity. BRACHY-HIFU sequence seems to be purveyor of many significant urinary side effects. A larger database is needed to confirm this conclusion. (authors)

  13. Salvage esophagectomy post definitive chemoradiotherapy or radiotherapy

    International Nuclear Information System (INIS)

    Hosokawa, Masao; Suzuki, Yasuhiro; Nisida, Yasunori

    2008-01-01

    Outcome of salvage esophagectomy (SE), which was done due to rest development or recurrence after radical treatment of the esophageal cancer with radio- (RT) or chemoradio-therapy (CRT), was retrospectively studied and discussed. Subjects were 61 patients (M 54, F 7: average age, 63.5 y) with the cancer at Stage I- early IVB who had undergone radical CRT (35 cases) and RT (26) with >50 Gy, had no lymphatic and remote metastases at the diagnosis of the recurrence and then received SE and reconstruction surgery. Rough 5-year survival was found to be 29.2% in CRT group and 32.3% in RT. Operation-related death was 1 case (sepsis) and the rate of complication was slightly higher than the ordinary SE. Based on above outcome, discussion was made on following tasks and/or measures in authors' hospital: diagnostic means like the combination with positron emission tomography (PET), dose/regions of irradiation (dose to the heart and lung should be < TD 5/5=tolerance dose to be <5% incidence of adverse effect within 5 years) and of chemotherapy, decision of the irradiation area with consideration of SE afterward, careful surgery to reduce complication, and sufficient preoperative evaluation for radical surgery by images like PET/CT. Operation with consideration of these items conceivably makes SE safer. (R.T.)

  14. A clinical trial protocol for second line treatment of malignant brain tumors with BNCT at University of Tsukuba

    Energy Technology Data Exchange (ETDEWEB)

    Aiyama, H. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan); Nakai, K., E-mail: knakai@Neurosurg-tsukuba.com [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan); Yamamoto, T. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan)] [Department of Radiation Oncology, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan); Nariai, T. [Department of Neurosurgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyouku (Japan); Kumada, H. [Department of Radiation Oncology, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan); Ishikawa, E. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan); Isobe, T. [Department of Radiation Oncology, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan); Endo, K.; Takada, T.; Yoshida, F.; Shibata, Y.; Matsumura, A. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan)

    2011-12-15

    We have evaluated the efficacy and safety of boron neutron capture therapy (BNCT) for recurrent glioma and malignant brain tumor using a new protocol. One of the two patients enrolled in this trial is a man with recurrent glioblastoma and the other is a woman with anaplastic meningioma. Both are still alive and no severe adverse events have been observed. Our findings suggest that NCT will be safe as a palliative therapy for malignant brain tumors. - Highlights: Black-Right-Pointing-Pointer Boron neutron capture therapy (BNCT) for recurrent glioma and malignant brain tumor. Black-Right-Pointing-Pointer Two cases with recurrent glioblastoma and anaplastic meningioma. Black-Right-Pointing-Pointer No severe adverse events have been observed using BNCT. Black-Right-Pointing-Pointer BNCT has a possibility of a safe palliative therapy for malignant brain tumors.

  15. Cost-Effectiveness of Everolimus for Second-Line Treatment of Metastatic Renal Cell Carcinoma in Serbia

    NARCIS (Netherlands)

    Mihajlovic, Jovan; Pechlivanoglou, Petros; Sabo, Ana; Tomic, Zdenko; Postma, Maarten J.

    2013-01-01

    Background: New targeted therapeutics for metastatic renal cell carcinoma (mRCC) enable an increment in progression-free survival (PFS) ranging from 2 to 6 months. Compared with best supportive care, everolimus demonstrated an additional PFS of 3 months in patients with mRCC whose disease had

  16. A clinical trial protocol for second line treatment of malignant brain tumors with BNCT at University of Tsukuba

    International Nuclear Information System (INIS)

    Aiyama, H.; Nakai, K.; Yamamoto, T.; Nariai, T.; Kumada, H.; Ishikawa, E.; Isobe, T.; Endo, K.; Takada, T.; Yoshida, F.; Shibata, Y.; Matsumura, A.

    2011-01-01

    We have evaluated the efficacy and safety of boron neutron capture therapy (BNCT) for recurrent glioma and malignant brain tumor using a new protocol. One of the two patients enrolled in this trial is a man with recurrent glioblastoma and the other is a woman with anaplastic meningioma. Both are still alive and no severe adverse events have been observed. Our findings suggest that NCT will be safe as a palliative therapy for malignant brain tumors. - Highlights: ► Boron neutron capture therapy (BNCT) for recurrent glioma and malignant brain tumor. ► Two cases with recurrent glioblastoma and anaplastic meningioma. ► No severe adverse events have been observed using BNCT. ► BNCT has a possibility of a safe palliative therapy for malignant brain tumors.

  17. Cost-effectiveness of HIV drug resistance testing to inform switching to second line antiretroviral therapy in low income settings

    DEFF Research Database (Denmark)

    Phillips, Andrew; Cambiano, Valentina; Nakagawa, Fumiyo

    2014-01-01

    BACKGROUND: To guide future need for cheap resistance tests for use in low income settings, we assessed cost-effectiveness of drug resistance testing as part of monitoring of people on first line ART - with switching from first to second line ART being conditional on NNRTI drug resistance mutations...... being identified. METHODS: An individual level simulation model of HIV transmission, progression and the effect of ART which accounts for adherence and resistance development was used to compare outcomes of various potential monitoring strategies in a typical low income setting in sub-Saharan Africa....... Underlying monitoring strategies considered were based on clinical disease, CD4 count or viral load. Within each we considered a strategy in which no further measures are performed, one with a viral load measure to confirm failure, and one with both a viral load measure and a resistance test. Predicted...

  18. Impact of acute hyperglycemia on myocardial infarct size, area at risk and salvage in patients with ST elevation myocardial infarction and the association with exenatide treatment - results from a randomized study

    DEFF Research Database (Denmark)

    Lønborg, Jacob Thomsen; Vejlstrup, Niels Grove; Kelbæk, Henning Skov

    2014-01-01

    Hyperglycemia upon hospital admission in patients with ST-segment elevation myocardial infarction (STEMI) occurs frequently and is associated with adverse outcomes. It is, however, unsettled as to whether an elevated blood glucose level is the cause or consequence of increased myocardial damage....... In addition, whether the cardioprotective effect of exenatide, a glucose-lowering drug, is dependent on hyperglycemia remains unknown. The objectives of this substudy were to evaluate the association between hyperglycemia and infarct size, myocardial salvage, and area at risk, and to assess the interaction...... between exenatide and hyperglycemia. A total of 210 STEMI patients were randomized to receive intravenous exenatide or placebo before percutaneous coronary intervention. Hyperglycemia was associated with larger area at risk and infarct size compared with patients with normoglycemia, but the salvage index...

  19. Limb Salvage After Bone Cancer

    Science.gov (United States)

    ... Childhood Cancer Statistics Webinars Video Library Types of Children’s Cancer Leukemia Lymphoma Solid Tumors (Sarcomas) More… During Treatment Tests and Procedures Treatment Options Treatment Side Effects ...

  20. Multicenter, randomized, double-blind phase 2 trial of FOLFIRI with regorafenib or placebo as second-line therapy for metastatic colorectal cancer.

    Science.gov (United States)

    Sanoff, Hanna K; Goldberg, Richard M; Ivanova, Anastasia; O'Reilly, Seamus; Kasbari, Samer S; Kim, Richard D; McDermott, Ray; Moore, Dominic T; Zamboni, William; Grogan, William; Cohn, Allen Lee; Bekaii-Saab, Tanios S; Leonard, Gregory; Ryan, Theresa; Olowokure, Olugbenga O; Fernando, Nishan H; McCaffrey, John; El-Rayes, Bassel F; Horgan, Anne M; Sherrill, Gary Bradley; Yacoub, George Hosni; O'Neil, Bert H

    2018-06-15

    Regorafenib, a multikinase inhibitor that inhibits angiogenesis, growth, and proliferation, prolongs survival as monotherapy in patients with refractory colorectal cancer. This international, double-blind, placebo-controlled, multicenter trial assessed the efficacy of regorafenib with folinic acid, fluorouracil, and irinotecan (FOLFIRI) as a second-line treatment for metastatic colorectal cancer. Patients with metastatic colorectal cancer who progressed on first-line oxaliplatin and fluoropyrimidine enrolled at 45 sites in the United States and Ireland. Patients, stratified by prior bevacizumab use, were randomized 2:1 to regorafenib or placebo. The treatment consisted of FOLFIRI on days 1 and 2 and days 15 and 16 with 160 mg of regorafenib or placebo on days 4 to 10 and days 18 to 24 of every 28-day cycle. Crossover was not allowed. The primary endpoint was progression-free survival (PFS). Under the assumption of a 75% event rate, 180 patients were required for 135 events to achieve 90% power to detect a hazard ratio (HR) of 0.65 with a 1-sided α value of .1. One hundred eighty-one patients were randomized (120 to regorafenib-FOLFIRI and 61 to placebo-FOLFIRI) with a median age of 62 years. Among these, 117 (65%) received prior bevacizumab or aflibercept. PFS was longer with regorafenib-FOLFIRI than placebo-FOLFIRI (median, 6.1 vs 5.3 months; HR, 0.73; 95% confidence interval [CI], 0.53-1.01; log-rank P = .056). The median overall survival was not longer (HR, 1.01; 95% CI, 0.71-1.44). The response rate was higher with regorafenib-FOLFIRI (34%; 95% CI, 25%-44%) than placebo-FOLFIRI (21%; 95% CI, 11%-33%; P = .07). Grade 3/4 adverse events with a >5% absolute increase from regorafenib included diarrhea, neutropenia, febrile neutropenia, hypophosphatemia, and hypertension. The addition of regorafenib to FOLFIRI as second-line therapy for metastatic colorectal cancer only modestly prolonged PFS over FOLFIRI alone. Cancer 2018. © 2018 American Cancer

  1. Risk factors predicting the outcome of salvage radiotherapy in patients with biochemical recurrence after radical prostatectomy

    International Nuclear Information System (INIS)

    Kinoshita, Hidefumi; Shimizu, Yosuke; Mizowaki, Takashi

    2013-01-01

    Salvage radiotherapy is the only curative treatment for patients with prostate cancer showing biochemical progression after radical prostatectomy. In this study, we evaluated the clinicopathological parameters that influence the outcome of salvage radiotherapy. Medical records of 49 patients who underwent salvage radiotherapy after radical prostatectomy from 1997 to 2008 at the Graduate School of Medicine, Kyoto University, were retrospectively reviewed. Radiotherapy was carried out with 66 Gy on the prostatic bed. Biochemical progression-free survival after salvage radiotherapy at 2, 5 and 7 years was 51.0%, 42.2% and 42.2%, respectively. Significant parameters predicting biochemical progression after salvage radiotherapy by Cox regression analysis were prostatectomy Gleason score sum ≥8 (hazard ratio 0.08; 95% confidence interval 0.03-0.22; P=0.001), prostate-specific antigen nadir after radical prostatectomy ≥0.04 ng/mL (hazard ratio 0.30; 95% confidence interval 0.13-0.69; P=0.005) and negative surgical margin (hazard ratio 0.28; 95% confidence interval 0.12-0.70; P=0.006). When the patients were subgrouped by these risk factors, the 5-year progression-free survival rates after salvage radiotherapy were 77.8%, 50.0% and 6.7% in patients with 0, 1 and ≥2 predictors, respectively. In order to discriminate favorable candidates for salvage radiotherapy, Gleason score of prostatectomy, prostate-specific antigen nadir after prostatectomy and positive surgical margin represent independent predictors. Thus, progression-free survival might be more precisely predicted according to the presence/absence of these risk factors. The significance of this risk classification should be confirmed by large prospective studies. (author)

  2. Effects of definitive and salvage radiotherapy on the distribution of lymphocyte subpopulations in prostate cancer patients

    International Nuclear Information System (INIS)

    Sage, Eva K.; Gehrmann, Mathias; Sedelmayr, Michael; Schmid, Thomas E.; Combs, Stephanie E.; Multhoff, Gabriele; Geinitz, Hans; Duma, Marciana N.

    2017-01-01

    Radiotherapy (RT) is an established treatment for patients with primary and recurrent prostate cancer. Herein, the effects of definitive and salvage RT on the composition of lymphocyte subpopulations were investigated in patients with prostate cancer to study potential immune effects. A total of 33 prostate cancer patients were treated with definitive (n = 10) or salvage RT (n = 23) after biochemical relapse. The absolute number of lymphocytes and the distribution of lymphocyte subpopulations were analyzed by multiparameter flow cytometry before RT, at the end of RT, and in the follow-up period. Absolute lymphocyte counts decreased significantly after RT in both patient groups and a significant drop was observed in the percentage of B cells directly after RT from 10.1 ± 1.3 to 6.0 ± 0.7% in patients with definitive RT and from 9.2 ± 0.8 to 5.8 ± 0.7% in patients with salvage RT. In contrast, the percentages of T and natural killer (NK) cells remained unaltered directly after RT in both patient groups. However, 1 year after RT, the percentage of CD3 + T cells was significantly lower in patients with definitive and salvage RT. The percentage of regulatory T cells was slightly upregulated in primary prostate cancer patients after definitive RT, but not after salvage RT. Definitive and salvage RT exert similar effects on the composition of lymphocyte subpopulations in prostate cancer patients. Total lymphocyte counts are lower in both patient groups compared to healthy controls and further decreased after RT. B cells are more sensitive to definitive and salvage RT than T and NK cells. (orig.) [de

  3. Targeted therapies in the treatment of urothelial cancers.

    Science.gov (United States)

    Aragon-Ching, Jeanny B; Trump, Donald L

    2017-07-01

    Progress has been slow in systemic management of locally advanced and metastatic bladder cancer over the past 20 years. However, the recent approval of immunotherapy with atezolizumab and nivolumab for second-line salvage therapy may usher in an era of more rapid improvement. Systemic treatment is suboptimal and is an area of substantial unmet medical need. The recent findings from The Cancer Genome Atlas project revealed promising pathways that may be amenable to targeted therapies. Promising results with treatment using vascular endothelial growth factor inhibitors such as ramucirumab, sunitinib or bevacizumab, and human epidermal growth factor receptor 2 targeted therapies, epidermal growth factor receptor inhibitors, and fibroblast growth factor receptor inhibitors, are undergoing clinical trials and are discussed later. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Salvage Islet Auto Transplantation After Relaparatomy.

    Science.gov (United States)

    Balzano, Gianpaolo; Nano, Rita; Maffi, Paola; Mercalli, Alessia; Melzi, Raffaelli; Aleotti, Francesca; Gavazzi, Francesca; Berra, Cesare; De Cobelli, Francesco; Venturini, Massimo; Magistretti, Paola; Scavini, Marina; Capretti, Giovanni; Del Maschio, Alessandro; Secchi, Antonio; Zerbi, Alessandro; Falconi, Massimo; Piemonti, Lorenzo

    2017-10-01

    To assess feasibility, safety, and metabolic outcome of islet auto transplantation (IAT) in patients undergoing completion pancreatectomy because of sepsis or bleeding after pancreatic surgery. From November 2008 to October 2016, approximately 22 patients were candidates to salvage IAT during emergency relaparotomy because of postpancreatectomy sepsis (n = 11) or bleeding (n = 11). Feasibility, efficacy, and safety of salvage IAT were compared with those documented in a cohort of 36 patients who were candidate to simultaneous IAT during nonemergency preemptive completion pancreatectomy through the pancreaticoduodenectomy. The percentage of candidates that received the infusion of islets was significantly lower in salvage IAT than simultaneous IAT (59.1% vs 88.9%, P = 0.008), mainly because of a higher rate of inadequate islet preparations. Even if microbial contamination of islet preparation was significantly higher in candidates to salvage IAT than in those to simultaneous IAT (78.9% vs 20%, P < 0.001), there was no evidence of a higher rate of complications related to the procedure. Median follow-up was 5.45 ± 0.52 years. Four (36%) of 11 patients reached insulin independence, 6 patients (56%) had partial graft function, and 1 patient (9%) had primary graft nonfunction. At the last follow-up visit, median fasting C-peptide was 0.43 (0.19-0.93) ng/mL; median insulin requirement was 0.38 (0.04-0.5) U/kg per day, and median HbA1c was 6.6% (5.9%-8.1%). Overall mortality, in-hospital mortality, metabolic outcome, graft survival, and insulin-free survival after salvage IAT were not different from those documented after simultaneous IAT. Our data demonstrate the feasibility, efficacy, and safety of salvage IAT after relaparotomy.

  5. Effects of definitive and salvage radiotherapy on the distribution of lymphocyte subpopulations in prostate cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Sage, Eva K.; Gehrmann, Mathias; Sedelmayr, Michael [Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); Schmid, Thomas E.; Combs, Stephanie E.; Multhoff, Gabriele [Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); HelmholtzZentrum Muenchen, Department of Radiation Sciences (DRS), Institute of Innovate Radiotherapy (iRT), Munich (Germany); Deutsches Konsortium fuer Translationale Krebsforschung (DKTK), Partner Site Munich, Munich (Germany); Geinitz, Hans [Johannes Kepler University, Department of Radiation Oncology, Ordensklinikum Linz, Krankenhaus der Barmherzigen Schwestern and Medical Faculty, Linz (Austria); Duma, Marciana N. [Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); HelmholtzZentrum Muenchen, Department of Radiation Sciences (DRS), Institute of Innovate Radiotherapy (iRT), Munich (Germany)

    2017-08-15

    Radiotherapy (RT) is an established treatment for patients with primary and recurrent prostate cancer. Herein, the effects of definitive and salvage RT on the composition of lymphocyte subpopulations were investigated in patients with prostate cancer to study potential immune effects. A total of 33 prostate cancer patients were treated with definitive (n = 10) or salvage RT (n = 23) after biochemical relapse. The absolute number of lymphocytes and the distribution of lymphocyte subpopulations were analyzed by multiparameter flow cytometry before RT, at the end of RT, and in the follow-up period. Absolute lymphocyte counts decreased significantly after RT in both patient groups and a significant drop was observed in the percentage of B cells directly after RT from 10.1 ± 1.3 to 6.0 ± 0.7% in patients with definitive RT and from 9.2 ± 0.8 to 5.8 ± 0.7% in patients with salvage RT. In contrast, the percentages of T and natural killer (NK) cells remained unaltered directly after RT in both patient groups. However, 1 year after RT, the percentage of CD3{sup +} T cells was significantly lower in patients with definitive and salvage RT. The percentage of regulatory T cells was slightly upregulated in primary prostate cancer patients after definitive RT, but not after salvage RT. Definitive and salvage RT exert similar effects on the composition of lymphocyte subpopulations in prostate cancer patients. Total lymphocyte counts are lower in both patient groups compared to healthy controls and further decreased after RT. B cells are more sensitive to definitive and salvage RT than T and NK cells. (orig.) [German] Die Strahlentherapie (RT) ist eine bewaehrte Behandlung beim primaeren und rezidivierten Prostatakarzinoms. In dieser Studie wurde der Einfluss einer definitiven und Salvage RT auf die Zusammensetzung der Lymphozytensubpopulationen verglichen, um potenzielle Immuneffekte einer RT zu analysieren. In die Studie wurden 33 Prostatakarzinompatienten eingeschlossen

  6. Busulfan is effective second-line therapy for older patients with Philadelphia-negative myeloproliferative neoplasms intolerant of or unresponsive to hydroxyurea.

    Science.gov (United States)

    Douglas, Genevieve; Harrison, Claire; Forsyth, Cecily; Bennett, Michael; Stevenson, William; Hounsell, John; Ratnasingam, Sumita; Ritchie, David; Ross, David M; Grigg, Andrew

    2017-01-01

    Hydroxyurea (Hu) is widely used as first-line cytoreductive therapy for patients with high-risk Philadelphia-negative myeloproliferative neoplasms (Ph-neg MPN), but a small proportion of patients have refractory disease or experience adverse effects. Studies have demonstrated busulfan (Bu) to be an active first-line agent, but data on its role as second-line or later therapy are minimal. To evaluate its efficacy and safety in this context, we undertook a multicenter audit of Ph-neg MPN patients who had received Bu as therapy for Hu intolerance or failure. Of 51 patients identified, 38 (75%) achieved either complete or partial hematological response following at least one Bu cycle. Bu was generally well tolerated, with only 21/135 (15%) cycles complicated by adverse effects, predominantly cytopenia; only 6% of cycles were ceased due to treatment complications. Bu is an effective and well-tolerated agent in patients with Ph-neg MPN in the setting of Hu intolerance or unresponsiveness.

  7. SGLT2 inhibitors or GLP-1 receptor agonists as second-line therapy in type 2 diabetes: patient selection and perspectives

    Directory of Open Access Journals (Sweden)

    Gurgle HE

    2016-06-01

    Full Text Available Holly E Gurgle, Karen White, Carrie McAdam-Marx Department of Pharmacotherapy, University of Utah College of Pharmacy, Salt Lake City, UT, USA Abstract: Controversy exists regarding the selection of second-line therapy for patients with type 2 diabetes mellitus (T2DM who are unable to achieve glycemic control with metformin therapy alone. Newer pharmacologic treatments for T2DM include glucagon-like peptide-1 receptor agonists and sodium–glucose cotransporter 2 inhibitors. Both the classes of medication are efficacious, exhibit positive effects on weight, and are associated with minimal risk of hypoglycemia. The purpose of this review is to compare the clinical trial and real-world effectiveness data of glucagon-like peptide-1 receptor agonists versus sodium–glucose cotransporter 2 inhibitors related to A1c reduction, weight loss, cost-effectiveness, cardiovascular outcomes, and safety in patients with T2DM. This review summarizes comparative evidence for providers who are determining which of the two classes may be the most appropriate for a specific patient. Keywords: type 2 diabetes mellitus, GLP-1 receptor agonist, SGLT2 inhibitor, A1c, weight loss, adverse effect

  8. HIV drug resistance testing among patients failing second line antiretroviral therapy. Comparison of in-house and commercial sequencing.

    Science.gov (United States)

    Chimukangara, Benjamin; Varyani, Bhavini; Shamu, Tinei; Mutsvangwa, Junior; Manasa, Justen; White, Elizabeth; Chimbetete, Cleophas; Luethy, Ruedi; Katzenstein, David

    2017-05-01

    HIV genotyping is often unavailable in low and middle-income countries due to infrastructure requirements and cost. We compared genotype resistance testing in patients with virologic failure, by amplification of HIV pol gene, followed by "in-house" sequencing and commercial sequencing. Remnant plasma samples from adults and children failing second-line ART were amplified and sequenced using in-house and commercial di-deoxysequencing, and analyzed in Harare, Zimbabwe and at Stanford, U.S.A, respectively. HIV drug resistance mutations were determined using the Stanford HIV drug resistance database. Twenty-six of 28 samples were amplified and 25 were successfully genotyped. Comparison of average percent nucleotide and amino acid identities between 23 pairs sequenced in both laboratories were 99.51 (±0.56) and 99.11 (±0.95), respectively. All pairs clustered together in phylogenetic analysis. Sequencing analysis identified 6/23 pairs with mutation discordances resulting in differences in phenotype, but these did not impact future regimens. The results demonstrate our ability to produce good quality drug resistance data in-house. Despite discordant mutations in some sequence pairs, the phenotypic predictions were not clinically significant. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Sensitivity Pattern of Second Line Anti-Tuberculosis Drugs against Clinical Isolates of Multidrug Resistant Mycobacterium Tuberculosis

    International Nuclear Information System (INIS)

    Ghafoor, T.; Ikram, A.; Abbasi, S. A.; Zaman, G.; Ayyub, M.; Palomino, J. C.; Vandamme, P.; Martin, A.

    2015-01-01

    Objective:To determine the current sensitivity pattern of second line anti-tuberculosis drugs against clinical isolates of Multidrug Resistant Mycobacterium tuberculosis (MDR-TB). Study Design: A cross-sectional study. Place and Duration of Study: Department of Microbiology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from November 2011 to April 2013. Methodology: Samples received during the study period were processed on BACTEC MGIT 960 system for Mycobacterium tuberculosis (MTB) culture followed by first line drugs susceptibility testing of culture proven MTB isolates. On the basis of resistance to rifampicin and isoniazid, 100 clinical isolates of MDR-TB were further subjected to susceptibility testing against amikacin (AMK), capreomycin (CAP), ofloxacin (OFL) and ethionamide (ETH) as per standard BACTEC MGIT 960 instructions. Results: Out of 100 MDR-TB isolates, 62% were from male patients and 38% from female patients. 97% were sensitive to AMK, 53% to OFL, 87% to CAP; and 87% were sensitive to ETH. Conclusion: The majority of the MDR-TB isolates showed excellent sensitivity against AMK, CAP and ETH. However, sensitivity of MDR-TB isolates against fluoroquinolones like OFL was not encouraging. (author)

  10. Adjuvant and Salvage Radiotherapy After Prostatectomy for Prostate Cancer: A Literature Review

    International Nuclear Information System (INIS)

    Pasquier, David; Ballereau, Charles

    2008-01-01

    Purpose: Given that postprostatectomy recurrence of prostate cancer occurs in 10-40% of patients, the best use of immediate postoperative radiotherapy (RT) in high-risk patients and salvage RT for biochemical recurrence remains a topic of debate. We assessed the levels of evidence (in terms of efficacy, prognostic factors, and toxicity) for the following treatment strategies: immediate postoperative RT alone, salvage RT alone, and the addition of androgen deprivation therapy to the two RT strategies. Methods and Materials: A systematic literature search for controlled randomized trials, noncontrolled trials, and retrospective studies between 1990 and 2008 was performed on PubMed, CancerLit, and MEDLINE. Only relevant articles that had appeared in peer-reviewed journals were selected. We report on the levels of evidence (according to the National Cancer Institute guidelines) supporting the various treatment strategies. Results: Immediate postoperative RT improves biochemical and clinical progression-free survival (Level of evidence, 1.ii) but has no significant effect on metastasis-free survival or overall survival. A pathologic review is of particular importance for correctly analyzing the treatment strategies. Low-grade morbidity has been significantly greater in the postoperative groups, but no severe toxicity has been observed. The influence of immediate postoperative RT on postprostatectomy continence appears to be slight; therefore, immediate postoperative RT should be considered in patients with major risk factors for local relapse (Level of evidence, 1.ii). On the basis of extensive retrospective data, salvage RT is effective in biochemical relapse after prostatectomy; some patients with few adverse prognostic factors might also benefit from salvage RT (Level of evidence, 3.ii). The addition of androgen deprivation therapy to immediate postoperative or salvage RT has only been supported by weak, retrospective data (Level of evidence, 3.ii). Conclusion

  11. The methionine salvage pathway in Bacillus subtilis

    Directory of Open Access Journals (Sweden)

    Danchin Antoine

    2002-04-01

    Full Text Available Abstract Background Polyamine synthesis produces methylthioadenosine, which has to be disposed of. The cell recycles it into methionine through methylthioribose (MTR. Very little was known about MTR recycling for methionine salvage in Bacillus subtilis. Results Using in silico genome analysis and transposon mutagenesis in B. subtilis we have experimentally uncovered the major steps of the dioxygen-dependent methionine salvage pathway, which, although similar to that found in Klebsiella pneumoniae, recruited for its implementation some entirely different proteins. The promoters of the genes have been identified by primer extension, and gene expression was analyzed by Northern blotting and lacZ reporter gene expression. Among the most remarkable discoveries in this pathway is the role of an analog of ribulose diphosphate carboxylase (Rubisco, the plant enzyme used in the Calvin cycle which recovers carbon dioxide from the atmosphere as a major step in MTR recycling. Conclusions A complete methionine salvage pathway exists in B. subtilis. This pathway is chemically similar to that in K. pneumoniae, but recruited different proteins to this purpose. In particular, a paralogue or Rubisco, MtnW, is used at one of the steps in the pathway. A major observation is that in the absence of MtnW, MTR becomes extremely toxic to the cell, opening an unexpected target for new antimicrobial drugs. In addition to methionine salvage, this pathway protects B. subtilis against dioxygen produced by its natural biotope, the surface of leaves (phylloplane.

  12. 19 CFR 4.97 - Salvage vessels.

    Science.gov (United States)

    2010-04-01

    ... United States and Great Britain ‘concerning reciprocal rights for United States and Canada in the... meaning of this statute. (e) A Mexican vessel may engage in a salvage operation on a Mexican vessel in any territorial waters of the United States in which Mexican vessels are permitted to conduct such operations by...

  13. Limb Salvage After Failed Initial Operative Management of Bimalleolar Ankle Fractures in Diabetic Neuropathy.

    Science.gov (United States)

    Vaudreuil, Nicholas J; Fourman, Mitchell S; Wukich, Dane K

    2017-03-01

    Ankle fractures in patients with diabetes mellitus (DM) can be difficult to manage, especially in the presence of peripheral neuropathy. In patients who fail initial operative management, attempts at limb salvage can be challenging, and no clear treatment algorithm exists. This study examined outcomes of different procedures performed for limb salvage in this population. This study retrospectively reviewed 17 patients with DM complicated by peripheral neuropathy who sustained a bimalleolar ankle fracture and failed initial operative management. Patients were treated with revision open reduction internal fixation (ORIF) (3/17), closed reduction external fixation (CREF) (8/17), or primary ankle joint fusion (3/17 tibiotalocalcaneal fusion with hindfoot nail [TTCN] and 3/17 with tibiotalar arthrodesis using plates and screws [TTA]). Median follow-up was 20 months. The overall rate of limb salvage was 82.3% (14/17). All patients who went on to amputation presented with infection and were treated initially with CREF (3/3). All patients who achieved successful limb salvage ended up with a clinically fused ankle joint (14/14); 9 underwent a primary or delayed formal fusion and 5 had a clinically fused ankle joint at study conclusion after undergoing revision ORIF or CREF with adjunctive procedures. This small study suggests that in this complicated group of patients it is difficult to achieve limb salvage with an end result of a functional ankle joint. CREF can be a viable option in cases where underlying infection or poor bone quality is present. Treatment with revision ORIF frequently requires supplementary external fixator or tibiotalar Steinman pin placement for additional stability. All patients who underwent revision ORIF ended up with clinically fused ankle joints at the end of the study period. Primary fusion procedures (TTA, TTCN) were associated with a high rate of limb salvage and a decreased number of operations. Level III, retrospective case series.

  14. Is there a progression-free survival benefit of first-line crizotinib versus standard chemotherapy and second-line crizotinib in ALK-positive advanced lung adenocarcinoma? A retrospective study of Chinese patients.

    Science.gov (United States)

    Cui, Shaohua; Zhao, Yizhuo; Dong, Lili; Gu, Aiqin; Xiong, Liwen; Qian, Jialin; Zhang, Wei; Niu, Yanjie; Pan, Feng; Jiang, Liyan

    2016-06-01

    Although crizotinib has demonstrated promising efficacy and acceptable toxicity in patients with advanced non-small cell lung cancer (NSCLC), the available evidence in Chinese populations is currently limited. This study compared the progression-free survival (PFS) of Chinese patients with anaplastic lymphoma kinase (ALK)-positive, advanced lung adenocarcinoma who received first-line crizotinib therapy with that of patients who received first-line standard chemotherapy, and also the PFS benefit of first-line versus second-line crizotinib treatment. Data on 80 patients with ALK-positive, advanced lung adenocarcinoma who received crizotinib or standard chemotherapy as first-line treatments between June 2013 and December 2014 were retrospectively collected; 26 of the patients received crizotinib as second-line therapy after progressive disease (PD) occurred on first-line chemotherapy. Tumor responses were assessed using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The median PFS was 13.3 months (95% CI: 6.5-20.0 months) in patients who received first-line crizotinib as compared with 5.4 months (95% CI: 4.4-6.5 months) in patients who received first-line standard chemotherapy (adjusted hazard ratio for progression or death with crizotinib, 0.20; 95% CI: 0.11-0.36; P benefit of first-line crizotinib versus first-line standard chemotherapy in Chinese patients with ALK-positive lung adenocarcinoma. Additionally, crizotinib showed promising efficacy in patients who received it as second-line therapy after PD had occurred on first-line chemotherapy. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  15. Cost-effectiveness of saxagliptin vs glimepiride as a second-line therapy added to metformin in Type 2 diabetes in China.

    Science.gov (United States)

    Gu, Shuyan; Deng, Jing; Shi, Lizheng; Mu, Yiming; Dong, Hengjin

    2015-01-01

    This study aims to estimate the long-term cost-effectiveness of saxagliptin + metformin (SAXA + MET) vs glimepiride + metformin (GLI + MET) in patients with Type 2 diabetes mellitus (T2DM) inadequately controlled with MET in China. The Cardiff Model was used to simulate disease progression and estimate the long-term effect of treatments on patients. Systematic literature reviews and hospital surveys were conducted to obtain patients profiles, clinical data, and costs. Health insurance costs (2014¥) were estimated over a 40-year period. One-way and probabilistic sensitivity analyses were performed. SAXA + MET had lower predicted incidences of cardiovascular and hypoglycemia events and a decreased total cost compared with GLI + MET (¥241,072,807 vs ¥285,455,177). There were increased numbers of quality-adjusted life-years (QALYs; 1.01/patient) and life-years (Lys; 0.03/patient) gained with SAXA + MET compared with GLI + MET, and the incremental cost of SAXA + MET vs GLI + MET (-¥44,382) resulted in -¥43,883/QALY and -¥1,710,926/LY gained with SAXA + MET. Sensitivity analyses confirmed that the results were robust. In patients with T2DM in China, SAXA + MET was more cost-effective and was well tolerated with fewer adverse effects (AEs) compared with GLI + MET. As a second-line therapy for T2DM, SAXA may address some of the unmet medical needs attributable to AEs in the treatment of T2DM.

  16. The efficacy and safety of Oxaliplatin-Vinorelbine as a second-line chemotherapy combination in patients with platinum-resistant pretreated epithelial ovarian cancer: A retrospective study

    Directory of Open Access Journals (Sweden)

    Fidia Mumtahana

    2014-12-01

    Full Text Available Purpose: The main purpose of this study was to analyze the effects and tolerability of Oxaliplatin-Vinorelbine combination on Platinum-resistant epithelial ovarian carcinoma (EOC patients.Methods: A single centered retrospective study comprising of 34 patients was conducted, and all 34 patients were treated with Vinorelbine 30 mg/m2 on day 1 and 8 along with Oxaliplatin 100 mg/m2 on day 1 of 3 weeks treatment cycle following progressive platinum-resistant EOC. Results: The combination showed an overall response rate (ORR of 18% (95% CI, 4.4 - 31.6 where 2 (6% patients had complete response and 4 (12% patients had partial response. Stable disease was observed in 9 (26% patients and progressive disease in 19 (56% patients. Median diseases free survival, median relapse free survival and median time to progression was 17.05 months, 4.4 months, and 1.25 months, respectively. Hematological toxicities were mild; only 1 (2.9% patient had G3 anemia and major non-hematological toxicities include nausea-vomiting, diarrhea, constipation, hepatotoxicity, fatigueness and alopecia, which are mainly limited to G1-G2 and reversible. Conclusion: The effect of this combination is moderate as a second line treatment of platinum resistant EOC; however, in comparison with other regimens of Vinorelbine and Oxaliplatin, the activity is substandard but the toxicity profile is well tolerable. Further multicenter evaluation is needed for the better understanding of the therapeutic efficacy of the combination.

  17. Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    van Imhoff, Gustaaf W; McMillan, Andrew; Matasar, Matthew J

    2017-01-01

    Purpose We compared the efficacy of ofatumumab (O) versus rituximab (R) in combination with cisplatin, cytarabine, and dexamethasone (DHAP) salvage treatment, followed by autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Pat...

  18. A phase I/II study of biweekly capecitabine and irinotecan plus bevacizumab as second-line chemotherapy in patients with metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Suenaga M

    2015-03-01

    Full Text Available Mitsukuni Suenaga,1 Nobuyuki Mizunuma,1 Satoshi Matsusaka,1 Eiji Shinozaki,1 Masato Ozaka,1 Mariko Ogura,1 Keisho Chin,1 Toshiharu Yamaguchi2 1Department of Gastroenterology, 2Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake, Koto-ku, Tokyo, Japan Background: Triweekly capecitabine plus irinotecan (XELIRI is not completely regarded as a valid substitute for fluorouracil, leucovorin, and irinotecan (FOLFIRI in metastatic colorectal cancer (mCRC because of the potential for greater toxicity. We conducted a phase I/II study to assess the efficacy and safety of biweekly XELIRI plus bevacizumab (BV as second-line chemotherapy for mCRC.Methods: Patients with mCRC who had received prior chemotherapy including oxaliplatin and BV and had a UGT1A1 genotype of wild-type or heterozygous for UGT1A1*6 or *28 were eligible for this study. Treatment comprised capecitabine 1,000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous irinotecan on day 1, and BV 5 mg/kg on day 1 every 2 weeks. The phase I study consisted of two steps (irinotecan 150 and 180 mg/m2, and dose-limiting toxicity was assessed during the first treatment cycle. The primary endpoint of the phase II study was progression-free survival (PFS.  Results: The recommended dose of irinotecan was determined to be 180 mg/m2 in the phase I study. Between November 2010 and August 2013, 44 patients were enrolled in phase II. The patients’ characteristics were as follows (N=44: median age, 60 years (range 32–80; male/female, 21/23; and UGT1A1 wild-type/heterozygous, 29/15. The median PFS was 6.8 months (95% confidence interval, 5.3–8.2 months, and the primary endpoint was met. Median overall survival was 18.3 months. The response rate was 22.7%. There was no significant difference in PFS or overall survival according to UGT1A1 status. Grade 3 or higher adverse events were mainly neutropenia in six

  19. Second salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer

    Directory of Open Access Journals (Sweden)

    Metha Maenhout

    2017-04-01

    Full Text Available Purpose : Salvage treatments for localized radiorecurrent prostate cancer can be performed safely when a focal and image guided approach is used. Due to the low toxicity, the opportunity exists to investigate a second salvage treatment when a second locally recurrent prostate cancer occurs. Here, we describe a second salvage treatment procedure of 4 patients. Material and methods : Four patients with a pathologically proven second local recurrence were treated in an outpatient magnetic resonance imaging (MRI-guided setting with a single fraction of 19 Gy focal high-dose-rate brachytherapy (HDR-BT. Delineation was performed using choline-PET-CT or a 68Ga-PSMA PET in combination with multiparametric 3 Tesla MRI in all four patients. Toxicity was measured using common toxicity criteria for adverse events (CTCAE version 4.0. Results : With a median follow-up of 12 months (range, 6-15, there were 2 patients with biochemical recurrence as defined by the Phoenix-definition. There were no patients with grade 3 or more toxicity. In all second salvage HDR-BT treatments, the constraints for rectum, bladder, and urethra were met. Median treatment volume (GTV was 4.8 cc (range, 1.9-6.6 cc. A median of 8 catheters (range, 6-9 were used, and the median dose to the treatment volume (GTV was a D95: 19.3 Gy (SD 15.5-19.4 Gy. Conclusions : Second focal salvage MRI-guided HDR-BT for a select group of patients with a second locally recurrent prostate cancer is feasible. There was no grade 3 or more acute toxicity for these four patients.

  20. Adjuvant and salvage irradiation following radical prostatectomy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Morris, M M; Dallow, K C; Zietman, A L; Althausen, A F; Heney, N M; McGovern, F J; Shipley, W U

    1995-07-01

    Purpose: To assess the ability of adjuvant irradiation to prevent PSA failure in cases of pT3N0 disease, and of salvage irradiation to durably suppress a rising PSA following radical prostatectomy. Methods and Materials: 62 patients treated by post-operative radiation therapy (60-64Gy in 1.8Gy fractions to the tumor bed) between 1988 and 1993 were evaluated. All had complete pre- and post-radiation PSA data. Median follow up was 3.2 years from time of surgery and 2.2 years from irradiation. 20 patients had Gleason grade 3 disease (moderately differentiated) and 41 Gleason 4-5 (poorly differentiated). 46 had positive inked surgical margins, 18 involved seminal vesicles and 5 had palpable recurrent disease. None had known nodal or metastatic disease. 32 patients underwent adjuvant treatment (undetectable PSA at time of irradiation) and 30 salvage (detectable PSA at time of irradiation). Kaplan-Meier life table analysis was employed. The endpoint studied was freedom from biochemical failure. This was defined as a rise in the PSA of greater than 10% (intra laboratory error <8%) or a previously undetectable PSA becoming detectable. Results: The overall actuarial freedom from biochemical failure at 4 years from radiotherapy was 59%. A significant difference was seen between those receiving adjuvant and those receiving salvage irradiation (71% vs 51%, p=0.03). Amongst those in the salvage group neither the PSA prior to surgery, the PSA at the time of irradiation, the seminal vesicle status, nor the Gleason score (3 vs 4-5) correlated significantly with outcome. The time interval between surgery and irradiation was, however, significant. Those being treated within 6 months fared better than those treated later (60% vs 36%, p=0.04). Further, those treated early were more likely to achieve an undetectable nadir PSA level (94% vs 71%). Conclusion: The addition of adjuvant irradiation appears to improve the 4 year biochemical disease-free survival of patients with poor

  1. Salvage Therapy of Multiple Myeloma: The New Generation Drugs

    Directory of Open Access Journals (Sweden)

    Alessandra Romano

    2014-01-01

    Full Text Available During the past decade, overall results of treatment of multiple myeloma (MM have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs. However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways.

  2. Salvage Therapy of Multiple Myeloma: The New Generation Drugs

    Science.gov (United States)

    Romano, Alessandra; Conticello, Concetta; Di Raimondo, Cosimo; Schinocca, Elena; La Fauci, Alessia; Parrinello, Nunziatina Laura; Chiarenza, Annalisa

    2014-01-01

    During the past decade, overall results of treatment of multiple myeloma (MM) have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs). However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways. PMID:24967371

  3. Salvage Stereotactic Body Radiotherapy (SBRT) Following In-Field Failure of Initial SBRT for Spinal Metastases.

    Science.gov (United States)

    Thibault, Isabelle; Campbell, Mikki; Tseng, Chia-Lin; Atenafu, Eshetu G; Letourneau, Daniel; Yu, Eugene; Cho, B C John; Lee, Young K; Fehlings, Michael G; Sahgal, Arjun

    2015-10-01

    We report our experience in salvaging spinal metastases initially irradiated with stereotactic body radiation therapy (SBRT), who subsequently progressed with imaging-confirmed local tumor progression, and were re-irradiated with a salvage second SBRT course to the same level. From a prospective database, 56 metastatic spinal segments in 40 patients were identified as having been irradiated with a salvage second SBRT course to the same level. In addition, 24 of 56 (42.9%) segments had initially been irradiated with conventional external beam radiation therapy before the first course of SBRT. Local control (LC) was defined as no progression on magnetic resonance imaging at the treated segment, and calculated according to the competing risk model. Overall survival (OS) was evaluated for each patient treated by use of the Kaplan-Meier method. The median salvage second SBRT total dose and number of fractions was 30 Gy in 4 fractions (range, 20-35 Gy in 2-5 fractions), and for the first course of SBRT was 24 Gy in 2 fractions (range, 20-35 Gy in 1-5 fractions). The median follow-up time after salvage second SBRT was 6.8 months (range, 0.9-39 months), the median OS was 10.0 months, and the 1-year OS rate was 48%. A longer time interval between the first and second SBRT courses predicted for better OS (P=.02). The crude LC was 77% (43/56), the 1-year LC rate was 81%, and the median time to local failure was 3.0 months (range, 2.7-16.7 months). Of the 13 local failures, 85% (11/13) and 46% (6/13) showed progression within the epidural space and paraspinal soft tissues, respectively. Absence of baseline paraspinal disease predicted for better LC (Pinitial SBRT is a feasible and efficacious salvage treatment option. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Optimal timing of salvage radiotherapy for biochemical recurrence after radical prostatectomy: is ultra-early salvage radiotherapy beneficial?

    International Nuclear Information System (INIS)

    Taguchi, Satoru; Shiraishi, Kenshiro; Fukuhara, Hiroshi; Nakagawa, Keiichi; Morikawa, Teppei; Naito, Akihiro; Kakutani, Shigenori; Takeshima, Yuta; Miyazaki, Hideyo; Nakagawa, Tohru; Fujimura, Tetsuya; Kume, Haruki; Homma, Yukio

    2016-01-01

    The optimal timing of salvage radiotherapy for biochemical recurrence after radical prostatectomy is controversial. In particular, the prognostic significance of salvage radiotherapy delivered before a current definition of biochemical recurrence, i.e. ultra-early salvage radiotherapy, is unclear. We reviewed 76 patients with pT2-3N0M0 prostate cancer who underwent salvage radiotherapy for post-prostatectomy biochemical recurrence at the following three timings: ultra-early salvage radiotherapy (n = 20) delivered before meeting a current definition of biochemical recurrence (two consecutive prostate-specific antigen [PSA] values ≥0.2 ng/mL); early salvage radiotherapy (n = 40) delivered after meeting the definition but before PSA reached 0.5 ng/mL; and delayed salvage radiotherapy (n = 16) delivered after PSA reached 0.5 ng/mL. The primary endpoint was failure of salvage radiotherapy, defined as a PSA value ≥0.2 ng/mL. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively. During the follow-up period (median: 70 months), four of 20 (20 %), nine of 40 (23 %) and seven of 16 (44 %) patients failed biochemically in the ultra-early, early and delayed salvage radiotherapy groups, respectively. On univariate analyses, the outcome of delayed salvage radiotherapy was worse than the others, while there was no significant difference between ultra-early and early groups. Multivariate analysis demonstrated the presence of Gleason pattern 5, perineural invasion and delayed salvage radiotherapy as independent predictors of poorer survival. No survival benefit of ultra-early salvage radiotherapy was demonstrated, whereas delayed salvage radiotherapy was associated with worse outcome as reported in previous studies. Our results may support the current recommendations that salvage radiotherapy should be undertaken after two consecutive PSA values ≥0.2 ng/mL and before reaching 0.5 ng/mL

  5. Accuracy of post-radiotherapy biopsy before salvage radical prostatectomy.

    Science.gov (United States)

    Meeks, Joshua J; Walker, Marc; Bernstein, Melanie; Kent, Matthew; Eastham, James A

    2013-08-01

    To determine whether post-radiotherapy (RT) biopsy (PRB) adequately predicts the presence, location, and histological features of cancer in the salvage radical prostatectomy (SRP) specimen. Before salvage treatment, a PRB is required to confirm the presence of locally recurrent or persistent cancer and to determine the extent and location of the prostate cancer. SRP was performed between 1998 and 2011 on 198 patients. All patients underwent a PRB. PRB and SRP specimens were evaluated by a genitourinary pathologist. Patients had external-beam RT alone (EBRT; 71%) or brachytherapy with or without EBRT (29%). Of the men undergoing SRP, 26 (14%) were clinical stage ≥T3, with 13% of PRBs with Gleason score ≥8. Cancer was unilateral in 120 (61%) biopsies, with contralateral or bilateral prostate cancer at SRP in 49%. In the SRP specimen, cancer was multifocal in 57%. Cancer was upgraded at SRP in 58% of men, with 20% having an increase in primary Gleason grade. The accuracy of PRB varied by region from 62% to 76%, with undetected cancers ranging from 12% to 26% and most likely to occur at the mid-gland. Radiation-recurrent prostate cancers were often multifocal, and biopsy missed up to 20% of tumours. More than half of the cancers were upgraded at SRP, and many that were unilateral on PRB were bilateral at SRP. © 2013 BJU International.

  6. Mechanisms of antibiotic resistance in Mycobacterium tuberculosis, validation of methods BACTECTM MGIT 960 and AnyplexM TII MTB / MDR / XDR Detection for detection of antibiotic resistance to first and second line in Mycobacterium tuberculosis strains

    International Nuclear Information System (INIS)

    Centeno Urena, Yadel

    2014-01-01

    A literature review is developed of drug-resistant TB in the world and in Costa Rica. The mechanisms of resistance to antibiotics are studied of the bacterium that causes tuberculosis; drug resistance to first-line and second-line, treatment regimen according to the World Health Organization and edge detection methods available in the market. The agreement between the results is studied by the phenotypic detection system of resistance of M. tuberculosis BACTEC MGIT960 and PCR, in real-time of commercial kit Anyplex II MTB/MDR/XDR, for genotypic identification of M. tuberculosis and related mutations to resistance with the referring results to thirty strains provided by the Pan American Health Organization, allowing a significant shortening in the time of obtaining reliable results. The results obtained have allowed to suggest a possible implementation at the Centro Nacional de Referencia en Micobacteriologia (CNRM), to perform antibiotic susceptibility testing and genotypic testing of multidrug cases respectively. The study results have allowed the implementation of the technology of genotypic detection of M. tuberculosis in the CNRM, obtaining for the first time in Costa Rica, information about genes of M. tuberculosis related to the generation of resistance to the major drugs of Primary treatment scheme as well as testing of resistance to second-line drug for resistant strains referred to the Centro Nacional de Referencia en Micobacteriologia in 2013. (author) [es

  7. Discontinuing VEGF-targeted Therapy for Progression Versus Toxicity Affects Outcomes of Second-line Therapies in Metastatic Renal Cell Carcinoma

    DEFF Research Database (Denmark)

    De Velasco, Guillermo; Xie, Wanling; Donskov, Frede

    2017-01-01

    BACKGROUND: A significant subgroup of metastatic renal cell carcinoma (mRCC) patients discontinue vascular endothelial growth factor-targeted therapies (VEGF-TT) because of toxicity. Whether clinical outcomes differ in patients who receive second-line (2L) targeted therapy on the basis of reason ...

  8. Evaluation of the Sensititre MycoTB plate for susceptibility testing of the Mycobacterium tuberculosis complex against first- and second-line agents.

    Science.gov (United States)

    Hall, Leslie; Jude, Kurt P; Clark, Shirley L; Dionne, Kim; Merson, Ryan; Boyer, Ana; Parrish, Nicole M; Wengenack, Nancy L

    2012-11-01

    The Sensititre MycoTB plate (TREK Diagnostic Systems, Cleveland, OH) uses a microtiter plate MIC format for susceptibility testing of Mycobacterium tuberculosis complex isolates against first- and second-line antituberculosis agents. Categorical agreement versus the agar proportion method for 122 M. tuberculosis complex isolates was 94% to 100%.

  9. Development of Composite Case Salvage Procedures

    Science.gov (United States)

    1982-04-01

    impacted by the high pressure water. Figure 25 shows damage to EPDM rubber from an MX case. Figure 26 shows the effect of the water on the V-45 ( NBR ... Rubber plus Polyester plus Degradation Elastomer Polyether Cleavage Recycling Reclamation Solvolysis Also: Salvage Rubber Reclamation Elastomers... rubber . 2. Analysis of the material extracted from the insu- lation showed that plasticizer (phthalates) was removed by the solvents. 3. After

  10. Dabrafenib Treatment in a Patient with an Epithelioid Glioblastoma and BRAF V600E Mutation

    Directory of Open Access Journals (Sweden)

    Garry Ceccon

    2018-04-01

    Full Text Available Novel therapeutic targets in malignant glioma patients are urgently needed. Point mutations of the v-Raf murine sarcoma viral oncogene homolog B (BRAF gene occur predominantly in melanoma patients, but may also occur in gliomas. Thus, this is a target of great interest for this group of patients. In a nine-year-old male patient, an anaplastic astrocytoma in the left temporoparietal region was diagnosed histologically. After first- and second-line treatment, a malignant progression to a secondary glioblastoma was observed ten years after the initial diagnosis. Within the following seven years, all other conventional treatment options were exhausted. At this time point, recurrent tumor histology revealed an epithelioid glioblastoma, without a mutation in the isocitrate dehydrogenase gene (IDH wild-type. In order to identify a potential target for an experimental salvage therapy, mutational tumor analysis showed a BRAF V600E mutation. Consecutively, dabrafenib treatment was initiated. The patient remained clinically stable, and follow-up magnetic resonance images (MRI were consistent with “Stable Disease” according to the Response Assessment in Neuro-Oncology Working Group (RANO criteria for the following ten months until tumor progression was detected. The patient died 16 months after dabrafenib treatment initiation. Particularly in younger glioma patients as well as in patients with an epithelioid glioblastoma, screening for a V600E BRAF mutation is promising since, in these cases, targeted therapy with BRAF inhibitors seems to be a useful salvage treatment option.

  11. Salvage definitive chemo-radiotherapy for locally recurrent oesophageal carcinoma after primary surgery: retrospective review

    International Nuclear Information System (INIS)

    Baxi, S. H.; Burmeister, B.; Harvey, J. A.; Smithers, M.; Thomas, J.

    2008-01-01

    Full text: To determine the overall survival and gastrointestinal toxicity for patients treated with salvage definitive chemo-radiotherapy after primary surgery for locoregional relapse of oesophageal carcinoma. A retrospective review of 525 patients who had a resection for oesophageal or oesophagogastric carcinoma at Princess Alexandra Hospital identified 14 patients treated with salvage definitive radiotherapy or chemo-radiotherapy, following localized recurrence of their disease. We analysed the patient and treatment characteristics to determine the median overall survival as the primary end point. Gastrointestinal toxicity was examined to determine if increased toxicity occurred when the stomach was irradiated within the intrathoracic radiotherapy field. The median overall survival for patients treated with curative intent using salvage definitive chemo-radiotherapy was 16 months and the 2-year overall survival is 21%. One patient is in clinical remission more than 5 years after therapy. Age <60 years old and nodal recurrence were favourable prognostic factors. Treatment compliance was 93% with only one patient unable to complete the intended schedule. Fourteen per cent of patients experienced grade 3 or 4 gastrointestinal toxicity. Salvage definitive chemo-radiotherapy should be considered for good performance status patients with oesophageal carcinoma who have a locoregional relapse after primary surgery. The schedule is tolerable with low toxicity and an acceptable median survival

  12. Post-fire salvage logging alters species composition and reduces cover, richness, and diversity in Mediterranean plant communities.

    Science.gov (United States)

    Leverkus, Alexandro B; Lorite, Juan; Navarro, Francisco B; Sánchez-Cañete, Enrique P; Castro, Jorge

    2014-01-15

    An intense debate exists on the effects of post-fire salvage logging on plant community regeneration, but scant data are available derived from experimental studies. We analyzed the effects of salvage logging on plant community regeneration in terms of species richness, diversity, cover, and composition by experimentally managing a burnt forest on a Mediterranean mountain (Sierra Nevada, S Spain). In each of three plots located at different elevations, three replicates of three treatments were implemented seven months after the fire, differing in the degree of intervention: "Non-Intervention" (all trees left standing), "Partial Cut plus Lopping" (felling 90% of the trees, cutting the main branches, and leaving all the biomass in situ), and "Salvage Logging" (felling and piling the logs, and masticating the woody debris). Plant composition in each treatment was monitored two years after the fire in linear point transects. Post-fire salvage logging was associated with reduced species richness, Shannon diversity, and total plant cover. Moreover, salvaged sites hosted different species assemblages and 25% lower cover of seeder species (but equal cover of resprouters) compared to the other treatments. Cover of trees and shrubs was also lowest in Salvage Logging, which could suggest a potential slow-down of forest regeneration. Most of these results were consistent among the three plots despite plots hosting different plant communities. Concluding, our study suggests that salvage logging may reduce species richness and diversity, as well as the recruitment of woody species, which could delay the natural regeneration of the ecosystem. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Hemipelvectomy- only a salvage therapy?

    Directory of Open Access Journals (Sweden)

    Christian Wedemeyer

    2011-03-01

    Full Text Available After the first hemipelvectomy in 1891 significant advances have been made in the fields of preoperative diagnosis, surgical technique and adjuvant treatment in patients with pelvic tumors. The challenging surgical removal of these rare malignant bone or soft tissue tumors accompanied by interdisciplinary therapy is mostly the only chance of cure, but bares the risk of intensive bleeding and infection. The reconstruction after hemipelvectomy is of importance for the later outcome and quality of life for the patient. Here, plastic surgery with microvascular free flaps or local rotational flaps improved the reconstruction and reduced infection rates. Average local recurrence rates of 14% demonstrate good surgical results, but 5 year survival rates of only 50% are described for some tumor entities, showing the importance of a multimodal collaboration. On a basis of a selective literature review the history, indications, treatment options and outcome of hemipelvectomies are presented.

  14. Salvage immunotherapy of malignant glioma.

    Science.gov (United States)

    Ingram, M; Jacques, S; Freshwater, D B; Techy, G B; Shelden, C H; Helsper, J T

    1987-12-01

    We present the preliminary results of a phase I trial of adoptive immunotherapy for recurrent or residual malignant glioma. The protocol is based on surgical debulking followed by implantation into the tumor bed of autologous lymphocytes that have been stimulated with phytohemagglutinin-P and then cultured in vitro in the presence of interleukin 2. Fifty-five patients with a mean Karnofsky rating of 64 were treated between February 1985 and March 1987. No significant toxicity was associated with the immunotherapy. Fifty patients had a positive initial response to therapy, nine patients had early recurrence (two to four months after treatment), and 22 patients died. We comment on major differences between the protocol described and other immunotherapy protocols.

  15. Survival outcomes following salvage surgery for oropharyngeal squamous cell carcinoma: systematic review.

    Science.gov (United States)

    Kao, S S; Ooi, E H

    2018-04-01

    Recurrent oropharyngeal squamous cell carcinoma causes great morbidity and mortality. This systematic review analyses survival outcomes following salvage surgery for recurrent oropharyngeal squamous cell carcinoma. A comprehensive search of various electronic databases was conducted. Studies included patients with recurrent or residual oropharyngeal squamous cell carcinoma treated with salvage surgery. Primary outcomes were survival rates following salvage surgery. Secondary outcomes included time to recurrence, staging at time of recurrence, post-operative complications, and factors associated with mortality and recurrence. Methodological appraisal and data extraction were conducted as per Joanna Briggs Institute methodology. Eighteen articles were included. The two- and five-year survival rates of the patients were 52 per cent and 30 per cent respectively. Improvements in treatment modalities for recurrent oropharyngeal squamous cell carcinoma were associated with improvements in two-year overall survival rates, with minimal change to five-year overall survival rates. Various factors were identified as being associated with long-term overall survival, thus assisting clinicians in patient counselling and selection for salvage surgery.

  16. Salvage cryotherapy for local recurrence after radiotherapy for prostate cancer.

    Science.gov (United States)

    Kvorning Ternov, Klara; Krag Jakobsen, Ane; Bratt, Ola; Ahlgren, Göran

    2015-04-01

    The aim of this study was to present the outcome of patients treated with salvage cryotherapy after radiotherapy for prostate cancer at one institution. Consecutive patients treated between 2007 and 2013 with transperineal cryotherapy for biopsy-verified local recurrence after radiotherapy were investigated. An external reviewer retrieved outcome data retrospectively from medical records. Complications were graded according to the Clavien classification. One patient with less than 1 year of follow-up was excluded from the analysis of side-effects. Thirty patients were included, 29 of whom had a follow-up of at least 1 year. The median follow-up was 2.7 years (range 1-6.5 years). Eleven of the 23 patients without hormonal treatment at the time of cryotherapy reached a prostate-specific antigen (PSA) nadir of less than 0.5 ng/ml. At the end of follow-up five of these 23 patients still had a PSA below 0.5 ng/ml and 10 were free from recurrence according to the Phoenix definition. Clinical recurrence (verified with imaging or biopsies) was detected in 13 patients, six of which were local. One patient died from prostate cancer. Eleven patients had urinary incontinence grade 1-2 and three had grade 3-4, seven had pelvic pain, three had severe but transitory tissue sloughing, three developed a urethral stricture or had prolonged urinary retention, and one developed a urinary fistula 4.5 years after cryotherapy. Salvage cryotherapy should be considered as an alternative to hormonal treatment and surgery for local recurrence after radiotherapy for prostate cancer. The results compare well to those reported from centres with longer experience.

  17. Randomized Phase II trial of paclitaxel plus valproic acid vs paclitaxel alone as second-line therapy for patients with advanced gastric cancer

    Directory of Open Access Journals (Sweden)

    Fushida S

    2015-04-01

    Full Text Available Sachio Fushida,1 Masahide Kaji,2 Katsunobu Oyama,1 Yasuo Hirono,3 Hideaki Nezuka,4 Toshiya Takeda,5 Tomoya Tsukada,1 Daisuke Fujimoto,3 Shigekazu Ohyama,6 Takashi Fujimura,7 Tetsuo Ohta1 On behalf of the Digestive Disease Support Organization (DDSO 1Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, 2Department of Surgery, Toyama Prefectural Central Hospital, Toyama, 3First Department of Surgery, Fukui University Hospital, Fukui, 4Department of Surgery, Yatsuo General Hospital, Toyama, 5Department of Surgery, Ishikawa Matto Central Hospital, Hakusan, 6Department of Surgery, Kanazawa Medical Center, Kanazawa, 7Toyama City Hospital, Toyama, Japan Abstract: The standard regimen of second-line chemotherapy for patients with unresectable gastric cancer has not been established. However, weekly paclitaxel (wPTX has become the preferable second-line chemotherapy in Japan. Histone deacetylase (HDAC inhibitors have been shown to have antiproliferative activity through cell-cycle arrest, differentiation, and apoptosis in gastric cancer cells. One HDAC inhibitor, valproic acid (VPA, also inhibits tumor growth by inducing apoptosis, and enhances the efficacy of paclitaxel in a mouse xenograft model of gastric cancer. wPTX plus VPA as a second-line chemotherapy is expected to improve survival in gastric cancer patients. A multicenter randomized Phase II study was conducted to compare the effects of wPTX plus VPA and wPTX alone. A total of 66 patients participated in this study. The primary end point of the study was overall survival, and secondary end points were progression-free survival, response rate, and assessment of peripheral neuropathy. Keywords: valproic acid, paclitaxel, second-line therapy, advanced gastric cancer 

  18. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer patients: prospective evaluation of activity, safety, and quality of life.

    Science.gov (United States)

    Palumbo, Raffaella; Sottotetti, Federico; Trifirò, Giuseppe; Piazza, Elena; Ferzi, Antonella; Gambaro, Anna; Spinapolice, Elena Giulia; Pozzi, Emma; Tagliaferri, Barbara; Teragni, Cristina; Bernardo, Antonio

    2015-01-01

    A prospective, multicenter trial was undertaken to assess the activity, safety, and quality of life of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer (MBC). Fifty-two women with HER2-negative MBC who were candidates for second-line chemotherapy for the metastatic disease were enrolled and treated at three centers in Northern Italy. All patients had previously received taxane-based chemotherapy in the adjuvant or first-line metastatic setting. Single-agent nab-paclitaxel was given at the dose of 260 mg/m(2) as a 30-minute intravenous infusion on day 1 each treatment cycle, which lasted 3 weeks, in the outpatient setting. No steroid or antihistamine premedication was provided. Treatment was stopped for documented disease progression, unacceptable toxicity, or patient refusal. All of the enrolled patients were evaluable for the study endpoints. The objective response rate was 48% (95% CI, 31.5%-61.3%) and included complete responses from 13.5%. Disease stabilization was obtained in 19 patients and lasted >6 months in 15 of them; the overall clinical benefit rate was 77%. The median time to response was 70 days (range 52-86 days). The median progression-free survival time was 8.9 months (95% CI, 8.0-11.6 months, range 5-21+ months). The median overall survival point has not yet been reached. Toxicities were expected and manageable with good patient compliance and preserved quality of life in patients given long-term treatment. Our results showed that single-agent nab-paclitaxel 260 mg/m(2) every 3 weeks is an effective and well tolerated regimen as second-line chemotherapy in HER2-negative, taxane-pretreated MBC patients, and that it produced interesting values of objective response rate and progression-free survival without the concern of significant toxicity. Specifically, the present study shows that such a regimen is a valid therapeutic option for that 'difficult to

  19. A population-based study of first and second-line drug-resistant tuberculosis in a high-burden area of the Mexico/United States border

    Directory of Open Access Journals (Sweden)

    Pola Becerril-Montes

    2013-04-01

    Full Text Available The resistance of 139 Mycobacterium tuberculosis (MTB isolates from the city of Monterrey, Northeast Mexico, to first and second-line anti-TB drugs was analysed. A total of 73 isolates were susceptible and 66 were resistant to anti-TB drugs. Monoresistance to streptomycin, isoniazid (INH and ethambutol was observed in 29 cases. Resistance to INH was found in 52 cases and in 29 cases INH resistance was combined with resistance to two or three drugs. A total of 24 isolates were multidrug-resistant (MDR resistant to at least INH and rifampicin and 11 MDR cases were resistant to five drugs. The proportion of MDR-TB among new TB cases in our target population was 0.72% (1/139 cases. The proportion of MDR-TB among previously treated cases was 25.18% (35/139 cases. The 13 polyresistant and 24 MDR isolates were assayed against the following seven second-line drugs: amikacin (AMK, kanamycin (KAN, capreomycin (CAP, clofazimine (CLF, ethionamide (ETH, ofloxacin (OFL and cycloserine (CLS. Resistance to CLF, OFL or CLS was not observed. Resistance was detected to ETH (10.80% and to AMK (2.70%, KAN (2.70% and CAP (2.70%. One isolate of MDR with primary resistance was also resistant to three second-line drugs. Monterrey has a high prevalence of MDR-TB among previously treated cases and extensively drug-resistant-MTB strains may soon appear.

  20. Is Angiosome-Targeted Angioplasty Effective for Limb Salvage and Wound Healing in Diabetic Foot? : A Meta-Analysis.

    Science.gov (United States)

    Chae, Kum Ju; Shin, Jin Yong

    2016-01-01

    Given that the efficacy of employing angiosome-targeted angioplasty in the treatment of diabetic foot remains controversial, this study was conducted to examine its efficacy. We performed a systematic literature review and meta-analysis using core databases, extracting the treatment modality of angiosome-targeted angioplasty as the predictor variable, and limb salvage, wound healing, and revision rate as the outcome variables. We used the Newcastle-Ottawa Scale to assess the study quality, along with the Cochrane Risk of Bias Tool. We evaluated publication bias using a funnel plot. The search strategy identified 518 publications. After screening these, we selected four articles for review. The meta-analysis revealed that overall limb salvage and wound healing rates were significantly higher (Odds ratio = 2.209, 3.290, p = 0.001, pdiabetic foot was more effective than nonangiosome-targeted angioplasty with respect to wound healing and limb salvage.

  1. Time of hepatocellular carcinoma recurrence after liver resection and alpha-fetoprotein are important prognostic factors for salvage liver transplantation.

    Science.gov (United States)

    Lee, Sanghoon; Hyuck David Kwon, Choon; Man Kim, Jong; Joh, Jae-Won; Woon Paik, Seung; Kim, Bong-Wan; Wang, Hee-Jung; Lee, Kwang-Woong; Suh, Kyung-Suk; Lee, Suk-Koo

    2014-09-01

    Salvage liver transplantation (LT) is considered a feasible option for the treatment of recurrent hepatocellular carcinoma (HCC). We performed this multicenter study to assess the risk factors associated with the recurrence of HCC and patient survival after salvage LT. Between January 2000 and December 2011, 101 patients who had previously undergone liver resection (LR) for HCC underwent LT at 3 transplant centers in Korea. Sixty-nine patients' data were retrospectively reviewed for the analysis. The recurrence of HCC was diagnosed at a median of 10.6 months after the initial LR, and patients underwent salvage LT. Recurrences were within the Milan criteria in 48 cases and were outside the Milan criteria in 21 cases. After salvage LT, 31 patients had HCC recurrence during a median follow-up period of 24.5 months. There were 24 deaths, and 20 were due to HCC recurrence. The 5-year overall survival rate was approximately 54.6%, and the 5-year recurrence-free survival rate was 49.3%. HCC recurrence within the 8 months after LR [hazard ratio (HR) = 3.124, P = 0.009], an alpha-fetoprotein level higher than 200 ng/mL (HR = 2.609, P = 0.02), and HCC outside the Milan criteria at salvage LT (HR = 2.219, P = 0.03) were independent risk factors for poor recurrence-free survival after salvage LT. In conclusion, the timing and extent of HCC recurrence after primary LR both play significant roles in the outcome of salvage LT. © 2014 American Association for the Study of Liver Diseases.

  2. Experimental test of postfire management in pine forests: impact of salvage logging versus partial cutting and nonintervention on bird-species assemblages.

    Science.gov (United States)

    Castro, Jorge; Moreno-Rueda, Gregorio; Hódar, José A

    2010-06-01

    There is an intense debate about the effects of postfire salvage logging versus nonintervention policies on regeneration of forest communities, but scant information from experimental studies is available. We manipulated a burned forest area on a Mediterranean mountain to experimentally analyze the effect of salvage logging on bird-species abundance, diversity, and assemblage composition. We used a randomized block design with three plots of approximately 25 ha each, established along an elevational gradient in a recently burned area in Sierra Nevada Natural and National Park (southeastern Spain). Three replicates of three treatments differing in postfire burned wood management were established per plot: salvage logging, nonintervention, and an intermediate degree of intervention (felling and lopping most of the trees but leaving all the biomass). Starting 1 year after the fire, we used point sampling to monitor bird abundance in each treatment for 2 consecutive years during the breeding and winter seasons (720 censuses total). Postfire burned-wood management altered species assemblages. Salvage logged areas had species typical of open- and early-successional habitats. Bird species that inhabit forests were still present in the unsalvaged treatments even though trees were burned, but were almost absent in salvage-logged areas. Indeed, the main dispersers of mid- and late-successional shrubs and trees, such as thrushes (Turdus spp.) and the European Jay (Garrulus glandarius) were almost restricted to unsalvaged treatments. Salvage logging might thus hamper the natural regeneration of the forest through its impact on assemblages of bird species. Moreover, salvage logging reduced species abundance by 50% and richness by 40%, approximately. The highest diversity at the landscape level (gamma diversity) resulted from a combination of all treatments. Salvage logging may be positive for bird conservation if combined in a mosaic with other, less-aggressive postfire

  3. Extended Salvage Pelvic Lymph Node Dissection in Patients with Recurrent Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Daniar K. Osmonov

    2014-01-01

    Full Text Available Background. Treatment of patients with a biochemical recurrence (BCR of prostate cancer (PCa is generally difficult and without valid treatment options. Since 2004 we have been developing therapeutic possibilities for these patients. Methods. We retrospectively analyzed a cohort of 41 patients with a BCR of PCa and a mean followup of 40.3±20.8 months. Group 1 (n=10: salvage radical prostatectomy (sRP with SePLND (salvage extended pelvic lymph nodes dissection (initial treatment: combined brachytherapy. Group 2 (n=22: SePLND (initial treatment: radical prostatectomy (RP. Group 3 (n=9: SePLND (initial treatment: RP and adjuvant radiation therapy (RT. We observed PSA, PSA-velocity, localization of LNs and LNs+, BCR-free period, and BR (biochemical response. Results. Group 1: 60% with BCR-freedom (mean 27.2 months. Group 2: 63.6% with BCR-freedom (mean 17.5 months. Group 3: 33.3% with BCR-freedom (mean 17.6 months. In total, BCR-freedom was observed in 23 of 41 patients (56.1% after salvage surgery. 75.6% of all patients showed a BR. 765 LNs were removed and 14.8% of these were LN+. Conclusions. The BCR-free period and BR are comparable in all three groups. Sensibility to ADT can be reestablished and prolonged as a result of SePLND. Multicenter studies are needed for a reliable output.

  4. Adjuvant Versus Salvage Radiotherapy for Patients With Adverse Pathological Findings Following Radical Prostatectomy: A Decision Analysis

    Directory of Open Access Journals (Sweden)

    Christopher J. D. Wallis MD

    2017-05-01

    Full Text Available Background: Patients undergoing surgery for prostate cancer who have adverse pathological findings experience high rates of recurrence. While there are data supporting adjuvant radiotherapy compared to a wait-and-watch strategy to reduce recurrence rates, there are no randomized controlled trials comparing adjuvant radiotherapy with the other standard of care, salvage radiotherapy (radiotherapy administered at the time of recurrence. Methods: We constructed a health state transition (Markov model employing two-dimensional Monte Carlo simulation using a lifetime horizon to compare the quality-adjusted survival associated with postoperative strategies using adjuvant or salvage radiotherapy. Prior to analysis, we calibrated and validated our model using the results of previous randomized controlled trials. We considered clinically important oncological health states from immediately postoperative to prostate cancer–specific death, commonly described complications from prostate cancer treatment, and other causes of mortality. Transition probabilities and utilities for disease states were derived from a literature search of MEDLINE and expert consensus. Results: Salvage radiotherapy was associated with an increased quality-adjusted life expectancy (QALE (58.3 months as compared with adjuvant radiotherapy (53.7 months, a difference of 4.6 months (standard deviation 8.8. Salvage radiotherapy had higher QALE in 53% of hypothetical cohorts. There was a minimal difference in overall life expectancy (-0.1 months. Examining recurrence rates, our model showed validity when compared with available randomized controlled data. Conclusions: A salvage radiotherapy strategy appears to provide improved QALE for patients with adverse pathological findings following radical prostatectomy, compared with adjuvant radiotherapy. As these findings reflect, population averages, specific patient and tumor factors, and patient preferences remain central for individualized

  5. Oncological and functional outcomes of salvage renal surgery following failed primary intervention for renal cell carcinoma

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    Fernando G. Abarzua-Cabezas

    2015-02-01

    Full Text Available Purpose To assess the oncologic and functional outcomes of salvage renal surgery following failed primary intervention for RCC. Materials and Methods We performed a retrospective review of patients who underwent surgery for suspected RCC during 2004-2012. We identified 839 patients, 13 of whom required salvage renal surgery. Demographic data was collected for all patients. Intraoperative and postoperative data included ischemic duration, blood loss and perioperative complications. Preoperative and postoperative assessments included abdominal CT or magnetic resonance imaging, chest CT and routine laboratory work. Estimated glomerular filtration rate (eGFR was calculated according to the Modification of Diet in Renal Disease equation. Results The majority (85% of the patients were male, with an average age of 64 years. Ten patients underwent salvage partial nephrectomy while 3 underwent salvage radical nephrectomy. Cryotherapy was the predominant primary failed treatment modality, with 31% of patients undergoing primary open surgery. Pre-operatively, three patients were projected to require permanent post-operative dialysis. In the remaining 10 patients, mean pre- and postoperative serum creatinine and eGFR levels were 1.35 mg/dL and 53.8 mL/min/1.73 m2 compared to 1.43 mg/dL and 46.6 mL/min/1.73 m2, respectively. Mean warm ischemia time in 10 patients was 17.4 min and for all patients, the mean blood loss was 647 mL. The predominant pathological stage was pT1a (8/13; 62%. Negative surgical margins were achieved in all cases. The mean follow-up was 32.9 months (3.5-88 months. Conclusion While salvage renal surgery can be challenging, it is feasible and has adequate surgical, functional and oncological outcomes.

  6. The evolutionary portrait of metazoan NAD salvage.

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    João Carneiro

    Full Text Available Nicotinamide Adenine Dinucleotide (NAD levels are essential for cellular homeostasis and survival. Main sources of intracellular NAD are the salvage pathways from nicotinamide, where Nicotinamide phosphoribosyltransferases (NAMPTs and Nicotinamidases (PNCs have a key role. NAMPTs and PNCs are important in aging, infection and disease conditions such as diabetes and cancer. These enzymes have been considered redundant since either one or the other exists in each individual genome. The co-occurrence of NAMPT and PNC was only recently detected in invertebrates though no structural or functional characterization exists for them. Here, using expression and evolutionary analysis combined with homology modeling and protein-ligand docking, we show that both genes are expressed simultaneously in key species of major invertebrate branches and emphasize sequence and structural conservation patterns in metazoan NAMPT and PNC homologues. The results anticipate that NAMPTs and PNCs are simultaneously active, raising the possibility that NAD salvage pathways are not redundant as both are maintained to fulfill the requirement for NAD production in some species.

  7. The evolutionary portrait of metazoan NAD salvage.

    Science.gov (United States)

    Carneiro, João; Duarte-Pereira, Sara; Azevedo, Luísa; Castro, L Filipe C; Aguiar, Paulo; Moreira, Irina S; Amorim, António; Silva, Raquel M

    2013-01-01

    Nicotinamide Adenine Dinucleotide (NAD) levels are essential for cellular homeostasis and survival. Main sources of intracellular NAD are the salvage pathways from nicotinamide, where Nicotinamide phosphoribosyltransferases (NAMPTs) and Nicotinamidases (PNCs) have a key role. NAMPTs and PNCs are important in aging, infection and disease conditions such as diabetes and cancer. These enzymes have been considered redundant since either one or the other exists in each individual genome. The co-occurrence of NAMPT and PNC was only recently detected in invertebrates though no structural or functional characterization exists for them. Here, using expression and evolutionary analysis combined with homology modeling and protein-ligand docking, we show that both genes are expressed simultaneously in key species of major invertebrate branches and emphasize sequence and structural conservation patterns in metazoan NAMPT and PNC homologues. The results anticipate that NAMPTs and PNCs are simultaneously active, raising the possibility that NAD salvage pathways are not redundant as both are maintained to fulfill the requirement for NAD production in some species.

  8. The relative contribution of mannose salvage pathways to glycosylation in PMI-deficient mouse embryonic fibroblast cells.

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    Fujita, Naonobu; Tamura, Ayako; Higashidani, Aya; Tonozuka, Takashi; Freeze, Hudson H; Nishikawa, Atsushi

    2008-02-01

    Mannose for mammalian glycan biosynthesis can be imported directly from the medium, derived from glucose or salvaged from endogenous or external glycans. All pathways must generate mannose 6-phosphate, the activated form of mannose. Imported or salvaged mannose is directly phosphorylated by hexokinase, whereas fructose 6-phosphate from glucose is converted to mannose 6-phosphate by phosphomannose isomerase (PMI). Normally, PMI provides the majority of mannose for glycan synthesis. To assess the contribution of PMI-independent pathways, we used PMI-null fibroblasts to study N-glycosylation of DNase I, a highly sensitive indicator protein. In PMI-null cells, imported mannose and salvaged mannose make a significant contribution to N-glycosylation. When these cells were grown in mannose-free medium along with the mannosidase inhibitor, swainsonine, to block the salvage pathways, N-glycosylation of DNase I was almost completely eliminated. Adding approximately 13 microm mannose to the medium completely restored normal glycosylation. Treatment with bafilomycin A(1), an inhibitor of lysosomal acidification, also markedly reduced N-glycosylation of DNase I, but in this case only 8 microm mannose was required to restore full glycosylation, indicating that a nonlysosomal source of mannose made a significant contribution. Glycosylation levels were greatly also reduced in glycoconjugate-free medium, when endosomal membrane trafficking was blocked by expression of a mutant SKD1. From these data, we conclude that PMI-null cells can salvage mannose from both endogenous and external glycoconjugates via lysosomal and nonlysosomal degradation pathways.

  9. High level of viral suppression and low switch rate to second-line antiretroviral therapy among HIV-infected adult patients followed over five years: retrospective analysis of the DART trial.

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    Cissy Kityo

    Full Text Available In contrast to resource-rich countries, most HIV-infected patients in resource-limited countries receive treatment without virological monitoring. There are few long-term data, in this setting, on rates of viral suppression or switch to second-line antiretroviral therapy. The DART trial compared clinically driven monitoring (CDM versus routine laboratory (CD4/haematology/biochemistry and clinical monitoring (LCM in HIV-infected adults initiating therapy. There was no virological monitoring in either study group during follow-up, but viral load was measured in Ugandan participants at trial closure. Two thousand three hundred and seventeen (2317 participants from this country initiated antiretroviral therapy with zidovudine/lamivudine plus tenofovir (n = 1717, abacavir (n = 300, or nevirapine (n = 300. Of 1896 (81.8% participants who were alive and in follow-up at trial closure (median 5.1 years after therapy initiation, 1507 (79.5% were on first-line and 389 (20.5% on second-line antiretroviral therapy. The overall switch rate after the first year was 5.6 per 100 person-years; the rate was substantially higher in participants with low baseline CD4 counts (<50 cells/mm3. Among 1207 (80.1% first-line participants with viral load measured, HIV RNA was <400 copies/ml in 963 (79.8%, 400-999 copies/ml in 37 (3.1%, 1,000-9,999 copies/ml in 110 (9.1%, and ≥10,000 copies/ml in 97 (8.0%. The proportion with HIV RNA <400 copies/ml was slightly lower (difference 7.1%, 95% CI 2.5 to 11.5% in CDM (76.3% than in LCM (83.4%. Among 252 (64.8% second-line participants with viral load measured (median 2.3 years after switch, HIV RNA was <400 copies/ml in 226 (89.7%, with no difference between monitoring strategies. Low switch rates and high, sustained levels of viral suppression are achievable without viral load or CD4 count monitoring in the context of high-quality clinical care.ISRCTN13968779.

  10. Predictors of biochemical failure in patients undergoing prostate whole-gland salvage cryotherapy: a novel risk stratification model.

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    Spiess, Philippe E; Levy, David A; Mouraviev, Vladimir; Pisters, Louis L; Jones, J Stephen

    2013-08-01

    What's known on the subject? and what does the study add?: Previous studies have identified the most important prognostic factors of the likely outcomes of salvage prostate whole-gland ablation, including initial clinical stage, biopsy Gleason score, and PSA (total and doubling time). There is potential for further optimization of candidate selection for salvage cryoablation with curative intent and nadir PSA achieved after whole-gland cryotherapy may provide additional prognostic value. The study shows that the most important prognostic factors of biochemical progression-free survival for patients who have undergone whole-gland salvage prostate cryotherapy are nadir PSA achieved after therapy and pre-therapy biopsy Gleason score. Based on these two prognostic variables, we have identified risk stratification groups (low, intermediate and high) which help predict the expected outcomes of salvage whole-gland prostate cryotherapy in a given patient. This risk stratification constitutes a useful clinical tool in defining which patients maybe best suited for this local salvage treatment method. To assess the prognostic variables predicting the risk of biochemical progression-free survival (bPFS) after salvage prostate whole-gland cryotherapy using the Phoenix definition of bPFS. A total of 132 patients underwent prostate whole-gland salvage cryotherapy with curative intent. No patient underwent neoadjuvant/adjuvant hormonal ablative therapy, and all had extended post-salvage prostate-specific antigen (PSA) follow-up data. Cox univariate and multivariate logistic regression analyses of potential predictors of bPFS were conducted. Kaplan-Meier analyses of bPFS was also performed. At a mean (range) follow-up of 4.3 (0.9-12.7) years, the median (range) post-cryotherapy nadir PSA achieved was 0.17 (0-33.9) ng/mL. On multivariate analysis, predictors of bPFS were nadir PSA post-cryotherapy and pre-salvage biopsy Gleason score (P 2.5 ng/mL or biopsy Gleason score ≥ 7, with

  11. National survey on the current status of salvage radiotherapy on holidays by the JASTRO committee for future scope

    International Nuclear Information System (INIS)

    Nagata, Yasushi; Ashino, Yasuo

    2002-01-01

    Recently, the impact of the overall treatment time on local tumor control has been reported by several authors. However, we in Japan have a long radiotherapy break because of the two large national holiday seasons in April-May and December-January. Therefore, a national survey on the current status of salvage radiotherapy on holidays was performed in 2001. Fifty-three % of the all institutes performed salvage radiotherapy on holidays. However, there are several problems to be solved, and a national consensus and an authorized proposal by the JASTRO are waited. (author)

  12. Bacterial variations on the methionine salvage pathway

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    Haas Dieter

    2004-03-01

    Full Text Available Abstract Background The thiomethyl group of S-adenosylmethionine is often recycled as methionine from methylthioadenosine. The corresponding pathway has been unravelled in Bacillus subtilis. However methylthioadenosine is subjected to alternative degradative pathways depending on the organism. Results This work uses genome in silico analysis to propose methionine salvage pathways for Klebsiella pneumoniae, Leptospira interrogans, Thermoanaerobacter tengcongensis and Xylella fastidiosa. Experiments performed with mutants of B. subtilis and Pseudomonas aeruginosa substantiate the hypotheses proposed. The enzymes that catalyze the reactions are recruited from a variety of origins. The first, ubiquitous, enzyme of the pathway, MtnA (methylthioribose-1-phosphate isomerase, belongs to a family of proteins related to eukaryotic intiation factor 2B alpha. mtnB codes for a methylthioribulose-1-phosphate dehydratase. Two reactions follow, that of an enolase and that of a phosphatase. While in B. subtilis this is performed by two distinct polypeptides, in the other organisms analyzed here an enolase-phosphatase yields 1,2-dihydroxy-3-keto-5-methylthiopentene. In the presence of dioxygen an aci-reductone dioxygenase yields the immediate precursor of methionine, ketomethylthiobutyrate. Under some conditions this enzyme produces carbon monoxide in B. subtilis, suggesting a route for a new gaseous mediator in bacteria. Ketomethylthiobutyrate is finally transaminated by an aminotransferase that exists usually as a broad specificity enzyme (often able to transaminate aromatic aminoacid keto-acid precursors or histidinol-phosphate. Conclusion A functional methionine salvage pathway was experimentally demonstrated, for the first time, in P. aeruginosa. Apparently, methionine salvage pathways are frequent in Bacteria (and in Eukarya, with recruitment of different polypeptides to perform the needed reactions (an ancestor of a translation initiation factor and Ru

  13. Outcome of salvage radiotherapy for biochemical failure after radical prostatectomy with or without hormonal therapy

    International Nuclear Information System (INIS)

    Cheung, Rex; Kamat, Ashish M.; Crevoisier, Renaud de; Allen, Pamela K.; Lee, Andrew K.; Tucker, Susan L.; Pisters, Louis; Babaian, Richard J.; Kuban, Deborah

    2005-01-01

    Background: This study analyzed the outcome of salvage radiotherapy for biochemical failure after radical prostatectomy (RP). By comparing the outcomes for patients who received RT alone and for those who received combined RT and hormonal therapy, we assessed the potential benefits of hormonal therapy. Patients and Methods: This cohort was comprised of 101 patients who received salvage RT between 1990 and 2001 for biochemical failure after RP. Fifty-nine of these patients also received hormone. Margin status (positive vs. negative), extracapsular extension (yes vs. no), seminal vesicle involvement (yes vs. no), pathologic stage, Gleason score, pre-RP PSA, post-RP PSA, pre-RT PSA, hormonal use, radiotherapy dose and technique, RP at M. D. Anderson Cancer Center, and time from RP to salvage RT were analyzed. Statistically significant variables were used to construct prognostic groups. Results: Independent prognostic factors for the RT-alone group were margin status and pre-RT PSA. RP at M. D. Anderson Cancer Center was marginally significant (p = 0.06) in multivariate analysis. Pre-RT PSA was the only significant prognostic factor for the combined-therapy group. We used a combination of margin status and pre-RT PSA to construct a prognostic model for response to the salvage treatment based on the RT group. We identified the favorable group as those patients with positive margin and pre-RT PSA ≤0.5 ng/mL vs. the unfavorable group as otherwise. This stratification separates patients into clinically meaningful groups. The 5-year PSA control probabilities for the favorable vs. the unfavorable group were 83.7% vs. 61.7% with radiotherapy alone (p = 0.03). Androgen ablation seemed to be most beneficial in the unfavorable group. Conclusion: After prostatectomy, favorable-group patients may fare well with salvage radiotherapy alone. These patients may be spared the toxicity of androgen ablation. The other patients may benefit most from a combined approach with hormonal

  14. An exploratory case study of the impact of expanding cost-effectiveness analysis for second-line nivolumab for patients with squamous non-small cell lung cancer in Canada: Does it make a difference?

    Science.gov (United States)

    Shafrin, Jason; Skornicki, Michelle; Brauer, Michelle; Villeneuve, Julie; Lees, Michael; Hertel, Nadine; Penrod, John R; Jansen, Jeroen

    2018-04-26

    Health technology appraisal agencies often rely on cost-effectiveness analyses to inform coverage decisions for new treatments. These assessments, however, frequently measure a treatment's value from the payer's perspective, and may not capture value generated from reduced caregiving costs, increased productivity, value based on patient risk preferences, option value or the insurance value to non-patients. To examine how using a broader societal perspective of treatment value affects cost-effectiveness estimates, this case study analyzed the net monetary benefit (NMB) of second-line nivolumab treatment of patients with squamous non-small cell lung cancer (NSCLC) in Canada. The comparator was treatment with docetaxel. NMB was measured from three perspectives: (i) traditional payer, (ii) traditional societal and (iii) broad societal. Nivolumab was more effective (increased quality-adjusted life years by 0.66 versus docetaxel), but also increased costs by $100,168 CAD. When valuing a quality-adjusted life year at $150,000, the net monetary benefit from the payer perspective suggested that costs modestly exceed benefits (NMB: -$1031). Adopting a societal perspective, however, nivolumab's benefits outweighed its costs (NMB: +$6752 and +$91,084 from the traditional and broad societal perspectives, respectively). Broadening cost-effectiveness analysis beyond the traditional payer perspective had a significant impact on the result and should be considered in order to capture all treatment benefits and costs of societal relevance. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Economic analysis of the TAX 317 trial: docetaxel versus best supportive care as second-line therapy of advanced non-small-cell lung cancer.

    Science.gov (United States)

    Leighl, Natasha B; Shepherd, Frances A; Kwong, Rita; Burkes, Ronald L; Feld, Ronald; Goodwin, Pamela J

    2002-03-01

    To determine the cost-effectiveness (CE) of second-line docetaxel compared with best supportive care (BSC) in the TAX 317 trial, a randomized clinical trial of second-line chemotherapy in non-small-cell lung cancer. A retrospective CE analysis of the TAX 317 trial was undertaken, evaluating direct medical costs of therapy from the viewpoint of Canada's public health care system. Costs were derived in 1999 Canadian dollars, and resource use was determined through prospective trial data. The incremental survival benefit in the docetaxel arm over BSC was 2 months (P =.047). The CE of docetaxel was $57,749 per year of life gained. For patients treated with docetaxel 75 mg/m(2), the CE was $31,776 per year of life gained. In univariate sensitivity analyses, CE estimates were most sensitive to changes in survival, ranging from $18,374 to $117,434 with 20% variation in survival at the recommended dose. The largest cost center in both arms was hospitalization, followed by the cost of drugs, investigations, radiotherapy, and community care. BSC patients had fewer hospitalizations than patients in the chemotherapy arm and were more often palliated at home. Although the decision to treat should not be based on economic considerations alone, our CE estimate of $31,776 per year of life gained (at the currently recommended dose of docetaxel) is within an acceptable range of health care expenditures, and the total costs of therapy are similar to those of second-line palliative chemotherapy for other solid tumors.

  16. Long-term follow-up of salvage radiotherapy in Hodgkin's lymphoma after chemotherapy failure

    International Nuclear Information System (INIS)

    Campbell, Belinda; Wirth, Andrew; Milner, Alvin; Di Iulio, Juliana; MacManus, Michael; Ryan, Gail M.

    2005-01-01

    Purpose: To evaluate the long-term results of salvage radiotherapy (SRT) for Hodgkin's lymphoma after chemotherapy failure. Methods and Materials: We reviewed 81 patients undergoing SRT for persistent or recurrent Hodgkin's lymphoma after chemotherapy; 19 also received conventional-dose salvage chemotherapy. Results: At SRT, the median patient age was 31 years. Of the 81 patients, 81% had Stage I-II, 25.9% had B symptoms, 14.8% had bulky disease, and 7.4% had extranodal disease. A less than a complete response (CR) to the last chemotherapy regimen occurred in 47%. SRT was generally limited to one side of the diaphragm, and the median dose was 36 Gy. After SRT, 75% of patients achieved a CR, with 82% retaining durable in-field control. In-field failure was associated with less than a CR to the last chemotherapy regimen (p = 0.0287). Most failures were at distant sites, with 60% in previously involved sites. The 10-year freedom from treatment failure and overall survival rates were 32.8% and 45.7%, respectively. The adverse prognostic factors for freedom from treatment failure were age >50 years (p 50 years (p < 0.001), B symptoms (p = 0.002), and less than a CR to the last chemotherapy regimen (p = 0.002). Favorable cohorts had a 10-year freedom from treatment failure rate of 51% and overall survival rate of 92%. Conclusions: Salvage radiotherapy is effective for selected patients with Hodgkin's lymphoma after chemotherapy failure and should be considered for incorporation into salvage programs

  17. The Prestige oil spill response in the French coastal waters : setting up a second-line response system

    International Nuclear Information System (INIS)

    Kerambrun, L.; Lavenant, M.; Cariou, G.; Poisson, H.; Goasguen, H.; Peltier, M.

    2005-01-01

    A heavy fuel oil spill from the Prestige oil tanker in early 2003 threatened the coastline of France, particularly the sensitive sandy dunes of the Aquitaine coast. The spill posed a long-term threat to two affected tourist islands that host a rich marine life, including the Marennes-Oleron oysters and juvenile eel fisheries. An oil spill response system was established by the French Maritime Affairs Department. The two-tiered response system was constructed with dynamic and static components and was adapted for strong tidal currents and muddy waters where fuel patches from the spill might not be visible. Local fishermen with knowledge of the waters used their trawlers and eel-fishing boats that were equipped with oil recovery trawls. A local netting device was also tested. The second response line for shallow waters consisted of small boats with net bags. The storage, transfer and treatment of the oily waste were controlled and available oil waste treatment procedures were assessed at local, regional and national levels for each type of oil waste fuel. 2 refs

  18. Associations between deepness of response and clinical outcomes among Japanese patients with metastatic colorectal cancer treated with second-line FOLFIRI plus cetuximab

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    Osumi H

    2015-08-01

    Full Text Available Hiroki Osumi, Satoshi Matsusaka, Mitsukuni Suenaga, Eiji Shinozaki, Nobuyuki Mizunuma Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan Background: In the FIRE-3 trial, overall survival (OS was significantly longer in patients treated with FOLFIRI plus cetuximab (C-mab than in those treated with FOLFIRI plus bevacizumab (Bev, but progression-free survival (PFS was not significantly different. This may be associated with the deepness of response (DpR in patients treated with FOLFIRI plus C-mab. We aimed to evaluate the relationship between clinical outcome and DpR in metastatic colorectal cancer (mCRC patients treated with second-line FOLFIRI plus C-mab.Methods: A total of 112 patients with histopathologically confirmed mCRC treated with second-line FOLFIRI in combination with C-mab (N=42 or Bev (N=70 were retrospectively enrolled between October 2008 and June 2013. The relationship between DpR and clinical outcome in patients treated with FOLFIRI plus C-mab or Bev was determined.Results: Forty-two patients treated with FOLFIRI plus C-mab had a mean DpR of 6.1% (interquartile range: -13.7%, 20.8% and a minimum DpR of -62.7%. On the other hand, 70 patients treated with FOLFIRI plus Bev had a mean DpR of 0% (interquartile range: -16%, 10% and a minimum DpR of -111%. DpR ≥30% was associated with significantly longer OS and PFS when compared with DpR ≤30% in patients given FOLFIRI plus C-mab. DpR (≥30% was independently associated with prolongation of OS and PFS. In patients treated with FOLFIRI plus C-mab, there was a moderate positive correlation between DpR and clinical outcomes (OS: r=0.51, P<0.001; PFS: r=0.54, P<0.001.Conclusion: FOLFIRI plus C-mab yielded a stronger correlation between DpR and clinical outcomes. These results indicate the potential of DpR as a new measure of efficacy in mCRC patients treated with second-line chemotherapy plus C-mab. Keywords: deepness of

  19. The outcome of rectal cancer after early salvage TME following TEM compared with primary TME: a case-matched study.

    Science.gov (United States)

    Levic, K; Bulut, O; Hesselfeldt, P; Bülow, S

    2013-08-01

    Transanal endoscopic microsurgery (TEM) allows locally complete resection of early rectal cancer as an alternative to conventional radical surgery. In case of unfavourable histology after TEM, or positive resection margins, salvage surgery can be performed. However, it is unclear if the results are equivalent to primary treatment with total mesorectal excision (TME). The aim of this retrospective study was to determine whether there is a difference in outcome between patients who underwent early salvage resection with TME after TEM, and those who underwent primary TME for rectal cancer. From 1997 to 2011, early salvage surgery with TME after TEM was performed in 25 patients in our institution. These patients were compared with 25 patients who underwent primary TME, matched according to gender, age (±2 years), cancer stage and operative procedure. Data were obtained from the patients' charts and reviewed retrospectively. No patients received preoperative chemotherapy. Perioperative data and oncological outcome were analysed. The Mann-Whitney U-test and Fisher's exact test were used to compare the results between the two groups. There was no significant difference between the two groups in median operating time (P = 0.39), median blood loss (P = 0.19) or intraoperative complications (P = 1.00). The 30-day mortality was 8 % (n = 2) among patients who underwent salvage TME after TEM, and no patients died in the primary TME group (P = 0.49). There was no significant difference between two groups of patients in the median number of harvested lymph nodes (P = 0.34), median circumferential resection margin (CRM) (P = 0.99) or the completeness of the mesorectal fascia plane. No local recurrences occurred among the patients with salvage TME, and there were 2 patients (8 %) with local recurrences among the patients with primary TME (P = 0.49). Distant metastasis occurred in one patient (4 %) after salvage TME and in 3 patients (12 %) with primary TME (P = 0.61). The median

  20. INDONESIAN SALVAGE LAW WITHIN THE FRAMEWORK OF CONTEMPORARY MARITIME LAW

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    Dhiana Puspitawati

    2015-12-01

    Full Text Available Located in a strategic position, that is between two great oceans and two land masses have made Indonesia a centre of international trade and shipping. In fact, 90% of international trades are carried out through the ocean. It is therefore crucial to assure that the activities in carrying goods across the ocean are incident free. However, if accident happens, assistance from professionals to preserve items of property is desirable. In such, salvage law emerged. This paper discusses comprehensively Indonesian salvage law within the framework of contemporary maritime law. While Indonesian maritime law is mostly based on its national law on the carriage of goods by the sea, in fact, the development of maritime law is highly affected by international practices which are largely based on international conventions and regulations. This research finds that while Indonesian salvage law can be found in Book II Chapter VII article 545-568k Wetboek Van Koophandel or known as Kitab Undang-undang Hukum Dagang (KUHD, which focused narrowly on the value of salved property as the primary measures of success, yet Indonesian salvage law has not been developed in accordance with current international salvage law, which adopted a broader and more balanced approached in both commercial and environmental aspects. Although it is believed that such approached is “culturally unrecognized” in Indonesia, this research argued that since Indonesian waters are part of international waters, all process by waters including salvage should confirm the relevant international practices and regulations. While Indonesia has taken out salvage law from KUHD and regulates it within Act Number 17/2008 on navigation, however, such act only provides one article for salvage stating that salvage will be regulates further by Ministry Regulation. Untill this paper was written no such government regulation produced yet by Indonesia. Since Indonesian waters is the centre of international

  1. Septic Shock following Prostate Biopsy: Aggressive Limb Salvage for Extremities after Pressor-Induced Ischemic Gangrene

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    Jocelyn Lu, BS

    2017-09-01

    Full Text Available Summary:. Vasopressors used to treat patients with septic shock can cause ischemic necrosis of appendages such as the ears and nose, as well as the extremities. Cases of quadruple-extremity necrosis have high morbidity and mortality, and a profound negative impact on quality of life. This case report details the successful limb salvage and return to function using free tissue transfer as a means to salvage bilateral lower extremities in a patient who suffered vasopressor-induced ischemia of upper and lower extremities after prostate biopsy–induced septic shock. Septic shock following transrectal ultrasound–guided prostate biopsy is a rare, yet life-threatening complication. Successful treatment included thorough planning and staging of therapies such as awaiting tissue demarcation and serial surgical debridement to adequately prepare the tissue bed for free tissue transfer. Adjunctive treatments such as hyperbaric oxygen therapy, negative-pressure wound therapy, and meticulous wound care played a crucial role in wound healing. This vigilant planning and coordinated care resulted in the successful lower extremity salvage, consisting of bilateral transmetatarsal amputations and free tissue transfer to both limbs. We present our long-term follow-up of a functional ambulatory patient after catastrophic, life-threatening infection and appropriate multidisciplinary care.

  2. Salvage radiotherapy for carcinoma of the ovary following chemotherapy

    International Nuclear Information System (INIS)

    Cheung, A.Y.

    1988-01-01

    Following single-agent or combination chemotherapy, 9 patients with epithelial carcinoma of the ovary had elective second-look laparotomy. Macroscopic intraperitoneal disease was resected in 4 patients. Therefore, after the laparotomy, all 9 patients had only biopsy-proven, microscopic residual disease, and they received whole abdominopelvic irradiation. Hematological tolerance was satisfactory, with only 2 patients developing asymptomatic thrombocytopenia. Mild gastrointestinal reactions, while frequent during radiotherapy, did not interrupt treatment in any patient. After follow-up ranging from 6 to 28 months (median 12 months), 2 patients died of cancer, 2 were alive with cancer, 3 were alive without clinical recurrence, and 2 were alive without biopsy-proven recurrence. Bowel complication occurred in 4 patients: 2 developed intestinal obstruction due to recurrent tumor, 1 developed subacute bowel obstruction which spontaneously resolved, and 1 patient required bowel resection because of a radiation complication. This study indicated that after single- or multiple-drug chemotherapy, most patients could complete the course of whole abdominopelvic irradiation. Gastrointestinal complications could be secondary to radiation damage or to recurrent tumor. While whole abdominopelvic irradiation was not an effective second-line treatment, some long-term survivors could still be expected

  3. Salvage Stereotactic Body Radiotherapy (SBRT) Following In-Field Failure of Initial SBRT for Spinal Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Thibault, Isabelle; Campbell, Mikki [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Tseng, Chia-Lin [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Atenafu, Eshetu G. [Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Letourneau, Daniel [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Yu, Eugene [Department of Radiology, University Health Network, University of Toronto, Toronto, Ontario (Canada); Cho, B.C. John [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Lee, Young K. [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Fehlings, Michael G. [Department of Radiology, University Health Network, University of Toronto, Toronto, Ontario (Canada); Sahgal, Arjun, E-mail: arjun.sahgal@sunnybrook.ca [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada)

    2015-10-01

    Purpose: We report our experience in salvaging spinal metastases initially irradiated with stereotactic body radiation therapy (SBRT), who subsequently progressed with imaging-confirmed local tumor progression, and were re-irradiated with a salvage second SBRT course to the same level. Methods and Materials: From a prospective database, 56 metastatic spinal segments in 40 patients were identified as having been irradiated with a salvage second SBRT course to the same level. In addition, 24 of 56 (42.9%) segments had initially been irradiated with conventional external beam radiation therapy before the first course of SBRT. Local control (LC) was defined as no progression on magnetic resonance imaging at the treated segment, and calculated according to the competing risk model. Overall survival (OS) was evaluated for each patient treated by use of the Kaplan-Meier method. Results: The median salvage second SBRT total dose and number of fractions was 30 Gy in 4 fractions (range, 20-35 Gy in 2-5 fractions), and for the first course of SBRT was 24 Gy in 2 fractions (range, 20-35 Gy in 1-5 fractions). The median follow-up time after salvage second SBRT was 6.8 months (range, 0.9-39 months), the median OS was 10.0 months, and the 1-year OS rate was 48%. A longer time interval between the first and second SBRT courses predicted for better OS (P=.02). The crude LC was 77% (43/56), the 1-year LC rate was 81%, and the median time to local failure was 3.0 months (range, 2.7-16.7 months). Of the 13 local failures, 85% (11/13) and 46% (6/13) showed progression within the epidural space and paraspinal soft tissues, respectively. Absence of baseline paraspinal disease predicted for better LC (P<.01). No radiation-induced vertebral compression fractures or cases of myelopathy were observed. Conclusion: A second course of spine SBRT, most often with 30 Gy in 4 fractions, for spinal metastases that failed initial SBRT is a feasible and efficacious salvage treatment option.

  4. Gynecologic examination and cervical biopsies after (chemo) radiation for cervical cancer to identify patients eligible for salvage surgery

    International Nuclear Information System (INIS)

    Nijhuis, Esther R.; Zee, Ate G.J. van der; Hout, Bertha A. in 't; Boomgaard, Jantine J.; Hullu, Joanne A. de; Pras, Elisabeth; Hollema, Harry; Aalders, Jan G.; Nijman, Hans W.; Willemse, Pax H.B.; Mourits, Marian J.E.

    2006-01-01

    Purpose: The aim of this study was to evaluate efficacy of gynecologic examination under general anesthesia with cervical biopsies after (chemo) radiation for cervical cancer to identify patients with residual disease who may benefit from salvage surgery. Methods and Materials: In a retrospective cohort study data of all cervical cancer patients with the International Federation of Gynecology and Obstetrics (FIGO) Stage IB1 to IVA treated with (chemo) radiation between 1994 and 2001 were analyzed. Patients underwent gynecologic examination under anesthesia 8 to 10 weeks after completion of treatment. Cervical biopsy samples were taken from patients judged to be operable. In case of residual cancer, salvage surgery was performed. Results: Between 1994 and 2001, 169 consecutive cervical cancer patients received primary (chemo) radiation, of whom 4 were lost to follow-up. Median age was 56 years (interquartile range [IQR], 44-71) and median follow-up was 3.5 years (IQR, 1.5-5.9). In each of 111 patients a biopsy sample was taken, of which 90 (81%) showed no residual tumor. Vital tumor cells were found in 21 of 111 patients (19%). Salvage surgery was performed in 13 of 21 (62%) patients; of these patients, 5 (38%) achieved long-term, complete remission after salvage surgery (median follow-up, 5.2 years; range, 3.9-8.8 years). All patients with residual disease who did not undergo operation (8/21) died of progressive disease. Locoregional control was more often obtained in patients who underwent operation (7 of 13) than in patients who were not selected for salvage surgery (0 of 8 patients) (p < 0.05). Conclusions: Gynecologic examination under anesthesia 8 to 10 weeks after (chemo) radiation with cervical biopsies allows identification of those cervical cancer patients who have residual local disease, of whom a small but significant proportion may be salvaged by surgery

  5. Postoperative internal iliac artery embolisation as salvage therapy ...

    African Journals Online (AJOL)

    Postoperative internal iliac artery embolisation as salvage therapy for ... of blood products. Damage control surgery was performed, and bleeding was ultimately only ... abdomen was packed with adrenalin-soaked swabs. Coagulation.

  6. Salvage prostate HDR brachytherapy combined with interstitial hyperthermia for local recurrence after radiation therapy failure

    Energy Technology Data Exchange (ETDEWEB)

    Kukielka, A.M.; Hetnal, M.; Dabrowski, T.; Walasek, T.; Brandys, P.; Reinfuss, M. [Centre of Oncology, M. Sklodowska - Curie Institute, Krakow Branch, Department of Radiotherapy, Krakow (Poland); Nahajowski, D.; Kudzia, R.; Dybek, D. [Centre of Oncology, M. Sklodowska - Curie Institute, Krakow Branch, Department of Medical Physics, Department of Radiotherapy, Krakow (Poland)

    2014-02-15

    The aim of the present retrospective study is to evaluate toxicity and early clinical outcomes of interstitial hyperthermia (IHT) combined with high-dose rate (HDR) brachytherapy as a salvage treatment in patients with biopsy-confirmed local recurrence of prostate cancer after previous external beam radiotherapy. Between September 2008 and March 2013, 25 patients with local recurrence of previously irradiated prostate cancer were treated. The main eligibility criteria for salvage prostate HDR brachytherapy combined with interstitial hyperthermia were biopsy confirmed local recurrence and absence of nodal and distant metastases. All patients were treated with a dose of 30 Gy in 3 fractions at 21-day intervals. We performed 62 hyperthermia procedures out of 75 planned (83 %). The aim of the hyperthermia treatment was to heat the prostate to 41-43 C for 60 min. Toxicity for the organs of the genitourinary system and rectum was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, v. 4.03). Determination of subsequent biochemical failure was based on the Phoenix definition (nadir + 2 ng/ml). The median age was 71 years (range 62-83 years), the median initial PSA level was 16.3 ng/ml (range 6.37-64 ng/ml), and the median salvage PSA level was 2.8 ng/ml (1.044-25.346 ng/ml). The median follow-up was 13 months (range 4-48 months). The combination of HDR brachytherapy and IHT was well tolerated. The most frequent complications were nocturia, weak urine stream, urinary frequency, hematuria, and urgency. Grade 2 rectal hemorrhage was observed in 1 patient. No grade 3 or higher complications were observed. The 2-year Kaplan-Meier estimate of biochemical control after salvage treatment was 74 %. The PSA in 20 patients decreased below the presalvage level, while 11 patients achieved a PSA nadir < 0.5 ng/ml. All patients are still alive. Of the 7 patients who experienced biochemical failure, bone metastases were found in 2 patients. IHT in combination

  7. Trauma center variation in splenic artery embolization and spleen salvage: a multicenter analysis.

    Science.gov (United States)

    Banerjee, Aman; Duane, Therese M; Wilson, Sean P; Haney, Starre; O'Neill, Patrick J; Evans, Heather L; Como, John J; Claridge, Jeffrey A

    2013-07-01

    This study aimed to evaluate if variation in management of blunt splenic injury (BSI) among Level I trauma centers is associated with different outcomes related to the use of splenic artery embolization (SAE). All adult patients admitted for BSI from 2008 to 2010 at 4 Level I trauma centers were reviewed. Use of SAE was determined, and outcomes of spleen salvage and nonoperative management (NOM) failure were evaluated. A priori, a 10% SAE rate was used to group centers into high- or low-use groups. There were 1,275 BSI patients. There were intercenter differences in age, injury severity, and grade of spleen injury (Spleen Injury Scale [SIS]). Mortality was similar by center; however, BSI treatment varied significantly by center. Overall, SAE use was highest at center A compared with B, C, and D (19%, 11%, 1%, and 4%, respectively; p trauma centers. Centers with higher rates of SAE use have higher spleen salvage and less NOM failure. SAE was shown to be an independent predictor of spleen salvage. Therapeutic study, level IV.

  8. Nicotinamidase participates in the salvage pathway of NAD biosynthesis in Arabidopsis.

    Science.gov (United States)

    Wang, Guodong; Pichersky, Eran

    2007-03-01

    Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which is derived from NAD, have important roles as a redox carriers in metabolism. A combination of de novo and salvage pathways contribute to the biosynthesis of NAD in all organisms. The pathways and enzymes of the NAD salvage pathway in yeast and animals, which diverge at nicotinamide, have been extensively studied. Yeast cells convert nicotinamide to nicotinic acid, while mammals lack the enzyme nicotinamidase and instead convert nicotinamide to nicotinamide mononucleotide. Here we show that Arabidopsis thaliana gene At2g22570 encodes a nicotinamidase, which is expressed in all tissues, with the highest levels observed in roots and stems. The 244-residue protein, designated AtNIC1, converts nicotinamide to nicotinic acid and has a Km value of 118 +/- 17 microM and a Kcat value of 0.93 +/- 0.13 sec(-1). Plants homozygous for a null AtNIC1 allele, nic1-1, have lower levels of NAD and NADP under normal growth conditions, indicating that AtNIC1 participates in a yeast-type NAD salvage pathway. Mutant plants also exhibit hypersensitivity to treatments of abscisic acid and NaCl, which is correlated with their inability to increase the cellular levels of NAD(H) under these growth conditions, as occurs in wild-type plants. We also show that the growth of the roots of wild-type but not nic1-1 mutant plants is inhibited and distorted by nicotinamide.

  9. Regulation of the Nampt-mediated NAD salvage pathway and its therapeutic implications in pancreatic cancer.

    Science.gov (United States)

    Ju, Huai-Qiang; Zhuang, Zhuo-Nan; Li, Hao; Tian, Tian; Lu, Yun-Xin; Fan, Xiao-Qiang; Zhou, Hai-Jun; Mo, Hai-Yu; Sheng, Hui; Chiao, Paul J; Xu, Rui-Hua

    2016-08-28

    Nicotinamide adenine dinucleotide (NAD) is a crucial cofactor for the redox reactions in the metabolic pathways of cancer cells that have elevated aerobic glycolysis (Warburg effect). Cancer cells are reported to rely on NAD recycling and inhibition of the NAD salvage pathway causes metabolic collapse and cell death. However, the underlying regulatory mechanisms and clinical implications for the NAD salvage pathway in pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study showed that the expression of Nampt, the rate-limiting enzyme of the NAD salvage pathway, was significantly increased in PDAC cells and PDAC tissues. Additionally, inhibition of Nampt impaired tumor growth in vitro and tumorigenesis in vivo, which was accompanied by a decreased cellular NAD level and glycolytic activity. Mechanistically, the Nampt expression was independent of Kras and p16 status, but it was directly regulated by miR-206, which was inversely correlated with the expression of Nampt in PDAC tissues. Importantly, pharmacological inhibition of Nampt by its inhibitor, FK866, significantly enhanced the antitumor activity of gemcitabine in PDAC cells and in orthotopic xenograft mouse models. In conclusion, the present study revealed a novel regulatory mechanism for Nampt in PDAC and suggested that Nampt inhibition may override gemcitabine resistance by decreasing the NAD level and suppressing glycolytic activity, warranting further clinical investigation for pancreatic cancer treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Postoperative blood salvage versus allogeneic blood transfusion in total knee and hip arthroplasty: a literature review.

    Science.gov (United States)

    Leigheb, Massimiliano; Pogliacomi, Francesco; Bosetti, Michela; Boccafoschi, Francesca; Sabbatini, Maurizio; Cannas, Mario; Grassi, Federico

    2016-04-15

    We aimed to compare Postoperative Blood Salvage (PBS) with Allogeneic Blood Transfusion (ABT) in patients undergoing Total Hip and Knee Arthroplasty (THA, TKA).  A bibliographic research was carried out in order to review the literature dedicated to postoperative blood salvage in major orthopaedic surgery, excluding papers dealing exclusively with preoperative autologous donation, intraoperative blood salvage and ABT. PBS and ABT were compared according to complications, costs and duration of hospitalization. PBS effectiveness in reducing ABT was also assessed. PBS system is useful for reducing the complication rate and the length of hospital stay if compared to ABT. Costs for the reinfusion of unwashed shed blood, washed blood, and allogeneic transfusion are controversial among the different authors. Several papers demonstrate that PBS significantly reduces the need of postoperative ABT in both THA and TKA, while there is low evidence that PBS does not affect the risk of surgical wound complications. To reduce potential risks related to PBS, including non-hemolytic febrile reaction, the reinfusion of saved blood should begin within 4-6 hours after the start of collection through the wound drainage. According to literature, PBS appears to be a valid alternative to ABT, which is the standard treatment for postoperative anemia in THA and TKA. Contraindications to PBS must be ruled out before recommending it to patients undergoing major orthopaedic procedures.

  11. Results of salvage surgery for mammary recurrence following breast-conserving therapy

    International Nuclear Information System (INIS)

    Kurtz, J.M.; Amalric, R.; Brandone, H.; Ayme, Y.; Spitalier, J.M.

    1988-01-01

    A retrospective analysis was performed of 118 surgically treated mammary recurrences, occurring following primary conservative excision and radiation therapy for clinical Stages I and II breast cancer. Actuarial cancer-specific survival following salvage surgery was 72% at 5 years and 58% at 10 years. With a median followup of 7 years, further local-regional recurrences were observed in 20 of the 118 patients, many of whom could be treated by further surgery. Actuarial survival after recurrence was significantly influenced by initial clinical stage, as well as by the disease-free interval following primary therapy, but was similar for both premenopausal and postmenopausal patients and for patients treated by radical or breast-conserving salvage operations. For recurrences after the fifth year, actuarial survival following salvage surgery was 83% and 68% at 5 and 10 years, respectively. Survival for Stage I patients was favorable regardless of disease-free interval. It is concluded that recurrences in the breast following primary treatment with limited surgery and irradiation have a considerably more favorable prognosis than that of local failures after primary radical surgery. Suggestions for the management of these recurrences are presented

  12. Natural recovery and leaf water potential after fire influenced by salvage logging and induced drought stress

    Directory of Open Access Journals (Sweden)

    D. Moya

    2013-01-01

    Full Text Available Salvage logging is one of the most common emergency actions in the short-term management after a fire. Several studies have been carried out and some obtained positive results which incite to carry it out but other, found negative effects on seedling establishment and regeneration. In addition, climatic changes will have large impacts on vegetation productivity and resilience since the regional models for south-eastern Spain predicts a rainfall decrease of about 20% and temperature increase of 4.5 ºC. Our aim was to determine how short-term forest management and induced drought affect the ecosystem recovery in Aleppo pine stands naturally recovered after a fire.In summer 2009, a mid-high severity fire burned 968 ha of Aleppo pine (Pinus halepensis Mill. forest in south-eastern Spain. Six months later, a salvage logging was carried out. The Aleppo pine recruitment was negligible. During summer 2010, twelve square plots (2m x 2m were set in the three scenarios: control, salvaged and drought induced. The surface cover and soil water availability for three dominant understory species were recorded in four field campaigns: Spring-2010, Fall-2010, Spring-2011 and Fall-2011.The season, management and the target species showed significant differences in growing and water stress. In general, Esparto grass showed lower water stress, mainly in Fall, a higher increase of total coverage. Both effects were showing their highest values in non-salvaged areas and no drought. Changes in leaf water potential and soil water content after the drought season influence the survival and development of individuals.Our results indicate that soil water content and ecosystem response can be modified by short-term silvicultural treatments. Therefore, management after fire could cause opposite effects to those initially foreseen, since they depend on fire severity, and type of ecosystem management response. So, their application must be evaluated and assessed before

  13. RECORD-4 multicenter phase 2 trial of second-line everolimus in patients with metastatic renal cell carcinoma: Asian versus non-Asian population subanalysis.

    Science.gov (United States)

    Yang, Lin; Alyasova, Anna; Ye, Dingwei; Ridolfi, Antonia; Dezzani, Luca; Motzer, Robert J

    2018-02-17

    RECORD-4 assessed everolimus in patients with metastatic renal cell carcinoma (mRCC) who progressed after 1 prior anti-vascular endothelial growth factor (VEGF) or cytokine and reinforced the clinical benefit of second-line everolimus. Because of the high percentage of patients from China enrolled in RECORD-4 (41%) and some reported differences in responses to certain targeted agents between Chinese and Western patients, this subanalysis evaluated outcomes in Asian versus non-Asian patients. RECORD-4 enrolled patients with clear cell mRCC into 3 cohorts based on prior first-line therapy: sunitinib, other anti-VEGF (sorafenib, bevacizumab, pazopanib, other), or cytokines. Patients received everolimus 10 mg/d until progression of disease (RECIST, v1.0) or intolerance. Primary end point was progression-free survival per investigator review. Data cutoff was Sept 1, 2014. Among Asian (n = 55) versus non-Asian (n = 79) patients, 98% versus 84% had good/intermediate MSKCC prognosis; 73% versus 65% were men, and 85% versus 73% were < 65 years of age. All (100%) Asian patients were of Chinese ethnicity. Median duration of exposure was 5.5 mo for Asian and 6.0 mo for non-Asian patients. Among Asian versus non-Asian patients, median progression-free survival (months) was 7.4 versus 7.8 overall, 7.4 versus 4.0 with prior sunitinib, and 5.7 versus 9.2 with prior other anti-VEGFs. Clinical benefit rate was similar between populations: 74.5% (95% CI 61.0-85.3) for Asian patients and 74.7% (95% CI 63.6-83.8) for non-Asian patients. Most patients achieved stable disease as best overall response (Asian, 63.6%; non-Asian, 69.6%). Overall rate of grade 3/4 adverse events appeared similar for Asian (58%) and non-Asian patients (54%). This RECORD-4 subanalysis demonstrated comparable efficacy and adverse event profiles of second-line everolimus in Asian and non-Asian patients. Efficacy and safety outcomes by prior therapy should be interpreted with caution because of small

  14. Molecular characterization of mutations associated with resistance to second-line tuberculosis drug among multidrug-resistant tuberculosis patients from high prevalence tuberculosis city in Morocco.

    Science.gov (United States)

    Oudghiri, Amal; Karimi, Hind; Chetioui, Fouad; Zakham, Fathiah; Bourkadi, Jamal Eddine; Elmessaoudi, My Driss; Laglaoui, Amin; Chaoui, Imane; El Mzibri, Mohammed

    2018-02-27

    The emergence of extensively drug-resistant tuberculosis (XDR-TB) has raised public health concern for global TB control. Although multi drug-resistant tuberculosis (MDR- TB) prevalence and associated genetic mutations in Morocco are well documented, scarce information on XDR TB is available. Hence, the evaluation of pre-XDR and XDR prevalence, as well as the mutation status of gyrA, gyrB, rrs, tlyA genes and eis promoter region, associated with resistance to second line drugs, is of great value for better management of M/XDR TB in Morocco. To evaluate pre-XDR and XDR prevalence, as well as the mutation status of gyrA, gyrB, rrs, tlyA genes and eis promoter region, associated with resistance to second line drug resistance, in 703 clinical isolates from TB patients recruited in Casablanca, and to assess the usefulness of molecular tools in clinical laboratories for better management of M/XDR TB in Morocco. Drug susceptibility testing (DST) was performed by the proportional method for first line drugs, and then the selected MDR isolates were tested for second line drugs (Ofloxacin, Kanamycin, Amikacin and Capreomycin). Along with DST, all samples were subjected to rpoB, katG and p-inhA mutation analysis by PCR and DNA sequencing. MDR isolates as well as 30 pan-susceptible strains were subjected to PCR and DNA sequencing of gyrA, gyrB, rrs, tlyA genes and eis promoter, associated with resistance to fluoroquinolones and injectable drugs. Among the 703 analysed strains, 12.8% were MDR; Ser531Leu and Ser315Thr being the most common recorded mutations within rpoB and katG genes associated with RIF and INH resistance respectively. Drug susceptibility testing for second line drugs showed that among the 90 MDR strains, 22.2% (20/90) were resistant to OFX, 2.22% (2/90) to KAN, 3.33% (3/90) to AMK and 1.11% (1/90) to CAP. Genotypic analysis revealed that 19 MDR strains harbored mutations in the gyrA gene; the most recorded mutation being Asp91Ala accounting for 47.6% (10

  15. Time from prior chemotherapy enhances prognostic risk grouping in the second-line setting of advanced urothelial carcinoma: a retrospective analysis of pooled, prospective phase 2 trials.

    Science.gov (United States)

    Sonpavde, Guru; Pond, Gregory R; Fougeray, Ronan; Choueiri, Toni K; Qu, Angela Q; Vaughn, David J; Niegisch, Guenter; Albers, Peter; James, Nicholas D; Wong, Yu-Ning; Ko, Yoo-Joung; Sridhar, Srikala S; Galsky, Matthew D; Petrylak, Daniel P; Vaishampayan, Ulka N; Khan, Awais; Vogelzang, Nicholas J; Beer, Tomasz M; Stadler, Walter M; O'Donnell, Peter H; Sternberg, Cora N; Rosenberg, Jonathan E; Bellmunt, Joaquim

    2013-04-01

    Outcomes for patients in the second-line setting of advanced urothelial carcinoma (UC) are dismal. The recognized prognostic factors in this context are Eastern Cooperative Oncology Group (ECOG) performance status (PS) >0, hemoglobin level (Hb) 0, LM, Hb statistic=0.638). Setting of prior chemotherapy (metastatic disease vs perioperative) and prior platinum agent (cisplatin or carboplatin) were not prognostic factors. External validation demonstrated a significant association of TFPC with PFS on univariable and most multivariable analyses, and with OS on univariable analyses. Limitations of retrospective analyses are applicable. Shorter TFPC enhances prognostic classification independent of ECOG-PS >0, Hb advanced UC. These data may facilitate drug development and interpretation of trials. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  16. Should CA-125 response criteria be preferred to response evaluation criteria in solid tumors (RECIST) for prognostication during second-line chemotherapy of ovarian carcinoma?

    DEFF Research Database (Denmark)

    Gronlund, Bo; Høgdall, Claus; Hilden, Jørgen

    2004-01-01

    -line chemotherapy. PATIENTS AND METHODS: From a single-institution registry of 527 consecutive patients with primary ovarian carcinoma, 131 records satisfied the inclusion criteria: ovarian carcinoma of International Federation of Gynecology and Obstetrics stage IC to IV, first-line chemotherapy with paclitaxel...... and a platinum compound, refractory or recurrent disease, and second-line chemotherapy consisting of topotecan or paclitaxel plus carboplatin. Univariate and multivariate analyses of survival were performed using the landmark method. RESULTS: In patients with measurable disease by RECIST and with assessable...... sites (solitary v multiple; hazard ratio, 0.47; P = .020) were identified as contributory prognostic factors for survival, whereas the parameters of RECIST (responders v nonresponders), as well as the remaining variables, had nonsignificant prognostic impact. CONCLUSION: The GCIG CA-125 response...

  17. 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.

    Science.gov (United States)

    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

    2012-06-01

    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 countries and predicted their impact on second-line drug susceptibility. A total of 2588 antiretroviral-naive individuals initiated ART consisting of different nucleoside reverse transcriptase inhibitor (NRTI) backbones (zidovudine, stavudine, tenofovir, or abacavir, plus lamivudine or emtricitabine) with either efavirenz or nevirapine. Population sequencing after 12 months of ART was retrospectively performed if HIV RNA was >1000 copies/mL. The 2010 International Antiviral Society-USA list was used to score major DRMs. The Stanford algorithm was used to predict drug susceptibility. HIV-1 sequences were generated for 142 participants who virologically failed ART, of whom 70% carried ≥1 DRM and 49% had dual-class resistance, with an average of 2.4 DRMs per sequence (range, 1-8). The most common DRMs were M184V (53.5%), K103N (28.9%), Y181C (15.5%), and G190A (14.1%). Thymidine analogue mutations were present in 8.5%. K65R was frequently selected by stavudine (15.0%) or tenofovir (27.7%). Among participants with ≥1 DRM, HIV-1 susceptibility was reduced in 93% for efavirenz/nevirapine, in 81% for lamivudine/emtricitabine, in 59% for etravirine/rilpivirine, in 27% for tenofovir, in 18% for stavudine, and in 10% for zidovudine. Early failure detection limited the accumulation of resistance. After stavudine failure in African populations, zidovudine rather than tenofovir may be preferred in second-line ART. Strategies to prevent HIV-1 resistance are a global priority.

  18. Deep Brain Stimulation Salvages a Flourishing Dental Practice: A Dentist with Essential Tremor Recounts his Experience.

    Science.gov (United States)

    Giacopuzzi, Guy; Lising, Melanie; Halpern, Casey H

    2016-10-22

    In recounting his experience with deep brain stimulation (DBS), a practicing dentist challenged with long-standing bilateral essential tremor of the hands shares insights into his diagnosis, treatments, and ultimately successful DBS surgery at Stanford University Medical Center, CA, USA. Now nearly one year after his surgery, his practice continues to flourish and he encourages others in his profession to consider the possibility of DBS as a definitive treatment for tremors of the hand, which may salvage their practice.

  19. Clinical results of salvage surgery in hypopharynx carcinoma after chemoradiotherapy

    International Nuclear Information System (INIS)

    Mitani, Hiroki; Gakibuchi, Masao; Asano, Takayuki; Sakurai, Hiroyuki; Kurita, Tomoyuki; Inoue, Youjiro

    2008-01-01

    The incidence of post-operative complications and treatment results of 60 cases of hypopharynx carcinoma receiving laryngo-pharyngo-esophagectomy followed by reconstruction with jejunum after chemoradiotherapy (CRT) from 1997 to 2006 in 6 hospitals was analyzed. The overall complication rate was 57%. There were 3 cases with carotid artery rupture (5%), 4 with jejunum necrosis (6%), 6 with major salivary fistula (10%), 8 with minor salivary fistula (13%), 8 with abscess alone (13%), 3 with trachea stoma necrosis (5%), and 3 with skin flap necrosis (5%). The death rate due to surgical complications was 3% (2/60). When the cases were divided into two groups, namely the cases with fistula and the cases without fistula, the number of days that permitted drinking was 18.1 in the latter and 81.8 in the former. The 5-year overall survival rate among all cases was 37%. We found that salvage surgery after CRT was effective for recurrent cases. These findings suggest that reconstruction with jejunum is a suitable type of operation with better surgical results. Care is required to reduce the incidence of post-operative complications. (author)

  20. Evaluation of ifosfamide salvage therapy for metastatic canine osteosarcoma.

    Science.gov (United States)

    Batschinski, K; Dervisis, N G; Kitchell, B E

    2014-12-01

    A retrospective study was performed to assess toxicity and response rate of ifosfamide salvage treatment for dogs diagnosed with metastatic osteosarcoma (OSA). Dogs diagnosed with OSA and previously treated with standard chemotherapy were included in the study. Nineteen dogs met the inclusion criteria, and 17 dogs were evaluable for response. Ifosfamide doses ranged from 375 to 425 mg m(-2) (median dose 375 mg m(-2)), with a median of two doses administered per dog (range 1-7 doses). The overall response to ifosfamide was 11.8% [complete response (CR) = 1/17, partial response (PR) = 1/17, stable disease (SD) = 2/17, progressive disease (PD) = 13/17]. Two dogs were hospitalized due to ifosfamide toxicosis. The median survival duration from the first dose of ifosfamide to death was 95 days. Ifosfamide was well tolerated, but minor anti-tumour activity was observed. © 2012 Blackwell Publishing Ltd.

  1. Salvage surgery for hypopharyngeal carcinoma and cervical esophageal carcinoma with local recurrence or residual tumor after chemoradiotherapy

    International Nuclear Information System (INIS)

    Takemura, Hirokazu; Hayashi, Ryuichi; Yamazaki, Mitsuo

    2008-01-01

    In this study, we present the treatment results of salvage surgery in 34 patients with residual primary tumor or local relapse tumor in the hypopharynx and cervical esophagus after radiotherapy (15 patients) or chemoradiotherapy (19 patients) at the Division of Head and Neck Surgery, National Cancer Center Hospital East between 1997 and 2006. All patients underwent total pharyngolaryngoesophagectomy (TPLE) as salvage surgery. Among these patients, postoperative complication was observed in 11 patients (32.4%). Fisher's exact test revealed no significant difference in postoperative complication rate between the radiotherapy (RT) group and chemoradiotherapy (CRT) group. Tumors in the neck recurred in 10 patients (55.6%) after surgical resection. The tumor recurrence control rate for cervical lymph nodes was 84.7% for patients with clinically N0 disease after CRT who had not undergone neck dissection. The median survival time was 392 days. We consider that salvage surgery can he safely performed by considering the necessity and method of operation, and the outcome of patients receiving CRT would he improved by salvage surgery. (author)

  2. Seminal vesicle involvement at salvage radical prostatectomy.

    Science.gov (United States)

    Meeks, Joshua J; Walker, Marc; Bernstein, Melanie; Eastham, James A

    2013-06-01

    To describe the incidence and clinical outcomes of seminal vesicle invasion (SVI) at salvage radical prostatectomy (SRP) and to describe the accuracy of SV biopsy. As SRP is used after biochemical recurrence (BCR) of prostate cancer after radiotherapy (RT) to gain local oncological control. The SVs receive lower doses of radiation from external-beam RT (EBRT) to avoid rectal exposure and are not targeted with brachytherapy (BT) with low-risk prostate cancer. SRP was performed on 206 men with BCR after RT at a tertiary care institution between 1998 and 2011. Post-RT biopsy and SRP specimens were reviewed by a genitourinary pathologist. SVI was detected in 65 (32%) of 206 patients. No difference was found between EBRT alone (65% vs 63%) and BT (29% vs 31%) with or without EBRT in patients with SVI. Men with SVI had higher rates of cT3 disease (20% vs 8%) and Gleason score ≥ 8 at SRP (52% vs 21%). BCR-free survival at 5 years was 18% and 56% in patients with and without SVI (hazard ratio 2.85, 95% confidence interval 1.87-4.36, P < 0.001), yet the rate of local recurrence was low (11%). Prostate cancer was identified in nine of 18 patients who underwent SV biopsy and was the only location of prostate cancer in two patients. SVI is a prognostic indicator for BCR after SRP, but local recurrence in patients with SVI after SRP remains low. We recommend SV biopsy to improve staging and cancer detection in men with BCR after radiotherapy. © 2013 BJU International.

  3. Coupled Responses of Sewol, Twin Barges and Slings During Salvage

    Science.gov (United States)

    Yao, Zong; Wang, Wei-ping; Jiang, Yan; Chen, Shi-hai

    2018-04-01

    Korean Sewol is successfully lifted up with the strand jack system based on twin barges. During the salvage operation, two barges and Sewol encounter offshore environmental conditions of wave, current and wind. It is inevitable that the relative motions among the three bodies are coupled with the sling tensions, which may cause big dynamic loads for the lifting system. During the project engineering phase and the site operation, it is necessary to build up a simulation model that can precisely generate the coupled responses in order to define a suitable weather window and monitor risks for the salvage operation. A special method for calculating multibody coupled responses is introduced into Sewol salvage project. Each body's hydrodynamic force and moment in multibody configuration is calculated in the way that one body is treated as freely moving in space, while other bodies are set as fixed globally. The hydrodynamic force and moment are then applied into a numerical simulation model with some calibration coefficients being inserted. These coefficients are calibrated with the model test results. The simulation model built up this way can predict coupled responses with the similar accuracy as the model test and full scale measurement, and particularly generate multibody shielding effects. Site measured responses and the responses only resulted from from the simulation keep project management simultaneously to judge risks of each salvage stage, which are important for success of Sewol salvage.

  4. Economic evaluation of nivolumab for the treatment of second-line advanced squamous NSCLC in Canada: a comparison of modeling approaches to estimate and extrapolate survival outcomes.

    Science.gov (United States)

    Goeree, Ron; Villeneuve, Julie; Goeree, Jeff; Penrod, John R; Orsini, Lucinda; Tahami Monfared, Amir Abbas

    2016-06-01

    Background Lung cancer is the most common type of cancer in the world and is associated with significant mortality. Nivolumab demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients with advanced squamous non-small cell lung cancer (NSCLC) who were previously treated. The cost-effectiveness of nivolumab has not been assessed in Canada. A contentious component of projecting long-term cost and outcomes in cancer relates to the modeling approach adopted, with the two most common approaches being partitioned survival (PS) and Markov models. The objectives of this analysis were to estimate the cost-utility of nivolumab and to compare the results using these alternative modeling approaches. Methods Both PS and Markov models were developed using docetaxel and erlotinib as comparators. A three-health state model was used consisting of progression-free, progressed disease, and death. Disease progression and time to progression were estimated by identifying best-fitting survival curves from the clinical trial data for PFS and OS. Expected costs and health outcomes were calculated by combining health-state occupancy with medical resource use and quality-of-life assigned to each of the three health states. The health outcomes included in the model were survival and quality-adjusted-life-years (QALYs). Results Nivolumab was found to have the highest expected per-patient cost, but also improved per-patient life years (LYs) and QALYs. Nivolumab cost an additional $151,560 and $140,601 per QALY gained compared to docetaxel and erlotinib, respectively, using a PS model approach. The cost-utility estimates using a Markov model were very similar ($152,229 and $141,838, respectively, per QALY gained). Conclusions Nivolumab was found to involve a trade-off between improved patient survival and QALYs, and increased cost. It was found that the use of a PS or Markov model produced very similar estimates of expected cost, outcomes, and incremental cost-utility.

  5. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer

    NARCIS (Netherlands)

    Peeters, Marc; Price, Timothy Jay; Cervantes, Andrés; Sobrero, Alberto F.; Ducreux, Michel; Hotko, Yevhen; André, Thierry; Chan, Emily; Lordick, Florian; Punt, Cornelis J. A.; Strickland, Andrew H.; Wilson, Gregory; Ciuleanu, Tudor-Eliade; Roman, Laslo; van Cutsem, Eric; Tzekova, Valentina; Collins, Simon; Oliner, Kelly S.; Rong, Alan; Gansert, Jennifer

    2010-01-01

    Panitumumab is a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody that improves progression-free survival (PFS) in chemotherapy-refractory metastatic colorectal cancer (mCRC). This trial evaluated the efficacy and safety of panitumumab plus fluorouracil, leucovorin, and

  6. Comparison of Alternative Androgen Receptor-axis-targeted Agent (ARATA) and Docetaxel as Second-line Therapy for Patients With Metastatic Castration-resistant Prostate Cancer With Progression After Initial ARATA in Real-world Clinical Practice in Japan.

    Science.gov (United States)

    Miyake, Hideaki; Sugiyama, Takayuki; Aki, Ryota; Matsushita, Yuto; Tamura, Keita; Motoyama, Daisuke; Ito, Toshiki; Otsuka, Atsushi

    2018-06-01

    The objective of the present study was to assess the oncologic outcomes of patients receiving second-line therapy against metastatic castration-resistant prostate cancer (mCRPC). The present study included 222 consecutive mCRPC patients with progression during initial androgen receptor-axis-targeted agent (ARATA) therapy with either abiraterone acetate (AA) or enzalutamide (Enz). Of these 222 patients, 108 subsequently received an alternative ARATA (AA-to-Enz, n = 49; Enz-to-AA, n = 59) and 114 received docetaxel (DTX; AA-to-DTX, n = 54; Enz-to-DTX, n = 60). The prostate-specific antigen (PSA) level in the 114 patients receiving DTX was significantly greater than that in the 108 patients receiving ARATA. However, no significant differences were found in the remaining parameters between the 2 groups. The PSA response rate, PSA progression-free survival (PFS), and overall survival (OS) during second-line therapy in the DTX group (n = 114) were significantly superior to those for the ARATA group (n = 108; PSA response rate, 42.1% vs. 21.3%; median PSA PFS, 7.2 vs. 4.2 months; median OS, 17.5 vs. 14.5 months). Similar trends were confirmed by comparing these outcomes among 4 therapy groups, with significant differences (PSA response rate, Enz-to-AA vs. AA-to-DTX and Enz-to-AA vs. Enz-to-DTX; PSA PFS, AA-to-Enz vs. Enz-to-AA, AA-to-Enz vs. AA-to-DTX, Enz-to-AA vs. AA-to-DTX, and Enz-to-AA vs. Enz-to-DTX; and OS, Enz-to-AA vs. AA-to-DTX and Enz-to-AA vs. Enz-to-DTX). Furthermore, the introduction of DTX was independently associated with improved PSA PFS, but not OS, on multivariate analysis. Favorable oncologic outcomes can be expected with DTX treatment, rather than with alternative ARATA, for mCRPC patients after failure of an initial ARATA. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Salvage brachytherapy for local recurrences of prostate cancer treated previously with radiotherapy.

    Science.gov (United States)

    Gawkowska-Suwinska, Marzena; Fijałkowski, Marek; Białas, Brygida; Szlag, Marta; Kellas-Ślęczka, Sylwia; Nowicka, Elżbieta; Behrendt, Katarzyna; Plewicki, Grzegorz; Smolska-Ciszewska, Beata; Giglok, Monika; Zajusz, Aleksander; Owczarek, Grzegorz

    2009-12-01

    The aim of the study was to analyze early effects and toxicity of salvage high dose rate brachytherapy for local recurrences of adenocarcinoma of the prostate after external beam radiotherapy (EBRT). In MCS Memorial Institute of Oncology in Gliwice a research programme on salvage HDR brachytherapy for local recurrences of prostate cancer treated previously with EBRT has been ongoing since February 2008. The treatment consisted of 3 fractions of 10 Gy each given every 14 days. Maximal urethral doses were constrained to be ≤ 120% of the prescribed dose. Maximal bladder and rectum doses were constrained to be ≤ 70% of the prescribed dose. Fifteen eligible patients were treated and analyzed from February 2008. All patients completed the treatment without major complications. The most common early complications were: macroscopic haematuria, pain in lower part of the abdomen, and transient dysuria. During the first week after the procedure a transient increase in IPSS score was noticed. The Foley catheter was removed on day 2 to 5. No complications after spinal anaesthesia were observed. Acute toxicity according to EORTC/RTOG was low. For bladder EORTC/RTOG score ranged from 0 to 2. Only in two patients grade 1 toxicity for rectum was observed. The follow-up ranged from 3 to 9 months. In one patient grade 2 rectal toxicity was observed, and one had urethral stricture. Other patients did not have any other significant late toxicity of the treatment. Two patients developed bone metastases. Salvage brachytherapy for localized prostate cancer (3 × 10 Gy every 14 days) seems to be a safe and well tolerated procedure. A significant decline in prostate-specific antigen (PSA) level is seen in patients with hormone-responsive cancer. Long-term efficiency and toxicity of the procedure are yet to be established.

  8. Time interval between primary radiotherapy and salvage laryngectomy: a predictor of pharyngocutaneous fistula formation.

    Science.gov (United States)

    Scotton, William J; Nixon, I J; Pezier, T F; Cobb, R; Joshi, A; Urbano, T Guerrero; Oakley, R; Jeannon, J P; Simo, R S

    2014-08-01

    Salvage laryngectomy (SL) is associated with high levels of morbidity. Rates of pharyngocutaneous fistulae (PCF) are as high as 35 % in some series. Patients at highest risk of such complications may be candidates for altered surgical management in terms of additional tissue transfer, or delayed tracheoesophageal puncture. This study investigates the relationship between the time from primary radiotherapy (RT) to salvage surgery and the development of PCF. 26 consecutive patients who underwent SL between 2000 and 2010 were identified from our institutional database. Demographic, staging, treatment and complication data were collected. Subgroup analysis was performed using the Student's t test or Mann-Whitney U test for continuous variables and either Chi-squared test or Fisher's Exact test for categorical variables. 26 patients underwent SL between October 2003 and July 2010. Of these, 15 (58 %) developed a PCF. On analysis of the time between pre-operative RT and surgery, a significant difference was seen, with a mean time of 19.5 months in those who developed a PCF versus 47.0 months in those who did not (p = 0.02). Patient characteristics, treatment, and pathology results were comparable between the two groups. There was no significant difference in distribution of the other covariates between the PCF and non-PCF groups. We reported a high rate of PCF and identified an association between PCF and a short time from primary treatment to salvage surgery. Identifying factors associated with higher rates of post-operative morbidity allows surgeons to adapt surgical planning in an attempt to minimize rates of PCF.

  9. Bacterial reduction by cell salvage washing and leukocyte depletion filtration.

    Science.gov (United States)

    Waters, Jonathan H; Tuohy, Marion J; Hobson, Donna F; Procop, Gary

    2003-09-01

    Blood conservation techniques are being increasingly used because of the increased cost and lack of availability of allogeneic blood. Cell salvage offers great blood savings opportunities but is thought to be contraindicated in a number of areas (e.g., blood contaminated with bacteria). Several outcome studies have suggested the safety of this technique in trauma and colorectal surgery, but many practitioners are still hesitant to apply cell salvage in the face of frank bacterial contamination. This study was undertaken to assess the efficacy of bacterial removal when cell salvage was combined with leukocyte depletion filtration. Expired packed erythrocytes were obtained and inoculated with a fixed amount of a stock bacteria (Escherichia coli American Type Culture Collections [ATCC] 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213, or Bacteroides fragilis ATCC 25285) in amounts ranging from 2,000 to 4,000 colony forming units/ml. The blood was processed via a cell salvage machine. The washed blood was then filtered using a leukocyte reduction filter. The results for blood taken during each step of processing were compared using a repeated-measures design. Fifteen units of blood were contaminated with each of the stock bacteria. From the prewash sample to the postfiltration sample, 99.0%, 99.6%, 100%, and 97.6% of E. coli, S. aureus, P. aeruginosa, and B. fragilis were removed, respectively. Significant but not complete removal of contaminating bacteria was seen. An increased level of patient safety may be added to cell salvage by including a leukocyte depletion filter when salvaging blood that might be grossly contaminated with bacteria.

  10. Prospective study of cyclophosphamide, thiotepa, carboplatin combined with adoptive DC-CIK followed by metronomic cyclophosphamide therapy as salvage treatment for triple negative metastatic breast cancers patients (aged <45).

    Science.gov (United States)

    Wang, X; Ren, J; Zhang, J; Yan, Y; Jiang, N; Yu, J; Di, L; Song, G; Che, L; Jia, J; Zhou, X; Yang, H; Lyerly, H K

    2016-01-01

    The recent immunotherapy treatment on triple-negative breast cancer (TNBC) leads to the breakthrough assignation. In this study, we have tried the new combinations of specific chemo with DC-CIKs immunotherapy to treat those patients. Twenty-three metastatic anthracyclines and taxanes pretreated TNBC younger (mean 41.5 years) patients were initially mobilized with cyclophosphamide (3 g/m(2)) for the preparation of CD34(+) peripheral blood mononuclear cells as the resources for generating DC/CIKs and marrow function supports. All cases were subsequently experienced 2 cycles of chemotherapy with cyclophosphamide 3 g/m(2), thiotepa 150 mg/m(2), and carboplatin AUC = 6, Q4w. The patients then received 3 infusions of DC-CIKs at the chemo intervals and followed by maintenance therapy with oral cyclophosphamide 50 mg daily. The endpoints were progression-free survival and overall survival. The partial response rate was 13.0 %, stable and progressive disease rates were 56.5 and 30.4 %, respectively. The median PFS was 13.5 months (95 % confidence interval (CI) 10.1-16.9 months) and OS was 15.2 months (95 % CI 12.5-18.1 months). The most common serious adverse events were neutropenia (100.0 %) and anemia (69.7 %) but without treatment-related mortality. These data suggested that such combination therapy model be effective and safe for younger metastatic TNBC exposure to previous anthracyclines and taxanes based adjuvant chemotherapy.

  11. Post-fire salvage logging reduces carbon sequestration in Mediterranean coniferous forest

    OpenAIRE

    Serrano-Ortiz, P.; Marañón-Jiménez, S.; Reverter, B.R.; Sánchez-Cañete, E.P.; Castro, J.; Zamora, R.; Kowalski, A.S.

    2011-01-01

    Post-fire salvage logging is a common silvicultural practice around the world, with the potential to alter the regenerative capacity of an ecosystem and thus its role as a source or a sink of carbon. However, there is no information on the effect of burnt wood management on the net ecosystem carbon balance. Here, we examine for the first time the effect of post-fire burnt wood management on the net ecosystem carbon balance by comparing the carbon exchange of two treatments in a burnt Mediterr...

  12. Efficacy of Second-line Targeted Therapy for Renal Cell Carcinoma According to Change from Baseline in International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Category

    DEFF Research Database (Denmark)

    Davis, Ian D; Xie, Wanling; Pezaro, Carmel

    2017-01-01

    BACKGROUND: We hypothesized that changes in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic category at start of second-line therapy (2L) for metastatic renal cell carcinoma (mRCC) might predict response. OBJECTIVE: To assess outcomes of 2L according to type...... of therapy and change in IMDC prognostic category. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review of the IMDC database for mRCC patients who received first-line (1L) VEGF inhibitors (VEGFi) and then 2L with VEGFi or mTOR inhibitors (mTORi). IMDC prognostic categories were defined......% confidence interval [CI] 12.0-19.0 for VEGFi; 20.2 mo, 95% CI 14.3-26.1 for mTORi; AHR 1.53, 95% CI 1.04-2.24; adjusted p=0.03). CONCLUSIONS: Changes in IMDC prognostic category predict the subsequent clinical course for patients with mRCC and provide a rational basis for selection of subsequent therapy...

  13. A pilot study to assess feasibility of value based pricing in Cyprus through pharmacoeconomic modelling and assessment of its operational framework: sorafenib for second line renal cell cancer.

    Science.gov (United States)

    Petrou, Panagiotis; Talias, Michael A

    2014-01-01

    The continuing increase of pharmaceutical expenditure calls for new approaches to pricing and reimbursement of pharmaceuticals. Value based pricing of pharmaceuticals is emerging as a useful tool and possess theoretical attributes to help health system cope with rising pharmaceutical expenditure. To assess the feasibility of introducing a value-based pricing scheme of pharmaceuticals in Cyprus and explore the integrative framework. A probabilistic Markov chain Monte Carlo model was created to simulate progression of advanced renal cell cancer for comparison of sorafenib to standard best supportive care. Literature review was performed and efficacy data were transferred from a published landmark trial, while official pricelists and clinical guidelines from Cyprus Ministry of Health were utilised for cost calculation. Based on proposed willingness to pay threshold the maximum price of sorafenib for the indication of second line renal cell cancer was assessed. Sorafenib value based price was found to be significantly lower compared to its current reference price. Feasibility of Value Based Pricing is documented and pharmacoeconomic modelling can lead to robust results. Integration of value and affordability in the price are its main advantages which have to be weighed against lack of documentation for several theoretical parameters that influence outcome. Smaller countries such as Cyprus may experience adversities in establishing and sustaining essential structures for this scheme.

  14. 78 FR 74128 - Proposed CERCLA Administrative Cost Recovery Settlement; Cadie Auto Salvage Site, Belvidere...

    Science.gov (United States)

    2013-12-10

    ... Recovery Settlement; Cadie Auto Salvage Site, Belvidere, Boone County, Illinois AGENCY: Environmental... Auto Salvage Site in Belvidere, Boone County, Illinois with the following settling parties: UOP, LLC... Cadie Auto Salvage Site, Belvidere, Boone County, Illinois and EPA Docket No. and should be addressed to...

  15. 78 FR 77673 - Proposed CERCLA Administrative Cost Recovery Settlement; Cadie Auto Salvage Site, Belvidere...

    Science.gov (United States)

    2013-12-24

    ... Recovery Settlement; Cadie Auto Salvage Site, Belvidere, Boone County, Illinois AGENCY: Environmental... Auto Salvage Site in Belvidere, Boone County, Illinois with the following settling party: Helen E... reference the Cadie Auto Salvage Site, Belvidere, Boone County, Illinois and EPA Docket No. and should be...

  16. Salvage therapies in relapsed and/or refractory myeloma: what is current and what is the future?

    Directory of Open Access Journals (Sweden)

    Thumallapally N

    2016-08-01

    Full Text Available Nishitha Thumallapally,1 Hana Yu,1 Divya Asti,1 Adarsh Vennepureddy,1 Terenig Terjanian2 1Department of Internal Medicine, 2Division of Hematology and Oncology, Staten Island University Hospital, New York, NY, USA Abstract: The treatment landscape for multiple myeloma (MM is evolving with our understanding of its pathophysiology. However, given the inevitable cohort heterogeneity in salvage therapy, response to treatment and overall prognoses tend to vary widely, making meaningful conclusions about treatment efficacy difficult to derive. Despite the hurdles in current research, progress is underway toward more targeted therapeutic approaches. Several new drugs with novel mechanism of action and less toxic profile have been developed in the past decade, with the potential for use as single agents or in synergy with other treatment modalities in MM therapy. As our discovery of these emerging therapies progresses, so too does our need to reshape our knowledge on knowing how to apply them. This review highlights some of the recent landmark changes in MM management with specific emphasis on salvage drugs available for relapsed and refractory MM and also discusses some of the upcoming cutting-edge therapies that are currently in various stages of clinical development. Keywords: multiple myeloma, novel drugs, relapsed and refractory myeloma, salvage chemotherapy 

  17. Outcome analysis of salvage radiotherapy for occult cervical cancer found after simple hysterectomy

    International Nuclear Information System (INIS)

    Koh, Hyeon-Kang; Jeon, Wan; Kim, Hak-Jae; Wu, Hong-Gyun; Kim, Kyubo; Chie, Eui-Kyu; Ha, Sung-W.

    2013-01-01

    The objective was to analyze the outcomes of the patients, who received salvage radiotherapy for incidentally discovered cervical cancer following simple hysterectomy, and to identify the influence of intracavitary radiotherapy on treatment outcomes. Data from 117 patients with occult cervical cancer who underwent simple hysterectomy followed by salvage radiotherapy from September 1979 to November 2010 were collected. All the patients received external beam radiotherapy with (n=45) or without (n=72) intracavitary radiotherapy. Local control, disease-free survival, overall survival and treatment-related toxicity were investigated. The median follow-up time was 75 months. The 5- and 10-year local control/disease-free survival/overall survival rates were 93/87/87% and 90/84/83%, respectively. Among 98 patients who had no residual disease and negative resection margin on surgical specimens, 32 (33%) received intracavitary radiotherapy and 66 (67%) did not. There were no differences in patient and tumor characteristics between patients treated with and without intracavitary radiotherapy. The 5-year local control rate for the non-intracavitary radiotherapy group was 93 versus 94% for the intracavitary radiotherapy group (P=0.564); the disease-free survival rate was 88 versus 94% (P=0.894); the overall survival rate was 95 versus 85% (P=0.106), respectively. Among all patients, there were 5% of Grade 3 or higher late toxicities. Patients with occult invasive cervical cancer discovered following simple hysterectomy could be treated safely and effectively with salvage radiotherapy. For patients with no residual disease and negative resection margin, intracavitary radiotherapy could be omitted. (author)

  18. Phase I/II trial of dendritic cell-based active cellular immunotherapy with DCVAC/PCa in patients with rising PSA after primary prostatectomy or salvage radiotherapy for the treatment of prostate cancer.

    Science.gov (United States)

    Fucikova, Jitka; Podrazil, Michal; Jarolim, Ladislav; Bilkova, Pavla; Hensler, Michal; Becht, Etienne; Gasova, Zdenka; Klouckova, Jana; Kayserova, Jana; Horvath, Rudolf; Fialova, Anna; Vavrova, Katerina; Sochorova, Klara; Rozkova, Daniela; Spisek, Radek; Bartunkova, Jirina

    2018-01-01

    Immunotherapy of cancer has the potential to be effective mostly in patients with a low tumour burden. Rising PSA (prostate-specific antigen) levels in patients with prostate cancer represents such a situation. We performed the present clinical study with dendritic cell (DC)-based immunotherapy in this patient population. The single-arm phase I/II trial registered as EudraCT 2009-017259-91 involved 27 patients with rising PSA levels. The study medication consisted of autologous DCs pulsed with the killed LNCaP cell line (DCVAC/PCa). Twelve patients with a favourable PSA response continued with the second cycle of immunotherapy. The primary and secondary objectives of the study were to assess the safety and determine the PSA doubling time (PSADT), respectively. No significant side effects were recorded. The median PSADT in all treated patients increased from 5.67 months prior to immunotherapy to 18.85 months after 12 doses (p PSA-reacting T lymphocytes were increased significantly already after the fourth dose, and a stable frequency was detected throughout the remainder of DCVAC/PCa treatment. Long-term immunotherapy of prostate cancer patients experiencing early signs of PSA recurrence using DCVAC/PCa was safe, induced an immune response and led to the significant prolongation of PSADT. Long-term follow-up may show whether the changes in PSADT might improve the clinical outcome in patients with biochemical recurrence of the prostate cancer.

  19. Advantages and disadvantages of using intravenous tissue Plasminogen activator as salvage therapy for inoperable HeartWare thrombosis.

    Science.gov (United States)

    Basken, Robyn; Bazzell, Charles M; Smith, Richard; Janardhanan, Rajesh; Khalpey, Zain

    2017-07-01

    Device thrombosis is a devastating complication of left ventricular assist devices. The definitive treatment has been device exchange or explant. Evidence of increasing morbidity and mortality with device exchange has shifted strategies toward conservative management. In this report, we detail the use of thrombolytics as salvage therapy in a patient with an occlusive HeartWare ventricular assist device (HeartWare Inc., Framingham, MA) thrombus, resulting in long-term survival without further intervention. © 2017 Wiley Periodicals, Inc.

  20. Posterior transpedicular approach with circumferential debridement and anterior reconstruction as a salvage procedure for symptomatic failed vertebroplasty

    OpenAIRE

    Chiu, Yen-Chun; Yang, Shih-Chieh; Chen, Hung-Shu; Kao, Yu-Hsien; Tu, Yuan-Kun

    2015-01-01

    Background Complications and failure of vertebroplasty, such as cement dislodgement, cement leakage, or spinal infection, usually result in spinal instability and neural element compression. Combined anterior and posterior approaches are the most common salvage procedure for symptomatic failed vertebroplasty. The purpose of this study is to evaluate the feasibility and efficacy of a single posterior approach technique for the treatment of patients with symptomatic failed vertebroplasty. Metho...

  1. Ipsilateral breast tumor recurrence after breast conservation therapy: Outcomes of salvage mastectomy vs. salvage breast-conserving surgery and prognostic factors for salvage breast preservation

    International Nuclear Information System (INIS)

    Alpert, Tracy E.; Kuerer, Henry M.; Arthur, Douglas W.; Lannin, Donald R.; Haffty, Bruce G.

    2005-01-01

    Purpose: To compare outcomes of salvage mastectomy (SM) and salvage breast-conserving surgery (SBCS) and study the feasibility of SBCS. Methods and Materials: Of 2,038 patients treated with breast-conserving therapy at Yale-New Haven Hospital before 1999, 166 sustained an ipsilateral breast tumor recurrence (IBTR). Outcomes and prognostic factors of patients treated with SM or SBCS were compared. Patients were considered amenable to SBCS if the recurrence was localized on mammogram and physical examination, and had pathologic size <3 cm, confined to the biopsy site, without skin or lymphovascular invasion, and with ≤3 positive nodes. Results: Of the 146 patients definitively managed at IBTR, surgery was SM (n = 116) or SBCS (n 30). The median length of follow-up after IBTR was 13.8 years. The SM and SBCS cohorts had no significant differences, except at IBTR the SM cohort had a greater tumor size (p = 0.049). Of the SM cohort, 65.5% were considered appropriate for SBCS, and a localized relapse was predicted by estrogen-receptor positive, diploid, and detection of recurrence by mammogram. Multicentric disease correlated with BRCA1/2 mutation, estrogen-receptor negative, lymph node positive at relapse, and detection of recurrence by physical examination. Survival after IBTR was 64.5% at 10 years, with no significant difference between SM (65.7%) and SBCS (58.0%). Only 2 patients in the SBCS cohort subsequently had a second IBTR, and were salvaged with mastectomy. Conclusions: While mastectomy is considered the standard surgical salvage of IBTR, SBCS is feasible and prognostic factors are related to favorable tumor biology and early detection. Patients with BRCA1/2 germline mutations may be less appropriate for SBCS, as multicentric disease was more prevalent. Patients who underwent SBCS had comparable outcomes as those who underwent SM, but remain at continued risk for IBTR. A prospective trial evaluating repeat lumpectomy and partial breast reirradiation is

  2. Outcome and renal function following salvage surgery for bilateral ...

    African Journals Online (AJOL)

    Objective: The aim of this study was to determine the surgical outcomes and renal function following salvage surgery for bilateral Wilms tumor (BWT). Summary background data The challenge for the surgeon treating BWT lies in striking a fine balance between renal preservation and oncological clearance. Methods: This is ...

  3. Dismal salvage of testicular torsion: A call to action! | Maranya ...

    African Journals Online (AJOL)

    ... were not subjected to orchidopexy. There was no occurrence of torsion after orchidopexy. Conclusion: Testicular torsions were associated with low salvage rates. Increased public awareness coupled with clinician, parental, teacher, teenage and adult male education with respect to the consequences of acute scrotal pain ...

  4. Reconstitution of an efficient thymidine salvage pathway in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Vernis, L.; Piskur, Jure; Diffley, J.F.X.

    2003-01-01

    The budding yeast Saccharomyces cerevisiae is unable to incorporate exogenous nucleosides into DNA. We have made a number of improvements to existing strategies to reconstitute an efficient thymidine salvage pathway in yeast. We have constructed strains that express both a nucleoside kinase as well...

  5. Salvage radiation therapy following radical prostatectomy. A national Danish study

    DEFF Research Database (Denmark)

    Ervandian, Maria; Høyer, Morten; Petersen, Stine Elleberg

    2015-01-01

    BACKGROUND: The purpose of this observational cohort study was to evaluate the outcome and prognostic factors following salvage radiotherapy (SRT) in a consecutive national cohort. MATERIAL AND METHODS: Between 2006 and 2010, 259 patients received SRT in Denmark. Patient- and cancer-related chara...

  6. Modified Pectoralis Major Tendon Transfer for Reanimation of Elbow Flexion as a Salvage Procedure in Complete Brachial Plexus Injury: A Case Report

    Directory of Open Access Journals (Sweden)

    S Taran

    2013-03-01

    Full Text Available Traumatic brachial plexus injuries rarely recover spontaneously and if the window period for neurotisation has elapsed, the only option for restoration of function lies in a salvage procedure. Many such salvage procedures have been described in the literature with variable functional results. We report the case of a 16-year-old boy who presented after unsuccessful treatment for a complete brachial plexus injury; we performed a pectoralis major tendon transfer to attain elbow flexion. Postoperatively, the elbow was splinted with flexion at 100°. After 4 weeks of immobilization the splint was removed and the patient could actively flex his elbow from 30° to 100°.

  7. Effectiveness and tolerability of second-line therapy with vildagliptin vs. other oral agents in type 2 diabetes: A real-life worldwide observational study (EDGE)

    Science.gov (United States)

    Mathieu, C; Barnett, A H; Brath, H; Conget, I; de Castro, J J; Göke, R; Márquez Rodriguez, E; Nilsson, P M; Pagkalos, E; Penfornis, A; Schaper, NC; Wangnoo, S K; Kothny, W; Bader, G

    2013-01-01

    Aim Real-life studies are needed to confirm the clinical relevance of findings from randomised controlled trials (RCTs). This study aimed to assess the effectiveness and tolerability of vildagliptin add-on vs. other oral antihyperglycaemic drugs (OADs) added to OAD monotherapy in a real-life setting, and to explore the advantages and limitations of large-scale ‘pragmatic’ trials. Methods EDGE was a prospective, 1-year, worldwide, real-life observational study in which 2957 physicians reported on the effects of second-line OADs in 45,868 patients with T2DM not reaching glycaemic targets with monotherapy. Physicians could add any OAD, and patients entered either vildagliptin or (pooled) comparator cohort. The primary effectiveness and tolerability end-point (PEP) evaluated proportions of patients decreasing HbA1c > 0.3%, without hypoglycaemia, weight gain, peripheral oedema or gastrointestinal side effects. The most clinically relevant secondary end-point (SEP 3) was attainment of end-point HbA1c vildagliptin-based regimen. The adjusted odds ratio was 1.49 (95% CI: 1.42, 1.55; p vildagliptin-based combination and by 23% of those receiving comparator combinations. The adjusted odds ratio was 1.96 (95% CI: 1.85, 2.07; p vildagliptin and other OADs were consistent with previous data. Conclusion EDGE demonstrates that in a ‘real-life’ setting, vildagliptin as second OAD can lower HbA1c to target without well-recognised OAD side effects, more frequently than comparator OADs. In addition, EDGE illustrates that conducting large-scale, prospective, real-life studies poses challenges but yields valuable clinical information complementary to RCTs. PMID:23961850

  8. Psychosocial reactions to upper extremity limb salvage: A case series.

    Science.gov (United States)

    Sposato, Lindsay; Yancosek, Kathleen; Cancio, Jill

    2017-11-30

    Case series. A salvaged limb is one that has undergone a major traumatic injury, followed by repeated surgical attempts in order to avoid amputation. Psychological recovery for individuals with lower extremity limb salvage has been examined in a number of studies. However, psychosocial reactions for individuals with upper extremity (UE) limb salvage are understudied in the literature. The purpose of this study was to explore the process of psychosocial adaptation for 3 trauma cases after UE limb salvage. The Reactions to Impairment and Disability Inventory was used to assess psychosocial adaptation. Physical function outcomes (pain, range of motion, edema, sensation, and dexterity) are presented. The Disabilities of the Arm, Shoulder, and Hand measure was used to assess perceived disability. Medical and rehabilitation history are discussed for each case, in order to provide in-depth understanding of the impact of these injuries. Reactions to injury varied across the cases; however, outcomes suggest that psychosocial adaptation may be influenced by the experience of pain, the ability to participate in valued roles and activities, and having a supportive social network. For this population, therapists may consider emphasizing pain management, focusing on client-centered goals and interventions, and facilitating peer support. Providers should closely monitor patients for signs of poor adaptation, such as hand-hiding behaviors. This study is among the first to examine psychological outcomes for the UE limb salvage population. Future research would be beneficial to provide deeper understanding of the psychosocial challenges for these individuals. Copyright © 2017 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

  9. Surgical complications of salvage surgery following concurrent chemoradiotherapy for laryngeal cancer

    International Nuclear Information System (INIS)

    Furuta, Yasushi; Homma, Akihiro; Oridate, Nobuhiko

    2007-01-01

    Surgical complication rates of salvage laryngectomy after chemoradiotherapy (CRT) have been reported to be high. Wound complications after salvage laryngectomy following concurrent chemoradiotherapy (CCRT) were analyzed. Eighty-six patients who had undergone total laryngectomy for laryngeal cancer at Hokkaido University Hospital between 1990 and 2006 were divided into three groups according to preoperative treatments received: total laryngectomy (TL) group (n=35) without radiotherapy (RT) or CCRT, RT-TL group (n=17) with RT alone, CRT-TL group (n=34) with low-dose CCRT. Major wound complications were defined as major pharyngocutaneous fistulas which caused inpatient care for more than eight weeks or which were closed by surgery, bleeding that required surgical reintervention, and wound infection or skin necrosis that caused inpatient care for more than eight weeks. Minor complications were self-limited, managed with local wound care, and did not prolong inpatient care for more than eight weeks. We also analyzed wound complications of larynx preservation surgery after CCRT. Overall wound complications, both major and minor, were observed in 26% of the TL group, 35% of the RT-TL group, and 47% of the CRT-TL group. Major wound complications were observed in 11%, 18%, and 29%, respectively. A considerable but not statistically significant increase in the incidence of overall and major wound complications was observed between the TL and CRT-TL groups (p=0.082 and 0.078, respectively). Pharyngocutaneous fistulas were the most common complication, occurring in 14/86 (16%) of patients. Patients who developed pharyngocutaneous fistulas after CCRT tended to require surgical reintervention and longer periods before the initiation of oral intake. Wound complications were observed in 2/3 (67%) of patients who had undergone larynx preservation surgery. High incidences of wound complications and poor wound recovery in patients undergoing salvage laryngectomy following CCRT should

  10. Effectiveness and Morbidity Associated With Reirradiation in Conservative Salvage Management of Recurrent Soft-Tissue Sarcoma

    International Nuclear Information System (INIS)

    Indelicato, Daniel J.; Meadows, Kenyon; Gibbs, Charles P.; Morris, Christopher G.; Scarborough, Mark T.; Zlotecki, Robert A.

    2009-01-01

    Purpose: The management of isolated local recurrence of soft-tissue sarcoma is therapeutically complex, and functional conservative management is preferable to radical or amputative salvage surgery. This study reviews University of Florida experience using conservative resection and reirradiation to manage isolated local recurrences of soft-tissue sarcoma. Methods and Materials: Between 1976 and 2005, a total of 14 patients who underwent primary conservative resection and irradiation developed isolated local recurrence and were managed with salvage conservative resection and reirradiation. Of the patients treated, 3 had tumors of the distal extremity, 8 had tumors of the proximal extremity, and 3 had tumors of the trunk. At the time of recurrence, 64% of tumors were greater than 5 cm and 79% were high grade. In combination with gross total resection, 13 of 14 patients received external beam radiotherapy with or without brachytherapy, and 1 patient was treated with brachytherapy alone. Two patients received chemotherapy. Results: The median follow-up was 30 months, and no living patients were lost during follow-up. From retreatment, the 5-year actuarial overall survival, cause-specific survival, and local control rates were 40%, 40%, and 18% respectively. There was a 50% incidence of serious complication requiring either reoperation or leading to permanent functional impairment. Of the 14 patients, only 1 has remained disease free and without significant complications. No treatment factors, including achieving wide surgical margins or delivering higher radiation dosages, seemed to confer an advantage in local control. Conclusions: Salvage therapy for management of locally recurrent soft-tissue sarcoma is challenging, and the effects of reoperation and reirradiation can be severe

  11. Implant salvage in breast reconstruction with severe peri-prosthetic infection.

    Science.gov (United States)

    Meybodi, Farid; Sedaghat, Negin; French, James; Keighley, Caitlin; Mitchell, David; Elder, Elisabeth

    2017-12-01

    Although treatment of mild peri-prosthetic infection in implant-based breast reconstruction results in high rates of resolution, successful management of severe peri-prosthetic infection remains a significant challenge. In this case series, a protocol utilizing a novel dressing - negative pressure wound therapy with instillation (NPWTi) - for the management of severe peri-prosthetic infection in breast reconstruction patients is described. This is an operative technique involving: (i) explantation of the breast prosthesis and application of the NPWTi dressing to the implant pocket; (ii) change of the NPWTi dressing; (iii) intraoperative fluid/tissue cultures; and (iv) reimplantation of the breast prosthesis when cultures yield no growth. This protocol was utilized in six cases of severe peri-prosthetic infection in five patients with immediate breast reconstruction for breast cancer or risk-reducing surgery. Cultures of fluid/tissue grew typical and/or unusual organisms. Only one case did not yield an organism. The hospital length of stay upon completion of the protocol ranged from 7-16 days (mean, 12 days). Successful implant salvage was achieved in five of six cases. The protocol was aborted in one case to allow for completion of adjuvant chemotherapy. Early findings from this case series suggest that in cases of severe peri-prosthetic infection this novel operative protocol may result in successful implant salvage for breast reconstruction patients. Further studies are needed to more fully elaborate the role of NPWTi to achieve implant salvage in challenging cases of peri-prosthetic infection. © 2015 Royal Australasian College of Surgeons.

  12. The use of a prosthetic inlay resurfacing as a salvage procedure for a failed cartilage repair.

    Science.gov (United States)

    Dhollander, Aad Alfons Maria; Almqvist, Karl Fredrik; Moens, Kris; Vandekerckhove, Pieter-Jan; Verdonk, René; Verdonk, Peter; Victor, Jan

    2015-08-01

    This study was designed to describe the clinical and radiographical outcome of the HemiCAP(®) resurfacing system as a salvage treatment for a failed index cartilage procedure. Fourteen patients were treated consecutively and clinically prospectively followed for a mean period of 26.1 ± 12.8 months. All patients were previously treated for their cartilage lesion. Radiographical data were analysed based on the Kellgren and Lawrence system. The patients involved in this study demonstrated a gradual clinical improvement in time. However, radiographically significant osteoarthritic changes were observed during the follow-up period. The position of the HemiCAP(®) resurfacing system was adequate in all cases, and no signs of loosening were observed during the follow-up period. The HemiCAP(®) resurfacing system is feasible as a salvage treatment for a failed index cartilage procedure and resulted in a gradual clinical improvement. However, the favourable clinical outcome was not confirmed by the radiographical findings. IV.

  13. Multivariable model development and internal validation for prostate cancer specific survival and overall survival after whole-gland salvage Iodine-125 prostate brachytherapy

    NARCIS (Netherlands)

    Peters, Max; van der Voort van Zyp, Jochem R N; Moerland, Marinus A; Hoekstra, Carel J; van de Pol, Sandrine; Westendorp, Hendrik; Maenhout, Metha; Kattevilder, Rob; Verkooijen, Helena M; van Rossum, Peter S N; Ahmed, Hashim U; Shah, Taimur T; Emberton, Mark; van Vulpen, Marco

    BACKGROUND: Whole-gland salvage Iodine-125-brachytherapy is a potentially curative treatment strategy for localised prostate cancer (PCa) recurrences after radiotherapy. Prognostic factors influencing PCa-specific and overall survival (PCaSS & OS) are not known. The objective of this study was to

  14. Responses of cavity-nesting birds to stand-replacement fire and salvage logging in ponderosa pine/Douglas-fir forests of southwestern Idaho

    Science.gov (United States)

    Victoria A. Saab; Jonathan G. Dudley

    1998-01-01

    From 1994 to 1996, researchers monitored 695 nests of nine cavity-nesting bird species and measured vegetation at nest sites and at 90 randomly located sites in burned ponderosa pine forests of southwestern Idaho. Site treatments included two types of salvage logging, and unlogged controls. All bird species selected nest sites with higher tree densities, larger...

  15. Reirradiation for recurrent head and neck cancer with salvage interstitial pulsed-dose-rate brachytherapy. Long-term results

    Energy Technology Data Exchange (ETDEWEB)

    Strnad, Vratislav; Lotter, Michael; Kreppner, Stephan; Fietkau, Rainer [University Hospital Erlangen, Dept. of Radiation Oncology, Erlangen (Germany)

    2015-01-10

    To assess the long-term results of protocol-based interstitial pulsed-dose-rate (PDR) brachytherapy as reirradiation combined with simultaneous chemotherapy and interstitial hyperthermia in selected patients with recurrent head and neck tumors. A total of 104 patients with biopsy-proven recurrent head and neck cancer were treated with interstitial PDR brachytherapy. Salvage surgery had also been undergone by 53/104 (51 %) patients (R1 or R2 resection in > 80 % of patients). Salvage brachytherapy alone was administered in 81 patients (78 %), with a median total dose of 56.7 Gy. Salvage brachytherapy in combination with external beam radiotherapy (EBRT) was performed in 23/104 patients (32 %), using a median total dose of D{sub REF} = 24 Gy. Simultaneously to PDR brachytherapy, concomitant chemotherapy was administered in 58/104 (55.8 %) patients. A single session of interstitial hyperthermia was also used to treat 33/104 (31.7 %) patients. The analysis was performed after a median follow-up of 60 months. Calculated according to Kaplan-Meier, local tumor control rates after 2, 5, and 10 years were 92.5, 82.4, and 58.9 %, respectively. Comparing results of salvage PDR brachytherapy with or without simultaneous chemotherapy, the 10-year local control rates were 76 vs. 39 % (p= 0014), respectively. No other patient- or treatment-related parameters had a significant influence on treatment results. Soft tissue necrosis or bone necrosis developed in 18/104 (17.3 %) and 11/104 (9.6 %) patients, respectively, but only 3 % of patients required surgical treatment. PDR interstitial brachytherapy with simultaneous chemotherapy is a very effective and, in experienced hands, also a safe treatment modality in selected patients with head and neck cancer in previously irradiated areas. (orig.) [German] Es erfolgte die Analyse der Langzeitergebnisse einer protokollbasierten interstitiellen Brachytherapie (Re-Bestrahlung) mit simultaner Chemotherapie und interstitieller Hyperthermie

  16. Risk factors for local failure requiring salvage neurosurgery after radiosurgery for brain metastases

    International Nuclear Information System (INIS)

    Weltman, Eduardo; Hanriot, Rodrigo de Morais; Prisco, Flavio Eduardo; Nadalin, Wladimir; Brandt, Reynaldo Andre; Moreira, Frederico Rafael

    2004-01-01

    Objective: the aim of this study is to select the risk factors for local failure requiring salvage neurosurgery in patients with brain metastases treated with stereotactic radiosurgery in a single institution. Methods: the follow-up of 123 patients, with 255 brain metastases treated with radiosurgery at the Radiation Oncology Department of the Hospital Israelita Albert Einstein from July 1993 to August 2001, was retrospectively analyzed. The criteria for salvage neurosurgery were tumor volume enlargement, or tumor persistence leading to severe neurological symptoms, life threatening situation or critical steroid dependence. We considered the case as local failure when the histopathologic evaluation showed morphologically preserved cancer cells (tumor recurrence, persistence or progression). We applied the Fisher's exact test to evaluate the statistical correlation between local failure and primary tumor histology, volume of the brain metastases, prescribed radiosurgery dose, and whole brain radiotherapy. Results: fourteen of 123 patients (11%) underwent salvage neurosurgery. Histology showed preserved cancer cells with necrosis and/or bleeding in 11 cases (9% of the total accrual), and only necrosis with or without bleeding (without preserved cancer cells) in three cases. The primary tumor histology among the 11 patients considered with active neoplasia was malignant melanoma in five cases (21% of the patients with melanoma), breast adenocarcinoma in three (16% of the patients with breast cancer), and other histology in the remaining three. Breast cancer diagnosis, non-elective whole brain irradiation, volume of the brain metastases, and the prescribed radiosurgery dose did not correlate with the risk of local failure. Patients treated with elective whole brain radiotherapy showed fewer local failures, when compared to all patients receiving whole brain radiotherapy, and to the patients not receiving this treatment, with incidence of failure in 4%,7% and 14

  17. Impact of salvage therapy for biochemical recurrence on health-related quality of life following radical prostatectomy

    International Nuclear Information System (INIS)

    Namiki, Shunichi; Saito, Seiichi; Arai, Yoichi; Tochigi, Tatsuo; Ioritani, Naomasa; Terai, Akito

    2007-01-01

    The objective of this study was to determine the impact of salvage therapy for prostate-specific antigen (PSA) recurrence on the health-related quality of life (HRQOL) of patients after radical retropubic prostatectomy (RP). Between January 2000 and December 2003, a total of 249 patients who underwent RP were available for 2-year follow up. Of the respondents, 203 men did not show evidence of recurrence (group A), and 46 men received salvage hormonal therapy and/or radiotherapy after RP because of a rise in PSA (group B). The general and prostate-target HRQOL was assessed with the Medical Outcomes Study 36-Item Short Form and University of California, Los Angeles Prostate Cancer Index, respectively. Patients completed the HRQOL instruments by mail at baseline and at 24 months after RP. All of the patients completed both questionnaires. At baseline no significant differences were found between the two groups in any of the HRQOL domains. There were significant improvements in mental health and social function for the patients without biochemical recurrence postoperatively. Repeated measure analysis of variance (ANOVA) revealed significantly different patterns of alteration in several general HRQOL domains among the treatment groups. The urinary and bowel domains were equivalent between the two treatment groups at baseline and 24 months after RP. The patients treated with salvage hormonal therapy tended to show delayed recovery of sexual function. Using a self-administered questionnaire, biochemical recurrence following RP was found to impose a substantial burden in patients with localized prostate cancer. (author)

  18. Salvage radical prostatectomy after external radiotherapy for prostate cancer: Indications, morbidity and results. Review from CCAFU prostate section

    International Nuclear Information System (INIS)

    Paparel, P.; Soulie, M.; Mongiat-Artus, P.; Cornud, F.; Borgogno, C.; Les membres du sous-comite prostate du CCAFU

    2010-01-01

    Local recurrence after external radiotherapy for prostate cancer occurs in 30 to 50 % and is often diagnosed by a rising PSA. The absence of local control after radiotherapy is a risk factor of metastases and specific mortality. There are several therapeutic options to treat these patients: surveillance, hormonotherapy and salvage therapies (radical prostatectomy, cysto-prostatectomy, brachytherapy, high intensity focused ultrasound [HIFU] and cryotherapy). Hormonotherapy is not a curative treatment and after a couple of years, the disease will progress again. Local salvage therapies are the only treatment to have the potential to cure these patients with the condition of very strict inclusion criteria. Among these therapies, only radical prostatectomy demonstrated his efficacy with a follow-up of 10 years on specific survival and survival without biological progression respectively from 70 to 77 % and from 30 to 43 %. During last decade, morbidity of RP has strongly decreased with a percentage of rectal and ureteral injury at 3 %. Nevertheless, percentage of urinary incontinence remains high from 29 to 50 %. Salvage mini-invasive therapies (cryotherapy, HIFU and cryotherapy) are under constant evolution due to progress of technology. Functional and oncological results are better with last generation devices but need to be evaluated and compared with radical prostatectomy. (authors)

  19. Clinical, virological and immunological responses in Danish HIV patients receiving raltegravir as part of a salvage regimen

    Directory of Open Access Journals (Sweden)

    Frederik N Engsig

    2010-05-01

    Full Text Available Frederik N Engsig1, Jan Gerstoft1, Gitte Kronborg2, Carsten S Larsen3, Gitte Pedersen4, Anne M Audelin5, Louise B Jørgensen5, Niels Obel11Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark; 2Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; 3Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark; 4Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark; 5Department of Virology, Statens Serum Institute, Copenhagen, DenmarkBackground: Raltegravir is the first integrase inhibitor approved for treatment of HIV-infected patients harboring multiresistant viruses.Methods: From a Danish population-based nationwide cohort of HIV patients we identified the individuals who initiated a salvage regimen including raltegravir and a matched cohort of HIV-infected patients initiating HAART for the first time. We compared these two cohorts for virological suppression, gain in CD4 count, and time to first change of initial regimen.Results: We identified 32 raltegravir patients and 64 HIV patients who initiated HAART for the first time in the period 1 January 2006 to 1 July 2009. The virological and immunological responses in the raltegravir patients were comparable to those seen in the control cohort. No patients in the two cohorts died and no patients terminated raltegravir treatment in the observation period. Time to first change of initial regimen was considerably shorter for HAART-naïve patients.Conclusion: We conclude that salvage regimens including raltegravir have high effectiveness in the everyday clinical setting. The effectiveness of the regimens is comparable to that observed for patients initiating HAART for the first time. The risk of change in the salvage regimens after initiation of raltegravir is low.Keywords: HIV, raltegravir, salvage regime, efficacy, matched cohort

  20. Salvage radiotherapy with or without concurrent chemotherapy for pelvic recurrence after hysterectomy alone for early-stage uterine cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang-Won [Ajou University School of Medicine, Department of Radiation Oncology, Yeongtong-gu, Suwon, Gyeonggi-do (Korea, Republic of); Konyang University School of Medicine, Department of Radiation Oncology, Daejeon (Korea, Republic of); Chun, Mison; Oh, Young-Taek [Ajou University School of Medicine, Department of Radiation Oncology, Yeongtong-gu, Suwon, Gyeonggi-do (Korea, Republic of); Ryu, Hee-Sug; Chang, Suk-Joon; Kong, Tae Wook [Ajou University School of Medicine, Department of Obstetrics and Gynecology, Yeongtong-gu, Suwon, Gyeonggi-do (Korea, Republic of); Lee, Eun Ju [Ajou University School of Medicine, Department of Radiology, Yeongtong-gu, Suwon, Gyeonggi-do (Korea, Republic of); Lee, Yong Hee [Ajou University School of Medicine, Department of Pathology, Yeongtong-gu, Suwon, Gyeonggi-do (Korea, Republic of)

    2017-07-15

    Treatment outcomes of patients with pelvic recurrence after hysterectomy alone for uterine cervical cancer who received salvage radiotherapy (RT) with or without concurrent chemotherapy were investigated. Salvage RT for recurrent cervical cancer confined to the pelvic cavity after hysterectomy alone was received by 33 patients. The median interval between initial hysterectomy and recurrence was 26 months. Whole-pelvic irradiation was delivered to median dose of 45 Gy, followed by a boost with a median dose of 16 Gy to the gross tumor volume. Cisplatin-based concurrent chemotherapy was administered to 29 patients. The median follow-up period was 53 months for surviving patients. Most patients (97.0%) completed salvage RT of ≥45 Gy. Complete response (CR) was achieved in 23 patients (69.7%). Pelvic sidewall involvement and evaluation with positron-emission tomography-computed tomography were significantly associated with CR. The 5-year progression-free survival (PFS), local control (LC), distant metastasis-free survival (DMFS), and overall survival (OS) rates were 62.7, 79.5, 72.5, and 60.1%, respectively. Initial International Federation of Gynecology and Obstetrics stage, pelvic sidewall involvement, and CR status were significant factors for PFS and OS rates in multivariate analysis. The incidence of severe acute and late toxicities (≥grade 3) was 12.1 and 3.0%, respectively. Aggressive salvage RT with or without concurrent chemotherapy for recurrent cervical cancer confined to the pelvic cavity was feasible, with promising treatment outcomes and acceptable toxicities. However, even more intensive novel treatment strategies should be investigated for patients with unfavorable prognostic factors. (orig.) [German] Untersuchung der Behandlungsergebnisse von Patientinnen mit Beckenrezidiv nach alleiniger Hysterektomie bei Zervixkarzinom, die eine Salvage-Radiotherapie (RT) mit oder ohne begleitende Chemotherapie erhalten hatten. Insgesamt 33 Patientinnen erhielten

  1. limb salvage procedures for mangled lower extremities

    African Journals Online (AJOL)

    Dixon

    This form of treatment for certain diseases is not yet fully and ... hence the need for alternative measures. One aim of ... with Type 111B Open tibial fractures without vascular compromise ..... avascular necrosis from severe infections. These can ...

  2. Salvage High-intensity Focused Ultrasound for the Recurrent Prostate Cancer after Radiotherapy

    International Nuclear Information System (INIS)

    Shoji, S.; Nakano, M.; Omata, T.; Harano, Y.; Nagata, Y.; Uchida, T.; Usui, Y.; Terachi, T.

    2010-01-01

    To investigate the use of minimally invasive high-intensity focused ultrasound (HIFU) as a salvage therapy in men with localized prostate cancer recurrence following external beam radiotherapy (EBRT), brachytherapy or proton therapy. A review of 20 cases treated using the Sonablate registered 500 HIFU device, between August 28, 2002 and September 1, 2009, was carried out. All men had presumed organ-confined, histologically confirmed recurrent prostate adenocarcinoma following radiation therapy. All men with presumed, organ-confined, recurrent disease following EBRT in 8 patients, brachytherapy in 7 patients or proton therapy in 5 patients treated with salvage HIFU were included. The patients were followed for a mean (range) of 16.0 (3-80) months. Biochemical disease-free survival (bDFS) rates in patients with low-intermediate and high risk groups were 86% and 50%, respectively. Side-effects included urethral stricture in 2 of the 16 patients (13%), urinary tract infection or dysuria syndrome in eight (26%), and urinary incontinence in one (6%). Recto-urethral fistula occurred in one patient (6%). Transrectal HIFU is an effective treatment for recurrence after radiotherapy especially in patients with low- and intermediate risk groups.

  3. Percutaneous Creation of Bare Intervascular Tunnels for Salvage of Thrombosed Hemodialysis Fistulas Without Recanalizable Outflow

    International Nuclear Information System (INIS)

    Chen, Matt Chiung-Yu; Wang, Yen-Chi; Weng, Mei-Jui

    2015-01-01

    PurposeThis study aimed to retrospectively assess the efficacy of a bare intervascular tunnel for salvage of a thrombosed hemodialysis fistula. We examined the clinical outcomes and provided follow-up images of the bare intervascular tunnel.Materials and MethodsEight thrombosed fistulas lacked available recanalizable outflow veins were included in this study. These fistulas were salvaged by re-directing access site flow to a new outflow vein through a percutaneously created intervascular tunnel without stent graft placement. The post-intervention primary and secondary access patency rates were calculated using the Kaplan–Meier method.ResultsThe procedural and clinical success rates were 100 %. Post-intervention primary and secondary access patency at 300 days were 18.7 ± 15.8 and 87.5 ± 11.7 %, respectively. The mean follow-up period was 218.7 days (range 10–368 days). One patient died of acute myocardial infarction 10 days after the procedure. No other major complications were observed. Minor complications, such as swelling, ecchymosis, and pain around the tunnel, occurred in all of the patients.ConclusionsPercutaneous creation of a bare intervascular tunnel is a treatment option for thrombosed hemodialysis fistulas without recanalizable outflow in selected patients

  4. Oncological outcome, complications, lower urinary tract symptoms, and health-related quality of life after low-dose-rate salvage brachytherapy for recurrent prostate cancer following primary radiotherapy: a report of 8 cases

    Directory of Open Access Journals (Sweden)

    Makito Miyake

    2017-07-01

    Full Text Available Purpose: We evaluated our experience with low-dose-rate salvage brachytherapy for local recurrence after primary prostate radiotherapy, and described the changes in lower urinary tract symptoms and health-related quality of life. Material and methods: Between 2011 and 2016, eight men with local recurrence after primary prostate radiotherapy underwent iodine-125 salvage brachytherapy with a prescribed dose of 110 or 145 Gy. Recurrence-free survival was evaluated with a post-treatment prostate-specific antigen profile. The toxicity and changes in lower urinary tract symptoms and health-related quality of life during the follow-up were evaluated on the Common Terminology Criteria for Adverse Events version 4.0, International Prostate Symptom Score, Short Form-8, and Expanded Prostate Cancer Index Composite, respectively. Results: The median follow-up was 12.2 months (range, 8.3-71.9 after salvage brachytherapy. Of all eight patients, two (25% experienced treatment failure, one of whom developed left seminal vesicle recurrence 36 months after salvage brachytherapy for the right seminal vesicle recurrence, while the other developed bone metastases after 6 months. The International Prostate Symptom Scores peaked at 3 months, and returned to baseline by 6 months. The scores of all domains of health-related quality of life remained unchanged during the 12-month follow-up after salvage brachytherapy. Early grade ≤ 2 genitourinary toxicity was observed in five patients (63%, and late grade 2 gastrointestinal toxicity in one patient (13% having persistent diarrhea. No patient required intermittent catheterization and no grade 3 or greater toxicity occurred during follow-up. Conclusions: The present study is our experiment of eight patients undergoing salvage brachytherapy, suggesting that this modality is noninvasive, safe, and an effective salvage local treatment in selected patients. To our knowledge, this is the first study to evaluate lower urinary

  5. Percutaneous Endovascular Salvage Techniques for Implanted Venous Access Device Dysfunction

    International Nuclear Information System (INIS)

    Breault, Stéphane; Glauser, Frédéric; Babaker, Malik; Doenz, Francesco; Qanadli, Salah Dine

    2015-01-01

    PurposeImplanted venous access devices (IVADs) are often used in patients who require long-term intravenous drug administration. The most common causes of device dysfunction include occlusion by fibrin sheath and/or catheter adherence to the vessel wall. We present percutaneous endovascular salvage techniques to restore function in occluded catheters. The aim of this study was to evaluate the feasibility, safety, and efficacy of these techniques.Methods and MaterialsThrough a femoral or brachial venous access, a snare is used to remove fibrin sheath around the IVAD catheter tip. If device dysfunction is caused by catheter adherences to the vessel wall, a new “mechanical adhesiolysis” maneuver was performed. IVAD salvage procedures performed between 2005 and 2013 were analyzed. Data included clinical background, catheter tip position, success rate, recurrence, and rate of complication.ResultsEighty-eight salvage procedures were performed in 80 patients, mostly women (52.5 %), with a mean age of 54 years. Only a minority (17.5 %) of evaluated catheters were located at an optimal position (i.e., cavoatrial junction ±1 cm). Mechanical adhesiolysis or other additional maneuvers were used in 21 cases (24 %). Overall technical success rate was 93.2 %. Malposition and/or vessel wall adherences were the main cause of technical failure. No complications were noted.ConclusionThese IVAD salvage techniques are safe and efficient. When a catheter is adherent to the vessel wall, mechanical adhesiolysis maneuvers allow catheter mobilization and a greater success rate with no additional risk. In patients who still require long-term use of their IVAD, these procedures can be performed safely to avoid catheter replacement

  6. Review of Maxillofacial Hardware Complications and Indications for Salvage

    OpenAIRE

    Hernandez Rosa, Jonatan; Villanueva, Nathaniel L.; Sanati-Mehrizy, Paymon; Factor, Stephanie H.; Taub, Peter J.

    2015-01-01

    From 2002 to 2006, more than 117,000 facial fractures were recorded in the U.S. National Trauma Database. These fractures are commonly treated with open reduction and internal fixation. While in place, the hardware facilitates successful bony union. However, when postoperative complications occur, the plates may require removal before bony union. Indications for salvage versus removal of the maxillofacial hardware are not well defined. A literature review was performed to identify instances w...

  7. Percutaneous Endovascular Salvage Techniques for Implanted Venous Access Device Dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Breault, Stéphane, E-mail: stephane.breault@chuv.ch [Lausanne University Hospital, Diagnostic and Interventional Radiology Department (Switzerland); Glauser, Frédéric, E-mail: frederic.glauser@chuv.ch [Lausanne University Hospital, Angiology and Diagnostic and Interventional Radiology Departments (Switzerland); Babaker, Malik, E-mail: malik.babaker@chuv.ch; Doenz, Francesco, E-mail: francesco.doenz@chuv.ch; Qanadli, Salah Dine, E-mail: salah.qanadli@chuv.ch [Lausanne University Hospital, Diagnostic and Interventional Radiology Department (Switzerland)

    2015-06-15

    PurposeImplanted venous access devices (IVADs) are often used in patients who require long-term intravenous drug administration. The most common causes of device dysfunction include occlusion by fibrin sheath and/or catheter adherence to the vessel wall. We present percutaneous endovascular salvage techniques to restore function in occluded catheters. The aim of this study was to evaluate the feasibility, safety, and efficacy of these techniques.Methods and MaterialsThrough a femoral or brachial venous access, a snare is used to remove fibrin sheath around the IVAD catheter tip. If device dysfunction is caused by catheter adherences to the vessel wall, a new “mechanical adhesiolysis” maneuver was performed. IVAD salvage procedures performed between 2005 and 2013 were analyzed. Data included clinical background, catheter tip position, success rate, recurrence, and rate of complication.ResultsEighty-eight salvage procedures were performed in 80 patients, mostly women (52.5 %), with a mean age of 54 years. Only a minority (17.5 %) of evaluated catheters were located at an optimal position (i.e., cavoatrial junction ±1 cm). Mechanical adhesiolysis or other additional maneuvers were used in 21 cases (24 %). Overall technical success rate was 93.2 %. Malposition and/or vessel wall adherences were the main cause of technical failure. No complications were noted.ConclusionThese IVAD salvage techniques are safe and efficient. When a catheter is adherent to the vessel wall, mechanical adhesiolysis maneuvers allow catheter mobilization and a greater success rate with no additional risk. In patients who still require long-term use of their IVAD, these procedures can be performed safely to avoid catheter replacement.

  8. Adjuvant and Salvage Radiation Therapy After Prostatectomy: American Society for Radiation Oncology/American Urological Association Guidelines

    Energy Technology Data Exchange (ETDEWEB)

    Valicenti, Richard K., E-mail: Richard.valicenti@ucdmc.ucdavis.edu [Department of Radiation Oncology, University of California, Davis School of Medicine, Davis, California (United States); Thompson, Ian [Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (United States); Albertsen, Peter [Division of Urology, University of Connecticut Health Center, Farmington, Connecticut (United States); Davis, Brian J. [Department of Radiation Oncology, Mayo Medical School, Rochester, Minnesota (United States); Goldenberg, S. Larry [Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia (Canada); Wolf, J. Stuart [Department of Urology, University of Michigan, Ann Arbor, Michigan (United States); Sartor, Oliver [Department of Medicine and Urology, Tulane Medical School, New Orleans, Louisiana (United States); Klein, Eric [Glickman Urological Kidney Institute, Cleveland Clinic, Cleveland, Ohio (United States); Hahn, Carol [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Michalski, Jeff [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Roach, Mack [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Faraday, Martha M. [Four Oaks, Inc (United States)

    2013-08-01

    Purpose: The purpose of this guideline was to provide a clinical framework for the use of radiation therapy after radical prostatectomy as adjuvant or salvage therapy. Methods and Materials: A systematic literature review using PubMed, Embase, and Cochrane database was conducted to identify peer-reviewed publications relevant to the use of radiation therapy after prostatectomy. The review yielded 294 articles; these publications were used to create the evidence-based guideline statements. Additional guidance is provided as Clinical Principles when insufficient evidence existed. Results: Guideline statements are provided for patient counseling, use of radiation therapy in the adjuvant and salvage contexts, defining biochemical recurrence, and conducting a restaging evaluation. Conclusions: Physicians should offer adjuvant radiation therapy to patients with adverse pathologic findings at prostatectomy (ie, seminal vesicle invastion, positive surgical margins, extraprostatic extension) and salvage radiation therapy to patients with prostate-specific antigen (PSA) or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiation therapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiation therapy as well as the potential benefits of preventing recurrence. The decision to administer radiation therapy should be made by the patient and the multidisciplinary treatment team with full consideration of the patient's history, values, preferences, quality of life, and functional status. The American Society for Radiation Oncology and American Urological Association websites show this guideline in its entirety, including the full literature review.

  9. Adjuvant and Salvage Radiation Therapy After Prostatectomy: American Society for Radiation Oncology/American Urological Association Guidelines

    International Nuclear Information System (INIS)

    Valicenti, Richard K.; Thompson, Ian; Albertsen, Peter; Davis, Brian J.; Goldenberg, S. Larry; Wolf, J. Stuart; Sartor, Oliver; Klein, Eric; Hahn, Carol; Michalski, Jeff; Roach, Mack; Faraday, Martha M.

    2013-01-01

    Purpose: The purpose of this guideline was to provide a clinical framework for the use of radiation therapy after radical prostatectomy as adjuvant or salvage therapy. Methods and Materials: A systematic literature review using PubMed, Embase, and Cochrane database was conducted to identify peer-reviewed publications relevant to the use of radiation therapy after prostatectomy. The review yielded 294 articles; these publications were used to create the evidence-based guideline statements. Additional guidance is provided as Clinical Principles when insufficient evidence existed. Results: Guideline statements are provided for patient counseling, use of radiation therapy in the adjuvant and salvage contexts, defining biochemical recurrence, and conducting a restaging evaluation. Conclusions: Physicians should offer adjuvant radiation therapy to patients with adverse pathologic findings at prostatectomy (ie, seminal vesicle invastion, positive surgical margins, extraprostatic extension) and salvage radiation therapy to patients with prostate-specific antigen (PSA) or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiation therapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiation therapy as well as the potential benefits of preventing recurrence. The decision to administer radiation therapy should be made by the patient and the multidisciplinary treatment team with full consideration of the patient's history, values, preferences, quality of life, and functional status. The American Society for Radiation Oncology and American Urological Association websites show this guideline in its entirety, including the full literature review

  10. Salvaging and Conserving Water Damaged Photographic Materials

    Science.gov (United States)

    Suzuki, Ryuji

    Degradation of water damaged photographic materials is discussed; the most vulnerable elements are gelatin layers and silver image. A simple and inexpensive chemical treatment is proposed, consisting of a bath containing a gelatin-protecting biocide and a silver image protecting agent. These ingredients were selected among those used in manufacturing of silver halide photographic emulsions or processing chemicals. Experiments confirmed that this treatment significantly reduced oxidative attacks to silver image and bacterial degradation of gelatin layers. The treated material was also stable under intense light fading test. Method of hardening gelatin to suppress swelling is also discussed.

  11. NAD+ salvage pathway in cancer metabolism and therapy.

    Science.gov (United States)

    Kennedy, Barry E; Sharif, Tanveer; Martell, Emma; Dai, Cathleen; Kim, Youra; Lee, Patrick W K; Gujar, Shashi A

    2016-12-01

    Nicotinamide adenine dinucleotide (NAD + ) is an essential coenzyme for various physiological processes including energy metabolism, DNA repair, cell growth, and cell death. Many of these pathways are typically dysregulated in cancer cells, making NAD + an intriguing target for cancer therapeutics. NAD + is mainly synthesized by the NAD + salvage pathway in cancer cells, and not surprisingly, the pharmacological targeting of the NAD + salvage pathway causes cancer cell cytotoxicity in vitro and in vivo. Several studies have described the precise consequences of NAD + depletion on cancer biology, and have demonstrated that NAD+ depletion results in depletion of energy levels through lowered rates of glycolysis, reduced citric acid cycle activity, and decreased oxidative phosphorylation. Additionally, depletion of NAD + causes sensitization of cancer cells to oxidative damage by disruption of the anti-oxidant defense system, decreased cell proliferation, and initiation of cell death through manipulation of cell signaling pathways (e.g., SIRT1 and p53). Recently, studies have explored the effect of well-known cancer therapeutics in combination with pharmacological depletion of NAD + levels, and found in many cases a synergistic effect on cancer cell cytotoxicity. In this context, we will discuss the effects of NAD + salvage pathway inhibition on cancer cell biology and provide insight on this pathway as a novel anti-cancer therapeutic target. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. In situ saphenous vein bypass for limb salvage.

    Science.gov (United States)

    Sarcina, A; Carlesi, R; Bellosta, R; Agrifoglio, G

    1993-02-01

    A total of 130 infrapopliteal in situ saphenous vein bypasses were performed in 128 patients between January 1980 and June 1991. The indication for surgery was critical ischaemia with impending limb loss in 121 patients; seven suffered from severe claudication. The distal anastomosis was to the popliteal artery below the knee in 60 cases (46.2%) and in 70 (53.8%) to the tibioperoneal arteries. The results, in terms of secondary patency and limb salvage rates, of the first 68 procedures (1980-1985) and subsequent 62 (1986-June 1991) were compared. In the first period, a secondary patency rate of 42.6% and a limb salvage rate of 67.0% were obtained, compared with 71.3 and 80.8% respectively in the second. These differences are significant for patency (P < 0.005) and limb salvage (P < 0.01). These results show that the in situ technique can give acceptable results but a learning period with a high percentage of early failures is to be expected.

  13. Use of Intra-Arterial Chemotherapy and Embolization Before Limb Salvage Surgery for Osteosarcoma of the Lower Extremity

    International Nuclear Information System (INIS)

    Zhang Huojun; Yang Jijin; Lu Jianping; Lai Chaojen; Sheng Jin; Li Yuxiao; Hao Qiang; Zhang Shunmin; Gupta, Sanjay

    2009-01-01

    We report our experience with the use of intra-arterial chemotherapy and embolization before limb salvage surgery in patients with osteosarcoma of the lower extremity. We evaluated the effect of this procedure on the degree of tumor necrosis and on the amount of blood loss during surgery. We reviewed the medical records of all patients who received intra-arterial chemotherapy and embolization before undergoing limb salvage surgery for osteosarcoma of the lower extremity at our institution between January 2003 and April 2008. Patient demographic, tumor characteristics, treatment details, postembolization complications, and surgical and pathological findings were recorded for each patient. We evaluated the operative time, estimated blood loss (EBL), and volume of blood transfusion during surgery and in the postoperative period in all patients in the study group. The same parameters were recorded for 65 other patients with lower extremity osteosarcoma who underwent limb salvage operation at our institution without undergoing preoperative intervention. The study included 47 patients (25 males and 22 females). Angiography showed that the tumors were hypervascular. Intra-arterial chemotherapy and embolization were performed successfully, resulting in a substantial reduction or complete disappearance of tumor stain in all patients. No major complications were encountered. At the time of surgery, performed 3-7 days after embolization, a fibrous edematous band around the tumor was observed in 43 of the 47 patients, facilitating surgery. The goal of limb salvage was achieved successfully in all cases. Percentage tumor necrosis induced by treatment ranged from 70.2% to 94.2% (average, 82.9%). EBL during surgery, EBL from drains in the postoperative period, total EBL, and transfusion volumes were significantly lower in the 47 study patients compared to the 65 patients who underwent surgery without preoperative treatment with intra-arterial chemotherapy and embolization. The

  14. Combined stent placement and high dose PGE1 drip infusion for chronic occlusion of the superficial femoral artery as a modality to salvage chronic critical limb ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Ikushima, Ichiro [Department of Radiology, Miyakonojo Medical Association Hospital, 5822-3 Oiwadacho, Miyakonojo 885-0062 (Japan)], E-mail: iku-i@fk.enjoy.ne.jp; Hirai, Toshinori [Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University (Japan); Ishii, Akihiko [Department of Radiology, Miyakonojo Medical Association Hospital, 5822-3 Oiwadacho, Miyakonojo 885-0062 (Japan); Yamashita, Yasuyuki [Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University (Japan)

    2008-04-15

    Purpose: To assess the initial effect, short-term patency, and limb salvage rates of combined stent placement and high-dose prostaglandin E-1 (PGE1) drip infusion for chronic occlusion of the superficial femoral artery (SFA). Materials and methods: A total of 15 arteriosclerotic occlusive lesions of the SFA were treated in 11 consecutive patients (mean age: 78.4 years old). All cases were of category 4 or 5, based on the criteria of the Society of Vascular Surgery and Intermittent Society for Cardiovascular Surgery (SVC/ISCVS). In all cases a self-expandable stainless steel stent was implanted. PGE1 treatment was started 3-5 days before stent placement and continued for 7-10 days after the intervention. The technical success, limb salvage outcomes, patency rates, and complications were examined. Results: In all cases, the technical success rate of the procedure was 100%. After stent implantation, the clinical status of all cases was improved by at least +2, and major amputation was not required in any cases. The 12-month primary, secondary patency rates, and limb salvage rate were 57%, 100%, and 100%, respectively. Conclusion: Combined stent placement and high-dose PGE1 drip infusion is a treatment of choice for salvaging the lower limb of a patient with chronic critical ischemia.

  15. Splenic injury diagnosis & splenic salvage after trauma

    NARCIS (Netherlands)

    Olthof, D.C.

    2014-01-01

    Non-operative management (NOM) has replaced surgery as the treatment of choice for hemodynamically stable patients with splenic injury after trauma. The growing use of NOM for blunt abdominal organ injury has been made possible by the progress in the quality and availability of the multidetector CT

  16. Salvage photodynamic therapy for recurrent nasopharyngeal carcinoma.

    Science.gov (United States)

    Succo, Giovanni; Rosso, S; Fadda, G L; Fantini, M; Crosetti, Erika

    2014-06-01

    To evaluate the feasibility of photodynamic therapy (NP-PDT) in the palliative management of recurrent/persistent nasopharyngeal cancer (NFC). Six patients with persistent/recurrent NPC underwent PDT with palliative intent. NP-PDT was delivered by three different methods depending on the localization, size and depth of the lesion: type I NP-PDT: transnasal direct illumination of postero-superior recurrence; type II NP-PDT: transnasal direct illumination of the whole nasopharynx; type III NP-PDT: transoral direct or interstitial illumination of lateral recurrence. In this case, the ENT-magnetic navigation system (MNS) was extremely useful in identifying the tumor and its distance from the ICA. Both patients treated with NP-PDT type I are free from disease at 38 and 71 months after treatment; both patients treated with NP-PDT type II experienced further local and loco-regional recurrence of disease within 16 months; one died of the disease while the second underwent a second palliative treatment, NP-PDT type I, and is currently living with the disease; of the two patients who underwent NP-PDT type III, one died as a result of regional and systemic recurrence without local recurrence while the second experienced a superficial recurrence. He underwent a second NP-PDT type III treatment and is currently free from disease at 21 months. NP-PDT is a non-invasive and simple treatment modality that may have an important role in the treatment of selected cases of persistent/recurrent NPC in its early stage, not suitable for a conventional therapeutic protocol. Coupling NP-PDT with the ENT-MNS can be an effective strategy to obtain more precise light delivery within the tumor, particularly in lateral and parapharyngeal localization. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Alternative salvage technique during postcardiotomy electrical storm.

    Science.gov (United States)

    Ryu, Y G; Baek, M J; Kim, H J

    2010-08-01

    Cardiac electrical storm is generally treated with antiarrhythmic drugs, electrical cardioversion, or catheter ablation. However, these conservative treatment modalities are considered neither curative nor preventive with regard to recurrent arrhythmias in postoperative electrical storm after open heart surgery. We present a case of surgical ventricular assist device placement for postcardiotomy electrical storm in a 38-year-old patient. Copyright (c) Georg Thieme Verlag KG Stuttgart-New York.

  18. Salvage central lymphatic irradiation in follicular lymphomas following failure of chemotherapy: a feasibility study

    International Nuclear Information System (INIS)

    Ha, Chul S.; Tucker, Susan L.; Blanco, Angel I.; Cabanillas, Fernando; Cox, James D.

    1999-01-01

    Purpose: Management of follicular lymphoma after chemotherapy failure has been controversial and has ranged from watchful waiting to high-dose chemotherapy. High-dose chemotherapy with bone marrow reconstitution may produce clinical and molecular complete responses at the risk of serious morbidity and mortality. It has been previously reported that central lymphatic irradiation (CLI) can achieve long-term relapse-free survival in patients with Stage I, II, or III follicular lymphoma. Therefore, we investigated the feasibility of treating patients in whom front-line chemotherapy failed with salvage CLI instead of instituting more intensive chemotherapy. Methods and Materials: Salvage CLI with curative intent for patients with follicular lymphoma was started at The University of Texas M. D. Anderson Cancer Center in 1992. Eleven patients whose disease showed poor response to or relapsed after chemotherapy were managed with this approach. The median age of the patients was 61 years. Criteria for exclusion included bone marrow involvement or other evidence of Ann Arbor Stage IV disease at any time during the course of the disease. Overall survival and relapse-free survival were calculated from the first day of CLI. Results: Ten patients were alive at a median follow-up of 25 months (range 9-73 months). The treatment was well tolerated in general. Two patients could not complete CLI: one 75-year-old patient owing to prolonged platelet count depression and deterioration in general medical condition, and a 66-year-old patient because of exacerbation of preexisting pancytopenia and worsening of heart disease. Everyone who completed CLI remains in remission at the time of this report, except for one patient who had a relapse in the right lacrimal gland at 32 months. This patient was treated with local radiation therapy and is free of disease. Eventual recovery of the blood counts was observed for the patients who completed CLI. Conclusion: These results demonstrate for the

  19. Real-world Direct Health Care Costs for Metastatic Colorectal Cancer Patients Treated With Cetuximab or Bevacizumab-containing Regimens in First-line or First-line Through Second-line Therapy.

    Science.gov (United States)

    Johnston, Stephen; Wilson, Kathleen; Varker, Helen; Malangone-Monaco, Elisabetta; Juneau, Paul; Riehle, Ellen; Satram-Hoang, Sacha; Sommer, Nicolas; Ogale, Sarika

    2017-12-01

    The present study examined real-world direct health care costs for metastatic colorectal cancer (mCRC) patients initiating first-line (1L) bevacizumab (BEV)- or cetuximab (CET)-containing regimen in 1L or 1L-through-second-line (1L-2L) therapy. Using a large US insurance claims database, patients with mCRC initiating 1L BEV- or 1L CET-containing regimen from January 1, 2008 to September 30, 2014 were identified. The per-patient per-month (PPPM) all-cause health care costs (2014 US dollars) were measured during 1L therapy and, for patients continuing to a 2L biologic-containing regimen, 1L-2L therapy. Multivariable regression analyses were used to compare PPPM total health care costs between patients initiating a 1L BEV- versus 1L CET-containing regimen. A total of 6095 patients initiating a 1L BEV- and 453 initiating a 1L CET-containing regimen were evaluated for 1L costs; 2218 patients initiating a 1L BEV- and 134 initiating a 1L CET-containing regimen were evaluated for 1L-2L costs. In 1L therapy, 1L CET had adjusted PPPM costs that were $3135 (95% confidence interval [CI], $1174-$5040; P < .001) greater on average than 1L BEV. In 1L-2L therapy, 1L BEV-2L CET had adjusted PPPM costs that were $1402 (95% CI, $1365-$1442; P = .010) greater than those for 1L BEV-2L BEV, and 1L CET-2L BEV had adjusted PPPM costs that were $4279 (95% CI, $4167-$4400; P = .001) greater on average than those for 1L BEV-2L BEV. The adjusted PPPM cost differences for 1L BEV-2L other biologic or 1L CET-2L other biologic agent were numerically greater but statistically insignificant. PPPM total health care costs for 1L and 2L therapy tended to be greater for patients treated with 1L CET-containing regimens than for 1L BEV-containing regimens. Also, continuing treatment with BEV-containing regimens 1L-2L was less costly than switching between BEV and CET. The cost differences between BEV and CET hold important implications for treatment decisions of mCRC patients in real-world clinical

  20. A cross-sectional study to evaluate second line virological failure and elevated bilirubin as a surrogate for adherence to atazanavir/ritonavir in two urban HIV clinics in Lilongwe, Malawi.

    Science.gov (United States)

    Ongubo, Dennis Miyoge; Lim, Robertino; Tweya, Hannock; Stanley, Christopher Chikhosi; Tembo, Petros; Broadhurst, Richard; Gugsa, Salem; Ngongondo, McNeil; Speight, Colin; Heller, Tom; Phiri, Sam; Hosseinipour, Mina C

    2017-07-03

    Malawi's national antiretroviral therapy program provides atazanavir/ritonavir-based second line regimens which cause concentration-dependent rise in indirect bilirubin. We sought to determine if elevated bilirubin, as a surrogate of atazanavir/ritonavir adherence, can aid in the evaluation of second line virological failure in Malawi. We conducted a cross-sectional study of HIV-infected patients ≥15 years who were on boosted protease inhibitor-based second line antiretroviral therapy for at least 6 months in two urban HIV clinics in Lilongwe, Malawi. Antiretroviral therapy history and adherence data were extracted from the electronic medical records and blood was drawn for viral load, complete blood count, total bilirubin, and CD4 cell count at a clinic visit. Factors associated with virological failure were assessed using multivariate logistic regression model. Out of 376 patients on second line antiretroviral therapy evaluated, 372 (98.9%) were on atazanavir/ritonavir-based therapy and 142 (37.8%) were male. Mean age was 40.9 years (SD ± 10.1), mean duration on second line antiretroviral therapy was 41.9 months (SD ± 27.6) and 256 patients (68.1%) had elevated bilirubin >1.3 mg/dL. Overall, 35 (9.3%) patients had viral load >1000 copies/ml (virological failure). Among the virologically failing vs. non-failing patients, bilirubin was elevated in 34.3% vs. 72.0% respectively (p bilirubin levels (aOR 5.4, p bilirubin levels better predicted virological failure than pill count adherence. Therefore, strategic use of bilirubin and viral load testing to target adherence counseling and support may be cost-effective in monitoring second line antiretroviral therapy adherence and virological failure. Drug resistance testing targeted for patients with virological failure despite elevated bilirubin levels would facilitate timely switch to third line antiretroviral regimens whenever available.

  1. 75 FR 54026 - Salvage and Marine Firefighting Requirements; Vessel Response Plans for Oil

    Science.gov (United States)

    2010-09-03

    ... information for resource providers for each vessel with appropriate equipment and resources located in each... appropriate salvage and marine firefighting resources were identified and available for responding to...

  2. Focal salvage iodine-125 brachytherapy for prostate cancer recurrences after primary radiotherapy: A retrospective study regarding toxicity, biochemical outcome and quality of life

    International Nuclear Information System (INIS)

    Peters, Max; Maenhout, Metha; Voort van Zyp, Jochem R.N. van der; Moerland, Marinus A.; Moman, Maaike R.; Steuten, Lotte M.G.; Deursen, Marijke J.H. van; Vulpen, Marco van

    2014-01-01

    Purpose: Whole-gland salvage for recurrent prostate cancer (PCa) shows high failure and toxicity rates. Early and adequate localization of recurrences enables focal salvage, thereby potentially improving functional outcomes, while maintaining cancer control. Materials and methods: Retrospective analysis yielded 20 focal salvage I125 brachytherapy patients for locally recurrent PCa after primary radiotherapy. Tumor was defined by multiparametric MRI and correspondence with transrectal biopsies. Dose data were obtained intra-operatively. The tumor was prescribed ⩾144 Gy. Toxicity was scored by the Common Terminology Criteria for Adverse Events version 4 (CTCAE-4). Biochemical failure (BF) was defined using the Phoenix criteria (PSA-nadir + 2.0 ng/ml). Quality of life (QoL) was measured by SF-36 Health Survey and European Organization of Research and Treatment of Cancer (EORTC) C30+3 and PR25 questionnaires. Results: With a median follow-up of 36 months (range 10–45), six patients experienced BF, of which three had no initial response. Grade 3 genitourinary (GU) toxicity occurred in one patient (a urethral stricture). The five previously potent patients retained erectile function. QoL remained decreased with regard to urinary symptoms. Conclusion: Focal salvage I125 brachytherapy showed one grade 3 GU toxicity in the 20 treated patients. Biochemical response and QoL were acceptable

  3. Robot-assisted Salvage Lymph Node Dissection for Clinically Recurrent Prostate Cancer.

    Science.gov (United States)

    Montorsi, Francesco; Gandaglia, Giorgio; Fossati, Nicola; Suardi, Nazareno; Pultrone, Cristian; De Groote, Ruben; Dovey, Zach; Umari, Paolo; Gallina, Andrea; Briganti, Alberto; Mottrie, Alexandre

    2017-09-01

    Salvage lymph node dissection has been described as a feasible treatment for the management of prostate cancer patients with nodal recurrence after primary treatment. To report perioperative, pathologic, and oncologic outcomes of robot-assisted salvage nodal dissection (RASND) in patients with nodal recurrence after radical prostatectomy (RP). We retrospectively evaluated 16 patients affected by nodal recurrence following RP documented by positive positron emission tomography/computed tomography scan. Surgery was performed using DaVinci Si and Xi systems. A pelvic nodal dissection that included lymphatic stations overlying the external, internal, and common iliac vessels, the obturator fossa, and the presacral nodes was performed. In 13 (81.3%) patients a retroperitoneal lymph node dissection that included all nodal tissue located between the aortic bifurcation and the renal vessels was performed. Perioperative outcomes consisted of operative time, blood loss, length of hospital stay, and complications occurred within 30 d after surgery. Biochemical response (BR) was defined as a prostate-specific antigen level <0.2 ng/ml at 40 d after RASND. Median operative time, blood loss, and length of hospital stay were 210min, 250ml, and 3.5 d. The median number of nodes removed was 16.5. Positive lymph nodes were detected in 11 (68.8%) patients. Overall, four (25.0%) and five (31.2%) patients experienced intraoperative and postoperative complications, respectively. Overall, one (6.3%) and four (25.0%) patients had Clavien I and II complications within 30 d after RASND, respectively. Overall, five (33.3%) patients experienced BR after surgery. Our study is limited by the small cohort of patients evaluated and by the follow-up duration. RASND represents a feasible procedure in patients with nodal recurrence after RP and provides acceptable short-term oncologic outcomes, where one out of three patients experience BR immediately after surgery. Long-term data are needed to

  4. Grande-Baie tugboat sinking and salvage operations

    International Nuclear Information System (INIS)

    Dussault, M.; Gauthier, F.

    2009-01-01

    This paper described the operations that took place during an oil spill that occurred in December 2007 when the Grande-Baie tugboat sank at the wharf in Port Alfred, in the Ha-Ha Bay on the Saguenay River, Quebec. Approximately 100 tonnes of diesel fuel was onboard the tug. Although the exact amount of diesel spilled during this event is not known, it is assumed that half of the ship's load in diesel was spilled into the ice-infested waters. Poor weather, the presence of pack ice and tides of 2.5 meters were present at the time. Two Canadian Coast Guard officers, one emergency officer from Environment Quebec and one from Environment Canada were called for response purposes, particularly to avoid spreading of the diesel fuel and to ensure that the oily water was recovered from inside the vessel during salvage operations. One of the key objectives was to prevent diesel spills by capping vessel vents, which proved to be very challenging. Oily water was pumped from inside the boat directly in the bay of the Saguenay River to facilitate salvage of the ship. This was the first time that this method was used in Canada, and was successful because of proper risk assessment. Many conditions were followed for the purpose of environmental protection, such as confinement, good observations by divers, agreed upon criteria to stop pumping, and adequate monitoring the the Regional Environmental Emergency Team (REET). The salvage operation lasted 19 days. The challenges associated with the migration and recovery of oil in icy waters were discussed along with the environmental issues associated with the spill, particularly with the imminent opening of the ice fishing season. 2 refs., 2 tabs.,5 figs.

  5. Synthesizing and salvaging NAD: lessons learned from Chlamydomonas reinhardtii.

    Directory of Open Access Journals (Sweden)

    Huawen Lin

    2010-09-01

    Full Text Available The essential coenzyme nicotinamide adenine dinucleotide (NAD+ plays important roles in metabolic reactions and cell regulation in all organisms. Bacteria, fungi, plants, and animals use different pathways to synthesize NAD+. Our molecular and genetic data demonstrate that in the unicellular green alga Chlamydomonas NAD+ is synthesized from aspartate (de novo synthesis, as in plants, or nicotinamide, as in mammals (salvage synthesis. The de novo pathway requires five different enzymes: L-aspartate oxidase (ASO, quinolinate synthetase (QS, quinolate phosphoribosyltransferase (QPT, nicotinate/nicotinamide mononucleotide adenylyltransferase (NMNAT, and NAD+ synthetase (NS. Sequence similarity searches, gene isolation and sequencing of mutant loci indicate that mutations in each enzyme result in a nicotinamide-requiring mutant phenotype in the previously isolated nic mutants. We rescued the mutant phenotype by the introduction of BAC DNA (nic2-1 and nic13-1 or plasmids with cloned genes (nic1-1 and nic15-1 into the mutants. NMNAT, which is also in the de novo pathway, and nicotinamide phosphoribosyltransferase (NAMPT constitute the nicotinamide-dependent salvage pathway. A mutation in NAMPT (npt1-1 has no obvious growth defect and is not nicotinamide-dependent. However, double mutant strains with the npt1-1 mutation and any of the nic mutations are inviable. When the de novo pathway is inactive, the salvage pathway is essential to Chlamydomonas for the synthesis of NAD+. A homolog of the human SIRT6-like gene, SRT2, is upregulated in the NS mutant, which shows a longer vegetative life span than wild-type cells. Our results suggest that Chlamydomonas is an excellent model system to study NAD+ metabolism and cell longevity.

  6. Endoscopic Transsphenoidal Salvage Surgery for Symptomatic Residual Cystic Craniopharyngioma after Radiotherapy.

    Science.gov (United States)

    Emanuelli, Enzo; Frasson, Giuliana; Cazzador, Diego; Borsetto, Daniele; Denaro, Luca

    2018-04-01

    Objectives  Ideal treatment of craniopharyngiomas is still controversial. Radiotherapy (RT) is considered effective for recurrences or after subtotal tumor removal (STR). About 40 to 50% of patients may experience tumor cyst expansion soon after RT; in these cases, the role of salvage surgery is debated. Design  Operative video. Setting  Tertiary care center. Participants  An 11-year-old boy diagnosed with persistent craniopharyngioma. In 2015, the patient underwent right frontotemporal craniotomy for STR at another center, complicated by panhypopituitarism. Two years later, fractionated 54-Gy RT was performed on growing residual tumor. After 3 months, he was admitted to our hospital due to persistent malaise, vomiting, pulsating headache, and epistaxis. Ophthalmologic evaluation evidenced left homonymous hemianopsia. Results  A contrast-enhanced magnetic resonance imaging (MRI) showed a 27-mm cystic component enlarging from the cranial end of the persistent craniopharyngioma lesion, extending into the third ventricle. Biventricular hydrocephalus and brain midline shift to the right were present. Compared with the early post-RT MRI, the cystic component of the tumor demonstrated growth. The patient underwent external ventricular drainage placement for emergent treatment of hydrocephalus and endoscopic transsphenoidal surgery. After cystic content drainage, the lesion was completely removed with its capsule. A "gasket seal" technique was performed for skull base reconstruction, with autologous fascia lata, septal bone, and mucoperiosteum from inferior turbinate. Histologic examination confirmed the craniopharyngioma diagnosis. Postoperative MRI showed resolution of the hydrocephalus and complete tumor removal. Conclusion  Although shrinkage of cystic components of craniopharyngioma residuals may occur within 5 to 6 months after RT, salvage surgery is indicated in symptomatic patients. The link to the video can be found at https://youtu.be/4x6Qe76bf60 .

  7. Salvage conformal radiotherapy for biochemical recurrent prostate cancer after radical prostatectomy

    Directory of Open Access Journals (Sweden)

    Carlos R. Monti

    2006-08-01

    Full Text Available OBJECTIVE: Assess the results of salvage conformal radiotherapy in patients with biochemical failure after radical prostatectomy and identify prognostic factors for biochemical recurrence and toxicity of the treatment. MATERIALS AND METHODS: From June 1998 to November 2001, 35 patients were submitted to conformal radiotherapy for PSA > 0.2 ng/mL in progression after radical prostatectomy and were retrospectively analyzed. The mean dose of radiation in prostatic bed was of 77.4 Gy (68-81. Variables related to the treatment and to tumor were assessed to identify prognostic factors for biochemical recurrence after salvage radiotherapy. RESULTS: The median follow-up was of 55 months (17-83. The actuarial survival rates free of biochemical recurrence and free of metastasis at a distance of 5 years were 79.7% e 84.7%, respectively. The actuarial global survival rate in 5 years was 96.1%.The actuarial survival rate free of biochemical recurrence in 5 years was 83.3% with PSA pre-radiotherapy 1 and 2 (p = 0.023. Dose > 70 Gy in 30% of the bladder volume implied in more acute urinary toxicity (p = 0.035. The mean time for the development of late urinary toxicity was 21 months (12-51. Dose > 55 Gy in 50% bladder volume implied in more late urinary toxicity (p = 0.018. A patient presented late rectal toxicity of 2nd grade. CONCLUSIONS: Conformal radiotherapy showed to be effective for the control of biochemical recurrence after radical prostatectomy. Patients with pre-therapy PSA < 2 ng/mL have more biochemical control.

  8. Salvage conformal radiotherapy for biochemical recurrent prostate cancer after radical prostatectomy

    International Nuclear Information System (INIS)

    Monti, Carlos R.; Nakamura, Ricardo A.; Ferrigno, Robson; Rossi Junior, Aristides; Kawakami, Neusa S.; Trevisan, Felipe A.

    2006-01-01

    Objective: Assess the results of salvage conformal radiotherapy in patients with biochemical failure after radical prostatectomy and identify prognostic factors for biochemical recurrence and toxicity of the treatment. Materials and methods: From June 1998 to November 2001, 35 patients were submitted to conformal radiotherapy for PSA ≥ 0.2 ng/mL in progression after radical prostatectomy and were retrospectively analyzed. The mean dose of radiation in prostatic bed was of 77.4 Gy (68-81). Variables related to the treatment and to tumor were assessed to identify prognostic factors for biochemical recurrence after salvage radiotherapy. Results: The median follow-up was of 55 months (17-83). The actuarial survival rates free of biochemical recurrence and free of metastasis at a distance of 5 years were 79.7% e 84.7%, respectively. The actuarial global survival rate in 5 years was 96.1%.The actuarial survival rate free of biochemical recurrence in 5 years was 83.3% with PSA pre-radiotherapy ≤ 1, 100% when > 1 and ≤ 2, and 57.1% when > 2 (p = 0.023). Dose > 70 Gy in 30% of the bladder volume implied in more acute urinary toxicity (p = 0.035). The mean time for the development of late urinary toxicity was 21 months (12-51). Dose > 55 Gy in 50% bladder volume implied in more late urinary toxicity (p = 0.018). A patient presented late rectal toxicity of second grade. Conclusions: Conformal radiotherapy showed to be effective for the control of biochemical recurrence after radical prostatectomy. Patients with pre-therapy PSA < 2 ng/mL have more biochemical control. (author)

  9. Benign aggressive lesions of femoral head and neck: Is salvage possible?

    Directory of Open Access Journals (Sweden)

    Yogesh Panchwagh

    2018-01-01

    Full Text Available Background: Benign aggressive bone lesions of the femoral head and neck are mostly seen in young adults and warrant treatment for pain, impending fracture or established fracture, and disease clearance. It becomes challenging to treat them effectively while attempting salvage of the femoral head and yet achieving long term disease control with minimum complications. We describe our technique and experience in dealing with these lesions which can achieve the above-mentioned goals and can be easily replicated. Materials and Methods: We analyzed 15 cases of surgically treated, biopsy-proven benign, locally aggressive lesions affecting the femoral head and neck in skeletally mature individuals. All cases were treated with extended curettage through anterolateral modified Smith–Petersen approach along with tricortical iliac crest bone graft (combined with fibular graft in some cases reconstruction with or without suitable internal fixation. Results: All, except one, patients were available for follow up. The age ranged from 18 to 43 years and the follow up ranged between 24 and 124 months (average 78 months. These included aneurysmal bone cysts (9, giant cell tumors (4, and fibrous dysplasia (2. The indication was pain (8, with impending (2 or established pathological neck femur fracture (5. In all cases, there was satisfactory healing of lesion and timely rehabilitation. Nonunion, avascular necrosis or local recurrences were not seen. The MSTS functional score was good or excellent in all (range 26–29, average 28. Conclusion: Benign aggressive lesions affecting femoral head and neck in young and middle-aged adults pose a treatment challenge. A sturdy, lasting reconstruct with acceptable functional outcome and minimal recurrence rate can be achieved by salvaging the femoral head and neck using curettage and reconstruction, obviating the need for replacement at such an early age.

  10. Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy

    DEFF Research Database (Denmark)

    Krzakowski, Maciej; Ramlau, Rodryg; Jassem, Jacek

    2010-01-01

    To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy.......To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy....

  11. Investigation of Susceptibility of Mycobacterium tuberculosis Complex Strains Isolated from Clinical Samples Against the First and Second-Line Anti-tuberculosis Drugs by the Sensititre MycoTB Plate Method

    Directory of Open Access Journals (Sweden)

    Figen KAYSERİLİ ORHAN

    2018-03-01

    Full Text Available Introduction: Phenotypic methods for drug susceptibility testing of Mycobacterium tuberculosis complex (MTC to second-line drugs are not yet standardized. The Sensititre MycoTB Plate is a microtiter plate containing lyophilized antibiotics and configured for determination of MIC to first and second-line anti-tuberculosis drugs. The purpose of this study is to detect the susceptibility rates of MTC strains isolated from patients’ specimens for first and second-line anti-tuberculosis drugs. Materials and Methods: This study included 50 MTC strains isolated from various clinical specimens. Out of the 50 strains, 38 were isolated from sputum, three from cerebrospinal fluid, three from bronchoalveolar lavage, and six from other samples in this study. The susceptibility of strains to anti-tuberculosis drugs were determined by the Sensititre MycoTB Plate Method. Thawed isolates were subcultured, and dilutions were inoculated into MycoTB wells. The results were read at days 7, 14 and 21. Results: At the end of study, out of 50 MTC isolates, 7 (14% showed resistance to Isoniazid (INH, 5 (10% to streptomycin (SM, 4 (8% to ethambutol (EMB, 4 (8% to ethionamide (ETH, 3 (6% to rifampicin (RIF, 3 (6% to rifabutin (RFB, 2 (4% to kanamycin (KAN, 2 (4% to ofloxacin (OFL, 2 (4% to P-aminosalicyclic acid (PAS, 1 (2% to moxiflocacin (MOX, and 1 (2% to cycloserine (CYC. All strains were found sensitive to amikacin while 2 strains (4% were identified as multidrug-resistant tuberculosis (MDR-TB. Thirty-five strains (70% were sensitive to all drugs. Extensively drug resistant tuberculosis (XDR-TB was not determined in this study. Conclusion: This is the first study that tests second line anti-tuberculosis drugs in our location and provides us valuable data regarding MDR-TB and XDR-TB rates. The Sensititre MycoTB Plate Method is a fast, reliable and practical method and can be used to determine the susceptibility of first and second-line anti-tuberculosis drugs.

  12. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial.

    Science.gov (United States)

    Bøtker, Hans Erik; Kharbanda, Rajesh; Schmidt, Michael R; Bøttcher, Morten; Kaltoft, Anne K; Terkelsen, Christian J; Munk, Kim; Andersen, Niels H; Hansen, Troels M; Trautner, Sven; Lassen, Jens Flensted; Christiansen, Evald Høj; Krusell, Lars R; Kristensen, Steen D; Thuesen, Leif; Nielsen, Søren S; Rehling, Michael; Sørensen, Henrik Toft; Redington, Andrew N; Nielsen, Torsten T

    2010-02-27

    Remote ischaemic preconditioning attenuates cardiac injury at elective surgery and angioplasty. We tested the hypothesis that remote ischaemic conditioning during evolving ST-elevation myocardial infarction, and done before primary percutaneous coronary intervention, increases myocardial salvage. 333 consecutive adult patients with a suspected first acute myocardial infarction were randomly assigned in a 1:1 ratio by computerised block randomisation to receive primary percutaneous coronary intervention with (n=166 patients) versus without (n=167) remote conditioning (intermittent arm ischaemia through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff). Allocation was concealed with opaque sealed envelopes. Patients received remote conditioning during transport to hospital, and primary percutaneous coronary intervention in hospital. The primary endpoint was myocardial salvage index at 30 days after primary percutaneous coronary intervention, measured by myocardial perfusion imaging as the proportion of the area at risk salvaged by treatment; analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00435266. 82 patients were excluded on arrival at hospital because they did not meet inclusion criteria, 32 were lost to follow-up, and 77 did not complete the follow-up with data for salvage index. Median salvage index was 0.75 (IQR 0.50-0.93, n=73) in the remote conditioning group versus 0.55 (0.35-0.88, n=69) in the control group, with median difference of 0.10 (95% CI 0.01-0.22; p=0.0333); mean salvage index was 0.69 (SD 0.27) versus 0.57 (0.26), with mean difference of 0.12 (95% CI 0.01-0.21; p=0.0333). Major adverse coronary events were death (n=3 per group), reinfarction (n=1 per group), and heart failure (n=3 per group). Remote ischaemic conditioning before hospital admission increases myocardial salvage, and has a favourable safety profile. Our findings merit a larger trial to establish the effect of remote

  13. 12 CFR 714.6 - Are you required to retain salvage powers over the leased property?

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Are you required to retain salvage powers over the leased property? 714.6 Section 714.6 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS LEASING § 714.6 Are you required to retain salvage powers over the leased...

  14. 28 CFR 25.56 - Responsibilities of junk yards and salvage yards and auto recyclers.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Responsibilities of junk yards and salvage yards and auto recyclers. 25.56 Section 25.56 Judicial Administration DEPARTMENT OF JUSTICE... Responsibilities of junk yards and salvage yards and auto recyclers. (a) By no later than March 31, 2009, and...

  15. Cell salvage as part of a blood conservation strategy in anaesthesia.

    Science.gov (United States)

    Ashworth, A; Klein, A A

    2010-10-01

    The use of intraoperative cell salvage and autologous blood transfusion has become an important method of blood conservation. The main aim of autologous transfusion is to reduce the need for allogeneic blood transfusion and its associated complications. Allogeneic blood transfusion has been associated with increased risk of tumour recurrence, postoperative infection, acute lung injury, perioperative myocardial infarction, postoperative low-output cardiac failure, and increased mortality. We have reviewed the current evidence for cell salvage in modern surgical practice and examined the controversial issues, such as the use of cell salvage in obstetrics, and in patients with malignancy, or intra-abdominal or systemic sepsis. Cell salvage has been demonstrated to be safe and effective at reducing allogeneic blood transfusion requirements in adult elective surgery, with stronger evidence in cardiac and orthopaedic surgery. Prolonged use of cell salvage with large-volume autotransfusion may be associated with dilution of clotting factors and thrombocytopenia, and regular laboratory or near-patient monitoring is required, along with appropriate blood product use. Cell salvage should be considered in all cases where significant blood loss (>1000 ml) is expected or possible, where patients refuse allogeneic blood products or they are anaemic. The use of cell salvage in combination with a leucocyte depletion filter appears to be safe in obstetrics and cases of malignancy; however, further trials are required before definitive guidance may be provided. The only absolute contraindication to the use of cell salvage and autologous blood transfusion is patient refusal.

  16. Salvage surgery for radiation failure in oral, oropharyngeal, and hypopharyngeal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Suzuki, Masahiro; Terada, Akihiro; Ogawa, Tetsuya; Suzuki, Hidenori; Hasegawa, Yasuhisa

    2007-01-01

    Few reports have covered salvage surgery after radiotherapy, especially with chemotherapy for oral, oropharyngeal, and hypopharyngeal squamous cell carcinoma. The feasibility of salvage surgery is unclear. We analyzed postoperative complications and prognosis after salvage surgery for local recurrence after definitive radiotherapy. Subjects were 37 patients with oral, oropharyngeal, and hypopharyngeal squamous cell carcinoma treated from 1994 to 2003. Of these, 14 (37.8%) had postoperative complications. The complication rate was significantly high in the reconstructive operation group (p=0.031) and the chemotherapy group (p=0.049). The 5-year overall survival rate after salvage surgery was 70.7%. Although there was no significant improvement, the prognosis was good in early-stage groups with primary tumors. We found that salvage surgery after definitive radiotherapy was effective for recurrent oral, oropharyngeal, and hypopharyngeal squamous cell carcinoma. We stress the need to pay attention to postoperative complications in reconstructive operation and chemotherapy groups. (author)

  17. Improvement of limb salvage procedure using intraoperative radiotherapy for osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Hirano, Toru; Iwasaki, Katsuo; Kamishiro,; Toshiyuki,; Hayashi, Yasuyuki [Nagasaki Univ. (Japan). School of Medicine

    1992-10-01

    Clinical outcome of limb salvage procedure combined with intraoperative irradiation was investigated in 6 patients with osteosarcoma in the distal part of femur (n=4) and proximal part of tibia (n=2). They ranged in age from 12 to 54 years, with a mean of 22.5. First, a lesion was separated from the surrounding soft tissue with curatively wide margin. Osteotomy was performed at the portion of diaphysis. After irradiation field was setted up by lifting the lesion, and was exposed to doses ranging from 60 Gy to 85 Gy of intraoperative irradiation, soft tissue and fragile tumor tissue, excluding joint capsule and ligament, were removed as soon as possible. Finally, bone was jointed by means of inner fixation or bone grafting. They had a median follow-up of one year and four months after surgery. Although superficial wound infection and delayed wound adhesion were encountered as postoperative complications in one and two patients, respectively, these were all healed. None of the patients had local recurrence. The ability of salvaged limb was excellent in one, good in 3, and fair in 2 patients. Because both of the two patients with sarcoma in the proximal part of tibia had excellent and good limb ability, this procedure was considered useful especially for sarcoma in the proximal part of tibia. (N.K.).

  18. Improvement of limb salvage procedure using intraoperative radiotherapy for osteosarcoma

    International Nuclear Information System (INIS)

    Hirano, Toru; Iwasaki, Katsuo; Kamishiro; Toshiyuki; Hayashi, Yasuyuki

    1992-01-01

    Clinical outcome of limb salvage procedure combined with intraoperative irradiation was investigated in 6 patients with osteosarcoma in the distal part of femur (n=4) and proximal part of tibia (n=2). They ranged in age from 12 to 54 years, with a mean of 22.5. First, a lesion was separated from the surrounding soft tissue with curatively wide margin. Osteotomy was performed at the portion of diaphysis. After irradiation field was setted up by lifting the lesion, and was exposed to doses ranging from 60 Gy to 85 Gy of intraoperative irradiation, soft tissue and fragile tumor tissue, excluding joint capsule and ligament, were removed as soon as possible. Finally, bone was jointed by means of inner fixation or bone grafting. They had a median follow-up of one year and four months after surgery. Although superficial wound infection and delayed wound adhesion were encountered as postoperative complications in one and two patients, respectively, these were all healed. None of the patients had local recurrence. The ability of salvaged limb was excellent in one, good in 3, and fair in 2 patients. Because both of the two patients with sarcoma in the proximal part of tibia had excellent and good limb ability, this procedure was considered useful especially for sarcoma in the proximal part of tibia. (N.K.)

  19. Phase II Study of Biweekly Plitidepsin as Second-Line Therapy for Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium

    Directory of Open Access Journals (Sweden)

    Sergio Szyldergemajn

    2009-09-01

    Full Text Available The objective of this exploratory, open-label, single-arm, phase II clinical trial was to evaluate plitidepsin (5 mg/m2 administered as a 3-hour continuous intravenous infusion every two weeks to patients with locally advanced/metastatic transitional cell carcinoma of the urothelium who relapsed/progressed after first-line chemotherapy. Treatment cycles were repeated for up to 12 cycles or until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. The primary efficacy endpoint was objective response rate according to RECIST. Secondary endpoints were the rate of SD lasting ≥6 months and time-to-event variables. Toxicity was assessed using NCI-CTC v. 3.0. Twenty-one patients received 57 treatment cycles. No objective tumor responses occurred. SD lasting <6 months was observed in two of 18 evaluable patients. With a median follow-up of 4.6 months, the median PFR and the median OS were 1.4 months and 2.3 months, respectively. The most common AEs were mild to moderate nausea, fatigue, myalgia and anorexia. Anemia, lymphopenia, and increases in transaminases, alkaline phosphatase and creatinine were the most frequent laboratory abnormalities. No severe neutropenia occurred. Treatment was feasible and generally well tolerated in this patient population; however the lack of antitumor activity precludes further studies of plitidepsin in this setting.

  20. Increasing the use of second-line therapy is a cost-effective approach to prevent the spread of drug-resistant HIV: a mathematical modelling study

    NARCIS (Netherlands)

    Nichols, Brooke E.; Sigaloff, Kim C. E.; Kityo, Cissy; Hamers, Raph L.; Baltussen, Rob; Bertagnolio, Silvia; Jordan, Michael R.; Hallett, Timothy B.; Boucher, Charles A. B.; de Wit, Tobias F. Rinke; van de Vijver, David A. M. C.

    2014-01-01

    Earlier antiretroviral therapy (ART) initiation reduces HIV-1 incidence. This benefit may be offset by increased transmitted drug resistance (TDR), which could limit future HIV treatment options. We analyze the epidemiological impact and cost-effectiveness of strategies to reduce TDR. We develop a

  1. Long term outcomes after salvage radiotherapy for postoperative locoregionally recurrent non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ji; Song, Chang Hoon; Kim, Jae Sung [Dept. of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Mi Young [Dept. of Radiation Oncology, Kyungpook National University Medical Center, Daegu (Korea, Republic of)

    2017-03-15

    The outcomes and toxicities of locoregionally recurrent non-small-cell lung cancer (NSCLC) patients treated with curative radiotherapy were evaluated in the modern era. Fifty-seven patients receiving radical radiotherapy for locoregionally recurrent NSCLC without distant metastasis after surgery from 2004 to 2014 were reviewed. Forty-two patients were treated with concurrent chemoradiotherapy (CCRT), and 15 patients with radiotherapy alone. The median radiation dose was 66 Gy (range, 45 to 70 Gy). Lung function change after radiotherapy was evaluated by comparing pulmonary function tests before and at 1, 6, and 12 months after radiotherapy. Median follow-up was 53.6 months (range, 12.0 to 107.5 months) among the survivors. The median overall survival (OS) and progression-free survival (PFS) were 54.8 months (range, 3.0 to 116.9 months) and 12.2 months (range, 0.8 to 100.2 months), respectively. Multivariate analyses revealed that single locoregional recurrence focus and use of concurrent chemotherapy were significant prognostic factors for OS (p = 0.048 and p = 0.001, respectively) and PFS (p = 0.002 and p = 0.026, respectively). There was no significant change in predicted forced expiratory volume in one second after radiotherapy. Although diffusing lung capacity for carbon monoxide decreased significantly at 1 month after radiotherapy (p < 0.001), it recovered to pretreatment levels within 12 months. Acute grade 3 radiation pneumonitis and esophagitis were observed in 3 and 2 patients, respectively. There was no chronic complication observed in all patients. Salvage radiotherapy showed good survival outcomes without severe complications in postoperative locoregionally recurrent NSCLC patients. A single locoregional recurrent focus and the use of CCRT chemotherapy were associated with improved survival. CCRT should be considered as a salvage treatment in patients with good prognostic factors.

  2. Salvaging of service exposed cast alloy 625 cracker tubes of ammonia based Heavy Water Plants

    International Nuclear Information System (INIS)

    Kumar, Niraj; Misra, B.; Mahajan, M.P.; Mittra, J.; Sundararaman, M.; Chakravartty, J.K.

    2006-01-01

    In ammonia based heavy water plants, cracking of ammonia vapour, enriched in deuterium is carried out inside a cracker tube, packed with catalyst. These cracker tubes are made of alloy 625 (either wrought or cast) having dimensions of about 12.5 metres long, 88 mm outer diameter and 7.9 mm wall thickness. Seventy such tubes are housed in a typical ammonia cracker unit. The anticipated design life of such tube is 1,00,000 hrs. when operated at 720 degC based on creep as main degradation mechanism. Presently, these tubes are being operated at 680 degC skin temperature. Alloy 625 tubes are costly and normally not manufactured in India and are being imported. The cast alloy 625 cracker tubes have outlived their design life of 100,000 hrs. Therefore it has been decided to salvage the cast cracker tubes and extend the life further as it had already been done for wrought tubes. Similar to the earlier attempt of resolutionising of wrought alloy 625 tubes, efforts are in progress to salvage these cast tubes. In this study, cast tubes samples were subjected to solution-annealing treatment at two different temperatures, 1100degC and 1160degC respectively for two hrs. Mechanical properties along with the microstructure of the samples, which were resolutionized at 1160degC were comparable with that of virgin material. The 12.5 metres long cast alloy 625 cracker tubes will also be shortly solution-annealed in a specially designed resistance heating furnace after completing some more tests. (author)

  3. Pancreas Transplant Venous Thrombosis: Role of Endovascular Interventions for Graft Salvage

    International Nuclear Information System (INIS)

    Stockland, Andrew H.; Willingham, Darrin L.; Paz-Fumagalli, Ricardo; Grewal, Hani P.; McKinney, J. Mark; Hughes, Christopher B.; Walser, Eric M.

    2009-01-01

    Venous thrombosis of pancreas transplant allografts often leads to graft loss. We evaluated the efficacy of emergent endovascular techniques to salvage thrombosed pancreatic allografts in a series of six patients. Of the 76 pancreas transplants performed between 2002 and 2006, six patients were diagnosed with venous thrombosis on MRI between 2 and 28 days posttransplant (mean, 9 days). Five patients were systemic-enteric (donor portal vein anastomosis to recipient iliac vein) and one patient was portal-enteric (donor portal vein anastomosis to recipient superior mesenteric vein). Conventional venography confirmed the diagnosis of venous thrombosis in all patients. One patient was treated with catheter-directed venous thrombolysis and balloon thrombectomy. Another patient was treated with rheolytic thrombectomy alone. The remaining four patients were treated with a combination of these mechanical and thrombolytic techniques. Completion venography revealed >50% clot reduction and resumption of venous drainage in all patients. One patient required additional intervention 16 days later for recurrent thrombosis. Two patients required metal stent placement for anastomotic stenoses or kinks. One patient required pancreatectomy 36 h after attempted salvage secondary to a major hemorrhage and graft necrosis. Two patients recovered pancreatic function initially but lost graft function at 8 and 14 months, respectively, from severe chronic rejection. Patient survival was 100%, long-term graft survival was 50%, rethrombosis rate was 16.6%, and graft loss from rejection was 33%. In conclusion, early recognition and treatment of venous thrombosis after pancreas transplantation has acceptable morbidity and no mortality using short-term endovascular pharmacomechanical therapy.

  4. Cytotect®CP as salvage therapy in patients with CMV infection following allogeneic hematopoietic cell transplantation: a multicenter retrospective study.

    Science.gov (United States)

    Alsuliman, Tamim; Kitel, Caroline; Dulery, Rémy; Guillaume, Thierry; Larosa, Fabrice; Cornillon, Jérôme; Labussière-Wallet, Helene; Médiavilla, Clémence; Belaiche, Stéphanie; Delage, Jeremy; Alain, Sophie; Yakoub-Agha, Ibrahim

    2018-04-13

    Cytomegalovirus is one of the main contributing factors to high mortality rates in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). The main factors of treatment failure are both drug resistance and intolerance. In some cases, Cytotect®CP CMV-hyperimmune globulin is used as salvage therapy. This study aims to investigate the safety and efficacy of Cytotect®CP as a salvage therapy in patients with CMV infection after allo-HCT. Twenty-three consecutive patients received Cytotect®CP for CMV infection after prior CMV therapy. At the time of Cytotect®CP introduction, 17 patients (74%) had developed acute GVHD and 15 patients (64%) were receiving steroid treatment; Cytotect®CP was used as monotherapy (n = 7) and in combination (n = 16). Overall, response was observed in 18 patients (78%) with a median time of 15 days (range: 3-51). Of the 18 responders, 4 experienced CMV reactivation, while 5 responders died within 100 days of beginning treatment. Of these 5 deaths, 4 were due to causes unrelated to CMV. Estimated 100-day OS from the introduction of Cytotect®CP was 69.6%. No statistically significant difference was observed in 100-day OS between responders and non-responders (73.7% vs 50.0%, p = 0.258). Cytotect®CP as salvage therapy is effective and well-tolerated. Given its safety profile, early treatment use should be considered.

  5. Nonoperative active management of critical limb ischemia: initial experience using a sequential compression biomechanical device for limb salvage.

    LENUS (Irish Health Repository)

    Sultan, Sherif

    2008-01-01

    Critical limb ischemia (CLI) patients are at high risk of primary amputation. Using a sequential compression biomechanical device (SCBD) represents a nonoperative option in threatened limbs. We aimed to determine the outcome of using SCBD in amputation-bound nonreconstructable CLI patients regarding limb salvage and 90-day mortality. Thirty-five patients with 39 critically ischemic limbs (rest pain = 12, tissue loss = 27) presented over 24 months. Thirty patients had nonreconstructable arterial outflow vessels, and five were inoperable owing to severe comorbidity scores. All were Rutherford classification 4 or 5 with multilevel disease. All underwent a 12-week treatment protocol and received the best medical treatment. The mean follow-up was 10 months (SD +\\/- 6 months). There were four amputations, with an 18-month cumulative limb salvage rate of 88% (standard error [SE] +\\/- 7.62%). Ninety-day mortality was zero. Mean toe pressures increased from 38.2 to 67 mm Hg (SD +\\/- 33.7, 95% confidence interval [CI] 55-79). Popliteal artery flow velocity increased from 45 to 47.9 cm\\/s (95% CI 35.9-59.7). Cumulative survival at 12 months was 81.2% (SE +\\/- 11.1) for SCBD, compared with 69.2% in the control group (SE +\\/- 12.8%) (p = .4, hazards ratio = 0.58, 95% CI 0.15-2.32). The mean total cost of primary amputation per patient is euro29,815 ($44,000) in comparison with euro13,900 ($20,515) for SCBD patients. SCBD enhances limb salvage and reduces length of hospital stay, nonoperatively, in patients with nonreconstructable vessels.

  6. Re-irradiation of the chest wall for local breast cancer recurrence. Results of salvage brachytherapy with hyperthermia

    Energy Technology Data Exchange (ETDEWEB)

    Auoragh, A. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); Hospital Fuerth, Department of Radiation Oncology, Fuerth (Germany); Strnad, V.; Ott, O.J.; Fietkau, R. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); Beckmann, M.W. [University Hospital Erlangen, Department of Gynecology and Obstetrics, Erlangen (Germany)

    2016-09-15

    Following mastectomy and adjuvant external beam radiation therapy in patients with breast cancer, the incidence of local or locoregional recurrence is approximately 9 % (2-20 %). Alongside the often limited possibilities of surgical treatment, radiation therapy combined with superficial hyperthermia is the most effective local therapy. In the present work, a retrospective analysis of salvage brachytherapy combined with superficial hyperthermia for chest wall recurrences is presented. Between 2004 and 2011, 18 patients with a total of 23 target volumes resulting from chest wall recurrences after previously mastectomy and external beam radiation therapy (median 56 Gy, range 50-68 Gy) were treated with superficial brachytherapy as salvage treatment: 8 patients (44 %) had macroscopic tumor, 3 (17 %) had microscopic tumor (R1), and 7 (39 %) had undergone R0 resection and were treated due to risk factors. A dose of 50 Gy was given (high-dose rate [HDR] and pulsed-dose rate [PDR] procedures). In all, 5 of 23 patients (22 %) received additional concurrent chemotherapy, and in 20 of 23 (87 %) target volumes additional superficial hyperthermia was carried out twice weekly. The 5-year local recurrence-free survival was 56 %, the disease-free survival was 28 %, and a 5-year overall survival was 22 %. Late side effects Common Toxicity Criteria (CTC) grade 3 were reported in 17 % of the patients: 2 of 18 (11 %) had CTC grade 3 fibrosis, and 1 of 18 (6 %) had a chronic wound healing disorder. Re-irradiation as salvage brachytherapy with superficial hyperthermia for chest wall recurrences is a feasible and safe treatment with good local control results and acceptable late side effects. (orig.) [German] Nach einer Mastektomie und adjuvanter Strahlentherapie bei Patientinnen mit Mammakarzinom kommt es bei 9 % (2-20 %) zum lokalen bzw. lokoregionaeren Rezidiv. Neben den oft limitierten operativen Behandlungsmoeglichkeiten ist die Strahlentherapie mit Oberflaechenhyperthermie die

  7. Vinorelbine-based salvage therapy in HER2-positive metastatic breast cancer patients progressing during trastuzumab-containing regimens: a retrospective study

    Directory of Open Access Journals (Sweden)

    Viale Giuseppe

    2008-07-01

    Full Text Available Abstract Background The vinka-alkaloyd vinorelbine is a potentially valuable treatment in patients with HER2-positive, trastuzumab-resistant advanced breast cancer. We sought to document the clinical activity of vinorelbine-based salvage treatments in this clinical setting. Methods We analyzed a cohort of 424 consecutive women receiving trastuzumab-based therapy for HER2-positive advanced breast cancer. Of these, 299 were identified as progressing during the initial trastuzumab-based treatment, and 77 received vinorelbine-based therapy as first salvage treatment. Central review of pathological specimens revealed that 70 patients had HER2-amplification detected by FISH. For these patients we determined overall response rate (ORR = complete-CR + partial-PR and clinical benefit (CB = CR+PR+ Stable disease lasting at least 6 months, time to progression (TTP and overall survival (OS from the initiation of vinorelbine-based salvage therapy. Results In 60 patients who were evaluable for tumor response, ORR and CB rates were 28% (95% C.I. 18%-41% and 50% (95% C.I. 38%-62%, respectively. Median follow-up from the initiation of salvage therapy was 15 months (range 1–63 months. Median TTP and OS were 7.1 months (95% C.I. 6.6–7.7 months and 21 months (95% C.I. 14.3–27.7 months, respectively. No differences in clinical outcomes were observed according to whether vinorelbine was administered as a single agent or in combination with other cytostatics, or whether trastuzumab was stopped or continued beyond disease progression. Conclusion our findings suggests that vinorelbine-based combinations are active and should be further evaluated in studies conducted in trastuzumab-resistant patients, including those evaluating newer HER2-targeting agents.

  8. Vibrio Phage KVP40 Encodes a Functional NAD+ Salvage Pathway.

    Science.gov (United States)

    Lee, Jae Yun; Li, Zhiqun; Miller, Eric S

    2017-05-01

    The genome of T4-type Vibrio bacteriophage KVP40 has five genes predicted to encode proteins of pyridine nucleotide metabolism, of which two, nadV and natV , would suffice for an NAD + salvage pathway. NadV is an apparent nicotinamide phosphoribosyltransferase (NAmPRTase), and NatV is an apparent bifunctional nicotinamide mononucleotide adenylyltransferase (NMNATase) and nicotinamide-adenine dinucleotide pyrophosphatase (Nudix hydrolase). Genes encoding the predicted salvage pathway were cloned and expressed in Escherichia coli , the proteins were purified, and their enzymatic properties were examined. KVP40 NadV NAmPRTase is active in vitro , and a clone complements a Salmonella mutant defective in both the bacterial de novo and salvage pathways. Similar to other NAmPRTases, the KVP40 enzyme displayed ATPase activity indicative of energy coupling in the reaction mechanism. The NatV NMNATase activity was measured in a coupled reaction system demonstrating NAD + biosynthesis from nicotinamide, phosphoribosyl pyrophosphate, and ATP. The NatV Nudix hydrolase domain was also shown to be active, with preferred substrates of ADP-ribose, NAD + , and NADH. Expression analysis using reverse transcription-quantitative PCR (qRT-PCR) and enzyme assays of infected Vibrio parahaemolyticus cells demonstrated nadV and natV transcription during the early and delayed-early periods of infection when other KVP40 genes of nucleotide precursor metabolism are expressed. The distribution and phylogeny of NadV and NatV proteins among several large double-stranded DNA (dsDNA) myophages, and also those from some very large siphophages, suggest broad relevance of pyridine nucleotide scavenging in virus-infected cells. NAD + biosynthesis presents another important metabolic resource control point by large, rapidly replicating dsDNA bacteriophages. IMPORTANCE T4-type bacteriophages enhance DNA precursor synthesis through reductive reactions that use NADH/NADPH as the electron donor and NAD

  9. Short-time effect of salvage harvesting on microbial soil properties in a Mediterranean area affected by a wildfire: preliminary results

    Science.gov (United States)

    Moltó, Jorge; Mataix-Solera, Jorge; Arcenegui, Victoria; Morugan, Alicia; Girona, Antonio; Garcia-orenes, Fuensanta

    2014-05-01

    In the Mediterranean region, wildfires are considered one of the main ecological factors, which, in addition to and in relation to changes in soil use, may cause soil loss and degradation, one of the most important environmental problems that humanity must face up to. As is well known, the soil-plant system is one of the key factors determining ecological recovery after the occurrence of a wildfire. Traditionally, a variety of forestry practices have been implemented on spanish sites after the incidence of a wildfire. Among them stands out the complete extraction of the burned wood, which consist in getting rid of the branches and other wooden debris using small controlled bonfires, splintering or mechanical extraction. This set of post-fire management practices is known as salvage logging or salvage harvesting. Despite the remarkable relevance and influence that this conjunction of techniques has on land management after a wildfire, very little experimental research focused on assessing the impact of salvage logging on the vegetal community has been done. Furthermore, even less research inquiring into the mode and grade of incidence that the salvage logging produces on soil properties has taken place. The aim of this research is to assess the effects that the salvage harvesting has on different soil microbial properties and other related properties. The study area is located in the Natural Park of the "Sierra de Mariola" in the province of Alicante, southeastern Spain. This location was affected by a wildfire whose extension reached more than 500 Ha in July 2012. Different post-fire treatments were proposed by the authorities, including salvage harvesting in some areas. Two different treatments were distinguished for the study, "control" (without any kind of burned wood removal) and "harvest" (where salvage logging was carried out), in each area three 4 m2 sampling plots were set up. These two treatments were established on the same slope with the same orography

  10. Reduced dose of salvage-line regorafenib monotherapy for metastatic colorectal cancer in Japan.

    Science.gov (United States)

    Hirano, Gen; Makiyama, Akitaka; Makiyama, Chinatsu; Esaki, Taito; Oda, Hisanobu; Uchino, Keita; Komoda, Masato; Tanaka, Risa; Matsushita, Yuzo; Mitsugi, Kenji; Shibata, Yoshihiro; Kumagai, Hozumi; Arita, Shuji; Ariyama, Hiroshi; Kusaba, Hitoshi; Akashi, Koichi; Baba, Eishi

    2015-01-01

    Salvage-line regorafenib monotherapy exhibited a marked survival benefit for metastatic colorectal cancer (mCRC). However, the toxicity of this regimen has resulted in the clinical use of a reduced dose of regorafenib. Thirty-two Japanese mCRC patients (median age=61 years) who had been treated with regorafenib were retrospectively examined. Best objective response rate was 0% and stable disease (SD) was 31%. Median progression-free survival was 81 days and median overall survival was 233 days. Adverse events of any grade were observed in all patients: 17 (53%) patients suffered grade 3 or 4 adverse events including fatigue (13%), anorexia (13%), hand-foot skin reaction (22%) and elevations of alanine aminotransferase/aspartate aminotransferase (19%/16%). One patient with grade 5 liver dysfunction was identified (3%). Twenty-nine (91%) patients required treatment dose reduction or a delay in treatment. The relative dose intensity was 59%. Regorafenib treatments were terminated because of disease progression (59%) or adverse events (34%). Despite a decrease in the intensity of regorafenib treatment, because of severe adverse events, a fairly favorable efficacy was achieved in Japanese patients. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  11. Psychosocial reactions to upper extremity limb salvage: A cross-sectional study.

    Science.gov (United States)

    Sposato, Lindsay; Yancosek, Kathleen; Lospinoso, Josh; Cancio, Jill

    2017-08-09

    Descriptive cross-sectional survey study. Limb salvage spares an extremity at risk for amputation after a major traumatic injury. Psychosocial recovery for individuals with lower extremity limb salvage has been discussed in the literature. However, to date, psychosocial reactions for individuals with upper extremity (UE) limb salvage have not been examined. To determine which factors may influence psychosocial adaptation to UE limb salvage. Participants (n = 30; 28 males) were adults (mean, 30.13; range, 18-61) who sustained an UE limb salvage from a traumatic event. Adaptation was measured using a modified version of the Reactions to Impairment and Disability Inventory. A linear mixed-effects regression found that worse psychosocial adaptation was associated with having less than a college degree, being less than 6 months post-injury, being older than 23 years, and having more pain. Dominant hand injuries were found to influence poor adaptation on the denial Reactions to Impairment and Disability Inventory subscale only. The results of this study indicate that there is potential for nonadaptive reactions and psychological distress with certain variables in UE limb salvage. Therapists may use these results to anticipate which clients may be at risk for poor psychosocial outcomes. This study indicates the need for early consideration to factors that affect psychological prognosis for the UE limb salvage population. However, future research is indicated to better understand the unique psychosocial challenges and needs of these individuals. 4. Copyright © 2017 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

  12. Deoxynucleoside salvage enzymes and tissue specific mitochondrial DNA depletion.

    Science.gov (United States)

    Wang, L

    2010-06-01

    Adequate mitochondrial DNA (mtDNA) copies are required for normal mitochondria function and reductions in mtDNA copy number due to genetic alterations cause tissue-specific mtDNA depletion syndrome (MDS). There are eight nuclear genes, directly or indirectly involved in mtDNA replication and mtDNA precursor synthesis, which have been identified as the cause of MDS. However, the tissue specific pathology of these nuclear gene mutations is not well understood. Here, mtDNA synthesis, mtDNA copy number control, and mtDNA turnover, as well as the synthesis of mtDNA precursors in relation to the levels of salvage enzymes are discussed. The question why MDS caused by TK2 and p53R2 mutations are predominantly muscle specific while dGK deficiency affected mainly liver will be addressed.

  13. A comparison of salvage surgery following CRT and following BRT for advanced hypopharyngeal cancer

    International Nuclear Infor