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Sample records for adjuvant systemic therapy

  1. Utility of adjuvant systemic therapy in melanoma.

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    A.M.M. Eggermont (Alexander); A. Testori (Alessandro); J. Marsden (Jeremy); P. Hersey (Peter); I. Quirt (Ian); T. Petrella; H. Gogas (Helen); R.M. MacKie; A. Hauschild (Axel)

    2009-01-01

    textabstractThe lack of effective drugs in stage IV melanoma has impacted the effectiveness of adjuvant therapies in stage II/III disease. To date, chemotherapy, immunostimulants and vaccines have been used with minimal success. Interferon (IFN) has shown an effect on relapse-free survival (RFS) in

  2. Timing of radiotherapy in breast-conserving therapy: a large prospective cohort study of node-negative breast cancer patients without adjuvant systemic therapy

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    Jobsen, J.J.; van der Palen, Jacobus Adrianus Maria; Baum, M.; Brinkhuis, M.; Struikmans, H.

    2013-01-01

    Background: To investigate the issue of timing of radiation therapy (RT) after lumpectomy in relation to recurrences and outcome. Methods: Analysis was done on 1107 breast-conserving therapies (BCT) with 1070 women, all without lymph node metastasis and without any adjuvant systemic therapy. Timing

  3. The effects of population-based mammography screening starting between age 40 and 50 in the presence of adjuvant systemic therapy.

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    de Gelder, Rianne; Heijnsdijk, Eveline A M; Fracheboud, Jacques; Draisma, Gerrit; de Koning, Harry J

    2015-07-01

    Adjuvant systemic therapy has been shown to be effective in reducing breast cancer mortality. The additional effect of mammography screening remains uncertain, in particular for women aged 40-49 years. We therefore assessed the effects of screening starting between age 40 and 50, as compared to the effects of adjuvant systemic therapy. The use of adjuvant endocrine therapy, chemotherapy and the combination of endocrine- and chemotherapy, as well as the uptake of mammography screening in the Netherlands was modeled using micro-simulation. The effects of screening and treatment were modeled based on randomized controlled trials. The effects of adjuvant therapy, biennial screening between age 50 and 74 in the presence of adjuvant therapy, and extending the screening programme by starting at age 40 were assessed by comparing breast cancer mortality in women aged 0-100 years in scenarios with and without these interventions. In 2008, adjuvant treatment was estimated to have reduced the breast cancer mortality rate in the simulated population by 13.9%, compared to a situation without treatment. Biennial screening between age 50 and 74 further reduced the mortality rate by 15.7%. Extending screening to age 48 would lower the mortality rate by 1.0% compared to screening from age 50; 10 additional screening rounds between age 40 and 49 would reduce this rate by 5.1%. Adjuvant systemic therapy and screening reduced breast cancer mortality in similar amounts. Expanding the lower age limit of screening would further reduce breast cancer mortality. © 2014 UICC.

  4. Extended Adjuvant Therapy for Breast Cancer

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    An NCI Cancer Currents blog on findings from a recent clinical trial which showed that extending adjuvant therapy with an aromatase inhibitor can have important benefits for some women with early-stage cancer.

  5. [Adjuvant antioxidant therapy in varicocele infertility].

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    Gamidov, S I; Ovchinnikov, R I; Popova, A Yu; Avakyan, A Yu; Sukhikh, G T

    2017-06-01

    Infertility affects an estimated 15% of couples globally. Male factor infertility accounts for about a half of infertility cases. About 40% of infertile men have varicocele. The aim of this study was to investigate the efficacy and safety of a complex of acetyl-L-carnitine, L-carnitine fumarate and alpha-lipoic acid (SpermActin-forte) (SA) for adjuvant antioxidant therapy after microsurgical varicocelectomy (MVE) in men with varicocele and assess its impact on the level of DNA fragmentation in sperm cells. This is an open, prospective, randomized trial comprising 114 men aged 25-45 (mean 34.1+/-12.1) years who underwent MVE. The patients were allocated to receive either adjuvant SA (n=38), SA in combination with a vitamin complex (VC) (n=38) or no adjuvant therapy (n=38). The efficacy was assessed at 3 months by testing standard semen parameters and the level of sperm DNA fragmentation. MVE led to a 21.7% increase in the progressive sperm motility compared to the baseline level. In patients receiving SA, this was by 76.7% due to active sperm motility (category A) at 3 months. MVE with concurrent supplementation of SA resulted in a 22.3% decrease in the level of sperm DNA fragmentation at 3 months. When used in the postoperative period after MVE, SA and VC resulted in a 27% increase in the sperm concentration at 3 months. There were no side effects of pharmacotherapy. The statistical significance of the change in variables was calculated using the Wilcoxon test. Critical level =0.05 was established for all criteria. Using nutraceuticals (SA) after MVE is an effective and safe adjuvant antioxidant therapy of male infertility in patients with varicocele which leads to an improvement in the basic sperm parameters (sperm concentration and motility) and a decrease in the level of sperm DNA fragmentation in the short term. Adjuvant antioxidant therapy of varicocele infertility potentiates the effects of monotherapy (both medical and surgical), leads to an increase in its

  6. Locoregional Failure in Early-Stage Breast Cancer Patients Treated With Radical Mastectomy and Adjuvant Systemic Therapy: Which Patients Benefit From Postmastectomy Irradiation?

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    Trovo, Marco, E-mail: marcotrovo33@hotmail.com [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Durofil, Elena [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Polesel, Jerry [Department of Epidemiology and Biostatistics, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Roncadin, Mario [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Perin, Tiziana [Department of Pathology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Mileto, Mario; Piccoli, Erica [Department of Surgery, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Quitadamo, Daniela [Scientific Direction, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Massarut, Samuele [Department of Surgery, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Carbone, Antonino [Department of Pathology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Trovo, Mauro G. [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy)

    2012-06-01

    Purpose: To assess the locoregional failure in patients with Stage I-II breast cancer treated with radical mastectomy and to evaluate whether a subset of these patients might be at sufficiently high risk of locoregional recurrence (LRR) to benefit from postmastectomy irradiation (PMRT). Methods and Materials: Stage I-II breast cancer patients (n = 150) treated with radical mastectomy without adjuvant irradiation between 1999 and 2005 were analyzed. The pattern of LRR was reported. Kaplan-Meier analysis was used to calculate rates of LRR, and Cox proportional hazards methods were used to evaluate potential risk factors. Results: Median follow-up was 75 months. Mean patient age was 56 years. One-hundred forty-three (95%) patients received adjuvant systemic therapy: 85 (57%) hormonal therapy alone, 14 (9%) chemotherapy alone, and 44 (29%) both chemotherapy and hormonal therapy. Statistically significant factors associated with increased risk of LRR were premenopausal status (p = 0.004), estrogen receptor negative cancer (p = 0.02), pathologic grade 3 (p = 0.02), and lymphovascular invasion (p = 0.001). T and N stage were not associated with increased risk of regional recurrence. The 5-year LRR rate for patients with zero or one, two, three, and four risk factors was 1%, 10.3%, 24.2%, and 75%, respectively. Conclusions: A subset of patients with early-stage breast cancer is at high risk of LRR, and therefore PMRT might be beneficial.

  7. Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

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    Ohri, Nitin, E-mail: ohri.nitin@gmail.com [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Garg, Madhur K. [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Aparo, Santiago; Kaubisch, Andreas [Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Tome, Wolfgang [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kennedy, Timothy J. [Department of Surgical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kalnicki, Shalom; Guha, Chandan [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)

    2013-06-01

    Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy.

  8. Spa adjuvant therapy improves diabetic lower extremity arterial disease.

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    Qiu, Yongbin; Zhu, Yi; Jia, Wei; Chen, Songhua; Meng, Qingzhou

    2014-08-01

    To investigate the effect of spa adjuvant therapy on diabetic lower extremity arterial disease (LEAD). 128 patients with type II diabetes were separated into three groups according to the degree of lower extremity vascular stenosis. Patients within each group were then randomly divided to receive no treatment (control) or spa adjuvant therapy (treatment). Clinical symptoms, blood pressure and hemodynamic analyses were compared between control and treatment groups by Chi square or t-test. After adjuvant therapy with spa, patients' pain, numbness, and cold sensation were significantly improved compared with control groups (PSpa adjuvant therapy also significantly increased the dorsalis pedis pulse and systolic peak velocity ratio of patients with mild lower extremity vascular stenosis compared with control groups (P0.05). Both in the spa and control groups, there were no significant differences before and after medication for fasting, 2-h postprandial blood glucose and glycosylated hemoglobin (HbA1C) analyses (P>0.05). Spa adjuvant therapy can significantly alleviate lower extremity pain, numbness, and cold sensory symptoms in diabetic LEAD patients with stenosis. Moreover, in LEAD patients with mild stenosis, spa adjuvant therapy also improves the dorsalis pedis pulse and systolic peak velocity ratio, suggesting a potential role for spa therapy as an early intervention strategy to treat the initial stages of disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Low-dose rituximab as an adjuvant therapy in pemphigus

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    Jaya Gupta

    2017-01-01

    Conclusion: Our results show that low-dose rituximab is a well-tolerated and beneficial adjuvant therapy in recalcitrant pemphigus which helps reduce both the severity of disease as well as the dose of steroids and immunosuppressants.

  10. The role of adjuvant therapy in uterine leiomyosarcoma.

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    Ducie, Jennifer A; Leitao, Mario M

    2016-01-01

    Uterine leiomyosarcoma (uLMS) is a rare mesenchymal tumor of the gynecologic tract. Although diagnosed in only 1-3% of patients with uterine cancer, uLMS accounts for the majority of uterine cancer-related deaths. The standard of care for patients with uLMS includes total hysterectomy and bilateral salpingo-oophorectomy (BSO). There are no standard recommendations regarding adjuvant or palliative therapy. Many cytotoxic and targeted agents have been studied in clinical trials in an effort to identify an effective therapy that may alter the natural history of this disease. Unfortunately, as of now, there are no adjuvant therapy regimens that improve overall survival in this patient population. There is, therefore, an unmet need to identify a novel therapy that will improve the survival of women diagnosed with this aggressive disease. Here we summarize the existing literature on adjuvant therapy in uLMS, specifically highlighting advances made in the last 5 years.

  11. Immunomodulatory adjuvant therapy in severe community-acquired pneumonia.

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    Morton, Ben; Pennington, Shaun Harry; Gordon, Stephen B

    2014-10-01

    Severe pneumonia has a high mortality (38.2%) despite evidence-based therapy. Rising rates of antimicrobial resistance increase the urgency to develop new treatment strategies. Multiple adjuvant therapies for pneumonia have been investigated but none are currently licensed. Profound immune dysregulation occurs in patients with severe infection. An initial hyper-inflammatory response is followed by a secondary hypo-inflammatory response with 'immune-paralysis'. There is focus on the development of immunostimulatory agents to improve host ability to combat primary infection and reduce secondary infections. Successful treatments must be targeted to immune response; promising biomarkers exist but have not yet reached common bedside practice. We explore evidence for adjuvant therapies in community-acquired pneumonia. We highlight novel potential treatment strategies using a broad-based search strategy to include publications in pneumonia and severe sepsis. We explore reasons for the failure to develop effective adjuvant therapies and highlight the need for targeted therapy specific to immune activity.

  12. Adjuvant therapy for gastric cancer: Current and future directions

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    Foo, Marcus; Leong, Trevor

    2014-01-01

    The management of gastric cancer continues to evolve. Whilst surgery alone is effective when tumours present early, a large proportion of patients are diagnosed with loco-regionally advanced disease, resulting in high loco-regional and distant relapse rates, with subsequent poor survival. Early attempts at improving outcomes following resection were disappointing; however, randomized trials have now established either post-operative chemoradiotherapy (INT0116) or peri-operative chemotherapy as standard adjuvant therapies in the Western world. There remain, however, significant differences in the approach to management between the West and East. In Asia, where there is the highest incidence of gastric cancer, extended resection followed by adjuvant chemotherapy represents the standard of care. This review discusses current standard adjuvant therapy in gastric adenocarcinoma, as well as recent and ongoing trials investigating novel (neo)adjuvant approaches, which hope to build on the successes of previous studies. PMID:25320509

  13. Adjuvant therapy for gastric cancer: current and future directions.

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    Foo, Marcus; Leong, Trevor

    2014-10-14

    The management of gastric cancer continues to evolve. Whilst surgery alone is effective when tumours present early, a large proportion of patients are diagnosed with loco-regionally advanced disease, resulting in high loco-regional and distant relapse rates, with subsequent poor survival. Early attempts at improving outcomes following resection were disappointing; however, randomized trials have now established either post-operative chemoradiotherapy (INT0116) or peri-operative chemotherapy as standard adjuvant therapies in the Western world. There remain, however, significant differences in the approach to management between the West and East. In Asia, where there is the highest incidence of gastric cancer, extended resection followed by adjuvant chemotherapy represents the standard of care. This review discusses current standard adjuvant therapy in gastric adenocarcinoma, as well as recent and ongoing trials investigating novel (neo)adjuvant approaches, which hope to build on the successes of previous studies.

  14. Adjuvant Biological Therapies in Chronic Leg Ulcers

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    Natalia Burgos-Alonso

    2017-11-01

    Full Text Available Current biological treatments for non-healing wounds aim to address the common deviations in healing mechanisms, mainly inflammation, inadequate angiogenesis and reduced synthesis of extracellular matrix. In this context, regenerative medicine strategies, i.e., platelet rich plasmas and mesenchymal stromal cell products, may form part of adjuvant interventions in an integral patient management. We synthesized the clinical experience on ulcer management using these two categories of biological adjuvants. The results of ten controlled trials that are included in this systematic review favor the use of mesenchymal stromal cell based-adjuvants for impaired wound healing, but the number and quality of studies is moderate-low and are complicated by the diversity of biological products. Regarding platelet-derived products, 18 controlled studies investigated their efficacy in chronic wounds in the lower limb, but the heterogeneity of products and protocols hinders clinically meaningful quantitative synthesis. Most patients were diabetic, emphasizing an unmet medical need in this condition. Overall, there is not sufficient evidence to inform routine care, and further clinical research is necessary to realize the full potential of adjuvant regenerative medicine strategies in the management of chronic leg ulcers.

  15. Adjuvant therapy for resectable pancreatic adenocarcinoma: review of the current treatment approaches and future directions.

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    Antoniou, G; Kountourakis, P; Papadimitriou, K; Vassiliou, V; Papamichael, D

    2014-02-01

    Adenocarcinoma of the pancreas carries a uniformly poor prognosis with high rates of loco-regional as well as systemic recurrence. Outcomes remain poor, even for early stage and resectable disease. It is perceived as inherently resistant to most of the currently available treatment options. Evidence supports the need for adjuvant chemotherapy but controversy remains in relation to the use of combined therapy, novel agents and the most appropriate timing of therapy. Despite no clear consensus, mainstay of treatment following resection is based primarily on single agent gemcitabine. Promising new agents and molecules of prognostic as well as predictive value under evaluation offer intriguing data, despite issues surrounding adjuvant therapy strategies. In this article, we sought to review the different therapeutic adjuvant modalities and future directions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Effect of adjuvant therapies on recurrence in aneurysmal bone cysts.

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    Keçeci, Burçin; Küçük, Levent; Isayev, Alovsat; Sabah, Dündar

    2014-01-01

    The aim of this study was to define the effective factors such as surgical method, age and cavity filling materials on local recurrence in the treatment of aneurysmal bone cysts. The study included 85 patients (mean age: 17.9 years) that received surgical treatment for primary aneurysmal bone cyst. Nine were treated with cyst excision and 76 with intralesional curettage. The intralesional curettage group was divided into 3 subgroups according to adjuvant therapies applied; the first group received no additional adjuvant therapy, the second group received additional high-speed burr and the third group received additional high-speed burr and alcohol/phenol adjuvant treatments. Bone graft or bone cement was used to fill in the cavity. Mean follow-up period was 107.5 months. Groups were analyzed statistically in terms of local recurrence. Onset of cyst in ages under 10 and 20 years were considered a negative prognostic factor and analyzed statistically. Local recurrence occurred in 10 (11.8%) patients. Mean duration between the initial operation and recurrence was 10 months. There was no significant difference in terms of local recurrence among the surgical treatment groups, adjuvant therapy groups, age groups and bone graft and bone cement groups. Careful curettage of the entire cyst wall remains the most important step in the intralesional treatment of aneurysmal bone cyst.

  17. Adjuvant Therapy for Stage II Colorectal Cancer: Who and with What?

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    Chung, Ki-Young Y; Kelsen, David

    2006-06-01

    The role of adjuvant chemotherapy for patients with stage II colon adenocarcinoma remains controversial. The high surgical cure rate for patients with "low-risk" stage II colon cancer, ranging from 75% to 80%, and the available clinical trials and meta-analyses provide conflicting recommendations for or against adjuvant chemotherapy for this group of patients. For fit "high-risk" stage II patients with clinical obstruction or perforation at presentation, in which the 5-year survival rate is 60% to 70%, there is little controversy, as these patients are routinely treated with adjuvant chemotherapy. Other potential high-risk factors, including high histologic grade, microsatellite instability, and loss of 18q, have yet to be validated in prospective trials. Patients with fewer than 12 regional lymph nodes identified in the surgical specimen have a statistically unclear risk of lymph node involvement. These patients may have stage III disease and should receive adjuvant therapy. The decision to use adjuvant chemotherapy to treat low-risk stage II colon cancer patients (no obstruction or perforation) should be an informed decision weighing the magnitude of a net 2% to 5% survival benefit, a 0.5% to 1.0% risk of mortality with chemotherapy in addition to 6 months of chemotherapy-related toxicities, other coexisting patient morbidities, and the anticipated life expectancy of each patient. As adjuvant chemotherapy is therapy addressing local or metastatic microscopic disease, and the effectiveness of systemic and biologically targeted therapy for advanced macroscopic colon cancer continues to improve rapidly, it remains to be determined by clinical trials whether therapies including newer agents such as cetuximab and bevacizumab administered in the adjuvant setting may affect survival for stage II cancer patients.

  18. Adjuvant Therapy of Triple Negative Breast Cancer

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    Perez, Edith A.; Moreno-Aspitia, Alvaro; Thompson, E. Aubrey; Andorfer, Cathy A

    2010-01-01

    Patients with the triple negative subtype of breast cancer have an overall poor outcome, with earlier relapses, distinct patterns of metastases, and lack of specific targets for treatment selection. Classification of these tumors has begun to be modified by inclusion of immunohistochemistry for various markers, and gene profiling, to further characterize this subtype of breast cancer, may aid in the identification of new targeted therapies. Anthracyclines and taxanes remain the standard of ca...

  19. Factors Affecting Adjuvant Therapy in Stage III Pancreatic Cancer—Analysis of the National Cancer Database

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    Mridula Krishnan

    2017-08-01

    Full Text Available Background: Adjuvant therapy after curative resection is associated with survival benefit in stage III pancreatic cancer. We analyzed the factors affecting the outcome of adjuvant therapy in stage III pancreatic cancer and compared overall survival with different modalities of adjuvant treatment. Methods: This is a retrospective study of patients with stage III pancreatic cancer listed in the National Cancer Database (NCDB who were diagnosed between 2004 and 2012. Patients were stratified based on adjuvant therapy they received. Unadjusted Kaplan-Meier and multivariable Cox regression analysis were performed. Results: We analyzed a cohort included 1731 patients who were recipients of adjuvant therapy for stage III pancreatic cancer within the limits of our database. Patients who received adjuvant chemoradiation had the longest postdiagnosis survival time, followed by patients who received adjuvant chemotherapy, and finally patients who received no adjuvant therapy. On multivariate analysis, advancing age and patients with Medicaid had worse survival, whereas Spanish origin and lower Charlson comorbidity score had better survival. Conclusions: Our study is the largest trial using the NCDB addressing the effects of adjuvant therapy specifically in stage III pancreatic cancer. Within the limits of our study, survival benefit with adjuvant therapy was more apparent with longer duration from date of diagnosis.

  20. Adjuvant radiation therapy in metastatic lymph nodes from melanoma

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    Penel Nicolas

    2011-02-01

    Full Text Available Abstract Purpose To analyze the outcome after adjuvant radiation therapy with standard fractionation regimen in metastatic lymph nodes (LN from cutaneous melanoma. Patients and methods 86 successive patients (57 men were treated for locally advanced melanoma in our institution. 60 patients (69% underwent LN dissection followed by radiation therapy (RT, while 26 patients (31% had no radiotherapy. Results The median number of resected LN was 12 (1 to 36 with 2 metastases (1 to 28. Median survival after the first relapse was 31.8 months. Extracapsular extension was a significant prognostic factor for regional control (p = 0.019. Median total dose was 50 Gy (30 to 70 Gy. A standard fractionation regimen was used (2 Gy/fraction. Median number of fractions was 25 (10 to 44 fractions. Patients were treated with five fractions/week. Patients with extracapsular extension treated with surgery followed by RT (total dose ≥50 Gy had a better regional control than patients treated by surgery followed by RT with a total dose Conclusion Adjuvant radiotherapy was able to increase regional control in targeted sub-population (LN with extracapsular extension.

  1. Exercise as an Adjuvant Therapy for Hematopoietic Stem Cell Mobilization

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    Emmons, Russell; Niemiro, Grace M.; De Lisio, Michael

    2016-01-01

    Hematopoietic stem cell transplant (HSCT) using mobilized peripheral blood hematopoietic stem cells (HSPCs) is the only curative strategy for many patients suffering from hematological malignancies. HSPC collection protocols rely on pharmacological agents to mobilize HSPCs to peripheral blood. Limitations including variable donor responses and long dosing protocols merit further investigations into adjuvant therapies to enhance the efficiency of HSPCs collection. Exercise, a safe and feasible intervention in patients undergoing HSCT, has been previously shown to robustly stimulate HSPC mobilization from the bone marrow. Exercise-induced HSPC mobilization is transient limiting its current clinical potential. Thus, a deeper investigation of the mechanisms responsible for exercise-induced HSPC mobilization and the factors responsible for removal of HSPCs from circulation following exercise is warranted. The present review will describe current research on exercise and HSPC mobilization, outline the potential mechanisms responsible for exercise-induced HSPC mobilization, and highlight potential sites for HSPC homing following exercise. We also outline current barriers to the implementation of exercise as an adjuvant therapy for HSPC mobilization and suggest potential strategies to overcome these barriers. PMID:27123008

  2. Exercise as an Adjuvant Therapy for Hematopoietic Stem Cell Mobilization.

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    Emmons, Russell; Niemiro, Grace M; De Lisio, Michael

    2016-01-01

    Hematopoietic stem cell transplant (HSCT) using mobilized peripheral blood hematopoietic stem cells (HSPCs) is the only curative strategy for many patients suffering from hematological malignancies. HSPC collection protocols rely on pharmacological agents to mobilize HSPCs to peripheral blood. Limitations including variable donor responses and long dosing protocols merit further investigations into adjuvant therapies to enhance the efficiency of HSPCs collection. Exercise, a safe and feasible intervention in patients undergoing HSCT, has been previously shown to robustly stimulate HSPC mobilization from the bone marrow. Exercise-induced HSPC mobilization is transient limiting its current clinical potential. Thus, a deeper investigation of the mechanisms responsible for exercise-induced HSPC mobilization and the factors responsible for removal of HSPCs from circulation following exercise is warranted. The present review will describe current research on exercise and HSPC mobilization, outline the potential mechanisms responsible for exercise-induced HSPC mobilization, and highlight potential sites for HSPC homing following exercise. We also outline current barriers to the implementation of exercise as an adjuvant therapy for HSPC mobilization and suggest potential strategies to overcome these barriers.

  3. Exercise as an Adjuvant Therapy for Hematopoietic Stem Cell Mobilization

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    Russell Emmons

    2016-01-01

    Full Text Available Hematopoietic stem cell transplant (HSCT using mobilized peripheral blood hematopoietic stem cells (HSPCs is the only curative strategy for many patients suffering from hematological malignancies. HSPC collection protocols rely on pharmacological agents to mobilize HSPCs to peripheral blood. Limitations including variable donor responses and long dosing protocols merit further investigations into adjuvant therapies to enhance the efficiency of HSPCs collection. Exercise, a safe and feasible intervention in patients undergoing HSCT, has been previously shown to robustly stimulate HSPC mobilization from the bone marrow. Exercise-induced HSPC mobilization is transient limiting its current clinical potential. Thus, a deeper investigation of the mechanisms responsible for exercise-induced HSPC mobilization and the factors responsible for removal of HSPCs from circulation following exercise is warranted. The present review will describe current research on exercise and HSPC mobilization, outline the potential mechanisms responsible for exercise-induced HSPC mobilization, and highlight potential sites for HSPC homing following exercise. We also outline current barriers to the implementation of exercise as an adjuvant therapy for HSPC mobilization and suggest potential strategies to overcome these barriers.

  4. Transcutaneous electrical nerve stimulation therapy: An adjuvant pain controlling modality in TMD patients - A clinical study

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    Muhammad Shanavas

    2014-01-01

    Conclusion: The observed data suggest that TENS therapy can be used as an adjuvant modality in the management of pain associated with TMDs. This study justifies the use of TENS therapy in the management of TMD.

  5. Exercise for women receiving adjuvant therapy for breast cancer.

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    Furmaniak, Anna C; Menig, Matthias; Markes, Martina H

    2016-09-21

    A huge clinical research database on adjuvant cancer treatment has verified improvements in breast cancer outcomes such as recurrence and mortality rates. On the other hand, adjuvant and neoadjuvant therapy with chemotherapy and radiotherapy impacts on quality of life due to substantial short- and long-term side effects. A number of studies have evaluated the effect of exercise interventions on those side effects. This is an updated version of the original Cochrane review published in 2006. The original review identified some benefits of physical activity on physical fitness and the resulting capacity for performing activities of daily life. It also identified a lack of evidence for other outcomes, providing clear justification for an updated review. To assess the effect of aerobic or resistance exercise interventions during adjuvant treatment for breast cancer on treatment-related side effects such as physical deterioration, fatigue, diminished quality of life, depression, and cognitive dysfunction. We carried out an updated search in the Cochrane Breast Cancer Group Specialised Register (30 March 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2015), MEDLINE (1966 to 30 March 2015), and EMBASE (1966 to 30 March 2015). We did not update the original searches in CINAHL (1982 to 2004), SPORTDiscus (1975 to 2004), PsycINFO (1872 to 2003), SIGLE (1880 to 2004), and ProQuest Digital Dissertations (1861 to 2004). We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov for ongoing trials on 30 March 2015. We screened references in relevant reviews and published clinical trials. We included randomised controlled trials that examined aerobic or resistance exercise or both in women undergoing adjuvant treatment for breast cancer. Published and unpublished trials were eligible. Two review authors independently performed data extraction, assessed trials, and graded the

  6. Probiotics as an adjuvant treatment in Helicobacter pylori eradication therapy.

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    Zhu, Xin Yan; Liu, Fei

    2017-04-01

    Over 80% of individuals infected with Helicobacter pylori (H. pylori) are asymptomatic. Increased resistance to antibiotics and decreased compliance to the therapeutic regimens have led to the failure of eradication therapy. Probiotics, with direct and indirect inhibitory effects on H. pylori in both animal models and clinical trials, have recently been used as a supplementary treatment in H. pylori eradication therapy. Probiotics have been considered useful because of the improvements in H. pylori eradication rates and therapy-related side effects although treatment outcomes using probiotics are controversial due to the heterogeneity of species, strains, doses and therapeutic duration of probiotics. Thus, despite the positive role of probiotics, several factors need to be further considered during their applications. Moreover, adverse events of probiotic use need to be noted. Further investigations into the safety of adjuvant probiotics to H. pylori eradication therapy are required. © 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  7. Eluation of adjuvant chemoradiation therapy for ampullary adenocarcinoma: the Johns Hopkins Hospital - Mayo Clinic collaborative study

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    Zhou Jessica

    2011-09-01

    Full Text Available Abstract Background The role of adjuvant chemoradiation therapy for ampullary carcinoma is unknown. Previous literature suggests that certain populations with high risk factors for recurrence may benefit from adjuvant chemoradiation. We combined the experience of two institutions to better delineate which patients may benefit from adjuvant chemoradiation. Methods Patients who underwent curative surgery for ampullary carcinoma at the Johns Hopkins Hospital (n = 290; 1992-2007 and at the Mayo Clinic (n = 130; 1977-2005 were reviewed. Patients with Results Median overall-survival was 39.9 months with 2- and 5-year survival rates of 62.4% and 39.1%. On univariate analysis, adverse prognostic factors for overall survival included T3/T4 stage disease (RR = 1.86, p = 0.002, node positive status (RR = 3.18, p Conclusions Node-positive patients with resected ampullary adenocarcinoma may benefit from 5-FU based adjuvant chemoradiation. Since a significant proportion of patients develop metastatic disease, there is a need for more effective systemic treatment.

  8. Adjuvant Therapies in Nonmetastatic Renal-Cell Carcinoma: A Review of the Literature.

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    Bandini, Marco; Smith, Ariane; Marchioni, Michele; Pompe, Raisa S; Martel, Tristan F; Cindolo, Luca; Montorsi, Francesco; Shariat, Shahrokh F; Briganti, Alberto; Kapoor, Anil; Capitanio, Umberto; Karakiewicz, Pierre I

    2018-02-02

    To conduct a review of literature on adjuvant therapy in nonmetastatic renal-cell carcinoma (nmRCC) treated with nephrectomy and to describe the efficacy of adjuvant agents on cancer control outcomes. A review of the literature was performed in January 2018 to identify all studies evaluating adjuvant therapy in patients with nmRCC treated with nephrectomy using PubMed, Embase, Medline, and Cochrane Library databases. The following keywords were used: adjuvant therapy, renal-cell carcinoma, nonmetastatic, targeted molecular therapy, kidney cancer. The ClinicalTrials.gov website was queried to identify ongoing trials. Traditional adjuvant therapy agents consisted of interferon α, interleukin 2, autologous tumor cell vaccines, and monoclonal antibodies. None provided survival benefit. Three contemporary studies (S-TRAC, ASSURE, and PROTECT) using targeted therapy compared sunitinib to placebo (S-TRAC), sunitinib or sorafenib to placebo (ASSURE), and pazopanib to placebo (PROTECT), with controversial results. In contrast to ASSURE and PROTECT, S-TRAC demonstrated improved disease-free survival. Several trials that use checkpoint immunotherapy agents or vascular endothelial growth factor receptor tyrosine kinase inhibitors are ongoing. Many traditional therapies have shown no success as adjuvant therapy for nmRCC after nephrectomy. Targeted adjuvant therapy for nmRCC after nephrectomy showed controversial results, and its routine use is not currently endorsed. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Adjuvant photodynamic therapy in surgical management of cerebral tumors

    Science.gov (United States)

    Chen, Zong-Qian; Wu, Si-En; Zhu, Shu-Gan

    1993-03-01

    We have performed high dose photoradiation therapy in patients with cerebral tumors. Twenty-seven patients had gliomas, two had metastatic cancer of the brain, one had malignant meningioma. Hematoporphyrin derivative was administered intravenously. All patients underwent a craniotomy with a radical or partial excision of the tumor. There was no evidence of increased cerebral edema and other toxicity from the therapy, and all patients were discharged from the hospital within 15 days after surgery. On the basis of animal experiments our institute started using photodynamic therapy (PDT) as an adjuvant measure to the operative therapy in 30 cases of cerebral tumors. Ten of these patients were excluded from this group because of the short postoperative following time. Here, the details of our experiences are presented as follows: 106 of C6 type glioma cell strain were implanted into the frontal lobe of a Chinese hamster. Fourteen days later intracranial gliomas developed, which were larger than 4 mm in diameter, HpD in a dosage of 4 mg/kg was injected into the tail vein of the animals. The fluorescence was seen 5 minutes later. The diagnostic laser used was He-Ca (Hc-type 15A, made at Shanghai Laser Institute) with a wavelength of 441.6 nm, power of 30 mw. The fluorescence reached its peak point 24 hours later, and the normal tissue can be identified by the lack of fluorescence. Then, the tumor tissue was further radiated with an Ar laser (made in Nanjing Electronic Factory, type 360), pumped dye-laser (made in Changchun Optic Machinery Institute, type 901) with a wavelength of 630 nm, and an energy density of more than 200 Joules/cm2, which might get the tumor cells destroyed selectively. The effect of photoradiation may reach as deep as 4 - 7 mm into the brain tissue without cerebral edema or necrosis.

  10. [Hyperbaric therapy and diving medicine - hyperbaric therapy part 2: adjuvant therapy].

    Science.gov (United States)

    Tetzlaff, Kay; Jüttner, Björn

    2015-10-01

    Hyperbaric oxygen therapy (HBOT), i. e. breathing pure oxygen at elevated ambient pressure, remains the gold standard of care in treating air or gas embolism and decompression illness. Guidelines are less clear on the value of HBOT in acute management of carbon monoxide (CO) poisoning or clostridial necrosis. To evaluate the evidence of clinical efficacy of HBOT we performed a systematic literature review. Part 1 assesses acute indications such as air or gas embolism, decompression sickness, CO-poisoning, clostridialmyonecrosis, necrotizing problem wounds, acute traumatic wounds and arterial retinal occlusion. Part 2 discusses further uses of HBOT as adjuvant treatment and highlights problems in assessing the value of HBOT using evidence-based medicine criteria. © Georg Thieme Verlag Stuttgart · New York.

  11. Comparative effects of adjuvant cimetidine and omeprazole during pancreatic enzyme replacement therapy

    NARCIS (Netherlands)

    Bruno, M. J.; Rauws, E. A.; Hoek, F. J.; Tytgat, G. N.

    1994-01-01

    In a double-blind, randomized crossover study, the hypotheses were tested that more powerful inhibition of gastric acid secretion by adjuvant omeprazole further improves the efficacy of pancreatic enzyme replacement therapy compared to adjuvant cimetidine and that excluding the influence of

  12. Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer

    Science.gov (United States)

    Viale, G.; Giobbie-Hurder, A.; Gusterson, B. A.; Maiorano, E.; Mastropasqua, M. G.; Sonzogni, A.; Mallon, E.; Colleoni, M.; Castiglione-Gertsch, M.; Regan, M. M.; Brown, R. W.; Golouh, R.; Crivellari, D.; Karlsson, P.; Öhlschlegel, C.; Gelber, R. D.; Goldhirsch, A.; Coates, A. S.

    2010-01-01

    Background: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. Patients and methods: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin–eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). Results: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. Conclusion: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy. PMID:19633051

  13. Adjuvant therapy of melanoma with interferon: lessons of the past decade

    Directory of Open Access Journals (Sweden)

    Kirkwood John M

    2008-10-01

    Full Text Available Abstract The effect of interferon alpha (IFNα2 given alone or in combination has been widely explored in clinical trials over the past 30 years. Despite the number of adjuvant studies that have been conducted, controversy remains in the oncology community regarding the role of this treatment. Recently an individual patient data (IPD meta-analysis at longer follow-up was reported, showing a statistically significant benefit for IFN in relation to relapse-free survival, without any difference according to dosage (p = 0.2 or duration of IFN therapy (p = 0.5. Most interestingly, there was a statistically significant benefit of IFN upon overall survival (OS that translates into an absolute benefit of at least 3% (CI 1–5% at 5 years. Thus, both the individual trials and this meta-analysis provide evidence that adjuvant IFNα2 significantly reduces the risk of relapse and mortality of high-risk melanoma, albeit with a relatively small absolute improvement in survival in the overall population. We have surveyed the international literature from the meta-analysis (2006 to summarize and assimilate current biological evidence that indicates a potent impact of this molecule upon the tumor microenvironment and STAT signaling, as well as the immunological polarization of the tumor tissue in vivo. In conclusion, we argue that there is a compelling rationale for new research upon IFN, especially in the adjuvant setting where the most pronounced effects of this agent have been discovered. These efforts have already shed light upon the immunological and proinflammatory predictors of therapeutic benefit from this agent – that may allow practitioners to determine which patients may benefit from IFN therapy, and approaches that may enable us to overcome resistance or enhance the efficacy of IFN. Future efforts may well build toward patient-oriented therapy based upon the knowledge of the unique molecular features of this disease and the immune system of each

  14. Women prefer adjuvant endocrine therapy to chemotherapy for breast cancer treatment.

    Science.gov (United States)

    Niikura, Naoki; Kimura, Morihiko; Iwamoto, Takayuki; Hayashi, Naoki; Shintoku, Junichi; Saito, Yuki; Suzuki, Yasuhiro; Tokuda, Yutaka

    2013-01-01

    We attempted to determine the preferences of women regarding the benefits they considered necessary to make adjuvant therapy worthwhile, and to compare preferences for adjuvant endocrine therapy, chemotherapy, and trastuzumab therapy. We also investigated the effect of information about cost on women's treatment preferences. Consecutive women who had a medical examination at the Breast Clinic, Ota General Hospital, were included in our study. We collected a questionnaire from a total of 365 women; 297 completed responses were included in the study. Among 297 women, 105 had breast cancer that had been treated and 192 did not have breast cancer; 38% of women judged that a 5% or less gain in the probability of survival was sufficient to make endocrine therapy worthwhile; 28% of participants judged that chemotherapy was worthwhile; 24% of participants judged that trastuzumab therapy was worthwhile. Women indicated that they were more likely to receive adjuvant endocrine therapy than chemotherapy or trastuzumab therapy, for the same gains in the probability of survival. Cost information about treatments did not affect women's treatment preferences. Younger women tended to judge improvements in survival sufficient to make adjuvant endocrine and chemotherapy worthwhile, as compared to older women. The comparisons were statistically significant in the 10 and 20% categories for endocrine therapy and chemotherapy. Women prefer endocrine therapy to chemotherapy or trastuzumab therapy, given the same projected treatment benefits. Younger women prefer both chemotherapy and endocrine therapy as compared with older woman.

  15. Systemic Cancer Therapy:

    Directory of Open Access Journals (Sweden)

    Michael Ostario Palumbo

    2013-05-01

    Full Text Available In the last half of the century, advances in the systemic therapy of cancer, including chemotherapy, hormonal therapy, targeted therapy and immunotherapy have been responsible for improvements in cancer related mortality in developed countries even as the population continues to age. Although such advancements have yet to benefit all cancer types, systemic therapies have led to an improvement in overall survival in both the adjuvant and metastatic setting for many cancers. With the pressure to make therapies available as soon as possible, the side-effects of systemic therapies, in particular long-term side-effects are not very well characterized and understood. Increasingly, a number of cancer types are requiring long-term and even lifelong systemic therapy. This is true for both younger and older patients with cancer and has important implications for each subset. Younger patients have an overall greater expected life-span, and as a result may suffer a greater variety of treatment related complications in the long-term, whereas older patients may develop earlier side-effects as a result of their frailty. Because the incidence of cancer in the world will increase over the next several decades and there will be more people living with cancer, it is important to have an understanding of the potential side effects of new systemic therapies. As an introductory article, in this review series, we begin by describing some of the major advances made in systemic cancer therapy along with some of their known side-effects and we also make an attempt to describe the future of systemic cancer therapy.

  16. Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis

    Directory of Open Access Journals (Sweden)

    Lima Carmen SP

    2011-03-01

    Full Text Available Abstract Background Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting. Methods Randomized controlled trials were searched comparing adjuvant therapy (chemotherapy, vaccine, immunotherapy, biochemotherapy versus no active treatment after surgery among renal cell cancer patients. Outcomes were overall survival (OS, disease-free survival (DFS, and severe toxicities. Risk ratios (RR, hazard ratios (HR and 95% confidence intervals were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by I2. Different strategies of adjuvant treatment were evaluated separately. Results Ten studies (2,609 patients were included. Adjuvant therapy provided no benefits in terms of OS (HR 1.07; 95%CI 0.89 to 1.28; P = 0.48 I2 = 0% or DFS (HR 1.03; 95%CI 0.87 to 1.21; P = 0.77 I2 = 15% when compared to no treatment. No subgroup analysis (immunotherapy, vaccines, biochemotherapy and hormone therapy had relevant results. Toxicity evaluation depicted a significantly higher frequency of serious adverse events in the adjuvant group. Conclusions This analysis provided no support for the hypothesis that the agents studied provide any clinical benefit for renal cancer patients although they increase the risk of toxic effects. Randomized trials are underway to test targeted therapies, which might open a new therapeutic frontier. Until these trials yield results, no adjuvant therapy can be recommended for patients who undergo surgical resection for renal cell cancer.

  17. Clinical impact of PET/CT imaging after adjuvant therapy in patients with oral cavity squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Huan-Chun [Chang Gung Memorial Hospital and Chang Gung University, Department of Nuclear Medicine and Molecular Imaging Center, Taoyuan (China); Kang, Chung-Jan; Huang, Shiang-Fu; Liao, Chun-Ta [Chang Gung Memorial Hospital and Chang Gung University, Department of Otorhinolaryngology, Head and Neck Surgery, Taoyuan (China); Wang, Hung-Ming [Chang Gung Memorial Hospital and Chang Gung University, Department of Medical Oncology, Taoyuan (China); Lin, Chien-Yu [Chang Gung Memorial Hospital and Chang Gung University, Department of Radiation Oncology, Taoyuan (China); Lee, Li-Yu [Chang Gung Memorial Hospital and Chang Gung University, Department of Pathology, Taoyuan (China); Yen, Tzu-Chen [Chang Gung Memorial Hospital and Chang Gung University, Department of Nuclear Medicine and Molecular Imaging Center, Taoyuan (China); Chang Gung Memorial Hospital at Linkou, Department of Nuclear Medicine, Taoyuan (China)

    2017-09-15

    This single-center retrospective study of prospectively collected data was aimed at comparing the clinical outcomes of positron emission tomography/computed tomography (PET/CT) for patients with oral cavity squamous cell carcinoma (OSCC) with symptomatic recurrences identified by PET/CT imaging following adjuvant therapy (Group A) versus those of cases with asymptomatic recurrences diagnosed through periodic post-adjuvant therapy PET/CT surveillance (Group B). We also sought to establish the priority of salvage therapy in the two study groups. We identified 111 patients with advanced resected OSCC who developed recurrences following adjuvant therapy (51 in Group A and 60 in Group B). Histopathology served as the gold standard for recurrent lesions. The impact of post-adjuvant therapy PET/CT surveillance was examined with Kaplan-Meier curves and Cox proportional hazards regression models. The 2-year DSS and OS rates were marginally or significantly higher in Group B than in Group A (P = 0.073 and P = 0.025, respectively). Time-dependent ROC curve analysis demonstrated that the optimal cutoff values for time to positive PET/CT findings in relation to OS were 12 months for Group A and 9 months for Group B, respectively. Independent risk factors identified in multivariate analyses were used to devise two prognostic scoring systems for 2-year DSS and OS in each study group (all P < 0.001). Scheduled periodic PET/CT surveillance is a valuable tool for early detection of recurrent lesion(s) in asymptomatic OSCC patients who bear risk factors for disease recurrence. The presence of clinical symptoms and a short time to positive PET/CT findings were adverse prognostic factors for clinical outcome in patients with advanced OSCC. The priority of salvage therapy is discussed in each patient subgroup according to the devised prognostic scoring systems. (orig.)

  18. Ready-to-use colloidal adjuvant systems for intranasal immunization.

    Science.gov (United States)

    Lee, Jeong-Jun; Shim, Aeri; Lee, Song Yi; Kwon, Bo-Eun; Kim, Seong Ryeol; Ko, Hyun-Jeong; Cho, Hyun-Jong

    2016-04-01

    Adjuvant systems based on oil-in-water (o/w) microemulsions (MEs) for vaccination via intranasal administration were prepared and evaluated. A ready-to-use blank ME system composed of mineral oil (oil), Labrasol (surfactant), Tween 80 (cosurfactant), and water was prepared and blended with antigen (Ag) solution prior to use. The o/w ME system developed exhibited nano-size droplets within the tested range of Ag concentrations and dilution factors. The maintenance of primary, secondary, and tertiary structural stability of ovalbumin (OVA) in ME, compared with OVA in solution, was demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), circular dichroism (CD), and fluorescence intensity measurements, respectively. The uptake efficiency in RAW 264.7 cells, evaluated by flow cytometry, of OVA in the ME group was significantly higher than that of the OVA solution group (p<0.05). In an intranasal immunization study with OVA ME in mice, elevated adjuvant effects in terms of mucosal immunization and Th1-dominant cell-mediated immune responses were identified. Given the convenience of use (simply mixing with Ag solution prior to use) and the adjuvant effects after intranasal immunization, the new o/w ME may be a practical and efficient adjuvant system for intranasal vaccination. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Electrocardiography changes during adjuvant breast cancer therapy: incidence and risk factors.

    Science.gov (United States)

    Elme, Anneli; Saarto, Tiina; Tötterman, Karl Johan; Utrianen, Meri; Kautiainen, Hannu; Järvenpää, Salme; Tenhuen, Mikko; Blomqvist, Carl

    2013-11-01

    Breast cancer survivors have a higher cardiovascular morbidity/mortality rate, when compared with healthy age-matched general population. Electrocardiography (ECG) changes have been found to be associated with chemo- and radiation therapy. In the present study we investigated changes in ECG patterns following modern adjuvant therapy for breast cancer. A standard 12-lead electrocardiogram was recorded at rest three times (prior and after adjuvant therapy) and retrospectively analyzed in 414 breast cancer patients, who participated in the open prospective phase III randomized trial (BREX) of exercise training 2005-2007. New electrocardiographic changes in the T-wave or ST-segment (depression or elevation) after the adjuvant therapy were recorded in 49 patients (13%). In multivariate analyses, hypertension treated with anti-hypertensive medication was the only significant factor associated with irreversible ECG changes (OR=4.71; 95% CI=1.36-16.38; p=0.015). New irreversible pathological electrocardiographic changes, which acquired during the adjuvant therapy, had a clear relationship with hypertension This patients subgroup needs to be studied further.

  20. The impact of repeated surgery and adjuvant therapy on survival for patients with recurrent glioblastoma.

    Science.gov (United States)

    De Bonis, Pasquale; Fiorentino, Alba; Anile, Carmelo; Balducci, Mario; Pompucci, Angelo; Chiesa, Silvia; Sica, Gigliola; Lama, Gina; Maira, Giulio; Mangiola, Annunziato

    2013-07-01

    Treatment of glioblastoma recurrence can have a palliative aim, after considering risks and potential benefits. The aim of this study is to verify the impact of surgery and of palliative adjuvant treatments on survival after recurrence. From January 2002 to June 2008, we treated 76 consecutive patients with recurrent glioblastoma. Treatment was: 1-surgery alone--17 patients; 2-adjuvant-therapy alone--24 patients; 3-surgery and adjuvant therapy--16 patients; no treatment--19 patients. The impact on median overall-survival (OS-time between recurrence and death/last follow-up) of age, Karnofsky performance scale (KPS), resection extent and adjuvant treatment scheme (Temozolomide alone vs low-dose fractionated radiotherapy vs others) was determined. Survival curves were obtained through the Kaplan-Meier method. Cox proportional-hazards was used for multivariate analyses. Significance was set at p<0.05. Median OS was 7 months. At univariate analysis, patients with a KPS≥70 had a longer OS (9 months vs 5 months--p<0.0001). OS was 6 months for patients treated with surgery alone, 5 months for patients that received no treatment, 8 months for patients treated with chemotherapy alone, 14 months for patients treated with surgery and adjuvant therapy--p=0.01. Patients with a KPS<70 were significantly at risk for death - HR 2.8 - p=0.001. Subgroup analysis showed no significant differences between patients receiving gross total or partial tumor resection and among patients receiving different adjuvant therapy schemes. Major surgical morbidity at tumor recurrence occurred in 16 out of 33 patients (48%). It is fundamental, before deciding to operate patients for recurrence, to carefully consider the impact of surgical morbidity on outcome. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

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    McMillan, Matthew T. [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Ojerholm, Eric [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Roses, Robert E., E-mail: Robert.Roses@uphs.upenn.edu [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Plastaras, John P.; Metz, James M. [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Mamtani, Ronac [Department of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Karakousis, Giorgos C.; Fraker, Douglas L.; Drebin, Jeffrey A. [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Stripp, Diana; Ben-Josef, Edgar [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Datta, Jashodeep [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States)

    2015-10-01

    Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiation therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered.

  2. Physician Beliefs and Practices for Adjuvant and Salvage Radiation Therapy After Prostatectomy

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    Showalter, Timothy N., E-mail: timothy.showalter@jeffersonhospital.org [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Ohri, Nitin; Teti, Kristopher G. [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Foley, Kathleen A. [Strategic Consulting, Thomson Reuters Healthcare, Cambridge, MA (United States); Keith, Scott W. [Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Trabulsi, Edouard J.; Lallas, Costas D. [Department of Urology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Dicker, Adam P. [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Hoffman-Censits, Jean [Department of Medical Oncology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Pizzi, Laura T. [School of Pharmacy, Thomas Jefferson University, Philadelphia, PA (United States); Gomella, Leonard G. [Department of Urology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States)

    2012-02-01

    Purpose: Despite results of randomized trials that support adjuvant radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer with adverse pathologic features (APF), many clinicians favor selective use of salvage RT. This survey was conducted to evaluate the beliefs and practices of radiation oncologists (RO) and urologists (U) regarding RT after RP. Methods and Materials: We designed a Web-based survey of post-RP RT beliefs and policies. Survey invitations were e-mailed to a list of 926 RO and 591 U. APF were defined as extracapsular extension, seminal vesicle invasion, or positive surgical margin. Differences between U and RO in adjuvant RT recommendations were evaluated by comparative statistics. Multivariate analyses were performed to evaluate factors predictive of adjuvant RT recommendation. Results: Analyzable surveys were completed by 218 RO and 92 U (overallresponse rate, 20%). Adjuvant RT was recommended based on APF by 68% of respondents (78% RO, 44% U, p <0.001). U were less likely than RO to agree that adjuvant RT improves survival and/or biochemical control (p < 0.0001). PSA thresholds for salvage RT were higher among U than RO (p < 0.001). Predicted rates of erectile dysfunction due to RT were higher among U than RO (p <0.001). On multivariate analysis, respondent specialty was the only predictor of adjuvant RT recommendations. Conclusions: U are less likely than RO to recommend adjuvant RT. Future research efforts should focus on defining the toxicities of post-RP RT and on identifying the subgroups of patients who will benefit from adjuvant vs. selective salvage RT.

  3. Altered Blood Flow Response to Small Muscle Mass Exercise in Cancer Survivors Treated With Adjuvant Therapy.

    Science.gov (United States)

    Didier, Kaylin D; Ederer, Austin K; Reiter, Landon K; Brown, Michael; Hardy, Rachel; Caldwell, Jacob; Black, Christopher; Bemben, Michael G; Ade, Carl J

    2017-02-07

    Adjuvant cancer treatments have been shown to decrease cardiac function. In addition to changes in cardiovascular risk, there are several additional functional consequences including decreases in exercise capacity and increased incidence of cancer-related fatigue. However, the effects of adjuvant cancer treatment on peripheral vascular function during exercise in cancer survivors have not been well documented. We investigated the vascular responses to exercise in cancer survivors previously treated with adjuvant cancer therapies. Peripheral vascular responses were investigated in 11 cancer survivors previously treated with adjuvant cancer therapies (age 58±6 years, 34±30 months from diagnosis) and 9 healthy controls group matched for age, sex, and maximal voluntary contraction. A dynamic handgrip exercise test at 20% maximal voluntary contraction was performed with simultaneous measurements of forearm blood flow and mean arterial pressure. Forearm vascular conductance was calculated from forearm blood flow and mean arterial pressure. Left ventricular ejection time index (LVETi) was derived from the arterial pressure wave form. Forearm blood flow was attenuated in cancer therapies compared to control at 20% maximal voluntary contraction (189.8±53.8 vs 247.9±80.3 mL·min(-1), respectively). Forearm vascular conductance was not different between groups at rest or during exercise. Mean arterial pressure response to exercise was attenuated in cancer therapies compared to controls (107.8±10.8 vs 119.2±16.2 mm Hg). LEVTi was lower in cancer therapies compared to controls. These data suggest an attenuated exercise blood flow response in cancer survivors ≈34 months following adjuvant cancer therapy that may be attributed to an attenuated increase in mean arterial pressure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  4. Efficacy of adjuvant therapy with fenofibrate for primary biliary cirrhosis: a Meta-analysis

    Directory of Open Access Journals (Sweden)

    YU Yuan

    2015-10-01

    Full Text Available ObjectiveTo assess the efficacy of adjuvant therapy with fenofibrate for primary biliary cirrhosis (PBC. MethodsCNKI, Wanfang Data, China Biology Medicine, PubMed, Embase, and Cochrane library were searched for the pertinent literature of randomized controlled trials (RCTs of adjuvant therapy with fenofibrate for PBC published up to December 31, 2014. Data extraction and quality assessment were carried out, and the data were statistically analyzed by Stata10.1 software. Respectively, for heterogeneity test. The fixed effect model is chosen for homogeneity, and the random effect model is chosen for heterogeneity. ResultsSix RCTs met the inclusion criteria. Treatment with fenofibrate was associated with significantly reduced levels of gamma-glutamyl transpeptidase, alanine aminotransferase, and alkaline phosphatase in PBC patients (SMD=-1.595, -0.447, and -2.125, respectively, all P<0.05. There were no significant changes in the levels of aspartate aminotransferase and total bilirubin after adjuvant therapy with fenofibrate (both P>0.05. Also, fenofibrate led to no significant improvement in immunoglobulin M (P>0.05. ConclusionFenofibrate, which improves the indicators of liver function but leads to no changes in immunological indicators, appears to be an effective adjuvant therapy in PBC patients. There is a critical need for more large-scale, multi-center, high-quality RCTs to determine its effect on liver disease-related morbidity and mortality.

  5. Perspectives of postmenopausal breast cancer survivors on adjuvant endocrine therapy-related symptoms.

    NARCIS (Netherlands)

    van Londen, G.J.; Donovan, H.S.; Beckjord, E.B.; Cardy, A.L.; Bovbjerg, D.H.; Davidson, N.E.; Morse, J.Q.; Switzer, G.E.; de Leeuw, I.M.; Dew, M.A.

    2014-01-01

    Purpose/Objectives: To conduct an investigation of women's experiences related to adjuvant endocrine therapy (AET) and managing AET-related symptoms. Research Approach: Qualitative, focus group design. Setting: Main campus of the University of Pittsburgh in Pennsylvania. Participants: 14 breast

  6. Adjuvant Therapy for the Reduction of Postoperative Intra-abdominal Adhesion Formation

    Directory of Open Access Journals (Sweden)

    Jason PY Cheung

    2009-07-01

    Conclusions: Only a limited number of adjuvant treatment methods are currently available for the reduction of postoperative adhesions. Seprafilm has been proven to be the efficacious method to reduce adhesions. Investigations into the novel therapies are showing promising results in experimental studies and clinical studies before their wider application.

  7. Adjuvant hormone therapy in patients undergoing high-intensity focused ultrasound therapy for locally advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    A. I. Neimark

    2014-01-01

    Full Text Available Objective: to evaluate the efficiency and safety of using the luteinizing hormone releasing hormone leuprorelin with the Atrigel delivery system in doses of 7.5, 22.5, and 45 mg as an adjuvant regimen in high- and moderate-risk cancer patients who have received high-intensity focused ultrasound (HIFU therapy.Subjects and methods. Moderate- and high-risk locally advanced prostate cancer (PC patients treated with HIFU (n = 28 and HIFU in combination with hormone therapy during 6 months (n = 31 were examined.Results. The investigation has shown that leuprorelin acetate monotherapy used within 6 months after HIFU therapy can achieve the highest reduction in prostate-specific antigen levels and positively affect the symptoms of the disease. HIFU in combination with androgen deprivation substantially diminishes the clinical manifestations of the disease and improves quality of life in HIFU-treated patients with PC, by reducing the degree of infravesical obstruction (according to uroflowmetric findings and IPSS scores, and causes a decrease in prostate volume as compared to those who have undergone HIFU only. Treatment with leuprorelin having the Atrigel delivery system has demonstrated the low incidence of adverse reactions and good tolerability.

  8. Sleep status of cervical cancer patients and predictors of poor sleep quality during adjuvant therapy.

    Science.gov (United States)

    Tian, Jun; Chen, Gui Lin; Zhang, Hai Rong

    2015-05-01

    This study was designed to detect the prevalence of poor sleep quality in cervical cancer patients before and after adjuvant therapy, determine whether the prevalence of poor sleep quality in cervical cancer patients is higher than that in the general population, and analyze the factors associated with poor sleep quality. A total of 76 stages I and II cervical cancer patients and 116 female residents completed the Pittsburgh Sleep Quality Index (PSQI). Patient Neurotoxicity Questionnaire (PNQ), Distress Thermometer (DT), Multidimensional Fatigue Inventory, and Hospital Anxiety and Depression Scale were used to measure the patients' chemotherapy-induced peripheral neurotoxicity (CIPN), psychological distress, fatigue, anxiety, and depression. Data on social support and exercise were collected by the questionnaire. Logistic regression was used to identify the factors associated with poor sleep quality. Prevalence rates of poor sleep quality were 27.59 % for female residents, 52.63 % for patients before adjuvant therapy, and 64.50 % for patients after adjuvant therapy. The distributions of the PSQI scores of the patients before (Z = 3.814, P poor sleep quality were high DT score (P = 0.045), depression (P = 0.028), anxiety (P = 0.027), high PNQ grade (P = 0.016), and chemotherapy + radiotherapy treatment (P = 0.017). Exercise was a protective factor for poor sleep quality (P =0.019). The prevalence of poor sleep quality in stages I and II cervical cancer patients was approximately twice than that of women in the communities. Cancer treatment considerably affected sleep quality. Psychological distress, depression, anxiety, and high grade of CIPN during adjuvant therapy were factors associated with poor sleep quality. Exercise during adjuvant therapy could reduce the risk of poor sleep quality.

  9. Decreased contralateral breast volume after mastectomy, adjuvant chemotherapy, and anti-estrogen therapy, in particular in breasts with high density.

    Science.gov (United States)

    Ishii, Naohiro; Ando, Jiro; Harao, Michiko; Takemae, Masaru; Kishi, Kazuo

    2017-10-01

    Adjuvant chemotherapy and anti-estrogenic therapy can result in decreased volume of the contralateral breast, following mastectomy for the treatment of breast cancer. However, no data on the effect of adjuvant therapy on contralateral breast volume have previously been reported. We aimed to evaluate the extent to which adjuvant therapy and differences in breast density contribute to decreased breast volume. We conducted a prospective cohort study, selecting 40 nonconsecutive patients who underwent immediate breast reconstruction with mastectomy and expander insertion followed by expander replacement. We measured the contralateral breast volume before each procedure. The extent of the change was analyzed with respect to adjuvant therapy and breast density measured by preoperative mammography. The greatest decrease in breast volume was 135.1 cm3. The decrease in breast volume was significantly larger in the adjuvant therapy (+) group, particularly in patients with high breast density, than in the adjuvant therapy (-) group. Significant differences between the chemotherapy (+), tamoxifen (+) group and the chemotherapy (-), tamoxifen (+) group were not found. Breast density scores had a range of 2.0-3.3 (mean: 2.8). In breast reconstruction, particularly when performed in one stage, preoperative mammography findings are valuable to plastic surgeons, and possible decreases in the contralateral breast volume due to adjuvant therapy, particularly in patients with high breast density, should be considered carefully. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  10. Risk factors for clinical metastasis in men undergoing radical prostatectomy and immediate adjuvant androgen deprivation therapy.

    Science.gov (United States)

    Taguchi, Satoru; Fukuhara, Hiroshi; Kakutani, Shigenori; Takeshima, Yuta; Miyazaki, Hideyo; Suzuki, Motofumi; Fujimura, Tetsuya; Nakagawa, Tohru; Igawa, Yasuhiko; Kume, Haruki; Homma, Yukio

    2014-01-01

    Adjuvant androgen deprivation therapy (ADT) is a treatment option for prostate cancer (PC) patients after radical prostatectomy (RP). Although it can achieve a good progression-free survival rate, some patients still develop clinical metastasis. We here investigated risk factors of clinical metastasis in post- prostatectomy patients who received immediate adjuvant ADT. We identified 197 patients with non-metastatic PC who underwent RP at our institution between 2000 and 2012, followed by adjuvant ADT. The associations of various clinicopathologic factors with clinical metastasis (primary endpoint) and cancer-specific survival (secondary endpoint) were assessed. Multivariate analysis was conducted using a Cox proportional hazards model. Median follow-up was 87 months after RP. Nine (4.6%) patients developed clinical metastasis and six (3.0%) died from PC. Eight of nine metastatic patients had a pathologic Gleason score (GS) 9 and developed bone metastasis, while the remaining one had pathologic GS 7 and developed metastasis only to para-aortic lymph nodes. On multivariate analyses, pathologic GS ≥9 and regional lymph node metastasis (pN1) were independent predictors of clinical metastasis and pathologic GS ≥9 was an independent predictor of cancer-specific death. Pathologic GS ≥9 and pN1 were independent predictors of clinical metastasis in post-prostatectomy patients who received immediate adjuvant ADT. Furthermore, pathologic GS ≥9 was an indispensable condition for bone metastasis, which may imply that patients with GS ≤8 on adjuvant ADT are unlikely to develop bone metastasis.

  11. Potential implications of adjuvant endocrine therapy for the oral health of postmenopausal women with breast cancer

    Science.gov (United States)

    Taichman, L. Susan; Havens, Aaron M.

    2012-01-01

    Current adjuvant treatment modalities for breast cancer that express the estrogen receptor or progesterone receptor include adjuvant anti-estrogen therapies, and tamoxifen and aromatase inhibitors. Bone, including the jaw, is an endocrine-sensitive organ, as are other oral structures. This review examines the potential links between adjuvant anti-estrogen treatments in postmenopausal women with hormone receptor positive breast cancer and oral health. A search of PubMed, EMBASE, CENTRAL, and the Web of Knowledge was conducted using combinations of key terms “breast,” “cancer,” “neoplasm,” “Tamoxifen,” “Aromatase Inhibitor,” “chemotherapy,” “hormone therapy,” “alveolar bone loss,” “postmenopausal bone loss,” “estrogen,” “SERM,” “hormone replacement therapy,” and “quality of life.” We selected articles published in peer-reviewed journals in the English. The authors found no studies reporting on periodontal diseases, alveolar bone loss, oral health, or oral health-related quality of life in association with anti-estrogen breast cancer treatments in postmenopausal women. Periodontal diseases, alveolar bone density, tooth loss, and conditions of the soft tissues of the mouth have all been associated with menopausal status supporting the hypothesis that the soft tissues and bone of the oral cavity could be negatively affected by anti-estrogen therapy. As a conclusion, the impact of adjuvant endocrine breast cancer therapy on the oral health of postmenopausal women is undefined. The structures of the oral cavity are influenced by estrogen; therefore, anti-estrogen therapies may carry the risk of oral toxicities. Oral health care for breast cancer patients is an important but understudied aspect of cancer survivorship. PMID:22986813

  12. The efficacy of adjuvant therapy for pancreatic invasive intraductal papillary mucinous neoplasm (IPMN).

    Science.gov (United States)

    McMillan, Matthew T; Lewis, Russell S; Drebin, Jeffrey A; Teitelbaum, Ursina R; Lee, Major K; Roses, Robert E; Fraker, Douglas L; Vollmer, Charles M

    2016-02-15

    The literature investigating pancreatic invasive intraductal papillary mucinous neoplasm (IPMN) has largely come from small institutional studies, preventing adequately powered comparisons of adjuvant therapy versus surgery alone (SA) within specific patient subgroups. Patients with resected, stage I through IV, invasive IPMN and conventional pancreatic ductal adenocarcinoma (PDAC) were identified in the National Cancer Data Base (1998-2010). Cox modeling of patients with invasive IPMN was used to compare overall survival (OS) between patients who received adjuvant therapy and those who underwent SA. A second model was used to compare OS between patients with invasive IPMN and those with PDAC. For the 1220 patients with invasive IPMN, the median OS was 28.9 months; the 1-year and 5-year actuarial survival rates were 76% and 17%, respectively; and 47% received adjuvant therapy. Cox modeling associated SA with worse OS (hazard ratio, 1.36; 95% confidence interval, 1.17-1.58; P = .00005) as well as American Joint Committee on Cancer (AJCC) TNM stage III/IV disease, positive lymph node status, positive margins, and poor tumor differentiation (all P ≤ .05). In addition, Cox modeling stratified by the following characteristics demonstrated improved OS with adjuvant therapy: AJCC TNM stage II or III/IV, positive lymph node status, positive margins, and poorly differentiated tumors. There was no survival advantage from adjuvant therapy for patients who had AJCC TNM stage I or lymph node-negative disease. Patients who had invasive IPMN had improved risk-adjusted OS compared with those who had PDAC (hazard ratio, 0.73; 95% confidence interval, 0.68-0.78; P < .00001). Invasive IPMN appears to be more indolent than conventional PDAC. Adjuvant therapy is associated with improved OS compared with SA in patients with invasive IPMN, especially for those with higher stage disease, positive lymph nodes, positive margins, or poorly differentiated tumors. Conversely

  13. Effect of adjuvant lithium on thyroxine (T4) concentration after radioactive iodine therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hammond, Emmanuel NiiBoye; Vangu, Mboyo-Di-Tamba Heben Willy [University of the Witwatersrand, Division of Nuclear Medicine and Molecular Imaging, Department of Radiation Sciences, Johannesburg (South Africa)

    2016-10-15

    To study the effect of adjuvant lithium on serum thyroxine (T4) concentrations in patients treated with radioactive iodine (RAI) therapy in our environment. This was a prospective simple randomized comparative, experimental cohort study of patients with hyperthyroidism referred for RAI ablation therapy in the two main academic hospitals in Johannesburg between February 2014 and September 2015. Amongst the 163 participants in the final analysis, 75 received RAI alone and 88 received RAI with lithium. The difference in mean T4 concentrations at 3 months between the RAI-only group (17.67 pmol/l) and the RAI with lithium group (11.55 pmol/l) was significant with a small effect size (U = 2328.5, Z = -2.700, p = 0.007, r = 0.01). Significant decreases in T4 concentrations were observed as early as 1 month after RAI (p = 0.0001) in the RAI with lithium group, but in the RAI-only group, significant decreases in T4 concentrations were observed only at 3 months after RAI therapy (p = 0.000). Women and patients with Graves' disease who received RAI with adjuvant lithium also showed significant decreases in T4 concentrations at 1 month (p = 0.002 and p = 0.003, respectively). Adjuvant lithium leads to an earlier and better response to RAI therapy with lower T4 concentrations that are achieved earlier. This earlier response and decrease in T4 concentrations were noted in patients with Graves' disease and nodular goitre, and in women with hyperthyroidism who received adjuvant lithium therapy. (orig.)

  14. Predicting the Toxicity of Adjuvant Breast Cancer Drug Combination Therapy

    Science.gov (United States)

    2013-03-01

    Combination With Trastuzumab in Patients With HER2-Positive, Metastatic Breast Cancer Recruiting No Results Available NO Drug: Lapatinib|Drug: Herceptin ...Trastuzumab ( Herceptin ) -Refractory, Metastatic Breast Cancer Active, not recruiting No Results Available NO Drug: Capecitabine|Drug: Lapatinib Lapatinib...Lapatinib Plus Herceptin With or Without Endocrine Therapy Recruiting No Results Available NO Drug: Herceptin |Drug: Lapatinib|Drug: Letrozole

  15. Thymoquinone as a Potential Adjuvant Therapy for Cancer Treatment: Evidence from Preclinical Studies

    Directory of Open Access Journals (Sweden)

    A.G.M. Mostofa

    2017-06-01

    Full Text Available Thymoquinone (TQ, the main bioactive component of Nigella sativa, has been found to exhibit anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Moreover, TQ can specifically sensitize tumor cells toward conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy and simultaneously minimize therapy-associated toxic effects in normal cells. In this review, we summarized the adjuvant potential of TQ as observed in various in vitro and in vivo animal models and discussed the pharmacological properties of TQ to rationalize its supplementary role in potentiating the efficacy of standard therapeutic modalities namely surgery, radiotherapy, chemotherapy, and immunotherapy. Altogether, we suggest further comprehensive evaluation of TQ in preclinical and clinical levels to delineate its implied utility as a novel complementary adjuvant therapy for cancer treatment.

  16. Influenza virosomes as vaccine adjuvant and carrier system.

    Science.gov (United States)

    Moser, Christian; Müller, Matthias; Kaeser, Matthias D; Weydemann, Ulrike; Amacker, Mario

    2013-07-01

    The basic concept of virosomes is the controlled in vitro assembly of virus-like particles from purified components. The first generation of influenza virosomes developed two decades ago is successfully applied in licensed vaccines, providing a solid clinical safety and efficacy track record for the technology. In the meantime, a second generation of influenza virosomes has evolved as a carrier and adjuvant system, which is currently applied in preclinical and clinical stage vaccine candidates targeting various prophylactic and therapeutic indications. The inclusion of additional components to optimize particle assembly, to stabilize the formulations, or to enhance the immunostimulatory properties have further improved and broadened the applicability of the platform.

  17. Penerapan Adjuvant Psychological Therapy (Apt) Terhadap Penurunan Tingkat Depresi Pada Penderita Kanker Serviks

    OpenAIRE

    Elwina, Lily; Fasikhah, Siti Suminarti; Karmiyati, Diah

    2012-01-01

    Penelitian ini dilaksanakan untuk mengetahui apakah penerapan Adjuvant Psychological Therapy (APT) dapat menurunkan tingkat depresi pada penderita kanker serviks. Desain penelitian yang digunakan single-case experimental designs dan rancangan dalam penelitian ini merupakan desain A-B-A' yang mempunyai tiga fase, yaitu A (baseline), B (intervensi) dan fase A' (follow-up). Metode pengumpulan data menggunakan instrumen BDI II yang berisi skor tingkat depresi subjek dan Self Monitoring dengan Sub...

  18. Prediction of biochemical recurrence after radical prostatectomy. New tool for selecting candidates for adjuvant radiation therapy.

    Science.gov (United States)

    Herranz-Amo, F; Molina-Escudero, R; Ogaya-Pinies, G; Ramírez-Martín, D; Verdú-Tartajo, F; Hernández-Fernández, C

    2016-03-01

    To design a risk summation to select patients for adjuvant radiation therapy after prostatectomy. A retrospective study was conducted on 629 patients with localised prostate cancer (pN0-pNx) who were treated with prostatectomy and with a prostate-specific antigen (PSA) value 0.4ng/mL. A multivariate Cox regression analysis was performed. A score (0-2) was assigned according to the hazard ratio of the significant variables. The score summation defined the risk summation. A total of 19.7% of the patients were pT3, 24.2% had a Gleason score ≥ 8, and 26.3% had positive surgical margins. The median follow-up was 82 months. Some 26.6% of the patients experienced biochemical recurrence. The identified prognostic variables independent of biochemical recurrence were a Gleason score =7 (4+3) (HR, 2.01; P=.008), a Gleason score ≥ 8 (HR, 3.07; P 50% survival free of biochemical recurrence at 5 and 8 years. In contrast, the patients with a risk summation ≥ 3 had <44% survival free of biochemical recurrence. The patients with a risk summation ≤ 2 did not benefit from adjuvant radiation therapy, while the patients with a risk summation ≥ 3 might benefit from adjuvant radiation therapy. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. The role of adjuvant external beam radiation therapy for papillary thyroid carcinoma invading the trachea

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Suk; Choi, Jae Hyuck; Kim, Kwang Sik [Jeju National University Hospital, Jeju National University School of Medicine, Jeju (Korea, Republic of); and others

    2017-06-15

    To evaluate the effect of adjuvant external beam radiation therapy (EBRT) on local failure-free survival rate (LFFS) for papillary thyroid cancer (PTC) invading the trachea. Fifty-six patients with locally advanced PTC invading the trachea were treated with surgical resection. After surgery, 21 patients received adjuvant EBRT and radioactive iodine therapy (EBRT group) and 35 patients were treated with radioactive iodine therapy (control group). The age range was 26–87 years (median, 56 years). The median follow-up period was 43 months (range, 4 to 145 months). EBRT doses ranged from 50.4 to 66 Gy (median, 60 Gy). Esophagus invasion and gross residual disease was more frequent in the EBRT group. In the control group, local recurrence developed in 9 (9/35, 26%) and new distant metastasis in 2 (2/35, 6%) patients, occurring 4 to 68 months (median, 37 months) and 53 to 68 months (median, 60 months) after surgery, respectively. Two patients had simultaneous local recurrence and new distant metastasis. There was one local failure in the EBRT group at 18 months after surgery (1/21, 5%). The 5-year LFFS was 95% in the EBRT group and 63% in the control group (p = 0.103). In the EBRT group, one late grade 2 xerostomia was developed. Although, EBRT group had a higher incidence of esophagus invasion and gross residual disease, EBRT group showed a better 5-year LFFS. Adjuvant EBRT may have contributed to the better LFFS in these patients.

  20. Survival Benefit of Adjuvant Radiation Therapy for Gastric Cancer following Gastrectomy and Extended Lymphadenectomy

    Directory of Open Access Journals (Sweden)

    R. A. Snyder

    2012-01-01

    Full Text Available Purpose. Although randomized trials suggest a survival benefit of adjuvant chemotherapy and radiation therapy (XRT for gastric adenocarcinoma, its use in patients who undergo an extended lymphadenectomy is less clear. The purpose of this study was to determine if a survival benefit exists in gastric cancer patients who receive adjuvant XRT following resection with extended lymphadenectomy. Methods. The SEER registry was queried for records of patients with resected gastric adenocarcinoma from 1988 to 2007. Multivariable Cox regression models were used to assess independent prognostic factors affecting overall survival (OS and disease-specific survival (DSS. Results. Of 15,060 patients identified, 3,208 (21% received adjuvant XRT. Adjuvant XRT was independently associated with improved OS (HR 0.67, CI 0.64–0.71 and DSS (HR 0.69, CI 0.65–0.73 in stages IB through IV (M0. This OS and DSS benefit persisted regardless of the extent of lymphadenectomy. Furthermore, lymphadenectomy with >25 LN resected was associated with improved OS and DSS compared with 25 LNs results in improved OS and DSS compared with patients who have fewer LNs resected.

  1. Adjuvant concurrent chemoradiation therapy (CCRT alone versus CCRT followed by adjuvant chemotherapy: Which is better in patients with radically resected extrahepatic biliary tract cancer?: a non-randomized, single center study

    Directory of Open Access Journals (Sweden)

    Kim Tae-You

    2009-09-01

    Full Text Available Abstract Background There is currently no standard adjuvant therapy for patients with curatively resected extrahepatic biliary tract cancer (EHBTC. The aim of this study was to analyze the clinical features and outcomes between patients undergoing adjuvant concurrent chemoradiation therapy (CCRT alone and those undergoing CCRT followed by adjuvant chemotherapy after curative resection. Methods We included 120 patients with EHBTC who underwent radical resection and then received adjuvant CCRT with or without further adjuvant chemotherapy between 2000 and 2006 at Seoul National University Hospital. Results Out of 120 patients, 30 received CCRT alone, and 90 received CCRT followed by adjuvant chemotherapy. Baseline characteristics were comparable between the two groups. Three-year disease-free survival (DFS rates for CCRT alone and CCRT followed by adjuvant chemotherapy were 26.6% and 45.2% (p = 0.04, respectively, and 3-year overall survival (OS rates were 30.8% and 62.6% (p Conclusion Adjuvant CCRT followed by adjuvant chemotherapy prolonged DFS and OS, compared with CCRT alone in patients with curatively resected EHBTC. Adjuvant chemotherapy deserves to consider after adjuvant CCRT. In the future, a randomized prospective study will be needed, with the objective of investigating the role of adjuvant chemotherapy.

  2. Use of propofol as adjuvant therapy in refractory delirium tremens

    Directory of Open Access Journals (Sweden)

    Rajiv Mahajan

    2010-01-01

    Full Text Available Delirium tremens is recognized as a potentially fatal and debilitating complication of alcohol withdrawal. Use of sedatives, particularly benzodiazepines, is the cornerstone of therapy for delirium tremens. But sometimes, very heavy doses of benzodiazepines are required to control delirious symptoms. We are reporting one such case of delirium tremens, which required very heavy doses of benzodiazepines and was ultimately controlled by using infusion of propofol. Thus propofol should always be considered as an option to treat patients with resistant delirium tremens.

  3. Adjuvant therapy of patients with chronic dermatoses using Bedan cream

    Directory of Open Access Journals (Sweden)

    Y.F. Kutasevych

    2016-02-01

    Full Text Available The paper is devoted to the problem of treatment of chronic dermatopathies. There are demonstrated the data of study of therapeutic efficiency and tolerance of Bedan cream I patients with dermatopathies. Bedan cream used in a complex therapy of chronic dermatopathies was shown to lead to earlier reduction of objective and subjective signs of chronic dermatosis and clinical regression. It was found a good tolerance of Bedan cream: its application was not associated with deterioration of general condition of skin, its irritation and allergization.

  4. Adjuvant combined ozone therapy for extensive wound over tibia

    Directory of Open Access Journals (Sweden)

    Prasham Shah

    2011-01-01

    Full Text Available Disinfectant and antibacterial properties of ozone are utilized in the treatment of nonhealing or ischemic wounds. We present here a case of 59 years old woman with compartment syndrome following surgical treatment of stress fracture of proximal tibia with extensively infected wound and exposed tibia to about 4/5 of its extent. The knee joint was also infected with active pus draining from a medial wound. At presentation the patient had already taken treatment for 15 days in the form of repeated wound debridements and parenteral antibiotics, which failed to heal the wound and she was advised amputation. Topical ozone therapy twice daily and ozone autohemotherapy once daily were given to the patient along with daily dressings and parenteral antibiotics. Within 5 days, the wound was healthy enough for spilt thickness skin graft to provide biological dressing to the exposed tibia bone. Topical ozone therapy was continued for further 5 days till the knee wound healed. On the 15th day, implant removal, intramedullary nailing, and latissimus dorsi pedicle flap were performed. Both the bone and the soft tissue healed without further complications and at 20 months follow-up, the patient was walking independently with minimal disability.

  5. Adjuvant combined ozone therapy for extensive wound over tibia.

    Science.gov (United States)

    Shah, Prasham; Shyam, Ashok K; Shah, Sambhav

    2011-07-01

    Disinfectant and antibacterial properties of ozone are utilized in the treatment of nonhealing or ischemic wounds. We present here a case of 59 years old woman with compartment syndrome following surgical treatment of stress fracture of proximal tibia with extensively infected wound and exposed tibia to about 4/5 of its extent. The knee joint was also infected with active pus draining from a medial wound. At presentation the patient had already taken treatment for 15 days in the form of repeated wound debridements and parenteral antibiotics, which failed to heal the wound and she was advised amputation. Topical ozone therapy twice daily and ozone autohemotherapy once daily were given to the patient along with daily dressings and parenteral antibiotics. Within 5 days, the wound was healthy enough for spilt thickness skin graft to provide biological dressing to the exposed tibia bone. Topical ozone therapy was continued for further 5 days till the knee wound healed. On the 15(th) day, implant removal, intramedullary nailing, and latissimus dorsi pedicle flap were performed. Both the bone and the soft tissue healed without further complications and at 20 months follow-up, the patient was walking independently with minimal disability.

  6. Adjuvant postoperative radiation therapy for carcinoma of the uterine cervix

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyung Ja; Moon, Hye Seong; Kim, Seung Cheol; Kim, Chong Il; Ahn, Jung Ja [College of Medicine, Ewha Womans Univ., Seoul (Korea, Republic of)

    2003-09-01

    This study was undertaken to evaluate the efficacy of postoperative radiotherapy, and to investigate the prognostic factors for FIGO stages IB-IIB cervical cancer patients who were treated with simple hysterectomy, or who had high-risk factors following radical hysterectomy and pelvic lymph node dissection. Between March 1986 and December 1998, 58 patients, with FIGO stages IB-IIB cervical cancer were included in this study, The indications for postoperative radiation therapy were based on the pathological findings, including lymph node metastasis, positive surgical margin, parametrial extension, Iymphovascular invasion, invasion of more than half the cervical stroma, uterine extension and the incidental finding of cervix cancer following simple hysterectomy. All patients received external pelvic radiotherapy, and 5 patients, received an additional intracavitary radiation therapy. The radiation dose from the external beam to the whole pelvis was 45 - 50 Gy. Vagina cuff irradiation was performed, after completion of the external beam irradiation, al a low-dose rate of CS-137, with the total dose of 4488-4932 chy (median: 4500 chy) at 5 mm depth from the vagina surface. The median follow-up period was 44 months (15-108 months), The 5-yr actuarial local control rate, distant free survival and disease-free survival rate were 98%, 95% and 94%, respectively. A univariate analysis of the clinical and pathological parameters revealed that the clinical stage (p=0.0145), status of vaginal resection margin (p=0.0002) and parametrial extension (p=0.0001) affected the disease-free survival. From a multivariate analysis, only a parametrial extension independently influenced the disease-free survival. Five patients (9%) experienced Grade 2 late treatment-related complications, such as radiation proctitis (1 patient), cystitis (3 patients) and lymphedema of the leg (1 patient). No patient had grade 3 or 4 complications. Our results indicate that postoperative radiation therapy can

  7. Probiotic bacteria: a viable adjuvant therapy for relieving symptoms of rheumatoid arthritis.

    Science.gov (United States)

    Wang, Peng; Tao, Jin-Hui; Pan, Hai-Feng

    2016-10-01

    The burgeoning use of probiotics has proliferated during the past two decades. However, the effect of probiotic administration for either the prevention or treatment of rheumatoid arthritis (RA) has been investigated in a limited number of studies. Randomized controlled clinical trials have provided evidences that specific probiotics supplementation exhibit anti-inflammatory effects, help to increase daily activities and alleviate symptoms in patients with RA. Therefore, using probiotic bacteria as an adjuvant therapy may be considered as a promising treatment option for RA. This review summarizes the available data about the therapeutic and preventive effect of probiotics in RA, together with probiotic supplement as a possible therapy in clinical treatment.

  8. Solitary uterine metastasis of invasive lobular carcinoma after adjuvant endocrine therapy: a case report.

    Science.gov (United States)

    Toyoshima, Masafumi; Iwahashi, Hideki; Shima, Takashi; Hayasaka, Atsushi; Kudo, Takako; Makino, Hiromitsu; Igeta, Saori; Matsuura, Rui; Ishigaki, Nobuko; Akagi, Kozo; Sakurada, Junko; Suzuki, Hiroyoshi; Yoshinaga, Kosuke

    2015-02-14

    Solitary uterine metastases from extragenital cancers are very rare. Breast cancer is the most frequent primary site of metastasis to the uterine corpus, with invasive lobular carcinoma more likely to spread to gynecologic organs than invasive ductal carcinoma. A 62-year-old postmenopausal Japanese woman was diagnosed with uterine leiomyomata more than 20 years ago and had been managed conservatively until menopause. Seven years prior to her presentation, she was diagnosed with breast cancer and underwent a partial resection of her right breast for stage IIA invasive lobular carcinoma. She underwent adjuvant chemotherapy, radiotherapy, and five years of anastrozole hormonal therapy. She presented with a growing uterine mass. Her tumor marker levels were markedly increased over the course of her follow-up, but a systemic examination revealed only a solitary uterine tumor. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. A histopathological examination, including detailed immunohistochemistry, confirmed metastatic invasive lobular carcinoma, infiltrating both her uterine myometrium and fibroid tissue. We report a very rare metastatic pattern of invasive lobular carcinoma and demonstrate that gross cystic disease fluid protein-15 and mammaglobin are useful in the diagnosis of metastatic breast cancer.

  9. Stage III Melanoma in the Axilla: Patterns of Regional Recurrence After Surgery With and Without Adjuvant Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Pinkham, Mark B., E-mail: mark.pinkham@health.qld.gov.au [Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane (Australia); University of Queensland, Brisbane (Australia); Foote, Matthew C. [Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane (Australia); Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane (Australia); Diamantina Institute, Brisbane (Australia); University of Queensland, Brisbane (Australia); Burmeister, Elizabeth [Nursing Practice Development Unit, Princess Alexandra Hospital, Brisbane (Australia); Research Centre for Clinical and Community Practice, Griffith University, Brisbane (Australia); Thomas, Janine [Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane (Australia); Meakin, Janelle [Clinical Trials Research Unit, Princess Alexandra Hospital, Brisbane (Australia); Smithers, B. Mark [Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane (Australia); University of Queensland, Brisbane (Australia); Burmeister, Bryan H. [Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane (Australia); Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane (Australia); University of Queensland, Brisbane (Australia)

    2013-07-15

    Purpose: To describe the anatomic distribution of regionally recurrent disease in patients with stage III melanoma in the axilla after curative-intent surgery with and without adjuvant radiation therapy. Methods and Materials: A single-institution, retrospective analysis of a prospective database of 277 patients undergoing curative-intent treatment for stage III melanoma in the axilla between 1992 and 2012 was completed. For patients who received radiation therapy and those who did not, patterns of regional recurrence were analyzed, and univariate analyses were performed to assess for potential factors associated with location of recurrence. Results: There were 121 patients who received adjuvant radiation therapy because their clinicopathologic features conferred a greater risk of regional recurrence. There were 156 patients who received no radiation therapy. The overall axillary control rate was 87%. There were 37 patients with regional recurrence; 17 patients had received adjuvant radiation therapy (14%), and 20 patients (13%) had not. The likelihood of in-field nodal recurrence was significantly less in the adjuvant radiation therapy group (P=.01) and significantly greater in sites adjacent to the axilla (P=.02). Patients with high-risk clinicopathologic features who did not receive adjuvant radiation therapy also tended to experience in-field failure rather than adjacent-field failure. Conclusions: Patients who received adjuvant radiation therapy were more likely to experience recurrence in the adjacent-field regions rather than in the in-field regions. This may not simply reflect higher-risk pathology. Using this data, it may be possible to improve outcomes by reducing the number of adjacent-field recurrences after adjuvant radiation therapy.

  10. ORAL DIETHYLCARBAMAZINE AS ADJUVANT THERAPY IN REFRACTORY VERNAL KERATOCONJUNCTIVITIS - A PROSPECTIVE STUDY

    Directory of Open Access Journals (Sweden)

    Roopashree

    2015-10-01

    Full Text Available PURPOSE: To evaluate the role of oral diethylcarbamazine as an adjuvant therapy in refractory vernal keratoconjunctivitis associated with eosinophilia. MATERIALS AND METHODS: Twenty four patients with bilateral refractory severe vernal keratoconjunctivitis (VKC and eosinophilia were included in the prospective study. The average age of patients was 8.25 years (range 3 to 14 years including 18 males (75% and 6 females (25%. The absolute eosinophil count (AEC in these pa tients was on an average 1065.79 cells/μL (range 530 to 3120 cells/μL. All the patients were given oral diethylcarbamazine (DEC as an adjuvant therapy for refractory VKC. RESULTS: At an average follow up of 7.2 months (range 6 to 11 months, only 2 cases (8.3% had recurrent exacerbation of VKC. Signs and symptoms of VKC improved significantly with remission in all the patients within 3 months. Absolute eosinophil count repeated after 3 months of starting DEC was on an average 376.25 cells/μL (range 200 t o 950 cells/μL. There was a statistically significant reduction in eosinophilia following oral DEC at p<0.0001. CONCLUSION: Oral DEC effectively reduces eosinophilia seen in refractory VKC. It is a cost effective and safe alternative as an adjuvant in ref ractory VKC with good clinical response

  11. Cyclophosphamide, methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high-risk, premenopausal breast cancer

    DEFF Research Database (Denmark)

    Ejlertsen, Bent Laursen; Mouridsen, Henning T; Jensen, Maj-Britt

    2010-01-01

    BACKGROUND: The Danish Breast Cancer Cooperative Group (DBCG) 77B trial examined the relative efficacy of levamisole, single-agent oral cyclophosphamide, and the classic combination of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) against no adjuvant systemic therapy in high-risk breast...... cancer patients. The authors report the results from that trial after a potential follow-up of 25 years. METHODS: Between 1977 and 1983, 1146 premenopausal patients who had tumors >5 cm or positive axillary lymph nodes were assigned randomly to 1 of 4 options: no systemic therapy, levamisole 5 mg weekly...... for 48 weeks (the levamisole arm), oral cyclophosphamide 130 mg/m(2) on Days 1 through 14 every 4 weeks for 12 cycles (the C arm), or oral cyclophosphamide 80 mg/m(2) on Days 1 through 14 plus methotrexate 30 mg/m(2) and fluorouracil 500 mg/m(2) intravenously on Days 1 and 8 every 4 weeks for 12 cycles...

  12. Emerging Adjuvant Therapy for Cancer: Propolis and its Constituents.

    Science.gov (United States)

    Patel, Seema

    2016-01-01

    Propolis is a bee-metabolized resinous substance (bee glue) from plant sap and gums. It has been in usage as a healing agent since antiquity, yet has not garnered global popularity as a health promoter. Its biological effects, which range from antimicrobial, antioxidant, anti-inflammatory, antidiabetic, dermatoprotective, anti-allergic, laxative and immunomodulatory to anticancer, have been validated. Propolis has shown efficacy against brain, head and neck, skin, breast, liver, pancreas, kidney, bladder, prostate, colon and blood cancers. The inhibition of matrix metalloproteinases, anti-angiogenesis, prevention of metastasis, cell-cycle arrest, induction of apoptosis and moderation of the chemotherapy-induced deleterious side effects have been deduced as the key mechanisms of cancer manipulation. The components conferring antitumor potentials have been identified as caffeic acid phenethyl ester, chrysin, artepillin C, nemorosone, galangin, cardanol, etc. These compounds target various genetic and biochemical pathways of cancer progression. Depending on the botanical sources and the geographical origin, biological activities of propolis vary. Despite phenomenal development in cancer research, conventional therapy falls short in complete malignancy management. The findings obtained so far build hope that propolis as a complementary medicine may address the lacunae. This review documents the recent advances and scope of amendement in cancer remediation with adequate emphasis on the mechanistic aspect of propolis.

  13. APPLICATION OF GENE PROFILING IN SELECTION OF ADJUVANT THERAPY IN BREAST CANCER IN A DEVELOPING COUNTRY.

    Science.gov (United States)

    Baitchu, Y; Apffelstaedt, J

    2017-09-01

    Outcome series for genetic profile tests (MammaPrint/70GP) with medium-term follow-up are rare. We present an outcome series with 5-year follow-up from a developing country. From 2006 to 2016, patients with histopathologically confirmed breast cancer (cT0-3 and cN0-1) were selected and decisions on adjuvant therapy post-surgery were based on 70GP. Data on outcomes were collected prospectively. There were 154 patients, 140 luminal type, 13 HER2 type and one triple negative; 57.8% were 70GP low-risk; only one of these did receive chemotherapy; 42.2% were high-risk; 3 patients did not receive chemotherapy. After an average follow-up of 54.1 months, only 3 systemic recurrences occurred (all skeletal metastases); all in the high-risk group that had received chemotherapy. Across both groups overall survival was 99.9% and compliance with the treatment recommendations based on 70GP was >95% in both arms. Two patients each had two tumours in the same breast with divergent 70GP results and were treated in accordance with the High-risk result. Six patients showed discordant 70GP and FISH results for HER2 where three patients did not receive Trastuzumab on basis of 70GP, none of these tumours recurred. A further 11 patients had equivocal immunohistochemistry and a FISH was not done, therapy was decided upon considering the 70GP result and none of these patients had any recurrences. Chemotherapy use was much reduced versus the rate of use with conventional methods using 70GP and it may possibly be reasonable to replace immunohistochemistry for ER, PR and HER2 with 70GP especially considering borderline expression.

  14. Provider perspectives on barriers and facilitators to adjuvant endocrine therapy-related symptom management.

    Science.gov (United States)

    Samuel, Cleo A; Turner, Kea; Donovan, Heidi A S; Beckjord, Ellen; Cardy, Alexandra; Dew, Mary Amanda; van Londen, G J

    2017-07-06

    Adjuvant endocrine therapy (AET) utilization is linked to improved clinical outcomes among breast cancer survivors (BCS); yet, AET adherence rates remain suboptimal. Little is known about provider perspectives regarding barriers and facilitators to AET-related symptom management (SM). In this study, we examined provider perspectives on the barriers and facilitators to AET-related SM among BCS and opportunities for improvement. We conducted three focus groups (FGs) with a multidisciplinary group of healthcare providers (n = 13) experienced in caring for BCS undergoing AET. We utilized semi-structured discussion guides to elicit provider perspectives on AET-related SM. FGs were audiotaped, transcribed, and analyzed using qualitative software to identify key themes. Providers described patient-, provider-, and system-level barriers and facilitators to AET-related SM. At the patient-level, barriers included competing demands, limited time/resources, and possible misattribution of some symptoms to AET, while family/social relationships and insurance emerged as important facilitators. Discomfort with SM, limited time, and challenges distinguishing AET-related symptoms from other conditions were key provider-level barriers. Provider-level facilitators included routine symptom documentation and strong provider relationships. Care fragmentation and complexity of the cancer care delivery system were described as system-level barriers; however, survivor clinics were endorsed by providers. Provider perspectives on AET-related SM can shed light on SM barriers and facilitators spanning multiple levels of the cancer care delivery system. Strategies for improving AET-related SM in BCS include increasing patients' knowledge and engagement in SM, equipping providers with efficient SM strategies, and improving coordination of symptom-related services through survivorship programs.

  15. Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

    Science.gov (United States)

    García-Albéniz, Xabier; Gallego, Rosa; Hofheinz, Ralf Dieter; Fernández-Esparrach, Gloria; Ayuso-Colella, Juan Ramón; Bombí, Josep Antoni; Conill, Carles; Cuatrecasas, Miriam; Delgado, Salvadora; Ginés, Angels; Miquel, Rosa; Pagés, Mario; Pineda, Estela; Pereira, Verónica; Sosa, Aarón; Reig, Oscar; Victoria, Iván; Feliz, Luis; María de Lacy, Antonio; Castells, Antoni; Burkholder, Iris; Hochhaus, Andreas; Maurel, Joan

    2014-01-01

    AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team. PMID:25400468

  16. Art therapy as an adjuvant treatment for depression in elderly women: a randomized controlled trial.

    Science.gov (United States)

    Ciasca, Eliana C; Ferreira, Rita C; Santana, Carmen L A; Forlenza, Orestes V; Dos Santos, Glenda D; Brum, Paula S; Nunes, Paula V

    2018-02-01

    There are few quantitative studies on art therapy for the treatment of depression. The objective of this study was to evaluate if art therapy is beneficial as an adjuvant treatment for depression in the elderly. A randomized, controlled, single-blind study was carried out in a sample of elderly women with major depressive disorder (MDD) stable on pharmacotherapy. The experimental group (EG) was assigned to 20 weekly art therapy sessions (90 min/session). The control group (CG) was not subjected to any adjuvant intervention. Patients were evaluated at baseline and after 20 weeks, using the Geriatric Depression Scale (GDS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and cognitive measures. Logistic regression analysis adjusted for age revealed that women in EG (n=31) had significant improvement in GDS (p = 0.007), BDI (p = 0.025), and BAI (p = 0.032) scores as compared with controls (n=25). No difference was found in the cognitive measures. Art therapy as an adjunctive treatment for MDD in the elderly can improve depressive and anxiety symptoms. RBR-2YXY7Z.

  17. Art therapy as an adjuvant treatment for depression in elderly women: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Eliana C. Ciasca

    2018-02-01

    Full Text Available Objective: There are few quantitative studies on art therapy for the treatment of depression. The objective of this study was to evaluate if art therapy is beneficial as an adjuvant treatment for depression in the elderly. Methods: A randomized, controlled, single-blind study was carried out in a sample of elderly women with major depressive disorder (MDD stable on pharmacotherapy. The experimental group (EG was assigned to 20 weekly art therapy sessions (90 min/session. The control group (CG was not subjected to any adjuvant intervention. Patients were evaluated at baseline and after 20 weeks, using the Geriatric Depression Scale (GDS, Beck Depression Inventory (BDI, Beck Anxiety Inventory (BAI, and cognitive measures. Results: Logistic regression analysis adjusted for age revealed that women in EG (n=31 had significant improvement in GDS (p = 0.007, BDI (p = 0.025, and BAI (p = 0.032 scores as compared with controls (n=25. No difference was found in the cognitive measures. Conclusion: Art therapy as an adjunctive treatment for MDD in the elderly can improve depressive and anxiety symptoms. Clinical trial registration: RBR-2YXY7Z

  18. Electronic brachytherapy as adjuvant therapy for early stage breast cancer: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    William C Dooley

    2011-01-01

    Full Text Available William C Dooley1, James C Wurzer2, Mohamed Megahy3, Gary Schreiber4, Tapan Roy5, Gary Proulx6, Susan Laduzinsky7, Steven Lane8, James Dalzell9, Kambiz Dowlatshahi10, Dwelvin Simmons11, John P Thropay12, Harish Ahuja13, Peter Beitsch14, Randall W Holt15, Charles A Lee161Oklahoma University Health Sciences Center, Oklahoma City, OK, USA; 2Atlanticare, Egg Harbor Township, NJ, USA; 3Maryville Oncology, Maryville, IL, USA; 4Swedish Covenant Hospital, Chicago, IL, USA; 5Cape Girardeau Cancer Center, Cape Girardeau, MO, USA; 6Exeter Hospital, Exeter, NH, USA; 7St. Elizabeth's Medical Center, Swansea, IL, USA; 8Brockton Hospital, Brockton, MA, USA; 9Nazha Cancer Center, Northfield, NJ, USA; 10Rush University Medical Center, Chicago, IL, USA; 11Florida Radiation Oncology Group, Jacksonville, FL, USA; 12Beverly Oncology and Imaging Center, Montebello, CA, USA; 13Aspirus Cancer Center, Wausau, WI, USA; 14Dallas Surgical Group, Dallas, TX, USA; 15Pacific Crest Medical Physics, Chico, CA, USA; 16Gulf Coast Cancer Treatment Center, Panama City, FL, USAPurpose: This multicenter, retrospective study evaluated treatment and clinical outcomes of patients with early stage breast cancer who received adjuvant high-dose rate (HDR electronic brachytherapy (EBT treatment post-lumpectomy using the Axxent® EBT system. Dosimetric data from the EBT treatment plans were compared with those based on iridium-192 HDR brachytherapy.Material and methods: Medical records of 63 patients with early stage breast cancer (Tis, T1a, T1b, T1c, and T2 who were treated post-lumpectomy with EBT alone or in combination with external beam radiation therapy were reviewed. The prescribed EBT dose was 34 Gy (10 fractions over 5 days, 3.4 Gy each to 1 cm from the balloon surface. Dosimetry data from 12 patients were compared with these of treatment plans using an iridium-192 source prepared for the same 12 patients.Results: The majority of patients (90.5% were older than 50 years and had one

  19. Probiotics as an Adjuvant Therapy in Major Depressive Disorder.

    Science.gov (United States)

    Vlainić, Josipa Vlainić; Šuran, Jelena; Vlainić, Toni; Vukorep, Antonella Letizia

    2016-01-01

    Major depressive disorder is a common, debilitating psychiatric disorder, which originates from the interaction of susceptibility genes and noxious environmental events, in particular stressful events. It has been shown that dysregulation of hypothalamus-pituitary-adrenal (HPA) axis, imbalance between anti- and pro-inflammatory cytokines, depletion of neurotransmitters (serotonin, norepinephrine and/or dopamine) in the central nervous system, altered glutamatergic and GABAergic transmission have an important role in the pathogenesis of depression. Due to numerous diverse biological events included in the pathophysiology of depression a large number of antidepressant drugs exerting distinct pharmacological effects have been developed. Nevertheless, clinical needs are still not solved. Relatively new research strategies advanced the understanding of psychiatric illness and their connections with disturbances in gastrointestinal tract. The existence of bidirectional communication between the brain and the gut has been proven, and an increasing body of evidence supports the hypothesis that cognitive and emotional processes are influenced through the brain-gut axis. On the other hand, microbiome may influence brain function and even behavior giving to the specific microorganisms a psychobiotic potential. In this review we discuss the possibilities of classical antidepressant drug treatment being supported with the psychobiotics/probiotic bacteria in patients suffering from major depressive disorder.

  20. Influenza virosomes as a vaccine adjuvant and carrier system.

    Science.gov (United States)

    Moser, Christian; Amacker, Mario; Zurbriggen, Rinaldo

    2011-04-01

    Influenza virosomes have been used for more than 10 years in commercial vaccines. The technology has been further developed as a carrier and adjuvant system for subunit vaccines, in particular for synthetic peptides. The extensive amount of preclinical and clinical data supports the notion that influenza virosomes represent a platform technology that ensures robust and long-lasting immune responses against subunit antigens with an excellent safety profile. Structurally and functionally, virosomes are enveloped virus-like particles, although they are assembled in vitro. This unique feature ensures a tight control of their composition and at the same time provides the flexibility to adapt the particle to various types of antigens. The mode of action of virosomes is complex and includes carrier as well as immune-stimulatory functions.

  1. Adjuvant Radiation Therapy and Survival for Pure Tubular Breast Carcinoma-Experience From the SEER Database

    Energy Technology Data Exchange (ETDEWEB)

    Li Baoqing, E-mail: bal9018@med.cornell.edu [Department of Radiation Oncology, Weill Cornell Medical College, New York, New York (United States); Chen, Margaret [Department of Surgery, Weill Cornell Medical College, New York, New York (United States); Nori, Dattatreyudu; Chao, K.S. Clifford [Department of Radiation Oncology, Weill Cornell Medical College, New York, New York (United States); Chen, Allen M. [Department of Radiation Oncology, University of California Davis Cancer Center, Sacramento, California (United States); Chen, Steven L. [Department of Surgery, University of California Davis Cancer Center, Sacramento, California (United States)

    2012-09-01

    Purpose: Pure tubular carcinoma of the breast (PTCB) represents a distinct subtype of invasive ductal carcinoma (IDC) that is generally thought to be associated with better prognosis than even low-grade IDC. There has been controversy as to the role of adjuvant radiation therapy (RT) in this population. We hypothesized that adjuvant RT would demonstrate a survival improvement. Methods and Materials: We queried the Surveillance, Epidemiology and End Results database for the years 1992-2007 to identify patients with pure tubular carcinomas of the breast. Patient demographics, tumor characteristics, and surgical and RT treatments were collected. Survival analysis was performed using the Kaplan-Meier method for univariate comparisons and Cox proportional hazards modeling for multivariate comparisons, stratifying on the basis of age with a cutoff age of 65. Results: A total of 6465 patients were identified: 3624 (56.1%) patients underwent lumpectomy with RT (LUMP+RT), 1525 (23.6%) patients underwent lumpectomy alone (LUMP), 1266 (19.6%) patients received mastectomy alone (MAST), and 50 (0.8%) patients underwent mastectomy with RT (MAST+RT). When we compared the LUMP+RT and LUMP groups directly, those receiving adjuvant RT tended to be younger and were less likely to be hormone receptor-positive. Overall survival was 95% for LUMP+RT and 90% for LUMP patients at 5 years. For those 65 or younger, the absolute overall survival benefit of LUMP+RT over LUMP was 1% at 5 years and 3% at 10 years. On stratified multivariate analysis, adjuvant RT remained a significant predictor in both age groups (P=.003 in age {<=}65 and P=.04 in age >65 patients). Other significant unfavorable factors were older age and higher T stage (age >65 only). Conclusions: Since sufficiently powered large scale clinical trials are unlikely, we would recommend that adjuvant radiation be considered in PTCB patients age 65 or younger, although consideration of the small absolute survival benefit is

  2. Physical Therapy Adjuvants to Promote Optimization of Walking Recovery after Stroke

    Directory of Open Access Journals (Sweden)

    Mark G. Bowden

    2011-01-01

    Full Text Available Stroke commonly results in substantial and persistent deficits in locomotor function. The majority of scientific inquiries have focused on singular intervention approaches, with recent attention given to task specific therapies. We propose that measurement should indicate the most critical limiting factor(s to be addressed and that a combination of adjuvant treatments individualized to target accompanying impairment(s will result in the greatest improvements in locomotor function. We explore training to improve walking performance by addressing a combination of: (1 walking specific motor control; (2 dynamic balance; (3 cardiorespiratory fitness and (4 muscle strength and put forward a theoretical framework to maximize the functional benefits of these strategies as physical adjuvants. The extent to which any of these impairments contribute to locomotor dysfunction is dependent on the individual and will undoubtedly change throughout the rehabilitation intervention. Thus, the ability to identify and measure the relative contributions of these elements will allow for identification of a primary intervention as well as prescription of additional adjuvant approaches. Importantly, we highlight the need for future studies as appropriate dosing of each of these elements is contingent on improving the capacity to measure each element and to titrate the contribution of each to optimal walking performance.

  3. Updated European Association of Urology Guidelines Regarding Adjuvant Therapy for Renal Cell Carcinoma.

    Science.gov (United States)

    Bex, Axel; Albiges, Laurence; Ljungberg, Börje; Bensalah, Karim; Dabestani, Saeed; Giles, Rachel H; Hofmann, Fabian; Hora, Milan; Kuczyk, Markus A; Lam, Thomas B; Marconi, Lorenzo; Merseburger, Axel S; Staehler, Michael; Volpe, Alessandro; Powles, Thomas

    2017-05-01

    The European Association of Urology Renal Cell Carcinoma (RCC) guidelines panel updated their recommendation on adjuvant therapy in unfavourable, clinically nonmetastatic RCC following the recently reported results of a second randomised controlled phase 3 trial comparing 1-yr sunitinib to placebo for high-risk RCC after nephrectomy (S-TRAC). On the basis of conflicting results from the two available studies, the panel rated the quality of the evidence, the harm-to-benefit ratio, patient preferences, and costs. Finally, the panel, including representatives from a patient advocate group (International Kidney Cancer Coalition) voted and reached a consensus to not recommend adjuvant therapy with sunitinib for patients with high-risk RCC after nephrectomy. In two studies, sunitinib was given for 1 yr and compared to no active treatment (placebo) in patients who had their kidney tumour removed and who had a high risk of cancer coming back after surgery. Although one study demonstrated that 1 yr of sunitinib therapy resulted in a 1.2-yr longer time before the disease recurred, the other study did not show a benefit and it has not been shown that patients live longer. Despite having been diagnosed with high-risk disease, many patients remain without recurrence, and the side effects of sunitinib are high. Therefore, the panel members, including patient representatives, do not recommend sunitinib after tumour removal in these patients. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  4. Vitamin E and N-Acetylcysteine as Antioxidant Adjuvant Therapy in Children with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Youssef Al-Tonbary

    2009-01-01

    Full Text Available Although cancer therapies have experienced great success nowadays, yet the associated toxic response and free radicals formation have resulted in significant number of treatment-induced deaths rather than disease-induced fatalities. Complications of chemotherapy have forced physicians to study antioxidant use as adjunctive treatment in cancer. This study aimed to evaluate the antioxidant role of vitamin E and N-acetyl cysteine (NAC in overcoming treatment-induced toxicity in acute lymphoblastic leukaemia (ALL during the intensive period of chemo-/radiotherapy, almost the first two months of treatment. Forty children newly diagnosed with ALL were enrolled in this study. Twenty children (group I have taken vitamin E and NAC supplementations with chemotherapy and the other twenty children (group II have not taken any adjuvant antioxidant therapy. They were evaluated clinically for the occurrence of complications and by the laboratory parameters (blood levels of glutathione peroxidase (Glu.PX antioxidant enzyme, malondialdehyde (MDA, tumor necrosis factor- (TNF-, liver enzymes, and bone marrow picture. Results revealed reduced chemotherapy and radiotherapy toxicity as evidenced by decreasing level of MDA, increasing level of Glu.Px and decreased occurrence of toxic hepatitis, haematological complications, and need for blood and platelet transfusions in group I compared to group II. We can conclude that vitamin E and NAC have been shown to be effective as antioxidant adjuvant therapy in children with ALL to reduce chemo-/radiotherapy-related toxicities during the initial period of treatment.

  5. Induction chemotherapy vs post-operative adjuvant therapy for malignant pleural mesothelioma.

    Science.gov (United States)

    Marulli, Giuseppe; Faccioli, Eleonora; Bellini, Alice; Mammana, Marco; Rea, Federico

    2017-08-01

    Malignant pleural mesothelioma (MPM) is an aggressive neoplasia. Multidisciplinary treatments, including the association of induction and/or adjuvant therapeutic regimens with surgery, have been reported to give encouraging results. Current therapeutic options are not well standardized yet, especially regarding the best association between surgery and medical treatments. The present review aims to assess safety, efficacy and outcomes of different therapies for MPM. Areas covered: This article focuses on the multimodality treatment of mesothelioma. A systematic review was performed by using electronic databases to identify studies that considered induction and adjuvant approaches in MPM therapy in a multidisciplinary setting, including surgery. Endpoints included overall survival, disease free survival, disease recurrence, and complications. Expert commentary: This systematic review offers a comprehensive view of current multidisciplinary therapeutic strategies for MPM, suggesting that multimodality therapy offers acceptable outcomes with better results reported for trimodality approaches. Individualization of care for each patient is fundamental in choosing the most appropriate treatment. The growing complexity of treatment protocols mandates that MPM patients be referred to specialized Centers, in which every component of the interdisciplinary team can provide the necessary expertise and quality of care.

  6. A Case of Therapy-Related Acute Myeloid Leukemia Associated with Adjuvant Temozolomide Chemotherapy for Anaplastic Astrocytoma.

    Science.gov (United States)

    Kosugi, Kenzo; Saito, Katsuya; Takahashi, Wataru; Tokuda, Yukina; Tomita, Hideyuki

    2017-05-01

    Temozolomide (TMZ) is now standard adjuvant therapy in combination with radiotherapy for patients with newly diagnosed malignant glioma. Treatment-related myelodysplastic syndrome and acute treatment-related leukemia (t-AML) associated with TMZ chemotherapy for patients with glioma is quite a rare complication. A 43-year-old man with an anaplastic astrocytoma received radiation therapy synchronized with ranimustine and adjuvant TMZ chemotherapy for 15 cycles. Close follow-up magnetic resonance imaging of the head during TMZ chemotherapy showed no evidence of tumor progression. One year after the completion of TMZ chemotherapy, a bone-marrow aspiration was performed because the patient's white blood cell count decreased. He was diagnosed with t-AML based on the bone marrow examination, and then he was referred to the cancer center for the treatment of t-AML. In this case study, we continued adjuvant TMZ therapy beyond the recommended 6 cycles. Currently, there is no consensus as to how long the adjuvant TMZ therapy should be continued for the treatment of residual tumor showing no apparent interval change. A new decision-making tool to assess the clinical benefits against the side effects for long-term adjuvant TMZ therapy is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. [Effect of adjuvant therapy with Dingguier umbilical paste on intestinal flora of diarrhea infants and its action characteristics].

    Science.gov (United States)

    Sun, Hai-Feng; Gao, Yan-Yun; An, Cui-Hong; Li, Yu-Lan; Duan, Li-Jun; Yu, Yu-Hong; Ren, Wu-Xian

    2014-07-01

    The applicator therapy is a unique method to treat infant diarrhea in traditional Chinese medicines and widely applied in clinical practice. Currently, many researchers have proved the rationality of the therapy based on the traditional Chinese medicine mechanism and on the data from clinical practice, but its action mechanism is uncertain at present. In this study, with the assistance of pediatric practitioners, the automated ribosomal intergenic-spacer analysis (ARISA) was adopted to study the effect of the adjuvant therapy with Dingguier umbilical paste on intestinal flora of diarrhea infants, in which Dingguier umbilical paste served as the adjuvant therapy in oral traditional Chinese medicines and fecal samples of infants with different diarrhea symptoms were collected and used as the study materials. The results showed that the adjuvant therapy had a significant effect on the shift of intestinal flora, which was associated with the decrease in the similarity difference to the normal control group and the increase in the number of operational taxonomic units (OTUs) shared with the normal control group. Additionally, adjuvant therapy with Dingguier umbilical paste also showed long action duration and increased OTUs number. These results indicated that Dingguier umbilical paste has the effect in restoring the micro-ecosystem of unbalanced intestinal bacteria. Intestinal flora may be one of major targets for the applicator therapy for the infant diarrhea, but not for the single oral traditional Chinese medicine for infant diarrhea.

  8. Effectiveness of transscleral cyclophotocoagulation as adjuvant therapy for refractory glaucoma in keratoprosthesis patients.

    Science.gov (United States)

    Wang, Dajiang; Yu, Jifeng; Tian, Lei; Wang, Liqiang; Huang, Yifei

    2015-01-01

    To evaluate the efficacy and safety of diode laser transscleral cyclophotocoagulation (DLTSC) as an adjuvant therapy to treat refractory glaucoma diagnosed before or after Moscow Eye Microsurgery Complex (MICOF) keratoprosthesis surgery. Fifteen patients underwent unilateral DLTSC to treat refractory glaucoma diagnosed before or after undergoing MICOF keratoprosthesis surgery. The cause for keratoprosthesis was alkali burn in 8 patients (53.33%); thermal burn, sulfuric acid burn, and Steven-Johnson syndrome in 2 patients (13.33%) each; and ocular cicatricial pemphigoid in 1 patient (6.67%). Best-corrected visual acuity (BCVA), intraocular pressure (IOP), any medications, and adverse events were recorded before DLTSC and on postoperative day 7; months 1, 3, and 6; and every 6 months afterwards. The patients were followed up for an average of 13.15 ± 9.35 months. The IOP was significantly less at postoperative months 6, 12, 24, and 36. There were no changes in BCVA after DLTSC. No significant changes in medication to treat ocular hypertension were prescribed. Diode laser transscleral cyclophotocoagulation is an effective treatment option for refractory glaucoma and can be used as a therapy adjuvant to keratoprosthesis. Long-term effects require further clinical observation.

  9. [Value of adjuvant basic therapy in chronic recurrent skin diseases. Neurodermatitis atopica/psoriasis vulgaris].

    Science.gov (United States)

    Schöpf, E; Mueller, J M; Ostermann, T

    1995-07-01

    Atopic dermatitis and psoriasis vulgaris belong to the most common diseases in dermatology. Since these chronical diseases progress over years and decades, they may lead to restrictions in private and professional life as well as to psychological stress of concerned patients. Therefore, a lasting, stabilising, stage-adjusted topical treatment is necessary. Main component of this treatment in a complete therapeutical concept consists in an adjuvant basic therapy with oil baths and with emollients containing urea or no drug additives at all. Thus the vehicle itself is therapeutically effective. Altered structure and function of the skin measured by increased transepidermal water loss, dysfunction of skin lipid barrier, augmented skin permeability and skin roughness can be improved. Due to this treatment clinical symptoms can be diminished and relapses can be avoided. Corticosteroids and other specific medications can be reduced by using basic therapeutics with little side effects. This means economical benefit as well. So far adjuvant basic treatment is an essential part in the therapy of chronic inflammatory skin diseases.

  10. Adjuvant electrochemotherapy in veterinary patients: a model for the planning of future therapies in humans

    Directory of Open Access Journals (Sweden)

    Baldi Alfonso

    2009-08-01

    Full Text Available Abstract The treatment of soft tissue tumors needs the coordinated adoption of surgery with radiation therapy and eventually, chemotherapy. The radiation therapy (delivered with a linear accelerator can be preoperative, intraoperative, or postoperative. In selected patients adjuvant brachytherapy can be adopted. The goal of these associations is to achieve tumor control while maximally preserving the normal tissues from side effects. Unfortunately, the occurrence of local and distant complications is still elevated. Electrochemotherapy is a novel technique that combines the administration of anticancer agents to the application of permeabilizing pulses in order to increase the uptake of antitumor molecules. While its use in humans is still confined to the treatment of cutaneous neoplasms or the palliation of skin tumor metastases, in veterinary oncology this approach is rapidly becoming a primary treatment. This review summarizes the recent progresses in preclinical oncology and their possible transfer to humans.

  11. A high level of estrogen-stimulated proteins selects breast cancer patients treated with adjuvant endocrine therapy with good prognosis

    DEFF Research Database (Denmark)

    L H Weischenfeldt, Katrine; Kirkegaard, Tove; Rasmussen, Birgitte B

    2017-01-01

    BACKGROUND: Adjuvant endocrine therapy has significantly improved survival of estrogen receptor α (ER)-positive breast cancer patients, but around 20% relapse within 10 years. High expression of ER-stimulated proteins like progesterone receptor (PR), Bcl-2 and insulin-like growth factor receptor I...... (IGF-IR) is a marker for estrogen-driven cell growth. Therefore, patients with high tumor levels of these proteins may have particularly good prognosis following adjuvant endocrine therapy. PATIENTS AND METHODS: Archival tumor tissue was available from 1323 of 1396 Danish breast cancer patients...

  12. Anaplastic astrocytoma: prognostic factors and survival in 4807 patients with emphasis on receipt and impact of adjuvant therapy.

    Science.gov (United States)

    Shin, Jacob Y; Diaz, Aidnag Z

    2016-09-01

    To determine the receipt and impact of adjuvant therapy on overall survival (OS) for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4807 patients with AA diagnosed from 2004 to 2013 who underwent surgery were identified. 3243 (67.5 %) received adjuvant chemoRT, 525 (10.9 %) adjuvant radiotherapy (RT) alone, 176 (3.7 %) adjuvant chemotherapy alone and 863 (18.0 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 (p = 0.022), were ≤ 50 years (p < 0.001), were male (p = 0.043), were Asian or White race (p < 0.001), had private insurance (p < 0.001), had income ≥$38,000 (p < 0.001), or underwent total resection (p < 0.003). Those who received adjuvant chemoRT had significantly better 5-year OS than the other adjuvant treatment types (41.8 % vs. 31.2 % vs. 29.8 % vs. 27.4 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age at diagnosis. Of those undergoing adjuvant chemoRT, those receiving ≥59.4 Gy had significantly better 5-year OS than those receiving <59.4 Gy (44.4 % vs. 25.9 %, p < 0.001). There was no significant difference in OS when comparing 59.4 Gy to higher RT doses. On multivariate analysis, receipt of adjuvant chemoRT, age at diagnosis, extent of disease, and insurance status were independent prognostic factors for OS. Adjuvant chemoRT is an independent prognostic factor for improved OS in AA and concomitant chemoRT should be considered for all clinically suitable patients who have undergone surgery for the disease.

  13. 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.

  14. Trastuzumab retreatment after relapse on adjuvant trastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer: final results of the Retreatment after HErceptin Adjuvant trial.

    Science.gov (United States)

    Láng, I; Bell, R; Feng, F Y; Lopez, R I; Jassem, J; Semiglazov, V; Al-Sakaff, N; Heinzmann, D; Chang, J

    2014-02-01

    Trastuzumab, in combination with chemotherapy, is the standard of care for patients with early and metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The Retreatment after HErceptin Adjuvant trial assessed the efficacy and safety of trastuzumab plus a taxane as first-line treatment for patients with metastatic breast cancer (MBC) who had relapsed after adjuvant trastuzumab for HER2-positive early breast cancer. In total, 43 patients with HER2-positive MBC who had received previous adjuvant trastuzumab for ≥10 months, with a relapse-free interval of ≥6 months after the last adjuvant trastuzumab dose, were recruited. Eligible patients (n = 41) were assigned to receive trastuzumab, either weekly or every 3 weeks, in combination with docetaxel or paclitaxel until disease progression. At the final analysis, with a median follow-up time of 40 months, a positive response was observed in 25/41 patients (61%; 95% confidence interval: 48.7-80.4%), stable disease in 7/41 (17.1%) and progressive disease in 6/41 (14.6%). Three patients had missing response assessments (one had no measurable lesions at baseline and two had no post-baseline tumour assessments). The median progression-free survival (PFS) was 8.0 months (95% confidence interval: 6-11 months) and the median overall survival was 25.0 months (16-33 months). No correlation was found between response rate, PFS or overall survival and the duration of adjuvant trastuzumab treatment, trastuzumab-free interval, relapse-free interval, hormone receptor status or type of pre-metastatic treatment. The most common adverse events (all grades) were alopecia (32%) and diarrhoea (32%). Six patients (14.6%) developed at least one serious adverse event. No congestive heart failure or any unexpected adverse events were reported. Trastuzumab, in combination with a taxane, is an effective and well-tolerated first-line treatment for MBC in patients who relapse after trastuzumab-based adjuvant therapy

  15. Antidepressive response of inpatients with major depression to adjuvant occupational therapy: a case-control study.

    Science.gov (United States)

    Edel, Marc-Andreas; Blackwell, Brian; Schaub, Markus; Emons, Barbara; Fox, Tanja; Tornau, Friederike; Vieten, Bernward; Roser, Patrik; Haussleiter, Ida Sibylle; Juckel, Georg

    2017-01-01

    Despite marked costs and limited evidence regarding effectiveness, occupational therapy (OT) is widely applied in psychiatric settings and financed by health insurance companies in European countries. This pilot study investigated the antidepressive effects of adjuvant OT for patients with major depression in a 6-week inpatient setting, stratified for females and males. A total of 114 inpatients with major depression were assigned to either a standard OT group (using basic handcraft) or an active control group that played board games (2 h daily, 5 days a week). HAMD-21 scores were assessed as the primary outcome parameter after 3-6 weeks. The OT intervention was not superior to "board game" (BG) activities in reducing depressive symptoms. However, significant interaction effects were found in favor of the OT group regarding anxiety measures and other variables. Male participants displayed more significant interaction effects than female participants. OT as an adjuvant short-term treatment for inpatients with major depression may be more efficacious than game interventions in terms of reducing anxiety and other symptoms, particularly in males. Trial registration The study was registered in the EU Clinical Trials Register as a multicenter trial (EudraCT Number 2009-016463-10; https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-016463-10/DE#A) However, because of the elaborate setting requirements, the original study design with four centers was transformed into a solution with those two centers facilitating the pertinent resources. Furthermore, "mono-therapy with mirtazapine" was changed into "preferably mono-therapy with any antidepressant drug".

  16. Effects of surgical and adjuvant therapies for breast cancer on sexuality, cognitive functions, and body weight.

    Science.gov (United States)

    Biglia, Nicoletta; Moggio, Giulia; Peano, Elisa; Sgandurra, Paola; Ponzone, Riccardo; Nappi, Rossella E; Sismondi, Piero

    2010-05-01

    Breast cancer and its treatment negatively affect the important aspects of a woman's life such as sexual health, cognitive functions, body image, and weight. Abrupt estrogen deficiency following chemotherapy and/or hormonal therapy plays an important role in worsening of sexuality. To evaluate the impact of breast cancer treatment on sexual functioning, cognitive function, and body weight in premenopausal women. Thirty-five women with a premenopausal diagnosis of breast cancer who are candidate to adjuvant treatment completed validated questionnaires on menopausal symptoms, sexuality, partner relationship, depression, body image, and cognitive functions after surgery (T0), then after chemotherapy or at least 6 months of endocrine therapy (T1), and after 1 year (T2). In addition, gynecological and dietological examinations were performed. The following validated questionnaires were used: Greene Climacteric Scale, Beck Depression Inventory, Body Attitude Test, McCoy revised Italian version McCoy Female Sexuality Questionnaire, Cues for Sexual Desire Scale, Dyadic Adjustment Scale, Numeric Matrix Test and Rey auditory-verbal learning test, to measure cognitive functions, a recall 24 H questionnaire to evaluate food intake, Minnesota Leisure Time Physical Activity questionnaire and Eating Attitude Test-40, while anthropometric and plicometry data were assessed by a dietitian. Low levels of sexual functioning were registered at baseline; a further decrease in sexual activity, quality of the partnered relationship, desire, and arousability was demonstrated at T1 and T2. We found a significant increase in hot flushes and anxiety. Nonsignificant deterioration of body image was demonstrated. Although women reported losing memory and concentration, "chemobrain" effect was not demonstrated as cognitive tests improved after 6 months, probably because of "learning effect." Women who had undergone chemotherapy gained weight and fat disposition was typically android. Young women

  17. A high level of estrogen-stimulated proteins selects breast cancer patients treated with adjuvant endocrine therapy with good prognosis

    DEFF Research Database (Denmark)

    L H Weischenfeldt, Katrine; Kirkegaard, Tove; Rasmussen, Birgitte B

    2017-01-01

    BACKGROUND: Adjuvant endocrine therapy has significantly improved survival of estrogen receptor α (ER)-positive breast cancer patients, but around 20% relapse within 10 years. High expression of ER-stimulated proteins like progesterone receptor (PR), Bcl-2 and insulin-like growth factor receptor I...... (IGF-IR) is a marker for estrogen-driven cell growth. Therefore, patients with high tumor levels of these proteins may have particularly good prognosis following adjuvant endocrine therapy. PATIENTS AND METHODS: Archival tumor tissue was available from 1323 of 1396 Danish breast cancer patients...... enrolled in BIG 1-98, a randomized phase-III clinical trial comparing adjuvant letrozole, tamoxifen or a sequence of the two drugs. Immunohistochemical staining for ER, HER-2, PR, Bcl-2 and IGF-IR was performed and determined by Allred scoring (ER, PR and Bcl-2) or HercepTest (HER-2 and IGF-IR). RESULTS...

  18. Extended adjuvant aromatase inhibition after sequential endocrine therapy (DATA): a randomised, phase 3 trial.

    Science.gov (United States)

    Tjan-Heijnen, Vivianne C G; van Hellemond, Irene E G; Peer, Petronella G M; Swinkels, Astrid C P; Smorenburg, Carolien H; van der Sangen, Maurice J C; Kroep, Judith R; De Graaf, Hiltje; Honkoop, Aafke H; Erdkamp, Frans L G; van den Berkmortel, Franchette W P J; de Boer, Maaike; de Roos, Wilfred K; Linn, Sabine C; Imholz, Alexander L T; Seynaeve, Caroline M

    2017-10-11

    The effect of extended adjuvant aromatase inhibition in hormone receptor-positive breast cancer after sequential endocrine therapy of tamoxifen followed by an aromatase inhibitor for a 5-year treatment period still needs clarification. To address this issue, we began the DATA study to assess different durations of anastrozole therapy after tamoxifen. DATA was a prospective, randomised, open-label, multicentre, phase 3 study done in 79 hospitals in the Netherlands. We randomly assigned postmenopausal women with hormone receptor-positive early breast cancer with no signs of disease recurrence after 2-3 years of adjuvant tamoxifen to either 3 or 6 years of anastrozole treatment (1 mg orally once a day) in a 1:1 ratio. We used TENALEA (Trans European Network for Clinical Trials Services) for the randomisation procedure. Stratification factors were nodal status, hormone receptor status, HER2 status, and tamoxifen treatment duration. The primary study endpoint of this analysis was disease-free survival starting beyond 3 years after randomisation (adapted disease-free survival). Here we report the final analysis from the DATA trial, which is registered with ClinicalTrials.gov, number NCT00301457. Between June 28, 2006, and Aug 10, 2009, we screened 1912 patients of whom 955 were assigned to the 3-year group and 957 to the 6-year anastrozole treatment group. 1860 patients were eligible (931 in the 6-year group and 929 in the 3-year group) and 1660 were disease free 3 years after randomisation. The 5-year adapted disease-free survival was 83·1% (95% CI 80·0-86·3) in the 6-year group and 79·4% (76·1-82·8) in the 3-year group (hazard ratio [HR] 0·79 [95% CI 0·62-1·02]; p=0·066). Patients in the 6-year treatment group had more adverse events than those in the 3-year treatment group, including all-grade arthralgia or myalgia (478 [58%] of 827 in the 6-year treatment group vs 438 [53%] of 833 in the 3-year treatment group) and osteopenia or osteoporosis (173 [21%] vs

  19. Herbal Medicine and Acupuncture for Breast Cancer Palliative Care and Adjuvant Therapy

    Directory of Open Access Journals (Sweden)

    Guo-Shiou Liao

    2013-01-01

    Full Text Available Breast cancer is a life-threatening disease among women worldwide with annual rates of reported incidence and death increasing alarmingly. Chemotherapy is a recommended and effective treatment option for breast cancer; however, the narrow therapeutic indices and varied side effects of currently approved drugs present major hurdles in increasing its effectiveness. An increasing number of literature evidence indicate that complementary and alternative medicine (CAM used in treatment-related symptom control and alleviation of side effects plays an important role in increasing survival rate and quality of life in breast cancer patients. This review focuses on the use of herbal medicines and acupuncture in palliative care and as adjuvants in the treatment of breast cancer. Herbal medicinal treatments, the correlation of clinical use with demonstrated in vitro and in vivo mechanisms of action, and the use of certain acupoints in acupuncture are summarized. The aim of this review is to facilitate an understanding of the current practice and usefulness of herbal medicine and acupuncture as adjuvants in breast cancer therapy.

  20. Influence of Adjuvant Therapy in Cancer Survivors on Endothelial Function and Skeletal Muscle Deoxygenation.

    Science.gov (United States)

    Ederer, Austin K; Didier, Kaylin D; Reiter, Landon K; Brown, Michael; Hardy, Rachel; Caldwell, Jacob; Black, Christopher D; Larson, Rebecca D; Ade, Carl J

    2016-01-01

    The cardiotoxic effects of adjuvant cancer treatments (i.e., chemotherapy and radiation treatment) have been well documented, but the effects on peripheral cardiovascular function are still unclear. We hypothesized that cancer survivors i) would have decreased resting endothelial function; and ii) altered muscle deoxygenation response during moderate intensity cycling exercise compared to cancer-free controls. A total of 8 cancer survivors (~70 months post-treatment) and 9 healthy controls completed a brachial artery FMD test, an index of endothelial-dependent dilation, followed by an incremental exercise test up to the ventilatory threshold (VT) on a cycle ergometer during which pulmonary V̇O2 and changes in near-infrared spectroscopy (NIRS)-derived microvascular tissue oxygenation (TOI), total hemoglobin concentration ([Hb]total), and muscle deoxygenation ([HHb] ≈ fractional O2 extraction) were measured. There were no significant differences in age, height, weight, and resting blood pressure between cancer survivors and control participants. Brachial artery FMD was similar between groups (P = 0.98). During exercise at the VT, TOI was similar between groups, but [Hb]total and [HHb] were significantly decreased in cancer survivors compared to controls (P muscle microvascular function was observed during moderate intensity cycling exercise. These data suggest that adjuvant cancer therapies have an effect on the integrated relationship between O2 extraction, V̇O2 and O2 delivery during exercise.

  1. Adjuvant therapy with aromatase inhibitors for postmenopausal women with early breast cancer: evidence and ongoing controversy.

    Science.gov (United States)

    Wheler, Jennifer; Johnson, Melissa; Seidman, Andrew

    2006-12-01

    Results of five major randomized trials have increased our understanding of the role of aromatase inhibitors in the adjuvant setting. Two of these trials, the Anastrozole or Tamoxifen Alone or in Combination (ATAC) trial and the International Breast Cancer Study Group's BIG 1-98 trial compared an aromatase inhibitor versus tamoxifen as initial hormonal therapy. Three other trial were designed as cross-over studies; the Intergroup Exemestane Study (IES) and the Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 8/German ARNO 95 trial compared a crossover from tamoxifen to an aromatase inhibitor versus continued tamoxifen in women who had completed 2 to 3 years of tamoxifen. The MA-17 trial compared the use of letrozole with placebo for 5 years, following 5 years of tamoxifen. Based on the results of these studies, the use of an aromatase inhibitor for the adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer has largely replaced the previous standard of 5 years of tamoxifen. Still unanswered, however, are questions regarding optimal sequencing, selection of aromatase inhibitor, and duration of treatment. This review will provide an overview of the major studies with an emphasis on these important questions.

  2. Clinical outcomes of adjuvant radiation therapy and prognostic factors in early stage uterine cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Ju; Rhee, Woo Joong; Choi, Seo Hee; Kim, Gwi Eon; Kim, Yong Bae [Dept. of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of); Nam, EunJi; Kim, Sang Wun; Kim, Sung Hoon [Dept. of Radiation Oncology, Obstetrics and Gynecology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    To evaluate the outcomes of adjuvant radiotherapy (RT) and to analyze prognostic factors of survival in the International Federation of Gynecology and Obstetrics (FIGO) IB-IIA uterine cervical cancer. We retrospectively reviewed the medical records of 148 patients with FIGO IB-IIA uterine cervical cancer who underwent surgery followed by adjuvant RT at the Yonsei Cancer Center between June 1997 and December 2011. Adjuvant radiotherapy was delivered to the whole pelvis or an extended field with or without brachytherapy. Among all patients, 57 (38.5%) received adjuvant chemotherapy either concurrently or sequentially. To analyze prognostic factors, we assessed clinicopathologic variables and metabolic parameters measured on preoperative {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). To evaluate the predictive performance of metabolic parameters, receiver operating characteristic curve analysis was used. Overall survival (OS) and disease-free survival (DFS) were analyzed by the Kaplan-Meier method. The median follow-up period was 63.2 months (range, 2.7 to 206.8 months). Locoregional recurrence alone occurred in 6 patients, while distant metastasis was present in 16 patients, including 2 patients with simultaneous regional failure. The 5-year and 10-year OSs were 87.0% and 85.4%, respectively. The 5-year and 10-year DFSs were 83.8% and 82.5%, respectively. In multivariate analysis, pathologic type and tumor size were shown to be significant prognostic factors associated with both DFS and OS. In subset analysis of 40 patients who underwent preoperative PET/CT, total lesion glycolysis was shown to be the most significant prognostic factor among the clinicopathologic variables and metabolic parameters for DFS. Our results demonstrated that adjuvant RT following hysterectomy effectively improves local control. From the subset analysis of preoperative PET/CT, we can consider that metabolic parameters may hold prognostic

  3. Treatment of Oral Cavity Squamous Cell Carcinoma With Adjuvant or Definitive Intensity-Modulated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Sher, David J., E-mail: dsher@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Thotakura, Vijaya [Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Balboni, Tracy A. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Norris, Charles M.; Haddad, Robert I.; Posner, Marshall R.; Lorch, Jochen [Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Goguen, Laura A.; Annino, Donald J. [Department of Surgery, Division of Otolaryngology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Tishler, Roy B. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States)

    2011-11-15

    Purpose: The optimal management of oral cavity squamous cell carcinoma (OCSCC) typically involves surgical resection followed by adjuvant radiotherapy or chemoradiotherapy (CRT) in the setting of adverse pathologic features. Intensity-modulated radiation therapy (IMRT) is frequently used to treat oral cavity cancers, but published IMRT outcomes specific to this disease site are sparse. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for OCSCC. Methods and Materials: Retrospective study of all patients treated at Dana-Farber Cancer Institute for OCSCC with adjuvant or definitive IMRT between August 2004 and December 2009. The American Joint Committee on Cancer disease stage criteria distribution of this cohort included 5 patients (12%) with stage I; 10 patients (24%) with stage II (n = 10, 24%),; 14 patients (33%) with stage III (n = 14, 33%),; and 13 patients (31%) with stage IV. The primary endpoint was overall survival (OS); secondary endpoints were locoregional control (LRC) and acute and chronic toxicity. Results: Forty-two patients with OCSCC were included, 30 of whom were initially treated with surgical resection. Twenty-three (77%) of 30 surgical patients treated with adjuvant IMRT also received concurrent chemotherapy, and 9 of 12 (75%) patients treated definitively without surgery were treated with CRT or induction chemotherapy and CRT. With a median follow-up of 2.1 years (interquartile range, 1.1-3.1 years) for all patients, the 2-year actuarial rates of OS and LRC following adjuvant IMRT were 85% and 91%, respectively, and the comparable results for definitive IMRT were 63% and 64% for OS and LRC, respectively. Only 1 patient developed symptomatic osteoradionecrosis, and among patients without evidence of disease, 35% experienced grade 2 to 3 late dysphagia, with only 1 patient who was continuously gastrostomy-dependent. Conclusions: In this single-institution series, postoperative IMRT was associated with promising LRC

  4. Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy.

    Science.gov (United States)

    Lecumberri, Elena; Dupertuis, Yves Marc; Miralbell, Raymond; Pichard, Claude

    2013-12-01

    Green tea catechins, especially epigallocatechin-3-gallate (EGCG), have been associated with cancer prevention and treatment. This has resulted in an increased number of studies evaluating the effects derived from the use of this compound in combination with chemo/radiotherapy. This review aims at compiling latest literature on this subject. Keywords including EGCG, cancer, chemotherapy, radiotherapy and side effects, were searched using PubMed and ScienceDirect databases to identify, analyze, and summarize the research literature on this topic. Most of the studies on this subject up to date are preclinical. Relevance of the findings, impact factor, and date of publication were critical parameters for the studies to be included in the review. Additive and synergistic effects of EGCG when combined with conventional cancer therapies have been proposed, and its anti-inflammatory and antioxidant activities have been related to amelioration of cancer therapy side effects. However, antagonistic interactions with certain anticancer drugs might limit its clinical use. The use of EGCG could enhance the effect of conventional cancer therapies through additive or synergistic effects as well as through amelioration of deleterious side effects. Further research, especially at the clinical level, is needed to ascertain the potential role of EGCG as adjuvant in cancer therapy. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  5. Cardiac monitoring during adjuvant trastuzumab therapy: Guideline adherence in clinical practice

    NARCIS (Netherlands)

    Visser, A.; Ven, E.M.W. van de; Ruczynski, L.I.; Blaisse, R.J.; Halteren, H.K. van; Aben, K.K.H.; Laarhoven, H.W.M. van

    2016-01-01

    BACKGROUND: Cardiotoxicity is an important adverse effect of adjuvant breast cancer treatment with trastuzumab and three monthly left ventricular ejection fraction (LVEF) monitoring is considered mandatory. The purpose of this study was to gain insight into LVEF monitoring during adjuvant

  6. Nomogram Prediction of Survival and Recurrence in Patients With Extrahepatic Bile Duct Cancer Undergoing Curative Resection Followed by Adjuvant Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Song, Changhoon [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Kyubo, E-mail: kyubokim@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Chie, Eui Kyu [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of); Kim, Jin Ho [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Jang, Jin-Young; Kim, Sun Whe [Department of Surgery, Seoul National University College of Medicine, Seoul (Korea, Republic of); Han, Sae-Won; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue [Department of Internal Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Ha, Sung W. [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of)

    2013-11-01

    Purpose: To develop nomograms for predicting the overall survival (OS) and relapse-free survival (RFS) in patients with extrahepatic bile duct cancer undergoing adjuvant chemoradiation therapy after curative resection. Methods and Materials: From January 1995 through August 2006, a total of 166 consecutive patients underwent curative resection followed by adjuvant chemoradiation therapy. Multivariate analysis using Cox proportional hazards regression was performed, and this Cox model was used as the basis for the nomograms of OS and RFS. We calculated concordance indices of the constructed nomograms and American Joint Committee on Cancer (AJCC) staging system. Results: The OS rate at 2 years and 5 years was 60.8% and 42.5%, respectively, and the RFS rate at 2 years and 5 years was 52.5% and 38.2%, respectively. The model containing age, sex, tumor location, histologic differentiation, perineural invasion, and lymph node involvement was selected for nomograms. The bootstrap-corrected concordance index of the nomogram for OS and RFS was 0.63 and 0.62, respectively, and that of AJCC staging for OS and RFS was 0.50 and 0.52, respectively. Conclusions: We developed nomograms that predicted survival and recurrence better than AJCC staging. With caution, clinicians may use these nomograms as an adjunct to or substitute for AJCC staging for predicting an individual's prognosis and offering tailored adjuvant therapy.

  7. Tissue-Doppler assessment of cardiac left ventricular function during short-term adjuvant epirubicin therapy for breast cancer

    DEFF Research Database (Denmark)

    Appel, Jon M; Sogaard, Peter; Mortensen, Christiane E

    2011-01-01

    It has been hypothesized that the extent of acute anthracycline-induced cardiotoxicity reflects the risk for late development of heart failure. The aim of this study was to examine if short-term changes in cardiac function can be detected even after low-dose adjuvant epirubicin therapy for breast...... cancer when using Doppler tissue imaging of longitudinal left ventricular function....

  8. Benefit of adjuvant interferon alfa-2b (IFN-α) therapy in melanoma patients with high serum MMP-8 levels

    DEFF Research Database (Denmark)

    Vihinen, Pia; Tervahartiala, Taina; Sorsa, Timo

    2015-01-01

    Matrix metalloproteinases (MMPs) are important enzymes in tissue turnover and various inflammatory processes. In this study, it was evaluated whether serum MMP-8 can predict the response to adjuvant interferon alfa-2b (IFN-α) therapy in patients with operated high-risk cutaneous melanoma. Pre...

  9. LHRH agonists for adjuvant therapy of early breast cancer in premenopausal women.

    Science.gov (United States)

    Sharma, Rohini; Hamilton, Anne; Beith, Jane

    2008-10-08

    Approximately 60% of breast cancer tumours in premenopausal women are hormone sensitive (ER+). These patients may be suitable for hormonal treatment. The goal of hormonal therapy is to reduce the availability of oestrogen to the cancer cell. This can be achieved by blocking oestrogen receptors with drugs such as tamoxifen, suppression of oestrogen synthesis by LHRH agonists, or ovarian ablation either surgically or by radiotherapy. Chemotherapy can also have a hormonal action by inducing amenorrhoea in premenopausal women. To assess LHRH agonists as adjuvant therapy for women with early breast cancer. The specialised register of the Cochrane Breast Cancer Group was searched on 19 December 2006. The reference lists of related reviews were checked. A final check of the list of trials maintained by the Early Breast Cancer Trialists' Collaborative Group was made in January 2008. Randomised trials of LHRH agonist versus LHRH agonist and tamoxifen, LHRH agonist versus chemotherapy, LHRH agonist versus ovarian ablation, or LHRH agonist versus LHRH agonist and chemotherapy, that recruited premenopausal women with early breast cancer. Data were collected from trial reports. We report estimates for the differences between treatments on recurrence free survival, overall survival, toxicity and quality of life using data available in the reports of each trial. Meta-analyses were not performed because of variability in the reporting of the trials and the need for more mature data. We identified 14 randomised trials, involving nearly 12,000 premenopausal women with operable breast cancer, most of whom were ER+. The LHRH agonist in most of these trials was goserelin. For most of the treatment comparisons there are too few trials, too few randomised patients or too little follow-up to draw reliable estimates of the relative effects of different treatments. Four trials (nearly 5000 women) addressed the integration of LHRH agonists into adjuvant hormonal therapy, showing that a

  10. Doxorubicin and deracoxib adjuvant therapy for canine splenic hemangiosarcoma: A pilot study

    Science.gov (United States)

    Kahn, S. Anthony; Mullin, Christine M.; de Lorimier, Louis-Philippe; Burgess, Kristine E.; Risbon, Rebecca E.; Fred, Rogers M.; Drobatz, Kenneth; Clifford, Craig A.

    2013-01-01

    Canine hemangiosarcoma (HSA) is a highly malignant tumor for which standard chemotherapy has done little to substantially improve survival. Cyclooxygenase-2 (Cox-2) plays a role in the formation, growth, and metastasis of tumors and inhibitors have demonstrated therapeutic benefit with certain canine cancers. In this prospective study, 21 dogs received adjuvant therapy combining the selective Cox-2 inhibitor deracoxib with doxorubicin, following splenectomy for HSA. The combination was well-tolerated with only low-grade gastrointestinal and hematologic toxicities noted. An overall median survival of 150 days (range; 21 to 1506 days) was noted. Although there was no significant difference in survival based upon stage of disease, dogs with stage III HSA (n = 11) had a median survival of 149 days, which appears to be longer than previously reported. Further studies are warranted to evaluate the potential benefit of Cox-2 inhibitors in the treatment of canine HSA. PMID:23997259

  11. Curative effect of ganglioside sodium for adjuvant therapy on acute severe craniocerebral injury

    Directory of Open Access Journals (Sweden)

    Yun-Liang Deng

    2017-01-01

    Full Text Available Objective: To study the effect of adjuvant therapy of ganglioside sodium on intracranial pressure (ICP, partial pressure of brain tissue oxygen (PbtO2, nerve injury molecules, nerve protection molecules and indexes of oxidative stress in patients with acute severe craniocerebral injury. Methods: Forty-seven patients with severe craniocerebral injury treated in the emergency department of our hospital during the period time from December 2012 to October 2015 were selected for retrospective analyses. They were divided into the ganglioside group and the normal treatment group according to the usage of ganglioside sodium in the process of the emergency treatment. At days 1, 3, 5 and 7 before and after treatment, the ICP and PbtO2 in patients of the two groups were measured. After 7 days of treatment, the nerve injury molecules, nerve protection molecules and the indexes of oxidative stress in serum of the patients of the two groups were determined. Results: At days 1, 3, 5 and 7 before and after treatment, the ICP in patients of the ganglioside group were all significantly lower than those of the normal treatment group, while the PbtO2 were all significantly higher than those of normal treatment group. After 7 days of treatment, the contents of serum methane dicarboxylic aldehyde, advanced oxidation protein products, 8-hydroxy-2'-deoxyguanosine urine, S100β, glial fibrillary acidic portein, neuron specific enolase, myelin basic protein, neuroglobin and ubiquitin carboxyl-terminal hydrolase L1 in patients of the ganglioside group were notably lower than those of the normal treatment group, while the contents of superoxidase dismutase, glutathione peroxidase, catalase, nerve growth factor and brain derived neurotrophic factor were significantly higher than those of the normal treatment group. Conclusions: The adjuvant therapy of ganglioside sodium in patients with severe craniocerebral injury can effectively reduce ICP, improve PbtO2 and alleviate

  12. Role of Adjuvant Radiation Therapy After Surgery for Abdominal Desmoplastic Small Round Cell Tumors

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    Atallah, Vincent [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Honore, Charles [Department of Digestive Surgery, Gustave-Roussy Institute, Paris (France); Orbach, Daniel; Helfre, Sylvie [Department of Pediatric Oncology, Curie Institute, Paris (France); Ducassou, Anne [Department of Radiation Oncology, Universitary Cancer Institute, Toulouse (France); Thomas, Laurence [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Levitchi, Mihai-Barbu [Department of Radiation Oncology, Alexis-Vautrin Center, Nancy (France); Mervoyer, Augustin [Department of Radiation Oncology, Cancerologie de l' ouest Institute, Nantes (France); Naji, Salem [Department of Radiation Oncology, Paoli-Calmette Institute, Marseille (France); Dupin, Charles [Department of Radiation Oncology, Universitary Hospital, Bordeaux (France); Bosco-Levy, Pauline J. [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Philippe-Chomette, Pascale [Department of Pediatric Surgery, University Paris 7 Denis Diderot, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, Paris (France); Kantor, Guy; Henriques de Figueiredo, Benedicte [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Sunyach, Marie-Pierre [Department of Radiation Oncology, Leon-Berard Center, Lyon (France); Sargos, Paul, E-mail: p.sargos@bordeaux.unicancer.fr [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France)

    2016-07-15

    Purpose: To identify the prognostic role of adjuvant abdominal radiation therapy (RT) on oncologic outcomes as a part of multimodal treatment in the management of desmoplastic small round cell tumor (DSRCT) and to determine its impact according to the quality of surgical resection. Methods and Materials: All patients treated for primary abdominal DSRCT in 8 French centers from 1991 to 2014 were included. Patients were retrospectively staged into 3 groups: group A treated with adjuvant RT after cytoreductive surgery, group B without RT after cytoreductive surgery, and group C by exclusive chemotherapy. Peritoneal progression-free survival (PPFS), progression-free survival (PFS), and overall survival (OS) were evaluated. We also performed a direct comparison between groups A and B to evaluate RT after cytoreductive surgery. Radiation therapy was also evaluated according to completeness of surgery: complete cytoreductive surgery (CCS) or incomplete cytoreductive surgery (ICS). Results: Thirty-seven (35.9%), thirty-six (34.9%), and thirty (28.0%) patients were included in groups A, B, and C, respectively. Three-year OS was 61.2% (range, 41.0%-76.0%), 37.6% (22.0%-53.1%), and 17.3% (6.3%-32.8%) for groups A, B, and C, respectively. Overall survival, PPFS, and PFS differed significantly among the 3 groups (P<.001, P<.001, and P<.001, respectively). Overall survival and PPFS were higher in group A (RT group) compared with group B (no RT group) (P=.045 and P=.006, respectively). Three-year PPFS was 23.8% (10.3%-40.4%) for group A and 12.51% (4.0%-26.2%) for group B. After CCS, RT improved PPFS (P=.024), but differences in OS and PFS were not significant (P=.40 and P=.30, respectively). After ICS, RT improved OS (P=.044). A trend of PPFS and PFS increase was observed, but the difference was not statistically significant (P=.073 and P=.076). Conclusions: Adjuvant RT as part of multimodal treatment seems to confer oncologic benefits for patients treated for abdominal DSRCT

  13. The treatment outcomes and the use of adjuvant therapies in breast cancer patients with severe co-morbidities.

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    Han, Jaihong; Lee, Han-Byoel; Lee, Eun-Shin; Kang, Young Joon; Kim, Yumi; Choi, Jihye; Rhu, Jiyoung; Shin, Hee-Chul; Han, Wonshik; Noh, Dong-Young; Moon, Hyeong-Gon

    2017-01-01

    Studies have suggested a potential role of patient's co-morbidity in determining the survival outcomes of breast cancer. In this study, we examined the long-term oncologic outcomes in breast cancer patients who underwent curative surgery according to their pre-existing comorbid conditions and analyzed the association between the co-morbidity and the use of adjuvant therapies. The medical records of 2,501 patients who underwent surgery for primary breast cancer from June 2006 to June 2010 were reviewed retrospectively. The patients were classified into three groups according to preoperative ASA status determined by the anesthesiologists. Clinico-pathologic characteristics and survival outcomes of the patients were compared among the different co-morbidity groups. There were 1,792 (71.6%), 665 (26.6%), and 44 (1.8%) patients in ASA I, II, and III, respectively. Total 95 (3.8%) deaths and 269 (10.8%) recurrences (loco-regional and distant) occurred during the median follow-up period of 71 months. Patients with high comorbidity showed significantly higher rate of deaths (51 (2.8%), 38 (5.7%) and 6 (13.6%) deaths in ASA I, II and III group, respectively, pco-morbidity group received adjuvant therapies (77 (4.3%), 44 (6.6%) and 8 (18.2%) in ASA I, II, and III, respectively, pco-morbidity conditions. In this study, high comorbidity was related to increased risk of death and recurrence in breast cancer. The increased risk of recurrence in high co-morbidity group was mostly seen in patients who did not receive adjuvant therapies. Considering the relatively low rates of serious adverse effects in high co-morbidity patients who received adjuvant therapies, active use of adjuvant therapies in selected patients may improve survival outcomes in breast cancer patients with severe co-morbidities.

  14. Adjuvants modulating mucosal immune responses or directing systemic responses towards the mucosa.

    Science.gov (United States)

    Cox, Eric; Verdonck, Frank; Vanrompay, Daisy; Goddeeris, Bruno

    2006-01-01

    In developing veterinary mucosal vaccines and vaccination strategies, mucosal adjuvants are one of the key players for inducing protective immune responses. Most of the mucosal adjuvants seem to exert their effect via binding to a receptor/or target cells and these properties were used to classify the mucosal adjuvants reviewed in the present paper: (1) ganglioside receptor-binding toxins (cholera toxin, LT enterotoxin, their B subunits and mutants); (2) surface immunoglobulin binding complex CTA1-DD; (3) TLR4 binding lipopolysaccharide; (4) TLR2-binding muramyl dipeptide; (5) Mannose receptor-binding mannan; (6) Dectin-1-binding ss 1,3/1,6 glucans; (7) TLR9-binding CpG-oligodeoxynucleotides; (8) Cytokines and chemokines; (9) Antigen-presenting cell targeting ISCOMATRIX and ISCOM. In addition, attention is given to two adjuvants able to prime the mucosal immune system following a systemic immunization, namely 1alpha, 25(OH)2D3 and cholera toxin.

  15. Efficacy of adjuvant therapy with procarbazine, MCNU, and vincristine for oligodendroglial tumors

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    Wakabayashi, Toshihiko; Kajita, Yasukazu; Mizuno, Masaaki; Yoshida, Jun [Nagoya Univ. (Japan). School of Medicine; Nagasaka, Tetsurou

    2001-03-01

    An adjuvant chemotherapy regimen consisting of procarbazine, MCNU, and vincristine (PMV) was evaluated for the treatment of malignant oligodendroglial tumors. Ten patients with histologically proven oligodendroglial tumors were treated with PMV therapy and the effectiveness was assessed using magnetic resonance imaging. Four patients with primary tumors underwent PMV after radiation therapy, and six patients with recurrent tumors were treated using PMV only. Tumor response was defined as radiological evidence of mass size change after completion of three courses of PMV. Complete or partial responses (more than 50% reduction in tumor mass) were noted in six patients, and tumor growth stabilized in four patients. In particular, inhibition of tumor growth using PMV was achieved in three patients with recurrent oligodendroglial tumors, despite the initial response after chemoradiation therapy (interferon-{beta}, MCNU, radiation) or nitrosourea chemotherapy (ACNU, MCNU). This PMV regimen (a modified PCV regimen using drugs available in Japan) is effective for treating malignant oligodendroglial tumors despite recurrence after other initial treatment procedures. (author)

  16. Antiepileptic, behavioral, and antidepressant effects of adjuvant lamotrigine therapy in drug-resistant epilepsy

    Directory of Open Access Journals (Sweden)

    Martinović Žarko J.

    2004-01-01

    Full Text Available Aim. To evaluate the behavioral effects of lamotrigine as add-on therapy in treatment-resistant epilepsy. Methods. An open, prospective, long-term study of lamotrigine as adjuvant therapy was performed in 56 patients with drug-resistant epilepsy (female/male ratio 35/21, age range 16-51 years. All the patients kept seizure diaries, and electroencephalograms were recorded at baseline and during 24 months of the treatment. Quality of life questionnaire, Hamilton depression scale (HMD, Beck depression scale (BDI, and Hamilton anxiety scale (HMA were used before and during lamotrigine therapy. Comparative assessments were made in an age- and sex-matched control group treated with other antiepileptic drugs. Results. Overall, seizure control was improved in 55.3% of the patients, remained unchanged in 39.3%, and deteriorated in 5.4%. Improvement in some quality of life measures occurred in 50% of the patients. The HMD subscales and BDI scale showed significant improvement in lamotrigine treated patients compared to the control group (ANOVA, p < 0.01. Negative behavioral effects occurred in 10.7% of the patients. Conclusion. Lamotrigine demonstrated significant antiepileptic long-term efficacy, and its positive effects on the mood and quality of life, which surpassed the negative behavioral effects, and contributed highly to the favorable treatment outcome.

  17. Identification of intermediate risk breast cancer patients with 1-3 positive lymph nodes and excellent survival after tamoxifen as only systemic adjuvant therapy by use of markers of proliferation and apoptosis.

    Science.gov (United States)

    Linderholm, B K; Linder, S; Arnesson, L-G; Stål, O

    2013-10-01

    According to current guidelines, patients with primary breast cancer and 1-3 lymph node metastases will in general be offered adjuvant chemotherapy. Our objective was to investigate the relationship between markers of proliferation and apoptosis with survival for patients subjected to adjuvant tamoxifen solely. Tumour cytosol samples from 409 consecutive patients with operable oestrogen receptor positive BC, stage I-III and treated with tamoxifen for 2 or 5 years were assessed for levels of caspase-cleaved cytokeratin-18 (ccCK18), an indicator of apoptosis, by use of an ELISA assay. Data on S-phase fraction (SPF) were available for 370 patients. Survival analyses were performed according to levels of ccCK18 and SPF separately, as well as combined. A wide range of ccCK18 protein levels was found, median 9.97, range 0.0-87.3 pg/μgDNA. Increasing SPFs were significantly associated with a lower distant recurrence-free survival (DRFS) (p = 0.025) and breast cancer survival (BCS) (p = 0.046). In the group with low SPF (below mean), low amounts of ccCK/18 correlated with a shorter DRFS (p = 0.0028) and BCS (p = 0.0027). A Proliferation Index (PI); a quotient of ccCK18/SPF was constructed. Low PI (high ccCK18/SPF ratios) were significantly correlated with an improved survival both when analysed as continuous variables; DRFS (p = 0.021), BCS (p = 0.038) and when divided into quartiles; DRFS (p < 0.001) and BCS (p = 0.0012). A similar correlation was found in patients with 1-3 lymph node metastases; DRFS (p = 0.089) and BCS (p = 0.019). A Cox's proportional hazard model including age, tumour size, lymph node status, PgR and ccCK18/SPF was used for multivariate analysis. High ccCK18/SPF ratios correlated with improved survival; DRFS (HR = 0.47 (0.22-0.98), p = 0.043), and BCS (HR = 0.39 (0.16-1.00), p = 0.049), respectively. By use of a proliferation index based on markers of proliferation and apoptosis, a group of patients with 1-3 lymph node metastases with good outcome

  18. The prognosis factor of adjuvant radiation therapy after surgery in uterine sarcomas

    Directory of Open Access Journals (Sweden)

    Hou HL

    2015-08-01

    Full Text Available Hai-Ling Hou, Mao-Bin Meng, Xiu-Li Chen, Lu-Jun Zhao, Li Zhu, Bai-Lin Zhang, Ping Wang Department of Radiation Oncology, CyberKnife Center, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People’s Republic of China Objective: This retrospective study evaluated the role of adjuvant radiotherapy (AR after surgery in patients with uterine sarcoma and analyzed the prognostic factors of local-regional failure-free survival (LRFFS and overall survival (OS.Patients and methods: A study of a total of 182 patients with uterine sarcoma was conducted between June 1994 and October 2014. Adjuvant radiotherapy was defined as postoperative external beam radiation to the pelvis (30–50 Gray/10–25 fractions at five fractions/week. The primary end point was LRFFS, and the secondary end point was OS. Kaplan–Meier curves were compared using the log-rank test. Cox regression analyses were used to determine prognosticators for LRFFS and OS.Results: The median follow-up time of all patients was 75 months, with a 5-year LRFFS of 62.1%. The 2-year and 5-year LRFFS rates were longer for those who received AR than for those who did not receive AR (83.4% vs 70.3%; 78% vs 55.3%; P=0.013. The 5-year OS of all patients was 56.2%, and no significant differences were observed in the 2-year and 5-year OS rates between these two groups (82.7% vs 71.4%; 64.1% vs 51.7%; P=0.067. Importantly, in patients with leiomyosarcoma, the 2-year and 5-year LRFFS and OS rates were longer for those who received AR than for those who did not receive AR (P=0.04 and P=0.02 for the 2-year and 5-year LRFFS, respectively.Conclusion: Patients with uterine sarcoma who were treated with AR after surgery demonstrated an improved LRFFS compared with those who were treated with surgery alone, especially those patients with leiomyosarcoma. Therefore, the role of personalized adjuvant

  19. Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants

    Science.gov (United States)

    Olafsdottir, Thorunn A.; Lindqvist, Madelene; Nookaew, Intawat; Andersen, Peter; Maertzdorf, Jeroen; Persson, Josefine; Christensen, Dennis; Zhang, Yuan; Anderson, Jenna; Khoomrung, Sakda; Sen, Partho; Agger, Else Marie; Coler, Rhea; Carter, Darrick; Meinke, Andreas; Rappuoli, Rino; Kaufmann, Stefan H. E.; Reed, Steven G.; Harandi, Ali M.

    2016-12-01

    A better understanding of the mechanisms of action of human adjuvants could inform a rational development of next generation vaccines for human use. Here, we exploited a genome wide transcriptomics analysis combined with a systems biology approach to determine the molecular signatures induced by four clinically tested vaccine adjuvants, namely CAF01, IC31, GLA-SE and Alum in mice. We report signature molecules, pathways, gene modules and networks, which are shared by or otherwise exclusive to these clinical-grade adjuvants in whole blood and draining lymph nodes of mice. Intriguingly, co-expression analysis revealed blood gene modules highly enriched for molecules with documented roles in T follicular helper (TFH) and germinal center (GC) responses. We could show that all adjuvants enhanced, although with different magnitude and kinetics, TFH and GC B cell responses in draining lymph nodes. These results represent, to our knowledge, the first comparative systems analysis of clinically tested vaccine adjuvants that may provide new insights into the mechanisms of action of human adjuvants.

  20. Adjuvant radiation therapy is associated with improved survival for adenoid cystic carcinoma of the breast.

    Science.gov (United States)

    Coates, Jodi M; Martinez, Steve R; Bold, Richard J; Chen, Steven L

    2010-09-15

    The role of adjuvant radiation therapy (RT) for adenoid cystic carcinoma (ACC) of the breast remains unclear. We queried the Surveillance, Epidemiology, and End Results database for patients with breast ACC resected between 1988 and 2005, and divided patients based on the receipt of RT. Univariate and multivariate survival comparisons were made for overall and disease-specific survival. Three hundred seventy six patients met criteria for inclusion. Demographics and staging were similar between groups. Univariate analysis revealed an absolute overall and cause-specific survival benefit of 21% and 7% at 10 years (P = 0.005 and P = 0.12 respectively). In the multivariate analysis, RT was a significant predictor of overall and cause-specific survival with hazard ratios of 0.44 (95% Confidence interval (CI) = 0.22-0.88) and 0.1 (95% CI: 0.01-0.88), respectively. RT after local surgical therapy for ACC of the breast improved both cause-specific and overall survival. Use of RT in this rare tumor should be considered in patients otherwise eligible for RT. (c) 2010 Wiley-Liss, Inc.

  1. [Clinical efficacy of adjuvant therapy with glucocorticoids in children with lobar pneumonia caused by Mycoplasma pneumoniae].

    Science.gov (United States)

    Wu, Yue-Jin; Sun, Jie; Zhang, Jian-Hua; Feng, Ling-Ling

    2014-04-01

    To study the clinical efficacy of adjuvant therapy with glucocorticoids in children with lobar pneumonia caused by Mycoplasma pneumoniae. One hundred and eight children with lobar pneumonia caused by Mycoplasma pneumoniae were randomly divided into routine treatment and hormone treatment groups. Both groups were treated with azithromycin and other symptomatic therapies. In addition to the basic treatment, the hormone treatment group was given dexamethasone 0.25-0.3 mg/(kg·d) by intravenous drip until the body temperature was normal. Then given oral prednisone tablets 0.5-1 mg/(kg·d) (gradually reduced) for a total treatment course of 7-10 days. Before and after treatment pulmonary functions were examined, and serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-2 (IL-2) and interleukin-6 (IL-6) were measured. The duration of fever, cough relief time and pulmonary shadow absorption time on chest X-ray were significantly shorter in the hormone treatment group than in the routine treatment group (PMycoplasma pneumoniae.

  2. Cytokine-Enhanced Vaccine and Interferon-β plus Suicide Gene Therapy as Surgery Adjuvant Treatments for Spontaneous Canine Melanoma.

    Science.gov (United States)

    Finocchiaro, Liliana M E; Fondello, Chiara; Gil-Cardeza, María L; Rossi, Úrsula A; Villaverde, Marcela S; Riveros, María D; Glikin, Gerardo C

    2015-06-01

    We present here a nonviral immunogene therapy trial for canine malignant melanoma, an aggressive disease displaying significant clinical and histopathological overlapping with human melanoma. As a surgery adjuvant approach, it comprised the co-injection of lipoplexes bearing herpes simplex virus thymidine kinase and canine interferon-β genes at the time of surgery, combined with the periodic administration of a subcutaneous genetic vaccine composed of tumor extracts and lipoplexes carrying the genes of human interleukin-2 and human granulocyte-macrophage colony-stimulating factor. Following complete surgery (CS), the combined treatment (CT) significantly raised the portion of local disease-free canine patients from 11% to 83% and distant metastases-free (M0) from 44% to 89%, as compared with surgery-only-treated controls (ST). Even after partial surgery (PS), CT better controlled the systemic disease (M0: 82%) than ST (M0: 48%). Moreover, compared with ST, CT caused a significant 7-fold (CS) and 4-fold (PS) rise of overall survival, and >17-fold (CS) and >13-fold (PS) rise of metastasis-free survival. The dramatic increase of PS metastasis-free survival (>1321 days) and CS recurrence- and metastasis-free survival (both >2251 days) demonstrated that CT was shifting a rapidly lethal disease into a chronic one. In conclusion, this surgery adjuvant CT was able of significantly delaying or preventing postsurgical recurrence and distant metastasis, increasing disease-free and overall survival, and maintaining the quality of life. The high number of canine patients involved in CT (301) and the extensive follow-up (>6 years) with minimal or absent toxicity warrant the long-term safety and efficacy of this treatment. This successful clinical outcome justifies attempting a similar scheme for human melanoma.

  3. The efficacy of Curcuma Longa L. extract as an adjuvant therapy in primary knee osteoarthritis: a randomized control trial.

    Science.gov (United States)

    Pinsornsak, Piya; Niempoog, Sunyarn

    2012-01-01

    Nonsteroidal anti-inflammatory Drugs (NSAIDs) is one of the most commonly use medication for treatment of knee osteoarthritis which has the analgesic and anti-inflammation by inhibition of prostaglandin synthesis via COX-1 and COX-2 isoenzyme. The problem of prolong using NSAIDs has side effect on kidney, liver and GI system. Curcumin longa extract Curcumin) is the Asian herbal medicine that has the anti-inflammatory effect by down regulate activation of NF-kappaB and proinflammatory cytokines such as Tumor Necrotic Factor-alpha, Interleukin-1, Interleukin-8, and Nitric Oxide Syntase. Many research data had advocate for the combination therapy which can increase safety and efficacy with less side effect compare with monotherapy regimen especially when the medicine has the different mechanism of action. The present study is the double blind prospective randomized control trial to evaluate the efficacy of curcumin as an adjuvant therapy of diclofenac in primary knee osteoarthritis. 44 patients were randomized to take NSAIDs (diclofenac) 75 mg/d with placebo and the other 44 took NSAIDs (diclofenac) 75 mg/d with curcumin 1,000 mg/d for 3 months. The authors evaluated the Visual Analog Scale (VAS) for pain and Knee Injury and Osteoarthritis Outcome Score (KOOS) every month for 3 months. At the end of study 36 patients were completed for the first group and 37 for the study group. There was no difference in VAS [p-value = 0.923 (F = 0.009)]. The KOOS was analyzed in 5 categories symptom, pain, function in daily living, function in sport and recreation and knee related quality of life. The curcumin with diclofenac group had tendency to be better in Pain and Function in daily living, but there were no statistic different in all group [p-value = 0.412 (F = 0.683), p-value = 0.814 (F = 0.056), p-value = 0.446 (F = 0.589), p-value = 0.224 (F = 1.511) and p-value = 0.938 (F = 0.006)]. In conclusion, the adjuvant therapy ofcurcumin with diclofenac has the potential beneficial

  4. Combination therapies in adjuvant with topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    Science.gov (United States)

    Yang, Deng-Fu; Hsu, Yih-Chih

    2012-03-01

    In Taiwan, oral cancer has becomes the fastest growth male cancer disease due to the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people. In order to eliminate the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when ALA reached its peak level in the lesional epithelial cells after topical application of ALA gel. We found that ALA reached its peak level in precancerous lesions about 2.5 hrs after topical application of ALA gel. The cancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 150 J/cm2 using LED 635 nm fiber-guided light device. Visual examination demonstrated that adjuvant topical ALA -mediated PDT group has shown better therapeutic results in compared to those of non-adjuvant topical ALA-mediated PDT group for DMBA-induced hamster buccal pouch precancerous lesions.

  5. Cutaneous adverse effects of hormonal adjuvant therapy for breast cancer: a case of localised urticarial vasculitis following anastrozole therapy and a review of the literature.

    Science.gov (United States)

    Bock, Vanessa L; Friedlander, Michael; Waring, Dale; Kossard, Steven; Wood, Glenda K

    2014-11-01

    Hormonal therapy with either tamoxifen or aromatase inhibitors is commonly used to treat women with breast cancer in both the adjuvant and recurrent disease setting. Cutaneous adverse reactions to these drugs have been rarely reported in the literature. We report an unusual case of urticarial vasculitis following the aromatase inhibitor anastrozole that localised to the unilateral trunk and mastectomy scar, and review the literature on the cutaneous adverse effects of hormonal therapy for breast cancer. © 2013 The Australasian College of Dermatologists.

  6. A cooperative randomized controlled study of adjuvant chemoendocrine therapy for breast cancer in Japan.

    Science.gov (United States)

    Abe, R; Tsuchiya, A; Koie, H; Ono, K; Abo, S; Saito, K; Tsukamoto, M; Sato, T; Mori, S; Kikuchi, K

    1994-04-01

    A randomized trial was carried out in 55 Japanese institutions to examine the significance of postoperative adjuvant chemoendocrine therapy in Stages II and IIIA breast cancer patients after radical mastectomy. A total of 619 patients were entered from November 1982 to November 1984, of whom 554 were eligible. Patients were administered MMC (13 mg/m2) after surgery, and were randomized by the envelope method into either group A (ftorafur, 400 mg/m2/day; 275 patients), or group B (ftorafur, 400 mg/m2/day, and tamoxifen, 20 mg/day; 279 patients). Treatment was continued for 1 year from postoperative day 7. There were no significant differences between the two groups with regard to age, menopausal status, ER status, method of operation, stage, or number of positive lymph nodes. There was also no significant difference between the two groups in the 5-year survival and disease-free survival (DFS) rates (Kaplan-Meier method). Stratification by ER status, nodal status, or menopausal status produced no significant differences between the groups. However, postmenopausal patients and lymph node-positive patients who were also ER-positive showed a significantly higher DFS in group B. Furthermore, group B in ER-positive patients with four or more positive lymph nodes also had a higher survival rate.

  7. C. sinensis ablates allograft vasculopathy when used as an adjuvant therapy with cyclosporin A.

    Science.gov (United States)

    Jordan, J L; Hirsch, G M; Lee, T D G

    2008-07-01

    Immunosuppressive treatments are available to suppress acute cardiac rejection; however, no viable treatment exists for long-term cardiac graft failure. Moreover, extended use of calcineurin inhibitor immunosuppressants, the mainstay of the current therapeutic for cardiac transplantation, leads to significant associated pathologies such as nephrotoxicity and increased risk of cardiac disease. For the last ten years alternatives to calcineurin inhibitors, or adjuvant therapies designed to complement their activities, have been explored. In tandem with this development, there has been considerable interest in Traditional Chinese Medicines (TCM) as sources for novel therapeutics. Our study examines the ability of the TCM Cordyceps sinensis to reduce acute and chronic rejection associated with cardiac transplantation. The objectives of this study were to first determine if oral delivery of the extract could reduce acute rejection in a rat heterotopic heart model of transplantation. The second objective was to determine, in vitro, if a sterile, aqueous extract of C. sinensis could decrease CD8+ T cell activity. The third objective was to determine if oral delivery of the extract could ablate allograft vasculopathy in a mouse abdominal aortic transplant model. We found that oral delivery of the extract demonstrated a reduction in acute rejection when used in conjunction with a sub-therapeutic dose of Cyclosporine. Further, we found, using a mixed lymphocyte reaction, that the extract was able to significantly reduce CD8+ T cell activity. Finally, we demonstrate that oral delivery of the extract, used with a therapeutic dose of Cyclosporine to suppress acute rejection, ablates allograft vasculopathy.

  8. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism

    Directory of Open Access Journals (Sweden)

    Bryan G. Allen

    2014-01-01

    Full Text Available Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS such as O2•−and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses.

  9. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism.

    Science.gov (United States)

    Allen, Bryan G; Bhatia, Sudershan K; Anderson, Carryn M; Eichenberger-Gilmore, Julie M; Sibenaller, Zita A; Mapuskar, Kranti A; Schoenfeld, Joshua D; Buatti, John M; Spitz, Douglas R; Fath, Melissa A

    2014-01-01

    Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS) such as O2(•-)and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses. © 2014 Published by Elsevier Ltd.

  10. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism

    Science.gov (United States)

    Allen, Bryan G.; Bhatia, Sudershan K.; Anderson, Carryn M.; Eichenberger-Gilmore, Julie M.; Sibenaller, Zita A.; Mapuskar, Kranti A.; Schoenfeld, Joshua D.; Buatti, John M.; Spitz, Douglas R.; Fath, Melissa A.

    2014-01-01

    Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS) such as O2•−and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses. PMID:25460731

  11. Doxycycline and its quaternary ammonium derivative for adjuvant therapies of chondrosarcoma.

    Science.gov (United States)

    Miladi, Imen; Vivier, Magali; Dauplat, Marie-Mélanie; Chatard, Morgane; Besse, Sophie; Vidal, Aurélien; Chassain, Karine; Jean, Betty; Forestier, Christiane; Chezal, Jean-Michel; Rédini, Francoise; Degoul, Francoise; Miot-Noirault, Elisabeth

    2017-09-01

    This study was conducted during the development of innovative treatment targeting the microenvironment of chondrosarcoma. In this context, MMP inhibitors were conjugated with a quaternary ammonium (QA) function as a targeting ligand to proteoglycans of chondrosarcoma extracellular matrix. Here we report the proof of concept of this strategy applied to the MMP13 inhibitor, doxycycline (Dox). A quaternary ammonium derivative of the MMP13 inhibitor doxycycline (QA-Dox) was synthesized, and its anticancer activity was evaluated in the Swarm rat chondrosarcoma (SRC) model compared with the parent drug doxycycline, in vitro and in vivo. In vivo, dox and QA-Dox efficiency was assessed at equimolar doses according to a q4dx4 schedule by monitoring tumour volume by MRI and PG-targeted scintigraphy. Molecular mechanism (MMP13 expression, proteoglycan level) and histology studies were performed on tumours. The link of QA targeting function to Dox maintained the MMP13 inhibitory activity in vitro. Interestingly, the bacteriostatic activity was lost. SRC cells incubated with both drugs were blocked in S and G2 M phases. Tumour growth inhibition (confirmed by histology) was observed for both Dox and QA-Dox. Undesirable blood effects (leukocyte decrease) were reduced when Dox was targeted to tumour tissue using the QA function. In the SRC model, the MMP13 inhibitor Dox and its QA derivative are promising as adjuvant therapies for chondrosarcoma management.

  12. Retinoblastoma regression patterns following chemoreduction and adjuvant therapy in 557 tumors.

    Science.gov (United States)

    Shields, Carol L; Palamar, Melis; Sharma, Pooja; Ramasubramanian, Aparna; Leahey, Ann; Meadows, Anna T; Shields, Jerry A

    2009-03-01

    To evaluate retinoblastoma regression patterns following chemoreduction and adjuvant therapy. A total of 557 retinoblastomas. A retrospective medical record review following 6 cycles of chemoreduction and tumor consolidation (thermotherapy or cryotherapy). Regression patterns included type 0 (no remnant), type 1 (calcified remnant), type 2 (noncalcified remnant), type 3 (partially calcified remnant), and type 4 (flat scar). Regression pattern. Retinoblastoma regressions were type 0 (n = 10), type 1 (n = 75), type 2 (n = 28), type 3 (n = 127), and type 4 (n = 317). Tumors with an initial thickness of 3 mm or less regressed most often to type 4 (92%), those 3 to 8 mm regressed to type 3 (34%) or type 4 (40%), and those thicker than 8 mm regressed to type 1 (40%) or type 3 (49%). Factors predictive of type 1 regression included larger tumor base and closer foveolar proximity. Factors predictive of type 3 included older age, larger tumor base, macular location, closer foveolar proximity, and lack of consolidation. Factors predictive of type 4 included familial hereditary pattern, smaller tumor base, greater foveolar distance, and tumor consolidation. Following chemoreduction, most small retinoblastomas result in a flat scar, intermediate tumors in a flat or partially calcified remnant, and large tumors in a more completely calcified remnant.

  13. Cytokines, Fatigue, and Cutaneous Erythema in Early Stage Breast Cancer Patients Receiving Adjuvant Radiation Therapy

    Directory of Open Access Journals (Sweden)

    Vitaliana De Sanctis

    2014-01-01

    Full Text Available We investigated the hypothesis that patients developing high-grade erythema of the breast skin during radiation treatment could be more likely to present increased levels of proinflammatory cytokines which may lead, in turn, to associated fatigue. Forty women with early stage breast cancer who received adjuvant radiotherapy were enrolled from 2007 to 2010. Fatigue symptoms, erythema, and cytokine levels (IL-1β, IL-2, IL6, IL-8, TNF-α, and MCP-1 were registered at baseline, during treatment, and after radiotherapy completion. Seven (17.5% patients presented fatigue without associated depression/anxiety. Grade ≥2 erythema was observed in 5 of these 7 patients. IL-1β, IL-2, IL-6, and TNF-α were statistically increased 4 weeks after radiotherapy (P<0.05. After the Heckman two-step analysis, a statistically significant influence of skin erythema on proinflammatory markers increase (P = 0.00001 was recorded; in the second step, these blood markers showed a significant impact on fatigue (P = 0.026. A seeming increase of fatigue, erythema, and proinflammatory markers was observed between the fourth and the fifth week of treatment followed by a decrease after RT. There were no significant effects of hormone therapy, breast volume, and anemia on fatigue. Our study seems to suggest that fatigue is related to high-grade breast skin erythema during radiotherapy through the increase of cytokines levels.

  14. Evolution of Long-Term Adjuvant Anti-hormone Therapy: Consequences and Opportunities. The St. Gallen Prize Lecture

    Science.gov (United States)

    Jordan, V. Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R.; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

    2012-01-01

    The successful translation of the scientific principles of targeting the breast tumour oestrogen receptor (ER) with the nonsteroidal anti-oestrogen tamoxifen and using extended durations (at least 5-years) of adjuvant therapy, dramatically increased patient survivorship and significantly enhanced a drop in national mortality rates from breast cancer. The principles are the same for the validation of aromatase inhibitors to treat post-menopausal patients but tamoxifen remains a cheap, life-saving medicine for the pre-menopausal patient. Results from the Oxford Overview Analysis illustrate the scientific principle of “longer is better” for adjuvant therapy in pre-menopausal patients. One-year of adjuvant therapy is ineffective at preventing disease recurrence or reducing mortality, whereas five-years of adjuvant tamoxifen reduces recurrence by 50% which is maintained for a further ten-years after treatment stops. Mortality is reduced but the magnitude continues to increase to 30% over a 15-year period. With this clinical database, it is now possible to implement simple solutions to enhance survivorship. Compliance with long-term anti-hormone adjuvant therapy is critical. In this regard, the use of selective serotonin reuptake inhibitors (SSRIs) to reduce severe menopausal side effects may be inappropriate. It is known that SSRIs block the CYP2D6 enzyme that metabolically activates tamoxifen to its potent anti-oestrogenic metabolite, endoxifen. The selective nor-epinephrine reuptake inhibitor, venlafaxine, does not block CYP2D6, and may be a better choice. Nevertheless, even with perfect compliance, the relentless drive of the breast cancer cell to acquire resistance to therapy persists. The clinical application of long-term anti-hormonal therapy for the early treatment and prevention of breast cancer, focused laboratory research on the discovery of mechanisms involved in acquired anti-hormone resistance. Decades of laboratory study to reproduce clinical

  15. The St. Gallen Prize Lecture 2011: evolution of long-term adjuvant anti-hormone therapy: consequences and opportunities.

    Science.gov (United States)

    Jordan, V Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

    2011-10-01

    The successful translation of the scientific principles of targeting the breast tumour oestrogen receptor (ER) with the nonsteroidal anti-oestrogen tamoxifen and using extended durations (at least 5 years) of adjuvant therapy, dramatically increased patient survivorship and significantly enhanced a drop in national mortality rates from breast cancer. The principles are the same for the validation of aromatase inhibitors to treat post-menopausal patients but tamoxifen remains a cheap, life-saving medicine for the pre-menopausal patient. Results from the Oxford Overview Analysis illustrate the scientific principle of "longer is better" for adjuvant therapy in pre-menopausal patients. One year of adjuvant therapy is ineffective at preventing disease recurrence or reducing mortality, whereas five years of adjuvant tamoxifen reduces recurrence by 50% which is maintained for a further ten years after treatment stops. Mortality is reduced but the magnitude continues to increase to 30% over a 15-year period. With this clinical database, it is now possible to implement simple solutions to enhance survivorship. Compliance with long-term anti-hormone adjuvant therapy is critical. In this regard, the use of selective serotonin reuptake inhibitors (SSRIs) to reduce severe menopausal side effects may be inappropriate. It is known that SSRIs block the CYP2D6 enzyme that metabolically activates tamoxifen to its potent anti-oestrogenic metabolite, endoxifen. The selective norepinephrine reuptake inhibitor, venlafaxine, does not block CYP2D6, and may be a better choice. Nevertheless, even with perfect compliance, the relentless drive of the breast cancer cell to acquire resistance to therapy persists. The clinical application of long-term anti-hormonal therapy for the early treatment and prevention of breast cancer, focused laboratory research on the discovery of mechanisms involved in acquired anti-hormone resistance. Decades of laboratory study to reproduce clinical experience

  16. Impact of concurrent versus adjuvant chemotherapy on the severity and duration of lymphopenia in glioma patients treated with radiation therapy.

    Science.gov (United States)

    Lin, Alexander J; Campian, Jian L; Hui, Caressa; Rudra, Soumon; Rao, Yuan J; Thotala, Dinesh; Hallahan, Dennis; Huang, Jiayi

    2018-01-01

    Prolonged severe lymphopenia has been shown to persist beyond a year in glioma patients after radiation therapy (RT) with concurrent and adjuvant chemotherapy. This study examines the differential impact of concurrent versus adjuvant chemotherapy on lymphopenia after RT. WHO grade II-III glioma patients who received RT with concurrent and/or adjuvant chemotherapy from 2007 to 2016 were retrospectively analyzed. Concurrent chemotherapy was temozolomide (TMZ), and adjuvant chemotherapy was either TMZ or procarbazine/lomustine/vincristine (PCV). Absolute lymphocyte count (ALC) was analyzed at baseline, 1.5, 3, 6, and 12 months after the start of RT. Univariable and multivariable logistic regression were used to identify the clinical variables in predicting acute or late lymphopenia. There were 151 patients with evaluable ALC: 91 received concurrent and adjuvant TMZ (CRT + ADJ), 32 received only concurrent TMZ (CRT), and 28 received only adjuvant TMZ or PCV (ADJ). There were 9 (10%) versus 6 (19%) versus 0 (0%) cases of grade 3 lymphopenia (ALC < 500/mm3) at 6 weeks and 4 (6%) versus 0 (0%) versus 3 (17%) cases at 12 months in CRT + ADJ, CRT and ADJ groups, respectively. On multivariable analyses, concurrent chemotherapy (odds ratio [OR] 72.3, p < 0.001), female sex (OR 10.8, p < 0.001), and older age (OR 1.06, p = 0.002) were the most significant predictors for any grade ≥ 1 lymphopenia (ALC < 1000/mm3) at 1.5 months. Older age (OR 1.08, p = 0.02) and duration of adjuvant chemotherapy (OR 1.19, p = 0.003) were significantly associated with grade ≥ 1 lymphopenia at 12 months. Thus, concurrent chemotherapy appears as the dominant contributor to the severity of acute lymphopenia after RT in WHO grade II-III glioma patients, and duration of adjuvant chemotherapy appears as the key factor to prolonged lymphopenia.

  17. Identification of microRNA-21 as a biomarker for chemoresistance and clinical outcome following adjuvant therapy in resectable pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Jin-Hyeok Hwang

    2010-05-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC has a dismal prognosis. The high risk of recurrence following surgical resection provides the rationale for adjuvant therapy. However, only a subset of patients benefit from adjuvant therapy. Identification of molecular markers to predict treatment outcome is therefore warranted. The aim of the present study was to evaluate whether expression of novel candidate biomarkers, including microRNAs, can predict clinical outcome in PDAC patients treated with adjuvant therapy.Formalin-fixed paraffin embedded specimens from a cohort of 82 resected Korean PDAC cases were analyzed for protein expression by immunohistochemistry and for microRNA expression using quantitative Real-Time PCR. Cox proportional hazards model analysis in the subgroup of patients treated with adjuvant therapy (N = 52 showed that lower than median miR-21 expression was associated with a significantly lower hazard ratio (HR for death (HR = 0.316; 95%CI = 0.166-0.600; P = 0.0004 and recurrence (HR = 0.521; 95%CI = 0.280-0.967; P = 0.04. MiR-21 expression status emerged as the single most predictive biomarker for treatment outcome among all 27 biological and 9 clinicopathological factors evaluated. No significant association was detected in patients not treated with adjuvant therapy. In an independent validation cohort of 45 frozen PDAC tissues from Italian cases, all treated with adjuvant therapy, lower than median miR-21 expression was confirmed to be correlated with longer overall as well as disease-free survival. Furthermore, transfection with anti-miR-21 enhanced the chemosensitivity of PDAC cells.Low miR-21 expression was associated with benefit from adjuvant treatment in two independent cohorts of PDAC cases, and anti-miR-21 increased anticancer drug activity in vitro. These data provide evidence that miR-21 may allow stratification for adjuvant therapy, and represents a new potential target for therapy in PDAC.

  18. Effectiveness of adjuvant occupational therapy in employees with depression: design of a randomized controlled trial.

    Science.gov (United States)

    Hees, Hiske L; Koeter, Maarten W J; de Vries, Gabe; Ooteman, Wendy; Schene, Aart H

    2010-09-17

    Major depressive disorder is among the medical conditions with the highest negative impact on work outcome. However, little is known regarding evidence-based interventions targeting the improvement of work outcomes in depressed employees. In this paper, the design of a randomized controlled trial is presented in order to evaluate the effectiveness of adjuvant occupational therapy in employees with depression. This occupational intervention is based on an earlier intervention, which was designed and proven effective by our research group, and is the only intervention to date that specifically targets work outcome in depressed employees. In a two-arm randomized controlled trial, a total of 117 participants are randomized to either 'care as usual' or ' care as usual' with the addition of occupational therapy. Patients included in the study are employees who are absent from work due to depression for at least 25% of their contract hours, and who have a possibility of returning to their own or a new job. The occupational intervention consists of six individual sessions, eight group sessions and a work-place visit over a 16-week period. By increasing exposure to the working environment, and by stimulating communication between employer and employee, the occupational intervention aims to enhance self-efficacy and the acquisition of more adaptive coping strategies. Assessments take place at baseline, and at 6, 12, and 18-month follow-ups. Primary outcome measure is work participation (hours of absenteeism and time until work resumption). Secondary outcome measures are work functioning, symptomatology, health-related quality of life, and neurocognitive functioning. In addition, cost-effectiveness is evaluated from a societal perspective. Finally, mechanisms of change (intermediate outcomes) and potential patient-treatment matching variables are investigated. This study hopes to provide valuable knowledge regarding an intervention to treat depression, one of the most common

  19. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET)

    DEFF Research Database (Denmark)

    Chan, Arlene; Delaloge, Suzette; Holmes, Frankie A

    2016-01-01

    breast cancer and had completed neoadjuvant and adjuvant trastuzumab therapy up to 2 years before randomisation. Inclusion criteria were amended on Feb 25, 2010, to include patients with stage 2-3 HER2-positive breast cancer who had completed trastuzumab therapy up to 1 year previously. Patients were...... randomly assigned (1:1) to receive oral neratinib 240 mg per day or matching placebo. The randomisation sequence was generated with permuted blocks stratified by hormone receptor status (hormone receptor-positive [oestrogen or progesterone receptor-positive or both] vs hormone receptor-negative [oestrogen...

  20. Expanded risk groups help determine which prostate radiotherapy sub-group may benefit from adjuvant androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Williams Scott G

    2008-04-01

    Full Text Available Abstract Purpose To assess whether an expanded (five level risk stratification system can be used to identify the sub-group of intermediate risk patients with prostate cancer who benefit from combining androgen deprivation therapy (ADT with external beam radiotherapy (EBRT. Materials and methods Using a previously validated 5-risk group schema, a prospective non-randomized data set of 1423 men treated at the British Columbia Cancer Agency was assessed for the primary end point of biochemical control (bNED with the RTOG-ASTRO "Phoenix" definition (lowest PSA to date + 2 ng/mL, both with and without adjuvant ADT. The median follow-up was 5 years. Results There was no bNED benefit for ADT in the low or low intermediate groups but there was a statistically significant bNED benefit in the high intermediate, high and extreme risk groups. The 5-year bNED rates with and without ADT were 70% and 73% respectively for the low intermediate group (p = non-significant and 72% and 58% respectively for the high intermediate group (p = 0.002. Conclusion There appears to be no advantage to ADT where the Gleason score is 6 or less and PSA is 15 or less. ADT is beneficial in patients treated to standard dose radiation with Gleason 6 disease and a PSA greater than 15 or where the Gleason score is 7 or higher.

  1. Adjuvant Radiation Therapy Improves Local Control After Surgical Resection in Patients With Localized Adrenocortical Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Sabolch, Aaron [Department of Radiation Oncology, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Else, Tobias [Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Griffith, Kent A. [Center for Cancer Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Mchigan (United States); Ben-Josef, Edgar [Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Williams, Andrew [University of Michigan Medical School, Ann Arbor, Mchigan (United States); Miller, Barbra S. [Division of Endocrine Surgery, Department of General Surgery, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Worden, Francis [Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Hammer, Gary D. [Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Jolly, Shruti, E-mail: shrutij@med.umich.edu [Department of Radiation Oncology, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States)

    2015-06-01

    Purpose: Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of local recurrence, though the benefit of postoperative radiation therapy (RT) has not been established. In this study of grossly resected ACC, we compare local control of patients treated with surgery followed by adjuvant RT to a matched cohort treated with surgery alone. Methods and Materials: We retrospectively identified patients with localized disease who underwent R0 or R1 resection followed by adjuvant RT. Only patients treated with RT at our institution were included. Matching to surgical controls was on the basis of stage, surgical margin status, tumor grade, and adjuvant mitotane. Results: From 1991 to 2011, 360 ACC patients were evaluated for ACC at the University of Michigan (Ann Arbor, MI). Twenty patients with localized disease received postoperative adjuvant RT. These were matched to 20 controls. There were no statistically significant differences between the groups with regard to stage, margins, grade, or mitotane. Median RT dose was 55 Gy (range, 45-60 Gy). Median follow-up was 34 months. Local recurrence occurred in 1 patient treated with RT, compared with 12 patients not treated with RT (P=.0005; hazard ratio [HR] 12.59; 95% confidence interval [CI] 1.62-97.88). However, recurrence-free survival was no different between the groups (P=.17; HR 1.52; 95% CI 0.67-3.45). Overall survival was also not significantly different (P=.13; HR 1.97; 95% CI 0.57-6.77), with 4 deaths in the RT group compared with 9 in the control group. Conclusions: Postoperative RT significantly improved local control compared with the use of surgery alone in this case-matched cohort analysis of grossly resected ACC patients. Although this retrospective series represents the largest study to date on adjuvant RT for ACC, its findings need to be prospectively confirmed.

  2. May adjuvant therapy play a role for the management of renal cell carcinoma? A review of literature and ongoing trials.

    Science.gov (United States)

    Messina, Carlo; Zanardi, Elisa; Boccardo, Francesco

    2017-02-13

    Renal cell carcinoma (RCC) is responsible for 4% of all neoplasms in adults and 80% of all primary renal tumours. In the European Union, there are almost 84000 new cases and 35000 deaths each year due to RCC. In the last five decade patients with localised RCC will develop recurrence of disease after nephrectomy in about 50% of cases. Considering the number of novel targeted therapies approved in the last years for the treatment of mRCC, there has been great interest to assess the efficacy of the same agents in the adjuvant setting. to provide a systematic review of literature on the available data to define whether might be a role for adjuvant treatment in the management of RCC. A literature search using PubMed was carried out with no date restriction up to November 2016. A computerized search of the abstracts reported at ASCO and ESMO library, and www.clinicaltrial.gov was performed in order to identify relevant unpublished studies and ongoing trials. the search strategy returned 908 entries: after the exclusion of 886 irrelevant publications, 22 studies were eligible for the systematic review. Currently there is no robust evidence for the adjuvant treatment for patients with localized RCC at high risk of recurrence post-nephrectomy and often data are conflicting. It's necessary to identify new prognostic factors that might better predict the risk of relapse after surgery. The enrolment in adjuvant trials should be encouraged for the identification of selected patients who might benefit from adjuvant treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. The issues regarding postoperative adjuvant therapy and prognostic risk factors for patients with stage I-II cervical cancer: A review.

    Science.gov (United States)

    Takekuma, Munetaka; Kasamatsu, Yuka; Kado, Nobuhiro; Kuji, Shiho; Tanaka, Aki; Takahashi, Nobutaka; Abe, Masakazu; Hirashima, Yasuyuki

    2017-04-01

    The treatment for most patients with early-stage cervical cancer involves radical hysterectomy and pelvic lymph node dissection, and indications for postoperative adjuvant therapy have been determined by evaluating the prognostic risk factors for recurrence in each case. The aim of this review is to raise and discuss the various issues that have not yet been resolved regarding the prognostic risk factors and postoperative adjuvant therapy. Several clinicopathological factors, such as tumor size, lymphovascular space involvement, deep stromal invasion, parametrial involvement and lymph node metastasis, have been identified to have prognostic significance in early-stage cervical cancer. However, this remains controversial because there is suggested to be substantial heterogeneity among patients after radical hysterectomy and lymphadenectomy and it would be difficult to define the risk groups clearly. This indicates the need to develop more convenient and accurate criteria to define risk groups. According to the currently available evidence, patients in the high-risk group should receive adjuvant concurrent chemoradiotherapy (CCRT) with cisplatin (CDDP) and fluolouracil. However, CCRT with CDDP administered weekly (CCRT-P) has instead been applied in a clinical context worldwide. Whether CCRT-P has a survival benefit compared with radiotherapy (RT) alone is unknown because no randomized phase III trials have been performed for patients in the high-risk group after radical surgery. Patients with high-risk factors have a high incidence of distant metastasis, for whom systemic chemotherapy might be a key to improving overall survival. The pivotal study that investigated the role of RT alone for patients with intermediate-risk factors after hysterectomy is the GOG092 trial. This trial showed a 47% reduction in the risk of recurrence after RT compared with no further treatment (NFT). However, the improvement in overall survival with RT did not reach statistical

  4. Regression patterns in treated retinoblastoma with chemotherapy plus focal adjuvant therapy.

    Science.gov (United States)

    Ghassemi, Fariba; Rahmanikhah, Elham; Roohipoor, Ramak; Karkhaneh, Reza; Faegh, Adeleh

    2013-04-01

    The aim of this study was evaluation of the regression patterns after 3, 6, and 8 months of treatment. A total of 100 retinoblastoma tumors (57 eyes of 35 patients) were treated with 6 (n = 8) or 8 (n = 92) cycles of systemic chemoreduction and tumor consolidation (transpupillary thermotherapy [TTT] or cryotherapy) during this prospective study. After 3 months of treatment, type 3 was the predominant pattern (n = 57%, 57%), while after 6 and 8 months of treatment the tumors regressed to type 4 most often (44% and 52%, respectively). Smaller tumors and the peripheral tumors were likely to regress to type 4, whereas larger tumors and those nearer to fovea were more likely to become type 1 pattern. Tumors consolidated with cryotherapy mostly showed type 4 regression (3rd month: 40%, 6th month: 90%, and 8th month: 87.5%). Whereas, those treated with TTT rather regressed to type 3 after 3 months (57.9%) and to type 4 after 6 and 8 months of treatment (51.4% and 59.5%, respectively). Recurrence of the tumor was 40% in our cases with defined correlation with tumor location, size, and subretinal seeds. We conclude that regression patterns of tumors in patients undergoing systemic chemoreduction with focal adjuvant treatments predominantly changed over time and their changes are dependent on tumor size, location, and type of treatment. It appears that subretinal seeds, tumor size, and location of tumors are the most important factors predicting tumor recurrence. Copyright © 2012 Wiley Periodicals, Inc.

  5. The iBRA-2 (immediate breast reconstruction and adjuvant therapy audit) study: protocol for a prospective national multicentre cohort study to evaluate the impact of immediate breast reconstruction on the delivery of adjuvant therapy.

    Science.gov (United States)

    Dave, Rajiv; O'Connell, Rachel; Rattay, Tim; Tolkien, Zoe; Barnes, Nicola; Skillman, Joanna; Williamson, Paula; Conroy, Elizabeth; Gardiner, Matthew; Harnett, Adrian; O'Brien, Ciara; Blazeby, Jane; Potter, Shelley; Holcombe, Chris

    2016-10-07

    Immediate breast reconstruction (IBR) is routinely offered to improve quality of life for women with breast cancer requiring a mastectomy, but there are concerns that more complex surgery may delay the delivery of adjuvant oncological treatments and compromise long-term oncological outcomes. High-quality evidence, however, is lacking. iBRA-2 is a national prospective multicentre cohort study that aims to investigate the effect of IBR on the delivery of adjuvant therapy. Breast and plastic surgery centres in the UK performing mastectomy with or without (±) IBR will be invited to participate in the study through the trainee research collaborative network. All women undergoing mastectomy ± IBR for breast cancer between 1 July and 31 December 2016 will be included. Patient demographics, operative, oncological and complication data will be collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR will be compared to determine the impact that IBR has on the time of delivery of adjuvant therapy. Prospective data on 3000 patients from ∼50 centres are anticipated. Research ethics approval is not required for this study. This has been confirmed using the online Health Research Authority decision tool. This novel study will explore whether IBR impacts the time to delivery of adjuvant therapy. The study will provide valuable information to help patients and surgeons make more informed decisions about their surgical options. Dissemination of the study protocol will be via the Mammary Fold Academic and Research Collaborative (MFAC) and the Reconstructive Surgery Trials Network (RSTN), the Association of Breast Surgery (ABS) and the British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS). Participating units will have access to their own data and collective results will be presented at relevant surgical conferences and published in appropriate peer-reviewed journals. Published by

  6. Adjuvant intraoperative photodynamic therapy (AIOPDT) after photosensitization with mTHPC in a CC531 colon carcinoma model in mice

    Science.gov (United States)

    Winkler, Steffi; Prosst, Ruediger L.; Stern, Josef; Rheinwald, Markus; Haase, Thomas; Herfarth, Christian; Gahlen, Johannes

    2001-01-01

    The effectiveness of PDT as an adjuvant alternative therapy method for diverse malignant tumors has been investigated in numerous studies. The therapeutic benefit and extent of side effects is mainly determined by the applied photoactive substance. The second generation photosensitizer (PS) mTHPC is capable of causing selective tumor cell death in colon carcinoma when combined with laser irradiation of a PS specific wavelength. Our study revealed PDT with mTHPC as an efficient adjuvant intraoperative modality after R1/R2 resection of a subcutaneously implanted colon tumor. There was a significant increase of postoperative recurrence-free survival time using PDT compared to a control group in a colon cancer model in nude mice. The accumulation of the PS determined by point spectrometry showed a high tumor-selectivity in the tumor, tumor bed, and overlying skin compared to muscle tissue as reference parameter.

  7. Efficacy of antimicrobial photodynamic therapy as an adjuvant in periodontal treatment in Down syndrome patients.

    Science.gov (United States)

    Martins, Fabiana; Simões, Alyne; Oliveira, Marcio; Luiz, Ana Claudia; Gallottini, Marina; Pannuti, Claudio

    2016-12-01

    Down syndrome (DS) has characteristics that include mental retardation, a characteristic phenotype, congenital heart defects, immune disorders, and increased risk of periodontal disease (PD). Antimicrobial photodynamic therapy (aPDT) is the combined use of photosensitizers associated with low-level laser (LLL) and oxygen, leading to singlet oxygen formation, which contributes to the antibacterial activity of the phagocytes, killing bacteria. The objective of this study was to evaluate the efficacy of aPDT as an adjuvant to conventional periodontal treatment of PD in DS patients. A double-blinded, controlled, randomized, split-mouth study was conducted. A total of 13 DS subjects who were 18 years or older and who presented at least one tooth in each quadrant of the mouth with probing pocket depth (PPD) equal to or greater than 5 mm were included. The patients were evaluated at three different times: at the baseline, PPD were obtained. After 1 week, conventional scaling and root planing (SRP) was performed, and two randomly selected quadrants also received aPDT. One month after SRP, all the patients were reevaluated. Periodontal conditions were improved among all the participants. The PDT-with-SRP group presented a nonsignificant reduction in PPD (mean = 1.27 mm, median = 1.17 mm) relative to that of the SRP group (mean = 1.00 mm, median = 0.95 mm). Changes over time were compared using the Wilcoxon test. A significant reduction in median PPD was observed in both groups (p = 0.001). Both types of periodontal treatment, with and without PDT, were similarly effective and were associated with good clinical response.

  8. Provider perspectives on patient-provider communication for adjuvant endocrine therapy symptom management.

    Science.gov (United States)

    Turner, Kea; Samuel, Cleo A; Donovan, Heidi As; Beckjord, Ellen; Cardy, Alexandra; Dew, Mary Amanda; van Londen, G J

    2017-04-01

    Providers' communication skills play a key role in encouraging breast cancer survivors to report symptoms and adhere to long-term treatments such as adjuvant endocrine therapy (AET). The purpose of this study was to examine provider perspectives on patient-provider communication regarding AET symptom management and to explore whether provider perspectives vary across the multi-disciplinary team of providers involved in survivorship care. We conducted three one-hour focus groups with a multi-disciplinary group of health care providers including oncology specialists, primary care physicians, and non-physician providers experienced in caring for breast cancer survivors undergoing AET (n = 13). Themes were organized using Epstein and Street's (2007) Framework for Patient-Centered Communication in Cancer Care. The findings of this study suggest providers' communication behaviors including managing survivors' uncertainty, responding to survivors' emotions, exchanging information, and enabling self-management influences the quality of patient-provider communication about AET symptoms. Additionally, lack of systematic symptom assessment tools for AET requires providers to use discretion in determining which symptoms to discuss with survivors resulting in approaches that vary based on providers' discipline. There may be AET-specific provider communication skills and behaviors that promote effective patient-provider communication but additional research is needed to identify practices and policies that encourage these skills and behaviors among the many providers involved in survivorship care. Efforts are also needed to coordinate AET symptom assessment across providers, clarify providers' roles in symptom assessment, and determine best practices for AET symptom communication.

  9. Benefit/risk for adjuvant breast cancer therapy with tamoxifen or aromatase inhibitor use by age, and race/ethnicity.

    Science.gov (United States)

    Chlebowski, R T; Haque, R; Hedlin, H; Col, N; Paskett, E; Manson, J E; Kubo, J T; Johnson, K C; Wactawski-Wende, J; Pan, K; Anderson, G

    2015-12-01

    In early adjuvant breast cancer trial reports, aromatase inhibitors more effectively reduced breast recurrence with lower risk of thromboembolic events and endometrial cancer than tamoxifen, while aromatase inhibitors had higher fracture and cardiovascular disease risk. We used data from updated patient-level meta-analyses of adjuvant trials in analyses to summarize the benefits and risks of these agents in various clinical circumstances. Baseline incidence rates for health outcomes by age and race/ethnicity, absent aromatase inhibitor, or tamoxifen use were estimated from the Women's Health Initiative. Aromatase inhibitor and tamoxifen effects on distant recurrence were obtained from a meta-analysis of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) and Breast International Group (Big-1-98) clinical trials. Impact on other health outcomes were obtained from meta-analyses of randomized trials comparing aromatase inhibitor to tamoxifen use and from placebo-controlled chemoprevention trials. All health outcomes were given equal weight when modeling net benefit/risk for aromatase inhibitor compared to tamoxifen use by breast cancer recurrence risk, age (decade), race/ethnicity, hysterectomy (yes/no), and by prior myocardial infarction. Over a 10-year period, the benefit/risk index was more favorable for aromatase inhibitor than for tamoxifen as adjuvant breast cancer therapy in almost all circumstances regardless of patient age, race/ethnicity, breast cancer recurrence risk, or presence or absence of a uterus. Only in older women with prior myocardial infarction and low recurrence risk was an advantage for tamoxifen seen. Using a benefit/risk index for endocrine adjuvant breast cancer therapy in postmenopausal women, benefit was higher for aromatase inhibitor use in almost all circumstances.

  10. Effectiveness of adjuvant occupational therapy in employees with depression: design of a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Hees Hiske L

    2010-09-01

    Full Text Available Abstract Background Major depressive disorder is among the medical conditions with the highest negative impact on work outcome. However, little is known regarding evidence-based interventions targeting the improvement of work outcomes in depressed employees. In this paper, the design of a randomized controlled trial is presented in order to evaluate the effectiveness of adjuvant occupational therapy in employees with depression. This occupational intervention is based on an earlier intervention, which was designed and proven effective by our research group, and is the only intervention to date that specifically targets work outcome in depressed employees. Methods/Design In a two-arm randomized controlled trial, a total of 117 participants are randomized to either 'care as usual' or ' care as usual' with the addition of occupational therapy. Patients included in the study are employees who are absent from work due to depression for at least 25% of their contract hours, and who have a possibility of returning to their own or a new job. The occupational intervention consists of six individual sessions, eight group sessions and a work-place visit over a 16-week period. By increasing exposure to the working environment, and by stimulating communication between employer and employee, the occupational intervention aims to enhance self-efficacy and the acquisition of more adaptive coping strategies. Assessments take place at baseline, and at 6, 12, and 18-month follow-ups. Primary outcome measure is work participation (hours of absenteeism and time until work resumption. Secondary outcome measures are work functioning, symptomatology, health-related quality of life, and neurocognitive functioning. In addition, cost-effectiveness is evaluated from a societal perspective. Finally, mechanisms of change (intermediate outcomes and potential patient-treatment matching variables are investigated. Discussion This study hopes to provide valuable knowledge

  11. The efficacy and safety of adjuvant interferon-alfa therapy in the evolving treatment landscape for resected high-risk melanoma.

    Science.gov (United States)

    Trinh, Van Anh; Zobniw, Chrystia; Hwu, Wen-Jen

    2017-08-01

    Patients with resected stage II or III melanoma are at high risk of recurrence, with 5-year mortality rate of 40-60%. Adjuvant interferon-alfa has demonstrated a small RFS and OS benefit versus observation in this patient population. However, the adjuvant treatment landscape is evolving rapidly. Areas covered: This review aims to summarize the safety and efficacy profiles of adjuvant IFNα/PEG-IFNα, revisit the controversy surrounding its application, and reappraise its position in the rapidly changing treatment landscape of resected melanoma. A literature search using PubMed database was undertaken using search words melanoma, interferon-alfa, pegylated interferon-alfa, adjuvant therapy. Expert opinion: Currently, there is no international consensus regarding the optimal dosing schedule for adjuvant IFNα, but HD IFNα-2b remains the most widely used regimen. The AEs of HD IFNα-2b are substantial; however, toxicity management experience amassed over the past 2 decades has significantly improved safety. Many exciting studies are ongoing to examine the roles of immune checkpoint inhibitors and BRAF-targeted therapies in the adjuvant setting and will further delineate the role of adjuvant IFNα.

  12. Application of “Systems Vaccinology” to Evaluate Inflammation and Reactogenicity of Adjuvanted Preventative Vaccines

    Directory of Open Access Journals (Sweden)

    David J. M. Lewis

    2015-01-01

    Full Text Available Advances in “omics” technology (transcriptomics, proteomics, metabolomics, genomics/epigenomics, etc. allied with statistical and bioinformatics tools are providing insights into basic mechanisms of vaccine and adjuvant efficacy or inflammation/reactogenicity. Predictive biomarkers of relatively frequent inflammatory reactogenicity may be identified in systems vaccinology studies involving tens or hundreds of participants and used to screen new vaccines and adjuvants in in vitro, ex vivo, animal, or human models. The identification of rare events (such as those observed with initial rotavirus vaccine or suspected autoimmune complications will require interrogation of large data sets and population-based research before application of systems vaccinology. The Innovative Medicine Initiative funded public-private project BIOVACSAFE is an initial attempt to systematically identify biomarkers of relatively common inflammatory events after adjuvanted immunization using human, animal, and population-based models. Discriminatory profiles or biomarkers are being identified, which require validation in large trials involving thousands of participants before they can be generalized. Ultimately, it is to be hoped that the knowledge gained from such initiatives will provide tools to the industry, academia, and regulators to select optimal noninflammatory but immunogenic and effective vaccine adjuvant combinations, thereby shortening product development cycles and identifying unsuitable vaccine candidates that would fail in expensive late stage development or postmarketing.

  13. Functionally fused antibodies--a novel adjuvant fusion system

    DEFF Research Database (Denmark)

    Larsen, Martin; Jensen, Kim Bak; Christensen, Peter Astrup

    2008-01-01

    Antibodies capable of recognizing key molecular targets isolated e.g. by phage display technology have been used in the pursuit of new and improved therapies for prevalent human diseases. These approaches often take advantage of non-immunogenic antibody fragments to achieve specific toxin-, radio...

  14. Long-Term Outcomes of Adjuvant Mitotane Therapy in Patients With Radically Resected Adrenocortical Carcinoma.

    Science.gov (United States)

    Berruti, Alfredo; Grisanti, Salvatore; Pulzer, Alina; Claps, Mélanie; Daffara, Fulvia; Loli, Paola; Mannelli, Massimo; Boscaro, Marco; Arvat, Emanuela; Tiberio, Guido; Hahner, Stefanie; Zaggia, Barbara; Porpiglia, Francesco; Volante, Marco; Fassnacht, Martin; Terzolo, Massimo

    2017-04-01

    In 2007, a retrospective case-control study provided evidence that adjuvant mitotane prolongs recurrence-free survival (RFS) in patients with radically resected adrenocortical carcinoma (ACC). We aimed to confirm the prognostic role of adjuvant mitotane in the same series after 9 additional years of follow-up. One hundred sixty-two ACC patients who did not recur or die after a landmark period of 3 months were considered. Forty-seven patients were enrolled in four Italian centers where adjuvant mitotane was routinely recommended (mitotane group), 45 patients in four Italian centers where no adjuvant strategy was undertaken (control group 1), and 70 German patients left untreated after surgery (control group 2). The primary aim was RFS, the secondary was overall survival. An increased risk of recurrence was found in both control cohorts [group 1: hazard ratio (HR) = 2.98; 95% confidence interval (CI), 1.75 to 5.09; P < 0.0001; group 2: HR = 2.61; 95% CI, 1.56 to 4.36; P < 0.0001] compared with the mitotane group. The risk of death was higher in control group 1 (HR = 2.03; 95% CI, 1.17 to 3.51; P = 0.011) but not in control group 2 (HR = 1.60; 95% CI, 0.94 to 2.74; P = 0.083), which had better prognostic factors and more aggressive treatment of recurrences than control group 1. The benefit of adjuvant mitotane on RFS was observed regardless of the hormone secretory status. Adjuvant mitotane is associated with prolonged RFS, without any apparent influence by the tumor secretory status. The retrospective nature of the study is a major limitation.

  15. Effect of probucol combined with atorvastatin adjuvant therapy on serum indexes of acute cerebral infarction patients during rehabilitation period

    Directory of Open Access Journals (Sweden)

    Li Zhang

    2016-06-01

    Full Text Available Objective: To analyze the effect of probucol combined with atorvastatin adjuvant therapy on serum indexes of acute cerebral infarction patients in rehabilitation period. Methods: A total of 102 patients with acute cerebral infarction were treated in our hospital from August 2011 to June 2015, were confirmed by magnetic resonance imaging and were randomly divided into observation group 51 cases and control group 51 cases according to the order of hospitalization. Control group received atorvastatin treatment alone, observation group received probucol combined with atorvastatin adjuvant therapy, and then differences in levels of serum CXCL16, HMGB1, CD40L and Fibulin-5, P-selectin, NPY, CGRP, visfatin and others, chemokines and inflammation-related factors, vascular endothelial cells and fibrinolytic function, etc were compared between two groups after treatment. Results: Serum CXCL16, HMGB1, CD40L and Fibulin-5 levels of observation group after treatment were lower than those of control group; serum P-selectin, NPY, visfatin, UCH-L1, sVCAM-1 and SAA levels of observation group after treatment were lower than those of control group while CGRP level was higher than that of control group; serum CCL-19, CCL-21, YKL-40, IL-33 and IL- 18 values of observation group after treatment were lower than those of control group; serum vWF, PAI-1 and plasminogen levels of observation group after treatment were lower than those of control group while 6-K-PGF1α and tPA levels were higher than those of control group. Conclusions: Probucol combined with atorvastatin adjuvant therapy for acute cerebral infarction patients in rehabilitation period can effectively optimize patients’ general status and avoid re-infarction in recovery period, and it has positive clinical significance.

  16. Nanoparticulate Tubular Immunostimulating Complexes: Novel Formulation of Effective Adjuvants and Antigen Delivery Systems

    Directory of Open Access Journals (Sweden)

    Nina Sanina

    2017-01-01

    Full Text Available New generation vaccines, based on isolated antigens, are safer than traditional ones, comprising the whole pathogen. However, major part of purified antigens has weak immunogenicity. Therefore, elaboration of new adjuvants, more effective and safe, is an urgent problem of vaccinology. Tubular immunostimulating complexes (TI-complexes are a new type of nanoparticulate antigen delivery systems with adjuvant activity. TI-complexes consist of cholesterol and compounds isolated from marine hydrobionts: cucumarioside A2-2 (CDA from Cucumaria japonica and monogalactosyldiacylglycerol (MGDG from marine algae or seagrass. These components were selected due to immunomodulatory and other biological activities. Glycolipid MGDG from marine macrophytes comprises a high level of polyunsaturated fatty acids (PUFAs, which demonstrate immunomodulatory properties. CDA is a well-characterized individual compound capable of forming stable complex with cholesterol. Such complexes do not possess hemolytic activity. Ultralow doses of cucumariosides stimulate cell as well as humoral immunity. Therefore, TI-complexes comprising biologically active components turned out to be more effective than the strongest adjuvants: immunostimulating complexes (ISCOMs and complete Freund’s adjuvant. In the present review, we discuss results published in series of our articles on elaboration, qualitative and quantitative composition, ultrastructure, and immunostimulating activity of TI-complexes. The review allows immersion in the history of creating TI-complexes.

  17. Imiquimod 5% as Adjuvant Therapy for Incompletely Excised Infiltrative Nodular Basal Cell Carcinoma and Dermoscopy to Monitor Treatment Response.

    Science.gov (United States)

    Roldán-Marín, Rodrigo; Toussaint-Caire, Sonia

    2015-12-01

    A relatively novel application for dermoscopy is its use in the monitoring of topical treatment response for non-melanoma skin cancer. Basal cell carcinoma (BCC) is the most frequent type of skin cancer in humans. Surgical excision is still considered the "gold-standard" of treatment. However, a number of topical therapies are now available for the treatment of different types of basal cell carcinoma. This case report exemplifies the usefulness of dermoscopy in the monitoring of residual disease after incomplete surgical excision and also in the monitoring of topical treatment response. Imiquimod 5% cream acts as a topical immune response modifier promoting a Th-1 immune response enhancing the removal of neoplastic cells and has proven to reduce deregulated Hedgehog (HH)/GLI signal strength independent of Toll-like receptor signaling, which makes it a valuable adjuvant topical therapy for the treatment of basal cell carcinoma. Imiquimod 5% cream is a valuable adjuvant therapy for the treatment of incompletely excised BCC. This case report adds further evidence to the usefulness of dermoscopy in the assessment and monitoring of treatment outcome.

  18. Differentiated thyroid cancer lymph-node relapse. Role of adjuvant radioactive iodine therapy after lymphadenectomy

    Energy Technology Data Exchange (ETDEWEB)

    Piccardo, Arnoldo; Bottoni, Gianluca; Dib, Bassam; Altrinetti, Vania; Massollo, Michela; Bossert, Irene; Cabria, Manlio [E.O. Ospedali Galliera, Department of Nuclear Medicine, Genoa (Italy); Puntoni, Matteo [Galliera Hospital, Clinical Trial Unit, Office of the Scientific Director, Genoa (Italy); Treglia, Giorgio; Giovanella, Luca [Oncology Institute of Southern Switzerland, Department of Nuclear Medicine and PET/CT Centre, Bellinzona (Switzerland); Foppiani, Luca [Galliera Hospital, Internal Medicine, Genoa (Italy); Bertoli, Mattia; Bertagna, Francesco [University of Brescia and Spedali Civili di Brescia, Department of Nuclear Medicine, Brescia (Italy); Catrambone, Ugo; Arlandini, Anselmo [Galliera Hospital, Department of Surgery, Thyroid Centre, Genoa (Italy)

    2017-06-15

    Our purpose as to evaluate the impact of adjuvant radioactive iodine therapy (RAI) on prognosis, as assessed by progression-free survival (PFS) and overall survival (OS), in patients affected by differentiated thyroid carcinoma (DTC) lymph-node relapse and previously treated with lymphadenectomy. We retrospectively evaluated DTC patients treated with lymph-node dissection for disease relapse. All patients had previously undergone total thyroidectomy and radioiodine remnant ablation (RRA). We used clinical and histological data obtained during follow-up to assess response and outcome. By means of univariate and multivariate time-to-event analyses, we assessed the impact of RAI on outcome (PFS and OS) and the prognostic role of thyroglobulin (Tg) levels under suppression with levothyroxine (Tg-on) measured 1-3 months after lymphadenectomy and of other risk factors. We evaluated 113 patients (age at diagnosis: median 41 years, interquartile range: 31-59), 64 of whom were treated with RAI. Over a median follow-up time of 5.7 years, 27 patients showed disease progression and 13 died. Kaplan-Meier PFS and OS curves showed that age on diagnosis, tumor histology, tumor size, DTC aggressive variant, and Tg-on were associated with prognosis. Patients with Tg-on ≥1 ng/ml treated with RAI showed a better PFS (Log-rank pp 0.001) and OS (p = 0.005) than untreated patients, while no effect of RAI was observed in patients with Tg-on <1 ng/ml. Multivariate models showed that age, Tg-on (≥1 vs. < 1 ng/ml, HR: 18.2, 95% CI: 5.09-64.8, p = 0.001) and RAI (Yes vs. No, HR: 0.36,95%CI: 0.15-0. 9, p = 0.02) remained the only independent factors associated with PFS, but only age and Tg-on remained significantly associated with OS (HR: 8.31, 95%CI:1.56-44.3, p = 0.01). Nonetheless, patients treated with RAI showed a lower risk of mortality (HR: 0.34, 95%CI: 0.1-1.15 p = 0.08) than untreated patients. RAI after lymphadenectomy for DTC relapse is significantly associated with better PFS

  19. High-Dose Adjuvant Radiotherapy After Radical Prostatectomy With or Without Androgen Deprivation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ost, Piet, E-mail: piet.ost@ugent.be [Department of Radiotherapy, Ghent University Hospital (Belgium); Cozzarini, Cesare [Department of Radiotherapy, Hospital San Raffaele, Milan (Italy); De Meerleer, Gert [Department of Radiotherapy, Ghent University Hospital (Belgium); Fiorino, Claudio [Department of Radiotherapy, Hospital San Raffaele, Milan (Italy); De Potter, Bruno [Department of Radiotherapy, Ghent University Hospital (Belgium); Briganti, Alberto [Department of Urology, San Raffaele Hospital, Vita-Salute University, Milan (Italy); Nagler, Evi V.T. [Department of Nephrology, Ghent University Hospital (Belgium); Montorsi, Francesco [Department of Urology, San Raffaele Hospital, Vita-Salute University, Milan (Italy); Fonteyne, Valerie [Department of Radiotherapy, Ghent University Hospital (Belgium); Di Muzio, Nadia [Department of Radiotherapy, Hospital San Raffaele, Milan (Italy)

    2012-07-01

    Purpose: To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (>69 Gy) adjuvant radiotherapy (HD-ART) and the impact of androgen deprivation therapy (ADT). Methods and Materials: Between 1999 and 2008, 225 node-negative patients were referred for HD-ART with or without ADT to two large academic institutions. Indications for HD-ART were extracapsular extension, seminal vesicle invasion (SVI), and/or positive surgical margins at radical prostatectomy (RP). A dose of at least 69.1 Gy was prescribed to the prostate bed and seminal vesicle bed. The ADT consisted of a luteinizing hormone-releasing hormone analog. The duration and indication of ADT was left at the discretion of the treating physician. The effect of HD-ART and ADT on biochemical (bRFS) and clinical (cRFS) relapse-free survival was examined through univariate and multivariate analysis, with correction for known patient- and treatment-related variables. Interaction terms were introduced to evaluate effect modification. Results: After a median follow-up time of 5 years, the 7-year bRFS and cRFS were 84% and 88%, respectively. On multivariate analysis, the addition of ADT was independently associated with an improved bRFS (hazard ratio [HR] 0.4, p = 0.02) and cRFS (HR 0.2, p = 0.008). Higher Gleason scores and SVI were associated with decreased bRFS and cRFS. A lymphadenectomy at the time of RP independently improved cRFS (HR 0.09, p = 0.009). The 7-year probability of late Grade 2-3 toxicity was 29% and 5% for genitourinary (GU) and gastrointestinal (GI) symptoms, respectively. The absolute incidence of Grade 3 toxicity was <1% and 10% for GI and GU symptoms, respectively. The study is limited by its retrospective design and the lack of a standardized use of ADT. Conclusions: This retrospective study shows significantly improved bRFS and cRFS rates with the addition of ADT to HD-ART, with low Grade 3 gastrointestinal toxicity and 10% Grade 3 genitourinary toxicity.

  20. Postsurgical adjuvant or metastatic renal cell carcinoma therapy models reveal potent antitumor activity of metronomic oral topotecan with pazopanib.

    Science.gov (United States)

    Jedeszko, Christopher; Paez-Ribes, Marta; Di Desidero, Teresa; Man, Shan; Lee, Christina R; Xu, Ping; Bjarnason, Georg A; Bocci, Guido; Kerbel, Robert S

    2015-04-08

    Renal cell carcinoma (RCC), normally considered an intrinsically chemotherapy-resistant cancer, is currently treated with targeted biologic therapies, including antiangiogenic tyrosine kinase inhibitors (TKIs), such as pazopanib. The efficacy of these agents is limited by both intrinsic and acquired resistance. Death is almost always due to advanced metastatic disease, a treatment circumstance seldom modeled in preclinical (mouse) drug testing. Similarly, therapy results using postsurgical adjuvant therapy models of microscopic disease have not been reported. Using in vivo selection and transfection of established human RCC cell lines (786-0 and SN12-PM6), we derived clonal luciferase-expressing variants capable of spontaneous metastasis from an orthotopic primary tumor to organs typical of clinical RCC, including bone, lungs, and brain. The bioluminescence and consistent metastatic spread of von Hippel-Lindau-wild type SN12-PM6-1 cells allowed for the establishment of perioperative therapy models of RCC. We report that the combination of daily low-dose metronomic topotecan with pazopanib has highly potent antiprimary tumor as well as both postsurgical adjuvant and metastatic therapy efficacy despite lack of an antimetastatic effect of pazopanib monotherapy. The combination therapy resulted in sustained metastatic tumor cell dormancy, but tumor progression occurred upon treatment cessation. We also obtained evidence for a direct effect of pazopanib on RCC cells, resulting in increased intracellular concentration of topotecan. Our results suggest that this type of treatment combination should be considered for clinical evaluation in early- or late-stage metastatic disease, even for tumors seemingly intrinsically "resistant" to antiangiogenic TKIs or chemotherapy. Copyright © 2015, American Association for the Advancement of Science.

  1. The association between timing of initiation of adjuvant therapy and the survival of early stage ovarian cancer patients - An analysis of NRG Oncology/Gynecologic Oncology Group trials.

    Science.gov (United States)

    Chan, John K; Java, James J; Fuh, Katherine; Monk, Bradley J; Kapp, Daniel S; Herzog, Thomas; Bell, Jeffrey; Young, Robert

    2016-12-01

    To determine the association between timing of adjuvant therapy initiation and survival of early stage ovarian cancer patients. Data were obtained from women who underwent primary surgical staging followed by adjuvant therapy from two Gynecologic Oncology Group trials (protocols # 95 and 157). Kaplan-Meier estimates and Cox proportional hazards model adjusted for covariates were used for analyses. Of 497 stage I-II epithelial ovarian cancer patients, the median time between surgery and initiation of adjuvant therapy was 23days (25th-75th%: 12-33days). The time interval from surgery to initiation of adjuvant therapy was categorized into three groups: 4weeks. The corresponding 5-year recurrence-free survival rates were 72.8%, 73.9%, and 79.5% (p=0.62). The 5-year overall survival rates were 79.4%, 81.9%, and 82.8%, respectively (p=0.51; p=0.33 - global test). As compared to 4weeks. Age, stage, grade, and cytology were important prognostic factors. Timing of adjuvant therapy initiation was not associated with survival in early stage epithelial ovarian cancer patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Effect of screening and adjuvant therapy on mortality from breast cancer

    NARCIS (Netherlands)

    D.A. Berry (Donald); K.A. Cronin (Kathleen); S.K. Plevritis (Sylvia); D.G. Fryback (Dennis); L. Clarke (Lauren); M. Zelen (Marvin); J.S. Mandelblatt (Jeanne); A.Y. Yakovlev (Andrei); J.D.F. Habbema (Dik); E. Feuer (Eric)

    2005-01-01

    textabstractBACKGROUND: We used modeling techniques to assess the relative and absolute contributions of screening mammography and adjuvant treatment to the reduction in breast-cancer mortality in the United States from 1975 to 2000. METHODS: A consortium of investigators developed seven independent

  3. External Validation and Optimization of International Consensus Clinical Target Volumes for Adjuvant Radiation Therapy in Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, Abhinav V. [Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States); Christodouleas, John P. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Wu, Tianming [Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States); Smith, Norman D.; Steinberg, Gary D. [Section of Urology, Department of Surgery, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States); Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.edu [Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States)

    2017-03-15

    Purpose: International consensus (IC) clinical target volumes (CTVs) have been proposed to standardize radiation field design in the treatment of patients at high risk of locoregional failure (LRF) after radical cystectomy. The purpose of this study was to externally validate the IC CTVs in a cohort of postsurgical patients followed up for LRF and identify revisions that might improve the IC CTVs' performance. Methods and Materials: Among 334 patients with pT3 to pT4 bladder cancer treated with radical cystectomy, LRF developed in 58 (17%), of whom 52 had computed tomography scans available for review. Images with LRF were exported into a treatment planning system, and IC CTVs were contoured and evaluated for adequacy of coverage of each LRF with respect to both the patient and each of 6 pelvic subsites: common iliac (CI) region, obturator region (OR), external and internal iliac region, presacral region, cystectomy bed, or other pelvic site. Revisions to the IC contours were proposed based on the findings. Results: Of the 52 patients with documented LRF, 13 (25%) had LRFs that were outside of the IC CTV involving 17 pelvic subsites: 5 near the CI CTV, 5 near the OR CTV, 1 near the external and internal iliac region, and 6 near the cystectomy bed. The 5 CI failures were located superior to the CTV, and the 5 OR failures were located medial to the CTV. Increasing the superior boundary of the CI to a vessel-based definition of the aortic bifurcation, as well as increasing the medial extension of the OR by an additional 9 mm, decreased the number of patients with LRF outside of the IC CTV to 7 (13%). Conclusions: Modified IC CTVs inclusive of a slight adjustment superiorly for the CI region and medially for the OR may reduce the risk of pelvic failure in patients treated with adjuvant radiation therapy.

  4. Aquolab ® ozone-therapy is an efficient adjuvant in the treatment of chronic periodontitis: A case-control study

    Directory of Open Access Journals (Sweden)

    Francesco Carinci

    2015-01-01

    Full Text Available Aim: The objective of this study was to compare the efficacy of supportive periodontal therapy (i.e., scaling and root planning [SRP] alone versus Aquolab ® ozone therapy used in association with SRP in the treatment of chronic periodontitis in adult patients. Materials and Methods: A total of 20 patients with a diagnosis of chronic periodontitis (40 localized chronic periodontitis sites were enrolled. None of these patients have previously received any surgical or nonsurgical periodontal therapy and demonstrated radiographic evidence of moderate bone loss. Two nonadjacent sites in separate quadrants were selected in each patient to verify treatment efficacy (split-mouth design. Microbial analysis was analyzed at baseline and the 7 th day after treatment. SPSS program and paired simple statistic t-test were used to detect statistically significant differences. Results: There was a statistically significant reduction of Tannerella forsythia loading in sites treated with ozone therapy respect to those treated with SPR alone. A similar trend was obtained also for additional 5 species and for total bacterial loading (CBT. These results were obtained with a single local application of ozone therapy just after SPR and with a molecular control 7 th day after treatment. Conclusion : Aquolab ® ozone therapy in is effective in reducing the CBT in pockets of patients affected by periodontitis. It is an efficacy medical device to be used as adjuvant therapy to be added to SRP in the management of moderate to severe chronic periodontitis.

  5. Quantitative detection of HER2 protein concentration in breast cancer tissue does not increase the number of patients eligible for adjuvant HER2-targeted therapy

    DEFF Research Database (Denmark)

    Bechmann, Troels; Olsen, Dorte Aalund; Jakobsen, Erik Hugger

    2013-01-01

    Human epidermal growth factor receptor-2 (HER2) is overexpressed in 15-20% of breast cancer patients and is associated with an aggressive tumor and a poor prognosis. Currently, patients are selected for adjuvant HER2-targeted therapy based on HER2 status by immunohistochemistry (IHC...... by Centaur, but not treated with adjuvant HER2-targeted therapy, compared to patients defined as HER2-positive by IHC/FISH and therefore treated with adjuvant HER2-targeted therapy. Tumor tissue was obtained at primary surgery from 415 breast cancer patients between 2004 and 2010. HER2 status was determined...... for invasive disease-free survival (IDFS) and 4.2 years for overall survival (OS). The quantitative Centaur assay defined a greater number of patients (100 patients, 26.4%) as HER2-positive than IHC/FISH (63 patients, 16.6%) (P...

  6. Antimicrobial Photodynamic Therapy as a Co-adjuvant in Endodontic Treatment of Deciduous Teeth: Case Series.

    Science.gov (United States)

    Okamoto, Camila Basilio; Motta, Lara Jasinski; Prates, Renato Araujo; da Mota, Ana Carolina Costa; Gonçalves, Marcela Leticia Leal; Horliana, Anna Carolina Ratto Tempestini; Mesquita Ferrari, Raquel Agnelli; Fernandes, Kristianne Porta Santos; Bussadori, Sandra Kalil

    2018-02-08

    To assure the success of endodontic treatment, the root canal must be completely decontaminated. Thus, some methods have been researched in an attempt to effectively eliminate microorganisms from the interior of the root canal system. Among them, is conventional endodontic therapy in conjunction with photodynamic therapy (PDT). Five anterior deciduous teeth were treated endodontically with the conventional technique and PDT. For PDT, 0.005% methylene blue was used as a photosensitizer and a 660nm laser. After the conventional endodontic therapy, the photosensitizer was applied inside the root canal, 3 minutes of pre-irradiation time and then the laser was applied for 40s with an energy of 4J. Afterwards, the canal was irrigated with saline solution and the sealing material of the root canal was placed. The microbiological analysis of the samples were collected before and after the treatments were performed. Observing the results obtained in this case series,which showed a bacterial reduction from 37.57% to 100%, and the clear difficulty in the success of endodontic treatment of deciduous teeth, antimicrobial photodynamic therapy can be considered an alternative of easy application, and that does not generate microbial resistance, to act as a support in the decontamination of the root canals. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Adjuvant dendritic cells vaccine combined with cytokine-induced-killer cell therapy after renal cell carcinoma surgery.

    Science.gov (United States)

    Zheng, Kai; Tan, Jian-Ming; Wu, Wei-Zhen; Qiu, Yu-Miao; Zhang, Hui; Xu, Ting-Zhao; Sun, Xing-Hui; Zhuo, Wen-Li; Wang, Dong; Zhang, Jian-Ping

    2015-01-01

    To observe the efficacy and side effects of adjuvant dendritic cells' (DCs) vaccine combined with cytokine-induced killer cell (CIK) therapy after renal cell carcinoma (RCC) surgery (RCCS). DCs vaccine and CIK that loaded the autologous tumor cell lysate were prepared in vitro. Four hundred and ten RCC patients were recruited, and the study group was given DCs-CIK immunotherapy, while the control group was given IFN-α therapy. Disease progression (recurrence, metastasis or death) showed significant differences between the two groups in clinical stage I and II patients, as well as in highly and moderately differentiated disease (pdisease (p>0.05). The 3- and 5-year overall survival rates of the DCs-CIK group (96% and 96%, respectively) exhibited significant difference compared to the IFN-α group (83% and 74%, respectively (p<0.01). Progression-free survival (PFS) between the two groups was significantly different (p<0.01). Tumor stage and DCs-CIK treatment were independent factors concerning prognosis of RCC (p<0.05). There was no severe toxicity observed in the DCs-CIK treatment group. Adjuvant post-RCCS DCs-CIK treatment prolonged PFS and reduced mortality, showing better overall activity compared to interferon treatment.

  8. Effect of adjuvant argatroban therapy on neurological function, endothelial injury and inflammation state in patient with acute cerebral infarction

    Directory of Open Access Journals (Sweden)

    Nan Che

    2016-08-01

    Full Text Available Objective: To analyze the effect of adjuvant argatroban therapy on neurological function, endothelial injury and inflammation state in patient with acute cerebral infarction. Methods: A total of 118 patients with acute cerebral infarction were divided into observation group and control group according to the random number table, control group received conventional treatment, observation group received argatroban + conventional treatment, and then differences in TCD cerebral blood flow, serum neurological function, endothelial injury and inflammatory marker levels were compared between two groups after treatment. Results: TCD MCA and ACA values of observation group after treatment were higher than those of control group (P<0.05; serum neurological function indexes copeptin, NT-proBNP, PAO and S-100B levels of observation group after treatment were lower than those of control group, endothelial injury index ET-1 level was lower than that of control group, NO and CGRP levels were higher than those of control group, and inflammatory markers hs-CRP, TNF-毩, IL-6, MMP-9 and Lp-PLA2 levels were lower than those of control group (P<0.05. Conclusions: Adjuvant argatroban therapy can optimize the overall condition in patients with acute cerebral infarction, and plays a positive role in improving the neurological function, reducing endothelial injury and inflammation state, etc.

  9. Music as an adjuvant therapy in control of pain and symptoms in hospitalized adults: a systematic review.

    Science.gov (United States)

    Cole, Linda C; LoBiondo-Wood, Geri

    2014-03-01

    The objective of this review is to evaluate the evidence regarding the use of music as an adjuvant therapy for pain control in hospitalized adults. The search terms music, music therapy, pain, adults, inpatient, and hospitalized were used to search the Cochrane Library, Cinahl, Medline, Natural Standard, and Scopus databases from January 2005 to March 2011. (A systematic review conducted by the Cochrane Collaboration has extensively covered the time frame from 1966 to 2004.) Seventeen randomized controlled trials met criteria for review and inclusion. Seven of the research studies were conducted with surgical patients, three with medical patients, one with medical-surgical patients, four with intensive care patients, and two with pregnant patients. The combined findings of these studies provide support for the use of music as an adjuvant approach to pain control in hospitalized adults. The use of music is safe, inexpensive, and an independent nursing function that can be easily incorporated into the routine care of patients. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  10. The Development of a Mindfulness-Based Music Therapy (MBMT) Program for Women Receiving Adjuvant Chemotherapy for Breast Cancer

    Science.gov (United States)

    Lesiuk, Teresa

    2016-01-01

    Problems with attention and symptom distress are common clinical features reported by women who receive adjuvant chemotherapy for breast cancer. Mindfulness practice significantly improves attention and mindfulness programs significantly reduce symptom distress in patients with cancer, and, more specifically, in women with breast cancer. Recently, a pilot investigation of a music therapy program, built on core attitudes of mindfulness practice, reported significant benefits of enhanced attention and decreased negative mood and fatigue in women with breast cancer. This paper delineates the design and development of the mindfulness-based music therapy (MBMT) program implemented in that pilot study and includes clients’ narrative journal responses. Conclusions and recommendations, including recommendation for further exploration of the function of music in mindfulness practice are provided. PMID:27517966

  11. The Development of a Mindfulness-Based Music Therapy (MBMT) Program for Women Receiving Adjuvant Chemotherapy for Breast Cancer.

    Science.gov (United States)

    Lesiuk, Teresa

    2016-08-09

    Problems with attention and symptom distress are common clinical features reported by women who receive adjuvant chemotherapy for breast cancer. Mindfulness practice significantly improves attention and mindfulness programs significantly reduce symptom distress in patients with cancer, and, more specifically, in women with breast cancer. Recently, a pilot investigation of a music therapy program, built on core attitudes of mindfulness practice, reported significant benefits of enhanced attention and decreased negative mood and fatigue in women with breast cancer. This paper delineates the design and development of the mindfulness-based music therapy (MBMT) program implemented in that pilot study and includes clients' narrative journal responses. Conclusions and recommendations, including recommendation for further exploration of the function of music in mindfulness practice are provided.

  12. A high level of estrogen-stimulated proteins selects breast cancer patients treated with adjuvant endocrine therapy with good prognosis.

    Science.gov (United States)

    L H Weischenfeldt, Katrine; Kirkegaard, Tove; Rasmussen, Birgitte B; Giobbie-Hurder, Anita; Jensen, Maj-Britt; Ejlertsen, Bent; Lykkesfeldt, Anne E

    2017-09-01

    Adjuvant endocrine therapy has significantly improved survival of estrogen receptor α (ER)-positive breast cancer patients, but around 20% relapse within 10 years. High expression of ER-stimulated proteins like progesterone receptor (PR), Bcl-2 and insulin-like growth factor receptor I (IGF-IR) is a marker for estrogen-driven cell growth. Therefore, patients with high tumor levels of these proteins may have particularly good prognosis following adjuvant endocrine therapy. Archival tumor tissue was available from 1323 of 1396 Danish breast cancer patients enrolled in BIG 1-98, a randomized phase-III clinical trial comparing adjuvant letrozole, tamoxifen or a sequence of the two drugs. Immunohistochemical staining for ER, HER-2, PR, Bcl-2 and IGF-IR was performed and determined by Allred scoring (ER, PR and Bcl-2) or HercepTest (HER-2 and IGF-IR). Data on all five markers were available from 969 patients with ER-positive, HER-2-negative tumors. These patients were classified in ER activity groups based on the level of PR, Bcl-2 and IGF-IR. High ER activity profile was found in 102 patients (10.5%) and compared with the remaining patients, univariate and multivariate analysis revealed HR (95% CI) and p values for disease-free survival (DFS) of 2.00 (1.20-3.22), 0.008 and 1.70 (1.01-2.84), 0.04 and for the overall survival (OS) of 2.33 (1.19-4.57), 0.01 and 1.90 (0.97-3.79), 0.06, respectively. The high ER activity profile did not disclose difference in DFS or OS according to treatment with tamoxifen or letrozole (p = .06 and .09, respectively). Stratifying endocrine-treated patients in ER activity profile groups disclosed that patient with high ER activity profile (10.5%) had significantly longer DFS and OS, and the profile was an independent marker for DFS. High ER activity is a marker for estrogen-driven tumor growth. We suggest further analyses to disclose whether the ER activity profile or other markers associated with estrogen-driven growth may be used to

  13. Multiple cardiac complications after adjuvant therapy for breast cancer: the importance of echocardiography. A case report and review of the literature.

    Science.gov (United States)

    Gurghean, Adriana Luminita; Savulescu-Fiedler, Ilinca; Mihailescu, Anca

    2017-01-31

    Cardiovascular complications induced by adjuvant cancer therapies may become symptomatic after many years, being responsible for increased morbidity and mortality in long-term survivors. We report a case of a 54-year old female admitted for severe heart failure induced by myocardial and valvular damage after postoperative adjuvant therapy for left breast cancer 6 years ago. Her recent history revealed nonST elevation myocardial infarction in the absence of significant cardiovascular risk factors. Transthoracic echocardiography, tissue Doppler imaging and speckle-tracking imaging revealed severe biventricular systolic dysfunction, severe mitral and tricuspid regurgitation and severe pulmonary hypertension.

  14. Effect of screening and adjuvant therapy on mortality from breast cancer.

    Science.gov (United States)

    Berry, Donald A; Cronin, Kathleen A; Plevritis, Sylvia K; Fryback, Dennis G; Clarke, Lauren; Zelen, Marvin; Mandelblatt, Jeanne S; Yakovlev, Andrei Y; Habbema, J Dik F; Feuer, Eric J

    2005-10-27

    We used modeling techniques to assess the relative and absolute contributions of screening mammography and adjuvant treatment to the reduction in breast-cancer mortality in the United States from 1975 to 2000. A consortium of investigators developed seven independent statistical models of breast-cancer incidence and mortality. All seven groups used the same sources to obtain data on the use of screening mammography, adjuvant treatment, and benefits of treatment with respect to the rate of death from breast cancer. The proportion of the total reduction in the rate of death from breast cancer attributed to screening varied in the seven models from 28 to 65 percent (median, 46 percent), with adjuvant treatment contributing the rest. The variability across models in the absolute contribution of screening was larger than it was for treatment, reflecting the greater uncertainty associated with estimating the benefit of screening. Seven statistical models showed that both screening mammography and treatment have helped reduce the rate of death from breast cancer in the United States. Copyright 2005 Massachusetts Medical Society.

  15. Aluminum in the central nervous system (CNS): toxicity in humans and animals, vaccine adjuvants, and autoimmunity.

    Science.gov (United States)

    Shaw, C A; Tomljenovic, L

    2013-07-01

    We have examined the neurotoxicity of aluminum in humans and animals under various conditions, following different routes of administration, and provide an overview of the various associated disease states. The literature demonstrates clearly negative impacts of aluminum on the nervous system across the age span. In adults, aluminum exposure can lead to apparently age-related neurological deficits resembling Alzheimer's and has been linked to this disease and to the Guamanian variant, ALS-PDC. Similar outcomes have been found in animal models. In addition, injection of aluminum adjuvants in an attempt to model Gulf War syndrome and associated neurological deficits leads to an ALS phenotype in young male mice. In young children, a highly significant correlation exists between the number of pediatric aluminum-adjuvanted vaccines administered and the rate of autism spectrum disorders. Many of the features of aluminum-induced neurotoxicity may arise, in part, from autoimmune reactions, as part of the ASIA syndrome.

  16. Influenza virosomes as a combined vaccine carrier and adjuvant system for prophylactic and therapeutic immunizations.

    Science.gov (United States)

    Moser, Christian; Amacker, Mario; Kammer, Andreas R; Rasi, Silvia; Westerfeld, Nicole; Zurbriggen, Rinaldo

    2007-10-01

    Influenza virosomes are an efficient antigen carrier and adjuvant system that are approved for the use in human vaccines. Structurally, virosomes are spherical vesicles of approximately 150 nm in diameter, composed of a lipid membrane with integrated envelope proteins derived from influenza virus, predominantly hemagglutinin. The particle structure, together with the functions of hemagglutinin--receptor binding, pH-dependent fusion activity and immunostimulation--is responsible for the adjuvant effect of virosomes. In contrast to most other virus-like particles, virosomes are semisynthetic particles reconstituted in vitro from lipids and from virus-derived proteins. The production process has proven to be robust at industrial scale and fully compatible with Good Manufacturing Practice guidelines. At the same time, the formulation procedure is sufficiently flexible to allow modifications of the composition and structure for the intended use, including the positioning of the antigens of interest.

  17. Beyond the dollar: Influence of sociodemographic marginalization on surgical resection, adjuvant therapy, and survival in patients with pancreatic cancer.

    Science.gov (United States)

    Kagedan, Daniel J; Abraham, Liza; Goyert, Nik; Li, Qing; Paszat, Lawrence F; Kiss, Alexander; Earle, Craig C; Mittmann, Nicole; Coburn, Natalie G

    2016-10-15

    The single-payer universal health care system in Ontario, Canada creates a setting with reduced socioeconomic barriers to treatment. Herein, the authors sought to elucidate the influence of sociodemographic marginalization on receipt of pancreatectomy, overall survival (OS), and receipt of adjuvant treatment among patients diagnosed with pancreatic cancer at the population level using an observational cohort study design. Patients diagnosed with pancreatic cancer in Ontario between January 2005 and January 2010 were identified using the provincial cancer registry and linked to administrative databases. Census data obtained from each patient's postal code were used as a proxy for that patient's median income, residential instability, material deprivation, ethnic concentration, and dependency (percentage aged 65 years, and unemployed). Surgical specimen pathology reports were abstracted for histopathology and margin status. Independent predictors of undergoing pancreatectomy, OS after surgical resection, and receipt of adjuvant treatment were identified by logistic regression and Cox proportional hazards analysis. Of the 6296 patients diagnosed with pancreatic cancer, 820 (13%) underwent resection of their tumor. Increasing levels of residential instability (odds ratio [OR], 0.86; 95% confidence interval [95% CI], 0.80-0.94) and material deprivation (OR, 0.86; 95% CI, 0.79-0.94) predicted a decreased likelihood of undergoing surgical resection. Patients living in rural areas (OR, 0.68; 95% CI, 0.51-0.91) and those living in urban areas with lower incomes (OR range, 0.49-0.77) were found to have a lower likelihood of undergoing surgical resection compared with patients in the urban areas with the highest income. After surgical resection, an association between sociodemographic marginalization with OS or receipt of adjuvant treatment was not identified. Sociodemographic marginalization exerts its influence early in the pancreatic cancer care continuum, and appears to

  18. COMPliance and Arthralgia in Clinical Therapy: the COMPACT trial, assessing the incidence of arthralgia, and compliance within the first year of adjuvant anastrozole therapy.

    Science.gov (United States)

    Hadji, P; Jackisch, C; Bolten, W; Blettner, M; Hindenburg, H J; Klein, P; König, K; Kreienberg, R; Rief, W; Wallwiener, D; Zaun, S; Harbeck, N

    2014-02-01

    This prospective study evaluated the relationship between arthralgia and compliance during the first year of adjuvant anastrozole therapy in postmenopausal women with hormone receptor-positive early breast cancer. COMPliance and Arthralgia in Clinical Therapy (COMPACT) was an open-label, multicenter, noninterventional study conducted in Germany. Patients had started adjuvant anastrozole 3-6 months before the study start. The primary end points were arthralgia, compliance, and the relationship between compliance and arthralgia, assessed at specific time points. Overall, 1916 patients received upfront anastrozole. Mean arthralgia scores were increased from baseline at each visit up to 9 months. Compliance with anastrozole therapy gradually decreased over time from baseline to 9 months (P95% of patients were compliant versus patient reports of <70%. There was a significant association between arthralgia mean scores and noncompliance at 6 months (P<0.0001), 9 months (P<0.0001), and overall (P<0.0001). Over time, new events or impairment of existing arthralgias were reported in 14% (3 months), 11% (6 months), and 9% (9 months) of patients. Arthralgia is important in the clinical management of women with early breast cancer and may contribute to noncompliance and clinical outcomes. NCT00857012.

  19. A cohort study of ethnic differences in use of adjuvant chemotherapy and radiation therapy for breast cancer in New Zealand.

    Science.gov (United States)

    Seneviratne, Sanjeewa; Campbell, Ian; Scott, Nina; Lawrenson, Ross

    2017-01-21

    Ethnic and socioeconomic inequities in use of breast cancer adjuvant therapy are well documented in many countries including the USA, and are known to contribute to lower breast cancer survival among minority ethnic and socioeconomically deprived women. We investigated ethnic and socioeconomic inequities in use of adjuvant radiotherapy and chemotherapy in a cohort of women with invasive breast cancer in New Zealand. All women with newly diagnosed invasive breast cancer during 1999-2012 were identified from the Waikato Breast Cancer Register. Rates of chemotherapy use and radiotherapy use were assessed in women who were deemed to be eligible for chemotherapy (n = 1212) and radiotherapy (n = 1708) based on guidelines. Factors associated with use of chemotherapy and radiation therapy were analysed in univariate and multivariate regression models, adjusting for covariates. Overall, rates of chemotherapy and radiotherapy use were 69% (n = 836) and 87.3% (n = 1491), respectively. In the multivariate model, significantly lower rates of radiotherapy use were associated with Māori compared with NZ European (Odds Ratio [OR] = 0.63, 0.40-0.98), presence of comorbidity (OR = 0.49, 0.34-0.72), distance from hospital of over 100km (OR = 0.47, 0.23-0.96), mastectomy compared with breast conserving surgery (OR = 0.32, 0.17-0.56) and non-screen compared with screen detection (OR = 0.53, 0.35-0.79). No significant associations were observed between chemotherapy use and ethnic or socio-demographic factors. Improving access for radiotherapy, especially for women who are at a higher risk of not receiving optimum cancer therapy due to ethnicity, geography or socioeconomic status need to be recognized as a priority to reduce inequities in breast cancer care in New Zealand.

  20. Phospholipids: a novel adjuvant in herbal drug delivery systems.

    Science.gov (United States)

    Khan, Mohammed S; Krishnaraj, K

    2014-01-01

    Phytoconstituents have been used extensively in modern science because of their various pharmacological actions with few side effects. Regardless of their excellent therapeutic activity, several phytoconstituents have shown poor bioavailability in vivo. Phytoconstituents possess properties such as poor lipid solubility, large molecular size, and degradation in the gut due to the acidic environment. Gastric enzymes always limit their use. Phospholipids seem to be a major carrier for plant active molecules, which not only interact with the plant constituents on a molecular level but also protect the active components of the plant from degradation and increase the bioavailability of the active components by imparting lipid solubility to them. Complexation techniques enable researchers to convert the phytophospholipids into various dosage forms, including tablets and capsules. In the cosmetic industry, however, these complexes have acquired wider applicability in the form of gels and emulsions. Complexation of phospholipids with active components of plants improves their bioavailability and is being extensively studied by researchers, and further research in this regard is expected in the future. This review highlights the unique property of phospholipids in drug delivery, their health benefits, and their use in the herbal medicine systems to improve the bioavailability of active herbal components.

  1. Prognostic factors and the role of adjuvant radiation therapy in non-melanoma skin cancer of the head and neck.

    Science.gov (United States)

    Porceddu, Sandro V

    2015-01-01

    Non-melanoma skin cancer (NMSC) is the most common cancer worldwide. Among the two types of NMSC, basal cell carcinoma (BCC) accounts for approximately 75% to 80% of cases and cutaneous squamous cell carcinoma (cSCC) accounts for 20% to 25% of cases. The majority of lesions are low risk and treated with simple surgical excision, which provides histopathologic information and is associated with high cure rates and acceptable cosmetic and functional outcomes. cSCCs are generally more aggressive than BCCs. NMSC commonly occurs in the sun-exposed head and neck region (80% to 90%). Approximately 5% of patients with NMSC (mainly cSCC) will have clinicopathologic features that predict for an increased risk for local and regional recurrence and, rarely, distant relapse. These features include locally advanced primary disease (stage T3-T4), regional nodal involvement, clinical perineural invasion, recurrent disease following treatment, and immunosuppression. Patients who have these features may warrant review by a multidisciplinary tumor board and might require combined modality treatment involving surgery and adjuvant radiation therapy (RT). This article focuses on our current understanding of the prognostic factors and role of adjuvant RT in high-risk NMSC of the head and neck.

  2. [Quality of life and depressiveness of women patients diagnosed with ovarian cancer treated with surgery and after previous adjuvant therapy].

    Science.gov (United States)

    Smorag, Leszek; Florkowski, Antoni; Nowacka, Agata; Zboralsk, Krzysztof; Przybyszewska, Monika; Macander, Marian; Sławińska, Anna; Wierzbiński, Piotr

    2014-10-01

    In the present study undertaken to assess the quality of life and depression of women patients diagnosed with ovarian cancer. The aim of the study was to assess quality of life and severity of depression of women diagnosed with ovarian cancer treated with surgery, and then underwent adjuvant radio or chemotherapy treatment. The principle of study was to included on random selection 42 women diagnosed with ovarian cancer who were treated surgically, and then subjected to adjuvant therapy. Quality of life was based on patient self-assessment using the EORTC QLQ C-30 form. The severity of depression was assessed by the Beck Depression Scale. Our results showed that in the vast majority the quality of life of women with ovarian cancer who develop depression, evaluate their own quality of life at a low level. In contrast patients who did not get depressed in most cases evaluated their own quality of life at the average level. In studies it has been shown that patients manifesting symptoms of depression compared to women not having these symptoms differ in a statistically significant way, in terms of quality of life. The results indicate that women diagnosed with ovarian cancer who have demonstrated the co-existence of depression presented a lower quality of life. The study indicates that in the majority of cases the severity of depression of patients diagnosed with ovarian cancer were mild.

  3. Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Park, In Ja [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Kim, Dae Yong [Center for Colorectal Cancer, National Cancer Center, Goyang-si (Korea, Republic of); Kim, Hee Cheol [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Nam Kyu [Section of Colon and Rectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Hyeong-Rok [Department of Surgery, Chonnam National University Hwansun Hospital, Gwangju (Korea, Republic of); Kang, Sung-Bum [Department of Surgery, Seoul National University Bungdang Hospital, Bundang (Korea, Republic of); Choi, Gyu-Seog [Division of Colorectal Cancer Center, Kyungpook National University Medical Center, Daegu (Korea, Republic of); Lee, Kang Young [Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Seon-Hahn [Department of Surgery, Korea University Anam Hospital, Seoul (Korea, Republic of); Oh, Seung Taek [Department of Surgery, Seoul St. Mary Hospital, Catholic University, Seoul (Korea, Republic of); Lim, Seok-Byung; Kim, Jin Cheon [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Oh, Jae Hwan; Kim, Sun Young [Center for Colorectal Cancer, National Cancer Center, Goyang-si (Korea, Republic of); Lee, Woo Yong [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, Jung Bok [Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Yu, Chang Sik, E-mail: csyu@amc.seoul.kr [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of)

    2015-07-01

    Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits.

  4. Resistance Exercise and Inflammation in Breast Cancer Patients Undergoing Adjuvant Radiation Therapy: Mediation Analysis From a Randomized, Controlled Intervention Trial

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Martina E., E-mail: m.schmidt@dkfz.de [Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg (Germany); Meynköhn, Anna; Habermann, Nina [Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg (Germany); Wiskemann, Joachim [Division of Medical Oncology, National Center for Tumor Diseases and University Hospital, Heidelberg (Germany); Oelmann, Jan; Hof, Holger; Wessels, Sabine [Department of Radiation Oncology, National Center for Tumor Diseases and University Hospital, Heidelberg (Germany); Klassen, Oliver [Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg (Germany); Debus, Jürgen; Potthoff, Karin [Department of Radiation Oncology, National Center for Tumor Diseases and University Hospital, Heidelberg (Germany); Steindorf, Karen; Ulrich, Cornelia M. [Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg (Germany)

    2016-02-01

    Purpose: To explore the mediating role of inflammatory parameters in the development of fatigue, pain, and potentially related depressive symptoms during radiation therapy for breast cancer and its mitigation by resistance exercise. Methods and Materials: Breast cancer patients scheduled for adjuvant radiation therapy were randomized to 12-week progressive resistance exercise training (EX) or a relaxation control group. Interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) were measured in serum samples collected before, at the end, and 6 weeks after radiation therapy from 103 chemotherapy-naïve participants. Fatigue was assessed with the multidimensional Fatigue Assessment Questionnaire, pain with the European Organization for Research and Treatment of Cancer QLQ-C30, and depressive symptoms with the Center for Epidemiologic Studies Depression Scale. Analysis of covariance models, partial correlations, Freedman-Schatzkin tests, and R{sup 2} effect-size measures for mediation were calculated. Results: The analysis of covariance models revealed a significant intervention effect on IL-6 (P=.010) and the IL-6/IL-1ra ratio (P=.018), characterized by a marked increase during radiation therapy among controls, but no significant change in EX. Interleukin-1 receptor antagonist did not change significantly in either group (P=.88). Increased IL-6 and IL-6/IL-1ra levels at the end of radiation therapy were significantly associated with increased physical fatigue and pain 6 weeks after radiation. We observed significant partial mediation by IL-6 and IL-6/IL-1ra of the effect of resistance exercise on physical fatigue (Freedman-Schatzkin P=.023 and P<.001) and pain (both P<.001). Hereby IL-6 and IL-6/IL-1ra mediated between 15% and 24% of the variance of physical fatigue and pain explained by the intervention. Conclusions: This randomized, controlled trial showed a significantly increased proinflammatory cytokine level after adjuvant radiation therapy in breast

  5. Adjuvant Radiation Therapy Following Radical Prostatectomy for Pathologic T3 or Margin-positive Prostate Cancer: Are the EAU Guidelines Correct?

    NARCIS (Netherlands)

    Kamphuis, Guido M.; Sodha, Hiren S.; de Reijke, Theo M.

    2011-01-01

    Objective: To present a critical review of the published data as to whether adjuvant radiation therapy (RT) is the preferred first line of management for pathologic T3 or margin-positive prostate cancer (PCa) after radical prostatectomy (RP), which has level 1B evidence in the European Association

  6. The impact of adjuvant therapy on contralateral breast cancer risk and the prognostic significance of contralateral breast cancer : a population based study in the Netherlands

    NARCIS (Netherlands)

    Schaapveld, Michael; Visser, Otto; Louwman, W. J.; Willemse, Pax H. B.; de Vries, Elisabeth G. E.; van der Graaf, Winette T. A.; Otter, Renee; Coebergh, Jan Willem W.; van Leeuwen, Flora E.

    Background The impact of age and adjuvant therapy on contralateral breast cancer (CBC) risk and prognostic significance of CBC were evaluated. Patients and Methods In 45,229 surgically treated stage I-IIIA patients diagnosed in the Netherlands between 1989 and 2002 CBC risk was quantified using

  7. The impact of adjuvant therapy on contralateral breast cancer risk and the prognostic significance of contralateral breast cancer: a population based study in the Netherlands.

    NARCIS (Netherlands)

    Schaapveld, M.; Visser, O.; Louwman, W.J.; Willemse, P.H.; Vries, EG de; Graaf, W.T.A. van der; Otter, R.; Coebergh, J.W.; Leeuwen, F.E. van

    2008-01-01

    BACKGROUND: The impact of age and adjuvant therapy on contralateral breast cancer (CBC) risk and prognostic significance of CBC were evaluated. PATIENTS AND METHODS: In 45,229 surgically treated stage I-IIIA patients diagnosed in the Netherlands between 1989 and 2002 CBC risk was quantified using

  8. The impact of adjuvant therapy on contralateral breast cancer risk and the prognostic significance of contralateral breast cancer: A population based study in the Netherlands

    NARCIS (Netherlands)

    M. Schaapveld (Michael); O.J. Visser (Otto); W.J. Louwman; P.H.B. Willemse (Pax); E.G.E. de Vries (Elisabeth); W.T.A. van der Graaf (Winette); R. Otter (Renée); J.W.W. Coebergh (Jan Willem); F.E. van Leeuwen (Flora)

    2008-01-01

    textabstractBackground: The impact of age and adjuvant therapy on contralateral breast cancer (CBC) risk and prognostic significance of CBC were evaluated. Patients and Methods: In 45,229 surgically treated stage I-IIIA patients diagnosed in the Netherlands between 1989 and 2002 CBC risk was

  9. The Use of Corticosteroids as Adjuvant Therapy for Painful Bone Metastases: A Large Cross-Sectional Survey of Palliative Care Providers.

    Science.gov (United States)

    White, Patrick; Arnold, Robert; Bull, Janet; Cicero, Brandon

    2018-01-01

    Bone metastases are a common complication in patients with advanced cancer but little is known regarding current practice patterns of palliative care providers when prescribing corticosteroids as adjuvant therapy for painful bone metastases. To identify current practice patterns among palliative care providers when prescribing corticosteroids for the treatment of painful bone metastases. A cross-sectional, online survey of the membership of the American Academy of Hospice and Palliative Medicine. Providers were asked to report how frequently they prescribed corticosteroids as adjuvant therapy in patients with painful bone metastases, and to specify the corticosteroid, dosage, treatment duration, and the gastroprotective strategy most frequently utilized. Seven hundred sixty-five participants responded to the survey and 600 (78%) of respondents completed the survey. Ninety-eight percent of respondents completing the survey reported having prescribed corticosteroids as adjuvant pain therapy, and 66% ordered corticosteroids for the majority of their patients with painful bone metastases. Dexamethasone was the most widely prescribed corticosteroid. Eight milligrams divided twice daily was the most common dosage selected and once started, it was usually continued indefinitely. Corticosteroids are commonly prescribed as adjuvant therapy in the treatment of painful bone metastases in patients with limited life expectancy. Dexamethasone is the most commonly selected corticosteroid by American palliative care providers with variation existing among providers regarding dosing schedule, treatment duration, and gastroprotective strategies. Clinical trials comparing a total daily dose of four versus eight milligrams of dexamethasone would be clinically useful to inform evidence-based practice.

  10. Efficacy and Safety Assessment of the Addition of Bevacizumab to Adjuvant Therapy Agents in Cancer Patients : A Systematic Review and Meta-Analysis of Randomized Controlled Trials

    NARCIS (Netherlands)

    Ahmadizar, Fariba; Onland-Moret, N Charlotte|info:eu-repo/dai/nl/26504362X; de Boer, Anthonius; Liu, Geoffrey; Maitland-van der Zee, Anke H

    2015-01-01

    AIM: To evaluate the efficacy and safety of bevacizumab in the adjuvant cancer therapy setting within different subset of patients. METHODS & DESIGN/ RESULTS: PubMed, EMBASE, Cochrane and Clinical trials.gov databases were searched for English language studies of randomized controlled trials

  11. Efficacy and safety assessment of the addition of bevacizumab to adjuvant therapy agents in cancer patients: A systematic review and meta-analysis of randomized controlled trials

    NARCIS (Netherlands)

    Ahmadizar, Fariba|info:eu-repo/dai/nl/369491440; Onland-Moret, N. Charlotte; De Boer, Anthonius|info:eu-repo/dai/nl/075097346; Liu, Geoffrey; Maitland-Van Der Zee, Anke H.|info:eu-repo/dai/nl/255164688

    2015-01-01

    Aim: To evaluate the efficacy and safety of bevacizumab in the adjuvant cancer therapy setting within different subset of patients. Methods & Design/Results: PubMed, EMBASE, Cochrane and Clinical trials.gov databases were searched for English language studies of randomized controlled trials

  12. Treatment results of high dose cabergoline as an adjuvant therapy in six patients with established severe ovarian hyper stimulation syndrome.

    Science.gov (United States)

    Saharkhiz, Nasrin; Akbari Sene, Azadeh; Salehpour, Saghar; Tamimi, Maryam; Vasheghani Farahani, Masoumeh; Sheibani, Kourosh

    2014-10-01

    The beneficial role of cabergoline as a prophylactic agent to prevent ovarian hyper stimulation syndrome (OHSS) among high-risk patients has been demonstrated in previous studies. But data for its role as a treatment for established severe OHSS is still limited. We represent the treatment results of high dose oral cabergoline in management of six patients after the syndrome is established. High-dose oral cabergoline (1 mg daily for eight days) was prescribed as an adjuvant to symptomatic treatment for six hospitalized patients with established severe OHSS following infertility treatment cycles. In two cases OHSS resolved rapidly despite the occurrence of ongoing pregnancy. Considering the treatment outcomes of our patients, high dose cabergoline did not eliminate the need for traditional treatments, but it was a relatively effective and safe therapy in management of established severe OHSS, and prevented the increase in its severity following the occurrence of pregnancy.

  13. Development and Validation of Consensus Contouring Guidelines for Adjuvant Radiation Therapy for Bladder Cancer After Radical Cystectomy

    Energy Technology Data Exchange (ETDEWEB)

    Baumann, Brian C. [Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Bosch, Walter R. [Washington University in St. Louis, St. Louis, Missouri (United States); Bahl, Amit [University Hospitals Bristol NHS Foundation Trust, Bristol (United Kingdom); Birtle, Alison J. [Royal Preston Hospital, Preston (United Kingdom); Breau, Rodney H. [University of Ottawa, Ottawa, Ontario (Canada); Challapalli, Amarnath [University Hospitals Bristol NHS Foundation Trust, Bristol (United Kingdom); Chang, Albert J. [University of California San Francisco, San Francisco, California (United States); Choudhury, Ananya [Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester (United Kingdom); The University of Manchester, Manchester Academic Heath Science Centre, Manchester (United Kingdom); Daneshmand, Sia [University of Southern California, Los Angeles, California (United States); El-Gayed, Ali [Saskatoon Cancer Centre, Saskatoon (Canada); Feldman, Adam [Massachusetts General Hospital, Boston, Massachusetts (United States); Finkelstein, Steven E. [Cancer Treatment Centers of America, Tulsa, Oklahoma (United States); Guzzo, Thomas J. [Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Hilman, Serena [University Hospitals Bristol NHS Foundation Trust, Bristol (United Kingdom); Jani, Ashesh [Emory University, Atlanta, Georgia (United States); Malkowicz, S. Bruce [Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Mantz, Constantine A. [21st Century Oncology, Scottsdale, Arizona (United States); 21st Century Oncology, Fort Myers, Florida (United States); Master, Viraj [Emory University, Atlanta, Georgia (United States); Mitra, Anita V. [University College London Hospital, London (United Kingdom); Murthy, Vedang [Tata Memorial Center, Mumbai (India); and others

    2016-09-01

    Purpose: To develop multi-institutional consensus clinical target volumes (CTVs) and organs at risk (OARs) for male and female bladder cancer patients undergoing adjuvant radiation therapy (RT) in clinical trials. Methods and Materials: We convened a multidisciplinary group of bladder cancer specialists from 15 centers and 5 countries. Six radiation oncologists and 7 urologists participated in the development of the initial contours. The group proposed initial language for the CTVs and OARs, and each radiation oncologist contoured them on computed tomography scans of a male and female cystectomy patient with input from ≥1 urologist. On the basis of the initial contouring, the group updated its CTV and OAR descriptions. The cystectomy bed, the area of greatest controversy, was contoured by another 6 radiation oncologists, and the cystectomy bed contouring language was again updated. To determine whether the revised language produced consistent contours, CTVs and OARs were redrawn by 6 additional radiation oncologists. We evaluated their contours for level of agreement using the Landis-Koch interpretation of the κ statistic. Results: The group proposed that patients at elevated risk for local-regional failure with negative margins should be treated to the pelvic nodes alone (internal/external iliac, distal common iliac, obturator, and presacral), whereas patients with positive margins should be treated to the pelvic nodes and cystectomy bed. Proposed OARs included the rectum, bowel space, bone marrow, and urinary diversion. Consensus language describing the CTVs and OARs was developed and externally validated. The revised instructions were found to produce consistent contours. Conclusions: Consensus descriptions of CTVs and OARs were successfully developed and can be used in clinical trials of adjuvant radiation therapy for bladder cancer.

  14. Prognostic factors and long term results of neo adjuvant therapy followed by surgery in stage IIIA N2 non-small cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Li Jing

    2009-01-01

    Full Text Available Background: Prognosis of stage IIIA N2 non-small cell lung cancer (NSCLC remains poor despite the changes in therapeutic strategies. Objectives: To assess long term results of neo adjuvant therapy followed by surgery for patients with stage IIIA N2 NSCLC and to analyze factors influencing survival. Materials and Methods: The methods adopted include: Retrospective review of medical records of 91 patients with stage IIIA N2 NSCLC, who received neo adjuvant therapy followed by surgery; collection of information on demographic information, staging procedure, preoperative therapy, clinical response, type of resection, pathologic response of tumor, status of lymph nodes and adjuvant chemotherapy; survival analysis by Kaplan-Meier and calculation of prognostic factors using log-rank and Cox regression model. Results: All patients received a platinum-based chemotherapy and 23 (29.1% had an associated radiotherapy. Eighty four patients underwent thoracotomy. Median survival was 26 months (95%CI, 22.6-30.8 months with three and five year survival rates of 31.6 and 20.9%, respectively. Prognostic factors for survival on univariate analysis was clinical response (P = 0.032, complete resection (P = 0.002, pathologic tumor response ( P < 0.001, and lymph nodal down staging (P = 0.001. Multivariate analyses identified complete resection, pathologic tumor response and lymph nodal down staging as independent prognostic factors. Conclusion: Survival of patients with stage IIIA N2 NSCLC who received neo adjuvant therapy is significantly influenced by clinical response, complete resection, pathologic tumor response, and lymph nodal down staging. These results can be helpful in guiding standard clinical practice and evaluating the outcome of neo adjuvant therapy followed by surgery in patients with stage IIIA N2 NSCLC.

  15. Evaluation of the efficacy and safety of adjuvant treatment to levodopa therapy in Parkinson s disease patients with motor complications.

    Science.gov (United States)

    Stowe, Rebecca; Ives, Natalie; Clarke, Carl E; Deane, Katherine; Wheatley, Keith; Gray, Richard; Handley, Kelly; Furmston, Alex

    2010-07-07

    One of the complications of long-term treatment of Parkinson's disease (PD) with levodopa is the development of motor complications. Generally, when motor complications develop, clinicians add in an additional drug (to the levodopa regimen) from one of three other classes of anti-Parkinsonian treatments (dopamine agonists, catechol-O-methyl transferase inhibitors (COMTIs) or monoamine oxidase type B inhibitors (MAOBIs)). However, despite trials having shown that these drugs are beneficial compared to placebo, it remains unclear as to the best way to treat patients experiencing motor complications and whether one class of drug is more effective than another. This meta-analysis aims to assess more reliably the benefits and risks of the three classes of drugs (dopamine agonists, COMTIs and MAOBIs) currently used as adjuvant treatment to levodopa in PD patients suffering from motor complications. The three drug classes were compared with the aim of determining whether one class of drug provides better symptomatic control than another. We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, PubMed, LILACS and Web of Science, plus major journals in the field, abstract books, conference proceedings and reference lists of retrieved publications. Randomised trials comparing an orally administered dopamine agonist, COMTI or MAOBI versus placebo, both on a background of levodopa therapy, in PD patients experiencing motor complications. Two authors independently extracted data on off-time, levodopa dose, motor complications, side-effects, treatment concordance, clinician-rated disability, mortality, quality of life and health economic data. Forty-four eligible trials, involving 8436 participants were identified. Compared to placebo, adjuvant therapy significantly reduced off-time (-1.05 hours/day, 95% confidence interval (CI) -1.19 to -0.90; Pclasses suggested that dopamine agonists were more efficacious in reducing off-time (dopamine agonist: -1.54 hours/day; COMTI: -0

  16. [Intraluminal Thrombus in Internal Carotid Artery Successfully Treated with Adjuvant Anticoagulant Therapy Followed by Carotid Endarterectomy:A Case Report].

    Science.gov (United States)

    Minamide, Hisato; Hayashi, Yutaka; Ueno, Megumi

    2016-10-01

    An intraluminal thrombus in the carotid artery is relatively rare. A high frequency of perioperative symptomatic stroke has been reported in patients undergoing carotid endarterectomy, and no standard therapy has yet been developed. A 69-year-old woman, with no history of trauma, presented with ischemic stroke and mild right hemiparesis. Computed tomography and MRI showed an infarction in the left parietal region. A carotid Doppler study showed carotid stenosis on the left side. Further investigation with digital subtraction angiography confirmed significant carotid artery stenosis with an intraluminal thrombus in the left internal carotid artery. She was treated with initial intravenous anticoagulant therapy followed by carotid endarterectomy with thrombus removal 14 days after admission(subacute phase). There was no postoperative complication and she had uneventful course over 3 years of follow-up. Initial adjuvant anticoagulant therapy for symptomatic intraluminal thrombus followed by carotid revascularization is an effective surgical strategy. A meticulous surgical procedure is required to perform a carotid endarterectomy in patients with an intraluminal thrombus.

  17. Use of electronic brachytherapy to deliver postsurgical adjuvant radiation therapy for endometrial cancer: a retrospective multicenter study

    Directory of Open Access Journals (Sweden)

    William C Dooley

    2010-09-01

    Full Text Available William C Dooley1, John P Thropay2, Gary J Schreiber3, Mohamed Y Puthawala4, Steven C Lane5, James C Wurzer6, Charles E Stewart7, Gordon L Grado8, Harish G Ahuja9, Gary M Proulx101University of Oklahoma Health Sciences Center, Oklahoma City, OK; 2Beverly Oncology and Imaging Center, Montebello, CA; 3Swedish Covenant Medical Center, Chicago, IL; 4Rhode Island Hospital, Providence, RI; 5Signature Healthcare Brockton Hospital, Brockton, MA; 6AtlantiCare Regional Medical Center, Egg Harbor Township, NJ; 7St Francis Medical Center, Tulsa, OK; 8Southwest Oncology Centers, Scottsdale, AZ; 9Aspirus Regional Medical Center, Wausau, WI; 10Exeter Hospital, Exeter, NH, USABackground: This retrospective, multicenter study evaluated the feasibility and safety of high-dose rate electronic brachytherapy (EBT as a postsurgical adjuvant radiation therapy for endometrial cancer.Methods: Medical records were reviewed from 41 patients (age 40–89 years with endometrial cancer (Federation of International Gynecology and Obstetrics stages IA–IIIC treated at nine centers between April 2008 and October 2009. Treatment included intracavitary vaginal EBT alone (n = l6 at doses of 18.0–24.0 Gy in 3–4 fractions and EBT in combination with external beam radiation therapy (EBRT, n = 25 at a total radiation dose range of 40.0–80.4 Gy. Doses were prescribed to a depth of 5 mm from the applicator surface and to the upper third (n = 15 and the upper half (n = 26 of the vagina.Results: Median follow-up was 3.8 (range 0.5–12.0 months. All 41 patients received the intended dose of radiation as prescribed. Adverse events occurred in 13 of 41 patients and were mild to moderate (Grade 1–2, consisting primarily of vaginal mucositis, rectal mucosal irritation and discomfort, and temporary dysuria and diarrhea. There were no Grade 3 adverse events in the EBT-only treatment group. One patient, who was being treated with the combination of EBT and EBRT for recurrent endometrial

  18. Adjuvant neutron therapy in complex treatment of patients with locally advanced breast cancer

    Science.gov (United States)

    Lisin, V. A.; Velikaya, V. V.; Startseva, Zh. A.; Popova, N. O.; Goldberg, V. E.

    2017-09-01

    The study included 128 patients with stage T2-4N0-3M0 locally advanced breast cancer. All patients were divided into two groups. Group I (study group) consisted of 68 patients, who received neutron therapy, and group II (control group) comprised 60 patients, who received electron beam therapy. Neutron therapy was well tolerated by the patients and 1-2 grade radiation skin reactions were the most common. Neutron therapy was shown to be effective in multimodality treatment of the patients with locally advanced breast cancer. The 8-year recurrence-free survival rate in the patients with locally advanced breast cancer was 94.5 ± 4.1% after neutron therapy and 81.4 ± 5.9% after electron beam therapy (p = 0.05).

  19. Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines

    Science.gov (United States)

    Nochi, Tomonori; Yuki, Yoshikazu; Takahashi, Haruko; Sawada, Shin-Ichi; Mejima, Mio; Kohda, Tomoko; Harada, Norihiro; Kong, Il Gyu; Sato, Ayuko; Kataoka, Nobuhiro; Tokuhara, Daisuke; Kurokawa, Shiho; Takahashi, Yuko; Tsukada, Hideo; Kozaki, Shunji; Akiyoshi, Kazunari; Kiyono, Hiroshi

    2010-07-01

    Nanotechnology is an innovative method of freely controlling nanometre-sized materials. Recent outbreaks of mucosal infectious diseases have increased the demands for development of mucosal vaccines because they induce both systemic and mucosal antigen-specific immune responses. Here we developed an intranasal vaccine-delivery system with a nanometre-sized hydrogel (`nanogel') consisting of a cationic type of cholesteryl-group-bearing pullulan (cCHP). A non-toxic subunit fragment of Clostridium botulinum type-A neurotoxin BoHc/A administered intranasally with cCHP nanogel (cCHP-BoHc/A) continuously adhered to the nasal epithelium and was effectively taken up by mucosal dendritic cells after its release from the cCHP nanogel. Vigorous botulinum-neurotoxin-A-neutralizing serum IgG and secretory IgA antibody responses were induced without co-administration of mucosal adjuvant. Importantly, intranasally administered cCHP-BoHc/A did not accumulate in the olfactory bulbs or brain. Moreover, intranasally immunized tetanus toxoid with cCHP nanogel induced strong tetanus-toxoid-specific systemic and mucosal immune responses. These results indicate that cCHP nanogel can be used as a universal protein-based antigen-delivery vehicle for adjuvant-free intranasal vaccination.

  20. [Resected non-small cell bronchogenic carcinoma stage pIIIA-N2. Which patients will benefit most from adjuvant therapy?].

    Science.gov (United States)

    Gómez, Ana M; Jarabo, José Ramón; Fernandez, Cristina; Calatayud, Joaquín; Fernández, Elena; Torres, Antonio J; Balibrea, José L; Hernando, Florentino

    2014-04-01

    Controversy persists as regards the indications and results of surgery in the treatment of patients with stage pIIIA-N2 non-small cell lung cancer (NSCLC). The objective of this study was to analyze the overall survival of a multicentre series of these patients and the role of adjuvant treatment, looking for factors that may define subgroups of patients with an increased benefit from this treatment. A retrospective study was conducted on 287 patients, with stage pIIIA-N2 NSCLC subjected to complete resection, taken from a multi-institutional database of 2.994 prospectively collected consecutive patients who underwent surgery for lung cancer. Adjuvant treatment was administered in 238 cases (82.9%). Analyses were made of the age, gender, histological type, administration of induction and adjuvant chemotherapy and/or radiation therapy treatments. The 5-year survival was 24%, with a median survival of 22 months. Survival was 26.5% among patients receiving with adjuvant treatment, versus 10.7% for those without it (P=.069). Age modified the effect of adjuvant treatment on survival (interaction P=.049). In patients under 70 years of age with squamous cell carcinoma, adjuvant treatment reduced the mortality rate by 37% (hazard ratio: 0,63; 95% CI; 0,42-0,95; P=.036). Completely resected patients with stage pIIIA-N2 NSCLC receiving adjuvant treatment reached higher survival rates than those who did not. Maximum benefit was achieved by the subgroup of patients under 70 years of age with squamous cell carcinoma. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

  1. Stadium IB - IIA cervical cancer patient’s survival rate after receiving definitive radiation and radical operation therapy followed by adjuvant radiation therapy along with analysis of factors affecting the patient’s survival rate

    Science.gov (United States)

    Ruslim, S. K.; Purwoto, G.; Widyahening, I. S.; Ramli, I.

    2017-08-01

    To evaluate the characteristics and overall survival rates of early stage cervical cancer (FIGO IB-IIA) patients who receive definitive radiation therapy and those who are prescribed adjuvant postoperative radiation and to conduct a factors analysis of the variables that affect the overall survival rates in both groups of therapy. The medical records of 85 patients with cervical cancer FIGO stages IB-IIA who were treated at the Department of Radiotherapy of Cipto Mangunkusumo Hospital were reviewed and analyzed to determine their overall survival and the factors that affected it between a definitive radiation group and an adjuvant postoperative radiation group. There were 25 patients in the definitive radiation and 60 patients in the adjuvant radiation group. The overall survival rates in the adjuvant radiation group at years one, two, and three were 96.7%, 95%, and 93.3%, respectively. Negative lymph node metastasis had an average association with overall survival (p 12 g/dl was a factor with an average association with the overall survival (p cervical cancer FIGO stage IB-IIA patients who received definitive radiation or adjuvant postoperative radiation. Negative lymph node metastasis had an effect on the overall survival rate in the adjuvant postoperative radiation group, while a preradiation Hb level >12 g/dl tended to affect the overall survival in the definitive radiation group patients.

  2. Systemic therapy for patients with colorectal cancer

    DEFF Research Database (Denmark)

    Pfeiffer, Per; Qvortrup, Camilla; Tabernero, Josep

    2015-01-01

    and 10–15 % in stage III. Targeted therapy is not recommended in the adjuvant setting. Treatment options in patients with non- resectable CRC are based on the extent of disease (resectable/potential resectable/non-resectable) and symptoms. Surgery fi rst or chemotherapy fi rst in patients...

  3. Triterpenoids from Ocimum labiatum Activates Latent HIV-1 Expression In Vitro: Potential for Use in Adjuvant Therapy

    Directory of Open Access Journals (Sweden)

    Petrina Kapewangolo

    2017-10-01

    Full Text Available Latent HIV reservoirs in infected individuals prevent current treatment from eradicating infection. Treatment strategies against latency involve adjuvants for viral reactivation which exposes viral particles to antiretroviral drugs. In this study, the effect of novel triterpenoids isolated from Ocimum labiatum on HIV-1 expression was measured through HIV-1 p24 antigen capture in the U1 latency model of HIV-1 infection and in peripheral blood mononuclear cells (PBMCs of infected patients on combination antiretroviral therapy (cART. The mechanism of viral reactivation was determined through the compound’s effect on cytokine production, histone deacetylase (HDAC inhibition, and protein kinase C (PKC activation. Cytotoxicity of the triterpenoids was determined using a tetrazolium dye and flow cytometry. The isolated triterpene isomers, 3-hydroxy-4,6a,6b,11,12,14b-hexamethyl-1,2,3,4,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-octadecahydropicene-4,8a-dicarboxylic acid (HHODC, significantly (p < 0.05 induced HIV-1 expression in a dose-dependent manner in U1 cells at non-cytotoxic concentrations. HHODC also induced viral expression in PBMCs of HIV-1 infected patients on cART. In addition, the compound up-regulated the production of interleukin (IL-2, IL-6, tumour necrosis factor (TNF-α, and interferon (IFN-γ but had no effect on HDAC and PKC activity, suggesting cytokine upregulation as being involved in latency activation. The observed in vitro reactivation of HIV-1 introduces the adjuvant potential of HHODC for the first time here.

  4. Indocyanine green (ICG) as a new adjuvant for the antimicrobial photo-dynamic therapy (aPDT) in dentistry

    Science.gov (United States)

    Meister, Joerg; Hopp, Michael; Schäfers, Johannes; Verbeek, Jonas; Kraus, Dominik; Frentzen, Matthias

    2014-02-01

    Clinical surveys show a continuous increase of antimicrobial resistance related to the frequency of the administrated medication. The antimicrobial photodynamic therapy (aPDT) is an effective adjuvant to reduce the need of antibiotics in dentistry, especially in periodontics. The antimicrobial effect of lightactivated photosensitizers in periodontics is demonstrated in clinical studies and case reports. Indocyanine green (ICG) as a new adjuvant shows the high potential of antiphlogistic and antimicrobial effects in combination with laser-light activation. In trying to answer the question of just how far the influence of temperature is acting on bacteria, this study was carried out. The influences of ICG at different concentrations (0.01 up to 1 mg/ml) in combination with a culture medium (brain-heart-infusion) and a bacteria culture (Streptococcus salivarius) at different optical densities (OD600 0.5 and 0.1) were investigated under laser-light activation. Laser activation was carried out with diode laser at 810 nm and two different power settings (100 mW/300 mW). The pulse repetition rate was 2 kHz. Taking account of the fiber diameter, distance and spot size on the sample surface, the applicated intensities were 6.2 and 18.7 W/cm2. Total irradiation time was 20 s for all meaurements. Transmitted laser power and temperature increase in the culture medium as well as in the bacteria culture were determined. Additionally the influence of ICG regarding bacterial growth and bactericidal effect was investigated in the bacteria culture without laser irradiation. Without laser, no bactericidal effect of ICG was observed. Only a bacteriostatic effect could be proved. In dependence of the ICG concentration and the applied intensities a temperature increase of ΔT up to 80°C was measured.

  5. Extended adjuvant endocrine therapy in hormone dependent breast cancer: the paradigm of the NCIC-CTG MA.17/BIG 1-97 trial.

    Science.gov (United States)

    Higgins, Michaela J; Liedke, Pedro E R; Goss, Paul E

    2013-04-01

    Early hormone-receptor-positive breast cancer is a chronic relapsing disease that can remain clinically silent for many years. The NCIC-CTG MA.17/BIG 1-97 trial randomized disease-free early breast cancer patients who had received five years of adjuvant tamoxifen to either letrozole or placebo and was the first to demonstrate a benefit with extended endocrine therapy. MA.17/BIG 1-97 was stopped at the first interim analysis because disease free survival was strongly prolonged in the letrozole arm. Subsequent subset analyses and longer follow up have shown that this therapy improved survival across all groups, particularly among women with node-positive disease and those that were pre-menopausal at time of study enrolment. The MA.17/BIG 1-97 study should be considered a paradigm for extended adjuvant endocrine therapy in hormone-receptor-positive early breast cancer. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  6. The influence of endocrine effects of adjuvant therapy on quality of life outcomes in younger breast cancer survivors.

    Science.gov (United States)

    Knobf, M Tish

    2006-02-01

    There are 2.2 million breast cancer survivors, and approximately 25%-30% of newly diagnosed women each year are quality of that survival is influenced by persistent and late effects of therapy. Knowledge of treatment outcomes will assist in the design of interventions to prevent or manage persistent and late effects in survivors. The purpose of this paper is to review the incidence of gonadal toxicity associated with adjuvant chemotherapy, side effects of endocrine therapy, quality of life outcomes, fertility concerns, and options to preserve fertility in young (cancer survivors. Alkylating agent-based chemotherapy causes destruction of primordial follicles and impairment of follicular maturation resulting in temporary preservation of menses, reversible amenorrhea, irregular menses (perimenopause), or irreversible amenorrhea (ovarian failure--menopause). Younger women have a lower risk for amenorrhea with chemotherapy because of sufficient follicular stores, although the gonadal toxicity will result in an earlier than expected menopause. Premature menopause is associated with poorer quality of life, decreased sexual functioning, menopausal symptom distress, psychosocial distress related to fertility concerns, infertility, and uncertainty about late effects of premature menopause. Routine discussion about the menopausal experience, risks for infertility, and fertility preservation options is recommended. This review identified adverse treatment outcomes for young and young midlife breast cancer survivors that can be minimized or prevented with targeted interventions.

  7. Adjuvant chemotherapy is associated with improved survival after esophagectomy without induction therapy for node-positive adenocarcinoma.

    Science.gov (United States)

    Speicher, Paul J; Englum, Brian R; Ganapathi, Asvin M; Mulvihill, Michael S; Hartwig, Matthew G; Onaitis, Mark W; D'Amico, Thomas A; Berry, Mark F

    2015-01-01

    This study investigated adjuvant chemotherapy (AC) use after esophagectomy without induction therapy for node-positive (pN+) adenocarcinoma using the National Cancer Database, including the impact of complications related to surgery (CRS) on outcomes. Predictors of AC use in 1694 patients in the National Cancer Data Base who underwent R0 esophagectomy from 2003-2011 without induction therapy for pN+ adenocarcinoma of the middle or lower esophagus and survived more than 30 days were identified with multivariable logistic regression. The impact of AC on survival was estimated using Kaplan-Meier and Cox-proportional hazards methods. AC was given to 874 of 1694 (51.6%) patients; 618 (70.7%) AC patients received radiation. Older age (adjusted odds ratio [AOR] 0.58/decade, p improved survival in multivariate analysis (hazard ratio 0.67, p = 0.008). Receiving radiation in addition to AC did not improve survival (p = 0.35). Although CRS was associated with worse survival, patients who had CRS but received AC had superior survival compared to patients who did not have CRS or get AC (p = 0.016). AC after esophagectomy is associated with improved survival but was only used in half of patients with pN+ esophageal adenocarcinoma. We also found that the addition of radiation to AC was not associated with a survival benefit. CRS predict worse long-term survival and lower the chance of getting AC, but even patients with CRS had improved survival when given AC.

  8. Bcl-2 inhibitor uploaded upconversion nanophotosensitizers to overcome the photodynamic therapy resistance of cancer through adjuvant intervention strategy.

    Science.gov (United States)

    Liu, Xiaomin; Fan, Zhongqi; Zhang, Li; Jin, Zheng; Yan, Dongmei; Zhang, Youlin; Li, Xiaodan; Tu, Langping; Xue, Bin; Chang, Yulei; Zhang, Hong; Kong, Xianggui

    2017-11-01

    Similar to many other anticancer therapies, photodynamic therapy (PDT) also suffers from the intrinsic cancer resistance mediated by cell survival pathways. These survival pathways are regulated by various proteins, among which anti-apoptotic protein Bcl-2 plays an important role in regulation of programmed cell death and has been proved to involve in protecting against oxidative stimuli. Confronted by this challenge, we propose and validate here a novel upconversion photosensitizing nanoplatform which enables significant reduction of cancer resistance and improve PDT efficacy. The upconversion nanophotosensitizer contains the photosensitizing molecules - Zinc phthalocyanine (ZnPc) and Bcl-2 inhibitor - ABT737 small molecules, denoted as ABT737@ZnPc-UCNPs. ABT737 molecules were encapsulated, in a pH sensitive way, into the nanoplatform through Poly (ethylene glycol)-Poly (l-histidine) diblock copolymers (PEG-b-PHis). This nanosystem exhibits the superiority of sensitizing tumor cells for PDT through adjuvant intervention strategy. Upon reaching to lysosomes, the acidic environment changes the solubility of PEG-b-PHis, resulting in the burst-release of ABT737 molecules which deplete the Bcl-2 level in tumor cells and leave the tumor cells out from the protection of anti-apoptotic survival pathway in advance. Owing to the sensitization effect of ABT737@ZnPc-UCNPs, the PDT therapeutic efficiency of cancer cells can be significantly potentiated in vitro and in vivo. Copyright © 2017. Published by Elsevier Ltd.

  9. New Natural Pigment Fraction Isolated from Saw Palmetto: Potential for Adjuvant Therapy of Hepatocellular Carcinoma.

    Science.gov (United States)

    Tan, Hor-Yue; Wang, Ning; Takahashi, Masao; Feng, Yigang; Li, Hongyun; Feng, Yibin

    2016-08-05

    For the first time, we discovered a small proportion of aqueous fraction from Saw Palmetto apart from the fatty acid-rich fraction exhibited pharmacological activity. Therefore, this study aims to explore the anti-tumor potential of red pigmented aqueous fraction of Saw Palmetto, NYG on human hepatocellular carcinoma and its possible targets. Subcutaneous xenograft and orthotopic implantation models of HCC were used to evaluate the tumor inhibitory effect of NYG. Human hepatocellular carcinoma (HCC) cell lines and human umbilical vein endothelial cells (HUVEC) were used as in vitro model. The mRNA expression was conducted by qPCR. Protein expression was monitored by immunoblotting and immunohistochemistry. Cell migration and blood vessel formation were determined by chamber assay and tube formation assay, respectively. Significant tumor inhibition of NYG in dose-dependent manner was observed on subcutaneous xenograft and orthotopic HCC model. NYG has no direct action on cell viability or VEGF secretion of HCC cells. However, NYG reduced in vitro migration and vessel formation activities of HUVEC cells, as well as in vivo intratumoral neovascularization. NYG attenuated extracellular signal-regulated kinases (ERK) activation in endothelial cells, which may be associated with the suppression of migration and tube formation of HUVEC. NYG suppressed tumor expansion of HCC via inhibiting neovascularization, and may be potential adjuvant treatment for HCC.

  10. New Natural Pigment Fraction Isolated from Saw Palmetto: Potential for Adjuvant Therapy of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Hor-Yue Tan

    2016-08-01

    Full Text Available For the first time, we discovered a small proportion of aqueous fraction from Saw Palmetto apart from the fatty acid-rich fraction exhibited pharmacological activity. Therefore, this study aims to explore the anti-tumor potential of red pigmented aqueous fraction of Saw Palmetto, NYG on human hepatocellular carcinoma and its possible targets. Subcutaneous xenograft and orthotopic implantation models of HCC were used to evaluate the tumor inhibitory effect of NYG. Human hepatocellular carcinoma (HCC cell lines and human umbilical vein endothelial cells (HUVEC were used as in vitro model. The mRNA expression was conducted by qPCR. Protein expression was monitored by immunoblotting and immunohistochemistry. Cell migration and blood vessel formation were determined by chamber assay and tube formation assay, respectively. Significant tumor inhibition of NYG in dose-dependent manner was observed on subcutaneous xenograft and orthotopic HCC model. NYG has no direct action on cell viability or VEGF secretion of HCC cells. However, NYG reduced in vitro migration and vessel formation activities of HUVEC cells, as well as in vivo intratumoral neovascularization. NYG attenuated extracellular signal-regulated kinases (ERK activation in endothelial cells, which may be associated with the suppression of migration and tube formation of HUVEC. NYG suppressed tumor expansion of HCC via inhibiting neovascularization, and may be potential adjuvant treatment for HCC.

  11. Current treatment of early breast cancer: adjuvant and neoadjuvant therapy [v1; ref status: indexed, http://f1000r.es/3l2

    Directory of Open Access Journals (Sweden)

    Elizabeth Miller

    2014-08-01

    Full Text Available Breast cancer is the most commonly diagnosed cancer in women. The latest world cancer statistics calculated by the International Agency for Research on Cancer (IARC revealed that 1,677,000 women were diagnosed with breast cancer in 2012 and 577,000 died. The TNM classification of malignant tumor (TNM is the most commonly used staging system for breast cancer. Breast cancer is a group of very heterogeneous diseases. The molecular subtype of breast cancer carries important predictive and prognostic values, and thus has been incorporated in the basic initial process of breast cancer assessment/diagnosis. Molecular subtypes of breast cancers are divided into human epidermal growth factor receptor 2 positive (HER2 +, hormone receptor positive (estrogen or progesterone +, both positive, and triple negative breast cancer. By virtue of early detection via mammogram, the majority of breast cancers in developed parts of world are diagnosed in the early stage of the disease. Early stage breast cancers can be completely resected by surgery. Over time however, the disease may come back even after complete resection, which has prompted the development of an adjuvant therapy. Surgery followed by adjuvant treatment has been the gold standard for breast cancer treatment for a long time. More recently, neoadjuvant treatment has been recognized as an important strategy in biomarker and target evaluation. It is clinically indicated for patients with large tumor size, high nodal involvement, an inflammatory component, or for those wish to preserve remnant breast tissue. Here we review the most up to date conventional and developing treatments for different subtypes of early stage breast cancer.

  12. Two different durations of adjuvant therapy with intermediate-dose interferon alfa-2b in patients with high-risk melanoma (Nordic IFN trial): a randomised phase 3 trial

    DEFF Research Database (Denmark)

    Hansson, Johan; Aamdal, Steinar; Bastholt, Lars

    2011-01-01

    Adjuvant high-dose interferon alfa-2b improves relapse-free survival (RFS) in patients with high-risk melanoma, although benefits in overall survival are uncertain. Because of the toxic effects of high-dose regimens, intermediate doses are being explored. We investigated whether adjuvant therapy...

  13. Adjuvant therapy of Dukes' C colon cancer by intra-arterial P-32 colloid for internal radiation therapy of the liver

    Energy Technology Data Exchange (ETDEWEB)

    Grady, E.D.

    1984-09-01

    To prevent probable occult metastatic liver cancer from progressing to clinical disease, the author used internal radiation therapy as an effective adjuvant to surgical excision of primary Dukes' C colonic cancer. A calculated radiation dose of 5000 rads was delivered to the liver by injecting radioactive 32-P chromic phosphate colloid through the superior mesenteric and celiac arteries. When this was done, the colloid passed through the intestines and was mixed thoroughly with the blood and delivered to the liver by the portal vein. The Kupffer cells in the liver trapped the colloid, and a minimum amount passed through the liver and got into the general circulation. This kept the amount of colloid deposited in the bone marrow to a minimum. In a phase-I pilot study in which nine patients were treated, no serious side effects were noted. In eight patients, the liver has remained free of cancer for more than 1 year.

  14. [Clonidine as adjuvant therapy for alcohol withdrawal syndrome in intensive care unit: case report.].

    Science.gov (United States)

    Braz, Leandro Gobbo; Camacho Navarro, Lais Helena; Braz, José Reinaldo Cerqueira; Silva, Ubirajara Teixeira da; Yamaguti, Fábio Akio; Cristovan, José Carlos

    2003-12-01

    Sedation of patients with past history of alcohol and drug abuse in Intensive Care Units (ICU) is a challenge due to the high incidence of sedative drugs tolerance and withdrawal syndromes. This report aimed at describing a case of a young patient admitted to the ICU who developed alcohol withdrawal syndrome and tolerance to sedatives, resolved only after clonidine administration. Male patient, 18 years old, alcohol, tobacco, cocaine and marijuana abuser, victim of firearm accident, who was admitted to the ICU in the first post-enterectomy day, after gastric content aspiration during tracheal re-intubation. Clinical evolution was: vasoactive drugs up to the 4th day; bilateral bronchopneumonia with pleural effusion and need for artificial ventilation up to the 15th day. Initial sedation scheme was the association of midazolam and fentanyl. As from the 4th day, patient presented with several psychomotor agitation episodes, even after the association of lorazepam in the 6th day. In the 9th day, patient received the largest doses but remained agitated. Dexmedetomidine was associated, which has decreased other drug doses in 35% and has improved agitation. In the 12th day, midazolam and dexmedetomidine were replaced by propofol infusion with worsening of agitation. In the 13th day, clonidine was associated to the sedation scheme with total resolution of agitation. Propofol was withdrawn in the 14th day, fentanyl was maintained and midazolam infusion was restarted, with doses 75% and 65% lower as compared to peak doses of such drugs. Patient was extubated in the 15th day and was discharged from ICU. Benzodiazepines should remain the drugs of choice for the treatment of acute alcohol withdrawal syndrome. However in this report, only adjuvant clonidine was able to adequately treat the patient.

  15. The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma.

    Directory of Open Access Journals (Sweden)

    Mohammed G Abdelwahab

    Full Text Available INTRODUCTION: The ketogenic diet (KD is a high-fat, low-carbohydrate diet that alters metabolism by increasing the level of ketone bodies in the blood. KetoCal® (KC is a nutritionally complete, commercially available 4:1 (fat:carbohydrate+protein ketogenic formula that is an effective non-pharmacologic treatment for the management of refractory pediatric epilepsy. Diet-induced ketosis causes changes to brain homeostasis that have potential for the treatment of other neurological diseases such as malignant gliomas. METHODS: We used an intracranial bioluminescent mouse model of malignant glioma. Following implantation animals were maintained on standard diet (SD or KC. The mice received 2×4 Gy of whole brain radiation and tumor growth was followed by in vivo imaging. RESULTS: Animals fed KC had elevated levels of β-hydroxybutyrate (p = 0.0173 and an increased median survival of approximately 5 days relative to animals maintained on SD. KC plus radiation treatment were more than additive, and in 9 of 11 irradiated animals maintained on KC the bioluminescent signal from the tumor cells diminished below the level of detection (p<0.0001. Animals were switched to SD 101 days after implantation and no signs of tumor recurrence were seen for over 200 days. CONCLUSIONS: KC significantly enhances the anti-tumor effect of radiation. This suggests that cellular metabolic alterations induced through KC may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas.

  16. Cognitive function and discontinuation of adjuvant hormonal therapy in older breast cancer survivors: CALGB 369901 (Alliance).

    Science.gov (United States)

    Bluethmann, Shirley M; Alfano, Catherine M; Clapp, Jonathan D; Luta, George; Small, Brent J; Hurria, Arti; Cohen, Harvey J; Sugarman, Steven; B Muss, Hyman; Isaacs, Claudine; Mandelblatt, Jeanne S

    2017-10-01

    To investigate the effects of cognitive function on discontinuation of hormonal therapy in breast cancer survivors ages 65+ ("older"). Older breast cancer survivors with invasive, non-metastatic disease, and no reported cognitive difficulties were recruited from 78 Alliance sites between 2004 and 2011. Eligible survivors (n = 1280) completed baseline interviews; follow-up was conducted annually for up to 7 years. Survivors with estrogen-receptor-positive (ER+) cancers who initiated hormonal therapy (n = 990) were included. Self-reported cognitive function was measured using the EORTC-QLQ30 scale; a difference of eight points on the 0-100 scale was considered clinically significant. Based on varying rates of discontinuation over time, discontinuation was evaluated separately for three time periods: early (3-5 years). Cox models for each time period were used to evaluate the effects of cognition immediately preceding discontinuation, controlling for age, chemotherapy, and other covariates. Survivors were 65-91 years old (mean 72.6 years), and 79% had stages 1 or 2A disease. Overall, 43% discontinued hormonal therapy before 5 years. Survivors who reported lower cognitive function in the period before discontinuation had greater hazards of discontinuing therapy at the treatment midpoint (HR 1.22 per 8-point difference, CI 1.09-1.40, p cognition was not related to discontinuation in the other periods. Self-reported cognitive problems were a significant risk factor for discontinuation of hormonal therapy 1-3 years post-initiation. Additional research is needed on the temporality of cognitive effects and hormonal therapy to support survivorship care needs of older survivors.

  17. Polydeoxyribonucleotide Dermal Infiltration in Male Genital Lichen Sclerosus: Adjuvant Effects during Topical Therapy

    Directory of Open Access Journals (Sweden)

    Luigi Laino

    2013-01-01

    Full Text Available Background. Lichen sclerosus (LS is an autoimmune inflammatory skin disease that leads to tissue sclerosis. Actually, the first-line treatment consists of local steroid as clobetasol propionate (CP. Polydeoxyribonucleotide (PDRN has demonstrated anti-inflammatory effects through the reduction of cytokine production and growth stimulation of fibroblast. Objective. To evaluate the efficacy of intradermal administration of PDRN in male patients suffering from genital lichen sclerosus in addition to topical 0.05% CP, as compared to administering 0.05% CP without PDRN injection. Patients/Methods. A group of male patients (n = 28; aged 25 to 65 suffering from LS were observed during topical therapy or subdermal in addition to topical therapy. Disease activity at baseline was evaluated on Investigator’s Global Assessment (IGA and the Dermatology Life Quality Index (DLQI. We used polydeoxyribonucleotide in a commercial preparation for human use and a topical CP emulsion. Results. After therapy, in all group A patients there has been a regression of most of clinical pathological signs, while there has been a moderate improvement in all group B patients. Conclusions. On site intradermal administration of PDRN, associated with CP 0.05% cream, seemed to be associated with a clinical improvement of lichen sclerosus better than CP used in single therapy.

  18. Adjuvant photodynamic therapy in head and neck cancer after tumor-positive resection margins

    NARCIS (Netherlands)

    van Doeveren, Thérèse E. M.; Karakullukçu, M. Barış; van Veen, Robert L. P.; Lopez-Yurda, Marta; Schreuder, Willem H.; Tan, I. Bing

    2017-01-01

    In case of close or positive resection margins after oncological resection in head and neck surgery, additional treatment is necessary. When conventional options are exhausted, photodynamic therapy (PDT) can play a role in achieving clear margins. The purpose of the current study was to evaluate the

  19. Adjuvant occupational therapy for work-related major depression works: randomized trial including economic evaluation

    NARCIS (Netherlands)

    Schene, Aart H.; Koeter, Maarten W. J.; Kikkert, Martijn J.; Swinkels, Jan A.; McCrone, Paul

    2007-01-01

    BACKGROUND: Major depression has far-reaching consequences for work functioning and absenteeism. In most cases depression is treated by medication and clinical management. The addition of occupational therapy (OT) might improve outcome. We determined the cost-effectiveness of the addition of OT to

  20. TERT promoter mutations contribute to IDH mutations in predicting differential responses to adjuvant therapies in WHO grade II and III diffuse gliomas.

    Science.gov (United States)

    Zhang, Zhen-Yu; Chan, Aden Ka-Yin; Ding, Xiao-Jie; Qin, Zhi-Yong; Hong, Christopher S; Chen, Ling-Chao; Zhang, Xin; Zhao, Fang-Ping; Wang, Yin; Wang, Yang; Zhou, Liang-Fu; Zhuang, Zhengping; Ng, Ho-Keung; Yan, Hai; Yao, Yu; Mao, Ying

    2015-09-22

    IDH mutations frequently occur in WHO grade II and III diffuse gliomas and have favorable prognosis compared to wild-type tumors. However, whether IDH mutations in WHO grade II and II diffuse gliomas predict enhanced sensitivity to adjuvant radiation (RT) or chemotherapy (CHT) is still being debated. Recent studies have identified recurrent mutations in the promoter region of telomerase reverse transcriptase (TERT) in gliomas. We previously demonstrated that TERT promoter mutations may be promising biomarkers in glioma survival prognostication when combined with IDH mutations. This study analyzed IDH and TERT promoter mutations in 295 WHO grade II and III diffuse gliomas treated with or without adjuvant therapies to explore their impact on the sensitivity of tumors to genotoxic therapies. IDH mutations were found in 216 (73.2%) patients and TERT promoter mutations were found in 112 (38%) patients. In multivariate analysis, IDH mutations (p IDH and TERT promoter mutations were not significant prognostic factors in patients who did not receive genotoxic therapies. Adjuvant RT and CHT were factors independently impacting PFS (RT p = 0.001, CHT p = 0.026) in IDH mutated WHO grade II and III diffuse gliomas but not in IDH wild-type group. Univariate and multivariate analyses demonstrated TERT promoter mutations further stratified IDH wild-type WHO grade II and III diffuse gliomas into two subgroups with different responses to genotoxic therapies. Adjuvant RT and CHT were significant parameters influencing PFS in the IDH wt/TERT mut subgroup (RT p = 0.015, CHT p = 0.015) but not in the IDH wt/TERT wt subgroup. Our data demonstrated that IDH mutated WHO grade II and III diffuse gliomas had better PFS and OS than their IDH wild-type counterparts when genotoxic therapies were administered after surgery. Importantly, we also found that TERT promoter mutations further stratify IDH wild-type WHO grade II and III diffuse gliomas into two subgroups with different responses to

  1. Adjuvant potential of virgin coconut oil extract on antiretroviral therapy-induced testicular toxicity: An ultrastructural study.

    Science.gov (United States)

    Ogedengbe, O O; Jegede, A I; Onanuga, I O; Offor, U; Peter, A I; Akang, E N; Naidu, E C S; Azu, O O

    2017-12-12

    The effects of Virgin coconut oil as an adjuvant to highly active antiretroviral therapy (HAART) were investigated on the testicular ultrastructure and biochemical markers in rats. Twenty male Sprague-Dawley rats, weighing 153-169 g were divided into four groups and treated as follows: control A (distilled water), B (HAART), C (HAART+Virgin coconut oil 10 ml/kg) and D (Virgin coconut oil [VCO] 10 ml/kg). Testicular segments were evaluated using transmission electron microscopy. Serum was assayed for testosterone, luteinising hormone, follicle stimulating hormone and testicular tissue for malondialdehyde and glutathione. Ultrastructure of basement membrane (Bm), mitochondria and spermatocytes was normal in the control group. HAART-treated group showed significant increase (p coconut oil-treated group showed thinning of Bm with otherwise normal ultrastructural features of organelles. HAART-treated group showed significant increase (p coconut oil improved testicular morphology and reversed HAART-induced ultrastructural alterations. Further studies on putative mechanism are required. © 2017 Blackwell Verlag GmbH.

  2. Inflammation and uPAR-Expression in Colorectal Liver Metastases in Relation to Growth Pattern and Neo-adjuvant Therapy

    DEFF Research Database (Denmark)

    Eefsen, R L; Engelholm, L; Alpizar-Alpizar, W

    2015-01-01

    Proteolytic activity and inflammation in the tumour microenvironment affects cancer progression. In colorectal cancer (CRC) liver metastases it has been observed that three different immune profiles are present, as well as proteolytic activity, determined by the expression of urokinase-type plasm......Proteolytic activity and inflammation in the tumour microenvironment affects cancer progression. In colorectal cancer (CRC) liver metastases it has been observed that three different immune profiles are present, as well as proteolytic activity, determined by the expression of urokinase......-type plasminogen activator (uPAR).The main objectives of this study were to investigate uPAR expression and the density of macrophages (CD68) and T cells (CD3) as markers of inflammation in resected CRC liver metastases, where patients were neo-adjuvantly treated with chemotherapy with or without the angiogenesis...... inhibitor bevacizumab. Chemonaive patients served as a control group. The markers were correlated to growth patterns (GP) of liver metastases, i.e. desmoplastic, pushing and replacement GP. It was hypothesised that differences in proteolysis and inflammation could reflect tumour specific growth and therapy...

  3. Phospholipid bilayer-coated aluminum nanoparticles as an effective vaccine adjuvant-delivery system.

    Science.gov (United States)

    Wang, Ting; Zhen, Yuanyuan; Ma, Xiaoyu; Wei, Biao; Wang, Ning

    2015-04-01

    The phospholipid bilayer-coated aluminum nanoparticles (PLANs), formed via chemisorption, were prepared by reverse ethanol injection-lyophilization (REIL) utilizing the phosphophilicity of aluminum. The anhydrous antigen-loaded PLANs obtained by REIL proved stable, satisfying using the controlled-temperature-chain instead of the integrated cold-chain for distribution, and could be rehydrated to reconstitute instantly an aqueous suspension of the antigen-PLANs, which were more readily taken up by antigen-presenting cells and, when given subcutaneously to mice, induced more robust antigen-specific humoral and cellular immunoresponses but less local inflammation than the antigen-alum. Thus, the PLANs are a useful vaccine adjuvant-delivery system with advantages over the widely used naked alum.

  4. Preoperative chemotherapy for operable breast cancer is associated with better compliance with adjuvant therapy in matched stage II and IIIA patients.

    Science.gov (United States)

    Komenaka, Ian K; Hsu, Chiu-Hsieh; Martinez, Maria Elena; Bouton, Marcia E; Low, Boo Ghee; Salganick, Jason A; Nodora, Jesse; Hibbard, Michael L; Jha, Chandra

    2011-01-01

    Preoperative chemotherapy (PC) for operable breast cancer has shown significant benefits in prospective trials. Many patients are treated in the community setting and some may question the applicability of PC outside the university setting. Retrospective review was performed of stage II and IIIA breast cancer patients treated from January 2002 to July 2009. Fifty-three of 57 patients who underwent PC were matched based on age, tumor size, and hormone receptor status with 53 patients who did not undergo PC. Differences in patient compliance with physician recommendations for all types of adjuvant therapy were evaluated. Crude odds ratios and adjusted odds ratios derived from conditional logistic regression models were calculated. There were 106 patients included. Patient compliance with chemotherapy was better in the PC group than in the adjuvant chemotherapy (AC) group (100% versus 70%; p = .0001). Similarly, more patients in the PC group completed radiation therapy (96% versus 65%; p = .0003) and initiated hormonal therapy (100% versus 62%; p = .0001). Conditional logistic regression revealed that higher pathologic stage and current cigarette smoking were associated with poorer compliance with chemotherapy. For radiation therapy, the univariate model revealed that compliance with chemotherapy and being employed were associated with completion of radiation, whereas current cigarette smoking and larger pathologic size were associated with poorer compliance with radiation. For hormonal therapy, current cigarette smokers were more likely to be noncompliant with initiation of hormonal therapy. PC for operable breast cancer can improve patient compliance with chemotherapy. Current cigarette smokers were more likely to be noncompliant with all types of adjuvant therapy.

  5. A randomised comparison of bicalutamide ('Casodex') 150 mg versus placebo as immediate therapy either alone or as adjuvant to standard care for early non-metastatic prostate cancer. First report from the Scandinavian Prostatic Cancer Group Study No. 6

    DEFF Research Database (Denmark)

    Iversen, P; Tammela, T L J; Vaage, S

    2002-01-01

    To assess the efficacy and tolerability of bicalutamide 150 mg ('Casodex'(1)) as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with early (T1b-T4, any N, M0) prostate cancer.......To assess the efficacy and tolerability of bicalutamide 150 mg ('Casodex'(1)) as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with early (T1b-T4, any N, M0) prostate cancer....

  6. Ozone therapy as an adjuvant for endondontic protocols: microbiological - ex vivo study and citotoxicity analyses.

    Science.gov (United States)

    Nogales, Carlos Goes; Ferreira, Marina Beloti; Montemor, Antonio Fernando; Rodrigues, Maria Filomena de Andrade; Lage-Marques, José Luiz; Antoniazzi, João Humberto

    2016-01-01

    This study evaluated the antimicrobial efficacy of ozone therapy in teeth contaminated with Pseudomonas aeruginosa, Enterococcus faecalis, and Staphylococcus aureus using a mono-species biofilm model. Parallel to this, the study aimed to evaluate the cytotoxicity of ozone for human gingival fibroblasts. Material and Methods: One hundred and eighty single-root teeth were contaminated with a mono-species biofilm of Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus. Groups were formed: Group I - control; Group II - standard protocol; Group III - standard protocol + ozone gas at 40 µg/mL; and Group IV - standard protocol + aqueous ozone at 8 µg/mL. In parallel, human gingival fibroblasts were submitted to the MTT test. Cells were plated, then ozone was applied as follows: Group I (control) - broth medium; Group II - aqueous ozone at 2 µg/mL; Group III - aqueous ozone at 5 µg/mL; and Group IV - aqueous ozone at 8 µg/mL. Data were submitted to the Kruskal Wallis test and Bonferroni post hoc analyses to assess microbiology and cytotoxicity, respectively (pozone therapy improved the decontamination of the root canal ex vivo. Ozone was toxic to the cells on first contact, but cell viability was recovered. Thus, these findings suggest that ozone might be useful to improve root canal results.

  7. Ozone therapy as an adjuvant for endondontic protocols: microbiological – ex vivo study and citotoxicity analyses

    Science.gov (United States)

    NOGALES, Carlos Goes; FERREIRA, Marina Beloti; MONTEMOR, Antonio Fernando; RODRIGUES, Maria Filomena de Andrade; Lage-MARQUES, José Luiz; ANTONIAZZI, João Humberto

    2016-01-01

    ABSTRACT Objectives This study evaluated the antimicrobial efficacy of ozone therapy in teeth contaminated with Pseudomonas aeruginosa, Enterococcus faecalis, and Staphylococcus aureus using a mono-species biofilm model. Parallel to this, the study aimed to evaluate the cytotoxicity of ozone for human gingival fibroblasts. Material and Methods: One hundred and eighty single-root teeth were contaminated with a mono-species biofilm of Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus. Groups were formed: Group I – control; Group II – standard protocol; Group III – standard protocol + ozone gas at 40 µg/mL; and Group IV – standard protocol + aqueous ozone at 8 µg/mL. In parallel, human gingival fibroblasts were submitted to the MTT test. Cells were plated, then ozone was applied as follows: Group I (control) – broth medium; Group II – aqueous ozone at 2 µg/mL; Group III – aqueous ozone at 5 µg/mL; and Group IV – aqueous ozone at 8 µg/mL. Data were submitted to the Kruskal Wallis test and Bonferroni post hoc analyses to assess microbiology and cytotoxicity, respectively (pozone therapy improved the decontamination of the root canal ex vivo. Ozone was toxic to the cells on first contact, but cell viability was recovered. Thus, these findings suggest that ozone might be useful to improve root canal results. PMID:28076466

  8. Ozone therapy as an adjuvant for endondontic protocols: microbiological – ex vivo study and citotoxicity analyses

    Directory of Open Access Journals (Sweden)

    Carlos Goes NOGALES

    Full Text Available ABSTRACT Objectives This study evaluated the antimicrobial efficacy of ozone therapy in teeth contaminated with Pseudomonas aeruginosa, Enterococcus faecalis, and Staphylococcus aureus using a mono-species biofilm model. Parallel to this, the study aimed to evaluate the cytotoxicity of ozone for human gingival fibroblasts. Material and Methods: One hundred and eighty single-root teeth were contaminated with a mono-species biofilm of Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus. Groups were formed: Group I – control; Group II – standard protocol; Group III – standard protocol + ozone gas at 40 µg/mL; and Group IV – standard protocol + aqueous ozone at 8 µg/mL. In parallel, human gingival fibroblasts were submitted to the MTT test. Cells were plated, then ozone was applied as follows: Group I (control – broth medium; Group II – aqueous ozone at 2 µg/mL; Group III – aqueous ozone at 5 µg/mL; and Group IV – aqueous ozone at 8 µg/mL. Data were submitted to the Kruskal Wallis test and Bonferroni post hoc analyses to assess microbiology and cytotoxicity, respectively (p<0.05%. Results The results revealed antimicrobial efficacy by Group IV with no CFU count. The cytotoxicity assay showed Groups III and IV to be the most aggressive, providing a decrease in cell viability at hour 0 from 100% to 77.3% and 68.6%, respectively. Such a decrease in cell viability was reverted, and after 72 hours Groups III and IV provided the greatest increase in cell viability, being statistically different from Groups I and II. Conclusion According to the applied methodology and the limitations of this study, it was possible to conclude that ozone therapy improved the decontamination of the root canal ex vivo. Ozone was toxic to the cells on first contact, but cell viability was recovered. Thus, these findings suggest that ozone might be useful to improve root canal results.

  9. Tumor Metabolism, the Ketogenic Diet and β-Hydroxybutyrate: Novel Approaches to Adjuvant Brain Tumor Therapy.

    Science.gov (United States)

    Woolf, Eric C; Syed, Nelofer; Scheck, Adrienne C

    2016-01-01

    Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD). The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate (βHB) in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma.

  10. Tumor Metabolism, the Ketogenic Diet and β-Hydroxybutyrate: Novel Approaches to Adjuvant Brain Tumor Therapy

    Science.gov (United States)

    Woolf, Eric C.; Syed, Nelofer; Scheck, Adrienne C.

    2016-01-01

    Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD). The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate (βHB) in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma. PMID:27899882

  11. Tumor metabolism, the ketogenic diet and β-hydroxybutyrate: novel approaches to adjuvant brain tumor therapy

    Directory of Open Access Journals (Sweden)

    Eric C. Woolf

    2016-11-01

    Full Text Available Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD. The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma.

  12. Adjuvant radiation therapy in locally advanced non-small cell lung cancer: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based clinical practice guideline.

    Science.gov (United States)

    Rodrigues, George; Choy, Hak; Bradley, Jeffrey; Rosenzweig, Kenneth E; Bogart, Jeffrey; Curran, Walter J; Gore, Elizabeth; Langer, Corey; Louie, Alexander V; Lutz, Stephen; Machtay, Mitchell; Puri, Varun; Werner-Wasik, Maria; Videtic, Gregory M M

    2015-01-01

    To provide guidance to physicians and patients with regard to the use of adjuvant external beam radiation therapy (RT) in locally advanced non-small cell lung cancer (LA NSCLC) based on available medical evidence complemented by consensus-based expert opinion. A panel authorized by the American Society for Radiation Oncology (ASTRO) Board of Directors and Guidelines Subcommittee conducted 2 systematic reviews on the following topics: (1) indications for postoperative adjuvant RT and (2) indications for preoperative neoadjuvant RT. Practice guideline recommendations were approved using an a priori-defined consensus-building methodology supported by ASTRO and approved tools for the grading of evidence quality and the strength of guideline recommendations. For patients who have undergone surgical resection, high-level evidence suggests that use of postoperative RT does not influence survival, but optimizes local control for patients with N2 involvement, and its use in the setting of positive margins or gross primary/nodal residual disease is recommended. No high-level evidence exists for the routine use of preoperative induction chemoradiation therapy; however, modern surgical series and a post-hoc Intergroup 0139 clinical trial analysis suggest that a survival benefit may exist if patients are properly selected and surgical techniques/postoperative care is optimized. A consensus and evidence-based clinical practice guideline for the adjuvant radiotherapeutic management of LA NSCLC has been created addressing 2 important questions. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Adjuvant occupational therapy for work-related major depression works: randomized trial including economic evaluation.

    Science.gov (United States)

    Schene, Aart H; Koeter, Maarten W J; Kikkert, Martijn J; Swinkels, Jan A; McCrone, Paul

    2007-03-01

    Major depression has far-reaching consequences for work functioning and absenteeism. In most cases depression is treated by medication and clinical management. The addition of occupational therapy (OT) might improve outcome. We determined the cost-effectiveness of the addition of OT to treatment as usual (TAU). Sixty-two adults with major depression and a mean absenteeism of 242 days were randomized to TAU (out-patient psychiatric treatment) or TAU+OT [6 months, including (i) diagnostic phase with occupational history and work reintegration plan, and (ii) therapeutic phase with individual sessions and group sessions]. Main outcome domains were depression, work resumption, work stress and costs. Assessments were at baseline and at 3, 6, 12 and 42 months. The addition of OT to TAU: (i) did not improve depression outcome, (ii) resulted in a reduction in work-loss days during the first 18 months, (iii) did not increase work stress, and (iv) had a 75.5% probability of being more cost-effective than TAU alone. Addition of OT to good clinical practice does not improve depression outcome, improves productivity without increasing work stress and is superior to TAU in terms of cost-effectiveness.

  14. Levetiracetam Extended Release as Adjuvant Therapy for the Control of Partial-onset Seizures

    Directory of Open Access Journals (Sweden)

    Hasan H. Sonmezturk

    2011-01-01

    Full Text Available Extended release (XR formulation of levetiracetam (LEV is approved by the Food and Drug Administration as an add-on to other antiepileptic drugs (AEDs for adults with partial onset seizures. This is based on class-I evidence demonstrating significant seizure reduction in once daily dosing. Keppra-XR is marketed with the brand name of Keppra XR since 2008 (UCB Pharma. Its original immediate release (IR formulation has been in the market since 2000. LEV has a unique molecular structure which is chemically unrelated to existing AEDs. The precise mechanism of action is unknown. Animal studies showed binding to synaptic vesicle protein SV2A, thought to be involved in modulating synaptic neurotransmitter release. LEV-IR is proven effective as adjunctive therapy for partial-onset seizures, primary generalized tonic-clonic seizures and myoclonic seizures. It was shown to be equivalent to carbamazepine as first-line treatment for partial-onset seizures. The extended release formulation added advantages such as better tolerance and increased compliance.

  15. Adjuvant use of acoustic pressure wound therapy for treatment of chronic wounds: a retrospective analysis.

    Science.gov (United States)

    Cole, Pamela S; Quisberg, Jennifer; Melin, M Mark

    2009-01-01

    Small studies have indicated that the addition of acoustic pressure wound therapy (APWT) to conventional wound care may hasten healing of chronic wounds. We evaluated our early clinical experience using APWT as an adjunct to conventional wound care. The study was a retrospective chart review of consecutive patients receiving APWT in addition to conventional wound care in a hospital-based, primarily outpatient setting. Medical records of all patients treated with APWT between August 2006 and October 2007 were reviewed. Analysis included the 41 patients with 52 wounds who received APWT at least 2 times per week during the study period. Statistical comparisons were made for wound dimensions, tissue characteristics, and pain at start versus end of APWT. Thirty-eight percent of wounds (N = 20) healed completely with a mean 6.8 weeks of APWT. Median wound area and volume decreased significantly (88% [P wounds with greater than 75% granulation tissue increased from 26% (n = 12) to 80% (n = 41) (P wounds (P = .006). This early experience supplementing conventional wound care with APWT suggests it may promote healing in chronic wounds, where the ordered cellular and molecular processes leading to healing have stalled.

  16. The role of imatinib mesylate in adjuvant therapy of extra-abdominal desmoid tumors.

    Science.gov (United States)

    Ioannou, Markos; Demertzis, Nikolaos; Iakovidou, Ioanna; Kottakis, Stamatios

    2007-01-01

    Extra-abdominal desmoid tumors are rare neoplasms with variable biological behavior. The mainstay of treatment is surgery. Complementary treatment with tyrosine-kinase receptor inhibitor drugs, particularly imatinib mesylate, has been reported in the literature. The purpose of this study was to determine the possible presence of tyrosine-kinase receptors in extra-abdominal desmoid tumors as a marker for imatinib mesylate therapy. From 1999 to 2004, immunohistochemical methods were carried-out in 14 patients with histologically confirmed extra-abdominal desmoid tumors to determine c-KIT positivity (existence of tyrosine-kinase receptors and PDGFRA and PDGFRB). All desmoid tumors were c-KIT negative, which demonstrates absence of tyrosine-kinase receptors. The histological c-KIT markup is an easy and reliable method that can detect whether a desmoid tumor is sensitive to additional treatment with a tyrosine-kinase receptor inhibitor. Molecular biological analysis for the identification of KIT and PDGFR mutation should be performed before imatinib mesylate is included in any treatment protocol.

  17. Ginkgo biloba: An adjuvant therapy for progressive normal and high tension glaucoma

    Science.gov (United States)

    Cybulska-Heinrich, A.K.; Mozaffarieh, M.

    2012-01-01

    Gingko biloba has been used for hundreds of years to treat various disorders such as asthma, vertigo, fatigue and, tinnitus or circulatory problems. Two of the main extracts are EGb761 and LI 1370. Most pharmacological, toxicological and clinical studies have focused on the neuroprotective value of these two main extracts. Neuroprotection is a rapidly expanding area of research. This area is of particular interest due to the fact that it represents a new avenue of therapy for a frustrating disease that may progress despite optimal treatment. One such disease is glaucoma. Glaucoma leads to the loss of retinal ganglion cells and their axons but also to tissue remodelling which involves both the optic nerve head and the retina. In the retina the astrocytes get activated. In addition, the optic nerve gets thinner and the cells of the lateral geniculate ganglion disappear partially. On average, ocular blood flow (OBF) is reduced in glaucoma patients in various tissues of the eye. Increased intraocular pressure (IOP) is a major risk factor for glaucomatous damage. Nevertheless, there is little doubt that other risk factors besides IOP are involved. One such risk factor is a primary vascular dysregulation (PVD) occurring in patients with a disturbed autoregulation, another risk factor is oxidative stress. PMID:22355250

  18. Adjuvant radiation therapy is associated with better oncological outcome compared with salvage radiation therapy in patients with pN1 prostate cancer treated with radical prostatectomy.

    Science.gov (United States)

    Tilki, Derya; Preisser, Felix; Tennstedt, Pierre; Tober, Patrick; Mandel, Philipp; Schlomm, Thorsten; Steuber, Thomas; Huland, Hartwig; Schwarz, Rudolf; Petersen, Cordula; Graefen, Markus; Ahyai, Sascha

    2017-05-01

    To analyse the comparative effectiveness of no treatment (NT) or salvage radiation therapy (sRT) at biochemical recurrence (BCR) vs adjuvant radiation therapy (aRT) in patients with lymph node (LN)-positive prostate cancer (PCa) after radical prostatectomy (RP). A total of 773 patients with LN-positive PCa at RP, with or without additional radiation therapy (RT), in the period 2005-2013, were retrospectively analysed. Cox regression analysis was used to assess factors influencing BCR and metastasis-free survival (MFS). Propensity score-matched analyses were performed. The median follow-up for the entire patient group was 33.8 months. Four-year BCR-free and MFS rates were 43.3% and 86.6%, respectively, for all patients. In multivariate analysis, NT/sRT (n = 505) was an independent risk factor for BCR and metastasis compared with aRT (n = 213). The superiority of aRT was confirmed after propensity score matching. The 4-year MFS in the matched cohort was 82.5% vs 91.8% for the NT/sRT and aRT groups, respectively (P = 0.02). Early sRT (pre-RT prostate-specific antigen [PSA] ≤0.5 ng/mL) compared with sRT at PSA >0.5 ng/mL was significantly associated with a lower risk of metastasis. Patients with LN-positive PCa who received aRT had a significantly better oncological outcome than patients with NT/sRT, independent of tumour characteristics. Patients with early sRT had higher rates of response and better MFS than patients with pre-RT PSA >0.5 ng/mL. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

  19. Curcumin Induces EGFR Degradation in Lung Adenocarcinoma and Modulates p38 Activation in Intestine: The Versatile Adjuvant for Gefitinib Therapy

    Science.gov (United States)

    Lee, Jen-Yi; Lee, Yee-Ming; Chang, Gee-Chen; Yu, Sung-Liang; Hsieh, Wan-Yu; Chen, Jeremy J. W.; Chen, Huei-Wen; Yang, Pan-Chyr

    2011-01-01

    Background Non-small cell lung cancer (NSCLC) patients with L858R or exon 19 deletion mutations in epidermal growth factor receptor (EGFR) have good responses to the tyrosine kinase inhibitor (TKI), gefitinib. However, patients with wild-type EGFR and acquired mutation in EGFR T790M are resistant to gefitinib treatment. Here, we showed that curcumin can improve the efficiency of gefitinib in the resistant NSCLC cells both in vitro and in vivo models. Methods/Principal Findings After screening 598 herbal and natural compounds, we found curcumin could inhibit cell proliferation in different gefitinib-resistant NSCLC cell lines; concentration-dependently down-regulate EGFR phosphorylation through promoting EGFR degradation in NSCLC cell lines with wild-type EGFR or T790M EGFR. In addition, the anti-tumor activity of gefitinib was potentiated via curcumin through blocking EGFR activation and inducing apoptosis in gefitinib-resistant NSCLC cell lines; also the combined treatment with curcumin and gefitinib exhibited significant inhibition in the CL1-5, A549 and H1975 xenografts tumor growth in SCID mice through reducing EGFR, c-MET, cyclin D1 expression, and inducing apoptosis activation through caspases-8, 9 and PARP. Interestingly, we observed that the combined treatment group represented better survival rate and less intestinal mucosal damage compare to gefitinib-alone therapy. We showed that curcumin attenuated the gefitinib-induced cell proliferation inhibition and apoptosis through altering p38 mitogen-activated protein kinase (MAPK) activation in intestinal epithelia cell. Conclusions/Significance Curcumin potentiates antitumor activity of gefitinib in cell lines and xenograft mice model of NSCLC through inhibition of proliferation, EGFR phosphorylation, and induction EGFR ubiquitination and apoptosis. In addition, curcumin attenuates gefitinib-induced gastrointestinal adverse effects via altering p38 activation. These findings provide a novel treatment strategy

  20. Curcumin induces EGFR degradation in lung adenocarcinoma and modulates p38 activation in intestine: the versatile adjuvant for gefitinib therapy.

    Directory of Open Access Journals (Sweden)

    Jen-Yi Lee

    Full Text Available BACKGROUND: Non-small cell lung cancer (NSCLC patients with L858R or exon 19 deletion mutations in epidermal growth factor receptor (EGFR have good responses to the tyrosine kinase inhibitor (TKI, gefitinib. However, patients with wild-type EGFR and acquired mutation in EGFR T790M are resistant to gefitinib treatment. Here, we showed that curcumin can improve the efficiency of gefitinib in the resistant NSCLC cells both in vitro and in vivo models. METHODS/PRINCIPAL FINDINGS: After screening 598 herbal and natural compounds, we found curcumin could inhibit cell proliferation in different gefitinib-resistant NSCLC cell lines; concentration-dependently down-regulate EGFR phosphorylation through promoting EGFR degradation in NSCLC cell lines with wild-type EGFR or T790M EGFR. In addition, the anti-tumor activity of gefitinib was potentiated via curcumin through blocking EGFR activation and inducing apoptosis in gefitinib-resistant NSCLC cell lines; also the combined treatment with curcumin and gefitinib exhibited significant inhibition in the CL1-5, A549 and H1975 xenografts tumor growth in SCID mice through reducing EGFR, c-MET, cyclin D1 expression, and inducing apoptosis activation through caspases-8, 9 and PARP. Interestingly, we observed that the combined treatment group represented better survival rate and less intestinal mucosal damage compare to gefitinib-alone therapy. We showed that curcumin attenuated the gefitinib-induced cell proliferation inhibition and apoptosis through altering p38 mitogen-activated protein kinase (MAPK activation in intestinal epithelia cell. CONCLUSIONS/SIGNIFICANCE: Curcumin potentiates antitumor activity of gefitinib in cell lines and xenograft mice model of NSCLC through inhibition of proliferation, EGFR phosphorylation, and induction EGFR ubiquitination and apoptosis. In addition, curcumin attenuates gefitinib-induced gastrointestinal adverse effects via altering p38 activation. These findings provide a novel

  1. Validating a Local Failure Risk Stratification for Use in Prospective Studies of Adjuvant Radiation Therapy for Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Baumann, Brian C. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); He, Jiwei; Hwang, Wei-Ting [Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Tucker, Kai N.; Bekelman, Justin E. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Herr, Harry W. [Memorial Sloan Kettering Cancer Center, New York, New York (United States); Lerner, Seth P. [Department of Urology, Baylor College of Medicine, Houston, Texas (United States); Guzzo, Thomas J.; Malkowicz, S. Bruce [Department of Urology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Christodouleas, John P., E-mail: christojo@uphs.upenn.edu [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2016-06-01

    Purpose: To inform prospective trials of adjuvant radiation therapy (adj-RT) for bladder cancer after radical cystectomy, a locoregional failure (LF) risk stratification was proposed. This stratification was developed and validated using surgical databases that may not reflect the outcomes expected in prospective trials. Our purpose was to assess sources of bias that may affect the stratification model's validity or alter the LF risk estimates for each subgroup: time bias due to evolving surgical techniques; trial accrual bias due to inclusion of patients who would be ineligible for adj-RT trials because of early disease progression, death, or loss to follow-up shortly after cystectomy; bias due to different statistical methods to estimate LF; and subgrouping bias due to different definitions of the LF subgroups. Methods and Materials: The LF risk stratification was developed using a single-institution cohort (n=442, 1990-2008) and the multi-institutional SWOG 8710 cohort (n=264, 1987-1998) treated with radical cystectomy with or without chemotherapy. We evaluated the sensitivity of the stratification to sources of bias using Fine-Gray regression and Kaplan-Meier analyses. Results: Year of radical cystectomy was not associated with LF risk on univariate or multivariate analysis after controlling for risk group. By use of more stringent inclusion criteria, 26 SWOG patients (10%) and 60 patients from the single-institution cohort (14%) were excluded. Analysis of the remaining patients confirmed 3 subgroups with significantly different LF risks with 3-year rates of 7%, 17%, and 36%, respectively (P<.01), nearly identical to the rates without correcting for trial accrual bias. Kaplan-Meier techniques estimated higher subgroup LF rates than competing risk analysis. The subgroup definitions used in the NRG-GU001 adj-RT trial were validated. Conclusions: These sources of bias did not invalidate the LF risk stratification or substantially change the model's LF

  2. Inducing Mucosal IgA: A Challenge for Vaccine Adjuvants and Delivery Systems.

    Science.gov (United States)

    Boyaka, Prosper N

    2017-07-01

    Mucosal IgA or secretory IgA (SIgA) are structurally equipped to resist chemical degradation in the harsh environment of mucosal surfaces and enzymes of host or microbial origin. Production of SIgA is finely regulated, and distinct T-independent and T-dependent mechanisms orchestrate Ig α class switching and SIgA responses against commensal and pathogenic microbes. Most infectious pathogens enter the host via mucosal surfaces. To provide a first line of protection at these entry ports, vaccines are being developed to induce pathogen-specific SIgA in addition to systemic immunity achieved by injected vaccines. Mucosal or epicutaneous delivery of vaccines helps target the inductive sites for SIgA responses. The efficacy of such vaccines relies on the identification and/or engineering of vaccine adjuvants capable of supporting the development of SIgA alongside systemic immunity and delivery systems that improve vaccine delivery to the targeted anatomic sites and immune cells. Copyright © 2017 by The American Association of Immunologists, Inc.

  3. ADJUVANT TREATMENT WITH BIPHOSPONATES IN COMPLEX THERAPY OF PAPILLARY THYROID CANCER BONE METASTASES

    Directory of Open Access Journals (Sweden)

    A. D. Kaprin

    2017-01-01

    Full Text Available Distant metastasis of thyroid cancer are founded in 10% of all metastases. Bone metastases are founded in 23% of distant metastasis. Complications associated with metastatic skeletal involvement often lead to a deterioration in the overall condition and a decrease in the quality of life of patients. Surgical treatment, chemotherapy are less effective, provide a higher injury rate and toxicity. This is a reason of increasing of cost of treatment. Bisphosphonates are a class of drugs that prevent the loss of bone mass, which can prolong the time to releasing bone complications: bone fracture, spine column fracture with spinal medulla compression, which decrease the QoL. Surgical treatment and chemotherapy have worse outcomes, higher injury rate, toxicity and increase cost of treatment. Bisphosphonates decrease the level of pain syndrome. Bisphosphonates are used in treatment of oncological patients since 1990. First medication was Fosamax (Aledronat. Later more medications with better efficacy and more useful were synthesised. The last one was Zoledronic acid. Rezorba (zoledronic acid was synthesised in 2006 in Russia. Rezorba has a same efficacy with other bisphosphonates, it was shown in clinical studies with groups of breast cancer and prostatic cancer. Clinical case of 67 y.o. male patient with diagnosis: Thyroid cancer IV c st pT1bN1bM1, right neck, paratraсheal, bone and lung metastasis. Complex treatment (surgery + radioiodine therapy + 5 courses of Rezorba was presented. After 3 courses the level of pain was decreased from 3 to 1,5. After 5 courses the ECOQ score was decreased from 2 to 1 point. Inclusion of Resorba in complex treatment of patients with bone metastasis after thyroid cancer at all stages of treatment decreases the score of pain syndrome and bone tissue reparation.

  4. Systemic antibody response to nano-size calcium phospate biocompatible adjuvant adsorbed HEV-71 killed vaccine

    OpenAIRE

    Saeed, Mohamed Ibrahim; Omar, Abd Rahaman; Hussein, Mohd Zobir; Elkhidir, Isam Mohamed; Sekawi, Zamberi

    2015-01-01

    Purpose Since 1980s, human enterovirus-71 virus (HEV-71) is one of the common infectious disease in Asian Pacific region since late 1970s without effective commercial antiviral or protective vaccine is unavailable yet. The work examines the role of vaccine adjuvant particle size and the route of administration on postvaccination antibody response towards HEV-71 vaccine adsorbed to calcium phosphate (CaP) adjuvant. Materials and Methods First, CaP nano-particles were compared to a commercial m...

  5. Retrospective analysis of drug utilization, health care resource use, and costs associated with IFN therapy for adjuvant treatment of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2015-07-01

    Full Text Available ≥Ying Zhang,1 Trong Kim Le,1 James W Shaw,2 Srividya Kotapati31Center for Observational Research and Data Sciences, Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb Research and Development, Hopewell, NJ, USA; 2Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb Research and Development, Princeton, NJ, USA; 3Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb Research and Development, Wallingford Center, CT, USABackground: This study examines real-world drug utilization patterns, health care resource use, and costs among patients receiving adjuvant treatment with IFN versus patients receiving no treatment ("observation" for malignant melanoma following surgery.Methods: A retrospective cohort study was conducted using administrative claims from Truven Health Analytics (MarketScan® to identify all adjuvant melanoma patients (aged ≥18 years diagnosed between June 2007 and June 2011 who had a lymph node dissection (ie, index surgery and were treated with IFN or subsequently observed. Health care resource use and costs of services were converted to 2012 US dollars and were evaluated and compared using multivariable regression.Results: Of 1,999 eligible subjects with melanoma surgery claims, 179 (9.0% were treated with IFN and 1,820 (91.0% were observed. The median duration (days and number of doses of IFN therapy were 73 and 36, respectively. Among IFN-treated patients, only 10.6% completed ≥80% of maintenance therapy. The total average cost for patients treated with IFN was US$60,755±$3,972 (n=179; significantly higher than for patients undergoing observation ($31,641±$2,471; P<0.0001. Similar trends were observed when evaluating total cost components, including melanoma-related and non-melanoma–related medical costs. Among the melanoma-related medical costs, outpatient services, including office visits and laboratory testing, represented between 33% and 53% of total costs and

  6. Dietary Selenium in Adjuvant Therapy of Viral and Bacterial Infections12

    Science.gov (United States)

    Steinbrenner, Holger; Al-Quraishy, Saleh; Dkhil, Mohamed A; Wunderlich, Frank; Sies, Helmut

    2015-01-01

    Viral and bacterial infections are often associated with deficiencies in macronutrients and micronutrients, including the essential trace element selenium. In selenium deficiency, benign strains of Coxsackie and influenza viruses can mutate to highly pathogenic strains. Dietary supplementation to provide adequate or supranutritional selenium supply has been proposed to confer health benefits for patients suffering from some viral diseases, most notably with respect to HIV and influenza A virus (IAV) infections. In addition, selenium-containing multimicronutrient supplements improved several clinical and lifestyle variables in patients coinfected with HIV and Mycobacterium tuberculosis. Selenium status may affect the function of cells of both adaptive and innate immunity. Supranutritional selenium promotes proliferation and favors differentiation of naive CD4-positive T lymphocytes toward T helper 1 cells, thus supporting the acute cellular immune response, whereas excessive activation of the immune system and ensuing host tissue damage are counteracted through directing macrophages toward the M2 phenotype. This review provides an up-to-date overview on selenium in infectious diseases caused by viruses (e.g., HIV, IAV, hepatitis C virus, poliovirus, West Nile virus) and bacteria (e.g., M. tuberculosis, Helicobacter pylori). Data from epidemiologic studies and intervention trials, with selenium alone or in combination with other micronutrients, and animal experiments are discussed against the background of dietary selenium requirements to alter immune functions. PMID:25593145

  7. Better Late than Never? Adherence to Adjuvant Therapy Guidelines for Stage III Colon Cancer in an Underserved Region.

    Science.gov (United States)

    Guerrero, Whitney; Wise, Amy; Lim, Garrett; Dong, Lei; Wan, Jim; Deneve, Jeremiah; Glazer, Evan; Dickson, Paxton; Daugherty, R Scott; Fleming, Martin; Shibata, David

    2018-01-01

    In 2008, the American College of Surgeons Commission on Cancer (CoC) issued a quality guideline for stage III colon cancer (CC) recommending adjuvant chemotherapy (AC) within 120 days of diagnosis. We examined adherence in a healthcare system serving a region with disparities in CC outcomes. In a retrospective analysis of patients (2005-2014) with stage III CC in a multi-hospital healthcare system, the associations between adherence, clinicopathologic, demographic, geographic, and socioeconomic data and overall survival (OS) were examined. Of 1171 CC patients, 438 (37.4%) had stage III disease with 63% (n = 276) receiving AC and 37% (n = 162) not. AC conferred a 5-year OS advantage (62.4 vs. 42.5%, p < 0.0001). Younger age independently predicted AC receipt (OR = 0.95, p < 0.0001). Of 252 AC patients < 80 years, 75.8% were CoC guideline compliant (GC) whereas 24.2% were not (nGC). Although there was no OS difference between GC and nGC, both had superior survival (p < 0.0001) compared to non-AC patients. Surgical complications trended towards independent association with non-compliance (p = 0.07) CONCLUSION: Guideline compliance in our system (63%) is lower than the CoC Estimated Performance Rate (72.4%). Age influenced absolute receipt of AC while surgical complications may impact guideline compliance. Even when administered beyond 120 days, AC was associated with a survival benefit.

  8. The Effect of Mindfulness-Based Music Therapy on Attention and Mood in Women Receiving Adjuvant Chemotherapy for Breast Cancer: A Pilot Study.

    Science.gov (United States)

    Lesiuk, Teresa

    2015-05-01

    To explore the efficacy of mindfulness-
based music therapy (MBMT) to improve attention and decrease mood distress experienced by women with breast cancer receiving adjuvant chemotherapy. Quantitative, descriptive, longitudinal approach. A comprehensive cancer hospital and a university in southern Florida. 15 women with a diagnosis of breast cancer, stages I-III, receiving adjuvant chemotherapy. Participants individually received MBMT for one hour per week for four weeks. The sessions consisted of varied music activities accompanied by mindfulness attitudes, or mental strategies that enhance moment-to-moment awareness, and weekly homework. Demographic information was collected at baseline. Attention was measured using Conners' Continuous Performance Test II. Mood was measured using the Profile of Mood States-Brief Form. Narrative comments collected from the homework assignments served to reinforce quantitative data. Repeated measures analysis of variance showed that attention improved significantly over time. Although all mood states significantly improved from the beginning to the end of each MBMT session, the mood state of fatigue decreased significantly more than the other mood states. MBMT enhances attention and mood, particularly the mood state of fatigue, in women with breast cancer receiving adjuvant chemotherapy. 
. A preferred music listening and mindfulness exercise may be offered to women with breast cancer who experience attention problems and mood distress.

  9. Two different durations of adjuvant therapy with intermediate-dose interferon alfa-2b in patients with high-risk melanoma (Nordic IFN trial): a randomised phase 3 trial

    DEFF Research Database (Denmark)

    Hansson, Johan; Aamdal, Steinar; Bastholt, Lars

    2011-01-01

    Adjuvant high-dose interferon alfa-2b improves relapse-free survival (RFS) in patients with high-risk melanoma, although benefits in overall survival are uncertain. Because of the toxic effects of high-dose regimens, intermediate doses are being explored. We investigated whether adjuvant therapy...... with intermediate-dose interferon alfa-2b for 1 or 2 years would improve outcomes in patients with stage IIB-IIC or III resected cutaneous melanoma....

  10. Adjuvant Hepatic Arterial Infusion Chemotherapy After Resection for Pancreatic Cancer Using Coaxial Catheter-Port System Compared with Conventional System

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Aya; Tanaka, Toshihiro, E-mail: toshihir@bf6.so-net.ne.jp [Nara Medical University, Department of Radiology (Japan); Sho, Masayuki [Nara Medical University, Department of Surgery (Japan); Nishiofuku, Hideyuki; Masada, Tetsuya; Sato, Takeshi; Marugami, Nagaaki [Nara Medical University, Department of Radiology (Japan); Anai, Hiroshi [Nara City Hospital, Department of Radiology (Japan); Sakaguchi, Hiroshi [Nara Prefectural Western Medical Center, Department of Radiology (Japan); Kanno, Masatoshi [Nara Medical University, Oncology Center (Japan); Tamamoto, Tetsuro; Hasegawa, Masatoshi [Nara Medical University, Department of Radiation Oncology (Japan); Nakajima, Yoshiyuki [Nara Medical University, Department of Surgery (Japan); Kichikawa, Kimihiko [Nara Medical University, Department of Radiology (Japan)

    2016-06-15

    PurposePrevious reports have shown the effectiveness of adjuvant hepatic arterial infusion chemotherapy (HAIC) in pancreatic cancer. However, percutaneous catheter placement is technically difficult after pancreatic surgery. The purpose of this study was to evaluate the feasibility and outcome of HAIC using a coaxial technique compared with conventional technique for postoperative pancreatic cancer.Materials and Methods93 consecutive patients who received percutaneous catheter-port system placement after pancreatectomy were enrolled. In 58 patients from March 2006 to August 2010 (Group A), a conventional technique with a 5-Fr indwelling catheter was used and in 35 patients from September 2010 to September 2012 (Group B), a coaxial technique with a 2.7-Fr coaxial catheter was used.ResultsThe overall technical success rates were 97.1 % in Group B and 86.2 % in Group A. In cases with arterial tortuousness and stenosis, the success rate was significantly higher in Group B (91.7 vs. 53.8 %; P = 0.046). Fluoroscopic and total procedure times were significantly shorter in Group B: 14.7 versus 26.7 min (P = 0.001) and 64.8 versus 80.7 min (P = 0.0051), respectively. No differences were seen in the complication rate. The 1 year liver metastasis rates were 9.9 % using the conventional system and 9.1 % using the coaxial system (P = 0.678). The overall median survival time was 44 months. There was no difference in the survival period between two systems (P = 0.312).ConclusionsThe coaxial technique is useful for catheter placement after pancreatectomy, achieving a high success rate and reducing fluoroscopic and procedure times, while maintaining the safety and efficacy for adjuvant HAIC in pancreatic cancer.

  11. Prognostic factors of early distant recurrence in hormone receptor-positive, postmenopausal breast cancer patients receiving adjuvant tamoxifen therapy: results of a retrospective analysis.

    Science.gov (United States)

    Debled, Marc; MacGrogan, Gaëtan; Brouste, Véronique; Mathoulin-Pelissier, Simone; Durand, Michel; Mauriac, Louis

    2007-06-01

    Current adjuvant hormone therapy in postmenopausal women with breast cancer is debatable between upfront aromatase inhibitors (AIs) and sequential treatment with tamoxifen. A major concern is the higher rate of early recurrences observed with sequential treatment. The authors conducted a retrospective analysis to identify risk factors of early recurrences in hormone receptor (HR)-positive, postmenopausal women within the first 3 years of adjuvant tamoxifen. Between 1986 and 2000, operable breast cancer patients who received exclusively adjuvant tamoxifen for at least 3 years were selected from the authors' institutional database. Age, histology, pathologic tumor size, modified Scarff-Bloom-Richardson (mSBR) grade, mitotic index, tumor necrosis, peritumoral vascular emboli (PVE), HR status, and the number of involved axillary lymph-node were considered as prognostic factors of recurrence. Among 715 patients who met the inclusion criteria, a distant recurrence occurred in 38 patients (5.3%) within the first 3 years of tamoxifen therapy. Significant prognostic factors of early recurrence were mSBR, axillary lymph node involvement, tumor necrosis, mitotic index, PVE, and pathologic tumor size. Grade 1 and/or lymph node-negative tumors were excluded from the multivariate analysis (1 recurrence in 208 patients). In this model, mSBR grade 3 was the only significant predictive factor of early recurrence (hazard ratio, 3.72; P<.001). In this study, a subset of patients was identified that was at low-risk of early recurrence (mSBR grade 1 and/or negative lymph node status). Women in that subset could be treated using sequential hormone therapy with tamoxifen and AIs. In women with mSBR grade 3 or lymph node-positive tumors, an upfront treatment with AIs seemed to be the current optimal strategy. (c) 2007 American Cancer Society.

  12. Efficacy of Curcumin as Adjuvant Therapy to Induce or Maintain Remission in Ulcerative Colitis Patients: an Evidence-based Clinical Review

    Directory of Open Access Journals (Sweden)

    Marcellus Simadibrata

    2018-01-01

    Full Text Available Background: treatment guidelines for ulcerative colitis (UC not yet established. Currently, mesalazine, corticosteroids, and immunomodulators are treatment options for UC. However, they are known to have unpleaseant side effects such as nausea, vomiting, headaches, hepatitis, and male infertility. Curcumin is found in Turmeric plants (Curcuma longa L., which possesses both anti-inflammatory and antioxidant properties. This study aimed to determine whether curcumin as adjuvant therapy can induce or maintain remission in UC patients. Methods: structured search in three database (Cochrane, PubMed, Proquest using “Curcumin”, “remission” and “Ulcerative Colitis” as keywords. Inclusion criteria is randomized controlled trials (RCTs, meta-analysis, or systematic review using curcumin as adjuvant therapy in adult UC patients. Results: we found 49 articles. After exclusion, three RCTs were reviewed; two examined curcumin efficacy to induce remission and one for remision maintenance in UC. Curcumin was significantly more effective than placebo in all RCTs. The efficacy of curcumin could be explained by its anti-inflammatory properties, which inhibit NF-kB pathway. Regulation of oxidant/anti-oxidant balance can modify the release of cytokines. However, methods varied between RCTs. Therefore, they cannot be compared objectively. Futhermore, the sample size were small (n= 50, 45, 89 therefore the statistical power was not enough to generate representative results in all UC patients. Conclusion: Available evidence showed that curcumin has the potential to induce and maintain remission in UC patients with no serious side effects. However, further studies with larger sample size are needed to recommend it as adjuvant therapy of ulcerative colitis.

  13. Patterns of Local Recurrence and Dose Fractionation of Adjuvant Radiation Therapy in 462 Patients With Soft Tissue Sarcoma of Extremity and Trunk Wall

    Energy Technology Data Exchange (ETDEWEB)

    Jebsen, Nina L., E-mail: nina.louise.jebsen@helse-bergen.no [Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen (Norway); Department of Oncology, Haukeland University Hospital, Bergen (Norway); Engellau, Jacob [Department of Oncology, Skåne University Hospital, Lund (Sweden); Engström, Katarina [Department of Oncology, Sahlgrenska University Hospital, Gothenburg (Sweden); Bauer, Henrik C. [Department of Molecular Medicine and Surgery, Section for Orthopaedics and Sports Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm (Sweden); Monge, Odd R. [Department of Oncology, Haukeland University Hospital, Bergen (Norway); Muren, Ludvig P. [Department of Physics and Technology, University of Bergen, Bergen (Norway); Department of Medical Physics, Aarhus University and Aarhus University Hospital, Aarhus (Denmark); Eide, Geir E. [Centre for Clinical Research, Haukeland University Hospital, Bergen (Norway); Department of Public Health and Primary Health Care, University of Bergen, Bergen (Norway); Trovik, Clement S. [Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen (Norway); Department of Oncology, Haukeland University Hospital, Bergen (Norway); Bruland, Øyvind S. [Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Institute of Clinical Medicine, University of Oslo, Oslo (Norway)

    2013-08-01

    Purpose: To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials: LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results: Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence interval [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions: No significant dose–response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma.

  14. EFFECTS OF BETAHISTINE DIHYDROCHLORIDE AS ADJUVANT TO ENALAPRIL THERAPY OF PATIENTS WITH CHRONIC HEART FAILURE CLASS II-II (NYHA SUFFERING FROM GIDDINESS

    Directory of Open Access Journals (Sweden)

    S. Y. Martsevich

    2008-01-01

    Full Text Available Aim. To study adjuvant effect of betahistine dihydrochloride to ACE inhibitors in patients with chronic heart failure (CHF class II-III suffering from giddiness.Material and methods. 61 patients with CHF class II-III, ejection fraction ≤45% (Simpson suffering from giddiness were involved into randomized open parallel study. Patients were randomized to Betahistine dihydrochloride plus basic CHF therapy or only basic therapy groups. Enalapril dose titration was performed in all patients. Quality of life and giddiness severity evaluation, electrocardiogram was performed initially and after treatment. Clinical examination results, drug therapy and adverse event were registered at each visit.Results. The target ACE inhibitor dose (≥20 mg daily was reached in 97 % of patients. It led to significant reduction of dyspnea, edemas, CHF class reduction and life quality increase. Significant differences between investigated groups were not found. Reduction of giddiness severity was shown in both groups. There was a trend to more prominent improvement of life quality (р=0,08 and more frequent achievement of target ACE inhibitor dose in patients treated with betahistine dihydrochloride.Conclusion. The target ACE inhibitor dose can be achieved more than in 90% of patients with CHF class II-III without hypotension symptoms. Adjuvant usage of betahistine dihydrochloride is necessary in patients with CHF still suffering from giddiness after achievement of target ACE inhibitor dose.

  15. Infectious olecranon and patellar bursitis: short-course adjuvant antibiotic therapy is not a risk factor for recurrence in adult hospitalized patients.

    Science.gov (United States)

    Perez, Cédric; Huttner, Angela; Assal, Mathieu; Bernard, Louis; Lew, Daniel; Hoffmeyer, Pierre; Uçkay, Ilker

    2010-05-01

    No evidence-based recommendations exist for the management of infectious bursitis. We examined epidemiology and risk factors for recurrence of septic bursitis. Specifically, we compared outcome in patients receiving bursectomy plus short-course adjuvant antibiotic therapy (7 days). Retrospective study of adult patients with infectious olecranon and patellar bursitis requiring hospitalization at Geneva University Hospital from January 1996 to March 2009. We identified 343 episodes of infectious bursitis (237 olecranon and 106 patellar). Staphylococcus aureus predominated among the 256 cases with an identifiable pathogen (85%). Three hundred and twelve cases (91%) were treated surgically; 142 (41%) with one-stage bursectomy and closure and 146 with two-stage bursectomy. All received antibiotics for a median duration of 13 days with a median intravenous component of 3 days. Cure was achieved in 293 (85%) episodes. Total duration of antibiotic therapy [odds ratio (OR) 0.9; 95% confidence interval (95% CI) 0.8-1.1] showed no association with cure. In multivariate analysis, only immunosuppression was linked to recurrence (OR 5.6; 95% CI 1.9-18.4). Compared with 14 days of antibiotic treatment (OR 0.9; 95% CI 0.1-10.7) was equivalent, as was the intravenous component (OR 1.1; 95% CI 1.0-1.3). In severe infectious bursitis requiring hospitalization, adjuvant antibiotic therapy might be limited to 7 days in non-immunosuppressed patients.

  16. Sorafenib or sunitinib as postoperative adjuvant therapy for Chinese patients with locally advanced clear cell renal cell carcinoma at high risk for disease recurrence.

    Science.gov (United States)

    Zhao, Juping; Zhu, Yu; Zhang, Chongyu; Wang, Xiaojing; He, Hongchao; Wang, Haofei; Wu, Yuxuan; Zhou, Wenlong; Shen, Zhoujun

    2013-11-01

    To evaluate the efficacy and safety of targeted agents (sorafenib and sunitinib) as postoperative adjuvant therapy in Chinese patients with clear cell renal cell carcinoma (CC-RCC) who are at high risk for disease recurrence. Forty-three patients treated at our center between December 2007 and December 2010 with locally advanced CC-RCC who were at a high risk for disease recurrence were enrolled into the study. The criteria for high risk of CC-RCC recurrence postoperatively were defined according to the Mayo Clinic stage, size, grade, and necrosis (SSIGN) score for CC-RCC. After radical nephrectomy, patients received either sorafenib (group A, n = 20) or sunitinib (group B, n = 23) and were followed up for at least 1 year to determine the efficacy and safety of the test products. The duration of maintenance targeted medication treatment was approximately 1 year. Group C consisted of 388 CC-RCC patients treated at our center between 1992 and 2007, who were at high risk for disease recurrence and who received no adjuvant therapy. The demography characteristics were similar among the 3 groups. The overall rate of recurrence in groups A and B was not different (15.0% and 17.4% (P > 0.05), respectively), which was lower than that of group C (38.7%, P Disease-free survival (DFS) was longer in groups A and B (18.9 ± 5.9 months and 16.9 ± 6.1 months [P > 0.05], respectively), compared with group C (13.3 ± 7.2 months, P therapy included hand-foot syndrome, fatigue, diarrhea, taste disturbance, rash, hypertension, alopecia, stomatitis, neutropenia, nausea, pruritus, hypothyroidism in groups A and B. The adverse effects were mild in both groups and the incidence was not significantly different between groups A and B. Targeted adjuvant therapy postoperatively with sorafenib or sunitinib in patients with CC-RCC who are at a high risk for disease recurrence was well tolerated and effective in reducing the rate of CC-RCC recurrence in these patients. This study is an attempt

  17. Camel milk as an adjuvant therapy for the treatment of type 1 diabetes: verification of a traditional ethnomedical practice.

    Science.gov (United States)

    Mohamad, Ragaa Hosny; Zekry, Zekry Khalid; Al-Mehdar, Hussain A; Salama, Omar; El-Shaieb, Siad Ebrahim; El-Basmy, Amany A; Al-said, Mohamad Gamil Abdel Monem; Sharawy, Sabry Mohamed

    2009-04-01

    There is a traditional belief in the Middle East that regular consumption of camel milk may aid in prevention and control of diabetes. The aim of this work was to evaluate the efficacy of camel milk as an adjuvant therapy in young type 1 diabetics. This 16-week randomized study enrolled 54 type 1 diabetic patients (average age 20 years) selected from those attending the outpatient diabetes clinic of the Menofia University Hospital, affiliated with Egypt's National Cancer Institute. Subjects were randomly divided into two groups of 27 patients: one received usual management (diet, exercise, and insulin), whereas the other received 500 mL of camel milk daily in addition to standard management. A control group of 10 healthy subjects was also assessed. The following parameters were evaluated at baseline and at 4 and 16 weeks: hemoglobin A1c (HbA1c), human C-peptide, lipid profile, serum insulin, anti-insulin antibodies, creatinine clearance, albumin in 24-hour urine, body mass index, and Diabetes Quality of Life score. The following parameters were significantly different between the usual-management group versus the camel milk group after 16 weeks: fasting blood sugar (227.2 +/- 17.7 vs. 98.9 +/- 16.2 mg/dL), HbA1c (9.59 +/- 2.05[%] vs. 7.16 +/- 1.84[%]), serum anti-insulin antibodies (26.20 +/- 7.69 vs. 20.92 +/- 5.45 microU/mL), urinary albumin excretion (25.17 +/- 5.43 vs. 14.54 +/- 5.62 mg/dL/24 hours), daily insulin dose (48.1 +/- 6.95 vs. 23 +/- 4.05 units), and body mass index (18.43 +/- 3.59 vs. 24.3 +/- 2.95 kg/m(2)). Most notably, C-peptide levels were markedly higher in the camel milk group (0.28 +/- 0.6 vs. 2.30 +/- 0.51 pmol/mL). These results suggest that, as an adjunct to standard management, daily ingestion of camel milk can aid metabolic control in young type 1 diabetics, at least in part by boosting endogenous insulin secretion.

  18. American Society of Clinical Oncology Clinical Practice Guideline: Update on Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer

    Science.gov (United States)

    Burstein, Harold J.; Prestrud, Ann Alexis; Seidenfeld, Jerome; Anderson, Holly; Buchholz, Thomas A.; Davidson, Nancy E.; Gelmon, Karen E.; Giordano, Sharon H.; Hudis, Clifford A.; Malin, Jennifer; Mamounas, Eleftherios P.; Rowden, Diana; Solky, Alexander J.; Sowers, MaryFran R.; Stearns, Vered; Winer, Eric P.; Somerfield, Mark R.; Griggs, Jennifer J.

    2010-01-01

    Purpose To develop evidence-based guidelines, based on a systematic review, for endocrine therapy for postmenopausal women with hormone receptor–positive breast cancer. Methods A literature search identified relevant randomized trials. Databases searched included MEDLINE, PREMEDLINE, the Cochrane Collaboration Library, and those for the Annual Meetings of the American Society of Clinical Oncology (ASCO) and the San Antonio Breast Cancer Symposium (SABCS). The primary outcomes of interest were disease-free survival, overall survival, and time to contralateral breast cancer. Secondary outcomes included adverse events and quality of life. An expert panel reviewed the literature, especially 12 major trials, and developed updated recommendations. Results An adjuvant treatment strategy incorporating an aromatase inhibitor (AI) as primary (initial endocrine therapy), sequential (using both tamoxifen and an AI in either order), or extended (AI after 5 years of tamoxifen) therapy reduces the risk of breast cancer recurrence compared with 5 years of tamoxifen alone. Data suggest that including an AI as primary monotherapy or as sequential treatment after 2 to 3 years of tamoxifen yields similar outcomes. Tamoxifen and AIs differ in their adverse effect profiles, and these differences may inform treatment preferences. Conclusion The Update Committee recommends that postmenopausal women with hormone receptor–positive breast cancer consider incorporating AI therapy at some point during adjuvant treatment, either as up-front therapy or as sequential treatment after tamoxifen. The optimal timing and duration of endocrine treatment remain unresolved. The Update Committee supports careful consideration of adverse effect profiles and patient preferences in deciding whether and when to incorporate AI therapy. PMID:20625130

  19. Elucidating the mechanisms of protein antigen adsorption to the CAF/NAF liposomal vaccine adjuvant systems

    DEFF Research Database (Denmark)

    Hamborg, Mette; Rose, Fabrice; Jorgensen, Lene

    2014-01-01

    The reverse vaccinology approach has recently resulted in the identification of promising protein antigens, which in combination with appropriate adjuvants can stimulate customized, protective immune responses. Although antigen adsorption to adjuvants influences vaccine efficacy and safety, little...... is generally known about how antigens and adjuvants interact at the molecular level. The aim of this study was to elucidate the mechanisms of interactions between the equally sized, but oppositely charged model protein antigens α-lactalbumin and lysozyme, and i) the clinically tested cationic liposomal...... interaction with the zwitterionic liposomes. In contrast, the net cationic lysozyme showed very little interaction with either types of liposome. Adsorption of α-lactalbumin altered its tertiary structure, affected lipid membrane packing below and above the phase transition temperature, and neutralized...

  20. Long-term persistence of systemic and mucosal immune response to HPV-16/18 AS04-adjuvanted vaccine in preteen/adolescent girls and young women

    DEFF Research Database (Denmark)

    Petäjä, T; Pedersen, Court; Poder, A

    2011-01-01

    Vaccination against oncogenic human papillomavirus (HPV) types is one key intervention for cervical cancer prevention. This follow-up study assessed the persistence of the systemic and mucosal immune responses together with the safety profile of the HPV-16/18 AS04-adjuvanted vaccine administered...... of transudation or exudation of serum IgG antibodies through the cervical epithelium. The HPV-16/18 AS04-adjuvanted vaccine had a clinically acceptable safety profile. In conclusion, this follow-up study shows that the HPV-16/18 AS04-adjuvanted vaccine administered to preteen/adolescents girls and young women...

  1. Adjuvants and delivery systems in veterinary vaccinology: current state and future developments

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Dedieu, Laurence; Johnson, Nicholas

    2011-01-01

    low immunogenicity themselves. The development of such adjuvants may take advantage of the increased knowledge of the molecular mechanisms and factors controlling these responses. However, knowledge of such molecular details of immune mechanisms is relatively scarce for species other than humans...

  2. Fluorescence imaging for investigating the efficiency of formulations, adjuvants and application systems

    NARCIS (Netherlands)

    Ruiter, de H.; Schoor, van der R.; Jalink, H.

    2005-01-01

    Several herbicides reduce, directly or indirectly, the efficiency of photosynthesis of plants. As a consequence, the fluorescence of the chlorophyll increases. The relative increase of fluorescence [(Fm-F0)/Fm] can be used to compare the influence of formulations and adjuvants on the activity of

  3. Cladribine therapy for systemic mastocytosis

    NARCIS (Netherlands)

    Kluin-Nelemans, HC; Oldhoff, JM; van Doormaal, JJ; van 't Wout, JW; Verhoef, G; Gerrits, WBJ; van Dobbenburgh, OA; Pasmans, SG; Fijnheer, R

    2003-01-01

    Patients with systemic mastocytosis (SM) can suffer from disabling symptoms related to mast cell mediator release or mast cell infiltration, requiring mast cell eradication. In the present absence of any curative therapy, a recent case report describing the efficacy of cladribine showed promising

  4. Adjuvant postoperative radiation therapy for colorectal carcinoma above the peritoneal reflection. II. Antimesenteric wall ascending and descending colon and cecum

    Energy Technology Data Exchange (ETDEWEB)

    Kopelson, G.

    1983-08-15

    From 1970 to 1981, 50 patients had curative surgery for carcinoma of the cecum, ascending, or descending colon and were Stage greater than or equal to B2. In 15 cases, the lesion originated on the antimesenteric (posterolateral) bowel wall. Of seven cases (with minimum three-year follow-up) not receiving adjuvant postoperative regional irradiation, four recurred in the tumor bed/abdominal wall versus 0/3 irradiated patients. Similarly, the five-year survival was improved in the irradiated group (2/3) versus only 2/9 in the unirradiated group. Patients with transmural extension of right or left colon cancers originating on the anti mesenteric (posterolateral) bowel wall may have a high incidence of postoperative regional failure which may be decreased by adjuvant postoperative regional irradiation.

  5. Effect of adjuvant recombinant EPO therapy on neural functional recovery, inflammation and erythrocyte glucose metabolism in patients with severe craniocerebral injury

    Directory of Open Access Journals (Sweden)

    Zeng Lu

    2017-02-01

    Full Text Available Objective: To study the effect of adjuvant recombinant EPO therapy on neural functional recovery, inflammation and erythrocyte glucose metabolism in patients with severe craniocerebral injury. Methods: A total of 78 patients with severe craniocerebral injury treated in our hospital between May 2013 and March 2016 were selected and randomly divided into the EPO group and control group who received recombinant human erythropoietin (rhEPO combined with conventional therapy and conventional therapy respectively. Before treatment as well as 7 d and 14 d after treatment, the degree of brain tissue hypoxia, nerve injury and inflammation as well as erythrocyte glucose metabolism were evaluated respectively. Results: PbtO2 levels, serum NGB and HGB content as well as PFK activity of both groups 7 d and 14 d after treatment were significantly higher than those before treatment while serum NF-H, NF-L, NF-M, NSE, S100β, IL-2, P-selectin and sICAM-1 content as well as G-6PD and AR activity were significantly lower than those before treatment; PbtO2 levels, serum NGB and HGB content as well as PFK activity of EPO group 7 d and 14 d after treatment were significantly higher than those of control group while serum NF-H, NF-L, NF-M, NSE, S100 β, IL-2, P-selectin and sICAM-1 content as well as G-6PD and AR activity were significantly lower than those of control group. Conclusion: Adjuvant recombinant EPO therapy can inhibit inflammation and improve erythrocyte glucose metabolism to reduce the nerve injury degree in patients with severe craniocerebral injury.

  6. Efficacy of Adjuvant 5-Fluorouracil Therapy for Patients with EMAST-Positive Stage II/III Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Yasushi Hamaya

    Full Text Available Elevated Microsatellite Alterations at Selected Tetranucleotide repeats (EMAST is a genetic signature found in up to 60% of colorectal cancers (CRCs that is caused by somatic dysfunction of the DNA mismatch repair (MMR protein hMSH3. We have previously shown in vitro that recognition of 5-fluorouracil (5-FU within DNA and subsequent cytotoxicity was most effective when both hMutSα (hMSH2-hMSH6 heterodimer and hMutSβ (hMSH2-hMSH3 heterodimer MMR complexes were present, compared to hMutSα > hMutSβ alone. We tested if patients with EMAST CRCs (hMutSβ defective had diminished response to adjuvant 5-FU chemotherapy, paralleling in vitro findings. We analyzed 230 patients with stage II/III sporadic colorectal cancers for which we had 5-FU treatment and survival data. Archival DNA was analyzed for EMAST (>2 of 5 markers mutated among UT5037, D8S321, D9S242, D20S82, D20S85 tetranucleotide loci. Kaplan-Meier survival curves were generated and multivariate analysis was used to determine contribution to risk. We identified 102 (44% EMAST cancers. Ninety-four patients (41% received adjuvant 5-FU chemotherapy, and median follow-up for all patients was 51 months. Patients with EMAST CRCs demonstrated improved survival with adjuvant 5FU to the same extent as patients with non-EMAST CRCs (P<0.05. We observed no difference in survival between patients with stage II/III EMAST and non-EMAST cancers (P = 0.36. There is improved survival for stage II/III CRC patients after adjuvant 5-FU-based chemotherapy regardless of EMAST status. The loss of contribution of hMSH3 for 5-FU cytotoxicity may not adversely affect patient outcome, contrasting patients whose tumors completely lack DNA MMR function (MSI-H.

  7. INFLUENCE OF INGARON UPON IMMUNE STATE OF THE PATIENTS WITH ADENOCARCINOMA OF LUNG IN THE COURSE OF ADJUVANT THERAPY

    Directory of Open Access Journals (Sweden)

    S. P. Pyltsin

    2014-01-01

    Full Text Available This clinical trial included 63 patients with lung adenocarcinoma who underwent radical surgical resection of the tumor at the Thoracic Surgery Department of Rostov Research Oncological Institute from 2009 to 2011, The patients were randomized in two groups, i.e., 33 patients (52% of the main group received adjuvant chemoimmunotherapy accomplished with Ingaron, whereas 30 cases (48% in control group were assigned to receive conventional adjuvant chemotherapy. Adjuvant chemoimmunotherapy was administered according to the following schedule: carboplatinum, AUC = 5 i.v. on day 1; etoposide, 100 mg/m2 i.v. on days 1,3,5; interferon-gamma, 500.000 I.E./m2 i.v. on days 2,4,6. In the patiens undergoing lobectomy, carboplatinum was replaced for cisplatinum 100 mg/m2 i.v. on day 1. Comparative evaluation of the both treatment regimens has shown a correcting effect of Ingaron upon cellular immunity links. The Ingaroncontaining chemoimmunotherapy may contribute to improvement of 3-year event-free survival among lung adenocarcinoma patients by 19 percent (p = 0.06607.

  8. Proton beam therapy control system

    Science.gov (United States)

    Baumann, Michael A.; Beloussov, Alexandre V.; Bakir, Julide; Armon, Deganit; Olsen, Howard B.; Salem, Dana

    2010-09-21

    A tiered communications architecture for managing network traffic in a distributed system. Communication between client or control computers and a plurality of hardware devices is administered by agent and monitor devices whose activities are coordinated to reduce the number of open channels or sockets. The communications architecture also improves the transparency and scalability of the distributed system by reducing network mapping dependence. The architecture is desirably implemented in a proton beam therapy system to provide flexible security policies which improve patent safety and facilitate system maintenance and development.

  9. Influence of adjuvant irradiation on the development of late arm lymphedema and impaired shoulder mobility after mastectomy for carcinoma of the breast

    Energy Technology Data Exchange (ETDEWEB)

    Ryttov, N.; Holm, N.V.; Qvist, N.; Blichert-Toft, M.

    1988-01-01

    The influence of postoperative radiation therapy on development of late arm lymphedema and shoulder joint disability following mastectomy was evaluated from a series of 57 women with operable carcinoma of the breast. The patients were divided into three groups. Common for all three groups was mastectomy and partial axillary dissection. In addition one group received postoperative irradiation plus systemic therapy and another group systemic therapy alone. The incidence of late arm lymphedema/impaired shoulder mobility was 11%/4% in the group of patients undergoing surgery alone, 46%/38% in the group of patients receiving adjuvant irradiation and 6%/12% in the group of patients receiving adjuvant systemic therapy. It is concluded that adjuvant irradiation to the axilla in patients with metastatic lymph nodes highly increases the risk of late physical sequelae following modified radical mastectomy. Adjuvant systemic therapy can be administered to high risk patients without increasing the risk of late arm lymphedema and shoulder disability.

  10. When does atopic dermatitis warrant systemic therapy?

    DEFF Research Database (Denmark)

    Simpson, Eric L; Bruin-Weller, Marjolein; Flohr, Carsten

    2017-01-01

    BACKGROUND: Although most patients with atopic dermatitis (AD) are effectively managed with topical medication, a significant minority require systemic therapy. Guidelines for decision making about advancement to systemic therapy are lacking. OBJECTIVE: To guide those considering use of systemic ...

  11. Systemic antibiotics in periodontal therapy.

    Science.gov (United States)

    Heitz-Mayfield, L J A

    2009-09-01

    Periodontitis is a biofilm infection with a mixed microbial aetiology. Periodontitis is generally treated by non-surgical mechanical debridement and regular periodontal maintenance care. Periodontal surgery may be indicated for some patients to improve access to the root surface for mechanical debridement. A range of systemic antibiotics for treatment of periodontitis has been documented, with some studies showing superior clinical outcomes following adjunctive antibiotics while others do not. This has resulted in controversy as to the role of systemic antibiotics in the treatment of periodontal diseases. Recent systematic reviews have provided an evidence-based assessment of the possible benefits of adjunctive antibiotics in periodontal therapy. This review aims to provide an update on clinical issues of when and how to prescribe systemic antibiotics in periodontal therapy.

  12. Induction of systemic and mucosal immunity against methicillin-resistant Staphylococcus aureus infection by a novel nanoemulsion adjuvant vaccine.

    Science.gov (United States)

    Sun, HongWu; Wei, Chao; Liu, BaoShuai; Jing, HaiMing; Feng, Qiang; Tong, YaNan; Yang, Yun; Yang, LiuYang; Zuo, QianFei; Zhang, Yi; Zou, QuanMing; Zeng, Hao

    2015-01-01

    The Gram-positive bacterial pathogen methicillin-resistant Staphylococcus aureus (MRSA) can cause infections in the bloodstream, endocardial tissue, respiratory tract, culture-confirmed skin, or soft tissue. There are currently no effective vaccines, and none are expected to become available in the near future. An effective vaccine capable of eliciting both systemic and mucosal immune responses is also urgently needed. Here, we reported a novel oil-in-water nanoemulsion adjuvant vaccine containing an MRSA recombination protein antigen, Cremophor EL-35(®) as a surfactant, and propylene glycol as a co-surfactant. This nanoemulsion vaccine, whose average diameter was 31.34±0.49 nm, demonstrated good protein structure integrity, protein specificity, and good stability at room temperature for 1 year. The intramuscular systemic and nasal mucosal immune responses demonstrated that this nanoemulsion vaccine could improve the specific immune responses of immunoglobulin (Ig)G and related subclasses, such as IgG1, IgG2a, and IgG2b, as well as IgA, in the serum after Balb/c mice intramuscular immunization and C57 mice nasal immunization. Furthermore, this nanoemulsion vaccine also markedly enhanced the interferon-γ and interleukin-17A cytokine cell immune response, improved the survival ratio, and reduced bacterial colonization. Taken together, our results show that this novel nanoemulsion vaccine has great potential and is a robust generator of an effective intramuscular systemic and nasal mucosal immune response without the need for an additional adjuvant. Thus, the present study serves as a sound scientific foundation for future strategies in the development of this novel nanoemulsion adjuvant vaccine to enhance both the intramuscular systemic and nasal mucosal immune responses.

  13. Impact of intratumoral expression levels of fluoropyrimidine-metabolizing enzymes on treatment outcomes of adjuvant S-1 therapy in gastric cancer.

    Directory of Open Access Journals (Sweden)

    Ji-Yeon Kim

    Full Text Available We analyzed the expression levels of fluoropyrimidine-metabolizing enzymes (thymidylate synthase [TS], dihydropyrimidine dehydrogenase [DPD], thymidine phosphorylase [TP] and orotate phosphoribosyltransferase [OPRT] to identify potential biomarkers related to treatment outcomes in gastric cancer (GC patients receiving adjuvant S-1 chemotherapy. In this study, 184 patients who received curative gastrectomy (D2 lymph node dissection and adjuvant S-1 were included. Immunohistochemistry and quantitative reverse transcription polymerase chain reaction were performed to measure the protein and mRNA levels of TS, DPD, TP, and OPRT in tumor tissue. In univariate analysis, low intratumoral DPD protein expression was related to poorer 5-year disease-free survival (DFS; 78% vs. 88%; P = 0.068. Low intratumoral DPD mRNA expression (1st [lowest] quartile was also related to poorer DFS (69% vs. 90%; P < 0.001 compared to high intratumoral DPD expression (2nd to 4th quartiles. In multivariate analyses, low intratumoral DPD protein or mRNA expression was related to worse DFS (P < 0.05, irrespective of other clinical variables. TS, TP, and OPRT expression levels were not related to treatment outcomes. Severe non-hematologic toxicities (grade ≥ 3 had a trend towards more frequent development in patients with low intratumoral DPD mRNA expression (29% vs. 16%; P = 0.068. In conclusion, GC patients with high intratumoral DPD expression did not have inferior outcome following adjuvant S-1 therapy compared with those with low DPD expression. Instead, low intratumoral DPD expression was related to poor DFS.

  14. Effect of Surgery, Adjuvant Therapy, and Other Prognostic Factors on Choroid Plexus Carcinoma: A Systematic Review and Individual Patient Data Analysis.

    Science.gov (United States)

    Mallick, Supriya; Benson, Rony; Melgandi, Wineeta; Rath, Goura K

    2017-12-01

    The optimal treatment of patients with choroid plexus carcinoma (CPC) is unclear. We conducted a systematic review and meta-analysis of individual patient information to determine the effect of surgery, adjuvant therapy, and other prognostic factors for CPC. A comprehensive search of the PubMed and Google Scholar databases was performed using the following MeSH terms to find all possible reports on CPC: choroid plexus tumor; choroid plexus carcinoma; choroid plexus carcinoma AND treatment; and choroid plexus carcinoma AND survival. We performed an individual patient data analysis to assess the strength of the potential associations between different variables and the outcomes for patients with CPC. Data from 284 patients were retrieved from 89 studies. The median patient age was 2 years, with 26% patients diagnosed in the first year of their life. Of these 284 patients, 52.8% had undergone gross total resection (GTR) or near total resection. The median follow-up period for the entire cohort was 10.8 months. The median progression-free survival (PFS) was 13 months (95% confidence interval 8.14-17.8). PFS was better for patients >aged 5 years and those who had undergone GTR. The median overall survival (OS) was 29 months (95% confidence interval 16.3-41.7). OS was better for patients aged >5 years, those who had undergone GTR, those who had received adjuvant treatment, and those with a parenchymal tumor site. CPC is an aggressive tumor, with a median PFS of 13 months and median OS of 29 months. All patients should undergo maximal safe resection, because GTR is associated with improved survival. The use of adjuvant radiation and chemotherapy were also associated with improved outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. The 2017 complete overhaul of adjuvant therapies for high-risk melanoma and its consequences for staging and management of melanoma patients.

    Science.gov (United States)

    Eggermont, Alexander M M; Dummer, Reinhard

    2017-11-01

    The spectacular outcomes of the phase III trials regarding nivolumab versus ipilimumab in fully resected stage IIIB/C-IV and of the combination of dabrafenib (D) plus trametinib (T) in BRAF-mutant stage III patients demonstrate that effective treatments in advanced melanoma are also highly effective in the adjuvant setting. In 2016, an overall survival benefit with adjuvant high-dose ipilimumab was demonstrated, and the European Organisation for Research and Treatment of Cancer trial 1325 comparing pembrolizumab versus placebo will complete the picture in the early 2018. Toxicity profiles are in line with the experience in advanced melanoma, i.e. favourable for the anti-PD1 agents and for D + T and problematic for ipilimumab. The 2017 outcomes are practice changing and put an end to the use of interferon (IFN) and ipilimumab. In countries with only access to IFN, its use can be restricted to patients with ulcerated melanoma, based on the individual patient data meta-analysis recently published. Because of the results of the Melanoma Sentinel Lymph node Trial-2 (MSLT-2) trial, completion lymph node dissection (CLND) will decrease sharply, leading to a lack of optimal prognostic information. Prognosis in sentinel node-positive stage IIIA/B patients is extremely heterogeneous with 5-year survival rates varying from 90% to 40% and depends mostly on the number of positive nodes identified by CLND. This information is crucial for clinical decision-making. How to guarantee optimal staging information needs to be discussed urgently. Further improvements of adjuvant therapies will have to address all these questions as well as the exploration of neoadjuvant use of active drugs and combination approaches. Important paradigm shifts in the management of high-risk melanoma patients are upon us. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. A De-O-acylated Lipooligosaccharide-Based Adjuvant System Promotes Antibody and Th1-Type Immune Responses to H1N1 Pandemic Influenza Vaccine in Mice

    Directory of Open Access Journals (Sweden)

    Ji In Ryu

    2016-01-01

    Full Text Available Vaccine adjuvants are agents that are used to promote immune responses to vaccine antigens and thereby to enhance the protective efficacy of the vaccines. In this study, we investigated the adjuvant activity of CIA06, an adjuvant system that is composed of a toll-like receptor 4 agonist de-O-acylated lipooligosaccharide (dLOS and aluminum hydroxide, on the H1N1 pandemic influenza vaccine Greenflu-S® in mice. CIA06 significantly enhanced influenza-specific serum IgG, hemagglutination-inhibition, and virus-neutralizing antibody titers, which eliminated vaccine dose-dependency in the antibody response. Mice immunized with the CIA06-adjuvanted Greenflu-S showed Th1-type-predominant cytokine profiles, and both CD4+ and CD8+ T cell responses were induced. Immunization of mice with the CIA06-adjuvanted vaccine reduced the mortality and morbidity of mice upon lethal challenges with influenza virus, and no excessive inflammatory responses were observed in the lung tissues of the immunized mice after viral infection. These data suggest that the dLOS-based adjuvant system CIA06 can be used to promote the immune responses to influenza vaccine or to spare antigen dose without causing harmful inflammatory responses.

  17. Vaccines, adjuvants and autoimmunity.

    Science.gov (United States)

    Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda

    2015-10-01

    Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Carbohydrate-based immune adjuvants

    Science.gov (United States)

    Petrovsky, Nikolai; Cooper, Peter D

    2011-01-01

    The role for adjuvants in human vaccines has been a matter of vigorous scientific debate, with the field hindered by the fact that for over 80 years, aluminum salts were the only adjuvants approved for human use. To this day, alum-based adjuvants, alone or combined with additional immune activators, remain the only adjuvants approved for use in the USA. This situation has not been helped by the fact that the mechanism of action of most adjuvants has been poorly understood. A relative lack of resources and funding for adjuvant development has only helped to maintain alum’s relative monopoly. To seriously challenge alum’s supremacy a new adjuvant has many major hurdles to overcome, not least being alum’s simplicity, tolerability, safety record and minimal cost. Carbohydrate structures play critical roles in immune system function and carbohydrates also have the virtue of a strong safety and tolerability record. A number of carbohydrate compounds from plant, bacterial, yeast and synthetic sources have emerged as promising vaccine adjuvant candidates. Carbohydrates are readily biodegradable and therefore unlikely to cause problems of long-term tissue deposits seen with alum adjuvants. Above all, the Holy Grail of human adjuvant development is to identify a compound that combines potent vaccine enhancement with maximum tolerability and safety. This has proved to be a tough challenge for many adjuvant contenders. Nevertheless, carbohydrate-based compounds have many favorable properties that could place them in a unique position to challenge alum’s monopoly over human vaccine usage. PMID:21506649

  19. Cardiovascular adverse events during adjuvant endocrine therapy for early breast cancer using letrozole or tamoxifen: safety analysis of BIG 1-98 trial.

    Science.gov (United States)

    Mouridsen, Henning; Keshaviah, Aparna; Coates, Alan S; Rabaglio, Manuela; Castiglione-Gertsch, Monica; Sun, Zhuoxin; Thürlimann, Beat; Mauriac, Louis; Forbes, John F; Paridaens, Robert; Gelber, Richard D; Colleoni, Marco; Smith, Ian; Price, Karen N; Goldhirsch, Aron

    2007-12-20

    Previous analyses of adjuvant studies of aromatase inhibitors versus tamoxifen, including the Breast International Group (BIG) 1-98 study, have suggested a small numerical excess of cardiac adverse events (AEs) on aromatase inhibitors, a reduction in the incidence of hypercholesterolemia on tamoxifen, and significantly higher incidence of thromboembolic AEs on tamoxifen. The purpose of the present study is to provide detailed updated information on these AEs in BIG 1-98. Eight thousand twenty-eight postmenopausal women with receptor-positive early breast cancer were randomly assigned (double-blind) between March 1998 and May 2003 to receive 5 years of adjuvant endocrine therapy with letrozole, tamoxifen, or a sequence of these agents. Seven thousand nine hundred sixty-three patients who actually received therapy are included in this safety analysis, which focuses on cardiovascular events. AE recording ceased 30 days after therapy completion (or after switch on the sequential arms). Baseline comorbidities were balanced. At a median follow-up time of 30.1 months, we observed similar overall incidence of cardiac AEs (letrozole, 4.8%; tamoxifen, 4.7%), more grade 3 to 5 cardiac AEs on letrozole (letrozole, 2.4%; tamoxifen, 1.4%; P = .001)--an excess only partially attributable to prior hypercholesterolemia--and more overall (tamoxifen, 3.9%; letrozole, 1.7%; P < .001) and grade 3 to 5 thromboembolic AEs on tamoxifen (tamoxifen, 2.3%; letrozole, 0.9%; P < .001). There was no significant difference between tamoxifen and letrozole in incidence of hypertension or cerebrovascular events. The present safety analysis, limited to cardiovascular AEs in BIG 1-98, documents a low overall incidence of cardiovascular AEs, which differed between treatment arms.

  20. Adjuvant tamoxifen but not aromatase inhibitor therapy decreases serum levels of the Wnt inhibitor dickkopf-1 while not affecting sclerostin in breast cancer patients.

    Science.gov (United States)

    Göbel, Andy; Kuhlmann, Jan D; Link, Theresa; Wimberger, Pauline; Browne, Andrew J; Rauner, Martina; Hofbauer, Lorenz C; Rachner, Tilman D

    2017-08-01

    Endocrine therapies, including tamoxifen or aromatase inhibitors, are indispensable for the treatment of patients with estrogen receptor (ER)- and/or progesterone-positive breast cancer. Whereas tamoxifen displays partial ER agonistic effects in bone, aromatase inhibitors increase bone resorption and fracture risk. The Wnt inhibitors dickkopf-1 (DKK-1) and sclerostin negatively impact bone formation and are considered targets for the treatment of bone disorders. However, the effect of endocrine therapies on serum DKK-1 and sclerostin levels in patients with primary breast cancer remains elusive. Serum DKK-1 and sclerostin levels were measured at primary diagnosis as well as 3-5 days and 12 months after surgery in a cohort of 45 pre- and postmenopausal women with primary estrogen receptor-positive breast cancer treated with adjuvant tamoxifen or aromatase inhibitors. Mean baseline levels ±SD for DKK-1 and sclerostin were 29.7 ± 14.6 and 27.1 ± 16.2 pmol/l, respectively. A significant negative correlation of DKK-1 levels and age was observed (r = -0.32; p < 0.05), but not for sclerostin. Of note, DKK-1 levels were significantly lower in peri- and postmenopausal women compared to premenopausal patients (-47%; p < 0.05). In tamoxifen-treated patients, DKK-1 levels were reduced by 35% (p < 0.01) one year after surgery but remained unaltered in patients treated with aromatase inhibitors. No significant changes were observed for sclerostin. DKK-1 serum levels were reduced in breast cancer patients receiving an adjuvant therapy with tamoxifen, possibly contributing to its bone-protective properties.

  1. Hyperbaric Oxygen Therapy is Ineffective as an Adjuvant to Daptomycin with Rifampicin Treatment in a Murine Model of Staphylococcus aureus in Implant-Associated Osteomyelitis

    Directory of Open Access Journals (Sweden)

    Nis Pedersen Jørgensen

    2017-04-01

    Full Text Available Implant-associated infections caused by bacterial biofilms are difficult to treat. Surgical intervention is often necessary to cure the patient, as the antibiotic recalcitrance of biofilms renders them untreatable with conventional antibiotics. Intermittent hyperbaric oxygen treatment (HBOT has been proposed as an adjuvant to conventional antibiotic treatment and it has been speculated that combining HBOT with antibiotics could improve treatment outcomes for biofilm infections. In this study we addressed whether HBOT could improve treatment outcomes of daptomycin and rifampicin combination therapy. The effect of HBOT on the treatment outcomes of daptomycin and rifampicin against implant-associated osteomyelitis was quantified in a murine model. In total, 80 mice were randomized into two groups receiving antibiotics, either alone or in combination with daily intermittent HBOT (304 kPa for 60 min following injection of antibiotics. Treatment was initiated 11 days after animals were infected with Staphylococcus aureus and treatment duration was 14 days. We found that HBOT did not improve the cure rate and did not reduce the bacterial load on the implant surface or in the surrounding tissue. Cure rates of daptomycin + rifampicin were 40% in infected tibias and 75% for implants while cure rates for HBOT-daptomycin + rifampicin were 50% and 85%, respectively, which were not significantly higher (Fisher’s exact test. While it is encouraging that the combination of daptomycin and rifampicin is very effective, our study demonstrates that this efficacy cannot be improved by adjuvant HBOT.

  2. Improvement of different vaccine delivery systems for cancer therapy

    Directory of Open Access Journals (Sweden)

    Safaiyan Shima

    2011-01-01

    Full Text Available Abstract Cancer vaccines are the promising tools in the hands of the clinical oncologist. Many tumor-associated antigens are excellent targets for immune therapy and vaccine design. Optimally designed cancer vaccines should combine the best tumor antigens with the most effective immunotherapy agents and/or delivery strategies to achieve positive clinical results. Various vaccine delivery systems such as different routes of immunization and physical/chemical delivery methods have been used in cancer therapy with the goal to induce immunity against tumor-associated antigens. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target antigen-presenting cells (APCs have demonstrated to be effective in animal models. New developments in vaccine delivery systems will improve the efficiency of clinical trials in the near future. Among them, nanoparticles (NPs such as dendrimers, polymeric NPs, metallic NPs, magnetic NPs and quantum dots have emerged as effective vaccine adjuvants for infectious diseases and cancer therapy. Furthermore, cell-penetrating peptides (CPP have been known as attractive carrier having applications in drug delivery, gene transfer and DNA vaccination. This review will focus on the utilization of different vaccine delivery systems for prevention or treatment of cancer. We will discuss their clinical applications and the future prospects for cancer vaccine development.

  3. Bisphosphonates in the adjuvant setting of breast cancer therapy--effect on survival: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Irit Ben-Aharon

    Full Text Available The role of bisphosphonates (BP in early breast cancer (BC has been considered controversial. We performed a meta-analysis of all randomized controlled trials (RCTs that appraised the effects of BP on survival in early BC.RCTs were identified by searching the Cochrane Library, MEDLINE databases and conference proceedings. Hazard ratios (HRs of overall survival (OS, disease-free survival (DFS and relative risks of adverse events were estimated and pooled.Thirteen trials met the inclusion criteria, evaluating a total of 15,762 patients. Meta-analysis of ten trials which reported OS revealed no statistically significant benefit in OS for BP (HR 0.89, 95% CI = 0.79 to 1.01. Meta-analysis of nine trials which reported the DFS revealed no benefit in DFS (HR 0.95 (0.81-1.12. Meta-analysis upon menopausal status showed a statistically significant better DFS in the BP-treated patients (HR 0.81(0.69-0.95. In meta-regression, chemotherapy was negatively associated with HR of survival.Our meta-analysis indicates a positive effect for adjuvant BP on survival only in postmenopausal patients. Meta-regression demonstrated a negative association between chemotherapy use BP effect on survival. Further large scale RCTs are warranted to unravel the specific subgroups that would benefit from the addition of BP in the adjuvant setting.

  4. A randomised comparison of bicalutamide ('Casodex') 150 mg versus placebo as immediate therapy either alone or as adjuvant to standard care for early non-metastatic prostate cancer. First report from the Scandinavian Prostatic Cancer Group Study No. 6

    DEFF Research Database (Denmark)

    Iversen, P; Tammela, T L J; Vaage, S

    2002-01-01

    To assess the efficacy and tolerability of bicalutamide 150 mg ('Casodex'(1)) as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with early (T1b-T4, any N, M0) prostate cancer....

  5. Adjuvant occupational therapy improves long-term depression recovery and return-to-work in good health in sick-listed employees with major depression: results of a randomised controlled trial

    NARCIS (Netherlands)

    Hees, Hiske L.; de Vries, Gabe; Koeter, Maarten W. J.; Schene, Aart H.

    2013-01-01

    To evaluate whether adjuvant occupational therapy (OT) can improve the effectiveness of treatment-as-usual (TAU) in sick-listed employees with major depression. In total, 117 employees sick-listed for a median duration of 4.8 months (IQR=2.6 to 10.1 months) because of major depression were

  6. Cell-Based Systems Biology Analysis of Human AS03-Adjuvanted H5N1 Avian Influenza Vaccine Responses: A Phase I Randomized Controlled Trial.

    Science.gov (United States)

    Howard, Leigh M; Hoek, Kristen L; Goll, Johannes B; Samir, Parimal; Galassie, Allison; Allos, Tara M; Niu, Xinnan; Gordy, Laura E; Creech, C Buddy; Prasad, Nripesh; Jensen, Travis L; Hill, Heather; Levy, Shawn E; Joyce, Sebastian; Link, Andrew J; Edwards, Kathryn M

    2017-01-01

    Vaccine development for influenza A/H5N1 is an important public health priority, but H5N1 vaccines are less immunogenic than seasonal influenza vaccines. Adjuvant System 03 (AS03) markedly enhances immune responses to H5N1 vaccine antigens, but the underlying molecular mechanisms are incompletely understood. We compared the safety (primary endpoint), immunogenicity (secondary), gene expression (tertiary) and cytokine responses (exploratory) between AS03-adjuvanted and unadjuvanted inactivated split-virus H5N1 influenza vaccines. In a double-blinded clinical trial, we randomized twenty adults aged 18-49 to receive two doses of either AS03-adjuvanted (n = 10) or unadjuvanted (n = 10) H5N1 vaccine 28 days apart. We used a systems biology approach to characterize and correlate changes in serum cytokines, antibody titers, and gene expression levels in six immune cell types at 1, 3, 7, and 28 days after the first vaccination. Both vaccines were well-tolerated. Nine of 10 subjects in the adjuvanted group and 0/10 in the unadjuvanted group exhibited seroprotection (hemagglutination inhibition antibody titer > 1:40) at day 56. Within 24 hours of AS03-adjuvanted vaccination, increased serum levels of IL-6 and IP-10 were noted. Interferon signaling and antigen processing and presentation-related gene responses were induced in dendritic cells, monocytes, and neutrophils. Upregulation of MHC class II antigen presentation-related genes was seen in neutrophils. Three days after AS03-adjuvanted vaccine, upregulation of genes involved in cell cycle and division was detected in NK cells and correlated with serum levels of IP-10. Early upregulation of interferon signaling-related genes was also found to predict seroprotection 56 days after first vaccination. Using this cell-based systems approach, novel mechanisms of action for AS03-adjuvanted pandemic influenza vaccination were observed. ClinicalTrials.gov NCT01573312.

  7. Advances and challenges in mucosal adjuvant technology.

    Science.gov (United States)

    Newsted, Daniel; Fallahi, Firouzeh; Golshani, Ashkan; Azizi, Ali

    2015-05-15

    Adjuvants play attractive roles in enhancement of immune response during vaccination; however, due to several challenges, only a limited number of adjuvants are licensed by health authorities. The lack of an effective mucosal adjuvant is even more significant as none of the licensed adjuvants revealed a strong enhancement in immune system after mucosal administration. Over the past two decades, several mucosal adjuvants have been developed to deliver antigens to the target cells in the mucosal immune system and increase specific immune responses. However, the safety and efficacy of these adjuvants for testing in human trials is still an important issue, requiring further study. In this article, we briefly review the challenges associated with most common mucosal adjuvants and discuss potential strategies for targeting the mucosal immune system. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Self-reported physical activity behavior of breast cancer survivors during and after adjuvant therapy: 12 months follow-up of two randomized exercise intervention trials.

    Science.gov (United States)

    Schmidt, Martina E; Wiskemann, Joachim; Ulrich, Cornelia M; Schneeweiss, Andreas; Steindorf, Karen

    2017-04-01

    Exercise during and after breast cancer treatment has shown several health benefits. However, little is known about the courses, patterns, and determinants of physical activity of breast cancer patients, and the role of exercise interventions on their physical activity behavior in the long run. Self-reported physical activity was assessed in 227 breast cancer survivors before, during, and three, six, and 12 months post-intervention within two randomized resistance exercise trials performed during adjuvant chemo- or radiotherapy, respectively, with similar designs. Multiple ordinal logistic regression analyses were performed to identify determinants of physical activity at these time points. While the intervention group exercised a median 1.8 h/week during adjuvant therapy (interquartile range 1.4-2.5), 68% of controls did not engage in any exercise. At 12-months follow-up 32% of patients did not engage in any exercise irrespective of the intervention. Of the patients who cycled for transportation pre-diagnosis about half stopped cycling in the long term in both groups. In contrast, walking was maintained over time. Major determinants of low levels of exercise at 12-months follow-up were low pre-diagnosis levels of exercise, lower education, being postmenopausal, and having breast problems or depressive symptoms. Further, the intervention appeared to influence the type of sports performed, with strength exercise being the most common type of exercise at follow-up in the exercise group, more frequently compared to the control group. The exercise intervention effectively countervailed the decrease in physical activity during cancer therapy and boosted strength exercise in the months following the intervention, but in the longer term many survivors were insufficiently active. Breast cancer survivors may need continued motivation and practical support tailored to their individual characteristics and physical activity history to incorporate exercise in everyday routine

  9. Overexpression of sphingosine kinase 1 is associated with salivary gland carcinoma progression and might be a novel predictive marker for adjuvant therapy

    Directory of Open Access Journals (Sweden)

    Liu Guanglin

    2010-09-01

    Full Text Available Abstract Background Overexpression of sphingosine kinase-1 (SPHK1 has been demonstrated to be associated with the development and progression in various types of human cancers. The current study was to characterize the expression of SPHK1 in salivary gland carcinomas (SGC and to investigate the association between SPHK1 expression and progression of SGC. Methods The expression of SPHK1 was examined in 2 normal salivary gland tissues, 8 SGC tissues of various clinical stages, and 5 pairs of primary SGC and adjacent salivary gland tissues from the same patient, using real-time PCR and western blot analysis. Furthermore, the SPHK1 protein expression was analyzed in 159 clinicopathologically characterized SGC cases by immunohistochemistry. Statistical analyses were performed to determine the prognostic and diagnostic associations. Results SPHK1 expression was found to be markedly upregulated in SGC tissues than that in the normal salivary gland tissues and paired adjacent salivary gland tissues, at both mRNA and protein levels. Statistical analysis revealed a significant correlation of SPHK1 expression with the clinical stage (P = 0.005, T classification (P = 0.017, N classification (P = 0.009, M classification (P = 0.002, and pathological differentiation (P = 0.013. Patients with higher SPHK1 expression had shorter overall survival time, whereas patients with lower SPHK1 expression had better survival. Importantly, patients in the group without adjuvant therapy who exhibited high SPHK1 expression had significantly lower overall survival rates compared with those with low SPHK1 expression. Moreover, multivariate analysis suggested that SPHK1 expression might be an independent prognostic indicator for the survival of SGC patients. Conclusions Our results suggest that SPHK1 expression is associated with SGC progression, and might represent as a novel and valuable predictor for adjuvant therapy to SGC patients.

  10. Implementation and evaluation of an Asbru-based decision support system for adjuvant treatment in breast cancer.

    Science.gov (United States)

    Eccher, Claudio; Seyfang, Andreas; Ferro, Antonella

    2014-11-01

    The domain of cancer treatment is a promising field for the implementation and evaluation of a protocol-based clinical decision support system, because of the algorithmic nature of treatment recommendations. However, many factors can limit such systems' potential to support the decision of clinicians: technical challenges related to the interoperability with existing electronic patient records and clinical challenges related to the inherent complexity of the decisions, often collectively taken by panels of different specialists. In this paper, we evaluate the performances of an Asbru-based decision support system implementing treatment protocols for breast cancer, which accesses data from an oncological electronic patient record. Focusing on the decision on the adjuvant pharmaceutical treatment for patients affected by early invasive breast cancer, we evaluate the matching of the system's recommendations with those issued by the multidisciplinary panel held weekly in a hospital. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Use of probiotics as an adjuvant to sequential H. pylori eradication therapy: impact on eradication rates, treatment resistance, treatment-related side effects, and patient compliance.

    Science.gov (United States)

    Çekin, Ayhan Hilmi; Şahintürk, Yasin; Akbay Harmandar, Ferda; Uyar, Seyit; Yolcular, Başak Oğuz; Çekin, Yeşim

    2017-01-01

    To evaluate the effect of probiotics administered as an adjuvant to sequential Helicobacter pylori (H. pylori) eradication therapy on treatment outcome and patient compliance. In total, 159 patients with H. pylori infection receiving sequential H. pylori eradication therapy were included in this randomized placebo-controlled study. Starting from day 0 of sequential eradication therapy (ERA), patients in the ERA+probiotic group [n=53, mean (SD) age: 47.7 (14.0) years, 54.7% were females] also received a probiotic supplement with Bifidobacterium animalis subsp. lactis B94 (1 capsule/day), patients in the ERA+placebo group [n=52, mean (SD) age: 46.4 (13.4) years, 51.9% were males] received placebo treatment (1 capsule/day), and patients in the ERA-only group [n=54, mean (SD) age: 46.3 (11.9) years, 55.6% were females] received no additional treatments. Eradication rates, patient compliance, and side effects of eradication therapy were recorded in each treatment group. Significantly higher eradication rates were noted in the ERA+probiotic group (86.8% vs. 70.8%, p=0.025) than in the combined ERA (ERA-only and ERA-placebo) group. Non-compliance with anti-H. pylori treatment was noted in 24 (15.1%) of 159 patients. Lower rates of first week treatment non-compliance due to diarrhea (1.88% vs. 12.26%, p=0.036) were noted in the ERA+probiotic group than in the combined ERA (ERA-only and ERA-placebo) group. Treatment resistance (p: 0.389) was similar between the groups, indicating pure antibiotic resistance without any compliance problems. The number needed to treat for an additional beneficial outcome (NNTB) was 6.2 (CI 95%, 3.5 to 28.9) for probiotic use. In conclusion, adjuvant administration of probiotic (B. animalis subsp. lactis) in 2-week sequential H. pylori eradication therapy is associated with a higher H. pylori eradication rate, lower first week diarrhea-related treatment discontinuation rates, less common self-reported side effects, and higher treatment

  12. Sequential FDG-PET/CT reliably predicts response of locally advanced rectal cancer to neo-adjuvant chemo-radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Capirci, Carlo [Hospital, Division of Radiotherapy, Rovigo (Italy); Rampin, Lucia; Banti, Elena [Hospital, Nuclear Medicine and PET Service, Rovigo (Italy); Erba, Paola A.; Mariani, Giuliano [Regional Center of Nuclear Medicine, Univ. Pisa (Italy); Galeotti, Fabrizio [Hospital, Division of Surgery, Rovigo (Italy); Crepaldi, Giorgio [Hospital, Division of Oncology, Rovigo (Italy); Gava, Marcello [Hospital, Medical Physics Service, Rovigo (Italy); Fanti, Stefano [Politecnico Bologna (Italy). Dept. of Nuclear Medicine; Muzzio, Pier C. [Dept. of Radiology, Ist. Oncologico, Padova (Italy); Rubello, Domenico [Rovigo Hospital, Istituto Oncologico Veneto (IOV)-IRCCS, Nuclear Medicine Service, PET Unit, Rovigo (Italy)

    2007-10-15

    Prediction of rectal cancer response to preoperative, neo-adjuvant chemo-radiation therapy (CRT) provides the opportunity to identify patients in whom a major response is expected and who may therefore benefit from alternative surgical approaches. Traditional morphological imaging techniques are effective in defining tumour extension in the initial diagnostic and staging work-up, but perform poorly in distinguishing residual neoplastic tissue from scarring post CRT, when restaging the patient before surgery. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is a promising tool for monitoring the effect of anti-tumour therapy. The aim of this study was to prospectively assess the value of sequential FDG-PET scans in predicting the response of locally advanced rectal cancer to neo-adjuvant CRT. Forty-four consecutive patients with locally advanced (cT3-4) primary rectal cancer and four patients with pelvic recurrence of rectal cancer were enrolled in this prospective study. Treatment consisted of external beam intensified radiotherapy, chemotherapy and, 8-10 weeks later, surgery with curative intent. All patients underwent FDG-PET/CT both before CRT and 5-6 weeks after completing CRT. One patient died before surgery because of acute myocardial infarction, and was therefore excluded from further analysis. Semi-quantitative measurements of FDG uptake (SUV{sub max}), absolute difference ({delta}SUV{sub max}) and percent SUV{sub max} difference (Response Index, RI) between pre- and post-CRT PET scans were considered. Results were correlated with pathological response, assessed both by histopathological staging of the surgical specimens (pTNM) and by the tumour regression grade (TRG) according to Mandard's criteria (patients with TRG1-2 being defined as responders and patients with TRG3-5 as non-responders). Following neo-adjuvant CRT, of the 45 patients submitted to surgery, 23 (51.1%) were classified as responders according to Mandard

  13. Adjuvant therapy after resection of brain metastases. Frameless image-guided LINAC-based radiosurgery and stereotactic hypofractionated radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Broemme, J.; Aebersold, D.M.; Pica, A. [Bern Univ., Bern Univ. Hospital (Switzerland). Dept. of Radiation Oncology; Abu-Isa, J.; Beck, J.; Raabe, A. [Bern Univ., Bern Univ. Hospital (Switzerland). Neurosurgery; Kottke, R.; Wiest, R. [Bern Univ., Bern Univ. Hospital (Switzerland). Neuroradiology; Malthaner, M.; Schmidhalter, D. [Bern Univ., Bern Univ. Hospital (Switzerland). Div. of Medical Radiation Physics

    2013-09-15

    Background: Tumor bed stereotactic radiosurgery (SRS) after resection of brain metastases is a new strategy to delay or avoid whole-brain irradiation (WBRT) and its associated toxicities. This retrospective study analyzes results of frameless image-guided linear accelerator (LINAC)-based SRS and stereotactic hypofractionated radiotherapy (SHRT) as adjuvant treatment without WBRT. Materials and methods: Between March 2009 and February 2012, 44 resection cavities in 42 patients were treated with SRS (23 cavities) or SHRT (21 cavities). All treatments were delivered using a stereotactic LINAC. All cavities were expanded by {>=} 2 mm in all directions to create the clinical target volume (CTV). Results: The median planning target volume (PTV) for SRS was 11.1 cm{sup 3}. The median dose prescribed to the PTV margin for SRS was 17 Gy. Median PTV for SHRT was 22.3 cm{sup 3}. The fractionation schemes applied were: 4 fractions of 6 Gy (5 patients), 6 fractions of 4 Gy (6 patients) and 10 fractions of 4 Gy (10 patients). Median follow-up was 9.6 months. Local control (LC) rates after 6 and 12 months were 91 and 77 %, respectively. No statistically significant differences in LC rates between SRS and SHRT treatments were observed. Distant brain control (DBC) rates at 6 and 12 months were 61 and 33 %, respectively. Overall survival (OS) at 6 and 12 months was 87 and 63.5 %, respectively, with a median OS of 15.9 months. One patient treated by SRS showed symptoms of radionecrosis, which was confirmed histologically. Conclusion: Frameless image-guided LINAC-based adjuvant SRS and SHRT are effective and well tolerated local treatment strategies after resection of brain metastases in patients with oligometastatic disease. (orig.)

  14. Review of levetiracetam, with a focus on the extended release formulation, as adjuvant therapy in controlling partial-onset seizures

    Directory of Open Access Journals (Sweden)

    Carol M Ulloa

    2009-09-01

    Full Text Available Carol M Ulloa, Allen Towfigh, Joseph SafdiehDepartment of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, USAAbstract: Levetiracetam is a second-generation antiepileptic drug (AED with a unique chemical structure and mechanism of action. The extended release formulation of levetiracetam (Keppra XR™; UCB Pharma was recently approved by the Food and Drug Administration for adjunctive therapy in the treatment of partial-onset seizures in patients 16 years of age and older with epilepsy. This approval is based on a double-blind, randomized, placebo-controlled, multicenter, multinational trial. Levetiracetam XR allows for once-daily dosing, which may increase compliance and, given the relatively constant plasma concentrations, may minimize concentration-related adverse effects. Levetiracetam’s mode of action is not fully elucidated, but it has been found to target high-voltage, N-type calcium channels as well as the synaptic vesicle protein 2A (SV2A. Levetiracetam has nearly ideal pharmacokinetics. It is rapidly and almost completely absorbed after oral ingestion, is ‹10% protein-bound, demonstrates linear kinetics, is minimally metabolized through a pathway independent of the cytochrome P450 system, has no significant drug–drug interactions, and has a wide therapeutic index. The most common reported adverse events with levetiracetam XR were somnolence, irritability, dizziness, nausea, influenza, and nasopharyngitis. Levetiracetam XR provides an efficacious and well-tolerated treatment option for adjunctive therapy in the treatment of partial-onset seizures.Keywords: levetiracetam, partial-onset seizures, antiepileptic drugs

  15. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98.

    Science.gov (United States)

    Coates, Alan S; Keshaviah, Aparna; Thürlimann, Beat; Mouridsen, Henning; Mauriac, Louis; Forbes, John F; Paridaens, Robert; Castiglione-Gertsch, Monica; Gelber, Richard D; Colleoni, Marco; Láng, István; Del Mastro, Lucia; Smith, Ian; Chirgwin, Jacquie; Nogaret, Jean-Marie; Pienkowski, Tadeusz; Wardley, Andrew; Jakobsen, Erik H; Price, Karen N; Goldhirsch, Aron

    2007-02-10

    Previous analyses of the Breast International Group (BIG) 1-98 four-arm study compared initial therapy with letrozole or tamoxifen including patients randomly assigned to sequential treatment whose information was censored at the time of therapy change. Because this presentation may unduly reflect early events, the present analysis is limited to patients randomly assigned to the continuous therapy arms and includes protocol-defined updated results. Four thousand nine hundred twenty-two of the 8,028 postmenopausal women with receptor-positive early breast cancer randomly assigned (double-blind) to the BIG 1-98 trial were assigned to 5 years of continuous adjuvant therapy with either letrozole or tamoxifen; the remainder of women were assigned to receive the agents in sequence. Disease-free survival (DFS) was the primary end point. At a median follow-up time of 51 months, we observed 352 DFS events among 2,463 women receiving letrozole and 418 events among 2,459 women receiving tamoxifen. This reflected an 18% reduction in the risk of an event (hazard ratio, 0.82; 95% CI, 0.71 to 0.95; P = .007). No predefined subsets showed differential benefit. Adverse events were similar to previous reports. Patients on tamoxifen experienced more thromboembolic events, endometrial pathology, hot flashes, night sweats, and vaginal bleeding. Patients on letrozole experienced more bone fractures, arthralgia, low-grade hypercholesterolemia, and cardiovascular events other than ischemia and cardiac failure. The present updated analysis, which was limited to patients on monotherapy arms in BIG 1-98, yields results similar to those from the previous primary analysis but more directly comparable with results from other trials of continuous therapy using a single endocrine agent.

  16. Effect of adjuvant systemic treatment on cosmetic outcome and late normal-tissue reactions after breast conservation

    DEFF Research Database (Denmark)

    Johansen, Jørgen; Overgaard, Jens; Overgaard, Marie

    2007-01-01

    -risk patients: premenopausal patients (n = 67) received eight cycles of CMF intravenously (600/40/600 mg per m(2)) every fourth week; postmenopausal patients (n = 27) received 30 mg of tamoxifen daily for one year. Clinical assessments included cosmetic outcome, breast fibrosis, skin telangiectasia....... In premenopausal patients, systemic treatment with CMF independently predicted a fair/poor cosmetic outcome, RR = 2.2 (95% CI 1.2-4.2), as well as increased skin telangiectasia, RR = 3.3 (1.4-8.2). There was no impact of tamoxifen treatment on cosmetic outcome in postmenopausal patients (p = 0.32). However.......8-10.3), respectively. Adjuvant systemic treatment with CMF given sequentially to radiotherapy independently predicted an adverse cosmetic outcome as well as increased skin telangiectasia after breast conserving treatment. Due to a strong interaction between tamoxifen administration and radiation to the regional lymph...

  17. Phase 2 Trial of Hypofractionated High-Dose Intensity Modulated Radiation Therapy With Concurrent and Adjuvant Temozolomide for Newly Diagnosed Glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Iuchi, Toshihiko, E-mail: tiuchi@chiba-c.jp [Division of Neurological Surgery, Chiba Cancer Center, Chiba (Japan); Hatano, Kazuo; Kodama, Takashi [Division of Radiation Oncology, Chiba Cancer Center, Chiba (Japan); Sakaida, Tsukasa [Division of Neurological Surgery, Chiba Cancer Center, Chiba (Japan); Yokoi, Sana [Division of Gene Diagnosis, Chiba Cancer Center, Chiba (Japan); Kawasaki, Koichiro; Hasegawa, Yuzo [Division of Neurological Surgery, Chiba Cancer Center, Chiba (Japan); Hara, Ryusuke [Division of Radiation Oncology, Chiba Cancer Center, Chiba (Japan)

    2014-03-15

    Purpose/Objectives: To assess the effect and toxicity of hypofractionated high-dose intensity modulated radiation therapy (IMRT) with concurrent and adjuvant temozolomide (TMZ) in 46 patients with newly diagnosed glioblastoma multiforme (GBM). Methods and Materials: All patients underwent postsurgical hypofractionated high-dose IMRT. Three layered planning target volumes (PTVs) were contoured. PTV1 was the surgical cavity and residual tumor on T1-weighted magnetic resonance images with 5-mm margins, PTV2 was the area with 15-mm margins surrounding the PTV1, and PTV3 was the high-intensity area on fluid-attenuated inversion recovery images. Irradiation was performed in 8 fractions at total doses of 68, 40, and 32 Gy for PTV1, PTV2, and PTV3, respectively. Concurrent TMZ was given at 75 mg/m{sup 2}/day for 42 consecutive days. Adjuvant TMZ was given at 150 to 200 mg/m{sup 2}/day for 5 days every 28 days. Overall and progression-free survivals were evaluated. Results: No acute IMRT-related toxicity was observed. The dominant posttreatment failure pattern was dissemination. During a median follow-up time of 16.3 months (range, 4.3-80.8 months) for all patients and 23.7 months (range, 12.4-80.8 months) for living patients, the median overall survival was 20.0 months after treatment. Radiation necrosis was diagnosed in 20 patients and was observed not only in the high-dose field but also in the subventricular zone (SVZ). Necrosis in the SVZ was significantly correlated with prolonged survival (hazard ratio, 4.08; P=.007) but caused deterioration in the performance status of long-term survivors. Conclusions: Hypofractionated high-dose IMRT with concurrent and adjuvant TMZ altered the dominant failure pattern from localized to disseminated and prolonged the survival of patients with GBM. Necrosis in the SVZ was associated with better patient survival, but the benefit of radiation to this area remains controversial.

  18. Adjuvant radiotherapy following radical hysterectomy for patients with stage IB and IIA cervical cancer

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    Soisson, A.P.; Soper, J.T.; Clarke-Pearson, D.L.; Berchuck, A.; Montana, G.; Creasman, W.T. (Duke Univ. Medical Center, Durham, NC (USA))

    1990-06-01

    From 1971 through 1984, 320 women underwent radical hysterectomy as primary therapy of stage IB and IIA cervical cancer. Two hundred forty-eight patients (78%) were treated with surgery alone and 72 patients (22%) received adjuvant postoperative external-beam radiotherapy. Presence of lymph node metastasis, large lesion (greater than 4 cm in diameter), histologic grade, race (noncaucasian), and age (greater than 40 years) were significant poor prognostic factors for the entire group of patients. Patients treated with surgery alone had a better disease-free survival than those who received combination therapy (P less than 0.001). However, patients receiving adjuvant radiation therapy had a higher incidence of lymphatic metastases, tumor involvement of the surgical margin, and large cervical lesions. Adjuvant pelvic radiation therapy did not improve the survival of patients with unilateral nodal metastases or those who had a large cervical lesion with free surgical margins and the absence of nodal involvement. Radiation therapy appears to reduce the incidence of pelvic recurrences. Unfortunately, 84% of patients who developed recurrent tumor after combination therapy had a component of distant failure. The incidence of severe gastrointestinal or genitourinary tract complications was not different in the two treatment groups. However, the incidence of lymphedema was increased in patients who received adjuvant radiation therapy. Although adjuvant radiation therapy appears to be tolerated without a significant increase in serious complications, the extent to which it may improve local control rates and survival in high-risk patients appears to be limited. In view of the high incidence of distant metastases in high-risk patients, consideration should be given to adjuvant systemic chemotherapy in addition to radiation therapy.

  19. Bcl-2 inhibitor uploaded upconversion nanophotosensitizers to overcome the photodynamic therapy resistance of cancer through adjuvant intervention strategy

    NARCIS (Netherlands)

    Liu, X.; Fan, Z.; Zhang, L.; Jin, Z.; Yan, D.; Zhang, Y.; Li, X.; Tu, L.; Xue, B.; Chang, Y.; Zhang, H.; Kong, X.

    2017-01-01

    Similar to many other anticancer therapies, photodynamic therapy (PDT) also suffers from the intrinsic cancer resistance mediated by cell survival pathways. These survival pathways are regulated by various proteins, among which anti-apoptotic protein Bcl-2 plays an important role in regulation of

  20. Qualitative immune modulation by interleukin-2 (IL-2 adjuvant therapy in immunological non responder HIV-infected patients.

    Directory of Open Access Journals (Sweden)

    Francesca Sabbatini

    Full Text Available BACKGROUND: Treatment of HIV-infected patients with interleukin-2 (IL-2 produces significant increases in CD4 T cell counts; however an associated qualitative improvement in cells function has yet to be conclusively demonstrated. By measuring mycobacterial killing activity, we evaluated IL-2-mediated functional immune enhancement ex vivo in immunological non-responders (INRs. METHODS AND FINDINGS: PBMC from 12 immunological non-responders (INRs (CD4+<200/µl, HIV-RNA<50 cp/ml on combination antiretroviral treatment (cART were collected at baseline, and after 3 IL-2 cycles. Eight INRs receiving only cART were studied as controls. After 21 days of PBMC incubation with a virulent M. avium suspension, counts of residual colony forming units (CFUs and concentrations of TNF-α, IL-10 and IFN-γ were determined. In IL-2 treated patients, a significant reduction in mean residual CFUs of PBMC cultures was observed (p<0.01. Moreover, following IL-2 treatment, significant increases in PBMC's IFNγ production (p = 0.02 and substantial reductions in IL-10 levels were observed. CONCLUSIONS: IL-2 therapy restores the ability of the lympho-monocyte system in eliciting an effective response against mycobacterial infections. Our data indicate the possibility of a clinical role held by IL-2 in enhancing the immune function of subjects unable to achieve immune competence through cART alone.

  1. Hyperthermic intraperitoneal chemotherapy plus high-frequency diathermic therapy followed by intravenous chemotherapy versus intravenous chemotherapy alone for postoperative adjuvant treatment of gastrointestinal cancer: a comparative research study.

    Science.gov (United States)

    Gao, Li-Zhen; Gao, E-Mei; Bai, Yun-Fei; Su, Hai-Long; Zhang, Fan; Ge, Mei-Qing; Liu, Dong-Lian; Huang, Yan-Kun

    2016-01-01

    To evaluate the therapeutic efficacy and toxicity of hyperthermic intraperitoneal chemotherapy (HIPEC) plus high-frequency diathermic therapy (HFDT) followed by intravenous chemotherapy vs intravenous chemotherapy alone for adjuvant treatment of postoperative gastrointestinal neoplasms. Fifty-two gastrointestinal carcinoma patients who were radically operated were enrolled and divided into the treatment group and the control group. In the treatment group, 25 patients were treated with combination of HIPEC+HFDT and subsequent intravenous chemotherapy, while in the control group 27 patients received intravenous chemotherapy alone. Post-therapeutic complications and adverse reactions, time to progression (TTP) and overall survival (OS) were compared between these two groups. Difference in toxic reactions between the two groups was not statistically significant (p>0.05). Postoperative progression- free survival (PFS) rate at 12 and 40 months after radical surgery was 72.0 and 54.0% respectively in the treatment group, and 65.8 and 11.5% respectively in the control group (p=0.108). TTP was statistically significantly longer in the treatment group than in the control group (median TTP 40.1 vs 18.5 months, p=0.027). Postoperative OS at 12 and 20 months after radical surgery was 88.0 and 78.0% respectively in the treatment group and 92.6 and 72.7% in the control group, without significant difference. After radical surgery, combination of HIPEC+HFDT and subsequent intravenous chemotherapy brings about superior PFS compared with intravenous adjuvant chemotherapy alone, while having no more complications and adverse reactions.

  2. E2F1/TS Immunophenotype and Survival of Patients with Colorectal Cancer Treated with 5FU-Based Adjuvant Therapy.

    Science.gov (United States)

    Sulzyc-Bielicka, Violetta; Domagala, Pawel; Bielicki, Dariusz; Safranow, Krzysztof; Rogowski, Wojciech; Domagala, Wenancjusz

    2016-07-01

    The predictive value of thymidylate synthase (TS) expression alone for 5FU-based treatment of colorectal cancer (CRC) has not been clinically confirmed. Little is known on the association of expression of E2F1, which controls the transcription of genes encoding proteins engaged in DNA synthesis including TS, and survival of patients with CRC. The purpose of this study is to assess the correlation between expression of both E2F1 and TS in CRCs and survival of patients administered adjuvant 5FU-based chemotherapy, in order to find a better predictor of treatment outcome than expression of TS or E2F1 alone. Nuclear TS and E2F1 were detected by immunohistochemistry in tissue microarrays from 190 CRCs (Astler-Coller stage B2 or C). Multivariate analysis identified significant association of the combined E2F1+TS+ immunophenotype with worse OS (HR = 3,78, P = 0,009) and DFS (HR = 2,30, P = 0,03) of patients with colon cancer. There were significant differences between E2F1+TS+ and E2F1-TS- Kaplan-Meier survival curves in relation to DFS (P = 0.008) and OS (P = 0.01). About 37 and 31 % difference in 3-year DFS and OS respectively were seen between patients with E2F1+TS+ vs. E2F1-TS- colon cancer immunophenotype. The E2F1+TS+ immunophenotype may be a marker of poor prognosis (the worst DFS and OS) of patients with colon cancer treated with 5FU-based adjuvant therapy. A subgroup of patients with this immunophenotype may require different and perhaps more aggressive treatment than 5FU-based chemotherapy. Thus, the combined E2F1/TS immunophenotype could be a potential indicator of colon cancer sensitivity to 5FU.

  3. The effect of adjuvant N-acetylcysteine effervescent tablets therapy on cardiopulmonary function and airway remodeling in patients with stable COPD

    Directory of Open Access Journals (Sweden)

    Gui-Fang Hu1

    2017-05-01

    Full Text Available Objective: To study the effect of adjuvant N-acetylcysteine (NAC effervescent tablets therapy on cardiopulmonary function and airway remodeling in patients with stable chronic obstructive pulmonary disease (COPD. Methods: Patients with stable COPD treated in Zigong Third People’s Hospital and West China Hospital, Sichuan University between May 2014 and October 2016 were selected and randomly divided into two groups, NAC group received N-acetylcysteine effervescent tablets combined with routine treatment, and control group received routine treatment. Before treatment as well as 2 weeks and 4 weeks after treatment, oxidative stress indexes and airway remodeling indexes in serum as well as inflammatory response indexes in peripheral blood were determined. Results: MDA, PC, 8-OHdG, MMP2, MMP3 and MMP9 contents in serum as well as NLRP3, ASC, p38MAPK and TREM-1 mRNA expression levels in peripheral blood mononuclear cells of both groups of patients after treatment were significantly lower than those before treatment while TAC levels as well as TIMP1 and TIMP2 contents in serum were significantly higher than those before treatment, and MDA, PC, 8-OHdG, MMP2, MMP3 and MMP9 contents in serum a well as NLRP3, ASC, p38MAPK and TREM-1 mRNA expression levels in peripheral blood mononuclear cells of NAC group after treatment were significantly lower than those of control group while TAC levels as well as TIMP1 and TIMP2 contents in serum were significantly higher than those of control group. Conclusion: Adjuvant NAC effervescent tablets treatment of stable COPD can improve the effect of oxidative stress and inflammatory response on cardiopulmonary function, and inhibit the airway remodeling caused by protease activation.

  4. Beliefs about medicine and illness are associated with fear of cancer recurrence in women taking adjuvant endocrine therapy for breast cancer.

    Science.gov (United States)

    Corter, Arden L; Findlay, Michael; Broom, Reuben; Porter, David; Petrie, Keith J

    2013-02-01

    Adjuvant endocrine therapy for early-stage breast cancer has greatly reduced the morbidity and mortality associated with breast cancer recurrence. Despite this, a significant proportion of women report fears of cancer recurrence. This study examined the associations between fear of cancer recurrence (FoR) and illness perceptions, medication beliefs, and treatment side effects in women taking adjuvant endocrine therapy following breast cancer. A total of 153 post-menopausal women with early-stage breast cancer completed a postal survey. Analyses were conducted to examine the association between FoR and illness perceptions, medication beliefs, treatment side effects, demographic factors, and emotional distress and to identify which of these factors would be most strongly associated with FoR in a regression model. All illness perceptions (apart from personal control) were associated with FoR, as were patient beliefs about endocrine therapy. Although treatment side effects, being unemployed, and higher levels of anxiety and depression were associated with FoR, only illness perceptions (identity, treatment control, timeline, and emotional representation) and medication necessity beliefs were significantly correlated with FoR in the final model. It appears that, in addition to directly targeting FoR, it may be worthwhile to address the illness and medication beliefs supporting the fear. Additionally, helping women to differentiate everyday symptoms from those indicative of breast cancer may help to reduce fear of recurrence. What is already known on this subject? A significant proportion of women report fear of cancer recurrence following breast cancer. The literature shows that illness perceptions, side effects of treatment, and beliefs about medicines are related to fear of recurrence among cancer patients. However, because these variables have often been looked at in isolation, it is not clear whether some perceptions or cues are more likely to relate to fear of

  5. Nomograms for Prediction of Outcome With or Without Adjuvant Radiation Therapy for Patients With Endometrial Cancer: A Pooled Analysis of PORTEC-1 and PORTEC-2 Trials

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    Creutzberg, Carien L., E-mail: c.l.creutzberg@lumc.nl [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands); Stiphout, Ruud G.P.M. van [Department of Radiation Oncology, MAASTRO, GROW, University Medical Centre Maastricht, Maastricht (Netherlands); Nout, Remi A. [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands); Lutgens, Ludy C.H.W. [Department of Radiation Oncology, MAASTRO, GROW, University Medical Centre Maastricht, Maastricht (Netherlands); Jürgenliemk-Schulz, Ina M. [Department of Radiation Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Jobsen, Jan J. [Department of Radiotherapy, Medisch Spectrum Twente, Enschede (Netherlands); Smit, Vincent T.H.B.M. [Department of Pathology, Leiden University Medical Center, Leiden (Netherlands); Lambin, Philippe [Department of Radiation Oncology, MAASTRO, GROW, University Medical Centre Maastricht, Maastricht (Netherlands)

    2015-03-01

    Background: Postoperative radiation therapy for stage I endometrial cancer improves locoregional control but is without survival benefit. To facilitate treatment decision support for individual patients, accurate statistical models to predict locoregional relapse (LRR), distant relapse (DR), overall survival (OS), and disease-free survival (DFS) are required. Methods and Materials: Clinical trial data from the randomized Post Operative Radiation Therapy for Endometrial Cancer (PORTEC-1; N=714 patients) and PORTEC-2 (N=427 patients) trials and registered group (grade 3 and deep invasion, n=99) were pooled for analysis (N=1240). For most patients (86%) pathology review data were available; otherwise original pathology data were used. Trial variables which were clinically relevant and eligible according to data constraints were age, stage, given treatment (pelvic external beam radiation therapy (EBRT), vaginal brachytherapy (VBT), or no adjuvant treatment, FIGO histological grade, depth of invasion, and lymph-vascular invasion (LVSI). Multivariate analyses were based on Cox proportional hazards regression model. Predictors were selected based on a backward elimination scheme. Model results were expressed by the c-index (0.5-1.0; random to perfect prediction). Two validation sets (n=244 and 291 patients) were used. Results: Accuracy of the developed models was good, with training accuracies between 0.71 and 0.78. The nomograms validated well for DR (0.73), DFS (0.69), and OS (0.70), but validation was only fair for LRR (0.59). Ranking of variables as to their predictive power showed that age, tumor grade, and LVSI were highly predictive for all outcomes, and given treatment for LRR and DFS. The nomograms were able to significantly distinguish low- from high-probability patients for these outcomes. Conclusions: The nomograms are internally validated and able to accurately predict long-term outcome for endometrial cancer patients with observation, pelvic EBRT, or VBT

  6. Evaluation of the Role of Monocular Video Game Play as an Adjuvant to Occlusion Therapy in the Management of Anisometropic Amblyopia.

    Science.gov (United States)

    Singh, Archita; Sharma, Pradeep; Saxena, Rohit

    2017-07-01

    To evaluate the role of monocular video game play as an adjuvant to occlusion therapy in the treatment of anisometropic amblyopia. In a prospective randomized study design, 68 children with ages ranging from 6 to 14 years who had anisometropic amblyopia with a best corrected visual acuity (BCVA) in the amblyopic eye of better than 6/36 and worse than 6/12 and no manifest strabismus were recruited. They were randomly allocated into two groups: 34 children received 1 hour per day of video game play for the first month plus 6 hours per day of occlusion therapy (video game and occlusion group) and 34 children received 6 hours per day of occlusion therapy alone (occlusion only group). Patients were then evaluated at baseline and 1 and 3 months after treatment for BCVA, stereoacuity, and contrast sensitivity. In the video game and occlusion group, BCVA improved from 0.61 ± 0.12 logarithm of the minimum angle of resolution (logMAR) at baseline to 0.51 ± 0.14 logMAR (P = .001) at 1 month and 0.40 ± 0.15 logMAR (P = .001) at 3 months. In the occlusion only group, BCVA improved from 0.65 ± 0.09 logMAR at baseline to 0.60 ± 0.10 logMAR (P = .001) at 1 month and 0.48 ± 0.10 logMAR (P = .001) at 3 months. There was significantly more improvement in the video game and occlusion group compared to the occlusion only group (P = .003 at 1 month and P = .027 at 3 months). Video game play plus occlusion therapy enhances the visual recovery in anisometropic amblyopia. [J Pediatr Ophthalmol Strabismus. 2017;54(4):244-249.]. Copyright 2017, SLACK Incorporated.

  7. Biocompatible Mater Constructed Microneedle Arrays as a Novel Vaccine Adjuvant- Delivery System for Cutaneous and Mucosal Vaccination.

    Science.gov (United States)

    Wang, Ting; Wang, Ning

    2015-01-01

    Vaccination is the most cost-effective and the best prophylactic strategy for the treatment of many diseases and, therefore, is widely used to improve human health. However, currently, most vaccines are given by injection which has a number of intrinsic disadvantages, such as inoculation needing professionals, waste metal needle pollution and infection, and low vaccination compliance. To overcome these drawbacks, in the past two decades a variety of microneedles have been developed and these are increasingly being widely tried to deliver vaccines due to many prominent advantages, such as their convenience, and effectiveness, over other delivery systems. In particular, the biocompatible material-constituted microneedle arrays (bioMMAs) that are fabricated with biocompatible materials in the form of a matrix or formulated micro/nanoparticles, such as liposomes, PLA/PLGA/ chitosan nanoparticles, hydrogels, polyelectrolyte multiplelayers (PEMs), plasmids, and nonvirulent pathogens, have proven an effective and stable vaccine adjuvant-delivery system (VADS) allowing painless vaccination via the cutaneous or mucosal route by minimally trained workers or by self-administration. When given to mammals through the skin or oral mucosa where affluent professional antigen-presenting cells (APCs), such as Langerhans cells, dendritic cells and macrophages, are actively patrolling for immune surveillance, the bioMMAs can efficiently elicit robust systemic as well as mucosal immunoresponses against the loaded antigens. In addition, when different vaccine adjuvants, such as TLR (toll-like receptor) ligands, have been incorporated, the bioMMAs can govern and redirect the immunoresponse toward a Th1, Th2 or a mixed Th1/Th2 pathway to establish cellular and humoral immunity to the target pathogens. In this review, various types of bioMMAs used as a VADS are described to show the latest advances and their diverse uses and potential applications in vaccine-related fields.

  8. Should oesophageal stents be used before neo-adjuvant therapy to treat dysphagia in patients awaiting oesophagectomy? Best evidence topic (BET).

    Science.gov (United States)

    Jones, Christopher M; Griffiths, Ewen A

    2014-11-01

    Patients who develop significant dysphagia secondary to a potentially curable oesophageal cancer pose a significant clinical problem. Their nutritional needs can be met either by dietary supplementation, insertion of an oesophageal stent or through nasogastric or surgical feeding tube placement. We sought to determine whether, in patients about to start neo-adjuvant therapy prior to oesophagectomy, the use of oesophageal stent improves clinical outcomes. A best evidence topic in upper gastrointestinal surgery was written according to a structured protocol in order to answer this question. Two hundred and forty eight papers were found, of which eleven level III and one level IV study were considered to best address the clinical question. These indicate that whilst oesophageal stents do successfully relieve dysphagia throughout neoadjuvant therapy, they are not consistently associated with maintenance of, or improvement in, serum albumin or body weight. They are, however, commonly associated with stent migration and chest discomfort, both of which may frequently result in the need for stent removal or replacement. There is additional evidence within the manuscripts reviewed to demonstrate that the use of oesophageal stents in the neoadjuvant setting can lead to significant complications in a small proportion of patients which can compromise opportunity for curative surgery. The use of stents in this situation cannot be recommended. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  9. Molecular Targeting of Her-2/neu Protein Is Not Recommended as an Adjuvant Therapy in Oral Squamous Cell Carcinoma and Oral Lichen Planus.

    Science.gov (United States)

    Kouhsoltani, Maryam; Aghbali, Amirala; Shokoohi, Behrooz; Ahmadzadeh, Ronak

    2015-12-01

    Target therapy against molecular markers of EGFR family has been recently used in the treatment protocol of several diseases. However, the role of Her-2/neu in OSCC is a matter of controversy and more studies are required to clarify the role of Her-2/neu in OSCC. We aimed to investigate the role of Her-2/neu in the process of carcinogenesis in oral epithelium as ELP is a premalignant and OSCC is a malignant lesion, but RLP shows no evidence of premalignancy and malignancy.To our Knowledge, this is the first study comparing Her-2/neu expression in erosive lichen planus (ELP), reticular lichen planus (RLP), and oral squamous cell carcinoma (OSCC). 60 samples, including 20 cases of RLP, 20 cases of ELP, and 20 cases of OSCC were evaluated immunohistochemically in this study. Our findings showed that there was not a significant increase in Her-2/neu expression from RLP to ELP and from ELP to OSCC. Therefore, Her-2/neu had no role in differentiating between RLP, ELP and OSCC and this protein does not contribute to the process of carcinogenesis in the oral epithelium. The lack of Her-2/neu overexpression indicates that molecular targeting of Her-2/neu protein is not recommended as an adjuvant therapy in OSCC and OLP.

  10. Adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma: a phase III randomized controlled trial of health-related quality of life and symptoms by the European Organisation for Research and Treatment of Cancer Melanoma Group.

    NARCIS (Netherlands)

    Bottomley, A.; Coens, C.; Suciu, S.; Santinami, M.; Kruit, W.; Testori, A.; Marsden, J.; Punt, C.J.A.; Sales, F.; Gore, M.; MacKie, R.; Kusic, Z.; Dummer, R.; Patel, P.; Schadendorf, D.; Spatz, A.; Keilholz, U.; Eggermont, A.M.M.

    2009-01-01

    PURPOSE: Interferon (IFN) -based adjuvant therapy in melanoma is associated with significant side effects, which necessitates evaluation of health-related quality of life (HRQOL). Our trial examined the HRQOL effects of adjuvant pegylated IFN-alpha-2b (PEG-IFN-alpha-2b) versus observation in

  11. Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial.

    Science.gov (United States)

    Zdenkowski, N; Forbes, J F; Boyle, F M; Kannourakis, G; Gill, P G; Bayliss, E; Saunders, C; Della-Fiorentina, S; Kling, N; Campbell, I; Mann, G B; Coates, A S; Gebski, V; Davies, L; Thornton, R; Reaby, L; Cuzick, J; Green, M

    2016-05-01

    Despite the effectiveness of adjuvant endocrine therapy in preventing breast cancer recurrence, breast cancer events continue at a high rate for at least 10 years after completion of therapy. This randomised open label phase III trial recruited postmenopausal women from 29 Australian and New Zealand sites, with hormone receptor-positive early breast cancer, who had completed ≥4 years of endocrine therapy [aromatase inhibitor (AI), tamoxifen, ovarian suppression, or sequential combination] ≥1 year prior, to oral letrozole 2.5 mg daily for 5 years, or observation. Treatment allocation was by central computerised randomisation, stratified by institution, axillary node status and prior endocrine therapy. The primary outcome was invasive breast cancer events (new invasive primary, local, regional or distant recurrence, or contralateral breast cancer), analysed by intention to treat. The secondary outcomes were disease-free survival (DFS), overall survival, and safety. Between 16 May 2007 and 14 March 2012, 181 patients were randomised to letrozole and 179 to observation (median age 64.3 years). Endocrine therapy was completed at a median of 2.6 years before randomisation, and 47.5% had tumours of >2 cm and/or node positive. At 3.9 years median follow-up (interquartile range 3.1-4.8), 2 patients assigned letrozole (1.1%) and 17 patients assigned observation (9.5%) had experienced an invasive breast cancer event (difference 8.4%, 95% confidence interval 3.8% to 13.0%, log-rank test P = 0.0004). Twenty-four patients (13.4%) in the observation and 14 (7.7%) in the letrozole arm experienced a DFS event (log-rank P = 0.067). Adverse events linked to oestrogen depletion, but not serious adverse events, were more common with letrozole. These results should be considered exploratory, but lend weight to emerging data supporting longer duration endocrine therapy for hormone receptor-positive breast cancer, and offer insight into reintroduction of AI therapy. Australian New

  12. The Adoption of New Adjuvant Radiation Therapy Modalities Among Medicare Beneficiaries With Breast Cancer: Clinical Correlates and Cost Implications

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, Kenneth B. [Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale Comprehensive Cancer Center and Yale University School of Medicine, New Haven, Connecticut (United States); Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States); Soulos, Pamela R. [Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale Comprehensive Cancer Center and Yale University School of Medicine, New Haven, Connecticut (United States); Section of General Internal Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut (United States); Herrin, Jeph [Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale Comprehensive Cancer Center and Yale University School of Medicine, New Haven, Connecticut (United States); Health Research and Educational Trust, Chicago, Illinois (United States); Yu, James B. [Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale Comprehensive Cancer Center and Yale University School of Medicine, New Haven, Connecticut (United States); Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States); Long, Jessica B. [Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale Comprehensive Cancer Center and Yale University School of Medicine, New Haven, Connecticut (United States); Section of General Internal Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut (United States); Dostaler, Edward [Section of General Internal Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut (United States); and others

    2013-04-01

    Purpose: New radiation therapy modalities have broadened treatment options for older women with breast cancer, but it is unclear how clinical factors, geographic region, and physician preference affect the choice of radiation therapy modality. Methods and Materials: We used the Surveillance, Epidemiology, and End Results-Medicare database to identify women diagnosed with stage I-III breast cancer from 1998 to 2007 who underwent breast-conserving surgery. We assessed the temporal trends in, and costs of, the adoption of intensity modulated radiation therapy (IMRT) and brachytherapy. Using hierarchical logistic regression, we evaluated the relationship between the use of these new modalities and patient and regional characteristics. Results: Of 35,060 patients, 69.9% received conventional external beam radiation therapy (EBRT). Although overall radiation therapy use remained constant, the use of IMRT increased from 0.0% to 12.6% from 1998 to 2007, and brachytherapy increased from 0.7% to 9.0%. The statistical variation in brachytherapy use attributable to the radiation oncologist and geographic region was 41.4% and 9.5%, respectively (for IMRT: 23.8% and 22.1%, respectively). Women undergoing treatment at a free-standing radiation facility were significantly more likely to receive IMRT than were women treated at a hospital-based facility (odds ratio for IMRT vs EBRT: 3.89 [95% confidence interval, 2.78-5.45]). No such association was seen for brachytherapy. The median radiation therapy cost per treated patient increased from $5389 in 2001 to $8539 in 2007. Conclusions: IMRT and brachytherapy use increased substantially from 1998 to 2007; overall, radiation therapy costs increased by more than 50%. Radiation oncologists played an important role in treatment choice for both types of radiation therapy, whereas geographic region played a bigger role in the use of IMRT than brachytherapy.

  13. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial.

    Science.gov (United States)

    Martin, Miguel; Holmes, Frankie A; Ejlertsen, Bent; Delaloge, Suzette; Moy, Beverly; Iwata, Hiroji; von Minckwitz, Gunter; Chia, Stephen K L; Mansi, Janine; Barrios, Carlos H; Gnant, Michael; Tomašević, Zorica; Denduluri, Neelima; Šeparović, Robert; Gokmen, Erhan; Bashford, Anna; Ruiz Borrego, Manuel; Kim, Sung-Bae; Jakobsen, Erik Hugger; Ciceniene, Audrone; Inoue, Kenichi; Overkamp, Friedrich; Heijns, Joan B; Armstrong, Anne C; Link, John S; Joy, Anil Abraham; Bryce, Richard; Wong, Alvin; Moran, Susan; Yao, Bin; Xu, Feng; Auerbach, Alan; Buyse, Marc; Chan, Arlene

    2017-12-01

    ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings. In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (≥20 years in Japan) with stage 1-3c (modified to stage 2-3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone receptor-positive vs hormone receptor-negative), nodal status (0 vs 1-3 vs or ≥4 positive nodes), and trastuzumab adjuvant regimen (given sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system, to receive 1 year of oral neratinib 240 mg/day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis was invasive disease-free survival, analysed by intention to treat. ExteNET is registered with ClinicalTrials.gov, number NCT00878709, and is closed to new participants. Between July 9, 2009, and Oct 24, 2011, 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and randomly assigned to receive neratinib (n=1420) or placebo (n=1420). After a median follow-up of 5·2 years (IQR 2·1-5·3), patients in the neratinib

  14. Phase 1/2a study of the malaria vaccine candidate apical membrane antigen-1 (AMA-1) administered in adjuvant system AS01B or AS02A.

    NARCIS (Netherlands)

    Spring, M.D.; Cummings, J.F.; Ockenhouse, C.F.; Dutta, S.; Reidler, R.; Angov, E.; Bergmann-Leitner, E.; Stewart, V.A.; Bittner, S.; Juompan, L.; Kortepeter, M.G.; Nielsen, R.; Krzych, U.; Tierney, E.; Ware, L.A.; Dowler, M.; Hermsen, C.C.; Sauerwein, R.W.; Vlas, S.J. de; Ofori-Anyinam, O.; Lanar, D.E.; Williams, J.L.; Kester, K.E.; Tucker, K.; Shi, M.; Malkin, E.; Long, C.; Diggs, C.L.; Soisson, L.; Dubois, M.C.; Ballou, W.R.; Cohen, J.; Heppner, D.G.

    2009-01-01

    BACKGROUND: This Phase 1/2a study evaluated the safety, immunogenicity, and efficacy of an experimental malaria vaccine comprised of the recombinant Plasmodium falciparum protein apical membrane antigen-1 (AMA-1) representing the 3D7 allele formulated with either the AS01B or AS02A Adjuvant Systems.

  15. Evaluation of mucosal and systemic immune responses elicited by GPI-0100- adjuvanted influenza vaccine delivered by different immunization strategies.

    Directory of Open Access Journals (Sweden)

    Heng Liu

    Full Text Available Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN or the intrapulmonary (IPL route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses.

  16. Validation of Nomograms for Survival and Metastases after Hysterectomy and Adjuvant Therapy in Uterine Cervical Cancer with Risk Factors

    Directory of Open Access Journals (Sweden)

    Won Sup Yoon

    2017-01-01

    Full Text Available Background. Three nomogram models for early stage uterine cervical cancer have been developed (KROG 13-03 for overall survival [OS], SNUH/AMC for disease-free survival [DFS], and KROG 12-08 for distant metastases-free survival [DMFS] after radical hysterectomy (RH and pelvic lymph node dissection (PLND. This study aimed to validate these models using our cohort with adjuvant radiotherapy. Methods. According to the eligibility criteria of nomogram studies, patients were enrolled in Group A (N=109 for the two KROG models (RH with PLND and whole pelvic irradiation and Group B (N=101 for the SNUH/AMC model (RH with PLND and squamous histology. Using Cox-regression hazard models, the prognostic factors of our cohorts were evaluated. The risk probabilities induced from published nomogram scores were calculated and the concordance indices were evaluated. Results. Group A had 88.1% 5-year OS and 86.0% 5-year DMFS. Group B had 83.0% 5-year DFS. In multivariate analyses, large tumor size for OS (HR 8.62, P<0.001 and DMFS (HR 5.13, P=0.003, young age (≤40 versus 41–64 years for OS (HR 4.63, P=0.097 and DFS (HR 3.44, P=0.051, and multiple lymph node metastases (0 versus ≥3 for DMFS (HR 4.03, P=0.031 and DFS (HR 3.90, P=0.038 were significantly correlated. The concordance indices for OS, DMFS, and DFS were 0.612 (P=0.002, 0.597 (P=0.014, and 0.587 (P=0.020, respectively. Conclusion. The developed nomogram models after RH and PLND are clinically useful in predicting various types of survival with significance.

  17. Effect of mitomycin c and 5-flurouracil adjuvant therapy on the outcomes of Ahmed glaucoma valve implantation.

    Science.gov (United States)

    Cui, Qi N; Hsia, Yen C; Lin, Shan C; Stamper, Robert L; Rose-Nussbaumer, Jennifer; Mehta, Nitisha; Porco, Travis C; Naseri, Ayman; Han, Ying

    2017-03-01

    To examine the effect of mitomycin c and 5-flurouracil on treatment outcomes following Ahmed glaucoma valve implantation. Retrospective consecutive case series. Fifty patients who received Ahmed glaucoma valve implantation from 1999 to 2013 in the San Francisco Veterans Administration Hospital. The +INJECTION group received intraoperative mitomycin c followed by postoperative mitomycin c and/or 5-flurouracil, whereas the -INJECTION group did not. Primary outcome was treatment success at 1 year post-implantation. Intraocular pressure, hypertensive phase, and the number of glaucoma medications were also examined. Twenty-six patients/eyes in the +INJECTION group and 24 patients/eyes in the -INJECTION group were included. Treatment success was higher in the +INJECTION compared with the -INJECTION group (86 vs. 58%; P = 0.04). Intraocular pressure was lower in the +INJECTION compared with the -INJECTION group at 1, 3, 6 and 12 months (P ≪ 0.00001, P = 0.00003, 0.0008 and 0.024). Hypertensive phase occurred less often in the +INJECTION compared with the -INJECTION group (3.8 vs. 54%; P = 0.021). The +INJECTION group required fewer medications compared with the -INJECTION group (P = 0.02, 0.002, 0.003 and 0.008 at 1, 3, 6 and 12 months). Complication rates were comparable between groups (46.2 and 54.2%; P = 0.63). Adjuvant treatment with antifibrotics following Ahmed glaucoma valve implantation decreased the hypertensive phase and improved surgical outcomes without impacting complication rates at 1 year. This study postulates a role for antifibrotics in the postoperative management of Ahmed glaucoma valves. © 2016 Royal Australian and New Zealand College of Ophthalmologists.

  18. Pre-operative MR evaluation of features that indicate the need of adjuvant therapies in early stage cervical cancer patients. A single-centre experience

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    Rizzo, Stefania, E-mail: stefania.rizzo@ieo.it [Department of Radiology, European Institute of Oncology, via Ripamonti 435, 20141 Milan (Italy); Calareso, Giuseppina [Department of Radiology, European Institute of Oncology, via Ripamonti 435, 20141 Milan (Italy); Maccagnoni, Sara; Angileri, Salvatore Alessio [Department of Health Sciences, University of Milan, via A.di Rudinì 8, 20142 Milan (Italy); Landoni, Fabio [Division of Gynecology, European Institute of Oncology, via Ripamonti 435, 20141 Milan (Italy); Raimondi, Sara; Pasquali, Elena [Division of Epidemiology and Biostatistics, European Institute of Oncology, via Ripamonti 435, 20141 Milan (Italy); Lazzari, Roberta [Division of Radiotherapy, European Institute of Oncology, via Ripamonti 435, 20141 Milan (Italy); Bellomi, Massimo [Department of Radiology, European Institute of Oncology, via Ripamonti 435, 20141 Milan (Italy); Department of Health Sciences, University of Milan, via A.di Rudinì 8, 20142 Milan (Italy)

    2014-05-15

    Objectives: This study compared the MR measurement of minimum uninvolved cervical stroma and maximum stromal invasion, and the detection of positive lymph nodes with the pathological results. In addition, tumour type and grade were correlated with nodal status and apparent diffusion coefficient (ADC) values. Methods: Patients who underwent surgery and MR at our centre for early stage cervical cancer (FIGO IA1-IIB) were included. Data recorded included: age, date of MR, clinical FIGO (International Federation of Gynacology and Obstetrics) stage, histological type and grade, adjuvant therapy, pre-surgical conisation. MR evaluation included: measurement of the minimum uninvolved stroma, maximum thickness of stromal involvement, presence and site of positive pelvic lymph nodes, calculation of ADC values. Statistical analysis was performed to compare MR and pathological results. The agreement between MR and pathology in measuring depth of stromal invasion was analysed by Bland–Altman plot, calculating the limits of agreement (LoA). Results: 113/217 patients underwent adjuvant therapies. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MR in evaluation of minimum thickness of uninvolved cervical stroma were 88%, 75%, 70%, 90% and 80%; the same values in evaluation of pelvic positive lymph nodes were 64%, 85%, 65%, 84% and 78%. The mean difference between MR and pathological results in measuring maximum depth of stromal invasion was −0.65 mm (95% LoA: −9.37 mm; 8.07 mm). Depth of stromal invasion was strongly related to positive nodal status (p < 0.001). ADC values (available in 51/217 patients) were not associated with the features assessed. Conclusions: Pre-surgical MR is accurate (80%) in evaluating the minimum thickness of uninvolved cervical stroma; MR measurements of maximum depth of stromal invasion differed ±9 mm from the pathological results in 95% of cases. Furthermore, a strong association was found between

  19. Efficacy of vitamin B complex as an adjuvant therapy for the treatment of complicated vulvovaginal candidiasis: An in vivo and in vitro study.

    Science.gov (United States)

    Sun, Mei-Guo; Huang, Ying; Xu, Yuan-Hong; Cao, Yun-Xia

    2017-04-01

    This study aimed to explore the efficacy of vitamin B complex as an adjuvant therapy for the treatment of complicated vulvovaginal candidiasis (VVC) in vitro and in vivo. One-hundred fifty-eight complicated VVC patients were randomly divided into group A (treated with suppository+oral antifungal agents), group B (treated with suppository+vaginal cream), and group C (treated with suppository+vaginal cream+oral vitamin B complex). A mouse model of VVC was established. Eighty VVC mice were randomly divided into 4 groups according to the dose of vitamin B complex (20 mice in each group): V1 group (injected with 150μL normal salin), V2 group (injected with 50μL vitamin B complex solution+100μL normal saline), V3 group (injected with 100μL vitamin B complex solution+50μL normal saline), and V4 group (injected with 150μL vitamin B complex solution). After 4 weeks of treatment, the vaginal secretion was obtained for microscopic smear examination. HE stainning was performed to observe histopathological changes of vaginal tissues. The expressions of inflammatory factors were detected by ELISA. Meanwhile, VVC model of vaginal epithelial cells was established. The effects of different concentrations of vitamin B complex on anti-fungal effect of fluconazole were detected in vitro. After the treatment, complicated patients in the group C had significantly higher effective rates than those in the group A and group B. After the intra-gastric administration, the microscopic smear examination found that obvious pseudohypha in cluster with a lot of blastospores can be seen in the vaginal secretions of mice in the V1 group under the microscope. There was significant difference between mice treated with different dosages of vitamin B complex. The inflammatory response of mice in the V1 group was significantly higher than those in other groups and the inflammation response reduced with the increase of vitamin B complex dosage. The vitamin B complex elevated the curative effects of

  20. Treatment Efficacy, Adherence, and Quality of Life Among Women Younger Than 35 Years in the International Breast Cancer Study Group TEXT and SOFT Adjuvant Endocrine Therapy Trials.

    Science.gov (United States)

    Saha, Poornima; Regan, Meredith M; Pagani, Olivia; Francis, Prudence A; Walley, Barbara A; Ribi, Karin; Bernhard, Jürg; Luo, Weixiu; Gómez, Henry L; Burstein, Harold J; Parmar, Vani; Torres, Roberto; Stewart, Josephine; Bellet, Meritxell; Perelló, Antonia; Dane, Faysal; Moreira, Antonio; Vorobiof, Daniel; Nottage, Michelle; Price, Karen N; Coates, Alan S; Goldhirsch, Aron; Gelber, Richard D; Colleoni, Marco; Fleming, Gini F

    2017-09-20

    Purpose To describe benefits and toxicities of adjuvant endocrine therapies in women younger than 35 years with breast cancer (n = 582) enrolled in the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT). Methods In SOFT, women still premenopausal after surgery with or without chemotherapy were randomly assigned to tamoxifen alone, tamoxifen plus ovarian function suppression (OFS), or exemestane plus OFS. In TEXT, all received OFS with or without concomitant chemotherapy and were randomly assigned to exemestane plus OFS or tamoxifen plus OFS. We summarize treatment efficacy, quality of life, and adherence of the cohort of women younger than 35 years in SOFT and TEXT, alongside data from the cohort of older premenopausal women. Results For 240 human epidermal growth factor receptor 2-negative patients younger than 35 years enrolled in SOFT after receiving chemotherapy, the 5-year breast cancer-free interval (BCFI) was 67.1% (95% CI, 54.6% to 76.9%) with tamoxifen alone, 75.9% with tamoxifen plus OFS (95% CI, 64.0% to 84.4%), and 83.2% with exemestane plus OFS (95% CI, 72.7% to 90.0%). For 145 human epidermal growth factor receptor 2-negative patients younger than 35 years in TEXT, 5-year BCFI was 79.2% (95% CI, 66.2% to 87.7%) with tamoxifen plus OFS and 81.6% (95% CI, 69.8% to 89.2%) with exemestane plus OFS. The most prominent quality of life symptom for patients younger than 35 years receiving OFS was vasomotor symptoms, with the greatest worsening from baseline at 6 months (on the order of 30 to 40 points), but loss of sexual interest and difficulties in becoming aroused were also clinically meaningful (≥ 8-point change). The level of symptom burden was similar in older premenopausal women. A total of 19.8% of women younger than 35 years stopped all protocol-assigned endocrine therapy early. Conclusion In women younger than 35 years with hormone receptor-positive breast cancer, adjuvant OFS combined with tamoxifen or

  1. Antiarrhythmic therapy as an adjuvant to promote post pulmonary vein isolation success-a meta-analysis.

    Science.gov (United States)

    Goldenberg, Gustavo R; Burd, Daniel; Lodzinski, Piotr; Stabile, Giuseppe; Udell, Jacob A; Newman, David; Shurrab, Mohammed; Crystal, Eugene

    2016-11-01

    Three months of empirical antiarrhythmic drug (AAD) therapy after atrial fibrillation ablation (AFA) is a common practice to prevent early arrhythmia recurrence; the data of influence of this practice on longer term ablation outcomes is limited. The aim of this study was to perform a meta-analysis of published controlled trials comparing temporary AAD therapy after AFA with no AAD therapy in patients after AFA. The primary outcome was recurrence of arrhythmia. 1Eight prospective trials were included. Among 2952 patients, 1991 (67 %) had paroxysmal AF, and 967 (32.7 %) had persistent AF. In total, 1502 patients were treated with AADs and 1450 patients served as a control group (no AAD therapy). Various class IC-III antiarrhythmics were used. Length of AAD administration varied between 6 and 12 weeks after start of AFA. The follow-up duration ranged from 1.5 to 17 months after stopping medication. Among AAD treated patients, the recurrence of arrhythmia rate was 30.69 vs. 33.79 % in control patients (odd ratio 0.86, 95 % CI 0.71-1.06, P = 0.15). In patients who received largely amiodarone, there was a trend for difference in recurrence of atrial arrhythmia (odds ratio 0.60, 95 % CI 0.34-1.09, P = 0.09). Short-term post pulmonary vein isolation (PVI) AAD therapy does not substantially reduce overall recurrence of AF after ablation.

  2. Targeted Therapy in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Murray Baron

    2016-10-01

    Full Text Available Targeted therapies use an understanding of the pathophysiology of a disease in an individual patient. Although targeted therapy for systemic sclerosis (SSc, scleroderma has not yet reached the level of patient-specific treatments, recent developments in the understanding of the global pathophysiology of the disease have led to new treatments based on the cells and pathways that have been shown to be involved in the disease pathogenesis. The presence of a B cell signature in skin biopsies has led to the trial of rituximab, an anti-CD20 antibody, in SSc. The well-known properties of transforming growth factor (TGF-β in promoting collagen synthesis and secretion has led to a small trial of fresolimumab, a human IgG4 monoclonal antibody capable of neutralizing TGF-β. Evidence supporting important roles for interleukin-6 in the pathogenesis of SSc have led to a large trial of tocilizumab in SSc. Soluble guanylate cyclase (sGC is an enzyme that catalyzes the production of cyclic guanosine monophosphate (cGMP upon binding of nitric oxide (NO to the sGC molecule. Processes such as cell growth and proliferation are regulated by cGMP. Evidence that sGC may play a role in SSc has led to a trial of riociguat, a molecule that sensitizes sGC to endogenous NO. Tyrosine kinases (TKs are involved in a wide variety of physiologic and pathological processes including vascular remodeling and fibrogenesis such as occurs in SSc. This has led to a trial of nintedanib, a next-generation tyrosine-kinase (TK inhibitor which targets multiple TKs, in SSc.

  3. Vaccine adjuvant activity of 3M-052: an imidazoquinoline designed for local activity without systemic cytokine induction.

    Science.gov (United States)

    Smirnov, Dmitri; Schmidt, Joshua J; Capecchi, John T; Wightman, Paul D

    2011-07-26

    The human Toll-like receptors (TLRs) are a family of receptors, which sense the presence of various structural elements of pathogens and damaged or effete components in the host. As they do so, they activate two critical arms of host defense, the rapid innate immune response and an adaptive immune response. The innate immune response is typified by the generation of Th1 cytokines, chemokines and type 1 interferons. As such, agonists for the TLRs have potential as antiviral and anticancer therapeutics. They are also well suited to function as vaccine adjuvants. 3M imidazoquinoline (IRM) molecules were the first synthetic small molecules identified as TLR agonists and can affect their biological activities through TLR7, TLR8, or both. The breadth of therapeutic opportunities for this family of molecules can require formulations tailored to the specific application. One consideration is specific formulations to avoid a systemic distribution of these TLR agonists and resulting cytokine storm-like effects on the host. 3M-052 is an IRM bearing a C18 lipid moiety and designed for slow dissemination from the site of application. In the present study 3M-052 has been evaluated for its in vitro TLR activity and for its efficacy as a vaccine adjuvant using a recombinant hemagglutinin from H1N1 A/Puerto Rico/8/34. Given subcutaneously, 3M-052 drives a strong Th1 response to hemagglutinin and serum neutralization of viable H1N1 A/Puerto Rico/8/34 virus in the absence of circulating TNFα or the induction of Th1 cytokines. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Asians with localized prostate cancer treated with 3-dimensional conformal radiation therapy and adjuvant hormonal therapy: comparing Phoenix and American Society of Therapeutic Radiology and Oncology (ASTRO) definitions in an Asian population.

    Science.gov (United States)

    Ramalingam, Mohan; Lau, Weber; Tan, Terence; Fook, Stephanie; Ngoi, Francis; Cheng, Christopher

    2008-03-01

    Conformal radiotherapy with adjuvant androgen suppression is used in our center to treat localized prostate cancer. We compare Phoenix as an alternative to American Society of Therapeutic Radiology and Oncology (ASTRO) for defining biochemical failure. Our primary aim was to assess the Phoenix and ASTRO definitions of biochemical failure in a population of mainly Asian men with early localized prostate cancer treated with conformal radiotherapy with and without androgen ablation. We retrospectively analyzed 141 patients who were treated for T1/T2 cancer of the prostate in our center from January 1997 to June 2002 with a mean duration of follow-up of 62 months. Outcomes were analyzed by using both Phoenix and ASTRO definitions of biochemical failure as well as clinical failure. The Phoenix definition of biochemical failure was superior as measured by sensitivity, specificity, positive and negative predictive values, accuracy, and a greater concordance with clinical outcome as measured by Kappa analysis. The ASTRO definition helped to standardize reporting of biochemical failures post-radiotherapy but inadequacies have been identified especially when adjuvant hormone therapy has been given. The Phoenix definition has been noted to be a more accurate and precise description of biochemical failure in international series, and we find this to be true in our Asian population as well.

  5. EFFICACY OF SPINAL-CORD STIMULATION AS ADJUVANT THERAPY FOR INTRACTABLE ANGINA-PECTORIS - A PROSPECTIVE, RANDOMIZED CLINICAL-STUDY

    NARCIS (Netherlands)

    DEJONGSTE, MJL; HAUTVAST, RWM; HILLEGE, HL; LIE, KI

    Objectives. In a prospective, randomized study with an 8-week follow-up period, we evaluated the efficacy of spinal cord stimulation an exercise capacity and quality of life in patients with intractable angina. Background. Despite important achievements in therapy for ischemic heart disease, there

  6. Sexual Functioning Among Endometrial Cancer Patients Treated With Adjuvant High-Dose-Rate Intra-Vaginal Radiation Therapy

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    Damast, Shari, E-mail: shari.damast@yale.edu [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Alektiar, Kaled M. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Goldfarb, Shari [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Eaton, Anne; Patil, Sujata [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Mosenkis, Jeffrey [Department of Comparative Human Development, University of Chicago, Chicago, Illinois (United States); Bennett, Antonia [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Atkinson, Thomas [Department of Psychiatry, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Jewell, Elizabeth; Leitao, Mario; Barakat, Richard; Carter, Jeanne [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Basch, Ethan [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2012-10-01

    Purpose: We used the Female Sexual Function Index (FSFI) to investigate the prevalence of sexual dysfunction (SD) and factors associated with diminished sexual functioning in early stage endometrial cancer (EC) patients treated with simple hysterectomy and adjuvant brachytherapy. Methods and Materials: A cohort of 104 patients followed in a radiation oncology clinic completed questionnaires to quantify current levels of sexual functioning. The time interval between hysterectomy and questionnaire completion ranged from <6 months to >5 years. Multivariate regression was performed using the FSFI as a continuous variable (score range, 1.2-35.4). SD was defined as an FSFI score of <26, based on the published validation study. Results: SD was reported by 81% of respondents. The mean ({+-} standard deviation) domain scores in order of highest-to-lowest functioning were: satisfaction, 2.9 ({+-}2.0); orgasm, 2.5 ({+-}2.4); desire, 2.4 ({+-}1.3); arousal, 2.2 ({+-}2.0); dryness, 2.1 ({+-}2.1); and pain, 1.9 ({+-}2.3). Compared to the index population in which the FSFI cut-score was validated (healthy women ages 18-74), all scores were low. Compared to published scores of a postmenopausal population, scores were not statistically different. Multivariate analysis isolated factors associated with lower FSFI scores, including having laparotomy as opposed to minimally invasive surgery (effect size, -7.1 points; 95% CI, -11.2 to -3.1; P<.001), lack of vaginal lubricant use (effect size, -4.4 points; 95% CI, -8.7 to -0.2, P=.040), and short time interval (<6 months) from hysterectomy to questionnaire completion (effect size, -4.6 points; 95% CI, -9.3-0.2; P=.059). Conclusions: The rate of SD, as defined by an FSFI score <26, was prevalent. The postmenopausal status of EC patients alone is a known risk factor for SD. Additional factors associated with poor sexual functioning following treatment for EC included receipt of laparotomy and lack of vaginal lubricant use.

  7. Brachytherapy with an improved MammoSite Radiation Therapy System

    Science.gov (United States)

    Karthik, Nanda; Keppel, Cynthia; Nazaryan, Vahagn

    2007-03-01

    Accelerated partial breast irradiation treatment utilizing the MammoSite Radiation Therapy System (MRTS) is becoming increasingly popular. Clinical studies show excellent results for disease control and localization, as well as for cosmesis. Several Phase I, II, and III clinical trials have found significant association between skin spacing and cosmetic results after treatment with MRTS. As a result, patients with skin spacing less then 7 mm are not recommended to undergo this treatment. We have developed a practical innovation to the MammoSite brachytherapy methodology that is directed to overcome the skin spacing problem. The idea is to partially shield the radiation dose to the skin where the skin spacing is less then 7 mm, thereby protecting the skin from radiation damage. Our innovation to the MRTS will allow better cosmetic outcome in breast conserving therapy (BCT), and will furthermore allow more women to take advantage of BCT. Reduction in skin radiation exposure is particularly important for patients also undergoing adjuvant chemotherapy. We will present the method and preliminary laboratory and Monte Carlo simulation results.

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

    Directory of Open Access Journals (Sweden)

    Fountzilas George

    2010-11-01

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

  9. Hypotonic water as adjuvant therapy for incompletely resected canine mast cell tumors: a randomized, double-blind, placebo-controlled study.

    Science.gov (United States)

    Brocks, Bouvien A W; Neyens, Isabelle J S; Teske, Erik; Kirpensteijn, Jolle

    2008-07-01

    To evaluate efficacy of hypotonic water as adjuvant therapy after marginal resection of canine mast cell tumors (MCT). Double-blinded, placebo-controlled, prospective, randomized study. Dogs (n=30) with spontaneous, cutaneous, solitary MCT. The wound bed of MCT, resected with margins hypotonic or isotonic water according to a standardized protocol. Follow-up was obtained by clinical examination at 1, 2, 3, 6, and 12 months and annual telephone contact with the owner. Eighteen dogs were treated with isotonic lactated Ringer's solution and 12 dogs with hypotonic distilled water. All MCT were stage 0 tumors and most grade II. Six tumors (4 isotonic, 2 hypotonic) recurred locally, 3 of these dogs died from disease-related reasons within 4 months. The surviving 3 dogs were alive with a median survival time (ST) of 1092 days. The calculated 2-year recurrence-free rate was 92.7%; the 2-year disease-free rate 79.1%; and the 2-year survival rate 89.5%. No significant differences in local recurrence and ST were observed between treatment groups. Histologic grading was the only significant prognosticator for ST and recurrence-free periods. No significant differences in local recurrence and ST were observed between adjunctive hypotonic water and placebo treatment after marginal resection of solitary MCT. Hypotonic water does not decrease the rate of local recurrence in dogs with solitary MCT after marginal surgical excision.

  10. Refractory heparin induced thrombocytopenia with thrombosis (HITT) treated with therapeutic plasma exchange and rituximab as adjuvant therapy.

    Science.gov (United States)

    Schell, Amy M; Petras, Melissa; Szczepiorkowski, Zbigniew M; Ornstein, Deborah L

    2013-10-01

    We report a case of refractory heparin-induced thrombocytopenia with thrombosis (HITT) with prolonged thrombocytopenia and multiple thrombotic complications that failed to improve despite aggressive treatment. A 60 year old female with a prior history of venous thromboembolism was admitted with an acute pulmonary embolism, and developed HITT after several days on heparin therapy. She suffered multiple complications including bilateral venous limb gangrene, acute renal failure, and refractory thrombocytopenia, leading us to use multimodality therapy including therapeutic plasma exchange (TPE) and rituximab immunosuppression. The patient had transient improvements in her thrombocytopenia with TPE, and rituximab was added in an attempt to reduce antibody production. She eventually required bilateral limb amputation, and only after removal of the gangrenous limbs did her platelet count show sustained improvement. We discuss the possible contribution of infection to her prolonged course. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. The use of dexmedetomidine as an adjuvant to benzodiazepine-based therapy to decrease the severity of delirium in alcohol withdrawal in adult intensive care unit patients: a systematic review.

    Science.gov (United States)

    Woods, Anne Dabrow; Giometti, Renee; Weeks, Susan M

    2015-01-01

    Chronic alcohol consumption is a prevalent issue. Healthcare professionals often discover their patient has an alcohol consumption issue when they are admitted to the hospital and no longer have access to alcohol. The global standard for treating alcohol withdrawal syndrome (AWS) symptoms are benzodiazepines; however this therapy is often inadequate to control symptoms of delirium in adult intensive care unit (ICU) patients due to an imbalance of inhibitory and excitatory neurotransmitters. The objective of the systematic review is to examine the clinical effectiveness of dexmedetomidine as an adjuvant to benzodiazepine-based therapy versus benzodiazepine-based therapy alone in decreasing the severity of delirium associated with AWS in adult ICU patients. This review considered studies that included adult ICU patients over the age of 18 who were experiencing delirium associated with alcohol withdrawal. Patients admitted to the ICU with the diagnosis of AWS were included in the study.This review considered studies that evaluated dexmedetomidine as an adjuvant therapy to benzodiazepine-based therapy, compared to the use of benzodiazepine-based therapy alone in ICU patients experiencing alcohol withdrawal delirium.This review considered randomized controlled trials, non-randomized controlled trials, quasi-experimental, before and after studies, prospective and retrospective cohort studies, case control studies, analytical cross sectional studies, case series, individual case reports and descriptive cross sectional studies for inclusion.The systematic review evaluated dexmedetomidine as an adjuvant to benzodiazepine-based therapy to decrease delirium severity in alcohol withdrawal in ICU patients. The general outcome of delirium severity was measured using the Clinical Institute Withdrawal Assessment Score - Revised (CIWA), the Ramsey scale, the Richmond Agitation Sedation Score (RASS) and the Confusion Assessment Method for the ICU (CAM-ICU). The search strategy aimed

  12. The application of adjuvant autologous antravesical macrophage cell therapy vs. BCG in non-muscle invasive bladder cancer: a multicenter, randomized trial

    Directory of Open Access Journals (Sweden)

    Kiss Tamas

    2010-06-01

    Full Text Available Abstract Introduction While adjuvant immunotherapy with Bacille Calmette Guérin (BCG is effective in non-muscle-invasive bladder cancer (BC, adverse events (AEs are considerable. Monocyte-derived activated killer cells (MAK are discussed as essential in antitumoural immunoresponse, but their application may imply risks. The present trial compared autologous intravesical macrophage cell therapy (BEXIDEM® to BCG in patients after transurethral resection (TURB of BC. Materials and methods This open-label trial included 137 eligible patients with TaG1-3, T1G1-2 plurifocal or unifocal tumours and ≥ 2 occurrences within 24 months and was conducted from June 2004 to March 2007. Median follow-up for patients without recurrence was 12 months. Patients were randomized to BCG or mononuclear cells collected by apheresis after ex vivo cell processing and activation (BEXIDEM. Either arm treatment consisted of 6 weekly instillations and 2 cycles of 3 weekly instillations at months 3 and 6. Toxicity profile (primary endpoint and prophylactic effects (secondary endpoint were assessed. Results Patient characteristics were evenly distributed. Of 73 treated with BCG and 64 with BEXIDEM, 85% vs. 45% experienced AEs and 26% vs. 14% serious AEs (SAE, respectively (p Discussion This initial report of autologous intravesical macrophage cell therapy in BC demonstrates BEXIDEM treatment to be safe. Recurrence rates were significantly lower with BCG however. As the efficacy of BEXIDEM remains uncertain, further data, e.g. marker lesions studies, are warranted. Trial registration The trial has been registered in the ISRCTN registry http://isrctn.org under the registration number ISRCTN35881130.

  13. Zoledronic acid for treatment of osteopenia and osteoporosis in women with primary breast cancer undergoing adjuvant aromatase inhibitor therapy: a 5-year follow-up.

    Science.gov (United States)

    Majithia, Neil; Atherton, Pamela J; Lafky, Jacqueline M; Wagner-Johnston, Nina; Olson, Janet; Dakhil, Shaker R; Perez, Edith A; Loprinzi, Charles L; Hines, Stephanie L

    2016-03-01

    This study was designed to explore whether zoledronic acid could prevent expected loss of bone mineral density (BMD) in postmenopausal women with pre-existing osteopenia or osteoporosis who were initiating adjuvant letrozole therapy for primary breast cancer. Between June 2006 and July 2007, 60 postmenopausal women with estrogen and/or progesterone receptor-positive breast cancer and a BMD T-score ≤-2.0 were enrolled. Participants received letrozole 2.5 mg and vitamin D 400 IU daily, calcium 500 mg twice daily, and zoledronic acid 4 mg every 6 months for a maximum of 5 years or until disease progression. BMD at the lumbar spine and femoral neck was recorded at the start of the study and annually for 5 years. Patients were evaluated for fractures every 6 months for the duration of the trial. After 5 years, mean BMD increased significantly by 11.6% (p = 0.01) at the lumbar spine and by 8.8% (p = 0.01) at combined sites. Femoral neck BMD increased by 4.2%, although this was not significant (p = 0.23). At the end of the trial, BMDs were consistent with osteoporosis in 7 % and osteopenia in 36% of the patients. A total of six fractures were reported after 417 individual assessments. Zoledronic acid appears to prevent further bone loss in postmenopausal breast cancer patients with osteopenia and osteoporosis starting treatment with letrozole. These findings were maintained at 5 years and support concurrent initiation of bisphosphonate and aromatase inhibitor therapy in this high-risk population.

  14. Renoprotective effects of berberine as adjuvant therapy for hypertensive patients with type 2 diabetes mellitus: Evaluation via biochemical markers and color Doppler ultrasonography.

    Science.gov (United States)

    Dai, Peifeng; Wang, Junhua; Lin, Lin; Zhang, Yanyan; Wang, Zhengping

    2015-09-01

    Diabetes and hypertension are complex and serious diseases that may ultimately lead to renal complications. Adequate control of blood glucose and blood pressure contributes to decreased renal risks, but may not be sufficient for certain patients. The current study was undertaken to investigate the renoprotective effects of berberine as an adjuvant therapy to standard hypotensive and hypoglycemic treatment in hypertensive patients with type 2 diabetes mellitus (T2DM). In this 2-year clinical study, 69 hypertensive patients with T2DM, whose blood pressure and fasting plasma glucose (FPG) were adequately controlled by hypotensive and oral hypoglycemic agents prior to the study, were enrolled and randomly assigned into control (33 cases) and add-on (36 cases) groups. Berberine was orally administrated to the patients in the add-on group concomitantly with standard hypotensive and hypoglycemic treatment. Baseline characteristics, including the levels of FPG, glycated hemoglobin, systolic blood pressure, diastolic blood pressure, serum creatinine, urinary albumin-to-creatine ratio (UACR), urinary osteopontin and kidney injury molecule-1 (KIM-1) were determined. Furthermore, the oxidative stress markers malondialdehyde, urinary 8-hydroxy-2'-deoxyguanosine, superoxide dismutase, glutathione peroxidase and total-antioxidant capacity, and the inflammatory parameters vascular adhesion molecule-1, C-reactive protein and high molecular weight-adiponectin were evaluated. In addition, ultrasonographic parameters, including peak systolic velocity, end diastolic velocity and renal arterial resistance index were determined. After treatment, it was observed that the control and add-on treatments were able to adequately control blood pressure and blood glucose. Patients in the add-on group exhibited significant reductions in renal damage biochemical markers (UACR, urinary osteopontin and KIM-1) and improved renal hemodynamics, in addition to reduced inflammation and oxidative stress

  15. Effect of bifidobacterium triple viable powder adjuvant therapy on the inflammatory factors and t lymphocytes subsets in patients with ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Xue-Jun Tang

    2017-06-01

    Full Text Available Objective: To investigate effect of bifidobacterium triple viable powder on inflammatory factors and T lymphocyte subsets in patients with ulcerative colitis. Method: 80 patients with ulcerative colitis were selected and divided into observation group and control group, 40 cases in each group. The control group was given dietary guide, mesalazine, vitamin C and other comprehensive treatment; The observation group was given bifidobacterium triple viable powder adjuvant therapy on the basis of conventional treatment. The level of IL-6, CRP, TNF-α and T lymphocyte subsets in the two groups was compared before treatment (T0, after treatment for 1 month (T1, after treatment for 3 months (T2. Results: (1 The levels of IL-6, CRP and TNF-α at T1 serum were lower than those in T0 in both groups, the levels of serum IL-6, CRP and TNF-α at T2 were lower than those of T0 and T1, these three levels in different time points were statistical significant difference; The levels of serum IL-6, CRP and TNF-α in observation group at T1 and T2 were significantly lower than those in control group, there was significant difference in both groups; (2The levels of CD3+, CD4+, CD4+/ CD8+ at T1 were higher than T0 in two groups, The levels of CD3+, CD4+, CD4+/CD8+ at T2 were superior than at T0 and T1. The level of CD8+ at T1 was below at T0, The level of CD8+ at T2 was inferior than those in T0 and T1, The levels of CD3+,CD4+,CD8+ and CD4+/CD8+ at different time points were significant difference. The levels of CD3+, CD4+, CD4+ /CD8+ in the observation group were significantly higher than those in the control group T1 and T2, CD8+ level was significantly lower than that in the control group at T1 and T2, difference between the two groups was statistically significant. Conclusion: Bifidobacterium triple viable powder adjuvant treatment ulcerative colitis was good for inhibiting body inflammatory response and improve immune function.

  16. Effect of adjuvant systemic treatment on cosmetic outcome and late normal-tissue reactions after breast conservation

    Energy Technology Data Exchange (ETDEWEB)

    Johansen, Joergen [Dept. of Oncology, Odense Univ. Hospital, Odense (Denmark); Overgaard, Jens [Dept. of Experimental Clinical Oncology, Danish Cancer Society, Aarhus (Denmark); Overgaard, Marie [Dept. of Oncology, Aarhus Univ. Hospital, Aarhus (Denmark)

    2007-05-15

    To investigate whether adjuvant treatment with CMF or tamoxifen predisposes to an unfavorable cosmetic outcome or increased breast morbidity after radiotherapy in breast conservation. Data from 266 patients who entered a randomized breast conservation trial (DBCG-82TM protocol) was analyzed. The patients were treated with lumpectomy and axillary dissection followed by external beam radiotherapy to the residual breast. High-risk patients (n 94), as well as 31 low-risk patients, received additional radiation to the regional lymph nodes. Adjuvant systemic treatment was given to all high-risk patients: premenopausal patients (n = 67) received eight cycles of CMF intravenously (600/40/600 mg/m{sup 2}) every fourth week; postmenopausal patients (n = 27) received 30 mg of tamoxifen daily for one year. Clinical assessments included cosmetic outcome, breast fibrosis, skin telangiectasia, and dyspigmentation which were scored on a 4-point categorical scale after median 6.6 years. The observations were analyzed in multivariate logistic regression analysis which included potential risk factors on outcome related to systemic treatment, surgery, radiation technique, tumor, and patient characteristics. In premenopausal patients, systemic treatment with CMF independently predicted a fair/poor cosmetic outcome, RR = 2.2 (95% CI 1.2-4.2), as well as increased skin telangiectasia, RR = 3.3 (1.4-8.2). There was no impact of tamoxifen treatment on cosmetic outcome in postmenopausal patients (p 0.32). However, univariate analysis showed that tamoxifen was significantly associated with breast fibrosis (p <0.004), as was radiation to the regional lymph nodes (p <0.0001). A strong interaction between axillary irradiation and tamoxifen treatment occurred since 26 of 27 high-risk postmenopausal patients had received both tamoxifen and axillary irradiation. In multivariate regression analysis, axillary irradiation independently predicted moderate/severe breast fibrosis with a relative risk of

  17. Improving the extraction and purification of immunoglobulin G by the use of ionic liquids as adjuvants in aqueous biphasic systems

    Science.gov (United States)

    Mondal, Dibyendu; Coutinho, João A. P.; Freire, Mara G.

    2017-01-01

    Immunoglobulins G (IgG) could become widespread biopharmaceuticals if cost-efficient processes for their extraction and purification are available. In this work, aqueous biphasic systems (ABS) composed of polyethylene glycols and a buffered salt, and with ionic liquids (ILs) as adjuvants, have been studied as alternative extraction and purification platforms of IgG from a rabbit serum source. Eleven ILs were investigated to provide insights on the chemical features which maximize the IgG partitioning. It is shown that in polymer-salt systems pure IgG preferentially partitions to the polymer-rich phase; yet, the complete extraction was never attained. Remarkably, after the addition of 5 wt% of adequate ILs to polymer-salt ABS, the complete extraction of pure IgG in a single-step was accomplished. The best systems and conditions were then applied to the extraction and purification of IgG directly from rabbit serum samples. The complete extraction of IgG in a single-step was maintained while its purity in the polymer-rich phase was enhanced by ca. 37% as compared to the IL-free ABS. The antibody stability was also evaluated revealing that appropriate ILs are able to maintain the IgG stability and can be used as phase-forming components of ABS when envisaging the purification of high-cost biopharmaceuticals. PMID:27568168

  18. A Phase 3 Trial of 2 Years of Androgen Suppression and Radiation Therapy With or Without Adjuvant Chemotherapy for High-Risk Prostate Cancer: Final Results of Radiation Therapy Oncology Group Phase 3 Randomized Trial NRG Oncology RTOG 9902.

    Science.gov (United States)

    Rosenthal, Seth A; Hunt, Daniel; Sartor, A Oliver; Pienta, Kenneth J; Gomella, Leonard; Grignon, David; Rajan, Raghu; Kerlin, Kevin J; Jones, Christopher U; Dobelbower, Michael; Shipley, William U; Zeitzer, Kenneth; Hamstra, Daniel A; Donavanik, Viroon; Rotman, Marvin; Hartford, Alan C; Michalski, Jeffrey; Seider, Michael; Kim, Harold; Kuban, Deborah A; Moughan, Jennifer; Sandler, Howard

    2015-10-01

    Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS). Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL and Gleason score [GS] ≥ 7 or clinical stage ≥ T2 and GS ≥ 8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was given as four 21-day cycles, delivered beginning 28 days after 70.2 Gy of RT. AS was given as luteinizing hormone-releasing hormone for 24 months, beginning 2 months before RT plus an oral antiandrogen for 4 months before and during RT. The study was designed based on a 6% improvement in OS from 79% to 85% at 5 years, with 90% power and a 2-sided alpha of 0.05. A total of 397 patients (380 eligible) were randomized. The patients had high-risk PCa, 68% with GS 8 to 10 and 34% T3 to T4 tumors, and median prostate-specific antigen of 22.6 ng/mL. The median follow-up period was 9.2 years. The trial closed early because of excess thromboembolic toxicity in the CT arm. The 10-year results for all randomized patients revealed no significant difference between the AS + RT and AS + RT + CT arms in OS (65% vs 63%; P=.81), biochemical failure (58% vs 54%; P=.82), local progression (11% vs 7%; P=.09), distant metastases (16% vs 14%; P=.42), or disease-free survival (22% vs 26%; P=.61). NRG Oncology RTOG 9902 showed no significant differences in OS, biochemical failure, local progression, distant metastases, or disease-free survival with the addition of adjuvant CT to LT AS + RT. The trial results provide valuable data regarding the natural history of high-risk PCa treated with LT AS + RT and have implications for the feasibility of clinical trial accrual and tolerability using CT for PCa

  19. Phase 1/2 Study of the Addition of Cisplatin to Adjuvant Chemotherapy With Image Guided High-Precision Radiation Therapy for Completely Resected Gastric Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Goody, Rebecca B. [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); MacKay, Helen [Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Pitcher, Bethany [Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Oza, Amit; Siu, Lillian L. [Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Kim, John; Wong, Rebecca K.S. [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Chen, Eric [Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Swallow, Carol [Department of Surgical Oncology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario (Canada); Knox, Jennifer [Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Kassam, Zahra [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Stronach Regional Cancer Centre, Newmarket, Ontario (Canada); Cummings, Bernard [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Feld, Ron; Hedley, David; Liu, Geoffrey; Krzyzanowska, Monika K. [Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Dinniwell, Robert; Brade, Anthony M.; Dawson, Laura A. [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Pintilie, Melania [Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); and others

    2016-12-01

    Purpose: Locoregional recurrence is common after surgery for gastric cancer. Adjuvant therapy improves outcomes but with toxicity. This phase 1/2 study investigated infusional 5-fluorouracil (5-FU) in combination with biweekly cisplatin delivered concurrently with image guided high-precision radiation therapy. Methods and Materials: Eligible patients had completely resected stage IB to IV (Union for International Cancer Control TNM 6th edition) nonmetastatic gastric adenocarcinoma. Treatment constituted 12 weeks of infusional 5-FU (200 mg/m{sup 2}/day) with cisplatin added in a standard 3 + 3 dose escalation protocol (0, 20, 30, and 40 mg/m{sup 2}) during weeks 1, 3, 5, and 7, and an additional week 9 dose in the final cohort. Radiation therapy (45 Gy in 25 fractions) was delivered during weeks 3 to 7. Maximum tolerated dose (MTD) was determined in phase 1 and confirmed in phase 2. Results: Among the 55 patients (median age, 54 years; range 28-77 years; 55% male), the median follow-up time was 3.0 years (range, 0.3-5.3 years). Five patients in phase 1 experienced dose-limiting toxicity, and MTD was determined as 4 cycles of 40 mg/m{sup 2} cisplatin. Twenty-seven patients were treated at MTD. Acute grade 3 to 4 toxicity rate was 37.0% at MTD and 29.1% across all dose levels. No treatment-related deaths occurred. Fourteen patients experienced recurrent disease. The 2-year overall survival (OS) and relapse-free survival were 85% and 74%, respectively. Median OS has not been reached. Quality of life (QOL) was impaired during treatment, but most scores recovered by 4 weeks. Conclusion: Cisplatin can be safely delivered with 5-FU–based chemoradiation therapy. Acute toxicity was acceptable, and patient-reported QOL showed the regimen was tolerable. Outcomes are encouraging and justify further study of this regimen.

  20. Long-term results of endosteal implants following radical oral cancer surgery with and without adjuvant radiation therapy.

    Science.gov (United States)

    Linsen, Sabine S; Martini, Markus; Stark, Helmut

    2012-04-01

    The aim of this study was to analyze the long-term survival of implants and implant-retained prostheses in patients after ablative surgery of oral cancer with or without adjunctive radiation therapy. Between 1997 and 2008, 66 patients who had undergone ablative tumor surgery in the oral cavity were treated with dental implants (n = 262). Thirty-four patients received radiation therapy in daily fractions of 2 Gy administered on 18 to 30 days. Implants were inserted in the maxilla (49; 18.7%) or mandible (213; 81.3%), in non-irradiated residual (65; 24.8%) or grafted bone (44; 16.8%) and in irradiated residual (15.6%) or grafted bone (39; 14.9%). Seventeen fixed protheses and 53 removable dentures (34 bar attachments, 9 telescopic and 10 ball retained dentures) were inserted. Mean follow-up after implant insertion was 47.99 (±34.31) months (range 12-140 months). The overall 1-, 5-, and 10-year survival rates of all implants were 96.6%, 96.6%, and 86.9%, respectively. Fourteen implants were lost in nine patients (5.3% of all implants); eight implants were primary losses, and five secondary losses because of an operation of tumor recurrence. There was no significantly lower implant survival for implants inserted into irradiated bone (p = .302), bone and/or soft-tissue grafts (p = .436), and maxilla or mandible (p = .563). All prosthetic restorations in patients without tumor recurrence could be maintained during the observation period. Implant survival is not significantly influenced by radiation therapy, grafts (bone and/or soft tissue), or location (maxilla or mandible). However, implants placed in irradiated bone exhibit a higher failure rate during the healing period than those placed in non-irradiated bone. No superstructure was particularly favorable. Osseointegrated implants can be used successfully in patients with prior history of ablative surgery with and without additional radiation therapy. © 2009 Wiley Periodicals, Inc.

  1. ER-positive breast cancer patients with more than three positive nodes or grade 3 tumors are at high risk of late recurrence after 5-year adjuvant endocrine therapy.

    Science.gov (United States)

    Song, Fangbin; Zhang, Jianbing; Li, Shanbao; Wu, Junyi; Jin, Tao; Qin, Jun; Wang, Ye; Wang, Min; Xu, Junming

    2017-01-01

    Currently, although several clinical trials available give strong suggestions that extension of endocrine therapy has benefits, the risk level at which patients may benefit from extended endocrine therapy remains uncertain. This study aimed to identify the proportion of patients at a substantial risk of late recurrence after 5-year adjuvant endocrine therapy. We reviewed 1,056 female patients with primary breast cancer who underwent curative resection between January 2006 and December 2011. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model to identify prognostic factors. A total of 327 eligible patients were eventually enrolled in this study. Among them, 42 (12.8%) patients suffered from distant metastasis and 34 (10.4%) patients experienced locoregional recurrence after 5-year adjuvant endocrine therapy. In multivariate analysis, patients with more than three positive nodes (hazard ratio [HR] =2.176, 95% CI=1.071-4.421; P =0.032) and histologic grade 3 disease (HR=2.098, 95% CI=1.300-3.385; P =0.002) were significantly associated with high risk of late recurrence. However, only histologic grade 3 (HR=2.212, 95% CI=1.166-4.194; P =0.015) was significantly associated with high risk of distant metastasis. Late relapse after completion of 5-year adjuvant endocrine therapy was still common, and grade 3 and more than three positive nodes were the risk factors of late recurrence, while grade 3 was the only risk factor of late distant metastasis. These patients might benefit from extended endocrine therapy.

  2. Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01-04) for women with stage II/III breast cancer.

    Science.gov (United States)

    Coleman, R; Woodward, E; Brown, J; Cameron, D; Bell, R; Dodwell, D; Keane, M; Gil, M; Davies, C; Burkinshaw, R; Houston, S J; Grieve, R J; Barrett-Lee, P J; Thorpe, H

    2011-06-01

    The AZURE trial is an ongoing phase III, academic, multi-centre, randomised trial designed to evaluate the role of zoledronic acid (ZOL) in the adjuvant therapy of women with stage II/III breast cancer. Here, we report the safety and tolerability profile of ZOL in this setting. Eligible patients received (neo)adjuvant chemotherapy and/or endocrine therapy and were randomised to receive neither additional treatment nor intravenous ZOL 4 mg. ZOL was administered after each chemotherapy cycle to exploit potential sequence-dependent synergy. ZOL was continued for 60 months post-randomisation (six doses in the first 6 months, eight doses in the following 24 months and five doses in the final 30 months). Serious (SAE) and non-serious adverse event (AE) data generated during the first 36 months on study were analysed for the safety population. 3,360 patients were recruited to the AZURE trial. The safety population comprised 3,340 patients (ZOL 1,665; control 1,675). The addition of ZOL to standard treatment did not significantly impact on chemotherapy delivery. SAE were similar in both treatment arms. No significant safety differences were seen apart from the occurrence of osteonecrosis of the jaw (ONJ) in the ZOL group (11 confirmed cases; 0.7%; 95% confidence interval 0.3-1.1%). ZOL in the adjuvant setting is well tolerated, and can be safely administered in addition to adjuvant therapy including chemotherapy. The adverse events were consistent with the known safety profile of ZOL, with a low incidence of ONJ.

  3. Efficacy of neo-adjuvant hormonal therapy before radiation therapy for localized carcinoma of the prostate; Evaluation clinique et biologique de la reponse a l`hormonotherapie neoadjuvante avant radiotherapie dans les cancers de la prostate non metastatiques

    Energy Technology Data Exchange (ETDEWEB)

    Richaud, P.; Salem, N.; Chacon, B.; Gaston, R.; Bussieres, E.; Mauriac, L. [Centre Regional de Lutte Contre le Cancer, 33 - Bordeaux (France). Institut Bergonie

    1998-01-01

    The aim of this study was to evaluate the clinical and biochemical response to neo-adjuvant hormonal therapy (NAHT) before radical external radiotherapy (EBRT) From june 1986 to June 1994, 105 patients with histologically proven and non-metastatic prostate adenocarcinoma (stage B2-C2) received a short induction hormonal therapy (median: 3 months) with a luteinizing hormone releasing hormone (LHRH) analog associated with an anti-androgen followed in all cases by EBRT (66 Gy). All patients underwent a prostate-specific acid (PSA) determination, pelvic computed tomography (CT) scan and bone scan before the combined treatment. Response, treatment toxicity and PSA concentration were analyzed after the NAHT, 3 months after the completion of radiotherapy and every 6 months there after. Relapse was defined by PSA elevations above 4 ng/mL or two consecutive elevation above 1 ng/mL. Median follow-up was 52 months. According to the Withmore-Jewett clinical classification, 85 tumors were stage C. Pre-treatment PSA (PSAi) was above 20 ng/mL in 63.8 % of the patients (median PSAi: 26 ng/mL). A clinical evaluation and a PSA determination (PSAPH) were both performed for all patients after NAHT. Most of the time, urinary obstructive symptoms disappeared with androgen ablation; tumor volume regression exceed 50 % in 99 cases and was complete in 50 cases. Median PSAPH was 0.6 ng/mL for the entire group. Clinical and biochemical tumor response were coherent: 84 % of patients with clinical total remission had a PSAPH < 1 ng/mL. PSAPH value was significantly correlated with tumor stage and pre-treatment PSAi: among the 11 patients with a PSAPH > ng/mL, ten were stage and nine had a PSAi > 20 ng/mL. A PSAPH value exceeding 4 NG/mL predicted biochemical relapse (P<0.0001). We conclude that biochemical response to hormonal therapy has a major prognostic value before EBRT can help to identify patients for an adjuvant hormonal therapy. (authors)

  4. Photobiomodulation therapy for the management of radiation-induced dermatitis : A single-institution experience of adjuvant radiotherapy in breast cancer patients after breast conserving surgery.

    Science.gov (United States)

    Strouthos, Iosif; Chatzikonstantinou, Georgios; Tselis, Nikolaos; Bon, Dimitra; Karagiannis, Efstratios; Zoga, Eleni; Ferentinos, Konstantinos; Maximenko, Julia; Nikolettou-Fischer, Vassiliki; Zamboglou, Nikolaos

    2017-06-01

    Radiation therapy (RT) comprises a key component in the treatment of breast cancer. Radiation-induced skin toxicity is the major adverse event experienced by patients; however, radiodermatitis (RD) prevention and management remains trivial. It is proven that photobiomodulation (PBM) therapy using light-emitting diode (LED) increases wound healing and depicts an anti-inflammatory effect. This single-institute study evaluates the beneficial role of PBM-LED in preventing/reducing RD during breast cancer RT. Of 70 consecutively treated patients, 25 patients were treated with PBM-LED twice a week prior to adjuvant 3D conformal RT after breast-conserving surgery. RD was reported using Common Toxicity Criteria for Adverse Events Version 4.0 and pain intensity using a visual analog scale (VAS). For comparison, a control group (n = 45) received RT without PBM-LED. In addition, a "matched" group (n = 25) was generated from the control group based on propensity for potentially confounding variables. In the PBM group, 22 patients (88%) presented grade 1 and 3 (12%) grade 2 RD. In the control group, 25 patients (55.6%) developed grade 1 reactions, 18 patients (40%) grade 2, and 2 (4.4%) patients grade 3 RD. Concerning pain intensity, 15 patients (60%) of the PBM treatment arm reported no pain, 5 patients (20%) VAS 2, and 5 (20%) VAS 3. In the control group, 13 patients (28.9%) reported no pain, 2 (4.4%) VAS 1, 7 (15.6%) VAS 2, 9 patients (20%) reported VAS 3, 12 (26.7%) patients VAS 4, and 2 (4.4%) patients VAS 5. PBM-LED therapy applied prior to RT might be effective in decreasing the incidence and sequelae of radiation-induced skin toxicity in breast cancer patients treated with breast-conserving surgery.

  5. Systemic therapy and attachment narratives: Attachment Narrative Therapy.

    Science.gov (United States)

    Dallos, Rudi; Vetere, Arlene

    2014-10-01

    This article outlines an integration of attachment theory with narrative theory and systemic theory and practice: Attachment Narrative Therapy (ANT). This integration offers a more powerful explanatory formulation of the development and maintenance of human distress in relationships, families and communities, and gives direction to psychotherapeutic intervention. © The Author(s) 2014.

  6. Cosmetic outcome 1-5 years after breast conservative surgery, irradiation and systemic therapy.

    Science.gov (United States)

    Kelemen, Gyöngyi; Varga, Zoltán; Lázár, György; Thurzó, László; Kahán, Zsuzsanna

    2012-04-01

    The late side-effects of the local therapy of early breast cancer depend on many patient- and therapy-related parameters. We aimed at investigating the factors that influence the cosmetic and functional outcomes among our breast cancer patients after breast-conserving surgery and conformal radiotherapy, with or without adjuvant systemic therapy. A study was made of the association of the cosmetic outcome after a median follow-up time of 2.4 years and the clinical data on 198 patients extracted from a prospectively compiled database. Breast tenderness occurred more frequently among patients ≤50 years old (p cosmetic outcome after breast-conserving surgery and postoperative radiotherapy.

  7. The impact of extended release exenatide as adjuvant therapy on hemoglobin A1C, weight, and total daily dose of insulin in patients with type 2 diabetes mellitus using U-500 insulin.

    Science.gov (United States)

    Farwig, Phillip A; Zielinski, Angela J; Accursi, Mallory L; Burant, Christopher J

    2017-12-01

    To evaluate the efficacy and safety of adjuvant exenatide extended release (ER) therapy in patients treated with regular U-500 insulin. In this retrospective chart review at an ambulatory care center in the Midwest, 18 patients with type 2 diabetes being treated with regular U-500 insulin and adjuvant exenatide ER were identified. These patients were evaluated for outcomes following the addition of exenatide ER. The primary outcome was change in HbA 1C from baseline to 3, 6, and 12months. Secondary outcomes included change in weight, total daily dose (TDD) of insulin, and hypoglycemia. Repeated measures ANOVA was performed to assess the differences in mean scores over four time periods. A total of 18 of 50 patients met inclusion criteria with sufficient data to be included in analysis. HbA 1C showed non-significant findings from baseline to 12months (8.08% vs. 8.23%; p=0.75). A non-significant, modest weight loss occurred (146.4kgvs. 144.2kg; -2.2kg; p=0.31). A significant decrease in TDD of insulin was observed (378 units vs. 326 units; pinsulin, adjuvant exenatide ER therapy showed no significant improvement in HbA 1C , but did show modest weight loss as well as decreased insulin requirements to achieve a HbA 1C that was comparable to baseline. Published by Elsevier B.V.

  8. Prolactin-induced protein as a potential therapy response marker of adjuvant chemotherapy in breast cancer patients.

    Science.gov (United States)

    Jablonska, Karolina; Grzegrzolka, Jedrzej; Podhorska-Okolow, Marzenna; Stasiolek, Mariusz; Pula, Bartosz; Olbromski, Mateusz; Gomulkiewicz, Agnieszka; Piotrowska, Aleksandra; Rys, Janusz; Ambicka, Aleksandra; Ong, Siew Hwa; Zabel, Maciej; Dziegiel, Piotr

    2016-01-01

    Many studies are dedicated to exploring the molecular mechanisms of chemotherapy-resistance in breast cancer (BC). Some of them are focused on searching for candidate genes responsible for this process. The aim of this study was typing the candidate genes associated with the response to standard chemotherapy in the case of invasive ductal carcinoma. Frozen material from 28 biopsies obtained from IDC patients with different responses to chemotherapy were examined using gene expression microarray, Real-Time PCR (RT-PCR) and Western blot (WB). Based on the microarray results, further analysis of candidate gene expression was evaluated in 120 IDC cases by RT-PCR and in 224 IDC cases by immunohistochemistry (IHC). The results were correlated with clinical outcome and molecular subtype of the BC. Gene expression microarray revealed Prolactin-Induced Peptide (PIP) as a single gene differentially expressed in BC therapy responder or non-responder patients (p <0.05). The level of PIP expression was significantly higher in the BC therapy responder group than in the non-responder group at mRNA (p=0.0092) and protein level (p=0.0256). Expression of PIP mRNA was the highest in estrogen receptor positive (ER+) BC cases (p=0.0254) and it was the lowest in triple negative breast cancer (TNBC) (p=0.0336). Higher PIP mRNA expression was characterized by significantly longer disease free survival (DFS, p=0.0093), as well as metastasis free survival (MFS, p=0.0144). Additionally, PIP mRNA and PIP protein expression levels were significantly higher in luminal A than in other molecular subtypes and TNBC. Moreover significantly higher PIP expression was observed in G1, G2 vs. G3 cases (p=0.0027 and p=0.0013, respectively). Microarray analysis characterized PIP gene as a candidate for BC standard chemotherapy response marker. Analysis of clinical data suggests that PIP may be a good prognostic and predictive marker in IDC patients. Higher levels of PIP were related to longer DFS and MFS

  9. Trends in vaccine adjuvants

    NARCIS (Netherlands)

    Schijns, V.E.J.C.; Lavelle, E.C.

    2011-01-01

    Adjuvants are essential components of most clinically used vaccines. This is because the majority of nonliving vaccines are relatively poor inducers of adaptive immunity unless effective adjuvants are co-administered. Aluminum salts (alum) have been used as adjuvants with great success for almost a

  10. Proteomic and systems biology analysis of monocytes exposed to securinine, a GABA(A receptor antagonist and immune adjuvant.

    Directory of Open Access Journals (Sweden)

    Matt Shipman

    Full Text Available Securinine, a GABA(A receptor antagonist, has been reported to enhance monocyte cell killing of Coxiella burnetii without obvious adverse effects in vivo. We employed multiplex 2D gel electrophoresis using Zdyes, a new generation of covalently linked fluorescent differential protein detection dyes to analyze changes in the monocyte proteome in response to Securinine. Securinine antagonism of GABA(A receptors triggers the activation of p38. We used the differential protein expression results to guide a search of the literature and network analysis software to construct a systems biology model of the effect of Securinine on monocytes. The model suggests that various metabolic modulators (fatty acid binding protein 5, inosine 5'-monophosphate dehydrogenase, and thioredoxin are at least partially reshaping the metabolic landscape within the monocytes. The actin bundling protein L-plastin, and the Ca(2+ binding protein S100A4 also appear to have important roles in the immune response stimulated by Securinine. Fatty acid binding protein 5 (FABP5 may be involved in effecting lipid raft composition, inflammation, and hormonal regulation of monocytes, and the model suggests that FABP5 may be a central regulator of metabolism in activated monocytes. The model also suggests that the heat shock proteins have a significant impact on the monocyte immune response. The model provides a framework to guide future investigations into the mechanisms of Securinine action and with elaboration may help guide development of new types of immune adjuvants.

  11. Epigallocatechin Gallate Nanodelivery Systems for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Andreia Granja

    2016-05-01

    Full Text Available Cancer is one of the leading causes of morbidity and mortality all over the world. Conventional treatments, such as chemotherapy, are generally expensive, highly toxic and lack efficiency. Cancer chemoprevention using phytochemicals is emerging as a promising approach for the treatment of early carcinogenic processes. (−-Epigallocatechin-3-gallate (EGCG is the major bioactive constituent in green tea with numerous health benefits including anti-cancer activity, which has been intensively studied. Besides its potential for chemoprevention, EGCG has also been shown to synergize with common anti-cancer agents, which makes it a suitable adjuvant in chemotherapy. However, limitations in terms of stability and bioavailability have hampered its application in clinical settings. Nanotechnology may have an important role in improving the pharmacokinetic and pharmacodynamics of EGCG. Indeed, several studies have already reported the use of nanoparticles as delivery vehicles of EGCG for cancer therapy. The aim of this article is to discuss the EGCG molecule and its associated health benefits, particularly its anti-cancer activity and provide an overview of the studies that have employed nanotechnology strategies to enhance EGCG’s properties and potentiate its anti-tumoral activity.

  12. Epigallocatechin Gallate Nanodelivery Systems for Cancer Therapy.

    Science.gov (United States)

    Granja, Andreia; Pinheiro, Marina; Reis, Salette

    2016-05-20

    Cancer is one of the leading causes of morbidity and mortality all over the world. Conventional treatments, such as chemotherapy, are generally expensive, highly toxic and lack efficiency. Cancer chemoprevention using phytochemicals is emerging as a promising approach for the treatment of early carcinogenic processes. (-)-Epigallocatechin-3-gallate (EGCG) is the major bioactive constituent in green tea with numerous health benefits including anti-cancer activity, which has been intensively studied. Besides its potential for chemoprevention, EGCG has also been shown to synergize with common anti-cancer agents, which makes it a suitable adjuvant in chemotherapy. However, limitations in terms of stability and bioavailability have hampered its application in clinical settings. Nanotechnology may have an important role in improving the pharmacokinetic and pharmacodynamics of EGCG. Indeed, several studies have already reported the use of nanoparticles as delivery vehicles of EGCG for cancer therapy. The aim of this article is to discuss the EGCG molecule and its associated health benefits, particularly its anti-cancer activity and provide an overview of the studies that have employed nanotechnology strategies to enhance EGCG's properties and potentiate its anti-tumoral activity.

  13. Epigallocatechin Gallate Nanodelivery Systems for Cancer Therapy

    Science.gov (United States)

    Granja, Andreia; Pinheiro, Marina; Reis, Salette

    2016-01-01

    Cancer is one of the leading causes of morbidity and mortality all over the world. Conventional treatments, such as chemotherapy, are generally expensive, highly toxic and lack efficiency. Cancer chemoprevention using phytochemicals is emerging as a promising approach for the treatment of early carcinogenic processes. (−)-Epigallocatechin-3-gallate (EGCG) is the major bioactive constituent in green tea with numerous health benefits including anti-cancer activity, which has been intensively studied. Besides its potential for chemoprevention, EGCG has also been shown to synergize with common anti-cancer agents, which makes it a suitable adjuvant in chemotherapy. However, limitations in terms of stability and bioavailability have hampered its application in clinical settings. Nanotechnology may have an important role in improving the pharmacokinetic and pharmacodynamics of EGCG. Indeed, several studies have already reported the use of nanoparticles as delivery vehicles of EGCG for cancer therapy. The aim of this article is to discuss the EGCG molecule and its associated health benefits, particularly its anti-cancer activity and provide an overview of the studies that have employed nanotechnology strategies to enhance EGCG’s properties and potentiate its anti-tumoral activity. PMID:27213442

  14. AMELIORATION OF QUALITY OF LIFE AND LUNG FUNCTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE BY PRANIC HEALING AS ADJUVANT THERAPY

    Directory of Open Access Journals (Sweden)

    Padukudru Anand Mahesh

    2017-08-01

    Full Text Available Aims To study the effects of Pranic Healing (PH, as a complementary therapy to improve lung function, physiological condition and quality of life of Chronic Obstructive Pulmonary Disease (COPD patients. Methods Randomised, double-blind, placebo-controlled, pilot study. 21 males with a mean age of 61.6 years and COPD stage II were randomly allocated to PH and control groups. The PH group received PH sessions thrice weekly during the study. The control group received Sham PH. Data was collected during baseline and four scheduled visits of the participants during six months. The primary outcome of the study was to access the reduction in COPD symptoms and to increase participation in physical and social activities by evaluating Spirometry, St George’s Respiratory Questionnaire (SGRQ, 6 Minute Walk Test (6MWT and Hamilton Rating Scale for Depression (HRSD. Results Significant improvement for PH group in Forced Expiratory Volume in the first second (p=0.02, SGRQ domains of Activity (p=0.006, Impact (p=0.002, Total (p=0.000, and non-significant change in Symptom domain (p=0.44. PH group showed a positive tendency in 6 MWT and HRSD scores with insignificant difference between the groups. No serious adverse events occurred during the study. Conclusion PH as an adjunct to conventional treatment can improve lung function and quality of life of COPD subjects.

  15. Prolactin-induced protein as a potential therapy response marker of adjuvant chemotherapy in breast cancer patients

    Science.gov (United States)

    Jablonska, Karolina; Grzegrzolka, Jedrzej; Podhorska-Okolow, Marzenna; Stasiolek, Mariusz; Pula, Bartosz; Olbromski, Mateusz; Gomulkiewicz, Agnieszka; Piotrowska, Aleksandra; Rys, Janusz; Ambicka, Aleksandra; Ong, Siew Hwa; Zabel, Maciej; Dziegiel, Piotr

    2016-01-01

    Many studies are dedicated to exploring the molecular mechanisms of chemotherapy-resistance in breast cancer (BC). Some of them are focused on searching for candidate genes responsible for this process. The aim of this study was typing the candidate genes associated with the response to standard chemotherapy in the case of invasive ductal carcinoma. Frozen material from 28 biopsies obtained from IDC patients with different responses to chemotherapy were examined using gene expression microarray, Real-Time PCR (RT-PCR) and Western blot (WB). Based on the microarray results, further analysis of candidate gene expression was evaluated in 120 IDC cases by RT-PCR and in 224 IDC cases by immunohistochemistry (IHC). The results were correlated with clinical outcome and molecular subtype of the BC. Gene expression microarray revealed Prolactin-Induced Peptide (PIP) as a single gene differentially expressed in BC therapy responder or non-responder patients (p G1, G2 vs. G3 cases (p=0.0027 and p=0.0013, respectively). Microarray analysis characterized PIP gene as a candidate for BC standard chemotherapy response marker. Analysis of clinical data suggests that PIP may be a good prognostic and predictive marker in IDC patients. Higher levels of PIP were related to longer DFS and MFS but not with OS. PMID:27293986

  16. Electrochemotherapy - Supplementary Treatment for Loco-regional Metastasized Breast Carcinoma Administered to Concomitant Systemic Therapy.

    Science.gov (United States)

    Grischke, Eva-Maria; Röhm, Carmen; Stauß, Eva; Taran, Florin-Andrei; Brucker, Sara Y; Wallwiener, Diethelm

    2017-09-01

    Electrochemotherapy (ECT) is an established procedure for treating breast cancer loco-regional recurrences following surgical intervention and/or radiotherapy. Limited information is available on ECT application as a concomitant procedure to systemic therapy in recurrent breast cancer. The primary objective of this study was to determine if the application of ECT in close temporal relation to systemic chemotherapy could lead to increased local and/or systemic side effects. For this purpose we evaluated the safety of ECT as a supplemental local therapy to systemic therapy. ECT local and systemic toxicity and side effects were recorded and whether the anticipated local therapeutic effect of ECT would be influenced by the concomitant use of systemic therapies was investigated. This is an observational study. Thirty three patients with loco-regional metastasized breast carcinoma were treated and observed over a period of three years with 46 ECT applications for local tumour control in addition to established systemic therapy. A specific timeline for ECT administration was not fixed up, but was generally performed one week before the following chemotherapy administration with the aim to avoid the so called nadir, this means the peak period with risk of neutropenia. Data was collected over a period of three years on a population of 33 metastatic patients. Fifteen patients, received neo-adjuvant therapy as part of their primary treatment, but still had an advanced stage tumour. Some patients received repeated ECT applications. Objective tumour response was observed in 90% of the treated patients. Patients showed no increased local toxicity, especially no higher dermal toxicity, e.g. formation of local necrosis. ECT proved to be an effective supplement to a cytotoxic systemic therapy, especially for high-risk patients who did not respond well to systemic therapy of loco-regional metastases, without creating any greater systemic or loco-regional toxicities.

  17. Electrochemotherapy – Supplementary Treatment for Loco-regional Metastasized Breast Carcinoma Administered to Concomitant Systemic Therapy

    Science.gov (United States)

    Röhm, Carmen; Stauß, Eva; Taran, Florin-Andrei; Brucker, Sara Y.; Wallwiener, Diethelm

    2017-01-01

    Abstract Background Electrochemotherapy (ECT) is an established procedure for treating breast cancer loco-regional recurrences following surgical intervention and/or radiotherapy. Limited information is available on ECT application as a concomitant procedure to systemic therapy in recurrent breast cancer. The primary objective of this study was to determine if the application of ECT in close temporal relation to systemic chemotherapy could lead to increased local and/or systemic side effects. For this purpose we evaluated the safety of ECT as a supplemental local therapy to systemic therapy. ECT local and systemic toxicity and side effects were recorded and whether the anticipated local therapeutic effect of ECT would be influenced by the concomitant use of systemic therapies was investigated. Patients and methods This is an observational study. Thirty three patients with loco-regional metastasized breast carcinoma were treated and observed over a period of three years with 46 ECT applications for local tumour control in addition to established systemic therapy. A specific timeline for ECT administration was not fixed up, but was generally performed one week before the following chemotherapy administration with the aim to avoid the so called nadir, this means the peak period with risk of neutropenia. Results Data was collected over a period of three years on a population of 33 metastatic patients. Fifteen patients, received neo-adjuvant therapy as part of their primary treatment, but still had an advanced stage tumour. Some patients received repeated ECT applications. Objective tumour response was observed in 90% of the treated patients. Patients showed no increased local toxicity, especially no higher dermal toxicity, e.g. formation of local necrosis. Conclusions ECT proved to be an effective supplement to a cytotoxic systemic therapy, especially for high-risk patients who did not respond well to systemic therapy of loco-regional metastases, without creating any

  18. Systemic therapies for psoriasis: understanding current and newly emerging therapies.

    Science.gov (United States)

    Sobell, Jeffrey M; Hallas, Stephen J

    2003-09-01

    The treatment of moderate to severe psoriasis is a rapidly expanding area. Recent insights into the pathogenesis of this disease as a T-cell mediated process has led to a greater understanding of the mechanisms of action of conventional FDA-approved systemic therapies such as methotrexate, cyclosporine, acitretin, and psoralen with ultraviolet A phototherapy. It has also led to the development of rationally targeted therapies against key components of the immune process critical in the generation of the psoriatic plaque. Safety and efficacy data from clinical studies of 4 biologic agents furthest along in their development are reviewed. These results are promising, adding to the armamentarium for treating this disease.

  19. Health-Related Quality of Life in Elderly Patients With Newly Diagnosed Glioblastoma Treated With Short-Course Radiation Therapy Plus Concomitant and Adjuvant Temozolomide

    Energy Technology Data Exchange (ETDEWEB)

    Minniti, Giuseppe, E-mail: gminniti@ospedalesantandrea.it [Department of Radiation Oncology, Sant' Andrea Hospital, University Sapienza, Rome (Italy); Department of Neurological Sciences, Neuromed Institute, Pozzilli (Italy); Scaringi, Claudia [Department of Radiation Oncology, Sant' Andrea Hospital, University Sapienza, Rome (Italy); Baldoni, Alessandra [Department of Medical Oncology, Sant' Andrea Hospital, University Sapienza, Rome (Italy); Lanzetta, Gaetano [Department of Neurological Sciences, Neuromed Institute, Pozzilli (Italy); De Sanctis, Vitaliana [Department of Radiation Oncology, Sant' Andrea Hospital, University Sapienza, Rome (Italy); Esposito, Vincenzo [Department of Neurological Sciences, Neuromed Institute, Pozzilli (Italy); Enrici, Riccardo Maurizi [Department of Radiation Oncology, Sant' Andrea Hospital, University Sapienza, Rome (Italy)

    2013-06-01

    Purpose: To describe the quality of life (QOL) in elderly patients with glioblastoma (GBM) treated with an abbreviated course of radiation therapy (RT; 40 Gy in 15 fractions) plus concomitant and adjuvant temozolomide (TMZ). Methods and Materials: Health-related QOL (HRQOL) was assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30, version 3) and EORTC Quality of Life Questionnaire Brain Cancer Module (QLQ-BN20). Changes from baseline in the score of 9 preselected domains (global QLQ, social functioning, cognitive functioning, emotional functioning, physical functioning, motor dysfunction, communication deficit, fatigue, insomnia) were determined 4 weeks after RT and thereafter every 8 weeks during the treatment until disease progression. The proportion of patients with improved HRQOL scores, defined as a change of 10 points or more, and duration of changes were recorded. Results: Sixty-five patients completed the questionnaires at baseline. The treatment was consistently associated with improvement or stability in most of the preselected HRQOL domains. Global health improved over time; mean score differed by 9.6 points between baseline and 6-month follow-up (P=.03). For social functioning and cognitive functioning, mean scores improved over time, with a maximum difference of 10.4 points and 9.5 points between baseline and 6-month follow-up (P=.01 and P=.02), respectively. By contrast, fatigue worsened over time, with a difference in mean score of 5.6 points between baseline and 4-month follow-up (P=.02). Conclusions: A short course of RT in combination with TMZ in elderly patients with GBM was associated with survival benefit without a negative effect on HRQOL until the time of disease progression.

  20. Survival Impact of Adjuvant Radiation Therapy in Masaoka Stage II to IV Thymomas: A Systematic Review and Meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Yu Jin; Kim, Eunji [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Hak Jae, E-mail: khjae@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Wu, Hong-Gyun [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of); Yan, Jinchun [Department of Radiation Oncology, Dalian Medical University, Liaoning (China); Department of Radiation Oncology, Fudan University Cancer Hospital, Shanghai (China); Liu, Qin [The Wistar Institute, Philadelphia, Pennsylvania (United States); Patel, Shilpen [Department of Radiation Oncology, University of Washington Medical Center, Seattle, Washington (United States)

    2016-04-01

    Purpose: To evaluate the survival impact of postoperative radiation therapy (PORT) in stage II to IV thymomas, using systematic review and meta-analysis. Methods and Materials: A database search was conducted with EMBASE, PubMed, Web of Science, Cochrane Library, and Ovid from inception to August 2015. Thymic carcinomas were excluded, and studies comparing overall survival (OS) with and without PORT in thymomas were included. The hazard ratios (HRs) of OS were extracted, and a random-effects model was used in the pooled analysis. Results: Seven retrospective series with a total of 1724 patients were included and analyzed. Almost all of the patients underwent macroscopically complete resection, and thymoma histology was confirmed by the World Health Organization criteria. In the overall analysis of stage II to IV thymomas, OS was not altered with the receipt of PORT (HR 0.79, 95% confidence interval [CI] 0.58-1.08). Although PORT was not associated with survival difference in Masaoka stage II disease (HR 1.45, 95% CI 0.83-2.55), improved OS was observed with the addition of PORT in the discrete pooled analysis of stage III to IV (HR 0.63, 95% CI 0.40-0.99). Significant heterogeneity and publication bias were not found in the analyses. Conclusions: From the present meta-analysis of sole primary thymomas, we suggest the potential OS benefit of PORT in locally advanced tumors with macroscopically complete resection, but not in stage II disease. Further investigations with sufficient survival data are needed to establish detailed treatment indications.

  1. Patterns and Predictors of Early Biochemical Recurrence After Radical Prostatectomy and Adjuvant Radiation Therapy in Men With pT{sub 3}N{sub 0} Prostate Cancer: Implications for Multimodal Therapies

    Energy Technology Data Exchange (ETDEWEB)

    Briganti, Alberto, E-mail: briganti.alberto@hsr.it [Department of Urology, San Raffaele Scientific Institute, Vita-Salute University, Milan (Italy); Joniau, Steven [Department of Urology, University Hospitals Leuven, Leuven (Belgium); Gandaglia, Giorgio [Department of Urology, San Raffaele Scientific Institute, Vita-Salute University, Milan (Italy); Cancer Prognostics and Health Outcomes Unit, University of Montreal, Montreal (Canada); Cozzarini, Cesare [Department of Radiotherapy, San Raffaele Scientific Institute, Milan (Italy); Sun, Maxine [Cancer Prognostics and Health Outcomes Unit, University of Montreal, Montreal (Canada); Tombal, Bertrand [Department of Urology, Université Catholique de Louvain, Brussels (Belgium); Haustermans, Karin [Department of Radiology, University Hospitals Leuven, Leuven (Belgium); Hinkelbein, Wolfgang [Department of Radiation Oncology, Charité Universitätsmedizin, Campus Benjamin Franklin, Berlin (Germany); Shariat, Shahrokh F. [Department of Urology, University of Vienna, Vienna (Austria); Karakiewicz, Pierre I. [Cancer Prognostics and Health Outcomes Unit, University of Montreal, Montreal (Canada); Montorsi, Francesco [Department of Urology, San Raffaele Scientific Institute, Vita-Salute University, Milan (Italy); Van Poppel, Hein [Department of Urology, University Hospitals Leuven, Leuven (Belgium); Wiegel, Thomas [Department of Radiation Oncology, University Hospital Ulm, Ulm (Germany)

    2013-12-01

    Purpose: The aim of our study was to evaluate patterns and predictors of early biochemical recurrence (eBCR) after radical prostatectomy (RP) and adjuvant radiation therapy (aRT) in order to identify which individuals might benefit from additional treatments. Methods and Materials: We evaluated 390 patients with pT{sub 3}N{sub 0} prostate cancer (PCa) receiving RP and aRT at 6 European centers between 1993 and 2006. Patients who were free from BCR at <2 years' follow-up were excluded. This resulted in 374 assessable patients. Early BCR was defined as 2 consecutive prostate-specific antigen (PSA) test values >0.2 ng/mL within 2 or 3 years after aRT. Uni- and multivariable Cox regression analyses predicting overall and eBCR after aRT were fitted. Covariates consisted of preoperative PSA results, surgical margins, pathological stage, Gleason score, and aRT dose. Results: Overall, 5- and 8-year BCR-free survival rates were 77.1% and 70.8%, respectively. At a median follow-up of 86 months after aRT, 33 (8.8%) and 55 (14.6%) men experienced BCR within 2 or 3 years after aRT, respectively. In multivariable analyses, Gleason scores of 8 to 10 represented the only independent predictor of eBCR after aRT (all, P≤.01). The risk of BCR was significantly higher in patients with a Gleason score of 8 to 10 disease than in those with Gleason 2 to 6 within 24 months after treatment, after adjusting for all covariates (all, P≤.04). However, given a 24-month BCR free period, the risk of subsequent BCR for men with poorly differentiated disease was equal to that of men with less aggressive disease (all, P≥.3). Conclusions: High Gleason score represents the only predictor of eBCR after RP and aRT in patients affected by pT{sub 3}N{sub 0} PCa. Given the association between early PSA recurrence, clinical progression, and mortality, these patients might be considered candidates for adjuvant medical therapy and/or prophylactic whole-pelvis radiation therapy in addition to a

  2. Results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy after early failure of adjuvant systemic chemotherapy.

    NARCIS (Netherlands)

    Klaver, Y.L.B.; Hingh, I.H.J.T. de; Boot, H.; Verwaal, V.J.

    2011-01-01

    BACKGROUND AND OBJECTIVES: Failure to respond to systemic chemotherapy is considered an exclusion criterion by some institutions for treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). However, it is unknown if these patients benefit from HIPEC treatment. This

  3. Photobiomodulation therapy for the management of radiation-induced dermatitis. A single-institution experience of adjuvant radiotherapy in breast cancer patients after breast conserving surgery

    Energy Technology Data Exchange (ETDEWEB)

    Strouthos, Iosif [Sana Klinikum Offenbach, Department of Radiation Oncology, Offenbach (Germany); Medical Center - Albert Ludwigs University of Freiburg, Department of Radiotherapy and Oncology, Freiburg (Germany); Chatzikonstantinou, Georgios; Tselis, Nikolaos [Sana Klinikum Offenbach, Department of Radiation Oncology, Offenbach (Germany); J.W. Goethe University, Department of Radiotherapy and Oncology, Frankfurt am Main (Germany); Bon, Dimitra [J.W. Goethe University, Institute of Biostatistics and Mathematical Modelling, Frankfurt am Main (Germany); Karagiannis, Efstratios [Sana Klinikum Offenbach, Department of Radiation Oncology, Offenbach (Germany); Otto von Guericke University, Department of Radiation Oncology, Magdeburg (Germany); Zoga, Eleni; Ferentinos, Konstantinos; Maximenko, Julia; Nikolettou-Fischer, Vassiliki; Zamboglou, Nikolaos [Sana Klinikum Offenbach, Department of Radiation Oncology, Offenbach (Germany)

    2017-06-15

    Radiation therapy (RT) comprises a key component in the treatment of breast cancer. Radiation-induced skin toxicity is the major adverse event experienced by patients; however, radiodermatitis (RD) prevention and management remains trivial. It is proven that photobiomodulation (PBM) therapy using light-emitting diode (LED) increases wound healing and depicts an anti-inflammatory effect. This single-institute study evaluates the beneficial role of PBM-LED in preventing/reducing RD during breast cancer RT. Of 70 consecutively treated patients, 25 patients were treated with PBM-LED twice a week prior to adjuvant 3D conformal RT after breast-conserving surgery. RD was reported using Common Toxicity Criteria for Adverse Events Version 4.0 and pain intensity using a visual analog scale (VAS). For comparison, a control group (n = 45) received RT without PBM-LED. In addition, a ''matched'' group (n = 25) was generated from the control group based on propensity for potentially confounding variables. In the PBM group, 22 patients (88%) presented grade 1 and 3 (12%) grade 2 RD. In the control group, 25 patients (55.6%) developed grade 1 reactions, 18 patients (40%) grade 2, and 2 (4.4%) patients grade 3 RD. Concerning pain intensity, 15 patients (60%) of the PBM treatment arm reported no pain, 5 patients (20%) VAS 2, and 5 (20%) VAS 3. In the control group, 13 patients (28.9%) reported no pain, 2 (4.4%) VAS 1, 7 (15.6%) VAS 2, 9 patients (20%) reported VAS 3, 12 (26.7%) patients VAS 4, and 2 (4.4%) patients VAS 5. PBM-LED therapy applied prior to RT might be effective in decreasing the incidence and sequelae of radiation-induced skin toxicity in breast cancer patients treated with breast-conserving surgery. (orig.) [German] Radiotherapie (RT) ist integrativer Bestandteil der multimodalen Therapie beim Mammakarzinom. Strahlentherapieinduzierte Hauttoxizitaet ist dabei das haeufigste unerwuenschte Ereignis; dennoch sind Praevention und Management der

  4. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

    Science.gov (United States)

    Chan, Arlene; Delaloge, Suzette; Holmes, Frankie A; Moy, Beverly; Iwata, Hiroji; Harvey, Vernon J; Robert, Nicholas J; Silovski, Tajana; Gokmen, Erhan; von Minckwitz, Gunter; Ejlertsen, Bent; Chia, Stephen K L; Mansi, Janine; Barrios, Carlos H; Gnant, Michael; Buyse, Marc; Gore, Ira; Smith, John; Harker, Graydon; Masuda, Norikazu; Petrakova, Katarina; Zotano, Angel Guerrero; Iannotti, Nicholas; Rodriguez, Gladys; Tassone, Pierfrancesco; Wong, Alvin; Bryce, Richard; Ye, Yining; Yao, Bin; Martin, Miguel

    2016-03-01

    Neratinib, an irreversible tyrosine-kinase inhibitor of HER1, HER2, and HER4, has clinical activity in patients with HER2-positive metastatic breast cancer. We aimed to investigate the efficacy and safety of 12 months of neratinib after trastuzumab-based adjuvant therapy in patients with early-stage HER2-positive breast cancer. We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 495 centres in Europe, Asia, Australia, New Zealand, and North and South America. Eligible women (aged ≥18 years, or ≥20 years in Japan) had stage 1-3 HER2-positive breast cancer and had completed neoadjuvant and adjuvant trastuzumab therapy up to 2 years before randomisation. Inclusion criteria were amended on Feb 25, 2010, to include patients with stage 2-3 HER2-positive breast cancer who had completed trastuzumab therapy up to 1 year previously. Patients were randomly assigned (1:1) to receive oral neratinib 240 mg per day or matching placebo. The randomisation sequence was generated with permuted blocks stratified by hormone receptor status (hormone receptor-positive [oestrogen or progesterone receptor-positive or both] vs hormone receptor-negative [oestrogen and progesterone receptor-negative]), nodal status (0, 1-3, or ≥4), and trastuzumab adjuvant regimen (sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system. Patients, investigators, and trial sponsors were masked to treatment allocation. The primary outcome was invasive disease-free survival, as defined in the original protocol, at 2 years after randomisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00878709. Between July 9, 2009, and Oct 24, 2011, we randomly assigned 2840 women to receive neratinib (n=1420) or placebo (n=1420). Median follow-up time was 24 months (IQR 20-25) in the neratinib group and 24 months (22-25) in the placebo group. At 2 year follow-up, 70

  5. Immunohistochemical Markers as Predictors of Histopathologic Response and Prognosis in Rectal Cancer Treated with Preoperative Adjuvant Therapy: State of the Art

    Directory of Open Access Journals (Sweden)

    Alessandro Del Gobbo

    2017-01-01

    Full Text Available We explain the state of the art of the immunohistochemical markers of response in rectal cancers treated with neoadjuvant medical therapies and its implication with prognosis. Neoadjuvant chemoradiotherapy is widely used to improve the outcome of patients with locally advanced rectal cancer, and the evaluation of the effects of medical therapy is to date based on histomorphological examination by applying four grading systems of response to therapy (tumor regression grade (TRG. The need to identify immunohistochemical markers that could ensure a better assessment of response and possibly provide additional prognostic information has emerged. We identified p53, p27kip1, Ki67, matrix metalloprotease-9, survivin, Ki67 proliferative index, CD133, COX2, CD44v6, thymidylate synthase, thymidine phosphorylase, and dihydropyrimidine dehydrogenase as the most common markers studied in literature to date, and we explained their prognostic potential and their implications in the evaluation of the response to preoperative therapies in rectal cancers.

  6. CpG Island Methylator Phenotype is Associated With Response to Adjuvant Irinotecan-Based Therapy for Stage 3 Colon Cancer

    Science.gov (United States)

    Shiovitz, Stacey; Bertagnolli, Monica M.; Renfro, Lindsay A.; Nam, Eunmi; Foster, Nathan R.; Dzieciatkowski, Slavomir; Luo, Yanxin; Lao, Victoria Valinluck; Monnat, Raymond J.; Emond, Mary J.; Maizels, Nancy; Niedzwiecki, Donna; Goldberg, Richard M.; Saltz, Leonard B.; Venook, Alan; Warren, Robert S.; Grady, William M.

    2014-01-01

    BACKGROUND & AIMS The CpG island methylator phenotype (CIMP), defined by a high frequency of aberrantly methylated genes, is a characteristic of a subclass of colon tumors with distinct clinical and molecular features. Cohort studies have produced conflicting results on responses of CIMP-positive tumors to chemotherapy. We assessed the association between tumor CIMP status and survival of patients receiving adjuvant fluorouracil and leucovorin alone or with irinotecan (IFL) METHODS We analyzed data from patients with stage 3 colon adenocarcinoma randomly assigned to groups given fluorouracil and leucovorin or IFL following surgery, from April 1999 through April 2001. The primary endpoint of the trial was overall survival and the secondary endpoint was disease-free survival. DNA isolated from available tumor samples (n=615) was used to determine CIMP status based on methylation patterns at the CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1 loci. The effects of CIMP on survival were modeled using Kaplan-Meier and Cox proportional hazards; interactions with treatment and BRAF, KRAS, and mismatch repair (MMR) status were also investigated. RESULTS Of the tumor samples characterized for CIMP status, 145 were CIMP positive (23%). Patients with CIMP-positive tumors had shorter overall survival times than patients with CIMP-negative tumors (hazard ratio [HR]=1.36; 95% confidence interval [CI], 1.01–1.84). Treatment with IFL showed a trend toward increased overall survival for patients with CIMP-positive tumors, compared to treatment with fluorouracil and leucovorin (HR=0.62; 95% CI, 0.37–1.05; P=.07), but not for patients with CIMP-negative tumors (HR=1.38; 95% CI, 1.00–1.89; P=.049). In a 3-way interaction analysis, patients with CIMP-positive, MMR-intact tumors benefited most from the addition of irinotecan to fluorouracil and leucovorin therapy (for the interaction, P=.01). CIMP was more strongly associated with response to IFL than MMR status. Results for disease

  7. Clonidine used as a perineural adjuvant to ropivacaine, does not prolong the duration of sensory block when controlling for systemic effects

    DEFF Research Database (Denmark)

    Andersen, Jakob Hessel; Jaeger, Pia; Sonne, Tobias Laier

    2017-01-01

    pain detection threshold. RESULTS: We enrolled 21 volunteers and all completed the trial. There was no difference in duration of sensory block assessed with an alcohol swab: Mean duration in the leg receiving ropivacaine + clonidine was 19.4h (SD 2.7) compared to 19.3h (SD 2.4) in the leg receiving......BACKGROUND: Clonidine used as an adjuvant to ropivacaine have been shown to prolong the duration of peripheral nerve blocks. The mechanism of action remains unclear. We hypothesized, that clonidine used as an adjuvant to ropivacaine extends the duration of an adductor canal block (ACB......) by a peripheral mechanism, compared to ropivacaine alone when controlling for systemic effects. METHODS: We conducted a paired, blinded, randomized trial in healthy volunteers. Participants received bilateral ACBs containing 20 ml ropivacaine 0.5% + 1 ml clonidine 150μg/ml in one leg and 20 ml ropivacaine 0...

  8. Overview of resistance to systemic therapy in patients with breast cancer.

    Science.gov (United States)

    Gonzalez-Angulo, Ana Maria; Morales-Vasquez, Flavia; Hortobagyi, Gabriel N

    2007-01-01

    Breast cancer is the most common cancer and the second leading cause of cancer death in American women. It was the second most common cancer in the world in 2002, with more than 1 million new cases. Despite advances in early detection and the understanding of the molecular bases of breast cancer biology, about 30% of patients with early-stage breast cancer have recurrent disease. To offer more effective and less toxic treatment, selecting therapies requires considering the patient and the clinical and molecular characteristics of the tumor. Systemic treatment of breast cancer includes cytotoxic, hormonal, and immunotherapeutic agents. These medications are used in the adjuvant, neoadjuvant, and metastatic settings. In general, systemic agents are active at the beginning of therapy in 90% of primary breast cancers and 50% of metastases. However, after a variable period of time, progression occurs. At that point, resistance to therapy is not only common but expected. Herein we review general mechanisms of drug resistance, including multidrug resistance by P-glycoprotein and the multidrug resistance protein family in association with specific agents and their metabolism, emergence of refractory tumors associated with multiple resistance mechanisms, and resistance factors unique to host-tumor-drug interactions. Important anticancer agents specific to breast cancer are described. Breast cancer is the most common type of cancer and the second leading cause of cancer death in American women. In 2002, 209,995 new cases of breast cancer were registered, and 42,913 patients died of it. In 5 years, the annual prevalence of breast cancer will reach 968,731 cases in the United States. World wide, the problem is just as significant, as breast cancer is the most frequent cancer after nonmelanoma skin cancer, with more than 1 million new cases in 2002 and an expected annual prevalence of more than 4.4 million in 5 years. Breast cancer treatment currently requires the joint efforts

  9. Induction (neo-adjuvant) chemotherapy: systemic and arterial delivery techniques and their clinical applications.

    Science.gov (United States)

    Stephens, F O

    1995-10-01

    Induction chemotherapy is a well tried method of improving the cure prospects of locally advanced or aggressive primary cancers. It is most simply administered by systemic (intravenous) delivery but for some cases a greater chemotherapy impact is both desirable and achievable with the use of a more concentrated regional delivery technique. Any advantage of regional chemotherapy will depend upon the type of tumour to be treated, its site and blood supply, the most effective doses, concentrations and exposure periods of the preferred agents to be used and the relative risks of systemic and regional toxicity and the techniques of delivery. In general, systemic chemotherapy is most appropriate in treating tumours without a single artery of supply; when certain agents which are inactive until modified in body tissues (such as cyclophosphamide or DTIC) are to be used; when satisfactory responses can be achieved more easily by systemic delivery; when technical skills and facilities for regional delivery are not available; or when the patient's general health, co-operation or long-term prognosis precludes the additional complexity of regional delivery. Intra-arterial infusion may have advantages in treating head and neck, gastric, liver, some locally advanced breast, limb, pelvic and possibly pancreatic malignancies. More complex techniques to achieve short-term highly concentrated chemotherapy include closed circuit perfusion; chemofiltration infusion and 'stop flow' perfusion; and regional limb infusion. These should remain the subject of ongoing studies in highly specialized units which treat tumours such as melanoma or pancreatic cancer which respond poorly to lower chemotherapy concentrations.

  10. Patterns of Care and Clinical Outcomes of First-Line Trastuzumab-Based Therapy in HER2-Positive Metastatic Breast Cancer Patients Relapsing After (Neo)Adjuvant Trastuzumab: An Italian Multicenter Retrospective Cohort Study

    Science.gov (United States)

    Ferreira, Arlindo R.; Poggio, Francesca; Puglisi, Fabio; Bernardo, Antonio; Montemurro, Filippo; Poletto, Elena; Pozzi, Emma; Rossi, Valentina; Risi, Emanuela; Lai, Antonella; Zanardi, Elisa; Sini, Valentina; Ziliani, Serena; Minuti, Gabriele; Mura, Silvia; Grasso, Donatella; Fontana, Andrea; Del Mastro, Lucia

    2015-01-01

    Background. We evaluated the patterns of care and clinical outcomes of metastatic breast cancer patients treated with first-line trastuzumab-based therapy after previous (neo)adjuvant trastuzumab. Materials and Methods. A total of 416 consecutive, HER2-positive metastatic breast cancer patients who had received first-line trastuzumab-based therapy were identified at 14 Italian centers. A total of 113 patients had presented with de novo stage IV disease and were analyzed separately. Dichotomous clinical outcomes were analyzed using logistic regression and time-to-event outcomes using Cox proportional hazards models. Results. In the 202 trastuzumab-naïve patients and 101 patients with previous trastuzumab exposure, we observed the following outcomes, respectively: overall response rate, 69.9% versus 61.3% (adjusted odds ratio [OR], 0.62; p = .131), clinical benefit rate, 79.1% versus 72.5% (adjusted OR, 0.73; p = .370), median progression-free survival (PFS), 16.1 months versus 12.0 months (adjusted hazards ratio [HR], 1.33; p = .045), and median overall survival (OS), 52.2 months versus 48.2 months (adjusted HR, 1.18; p = .404). Patients with a trastuzumab-free interval (TFI) trastuzumab-based therapy was an effective first-line treatment for patients relapsing after (neo)adjuvant trastuzumab. Previous trastuzumab exposure and the respective TFI, type of first site of disease relapse, and hormone receptor status should be considered in the choice of the best first-line treatment option for HER2-positive metastatic breast cancer patients. Implications for Practice: A paucity of data is available outlining the clinical outcomes of patients who receive trastuzumab as a part of their (neo)adjuvant treatment and then resume trastuzumab-based therapy in the metastatic setting. In the present study, despite an inferior median progression-free survival, trastuzumab-based therapy was shown to be an effective first-line treatment for patients relapsing after (neo)adjuvant

  11. Low-pressure balloon angioplasty with adjuvant pharmacological therapy in patients with acute ischemic stroke caused by intracranial arterial occlusions

    Energy Technology Data Exchange (ETDEWEB)

    Nogueira, Raul G. [Massachusetts General Hospital, Harvard Medical School, Department of Radiology, Endovascular Neurosurgery/Interventional Neuroradiology Section, Boston, MA (United States); Massachusetts General Hospital, Harvard Medical School, Department of Neurosurgery, Endovascular Neurosurgery/Interventional Neuroradiology Section, Boston, MA (United States); Massachusetts General Hospital, Harvard Medical School, Department of Neurology, Neurocritical Care and Vascular Neurology Section, Boston, MA (United States); Massachusetts General Hospital, Boston, MA (United States); Schwamm, Lee H.; Buonanno, Ferdinando S.; Koroshetz, Walter J. [Massachusetts General Hospital, Harvard Medical School, Department of Neurology, Neurocritical Care and Vascular Neurology Section, Boston, MA (United States); Yoo, Albert J.; Rabinov, James D.; Pryor, Johnny C.; Hirsch, Joshua A. [Massachusetts General Hospital, Harvard Medical School, Department of Radiology, Endovascular Neurosurgery/Interventional Neuroradiology Section, Boston, MA (United States); Massachusetts General Hospital, Harvard Medical School, Department of Neurosurgery, Endovascular Neurosurgery/Interventional Neuroradiology Section, Boston, MA (United States)

    2008-04-15

    The use of coronary balloons in the cerebral vasculature is limited due to their poor trackability and increased risk of vessel injury. We report our experience using more compliant elastomer balloons for thrombus resistant to intraarterial (IA) pharmacological and mechanical thrombolysis in acute stroke. We retrospectively analyzed 12 consecutive patients with an occluded intracranial artery treated with angioplasty using a low-pressure elastomer balloon. Angiograms were graded according to the Thrombolysis in Cerebral Infarction (TICI) and Qureshi grading systems. Outcomes were categorized as independent (modified Rankin scale, mRS, score {<=}2), dependent (mRS score 3-5), or dead (mRS score 6). Included in the study were 12 patients (mean age 66{+-}17 years, range 31-88 years; mean baseline National Institutes of Health stroke scale score 17{+-}3, range 12-23). The occlusion sites were: internal carotid artery (ICA) terminus (five patients, including two concomitant cervical ICA occlusions), M1 segment (two patients), and basilar artery (two patients). Pharmacological treatment included intravenous (IV) t-PA only (two patients), IA urokinase only (nine patients), both IV t-PA and IA urokinase (one patient), and IV and/or IA eptifibatide (eight patients). Mean time to treatment was 5.9{+-}3.9 h (anterior circulation) and 11.0{+-}7.2 h (posterior circulation). Overall recanalization rate (TICI grade 2/3) was 91.6%. Procedure-related morbidity occurred in one patient (distal posterior inferior cerebellar artery embolus). There were no symptomatic hemorrhages. Outcomes at 90 days were independent (five patients), dependent (three patients) and dead (four patients, all due to progression of stroke with withdrawal of care). Angioplasty of acutely occluded intracranial arteries with low-pressure elastomer balloons results in high recanalization rates with an acceptable degree of safety. Prior use of thrombolytics may increase the chances of recanalization, and

  12. A new strategy of CyberKnife treatment system based radiosurgery followed by early use of adjuvant bevacizumab treatment for brain metastasis with extensive cerebral edema.

    Science.gov (United States)

    Wang, Yang; Wang, Enmin; Pan, Li; Dai, Jiazhong; Zhang, Nan; Wang, Xin; Liu, Xiaoxia; Mei, Guanghai; Sheng, Xiaofang

    2014-09-01

    Bevacizumab blocks the effects of vascular endothelial growth factor in leakage-prone capillaries and has been suggested as a new treatment for cerebral radiation edema and necrosis. CyberKnife is a new, frameless stereotactic radiosurgery system. This work investigated the safety and efficacy of CyberKnife followed by early bevacizumab treatment for brain metastasis with extensive cerebral edema. The eligibility criteria of the patients selected for radiosurgery followed by early use of adjuvant bevacizumab treatment were: (1) brain tumors from metastasis with one solitary brain lesion and symptomatic extensive cerebral edema; (2) >18 years of age; (3) the patient refused surgery due to the physical conditions and the risk of surgery; (4) no contraindications for bevacizumab. (5) bevacizumab was applied for a minimum of 2 injections and a maximum of 6 injections with a 2-week interval between treatments, beginning within 2 weeks of the CyberKnife therapy; (6) Karnofsky performance status (KPS) ≥30. Tumor size and edema were monitored by magnetic resonance imaging (MRI). Dexamethasone dosage, KPS, adverse event occurrence and associated clinical outcomes were also recorded. Eight patients were accrued for this new treatment. Radiation dose ranged from 20 to 33 Gy in one to five sessions, prescribed to the 61-71 % isodose line. Bevacizumab therapy was administered 3-10 days after completion of CyberKnife treatment for a minimum of two cycles (5 mg/kg, at 2-week intervals). MRI revealed average reductions of 55.8 % (post-gadolinium) and 63.4 % (T2/FLAIR). Seven patients showed significant clinical neurological improvements. Dexamethasone was reduced in all patients, with five successfully discontinuing dexamethasone treatment 4 weeks after bevacizumab initiation. Hypertension, a bevacizumab-related adverse event, occurred in one patient. After 3-8 months, all patients studied were alive and primary brain metastases were under control, 2 developed new brain

  13. Histamine and mast cell activator compound 48/80 are safe but inefficient systemic adjuvants for gilthead seabream vaccination.

    Science.gov (United States)

    Gómez González, N E; Cabas, I; Montero, J; García Alcázar, A; Mulero, V; García Ayala, A

    2017-07-01

    Histamine has a key role in the regulation of inflammatory and innate immune responses in vertebrates. Gilthead seabream (Sparus aurata L.), a marine hermaphrodite teleost of great commercial value, was the first fish species shown to possess histamine-containing mast cells (MCs) at mucosal tissues. MCs are highly abundant in the peritoneal exudate of gilthead seabream and compound 48/80 (Co 48/80), often used to promote MC activation and histamine release, is able to promote histamine release from gilthead seabream MCs in vitro and in vivo. The aim of the present study was to analyze the effect of histamine and Co 48/80 on the immune responses of gilthead seabream. For this purpose, histamine and Co 48/80 were intraperitoneally injected alone or combined with 109 heat-killed Vibrio anguillarum cells and their effects on head kidney and peritoneal exudate were analyzed. The results indicated that although histamine and Co 48/80 were both able to alter the percentage of peritoneal exudate and head kidney immune cell types, only Co 48/80 increased reactive oxygen species production by peritoneal leukocytes. In addition, histamine, but not Co 48/80, was able to slightly impair the humoral adaptive immune response, i.e. production of specific IgM to V. anguillarum. Notably, both histamine and Co 48/80 reduced the expression of the gene encoding histamine receptor H2 in peritoneal exudate leukocytes. These results show for the first time in fish that although systemic administration of histamine and Co 48/80 is safe, neither compound can be regarded as an efficient adjuvant for gilthead seabream vaccination. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. [Influenza vaccine and adjuvant].

    Science.gov (United States)

    Nakayama, Tetsuo

    2011-01-01

    Adjuvant is originated from the Latin word "adjuvare" which means "help" in English to enhance the immunological responses when given together with antigens. The beginning of adjuvant was mineral oil which enhanced the immune response when it was given with inactivated Salmonella typhimurium. Aluminium salt was used to precipitate diphtheria toxoid and increased level of antibody response was demonstrated when administered with alum-precipitated antigens. Since 1930, aluminium salt has been used as DTaP (diphtheria-tetanus-acellular pertussis vaccine) adjuvant. Many candidates were tested for adjuvant activity but only aluminum salt is allowed to use for human vaccines. New adjuvant MF59, oil-in-water emulsion type, was developed for influenza vaccine for elderly (Fluad) and series of AS adjuvant are used for hepatitis B, pandemic flue, and human papiloma virus vaccines. Oil-adjuvanted influenza pandemic vaccines induced higher antibody response than alum-adjuvanted vaccine with higher incidence of adverse events, especially for local reactions. Alum-adjuvanted whole virion inactivated H5N1 vaccine was developed in Japan, and it induced relatively well immune responses in adults. When it applied for children, febrile reaction was noted in approximately 60% of the subjects, with higher antibodies. Recent investigation on innate immunity demonstrates that adjuvant activity is initiated from the stimulation on innate immunity and/or inflammasome, resulting in cytokine induction and antigen uptake by monocytes and macrophages. The probable reason for high incidence of febrile reaction should be investigated to develop a safe and effective influenza vaccine.

  15. Salivary proteomics: A new adjuvant approach to the early diagnosis of familial juvenile systemic lupus erythematosus.

    Science.gov (United States)

    Abrão, Aline Lauria P; Falcao, Denise Pinheiro; de Amorim, Rivadávio Fernandes Batista; Bezerra, Ana Cristina B; Pombeiro, Gilson Augusto N M; Guimarães, Luciano Junqueira; Fregni, Felipe; Silva, Luciano Paulino; da Mota, Licia Maria Henrique

    2016-04-01

    Systemic lupus erythematosus (SLE) is a chronic multisystemic disease characterized by autoimmune inflammatory disturbance. Pleomorphic manifestations are present and a potentially progressive and debilitating course can be detected. SLE rarely manifests before age 5, and its onset peaks is around puberty. Although clinical manifestations, immunological alterations and treatment do not differ between juvenile and adult SLE, children tend to present with a more aggressive disease course than adults. Hence, autoimmune rheumatic diseases are the most common cause of morbidity and mortality in pediatric populations. Blood serum analysis plays an especially important role in the detection and monitoring of autoantibodies in SLE. However, since blood sampling is an uncomfortable procedure, especially in children, novel less invasive techniques and approaches are of utmost importance to evaluate pediatric subjects. In this regard, saliva samples have several advantages, such as: easy access, fast collection, painless and riskless procedure. Saliva has antimicrobial, immunomodulatory and anti-inflammatory properties, as well as several other relevant features. The whole saliva is a complex mixture of major and minor salivary gland secretion, gingival crevicular fluid, transudates plasma protein, keratinocyte products and oral microbiota. This biological fluid reflects the physiological state of the body, including the emotional condition, and endocrine, nutritional and metabolic changes. Therefore, salivary proteomics is becoming increasingly used for the early diagnosis of several diseases such as breast cancer, oral cancer, Sjögren's syndrome, diffuse systemic sclerosis, rheumatoid arthritis, among others. Considering the detection of some potential markers related to SLE in serum and urine, this study aims to conduct an initial evaluation of the possible presence of such biomarkers in saliva. Furthermore, it is expected to track down new salivary proteins that could be

  16. Adjuvants: Classification, Modus Operandi, and Licensing

    Directory of Open Access Journals (Sweden)

    Juliana de Souza Apostólico

    2016-01-01

    Full Text Available Vaccination is one of the most efficient strategies for the prevention of infectious diseases. Although safer, subunit vaccines are poorly immunogenic and for this reason the use of adjuvants is strongly recommended. Since their discovery in the beginning of the 20th century, adjuvants have been used to improve immune responses that ultimately lead to protection against disease. The choice of the adjuvant is of utmost importance as it can stimulate protective immunity. Their mechanisms of action have now been revealed. Our increasing understanding of the immune system, and of correlates of protection, is helping in the development of new vaccine formulations for global infections. Nevertheless, few adjuvants are licensed for human vaccines and several formulations are now being evaluated in clinical trials. In this review, we briefly describe the most well known adjuvants used in experimental and clinical settings based on their main mechanisms of action and also highlight the requirements for licensing new vaccine formulations.

  17. Vaccine Adjuvants: Putting Innate Immunity to Work

    Science.gov (United States)

    Coffman, Robert L.; Sher, Alan; Seder, Robert A.

    2012-01-01

    Adjuvants enhance immunity to vaccines and experimental antigens by a variety of mechanisms. In the past decade, many receptors and signaling pathways in the innate immune system have been defined and these innate responses strongly influence the adaptive immune response. The focus of this review is to delineate the innate mechanisms by which adjuvants mediate their effects. We highlight how adjuvants can be used to influence the magnitude and alter the quality of the adaptive response in order to provide maximum protection against specific pathogens. Despite the impressive success of currently approved adjuvants for generating immunity to viral and bacterial infections, there remains a need for improved adjuvants that enhance protective antibody responses, especially in populations that respond poorly to current vaccines. However, the larger challenge is to develop vaccines that generate strong T cell immunity with purified or recombinant vaccine antigens. PMID:21029960

  18. Obesity and risk of recurrence or death after adjuvant endocrine therapy with letrozole or tamoxifen in the breast international group 1-98 trial

    DEFF Research Database (Denmark)

    Ewertz, Marianne; Gray, Kathryn P; Regan, Meredith M

    2012-01-01

    To examine the association of baseline body mass index (BMI) with the risk of recurrence or death in postmenopausal women with early-stage breast cancer receiving adjuvant tamoxifen or letrozole in the Breast International Group (BIG) 1-98 trial at 8.7 years of median follow-up.......To examine the association of baseline body mass index (BMI) with the risk of recurrence or death in postmenopausal women with early-stage breast cancer receiving adjuvant tamoxifen or letrozole in the Breast International Group (BIG) 1-98 trial at 8.7 years of median follow-up....

  19. Gestalt Therapy and General System Theory.

    Science.gov (United States)

    Whitner, Phillip A.

    While General Systems Theory (GST) concepts appear to be applicable in explaining some of the phenomena that occur in a Gestalt Therapy group, research is needed to support this assumption. General Systems Theory may not be a group theory per se. Instead, GST may be a theory about groups. A meta-theory exists where its value and usefulness is…

  20. Verifying therapy safety interlock system with spin

    CSIR Research Space (South Africa)

    Seotsanyana, M

    2009-11-01

    Full Text Available on the successful use of model checking in the design and verification of the Safety Interlock System (SIS) at iThemba LABS. SIS is part of proton therapy control system (TCS) and its main task is to monitor and evaluate the safety conditions in the TCS as a whole...

  1. Adjuvant occupational therapy improves long-term depression recovery and return-to-work in good health in sick-listed employees with major depression: results of a randomised controlled trial.

    Science.gov (United States)

    Hees, Hiske L; de Vries, Gabe; Koeter, Maarten W J; Schene, Aart H

    2013-04-01

    To evaluate whether adjuvant occupational therapy (OT) can improve the effectiveness of treatment-as-usual (TAU) in sick-listed employees with major depression. In total, 117 employees sick-listed for a median duration of 4.8 months (IQR=2.6 to 10.1 months) because of major depression were randomised to TAU (n=39) or adjuvant OT (TAU+OT; n=78). OT (18 sessions) focussed on a fast return to work (RTW) and improving work-related coping and self-efficacy. The primary outcome was work participation (hours of absenteeism+duration until partial/full RTW). Secondary outcomes were depression, at-work functioning, and health-related functioning. Intermediate outcomes were work-related, coping and self-efficacy. Blinded assessments occurred at baseline and 6, 12 and 18 months follow-up. The groups did not significantly differ in their overall work participation (adjusted group difference=-1.9, 95% CI -19.9 to +16.2). However, those in TAU+OT did show greater improvement in depression symptoms (-2.8, -5.5 to -0.2), an increased probability of long-term symptom remission (+18%, +7% to +30%), and increased probability of long-term RTW in good health (GH) (+24%, 12% to 36%). There were no significant group differences in the remaining secondary/intermediate outcomes. In a highly impaired population, we could not demonstrate significant benefit of adjuvant OT for improving overall work participation. However, adjuvant OT did increase long-term depression recovery and long-term RTW in GH (ie, full RTW while being remitted, and with better work and role functioning). TRIAL REGISTRATION DUTCH TRIAL REGISTER: NTR2057.

  2. Acute and late vaginal toxicity after adjuvant high-dose-rate vaginal brachytherapy in patients with intermediate risk endometrial cancer: is local therapy with hyaluronic acid of clinical benefit?

    Directory of Open Access Journals (Sweden)

    Concetta Laliscia

    2016-12-01

    Full Text Available Purpose : The aim of the present study was to evaluate the effectiveness of hyaluronic acid (HA in the prevention of acute and late vaginal toxicities after high-dose-rate (HDR vaginal brachytherapy (BT. Material and methods : Between January 2011 and January 2015, we retrospectively analyzed 126 patients with endometrial cancer who underwent extrafascial hysterectomy with or without lymphadenectomy and adjuvant HDR-vaginal BT +/– adjuvant chemotherapy. The total dose prescription was 21 Gy in 3 fractions (one fraction for week. Vaginal ovules containing 5 mg of HA were given for whole duration of vaginal BT and for the two following weeks. Acute and late toxicities were evaluated according to CTCAE vs 4.02. Results : According to the revised FIGO 2009 classification, most tumors were in stage IA (30.9% and in stage IB (57.9%. Thirty-three patients (26.2% received adjuvant chemotherapy before vaginal BT. Five-year disease-free survival (DFS and five-year overall survival (OS were 88% and 93%, respectively. The most common grade 1-2 acute toxicities were vaginal inflammation (18 patients, 14.3% and dyspareunia (7 patients, 5.5%. Two patients (1.6% had more than one toxicity. Late toxicity occurred in 20 patients (15.9%. Grade 1-2 late toxicities were fibrosis (14 patients, 11.1% and telangiectasias (7 patients, 5.5%. Six patients (4.8% had more than one late toxicity. No grade 3 or higher acute or late toxicities were observed. Conclusions : These results appear to suggest that the local therapy with HA is of clinical benefit for intermediate risk endometrial cancer patients who receive adjuvant HDR-vaginal BT after surgery. A randomized trial comparing HA treatment vs. no local treatment in this clinical setting is warranted to further evaluate the efficacy of HA in preventing vaginal BT-related vaginal toxicity.

  3. A systemic literature review of neuroimaging studies in women with breast cancer treated with adjuvant chemotherapy

    Directory of Open Access Journals (Sweden)

    Paulina Andryszak

    2017-03-01

    Full Text Available Chemotherapy-induced cognitive deficits in patients with breast cancer, predominantly in attention and verbal memory, have been observed in numerous studies. These neuropsychological findings are corroborated by the results of neuroimaging studies. The aim of this paper was to survey the reports on cerebral structural and functional alterations in women with breast cancer treated with chemotherapy (CTx. First, we discuss the host-related and disease-related mechanisms underlying cognitive impairment after CTx. We point out the direct and indirect neurotoxic effect of cytostatics, which may cause: a damage to neurons or glial cells, changes in neurotransmitter levels, deregulation of the immune system and/or cytokine release. Second, we focus on the results of neuroimaging studies on brain structure and function that revealed decreased: density of grey matter, integrity of white matter and volume of multiple brain regions, as well as their lower activation during cognitive task performance. Finally, we concentrate on compensatory mechanisms, which activate additional brain areas or neural connection to reach the premorbid cognitive efficiency.

  4. ER-positive breast cancer patients with more than three positive nodes or grade 3 tumors are at high risk of late recurrence after 5-year adjuvant endocrine therapy

    Directory of Open Access Journals (Sweden)

    Song F

    2017-10-01

    Full Text Available Fangbin Song,1 Jianbing Zhang,2 Shanbao Li,1 Junyi Wu,1 Tao Jin,1 Jun Qin,1 Ye Wang,1 Min Wang,1 Junming Xu1 1Department of General Surgery, 2Department of Pathology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China Purpose: Currently, although several clinical trials available give strong suggestions that extension of endocrine therapy has benefits, the risk level at which patients may benefit from extended endocrine therapy remains uncertain. This study aimed to identify the proportion of patients at a substantial risk of late recurrence after 5-year adjuvant endocrine therapy.Patients and methods: We reviewed 1,056 female patients with primary breast cancer who underwent curative resection between January 2006 and December 2011. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model to identify prognostic factors.Results: A total of 327 eligible patients were eventually enrolled in this study. Among them, 42 (12.8% patients suffered from distant metastasis and 34 (10.4% patients experienced locoregional recurrence after 5-year adjuvant endocrine therapy. In multivariate analysis, patients with more than three positive nodes (hazard ratio [HR] =2.176, 95% CI=1.071–4.421; P=0.032 and histologic grade 3 disease (HR=2.098, 95% CI=1.300–3.385; P=0.002 were significantly associated with high risk of late recurrence. However, only histologic grade 3 (HR=2.212, 95% CI=1.166–4.194; P=0.015 was significantly associated with high risk of distant metastasis.Conclusion: Late relapse after completion of 5-year adjuvant endocrine therapy was still common, and grade 3 and more than three positive nodes were the risk factors of late recurrence, while grade 3 was the only risk factor of late distant metastasis. These patients might benefit from extended endocrine therapy. Keywords: Ki-67, breast neoplasms, prognosis, extended endocrine

  5. The occurrence of fractures after adjuvant treatment of breast cancer

    DEFF Research Database (Denmark)

    Kristensen, Bent; Ejlertsen, Bent; Jensen, Maj-Britt

    2017-01-01

    BACKGROUND: Adjuvant treatment in breast cancer patients especially with aromatase inhibitors (AIs) has adverse effects on bone metabolism resulting in an increased occurrence of fractures. In order to demonstrate this occurrence, long-term follow-up studies are necessary. From several national...... menopause and tamoxifen treatment were associated with a lower occurrence and AI treatment, age and CCI were associated with a higher occurrence of fractures. CONCLUSION: Before advising adjuvant therapy with AIs fragile patients with chronic diseases should receive special attention in order to reduce...... of the analysis. These data were matched with data on all types of fractures from the Danish National Patient Register and vital data from the Danish Civil Registration System. RESULTS: After data cleaning 66,502 patients were available for analysis and 16,360 of these had incurred 20,341 fractures with 13...

  6. Inhalable drugs for systemic therapy.

    Science.gov (United States)

    Corkery, K

    2000-07-01

    Although oral and injectable drug formulations still dominate the market, interest in pulmonary delivery has been rising steadily. Given patients' desire for an alternative to injections, and recent advances in aerosol science and pulmonary medicine, the potential for improved disease management outcomes by using aerosols for systemic drug delivery should lead the way for a shift to inhalables.

  7. Biological Therapy in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Mariana Postal

    2012-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a prototypic inflammatory autoimmune disorder characterized by multisystem involvement and fluctuating disease activity. Symptoms range from rather mild manifestations such as rash or arthritis to life-threatening end-organ manifestations. Despite new and improved therapy having positively impacted the prognosis of SLE, a subgroup of patients do not respond to conventional therapy. Moreover, the risk of fatal outcomes and the damaging side effects of immunosuppressive therapies in SLE call for an improvement in the current therapeutic management. New therapeutic approaches are focused on B-cell targets, T-cell downregulation and costimulatory blockade, cytokine inhibition, and the modulation of complement. Several biological agents have been developed, but this encouraging news is associated with several disappointments in trials and provide a timely moment to reflect on biologic therapy in SLE.

  8. Long-term results of the randomized phase III trial EORTC 18991 of adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma

    NARCIS (Netherlands)

    A.M.M. Eggermont (Alexander); S. Suciu (Stefan); A. Testori (Alessandro); M. Santinami (Mario); W.H.J. Kruit (Wim); J. Marsden (Jeremy); C.J.A. Punt (Cornelis); F. Salès (François); R. Dummer (Reinhard); C. Robert (Caroline); D. Schadendorf (Dirk); P. Patel (Poulam); G. de Schaetzen (Gaetan); A. Spatz (Alan); U. Keilholz (Ulrich)

    2012-01-01

    textabstractPurpose: Adjuvant pegylated interferon alfa-2b (PEG-IFN-α-2b) was approved for treatment of resected stage III melanoma in 2011. Here, we present long-term follow-up results of this pivotal trial. Patients and Methods: In all, 1,256 patients with resected stage III melanoma were randomly

  9. Feasibility of adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent maintenance therapy with S-1 for completely resected non-small-cell lung cancer: results of the Setouchi Lung Cancer Group Study 1001.

    Science.gov (United States)

    Okumura, Norihito; Sonobe, Makoto; Okabe, Kazunori; Nakamura, Hiroshige; Kataoka, Masafumi; Yamashita, Motohiro; Nakata, Masao; Kataoka, Kazuhiko; Yamashita, Yoshinori; Soh, Junichi; Yoshioka, Hiroshige; Hotta, Katsuyuki; Matsuo, Keitaro; Sakamoto, Junichi; Toyooka, Shinichi; Date, Hiroshi

    2017-04-01

    This multicenter study evaluated the feasibility of novel adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent, long-term maintenance with S-1 in patients with completely resected stage II-IIIA non-small-cell lung cancer (NSCLC). Patients received four cycles of S-1 (80 mg/m2/day for 2 weeks, followed by 2 weeks rest) plus carboplatin (area under the curve 5, day 1) followed by S-1 (80 mg/m2/day for 2 weeks, followed by a 1-week rest). Patients unable to continue S-1 plus carboplatin because of severe toxicity converted to single-agent S-1 maintenance. The duration of adjuvant chemotherapy was 10 months in both situations. The primary endpoint was feasibility, defined as the proportion of patients who completed four cycles of S-1 plus carboplatin and single-agent S-1 maintenance for 10 months. The treatment completion rate was determined; treatment was considered feasible if the lower 90% confidence interval (CI) was ≥50%. Eighty-nine patients were enrolled, of whom 87 were eligible and assessable. Seventy-eight patients (89.7%) completed four cycles of S-1 plus carboplatin and 55 (63.2%) completed the following S-1 maintenance therapy for a total of 10 months. The treatment completion rate was 63.2% (90% CI, 54.4-71.2%), indicating feasibility. There were no treatment-related deaths. Grade 3/4 toxicities included neutropenia (13.8%), thrombocytopenia (11.5%), and anorexia (4.6%). The 2-year relapse-free survival rate was 59.8%. We concluded that adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent maintenance therapy with S-1 is feasible and tolerable in patients with completely resected NSCLC. UMIN000005041.

  10. Alliance and adherence in a systemic therapy

    NARCIS (Netherlands)

    Lange, A.M.C.; Rijken, R.E.A. van der; Delsing, M.J.M.H.; Busschbach, J.J.V. van; Horn, J.E. van; Scholte, R.H.J.

    2017-01-01

    Background: The client-therapist working alliance is a key contributor to effective adult psychotherapy. However, little is known about its role in family and systemic therapy. Moreover, few studies have assessed alliance longitudinally or have investigated how it interrelates with other process

  11. 21 CFR 892.5300 - Medical neutron radiation therapy system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Medical neutron radiation therapy system. 892.5300... therapy system. (a) Identification. A medical neutron radiation therapy system is a device intended to generate high-energy neutrons for radiation therapy. This generic type of device may include signal...

  12. Systemic therapy of childhood atopic dermatitis.

    Science.gov (United States)

    Slater, Nathaniel A; Morrell, Dean S

    2015-01-01

    Atopic dermatitis (AD) is a common childhood inflammatory disease that, in a small percentage of cases, can become severe enough to require potent systemic treatment. Many trials have been conducted with systemic agents for the treatment of severe pediatric AD; we review the evidence here. Although corticosteroids are widely used in practice, they are not generally recommended as a systemic treatment option for AD in children. Most patients experience a relatively rapid and robust response to cyclosporine. Treating children with cyclosporine long term is troubling; however, azathioprine, mycophenolate mofetil, and methotrexate are all reasonable alternatives for maintenance therapy in recalcitrant cases. Several additional options are available for the most refractory cases, including interferon-γ, intravenous immunoglobulin, and various biologics. Phototherapy is another modality that can be effective in treating severe AD. Ultimately the choice of agent is individualized. Systemic therapy options are associated with potentially severe adverse effects and require careful monitoring. Nonsystemic approaches toward prevention of flares and long-term control of atopic dermatitis in pediatric patients should be continued in conjunction with systemic therapy. In the future, more targeted systemic treatments hold the potential for effective control of disease with fewer side effects than broadly immunosuppressive agents. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. PREPARATION AND CHARACTERIZATION OF A NEAR-INFRARED LIGHT RESPONSIVE MICROCAPSULE SYSTEM FOR CANCER THERAPY

    Directory of Open Access Journals (Sweden)

    YINGFENG DI

    2014-01-01

    Full Text Available A novel near-infrared light responsive microcapsule system, gold nanorod-covered DOX-loaded hollow CaCO3 microcapsule (AuNR-HM-DOX is developed for cancer therapy. The hollow CaCO3 microcapsules were prepared based on the self-assembly between chitosan and sodium alginate on CaCO3 particles via layer-by-layer technique, and then covered with gold nanorods to obtain the microcapsule system. Upon near-infrared (NIR irradiation, microcapsule with gold nanorods can convert the absorbed NIR light into heat. Meanwhile, doxorubicin (DOX, a chemotherapy drug, is loaded into the microcapsule system via electrostatic adsorption for combined photothermal therapy and chemotherapy. Properties of AuNR-HM-DOX including grain diameter, optical spectra were characterized. Confocal fluorescence imaging was performed to observe the morphology of the capsules and existence of DOX in the core, confirming the successful loading of DOX. The release of DOX from the capsules under continuous NIR irradiation was investigated to evaluate the temperature responsiveness of AuNR-HM-DOX. Results indicate that AuNR-HM-DOX microcapsules possess uniform particle size and high light responsiveness. The combination of chemical and physical therapy of AuNR-HM-DOX features great potential as an adjuvant therapeutic alternative material for combined cancer therapy.

  14. Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy

    Science.gov (United States)

    2013-09-01

    10-1-0699 TITLE: Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after...apoptosis. WT1 protein is highly expressed in malignant pleural mesothelioma (MPM), and is a rational target for immunotherapy. We have developed a...this project is to conduct a multicenter, double-blinded, randomized trial comparing treatment with the WT-1 peptide vaccine + Montanide/GM-CSF to

  15. Immune Correlates of GM-CSF and Melanoma Peptide Vaccination in a Randomized Trial for the Adjuvant Therapy of Resected High-Risk Melanoma (E4697).

    Science.gov (United States)

    Butterfield, Lisa H; Zhao, Fengmin; Lee, Sandra; Tarhini, Ahmad A; Margolin, Kim A; White, Richard L; Atkins, Michael B; Cohen, Gary I; Whiteside, Theresa L; Kirkwood, John M; Lawson, David H

    2017-09-01

    Purpose: E4697 was a multicenter intergroup randomized placebo-controlled phase III trial of adjuvant GM-CSF and/or a multiepitope melanoma peptide vaccine for patients with completely resected, high-risk stage III/IV melanoma.Experimental Design: A total of 815 patients were enrolled from December 1999 to October 2006 into this six-arm study. GM-CSF was chosen to promote the numbers and functions of dendritic cells (DC). The melanoma antigen peptide vaccine (Tyrosinase368-376 (370D), gp100209-217 (210M), MART-127-35) in montanide was designed to promote melanoma-specific CD8+ T-cell responses.Results: Although the overall RFS and OS were not significantly improved with the vaccine or GM-CSF when compared with placebo, immunomodulatory effects were observed in peripheral blood and served as important correlates to this therapeutic study. Peripheral blood was examined to evaluate the impact of GM-CSF and/or the peptide vaccine on peripheral blood immunity and to investigate potential predictive or prognostic biomarkers. A total of 11.3% of unvaccinated patients and 27.1% of vaccinated patients developed peptide-specific CD8+ T-cell responses. HLA-A2+ patients who had any peptide-specific CD8+ T-cell response at day +43 tended to have poorer OS in univariate analysis. Patients receiving GM-CSF had significant reduction in percentages of circulating myeloid dendritic cells (mDC) and plasmacytoid DC (pDC) at day +43. In a subset of patients who received GM-CSF, circulating myeloid-derived suppressor cells (MDSC), and anti-GM-CSF-neutralizing antibodies (Nabs) were also modulated. The majority of patients developed anti-GM-CSF Nabs, which correlated with improved RFS and OS.Conclusions: The assessment of cellular and humoral responses identified counterintuitive immune system changes correlating with clinical outcome. Clin Cancer Res; 23(17); 5034-43. ©2017 AACR. ©2017 American Association for Cancer Research.

  16. Factors Associated with Adherence to Adjuvant Endocrine Therapy Among Privately Insured and Newly Diagnosed Breast Cancer Patients: A Quantile Regression Analysis.

    Science.gov (United States)

    Farias, Albert J; Hansen, Ryan N; Zeliadt, Steven B; Ornelas, India J; Li, Christopher I; Thompson, Beti

    2016-08-01

    Adherence to adjuvant endocrine therapy (AET) for estrogen receptor-positive breast cancer remains suboptimal, which suggests that women are not getting the full benefit of the treatment to reduce breast cancer recurrence and mortality. The majority of studies on adherence to AET focus on identifying factors among those women at the highest levels of adherence and provide little insight on factors that influence medication use across the distribution of adherence. To understand how factors influence adherence among women across low and high levels of adherence. A retrospective evaluation was conducted using the Truven Health MarketScan Commercial Claims and Encounters Database from 2007-2011. Privately insured women aged 18-64 years who were recently diagnosed and treated for breast cancer and who initiated AET within 12 months of primary treatment were assessed. Adherence was measured as the proportion of days covered (PDC) over a 12-month period. Simultaneous multivariable quantile regression was used to assess the association between treatment and demographic factors, use of mail order pharmacies, medication switching, and out-of-pocket costs and adherence. The effect of each variable was examined at the 40th, 60th, 80th, and 95th quantiles. Among the 6,863 women in the cohort, mail order pharmacies had the greatest influence on adherence at the 40th quantile, associated with a 29.6% (95% CI = 22.2-37.0) higher PDC compared with retail pharmacies. Out-of-pocket cost for a 30-day supply of AET greater than $20 was associated with an 8.6% (95% CI = 2.8-14.4) lower PDC versus $0-$9.99. The main factors that influenced adherence at the 95th quantile were mail order pharmacies, associated with a 4.4% higher PDC (95% CI = 3.8-5.0) versus retail pharmacies, and switching AET medication 2 or more times, associated with a 5.6% lower PDC versus not switching (95% CI = 2.3-9.0). Factors associated with adherence differed across quantiles. Addressing the use of mail order

  17. Adjuvant Radiation Therapy for Margin-Positive Vulvar Squamous Cell Carcinoma: Defining the Ideal Dose-Response Using the National Cancer Data Base

    Energy Technology Data Exchange (ETDEWEB)

    Chapman, Bhavana V.; Gill, Beant S. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Viswanathan, Akila N. [Department of Radiation Oncology Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD (United States); Balasubramani, Goundappa K. [Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Sukumvanich, Paniti [Department of Gynecologic Oncology, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Beriwal, Sushil, E-mail: beriwals@upmc.edu [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States)

    2017-01-01

    Purpose: Positive surgical margins after radical vulvectomy for vulvar cancer portend a high risk for local relapse, which may be challenging to salvage. We assessed the impact of adjuvant radiation therapy (aRT) on overall survival (OS) and the dose-response relationship using the National Cancer Data Base. Methods and Materials: Patients with vulvar squamous cell carcinoma who underwent initial extirpative surgery with positive margins from 1998 to 2012 were included. Factors associated with aRT and specific dose levels were analyzed using logistic regression. Log-rank and multivariable Cox proportional hazards modeling were used for OS analysis. Results: We identified 3075 patients with a median age of 66 years (range, 22-90 years); the median follow-up time was 36.4 months (interquartile range [IQR] 15.4-71.0 months). Stage IA/B disease represented 41.2% of the cohort. Sixty-three percent underwent lymph node assessment, with a 45% positivity rate. In total, 1035 patients (35.3%) received aRT, with a median dose of 54.0 Gy (IQR 48.6-60.0 Gy). The 3-year OS improved from 58.5% to 67.4% with aRT (P<.001). On multivariable analysis, age, Charlson-Deyo score ≥1, stage ≥II, tumors ≥4 cm, no aRT, and adverse nodal characteristics led to inferior survival. Dose of aRT was positively associated with OS as a continuous variable on univariate analysis (P<.001). The unadjusted 3-year OS for dose subsets 30.0 to 45.0 Gy, 45.1 to 53.9 Gy, 54.0 to 59.9 Gy, and ≥60 Gy was 54.3%, 55.7%, 70.1%, and 65.3%, respectively (P<.001). Multivariable analysis using a 4-month conditional landmark revealed that the greatest mortality reduction occurred in cumulative doses ≥54 Gy: 45.1 to 53.9 Gy (hazard ratio [HR] 0.94, P=.373), 54.0 to 59.9 Gy (HR 0.75, P=.024), ≥60 Gy (HR 0.71, P=.015). No survival benefit was seen with ≥60 Gy compared with 54.0 to 59.9 Gy (HR 0.95, P=.779). Conclusions: Patients with vulvar squamous cell carcinoma and positive surgical

  18. STAT3 single nucleotide polymorphism rs4796793 SNP does not correlate with response to adjuvant IFNα therapy in stage III melanoma patients

    Directory of Open Access Journals (Sweden)

    David eSchrama

    2014-11-01

    Full Text Available Interferon alpha (IFNα is approved for adjuvant treatment of stage III melanoma in Europe and the US. Its clinical efficacy, however, is restricted to a subpopulation of patients while side effects occur in most of treated patients. Thus, the identification of predictive biomarkers would be highly beneficial to improve the benefit to risk ratio. In this regard, STAT3 is important for signaling of the IFNα receptor. Moreover, the STAT3 single nucleotide polymorphism (SNP rs4796793 has recently been reported to be associated with IFNα sensitivity in metastatic renal cell carcinoma. To translate this notion to melanoma, we scrutinized the impact of rs4796793 functionally and clinically in this cancer. Interestingly, melanoma cells carrying the minor allele of rs4796793 were the most sensitive to IFNα in vitro. However, we did not detect a correlation between SNP genotype and STAT3 mRNA expression for either melanoma cells or for peripheral blood lymphocytes. Next, we analyzed the impact of rs4796793 on the clinical outcome of 259 stage III melanoma patients of which one third had received adjuvant IFNα treatment. These analyses did not reveal a significant association between the STAT3 rs4796793 SNP and patients’ progression free or overall survival when IFN treated and untreated patients were compared. In conclusion, STAT3 rs4796793 SNP is no predictive marker for the efficacy of adjuvant IFNα treatment in melanoma patients.

  19. Adjuvant granulocyte colony-stimulating factor therapy results in improved spatial learning and stimulates hippocampal neurogenesis in a mouse model of pneumococcal meningitis.

    Science.gov (United States)

    Schmidt, Anna Kathrin; Reich, Arno; Falkenburger, Björn; Schulz, Jörg B; Brandenburg, Lars Ove; Ribes, Sandra; Tauber, Simone C

    2015-01-01

    Despite the development of new antibiotic agents, mortality of pneumococcal meningitis remains high. In addition, meningitis results in severe long-term morbidity, most prominently cognitive deficits. Granulocyte colony-stimulating factor (G-CSF) stimulates proliferation and differentiation of hematopoietic progenitor cells and increases the number of circulating neutrophil granulocytes. This study investigated the effect of adjuvant G-CSF treatment on cognitive function after pneumococcal meningitis. C57BL/6 mice were infected by subarachnoid injection of Streptococcus pneumoniae serotype 3 and treated with ceftriaxone and G-CSF subcutaneously or ceftriaxone alone for 5 days. Clinical scores, motor performance, and mortality during bacterial meningitis were unaffected by adjuvant G-CSF treatment. No effect of G-CSF treatment on production of proinflammatory cytokines or activation of microglia or astrocytes was observed. The G-CSF treatment did, however, result in hippocampal neurogenesis and improved spatial learning performance 6 weeks after meningitis. These results suggest that G-CSF might offer a new adjuvant therapeutic approach in bacterial meningitis to reduce long-term cognitive deficits.

  20. Permanent alopecia in patients with breast cancer after taxane chemotherapy and adjuvant hormonal therapy: Clinicopathologic findings in a cohort of 10 patients.

    Science.gov (United States)

    Fonia, Athina; Cota, Carlo; Setterfield, Jane F; Goldberg, Lynne J; Fenton, David A; Stefanato, Catherine M

    2017-05-01

    Anagen effluvium with reversible scalp alopecia is a known side effect of chemotherapy. However, there are an increasing number of reports in the literature documenting permanent alopecia in patients treated with taxanes. We sought to describe the clinicopathologic features in breast cancer patients who underwent treatment with taxanes and adjuvant hormonal chemotherapy. We reviewed the clinical and histopathologic information of a cohort of 10 patients treated with taxanes and adjuvant hormonal chemotherapy. We have observed 3 types of clinical patterns of alopecia (types A, B, and C), and have validated the histopathologic features showing alopecia areata-like and female pattern hair loss. The study was based on a small sample size and retrospective retrieval of clinical information and histopathologic review of posttreatment slides. We hypothesize a clinicopathologic model of hair follicle cycle disruption in response to the chemoinflammatory and hormonal insults to the hair follicles resulting in permanent alopecia. Clinicopathologic correlation is paramount to the understanding of the morphobiologic pathways in chemotherapy-induced alopecia caused by taxanes and adjuvant hormonal treatment. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  1. Adjuvant radiation therapy for the treatment of endometrial cancer: experience with combination of external radiation therapy and high-dose rate brachytherapy; Radioterapia adjuvante no tratamento do cancer de endometrio: experiencia com a associacao de radioterapia externa e braquiterapia de alta taxa de dose

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Michael Jenwei; Novaes, Paulo Eduardo Ribeiro Soares; Pellizzon, Antonio Cassio de Assis; Ferrigno, Robson; Fogaroli, Ricardo Cesar; Maia, Maria Aparecida Conte; Salvajoli, Joao Victor [Hospital do Cancer A.C. Camargo, Sao Paulo, SP (Brazil). Dept. de Radioterapia]. E-mail: michael.chen@ig.com.br; Nishimoto, Ines Nobuko [Hospital do Cancer A.C. Camargo, Sao Paulo, SP (Brazil). Centro de Estudos

    2005-12-01

    Objective: To review the results of adjuvant external beam radiation therapy (EBRT) combined with high-dose rate brachytherapy (HDR-BT) for the treatment of endometrial carcinoma. Materials and methods: We retrospectively evaluated 141 patients treated with EBRT and HDR-BT after surgery between January 1993 and January 2001. EBRT was performed with a median dose of 45 Gy, and HDR-BT was performed with a median dose of 24 Gy, with four weekly insertions of 6 Gy. The median age of the patients was 63 years and the disease stage distribution was: CS I (FIGO), 52.4%; CS II, 13.5%; CS III, 29.8%; CS IV, 4.3%. Results: With a median follow-up of 53.7 months, the disease free survival (DFS) at five years was: CS I, 88.0%; CS II, 70.8%; CS III, 55.1%; CS IV, 50.0% (p = 0.0003). Global survival after five years was: CS I, 79.6%; CS II, 74.0%; CS III, 53.6%; CS IV, 100.0% (p = 0.0062). Factors affecting the DFS were histological grade and serous-papillary histology. Recurrence of the disease was observed in 33 cases, 13 (9.2%) of these occurred in the pelvis, vagina or vaginal vault. EBRT + HDR-BT of the vaginal vault allowed disease control in 90.8% of the cases. Conclusion: Radiation therapy is essential for loco-regional control of endometrial cancer and can achieve excellent cure rates in the initial stages. In more advanced stages, therapeutic failure frequently appears as distant metastases suggesting the need for complementary systemic therapy using new treatment modalities, particularly chemotherapy. (author)

  2. Quality of pathological reporting for renal cell cancer: implications for systemic therapy, prognostication and surveillance.

    Science.gov (United States)

    Shuch, Brian; Pantuck, Allan J; Pouliot, Frederic; Finley, David S; Said, Jonathan W; Belldegrun, Arie S; Saigal, Chris

    2011-08-01

    • To evaluate whether current nephrectomy pathology reports are sufficient to allow clinicians to use prognostic nomograms, tailor surveillance, enroll patients into adjuvant trials and select systemic therapy for renal cell carcinoma (RCC). • Nephrectomy pathology reports were obtained from the LA County Tumor Registry. Key reporting elements identified by the College of American Pathology (CAP) and utilized in RCC prognostic models were abstracted. Hospital type was coded as community, teaching or cancer centre. • Reporting quality was assessed across hospital type and year. • A total of 317 of 344 sampled reports (92.2%) met the inclusion criteria. Tumour size and margin status were commonly reported. Some 90.2% and 84.2% of reports provided data on histology and Fuhrman grade. Tumour classification was omitted in 27.8%. • Microvascular invasion and necrosis were infrequently reported (44.5% and 25.6%, respectively). Only 59.9% of reports met CAP guidelines for tumour classification, margin, size, histology and grade. • Two prognostic nomograms (Stage, Size, Grade and Necrosis system and Kattan) could rarely be utilized (15.8% and 12.3%, respectively), whereas the UCLA Integrated Staging System could be used frequently (65.6%). There were discrepancies satisfying CAP guidelines between community, teaching and cancer centre hospitals, with 54.7%, 70.5% and 75% of reports meeting CAP criteria (P= 0.0102). • Current RCC pathology reporting fails to satisfy CAP guidelines, does not permit the use of prognostic systems, and may hinder enrollment into adjuvant trials and the selection of systemic therapy. Important reporting discrepancies exist between hospital types, with cancer centres performing best. • Quality improvement initiatives to encourage consistent, comprehensive and clinically relevant pathology reports would improve the quality of RCC patient care. © 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.

  3. Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

    Directory of Open Access Journals (Sweden)

    Samantha Sayers

    2012-01-01

    Full Text Available Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO in the Web Ontology Language (OWL format.

  4. Intravenous immunoglobulin therapy and systemic lupus erythematosus.

    Science.gov (United States)

    Zandman-Goddard, Gisele; Levy, Yair; Shoenfeld, Yehuda

    2005-12-01

    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with diverse manifestations. We suggest that intravenous immunoglobulin (IVIg) therapy may be beneficial and safe for various manifestations in SLE. A structured literature search of articles published on the efficacy of IVIg in the treatment of SLE between 1983 and 2005 was conducted. We searched the terms "IVIg," "intravenous immunoglobulin," "lupus," "SLE," and "systemic lupus erythematosus." The various clinical manifestations of SLE that were reported to be successfully treated by IVIg in case reports include autoimmune hemolytic anemia, acquired factor VIII inhibitors, acquired von Willebrand disease, pure red cell aplasia, thrombocytopenia, pancytopenia, myelofibrosis, pneumonitis, pleural effusion, pericarditis, myocarditis, cardiogenic shock, nephritis, end-stage renal disease, encephalitis, neuropsychiatric lupus, psychosis, peripheral neuropathy, polyradiculoneuropathy, and vasculitis. The most extensive experience is with lupus nephritis. There are only a few case series of IVIg use in patients with SLE with various manifestations, in which the response rate to IVIg therapy ranged from 33 to 100%. We suggest that IVIg devoid of sucrose, at a dose of 2 g/kg over a 5-d period given uniformly and at a slow infusion rate in patients without an increased risk for thromboembolic events or renal failure, is a safe and beneficial adjunct therapy for cases of SLE that are resistant to or refuse conventional treatment. The duration of therapy is yet to be established. Controlled trials are warranted.

  5. A Fasciola hepatica-derived fatty acid binding protein induces protection against schistosomiasis caused by Schistosoma bovis using the adjuvant adaptation (ADAD) vaccination system.

    Science.gov (United States)

    Vicente, Belén; López-Abán, Julio; Rojas-Caraballo, José; Pérez del Villar, Luis; Hillyer, George V; Martínez-Fernández, Antonio R; Muro, Antonio

    2014-10-01

    Several efforts have been made to identify anti-schistosomiasis vaccine candidates and new vaccination systems. The fatty acid binding protein (FAPB) has been shown to induce a high level of protection in trematode infection. The adjuvant adaptation (ADAD) vaccination system was used in this study, including recombinant FABP, a natural immunomodulator and saponins. Mice immunised with the ADAD system were able to up-regulate proinflammatory cytokines (IL-1 and IL-6) and induce high IgG2a levels. Moreover, there was a significant reduction in worm burden, egg liver and hepatic lesion in vaccinated mice in two independent experiments involving Schistosoma bovis infected mice. The foregoing data shows that ADAD system using FABP provide a good alternative for triggering an effective immune response against animal schistosomiasis. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Mannose derivative and lipid A dually decorated cationic liposomes as an effective cold chain free oral mucosal vaccine adjuvant-delivery system.

    Science.gov (United States)

    Wang, Ning; Wang, Ting; Zhang, Meiling; Chen, Ruonan; Niu, Ruowen; Deng, Yihui

    2014-09-01

    To develop convenient, effective cold chain-free subunit vaccines, a mannose-PEG-cholesterol conjugate (MPC) was synthesized as a lectin binding molecule and anchored onto liposomes which entrapped lipid A and model antigen to form a vaccine adjuvant-delivery system targeting antigen presenting cells. With MPC, soy phosphatidylcholine, stearylamine and monophosphoryl lipid A as emulsifiers dissolved in oil phase (O), and sucrose and BSA in water phase (W), the O/W emulsions were prepared and subsequently lyophilized. The lyophilized product was stable enough to be stored at room temperature and, upon rehydration, formed MPC-/lipid A-liposomes (MLLs) with a size under 300 nm and antigen association rates of around 36%. The MLLs given to mice via oral mucosal (o.m.) administration showed no side effects but induced potent immune responses as evidenced by the high levels of IgG in the sera and IgA in the salivary, intestinal and vaginal secretions of mice. High levels of IgG2a and IFN-γ in treated mice revealed that MLLs via o.m. vaccination induced a mixed Th1/Th2 response against antigens, establishing both humoral and cellular immunity. Thus, the MLLs may be a potent cold chain-free oral mucosal vaccine adjuvant-delivery system. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Using procedure of emulsification-lyophilization to form lipid A-incorporating cochleates as an effective oral mucosal vaccine adjuvant-delivery system (VADS).

    Science.gov (United States)

    Wang, Ning; Wang, Ting; Zhang, Meiling; Chen, Ruonan; Deng, Yihui

    2014-07-01

    Using a procedure of emulsification-lyophilization (PEL), adjuvant lipid A-cochleates (LACs) were prepared as a carrier for model antigen bovine serum albumin (BSA). With phosphatidylserine and lipid A as emulsifiers dissolved in oil phase (O), sucrose and CaCl2 in the inner water phase (W1), and BSA, sucrose and PEG2000 in the outer water phase (W2), the W1/O/W2 emulsions were prepared and subsequently lyophilized to form a dry product which was stable enough to be stored at room temperature. Upon rehydration of the dry products, cochleates formed with a size of 800 nm and antigen association rates of 38%. After vaccination of mice through oral mucosal (o.m.) administration, LACs showed no side effects but induced potent immune responses as evidenced by high levels of IgG in the sera and IgA in the salivary, intestinal and vaginal secretions of mice. In addition, high levels of IgG2a and IFN-γ in the sera or culture supernatants of splenocytes of the immunized mice were also detected. These results revealed that LACs induced a mixed Th1/Th2 response against the loaded antigens. Thus, the LACs prepared by PEL were able to induce both systemic and mucosal immune responses and may act as a potent cold-chain-free oral mucosal vaccine adjuvant delivery system (VADS). Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Biological Effects of Anti-Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Antibody Formation in Patients Treated With GM-CSF (Sargramostim) as Adjuvant Therapy of Melanoma.

    Science.gov (United States)

    Spitler, Lynn E; Cao, Huynh; Piironen, Timo; Whiteside, Theresa L; Weber, Robert W; Cruickshank, Scott

    2017-04-01

    We investigated the development of binding and neutralizing antibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients receiving prolonged therapy with GM-CSF as adjuvant therapy of melanoma and the impact of these antibodies on biological effects. Fifty-three patients with high-risk melanoma that had been surgically excised were treated with GM-CSF, 125 μg/m daily for 14 days every 28 days for 1 year after surgical resection of disease. Serum samples for antibodies to GM-CSF were measured before treatment and on study days 155 and 351. Blood draws for testing biological effects were keyed to GM-CSF administration: days 0 (before), 15 (after 14 d on GM-CSF), 29 (after 14 d off GM-CSF), 155, and 351 (after 14 d on GM-CSF in the sixth and 13th cycle of treatment). Of 53 patients enrolled, 43 were evaluable for the development of anti-GM-CSF antibodies. Of these, 93% developed binding antibodies and 42% developed both binding and neutralizing antibodies. The increase in the white blood cell count, percent eosinophils, or neopterin levels engendered by GM-CSF administration was abrogated or markedly decreased in patients with neutralizing antibodies but not in patients who developed only binding antibodies. Ninety-three percent of patients with melanoma treated with GM-CSF as adjuvant therapy develop antibodies to GM-CSF. In those with neutralizing antibodies, a diminution of the biological effects of GM-CSF was observed. The development of neutralizing antibodies might also abrogate the potential clinical benefit of this treatment and should be considered in the design of future clinical trials.

  9. Chemoradiotherapy, with adjuvant surgery for local control, confers a durable survival advantage in adenocarcinoma and squamous cell carcinoma of the oesophagus.

    LENUS (Irish Health Repository)

    Bass, G A

    2014-04-01

    Oesophageal cancer usually presents with systemic disease, necessitating systemic therapy. Neo-adjuvant chemoradiotherapy improves short-term survival, but its long-term impact is disputed because of limited accrual, treatment-protocol heterogeneity and a short follow-up of randomised trials.

  10. A Lipopolysaccharide from Pantoea Agglomerans Is a Promising Adjuvant for Sublingual Vaccines to Induce Systemic and Mucosal Immune Responses in Mice via TLR4 Pathway.

    Directory of Open Access Journals (Sweden)

    Masahiro Fukasaka

    Full Text Available A lipopolysaccharide from Pantoea agglomerans (LPSpa has been applied to various fields for human use as a Toll-like receptor 4 ligand and its safety has been confirmed. Here, we showed for the first time the application of LPSpa as an effective mucosal adjuvant for activating vaccine-induced antigen specific immune responses. Mice sublingually immunized with influenza vaccine (HA split vaccine with LPSpa induced both HA-specific IgG (systemic and IgA (mucosal antibody responses, which led to a significant increase in survival rate against lethal influenza virus challenge compared with subcutaneous vaccination. After sublingual administration of ovalbumin with LPSpa, ovalbumin-specific mucosal IgA responses were induced at both mucosal surfaces close to the immunized site and at remote mucosal surfaces. Sublingual administration of LPSpa evoked local antigen-uptake by dendritic cells in cervical lymph nodes. LPSpa induced cytokine production and the maturation and proliferation of innate immune cells via Toll-like receptor 4 in dendritic cells. Collectively, these results suggest that LPSpa can be used as an effective mucosal adjuvant to stimulate and activate local innate immune cells to improve and enhance mucosal vaccine potency against various pathogens.

  11. Semecarpus anacardium Linn. nut milk extract, an indigenous drug preparation, modulates reactive oxygen/nitrogen species levels and antioxidative system in adjuvant arthritic rats.

    Science.gov (United States)

    Ramprasath, Vanu Ramkumar; Shanthi, Palanivelu; Sachdanandam, Panchanatham

    2005-08-01

    Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are highly reactive transient chemical species, which play an important role in the etiology of tissue injury in rheumatoid arthritis (RA). The effects of milk extract of Semecarpus anacardium Linn. nut (SA) was studied on adjuvant arthritis in rats. Arthritis was induced by injecting 0.1 ml of heat killed mycobacterium tuberculosis (10 mg/ml of paraffin oil) intradermally into the left hind paw. A significant increase in the levels of lipid peroxides (LPO), ROS (superoxide radical, hydroxyl radical, H(2)O(2) and myeloperoxidase) and RNS (nitrate+nitrite) observed in adjuvant arthritic animals were found to be significantly decreased on administration of the drug at 150 mg/kg body weight/day. The antioxidant defense system studied in arthritic animals were altered significantly as evidenced by the decrease in antioxidants. Treatment with SA recouped the altered antioxidant defense components to near normal levels. These evidences suggest that the free radical mediated damage during arthritis could have been controlled by SA by its free radical quenching and antioxidative potential. (Mol Cell Biochem 276: 97-104, 2005).

  12. Surgical adjuvant immunotherapy for colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Enker, W.E.; Jacobitz, J.L.; Craft, K.; Wissler, R.W.

    1978-01-01

    One hundred forty-four Wistar-Furth rats in 12 therapeutic groups have been studied in a long-term comparison of the effectiveness of nonspecific immunotherapy with MER (methanol extraction residue) vs active-specific immunotherapy with neuraminidase-modified tumor cells. Six months after surgical adjuvant immunotherapy a 100% improvement in survival was achieved with MER immunotherapy compared to untreated control animals. In addition, the use of MER enhanced the value of active-specific immunotherapy where both modalities were combined in sequence. The predicted value of MER-BCG (Bacillus Calmette-Guerin) for the immunotherapy of solid tumors was borne out by these results suggesting that present ongoing clinical trials of MER as adjuvant therapy for large bowel cancer should prove to be successful if properly controlled. The pattern of survival in these experiments suggests that surgical adjuvant immunotherapy is cytostatic rather than cytocidal, and implies the need for long-term, repeated immunizations.

  13. Testosterone Replacement Therapy and the Cardiovascular System.

    Science.gov (United States)

    Naderi, Sahar

    2016-04-01

    As testosterone replacement therapy (TRT) has emerged as a commonly prescribed therapy for symptomatic low testosterone, conflicting data have been reported in terms of both its efficacy and potential adverse outcomes. One of the most controversial associations has been that of TRT and cardiovascular morbidity and mortality. This review briefly provides background on the history of TRT, the indications for TRT, and the data behind TRT for symptomatic low testosterone. It then specifically delves into the rather limited data for cardiovascular outcomes of those with low endogenous testosterone and those who receive TRT. The available body of literature strongly suggests that more work, by way of clinical trials, needs to be done to better understand the impact of testosterone and TRT on the cardiovascular system.

  14. 21 CFR 892.5750 - Radionuclide radiation therapy system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Radionuclide radiation therapy system. 892.5750... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Therapeutic Devices § 892.5750 Radionuclide radiation therapy system. (a) Identification. A radionuclide radiation therapy system is a device intended to permit an...

  15. 21 CFR 892.5840 - Radiation therapy simulation system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Radiation therapy simulation system. 892.5840... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Therapeutic Devices § 892.5840 Radiation therapy simulation system. (a) Identification. A radiation therapy simulation system is a fluoroscopic or radiographic x-ray...

  16. Long-term persistence of systemic and mucosal immune response to HPV-16/18 AS04-adjuvanted vaccine in preteen/adolescent girls and young women

    DEFF Research Database (Denmark)

    Petäjä, T; Pedersen, C; Andersen, Anne Poder

    2010-01-01

    Vaccination against oncogenic human papillomavirus (HPV) types is one key intervention for cervical cancer prevention. This follow-up study assessed the persistence of the systemic and mucosal immune responses together with the safety profile of the HPV-16/18 AS04-adjuvanted vaccine administered...... induces long-term systemic and mucosal immune response and has a clinically acceptable safety profile up to four years after the first vaccine dose....... seropositive for serum anti-HPV-16 and -18 antibodies. As previously observed, anti-HPV-16 and -18 antibody levels (ELISA Units/mL) were higher in subjects vaccinated at the age of 10-14 years (2862.2 and 940.8) compared to subjects vaccinated at the age of 15-25 years (1186.2 and 469.8). Moreover, anti-HPV-16...

  17. Activity of glycated chitosan and other adjuvants to PDT vaccines

    Science.gov (United States)

    Korbelik, Mladen; Banáth, Judit; Čiplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

    2015-03-01

    Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

  18. Potential of polymeric particles as future vaccine delivery systems/adjuvants for parenteral and non-parenteral immunization against tuberculosis: A systematic review

    Directory of Open Access Journals (Sweden)

    Farzad Khademi

    2018-02-01

    Full Text Available Objective(s: Production of effective tuberculosis (TB vaccine is necessity. However, the development of new subunit vaccines is faced with concerns about their weak immunogenicity. To overcome such problems, polymers-based vaccine delivery systems have been proposed to be used via various routes. The purpose of this study was to determine the potential of polymeric particles as future vaccine delivery systems/adjuvants for parenteral and non-parenteral immunization against TB. Materials and Methods: PubMed, Scopus, Science-Direct, and the ISI web of knowledge databases were searched for related keywords. A total of 420 articles, written up to June 25, 2016, were collected on the potential of polymeric particles as TB vaccine delivery systems after parenteral and non-parenteral immunization. Thirty-one relevant articles were selected by applying inclusion and exclusion criteria. Results: It was shown that the immunogenicity of TB vaccines had been improved by using biodegradable and non-biodegradable synthetic polymers as well as natural polymers and they are better able to enhance the humoral and cellular immune responses, compared to TB vaccines alone. The present study revealed that various polymeric particles, after M. tuberculosis challenge in animal models, provide long-lasting protection against TB. PLGA (poly (lactide-co-glycolide and chitosan polymers were widely used as TB vaccine delivery systems/adjuvants. Conclusion: It seems that PLGA and chitosan polymers are well-suited particles for the parenteral and non-parenteral administration of TB vaccines, respectively. Non-biodegradable synthetic polymers in comparison with biodegradable synthetic and natural polymers have been used less frequently. Therefore, further study on this category of polymers is required.

  19. BCG+MMC trial: adding mitomycin C to BCG as adjuvant intravesical therapy for high-risk, non-muscle-invasive bladder cancer: a randomised phase III trial (ANZUP 1301).

    Science.gov (United States)

    Hayne, Dickon; Stockler, Martin; McCombie, Steve P; Chalasani, Venu; Long, Anne; Martin, Andrew; Sengupta, Shomik; Davis, Ian D

    2015-05-27

    Despite adequate trans-urethral resection of the bladder tumour (TURBT), non-muscle-invasive bladder cancer (NMIBC) is associated with high rates of recurrence and progression. Instillation of Bacillus Calmette-Guérin (BCG) into the urinary bladder after TURBT (adjuvant intravesical administration) reduces the risk of both recurrence and progression, and this is therefore the standard of care for high-risk tumours. However, over 30 % of people still recur or progress despite optimal delivery of BCG. Our meta-analysis suggests that outcomes might be improved further by using an adjuvant intravesical regimen that includes both mitomycin and BCG. These promising findings require corroboration in a definitive, large scale, randomised phase III trial using standard techniques for intravesical administration. The BCG + MMC trial (ANZUP 1301) is an open-label, randomised, stratified, two-arm multi-centre phase III trial comparing the efficacy and safety of standard intravesical therapy (BCG alone) against experimental intravesical therapy (BCG and mitomycin) in the treatment of adults with resected, high-risk NMIBC. Participants in the control group receive standard treatment with induction (weekly BCG for six weeks) followed by maintenance (four-weekly BCG for ten months). Participants in the experimental group receive induction (BCG weeks 1, 2, 4, 5, 7, and 8; mitomycin weeks 3, 6, and 9) followed by four-weekly maintenance (mitomycin weeks 13, 17, 25, 29, 37, and 41; BCG weeks 21, 33, and 45). The trial aims to include 500 participants who will be centrally randomised to one of the two treatment groups in a 1:1 ratio stratified by T-stage, presence of CIS, and study site. The primary endpoint is disease-free survival; secondary endpoints are disease activity, time to recurrence, time to progression, safety, health-related quality of life, overall survival, feasibility, and resource use. This trial is registered with the Australian New Zealand Clinical Trials Registry

  20. Laser puncture therapy of nervous system disorders

    Energy Technology Data Exchange (ETDEWEB)

    Anishchenko, G.; Kochetkov, V.

    1984-08-29

    The authors discuss experience with treatment of nervous system disorders by means of laser-puncture therapy. Commenting on the background of the selection of this type of treatment, they explain that once researchers determined the biological action of laser light on specific nerve receptors of the skin, development of laser apparatus capable of concentrating the beam in the millimeter band was undertaken. The devices that are being used for laser-puncture are said to operate in the red helium-neon band of light. The authors identify beam parameters that have been selected for different groups of acupuncture points of the skin, and the courses of treatment (in seconds of radiation) and their time intervals. They go on to discuss the results of treatment of over 800 patients categorized in a group with disorders of the peripheral nervous system and a second group with disorders of the central nervous system.

  1. Salvage interstitial brachytherapy based on computed tomography for recurrent cervical cancer after radical hysterectomy and adjuvant radiation therapy: case presentations and introduction of the technique

    Directory of Open Access Journals (Sweden)

    Zhong-Shan Liu

    2016-10-01

    Full Text Available Purpose : Locally recurring cervical cancer after surgery and adjuvant radiotherapy remains a major therapeutic challenge. This paper presents a new therapeutic technique for such patients: interstitial brachytherapy (BT guided by real-time three-dimensional (3D computed tomography (CT. Material and methods : Sixteen patients with recurrent cervical cancer after radical surgery and adjuvant external-beam radiotherapy (EBRT were included in this study. These patients underwent high-dose-rate (HDR interstitial BT with free-hand placement of metal needles guided by real-time 3D-CT. Six Gy in 6 fractions were prescribed for the high-risk clinical target volume (HR-CTV. D 90 and D 100 for HR-CTV of BT, and the cumulative D 2cc for the bladder, rectum, and sigmoid, including previous EBRT and present BT were analyzed. Treatment-related complications and 3-month tumor-response rates were investigated. Results: The mean D 90 value for HR-CTV was 52.5 ± 3.3 Gy. The cumulative D 2cc for the bladder, rectum, and sigmoid were 85.6 ± 5.8, 71.6 ± 6.4, and 69.6 ± 5.9 Gy, respectively. The mean number of needles was 6.1 ± 1.5, with an average depth of 3.5 ± 0.9 cm for each application. Interstitial BT was associated with minor complications and passable tumor-response rate. Conclusions : Interstitial BT guided by real-time 3D-CT for recurrent cervical cancer results in good dose-volume histogram (DVH parameters. The current technique may be clinically feasible. However, long-term clinical outcomes should be further investigated.

  2. Epidermal electronic systems for sensing and therapy

    Science.gov (United States)

    Lu, Nanshu; Ameri, Shideh K.; Ha, Taewoo; Nicolini, Luke; Stier, Andrew; Wang, Pulin

    2017-04-01

    Epidermal electronic system is a class of hair thin, skin soft, stretchable sensors and electronics capable of continuous and long-term physiological sensing and clinical therapy when applied on human skin. The high cost of manpower, materials, and photolithographic facilities associated with its manufacture limit the availability of disposable epidermal electronics. We have invented a cost and time effective, completely dry, benchtop "cut-and-paste" method for the green, freeform and portable manufacture of epidermal electronics within minutes. We have applied the "cut-and-paste" method to manufacture epidermal electrodes, hydration and temperature sensors, conformable power-efficient heaters, as well as cuffless continuous blood pressure monitors out of metal thin films, two-dimensional (2D) materials, and piezoelectric polymer sheets. For demonstration purpose, we will discuss three examples of "cut-and-pasted" epidermal electronic systems in this paper. The first will be submicron thick, transparent epidermal graphene electrodes that can be directly transferred to human skin like a temporary transfer tattoo and can measure electrocardiogram (ECG) with signal-to-noise ratio and motion artifacts on par with conventional gel electrodes. The second will be a chest patch which houses both electrodes and pressure sensors for the synchronous measurements of ECG and seismocardiogram (SCG) such that beat-to-beat blood pressure can be inferred from the time interval between the R peak of the ECG and the AC peak of the SCG. The last example will be a highly conformable, low power consumption epidermal heater for thermal therapy.

  3. Comparison of BCG, MPL and cationic liposome adjuvant systems in leishmanial antigen vaccine formulations against murine visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Bhowmick Sudipta

    2010-06-01

    Full Text Available Abstract Background The development of an effective vaccine against visceral leishmaniasis (VL caused by Leishmania donovani is an essential aim for controlling the disease. Use of the right adjuvant is of fundamental importance in vaccine formulations for generation of effective cell-mediated immune response. Earlier we reported the protective efficacy of cationic liposome-associated L. donovani promastigote antigens (LAg against experimental VL. The aim of the present study was to compare the effectiveness of two very promising adjuvants, Bacille Calmette-Guerin (BCG and Monophosphoryl lipid A (MPL plus trehalose dicorynomycolate (TDM with cationic liposomes, in combination with LAg, to confer protection against murine VL. Results All the three formulations afforded significant protection against L. donovani in both the visceral organs, liver and spleen. Although comparable level of protection was observed in BCG+LAg and MPL-TDM+LAg immunized mice, highest level of protection was exhibited by the liposomal LAg immunized group. Significant increase in anti-LAg IgG levels were detected in both MPL-TDM+LAg and liposomal LAg immunized animals with higher levels of IgG2a than IgG1. But BCG+LAg failed to induce any antibody response. As an index of cell-mediated immunity DTH responses were measured and significant response was observed in mice vaccinated with all the three different formulations. However, highest responses were observed with liposomal vaccine immunization. Comparative evaluation of IFN-γ and IL-4 responses in immunized mice revealed that MPL-TDM+LAg group produced the highest level of IFN-γ but lowest IL-4 level, while BCG+LAg demonstrated generation of suboptimum levels of both IFN-γ and IL-4 response. Elicitation of moderate levels of prechallenge IFN-γ along with optimum IL-4 corresponds with successful vaccination with liposomal LAg. Conclusion This comparative study reveals greater effectiveness of the liposomal vaccine for

  4. Comparison of BCG, MPL and cationic liposome adjuvant systems in leishmanial antigen vaccine formulations against murine visceral leishmaniasis.

    Science.gov (United States)

    Ravindran, Rajesh; Bhowmick, Sudipta; Das, Amrita; Ali, Nahid

    2010-06-24

    The development of an effective vaccine against visceral leishmaniasis (VL) caused by Leishmania donovani is an essential aim for controlling the disease. Use of the right adjuvant is of fundamental importance in vaccine formulations for generation of effective cell-mediated immune response. Earlier we reported the protective efficacy of cationic liposome-associated L. donovani promastigote antigens (LAg) against experimental VL. The aim of the present study was to compare the effectiveness of two very promising adjuvants, Bacille Calmette-Guerin (BCG) and Monophosphoryl lipid A (MPL) plus trehalose dicorynomycolate (TDM) with cationic liposomes, in combination with LAg, to confer protection against murine VL. All the three formulations afforded significant protection against L. donovani in both the visceral organs, liver and spleen. Although comparable level of protection was observed in BCG+LAg and MPL-TDM+LAg immunized mice, highest level of protection was exhibited by the liposomal LAg immunized group. Significant increase in anti-LAg IgG levels were detected in both MPL-TDM+LAg and liposomal LAg immunized animals with higher levels of IgG2a than IgG1. But BCG+LAg failed to induce any antibody response. As an index of cell-mediated immunity DTH responses were measured and significant response was observed in mice vaccinated with all the three different formulations. However, highest responses were observed with liposomal vaccine immunization. Comparative evaluation of IFN-gamma and IL-4 responses in immunized mice revealed that MPL-TDM+LAg group produced the highest level of IFN-gamma but lowest IL-4 level, while BCG+LAg demonstrated generation of suboptimum levels of both IFN-gamma and IL-4 response. Elicitation of moderate levels of prechallenge IFN-gamma along with optimum IL-4 corresponds with successful vaccination with liposomal LAg. This comparative study reveals greater effectiveness of the liposomal vaccine for protection against progressive VL in BALB

  5. Compact superconducting synchrocyclotron systems for proton therapy

    Science.gov (United States)

    Blosser, H. G.

    1989-04-01

    Conventional room temperature synchrocyclotrons are widely used as a source for medical proton beams. If the synchrocyclotron is changed to a superconducting design, weight is reduced more than tenfold and the resulting accelerator is beautifully compact and of moderate cost. Engineering studies indicate that the traditional reliability of the synchrocyclotron will not be impinged by the change to a much smaller structure. Design studies for 70 and 250 MeV systems have been made. The 70 MeV machine would be a stond-alone facility for eye treatment, whereas the 250 MeV unit is for general, anywhere-in-the-body proton therapy. The 250 MeV machine is small enough to permit the option of directly mounting the cyclotron on an isocentric gantry, thereby greatly reducing the complexity of the beam transport system.

  6. Mixed adjuvant formulations reveal a new combination that elicit antibody response comparable to Freund's adjuvants.

    Directory of Open Access Journals (Sweden)

    Rachel P J Lai

    Full Text Available Adjuvant formulations capable of inducing high titer and high affinity antibody responses would provide a major advance in the development of vaccines to viral infections such as HIV-1. Although oil-in-water emulsions, such as Freund's adjuvant (FCA/FIA, are known to be potent, their toxicity and reactogenicity make them unacceptable for human use. Here, we explored different adjuvants and compared their ability to elicit antibody responses to FCA/FIA. Recombinant soluble trimeric HIV-1 gp140 antigen was formulated in different adjuvants, including FCA/FIA, Carbopol-971P, Carbopol-974P and the licensed adjuvant MF59, or combinations of MF59 and Carbopol. The antigen-adjuvant formulation was administered in a prime-boost regimen into rabbits, and elicitation of antigen binding and neutralizing antibodies (nAbs was evaluated. When used individually, only FCA/FIA elicited significantly higher titer of nAbs than the control group (gp140 in PBS (p<0.05. Sequential prime-boost immunizations with different adjuvants did not offer improvements over the use of FCA/FIA or MF59. Remarkably however, the concurrent use of the combination of Carbopol-971P and MF59 induced potent adjuvant activity with significantly higher titer nAbs than FCA/FIA (p<0.05. This combination was not associated with any obvious local or systemic adverse effects. Antibody competition indicated that the majority of the neutralizing acti