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Sample records for adjuvant pharmacological therapy

  1. Low-pressure balloon angioplasty with adjuvant pharmacological therapy in patients with acute ischemic stroke caused by intracranial arterial occlusions

    International Nuclear Information System (INIS)

    Nogueira, Raul G.; Schwamm, Lee H.; Buonanno, Ferdinando S.; Koroshetz, Walter J.; Yoo, Albert J.; Rabinov, James D.; Pryor, Johnny C.; Hirsch, Joshua A.

    2008-01-01

    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 glycoprotein IIb

  2. Pharmacological therapy for amblyopia

    Directory of Open Access Journals (Sweden)

    Anupam Singh

    2017-01-01

    Full Text Available Amblyopia is the most common cause of preventable blindness in children and young adults. Most of the amblyopic visual loss is reversible if detected and treated at appropriate time. It affects 1.0 to 5.0% of the general population. Various treatment modalities have been tried like refractive correction, patching (both full time and part time, penalization and pharmacological therapy. Refractive correction alone improves visual acuity in one third of patients with anisometropic amblyopia. Various drugs have also been tried of which carbidopa & levodopa have been popular. Most of these agents are still in experimental stage, though levodopa-carbidopa combination therapy has been widely studied in human amblyopes with good outcomes. Levodopa therapy may be considered in cases with residual amblyopia, although occlusion therapy remains the initial treatment choice. Regression of effect after stoppage of therapy remains a concern. Further studies are therefore needed to evaluate the full efficacy and side effect profile of these agents.

  3. Pharmacological therapy for amblyopia

    Science.gov (United States)

    Singh, Anupam; Nagpal, Ritu; Mittal, Sanjeev Kumar; Bahuguna, Chirag; Kumar, Prashant

    2017-01-01

    Amblyopia is the most common cause of preventable blindness in children and young adults. Most of the amblyopic visual loss is reversible if detected and treated at appropriate time. It affects 1.0 to 5.0% of the general population. Various treatment modalities have been tried like refractive correction, patching (both full time and part time), penalization and pharmacological therapy. Refractive correction alone improves visual acuity in one third of patients with anisometropic amblyopia. Various drugs have also been tried of which carbidopa & levodopa have been popular. Most of these agents are still in experimental stage, though levodopa-carbidopa combination therapy has been widely studied in human amblyopes with good outcomes. Levodopa therapy may be considered in cases with residual amblyopia, although occlusion therapy remains the initial treatment choice. Regression of effect after stoppage of therapy remains a concern. Further studies are therefore needed to evaluate the full efficacy and side effect profile of these agents. PMID:29018759

  4. Pharmacological therapy of spondyloarthritis.

    Science.gov (United States)

    Palazzi, Carlo; D'Angelo, Salvatore; Gilio, Michele; Leccese, Pietro; Padula, Angela; Olivieri, Ignazio

    2015-01-01

    The current pharmacological therapy of spondyloarthritis (SpA) includes several drugs: Non-steroidal anti-inflammatory drugs, corticosteroids, traditional disease-modifying antirheumatic drugs and biologic drugs. A systematic literature search was completed using the largest electronic databases (Medline, Embase and Cochrane), starting from 1995, with the aim to review data on traditional and biologic agents commercialised for SpA treatment. Randomised controlled trials and large observational studies were considered. In addition, studies performed in SpA patients treated with other, still unapproved, drugs (rituximab, anti-IL6 agents, apremilast, IL17 inhibitors and anakinra) were also taken into account. Biologic agents, especially anti-TNF drugs, have resulted in significant progress in improving clinical symptoms and signs, reducing inflammatory features in laboratory tests and imaging findings, and recovering all functional indexes. Anti-TNF drugs have radically changed the evolution of radiographic progression in peripheral joints; the first disappointing data concerning their efficacy on new bone formation of axial SpA has been recently challenged by studies enrolling patients who have been earlier diagnosed and treated. The opportunity to extend the interval of administration or to reduce the doses of anti-TNF agents can favourably influence the costs. Ustekinumab, the first non-anti-TNF biologic drug commercialised for psoriatic arthritis, offers new chances to patients that are unresponsive to anti-TNF.

  5. Extended Adjuvant Therapy for Breast Cancer

    Science.gov (United States)

    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.

  6. [Pharmacological therapy of obesity].

    Science.gov (United States)

    Pagotto, Uberto; Vanuzzo, Diego; Vicennati, Valentina; Pasquali, Renato

    2008-04-01

    Obesity is reaching epidemic proportions worldwide and it is correlated with various comorbidities, among which the most relevant are diabetes mellitus, arterial hypertension, and cardiovascular diseases. Obesity management is a modern challenge because of the rapid evolution of unfavorable lifestyles and unfortunately there are no effective treatments applicable to the large majority of obese/overweight people. The current medical attitude is to treat the complications of obesity (e.g. dyslipidemia, hypertension, diabetes, and cardiovascular diseases). However, the potential of treating obesity is enormous, bearing in mind that a volitional weight loss of 10 kg is associated with important risk factor improvement: blood pressure -10 mmHg, total cholesterol -10%, LDL cholesterol -15%, triglycerides -30%, fasting glucose -50%, HDL cholesterol +8%. Drug treatment for obesity is an evolving branch of pharmacology, burdened by severe side effects and consequences of the early drugs, withdrawn from the market, and challenged by the lack of long-term data on the effect of medications on obesity-related morbidity and mortality, first of all cardiovascular diseases. In Europe three antiobesity drugs are currently licensed: sibutramine, orlistat, and rimonabant; important trials with clinical endpoints are ongoing for sibutramine and rimonabant. While waiting for their results, it is convenient to evaluate these drugs for their effects on body weight and cardiometabolic risk factors. Sibutramine is a centrally acting serotonin/noradrenaline reuptake inhibitor that mainly increases satiety. At the level of brown adipose tissue, sibutramine can also facilitate energy expenditure by increasing thermogenesis. The long-term studies (five) documented a mean differential weight reduction of 4.45 kg for sibutramine vs placebo. Considering the principal studies, attrition rate was 43%. This drug not only reduces body weight and waist circumference, but it decreases triglycerides and

  7. Pharmacologic therapy for acute pancreatitis

    Science.gov (United States)

    Kambhampati, Swetha; Park, Walter; Habtezion, Aida

    2014-01-01

    While conservative management such as fluid, bowel rest, and antibiotics is the mainstay of current acute pancreatitis management, there is a lot of promise in pharmacologic therapies that target various aspects of the pathogenesis of pancreatitis. Extensive review of preclinical studies, which include assessment of therapies such as anti-secretory agents, protease inhibitors, anti-inflammatory agents, and anti-oxidants are discussed. Many of these studies have shown therapeutic benefit and improved survival in experimental models. Based on available preclinical studies, we discuss potential novel targeted pharmacologic approaches that may offer promise in the treatment of acute pancreatitis. To date a variety of clinical studies have assessed the translational potential of animal model effective experimental therapies and have shown either failure or mixed results in human studies. Despite these discouraging clinical studies, there is a great clinical need and there exist several preclinical effective therapies that await investigation in patients. Better understanding of acute pancreatitis pathophysiology and lessons learned from past clinical studies are likely to offer a great foundation upon which to expand future therapies in acute pancreatitis. PMID:25493000

  8. Future pharmacological therapy in hypertension.

    Science.gov (United States)

    Stewart, Merrill H; Lavie, Carl J; Ventura, Hector O

    2018-04-26

    Hypertension (HTN) is a widespread and growing disease, with medication intolerance and side-effect present among many. To address these obstacles novel pharmacotherapy is an active area of drug development. This review seeks to explore future drug therapy for HTN in the preclinical and clinical arenas. The future of pharmacological therapy in HTN consists of revisiting old pathways to find new targets and exploring wholly new approaches to provide additional avenues of treatment. In this review, we discuss the current status of the most recent drug therapy in HTN. New developments in well trod areas include novel mineralocorticoid antagonists, aldosterone synthase inhibitors, aminopeptidase-A inhibitors, natriuretic peptide receptor agonists, or the counter-regulatory angiotensin converting enzyme 2/angiotensin (Ang) (1-7)/Mas receptor axis. Neprilysin inhibitors popularized for heart failure may also still hold HTN potential. Finally, we examine unique systems in development never before used in HTN such as Na/H exchange inhibitors, vasoactive intestinal peptide agonists, and dopamine beta hydroxylase inhibitors. A concise review of future directions of HTN pharmacotherapy.

  9. Postoperative adjuvant therapy of colorectal carcinoma

    International Nuclear Information System (INIS)

    Scheithauer, W.

    1989-01-01

    Evaluating the results of controlled clinical trials, an attempt has been made to summarize the current status of adjuvant therapy in colorectal cancer. Several different adjuvant treatment approaches including immunotherapy, postoperative fibrinolysis, anticoagulation, pre- and postoperative radiotherapy when used as a single modality, have not resulted in any long-term survival benefit. Rather in contrast to previous experiences, recent prospective randomized trials have provided evidence for the efficacy of chemotherapy in the adjuvant treatment of colon and rectal cancer. Whereas its definitive role in the former disease remains somewhat controversial, for rectal cancer, it seems clear that combined modality therapy including polychemotherapy with or without radiation prolongs the disease-free interval, lowers the local recurrence rate, and may improve survival compared to surgery alone. Questions which remain to be answered by future clinical trials are related to the optimal duration and sequence of combined modality, to the role of different radiation sensitizers, and in both colon and rectal cancer, to the choice of the most effective systemtic chemotherapeutic drugs. (orig./MG) [de

  10. Adjuvant Therapy: Treatment to Keep Cancer from Returning

    Science.gov (United States)

    ... significant side effects, and these treatments don't benefit everyone. Types of cancer treatment that are used as adjuvant therapy include: Chemotherapy. Chemotherapy uses drugs to kill cancer cells throughout ...

  11. Pharmacological therapy of chronic obstructive pulmonary disease

    African Journals Online (AJOL)

    patients with COPD require pharmacological therapy. ... pulmonary dysfunction. Clearly the patient's tolerance to the various drugs will influence the choice of long-term maintenance treatment. The other important factor in the .... blocking cervical immune responses might leave her less protected against other infections.

  12. Emerging pharmacological therapy for functional dyspepsia.

    Science.gov (United States)

    Hojo, Mariko; Nagahara, Akihito; Asaoka, Daisuke; Watanabe, Sumio

    2013-10-01

    Functional dyspepsia (FD) is a multifactorial disease with complex underlying pathophysiology. To date, there is no established treatment for FD. This review summarizes recent progress in pharmacological therapy for the disease. A newly developed drug, acotiamide, is expected to improve symptoms of postprandial distress syndrome. Herbal medicines are also expected to become options for FD treatment.

  13. Phage Therapy: Eco-Physiological Pharmacology

    Directory of Open Access Journals (Sweden)

    Stephen T. Abedon

    2014-01-01

    Full Text Available Bacterial virus use as antibacterial agents, in the guise of what is commonly known as phage therapy, is an inherently physiological, ecological, and also pharmacological process. Physiologically we can consider metabolic properties of phage infections of bacteria and variation in those properties as a function of preexisting bacterial states. In addition, there are patient responses to pathogenesis, patient responses to phage infections of pathogens, and also patient responses to phage virions alone. Ecologically, we can consider phage propagation, densities, distribution (within bodies, impact on body-associated microbiota (as ecological communities, and modification of the functioning of body “ecosystems” more generally. These ecological and physiological components in many ways represent different perspectives on otherwise equivalent phenomena. Comparable to drugs, one also can view phages during phage therapy in pharmacological terms. The relatively unique status of phages within the context of phage therapy as essentially replicating antimicrobials can therefore result in a confluence of perspectives, many of which can be useful towards gaining a better mechanistic appreciation of phage therapy, as I consider here. Pharmacology more generally may be viewed as a discipline that lies at an interface between organism-associated phenomena, as considered by physiology, and environmental interactions as considered by ecology.

  14. Role of chemoradiotherapy in oesophageal cancer -- adjuvant and neoadjuvant therapy

    NARCIS (Netherlands)

    Gwynne, S.; Wijnhoven, B. P. L.; Hulshof, M.; Bateman, A.

    2014-01-01

    Despite low postoperative mortality rates, the long-term outcomes from surgical-based treatment for oesophageal cancer remain poor. Chemoradiotherapy (CRT), either given before surgical resection as neoadjuvant therapy or after resection as adjuvant therapy, has been postulated to improve these

  15. Adjuvant Biological Therapies in Chronic Leg Ulcers

    Directory of Open Access Journals (Sweden)

    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.

  16. Adjuvant therapy for ampullary carcinomas: The Mayo Clinic experience

    International Nuclear Information System (INIS)

    Bhatia, Sumita; Miller, Robert C.; Haddock, Michael G.; Donohue, John H.; Krishnan, Sunil

    2006-01-01

    Purpose: To determine the effects of adjuvant radiotherapy and chemotherapy for carcinoma of the ampulla of Vater. Methods and Materials: We retrospectively reviewed the records of 125 patients who underwent definitive surgery for carcinomas involving the ampulla of Vater between April 1977 and February 2005 and who survived more than 50 days after surgery. Twenty-nine of the patients also received adjuvant radiotherapy (median dose, 50.4 Gy in 28 fractions) with concurrent 5-fluorouracil chemotherapy. Adverse prognostic factors were investigated, and overall survival (OS) and local and distant failure were estimated. Results: Adverse prognostic factors for decreased OS by univariate analysis included lymph node (LN) involvement, locally advanced tumors (T3/T4), and poor histologic grade. By multivariate analysis, positive LN status (p = 0.02) alone was associated with decreased OS. The addition of adjuvant radiotherapy and chemotherapy improved OS for patients with positive LN (p = 0.01). Median survival for positive LN patients receiving adjuvant therapy was 3.4 years, vs. 1.6 years for those with surgery alone. Conclusions: The addition of adjuvant radiotherapy and 5-fluorouracil chemotherapy may improve OS in patients with LN involvement. The effect of adjuvant therapy on outcomes for patients with poor histologic grade or T3/T4 tumors without LN involvement could not be assessed

  17. Immunomodulators as adjuvants for vaccines and antimicrobial therapy.

    Science.gov (United States)

    Nicholls, Erin F; Madera, Laurence; Hancock, Robert E W

    2010-12-01

    A highly effective strategy for combating infectious diseases is to enhance host defenses using immunomodulators, either preventatively, through vaccination, or therapeutically. The effectiveness of many vaccines currently in use is due in part to adjuvants, molecules that have little immunogenicity by themselves but which help enhance and appropriately skew the immune response to an antigen. The development of new vaccines necessitates the development of new types of adjuvants to ensure an appropriate immune response. Herein, we review commonly used vaccine adjuvants and discuss promising adjuvant candidates. We also discuss various other immunomodulators (namely cytokines, Toll-like receptor agonists, and host defense peptides) that are, or have potential to be, useful for antimicrobial therapies that exert their effects by boosting host immune responses rather than targeting pathogens directly.

  18. 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.

  19. Adjuvant Chemoradiation Therapy for Pancreatic Adenocarcinoma: Who Really Benefits?

    Science.gov (United States)

    Merchant, Nipun B; Rymer, Jennifer; Koehler, Elizabeth AS; Ayers, G Daniel; Castellanos, Jason; Kooby, David A; Weber, Sharon H; Cho, Clifford S; Schmidt, C Max; Nakeeb, Atilla; Matos, Jesus M; Scoggins, Charles R; Martin, Robert CG; Kim, Hong Jin; Ahmad, Syed A; Chu, Carrie K; McClaine, Rebecca; Bednarski, Brian K; Staley, Charles A; Sharp, Kenneth; Parikh, Alexander A

    2014-01-01

    BACKGROUND The role of adjuvant chemoradiation therapy (CRT) in pancreatic cancer remains controversial. The primary aim of this study was to determine if CRT improved survival in patients with resected pancreatic cancer in a large, multiinstitutional cohort of patients. STUDY DESIGN Patients undergoing resection for pancreatic adenocarcinoma from seven academic medical institutions were included. Exclusion criteria included patients with T4 or M1 disease, R2 resection margin, preoperative therapy, chemotherapy alone, or if adjuvant therapy status was unknown. RESULTS There were 747 patients included in the initial evaluation. Primary analysis was performed between patients that had surgery alone (n = 374) and those receiving adjuvant CRT (n = 299). Median followup time was 12.2 months and 14.5 months for survivors. Median overall survival for patients receiving adjuvant CRT was significantly longer than for those undergoing operation alone (20.0 months versus 14.5 months, p = 0.001). On subset and multivariate analysis, adjuvant CRT demonstrated a significant survival advantage only among patients who had lymph node (LN)-positive disease (hazard ratio 0.477, 95% CI 0.357 to 0.638) and not for LN-negative patients (hazard ratio 0.810, 95% CI 0.556 to 1.181). Disease-free survival in patients with LN-negative disease who received adjuvant CRT was significantly worse than in patients who had surgery alone (14.5 months versus 18.6 months, p = 0.034). CONCLUSIONS This large multiinstitutional study emphasizes the importance of analyzing subsets of patients with pancreas adenocarcinoma who have LN metastasis. Benefit of adjuvant CRT is seen only in patients with LN-positive disease, regardless of resection margin status. CRT in patients with LN-negative disease may contribute to reduced disease-free survival. PMID:19476845

  20. Adjuvant Therapy for Gallbladder Carcinoma: The Mayo Clinic Experience

    International Nuclear Information System (INIS)

    Gold, Douglas G.; Miller, Robert C.; Haddock, Michael G.; Gunderson, Leonard L.; Quevedo, Fernando; Donohue, John H.; Bhatia, Sumita; Nagorney, David M.

    2009-01-01

    Purpose: To analyze the effect of adjuvant chemoradiotherapy on gallbladder carcinoma. Methods and Materials: We retrospectively reviewed the records from consecutive patients who underwent R0 resection of gallbladder carcinoma between January 1, 1985, and December 31, 2004. Patients had either Stage I (T1-T2N0M0) or Stage II (T3N0M0 or T1-T3N1M0) disease. Patients undergoing adjuvant therapy received 5-fluorouracil chemotherapy concurrently with radiotherapy (median dosage, 50.4 Gy in 28 fractions). Adverse prognostic factors and the effect of adjuvant treatment on overall survival (OS) were evaluated. Results: A total of 73 patients were included in the analysis; of these, 25 received adjuvant chemoradiotherapy. On univariate analysis, no adverse prognostic factors for OS reached statistical significance, but trends were noted for Stage N1 vs. N0 (p = .06), Nx vs. N0 (p = .09), Stage T3 vs. T1-T2 (p = .06), and histologic findings other than adenocarcinoma (p = .13). The median OS for patients receiving adjuvant chemoradiotherapy vs. surgery alone was 4.8 years and 4.2 years, respectively (log-rank test, p = .56). However, a significantly greater percentage of patients receiving adjuvant chemoradiotherapy had Stage II disease (p <.001). In the multivariate Cox model, increasing T and N category and histologic findings other than adenocarcinoma were significant predictors of decreased OS. Additionally, adjuvant chemoradiotherapy was a significant predictor of improved OS after adjusting for these prognostic factors (hazard ratio for death, 0.3; 95% confidence interval, 0.13-0.69; p = .004). Conclusion: After adjusting for the stage parameters and histologic findings, our data suggest that adjuvant chemoradiotherapy might improve OS for patients with gallbladder cancer.

  1. Selective use of adjuvant radiation therapy in resectable colorectal adenocarcinoma

    International Nuclear Information System (INIS)

    Cohen, A.M.; Gunderson, L.L.; Welch, C.E.

    1981-01-01

    Colorectal cancer recurs within the operative field in 10-20 per cent of patients undergoing potentially curative surgery. In certain subgroups, the recurrence rate is 20-50 per cent. There are some data to suggest either preoperative or postoperative radiation therapy as an adjuvant to potentially curative surgery can reduce the local operative failure rate. However, since radiation therapy has significant side effects, patient selection to maximize the therapeutic ratio is important. This report defines the criteria at the Massachusetts General Hospital for selection of patients with colorectal cancer for adjuvant radiation therapy, defines radiation therapy-surgery sequencing alternatives used, and describes techniques to reduce radiation side effects. Over a period of three and a half years, 196 patients received adjuvant radiation therapy: 51 patients received either moderate or low dose preoperative radiation therapy to rectal or rectosigmoid cancers, and 161 patients received postoperative radiation therapy to the pelvis or extrapelvic colonic tumor-lymph node beds. Some patients who received low-dose preoperative radiation therapy also received moderate-dose postoperative radiation therapy. We prefer moderate-dose postoperative radiation therapy as the approach most likely to decrease the local recurrence rate with minimal interference with surgical procedures and late small-bowel complications. Patients who received postoperative radiation therapy were those without distant metastases, whose primary tumor pathology revealed macroscopic or extensive microscopic transmural tumor penetration into extraperitoneal tissues. Careful case selection, multiple field techniques, the use of reperitonealization, omental flaps, and retroversion of the uterus into the pelvis were combined with postoperative small-bowel x-rays, bladder distention, and lateral portals to minimize radiation damage to normal structures

  2. Postoperative adjuvant therapy of breast cancer. Oncology Overview

    International Nuclear Information System (INIS)

    1984-12-01

    Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Postoperative chemotherapy; Postoperative radiotherapy; Postoperative hormone therapy; Postoperative immunotherapy and chemoimmunotherapy; Postoperative multimodal therapy; Prognostic factors in postoperative adjuvant therapy

  3. Corticosteroids as adjuvant therapy for ocular toxoplasmosis.

    Science.gov (United States)

    Jasper, Smitha; Vedula, Satyanarayana S; John, Sheeja S; Horo, Saban; Sepah, Yasir J; Nguyen, Quan Dong

    2017-01-26

    Ocular infection caused by Toxoplasma gondii, a parasite, may result in inflammation in the retina, choroid, and uvea, and consequently lead to complications such as glaucoma, cataract, and posterior synechiae. The objective of this systematic review was to assess the effects of adjunctive use of corticosteroids to anti-parasitic therapy versus anti-parasitic therapy alone for ocular toxoplasmosis. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register (2016; Issue 11)), MEDLINE Ovid, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, MEDLINE Ovid Daily (January 1946 to December 2016), Embase (January 1980 to December 2016), Latin American and Caribbean Literature on Health Sciences (LILACS (January 1982 to December 2016)), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 7 December 2016. We had planned to include randomized and quasi-randomized controlled trials. Eligible trials would have enrolled participants of any age who were immunocompetent and were diagnosed with acute ocular toxoplasmosis. Included trials would have compared anti-parasitic therapy plus corticosteroids versus anti-parasitic therapy alone, different doses or times of initiation of corticosteroids. Two authors independently screened titles and abstracts retrieved through the electronic searches. We retrieved full-text reports of studies categorized as 'unsure' or 'include' after we reviewed the abstracts. Two authors independently reviewed each full-text report for eligibility. Discrepancies were resolved through discussion. We identified no completed or ongoing trial that was eligible for this Cochrane review. Although research has identified a wide

  4. Clinical evaluation of a nutraceutical diet as an adjuvant to pharmacological treatment in dogs affected by Keratoconjunctivitis sicca.

    Science.gov (United States)

    Destefanis, Simona; Giretto, Daniela; Muscolo, Maria Cristina; Di Cerbo, Alessandro; Guidetti, Gianandrea; Canello, Sergio; Giovazzino, Angela; Centenaro, Sara; Terrazzano, Giuseppe

    2016-09-22

    Canine keratoconjunctivitis sicca (cKCS) is an inflammatory eye condition related to a deficiency in the tear aqueous fraction. Etiopathogenesis of such disease is substantially multifactorial, combining the individual genetic background with environmental factors that contribute to the process of immunological tolerance disruption and, as a consequence, to the emergence of autoimmunity disease. In this occurrence, it is of relevance the role of the physiological immune-dysregulation that results in immune-mediated processes at the basis of cKCS. Current therapies for this ocular disease rely on immunosuppressive treatments. Clinical response to treatment frequently varies from poor to good, depending on the clinical-pathological status of eyes at diagnosis and on individual response to therapy. In the light of the variability of clinical response to therapies, we evaluated the use of an anti-inflammatory/antioxidant nutraceutical diet with potential immune-modulating activity as a therapeutical adjuvant in cKCS pharmacological treatment. Such combination was administered to a cohort of dogs affected by cKCS in which the only immunosuppressive treatment resulted poorly responsive or ineffective in controlling the ocular symptoms. Fifty dogs of different breeds affected by immune-mediated cKCS were equally distributed and randomly assigned to receive either a standard diet (control, n = 25) or the nutraceutical diet (treatment group, n = 25) both combined with standard immunosuppressive therapy over a 60 days period. An overall significant improvement of all clinical parameters (tear production, conjunctival inflammation, corneal keratinization, corneal pigment density and mucus discharge) and the lack of food-related adverse reactions were observed in the treatment group (p metabolic changes could affect the immune response orchestration in a model of immune-mediated ocular disease, as represented by cKCS.

  5. 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.

  6. Controversies in breast cancer: adjuvant and neoadjuvant therapy.

    Science.gov (United States)

    Montemurro, Filippo; Redana, Stefania; Valabrega, Giorgio; Aglietta, Massimo

    2005-06-01

    Initial randomised studies of chemotherapy and endocrine therapy showed that systemic treatments had a substantial impact on the survival of women with early breast cancer. The original assumption was that the efficacy of these treatments was limited to those patients presenting with more adverse prognostic features. Subsequently, meta-analyses of randomised trials revealed that the benefits of chemotherapy and endocrine therapy are not mutually exclusive and extend to all the prognostic subgroups. However, the absolute benefit varies according to baseline characteristics such as tumour stage and other biological factors. Over the last 10 years, considerable progress has been made with the introduction of new drugs into the adjuvant and neoadjuvant treatment of women with breast cancer. Taxanes and third-generation aromatase inhibitors are providing proof of additional benefits compared with standard reference treatments. In parallel, research on the biology of breast cancer is establishing novel prognostic and predictive factors, which may allow better treatment tailoring. Currently, however, women with early breast cancer and their doctors face the difficult task of making therapeutic decisions often based on early results from positive studies. In a disease where follow up is crucial to fully assess the benefit and long-term toxicities of an intervention, current knowledge leaves unanswered questions that generate debate and controversy. This review will summarise recent results from randomised trials of adjuvant and neoadjuvant therapy in women with early breast cancer and focus on the current controversies.

  7. Adjuvant radiation therapy versus surgery alone in operable breast cancer

    International Nuclear Information System (INIS)

    Rutqvist, L.E.; Pettersson, D.; Johansson, H.

    1993-01-01

    This paper presents long-term results from a randomized trial of pre- or postoperative megavoltage radiation therapy versus surgery alone in pre- and postmenopausal women with operable breast cancer. Treatment outcome after relapse among patients who developed loco-regional recurrences was also analyzed. A total of 960 patients were included in the trial. The mean follow-up was 16 years (range: 13-19 years). The radiation therapy was individually planned. It included the chest wall (and the breast in the preoperative cases) and the regional lymph nodes. The tumor dose was 45 Gy/5 weeks. No adjuvant systemic therapy was used. The results showed a significant benefit with radiation therapy in terms of recurrence-free survival during the entire follow-up period. There was also an overall survival difference - corresponding to 16% reduction of deaths - in favour of the irradiated patients which, however, was not statistically significant (p=0.09). Among those 169 patients who developed loco-regional recurrences long-term control was only achieved in about one-third of the cases. This figure was similar among those who had received adjuvant radiation therapy (34%) compared to those initially treated with surgery alone (32%). This implied that the overall proportion of patients who eventually developed uncontrolled local disease was significantly higher among those initially allocated to surgery alone (16%) compared to those allocated to pre- or postoperative radiation therapy (6%, p<0.01). These results suggest that local undertreatment may be deleterious in subgroups of patients. (author) 5 tabs

  8. Adjuvant radiation therapy for pancreatic cancer: a 15-year experience

    International Nuclear Information System (INIS)

    Dobelbower, Ralph R.; Merrick, Hollis W.; Khuder, Sadik; Battle, Joyce A.; Herron, Lisa M.; Pawlicki, Todd

    1997-01-01

    Purpose: A retrospective analysis to determine differences in survival of patients with pancreatic aden carcinoma treated by radical surgery with and without adjuvant radiation therapy. Methods and Materials: Between 1980 and 1995, 249 patients with pancreatic tumors were identified at the Medical College of Ohio. Forty-four of these patients underwent radical surgical procedures with curative intent. These patients were divided into four groups according to treatment: surgery alone (n = 14), surgery plus intraoperative radiation therapy (IORT) (n = 6), surgery plus external beam radiation therapy (EBRT) (n = 14), or surgery plus both IORT and EBRT (n = 10). Outcome and survival were analyzed among the four groups. Results: The median survival time of patients treated with radical surgery alone was 6.5 months. The median survival time for the surgery plus IORT group was 9 months; however, 33.3% (two of six) of these patients survived longer than 5 years. This survival pattern was borderline significantly better than that for the surgery alone group (p = 0.0765). The surgery plus EBRT and the surgery plus IORT and EBRT groups had median survival times of 14.5 and 17.5 months, respectively. These were significantly better than that of the surgery alone group (p = 0.0004 and p = 0.0002, respectively). The addition of radiation therapy did not affect the treatment complication rate. Conclusion: The survival of patients who were treated with radical surgery alone was significantly poorer than that of patients who received adjuvant radiation therapy. These results are consistent with other studies in the literature. Patients treated with all three modalities (surgery, IORT, and EBRT) displayed the best median survival time

  9. Does adjuvant systemic therapy with interferon-alpha for stage II-III melanoma prolong survival?

    NARCIS (Netherlands)

    Eggermont, Alexander M. M.; Punt, Cornelis J. A.

    2003-01-01

    The experience with interferon-alpha in malignant melanoma resembles, to some degree, the experience with various kinds of adjuvant immunotherapeutic agents where 25 years of phase III trials of adjuvant therapy in stage II-IIII melanoma have not defined a standard therapy. Most trials failed to

  10. Influence of adjuvant detached mindfulness and stress management training compared to pharmacologic treatment in primiparae with postpartum depression.

    Science.gov (United States)

    Ahmadpanah, Mohammad; Nazaribadie, Marzieh; Aghaei, Elham; Ghaleiha, Ali; Bakhtiari, Azade; Haghighi, Mohammad; Bahmani, Dena Sadeghi; Akhondi, Amineh; Bajoghli, Hafez; Jahangard, Leila; Holsboer-Trachsler, Edith; Brand, Serge

    2018-02-01

    Ten to 15% of mothers experience postpartum depression (PPD). If untreated, PPD may negatively affect mothers' and infants' mental health in the long term. Accordingly, effective treatments are required. In the present study, we investigated the effect of detached mindfulness (DM) and stress management training (SMT) as adjuvants, compared to pharmacologic treatment only, on symptoms of depression in women with PPD. Forty-five primiparae (mean age: M = 24.5 years) with diagnosed PPD and treated with an SSRI (citalopram; CIT) took part in the study. At baseline, they completed questionnaires covering socio-demographic data and symptoms of depression. Experts rated also symptoms of depression. Next, participants were randomly assigned to one of the following study conditions: adjuvant detached mindfulness (CIT+DM); adjuvant stress management training (CIT+SMT); control condition (CIT). Self- and experts' ratings were completed at the end of the study 8 weeks later, and again at 8 weeks follow-up. Symptoms of depression decreased significantly over time, but more so in the CIT+DM and CIT+SMT group, compared to the control condition. The pattern of results remained stable at follow-up. In primiparae with PPD and treated with a standard SSRI, adjuvant psychotherapeutic interventions led to significant and longer-lasting improvements.

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

    Science.gov (United States)

    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.

  12. Adjuvant psychological therapy in long-term endocrine conditions.

    Science.gov (United States)

    Daniels, J; Turner-Cobb, J M

    2017-06-01

    Consideration of psychological distress in long-term endocrine conditions is of vital importance given the prevalence of anxiety and depression in such disorders. Poor mental health can lead to compromised self-care, higher utilization of health services, lower rates of adherence, reduced quality of life and ultimately poorer outcomes. Adjuvant psychological therapy offers an effective resource to reduce distress in endocrine conditions. While the vast majority of work in this area has focused on psychological screening and intervention in diabetes, identification and recognition of psychological distress are equally important in other endocrinological conditions, with supportive evidence in polycystic ovary syndrome and Addison's disease. Referral pathways and recommendations set out by UK guidelines and the Department of Health mandate requires greater attention across a wider range of long-term endocrine conditions to facilitate improved quality of life and health outcome. © 2017 John Wiley & Sons Ltd.

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

    International Nuclear Information System (INIS)

    Ohri, Nitin; Garg, Madhur K.; Aparo, Santiago; Kaubisch, Andreas; Tome, Wolfgang; Kennedy, Timothy J.; Kalnicki, Shalom; Guha, Chandan

    2013-01-01

    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

  14. Physical activity for women with breast cancer after adjuvant therapy.

    Science.gov (United States)

    Lahart, Ian M; Metsios, George S; Nevill, Alan M; Carmichael, Amtul R

    2018-01-29

    Women with a diagnosis of breast cancer may experience short- and long-term disease and treatment-related adverse physiological and psychosocial outcomes. These outcomes can negatively impact prognosis, health-related quality of life (HRQoL), and psychosocial and physical function. Physical activity may help to improve prognosis and may alleviate the adverse effects of adjuvant therapy. To assess effects of physical activity interventions after adjuvant therapy for women with breast cancer. We searched the Cochrane Breast Cancer Group (CBCG) Specialised Registry, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Physiotherapy Evidence Database (PEDro), SPORTDiscus, PsycINFO, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform, on 18 September 2015. We also searched OpenGrey and Healthcare Management Information Consortium databases. We searched for randomised and quasi-randomised trials comparing physical activity interventions versus control (e.g. usual or standard care, no physical activity, no exercise, attention control, placebo) after adjuvant therapy (i.e. after completion of chemotherapy and/or radiation therapy, but not hormone therapy) in women with breast cancer. Two review authors independently selected studies, assessed risk of bias, and extracted data. We contacted trial authors to ask for additional information when needed. We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome and used GRADE to assess the quality of evidence for the most important outcomes. We included 63 trials that randomised 5761 women to a physical activity intervention (n = 3239) or to a control (n = 2524). The duration of interventions ranged from 4 to 24 months, with most lasting 8 or 12 weeks (37 studies). Twenty-eight studies included aerobic exercise only, 21 involved aerobic

  15. Pharmacological Treatment of Pain in Cancer Patients : The Role of Adjuvant Analgesics, a Systematic Review

    NARCIS (Netherlands)

    van den Beuken-van Everdingen, Marieke H J; de Graeff, Alexander; Jongen, Joost L M; Dijkstra, Denise; Mostovaya, Irina; Vissers, Kris C P

    2017-01-01

    CONTEXT: In patients with cancer, pain is one of the most feared and burdensome symptoms. Adjuvant analgesics are an important cornerstone on which treatment of pain in patients with cancer is based. OBJECTIVES: To update our guidelines for the treatment of pain in patients with cancer, we performed

  16. The Role of Pharmacology in Ureteral Physiology and Expulsive Therapy

    Science.gov (United States)

    Jerde, Travis J.; Nakada, Stephen Y.

    2007-04-01

    Research in the field of ureteral physiology and pharmacology has traditionally been directed toward relaxation of ureteral spasm as a mechanism of analgesia during painful ureteral obstruction, most often stone-induced episodes. However, interest in this field has expanded greatly in recent years with the expanded use of alpha-blocker therapy for inducing stone passage, a usage now termed "medical expulsive therapy". While most clinical reports involving expulsive therapy have focused on alpha receptor or calcium channel blockade, there are diverse studies investigating pharmacological ureteral relaxation with novel agents including cyclooxygenase inhibitors, small molecule beta receptor agonists, neurokinin antagonists, and phosphodiesterase inhibitors. In addition, cutting edge molecular biology research is revealing promising potential therapeutic targets aimed at specific molecular changes that occur during the acute obstruction that accompanies stone disease. The purpose of this report is to review the use of pharmacological agents as ureteral smooth muscle relaxants clinically, and to look into the future of expulsive therapy by reviewing the available literature of ureteral physiology and pharmacology research.

  17. 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

    >Conclusions: The adjuvant therapy of ganglioside sodium in patients with severe craniocerebral injury can effectively reduce ICP, improve PbtO2 and alleviate the injuries of neurons and glial cells caused by oxidative stress.

  18. Process Pharmacology: A Pharmacological Data Science Approach to Drug Development and Therapy.

    Science.gov (United States)

    Lötsch, Jörn; Ultsch, Alfred

    2016-04-01

    A novel functional-genomics based concept of pharmacology that uses artificial intelligence techniques for mining and knowledge discovery in "big data" providing comprehensive information about the drugs' targets and their functional genomics is proposed. In "process pharmacology", drugs are associated with biological processes. This puts the disease, regarded as alterations in the activity in one or several cellular processes, in the focus of drug therapy. In this setting, the molecular drug targets are merely intermediates. The identification of drugs for therapeutic or repurposing is based on similarities in the high-dimensional space of the biological processes that a drug influences. Applying this principle to data associated with lymphoblastic leukemia identified a short list of candidate drugs, including one that was recently proposed as novel rescue medication for lymphocytic leukemia. The pharmacological data science approach provides successful selections of drug candidates within development and repurposing tasks. © 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  19. Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0268 TITLE: Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer PRINCIPAL INVESTIGATOR...Eric Winer CONTRACTING ORGANIZATION: Dana-Farber Cancer Institute Boston, MA 02215 REPORT DATE: OCTOBER 2017 TYPE OF REPORT: ANNUAL PREPARED FOR...CONTRACT NUMBER Randomized Trial of Asprin as Adjuvant Therapy for Node- Positive Breast Cancer 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

  20. Magnetic nanoparticle hyperthermia as an adjuvant cancer therapy with chemotherapy

    Science.gov (United States)

    Petryk, Alicia Ailie

    Magnetic nanoparticle hyperthermia (mNPH) is an emerging cancer therapy which has shown to be most effective when applied in the adjuvant setting with chemotherapy, radiation or surgery. Although mNPH employs heat as a primary therapeutic modality, conventional heat may not be the only cytotoxic effect. As such, my studies have focused on the mechanism and use of mNPH alone and in conjunction with cisplatinum chemotherapy in murine breast cancer cells and a related in vivo model. MNPH was compared to conventional microwave tumor heating, with results suggesting that mNPH (mNP directly injected into the tumor and immediately activated) and 915 MHz microwave hyperthermia, at the same thermal dose, result in similar tumor regrowth delay kinetics. However, mNPH shows significantly less peri-tumor normal tissue damage. MNPH combined with cisplatinum also demonstrated significant improvements in regrowth delay over either modality applied as a monotherapy. Additional studies demonstrated that a relatively short tumor incubation time prior to AMF exposure (less than 10 minutes) as compared to a 4-hour incubation time, resulted in faster heating rates, but similar regrowth delays when treated to the same thermal dose. The reduction of heating rate correlated well with the observed reduction in mNP concentration in the tumor observed with 4 hour incubation. The ability to effectively deliver cytotoxic mNPs to metastatic tumors is the hope and goal of systemic mNP therapy. However, delivering relevant levels of mNP is proving to be a formidable challenge. To address this issue, I assessed the ability of cisplatinum to simultaneously treat a tumor and improve the uptake of systemically delivered mNPs. Following a cisplatinum pretreatment, systemic mNPs uptake was increased by 3.1 X, in implanted murine breast tumors. Additional in vitro studies showed the necessity of a specific mNP/ Fe architecture and spatial relation for heat-based cytotoxicity in cultured cells.

  1. 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

    described not only the unique mechanism of selective ER modulator (SERM)-stimulated breast cancer growth, but also a new apoptotic biology of oestradiol action in breast cancer, following 5 years of anti-hormonal treatment. Oestradiol-induced apoptotic therapy is currently shown to be successful for the short-term treatment of metastatic ER positive breast cancer following exhaustive treatment with anti-hormones. The "oestrogen purge" concept is now being integrated into trials of long-term adjuvant anti-hormone therapy. The Study of Letrazole Extension (SOLE) trial employs "anti-hormonal drug holidays" so that a woman's own oestrogen may periodically purge and kill the nascent sensitized breast cancer cells that are developing. This is the translation of an idea first proposed at the 1992 St. Gallen Conference. Although tamoxifen is the first successful targeted therapy in cancer, the pioneering medicine is more than that. A study of the pharmacology of tamoxifen opened the door for a pioneering application in cancer chemoprevention and created a new drug group: the SERMs, with group members (raloxifene and lasofoxifene) approved for the treatment and prevention of osteoporosis with a simultaneous reduction of breast cancer risk. Thus, the combined strategies of long-term anti-hormone adjuvant therapy, targeted to the breast tumour ER, coupled with the expanding use of SERMs to prevent osteoporosis and prevent breast cancer as a beneficial side effect, have advanced patient survivorship significantly and promise to reduce breast cancer incidence. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Adjuvant therapy in renal cell carcinoma: does higher risk for recurrence improve the chance for success?

    Science.gov (United States)

    Figlin, R A; Leibovich, B C; Stewart, G D; Negrier, S

    2018-02-01

    The success of targeted therapies, including inhibitors of the vascular endothelial growth factor pathway or the mammalian target of rapamycin, in the treatment of metastatic renal cell carcinoma led to interest in testing their efficacy in the adjuvant setting. Results from the first trials are now available, with other studies due to report imminently. This review provides an overview of adjuvant targeted therapy in renal cell carcinoma, including interpretation of currently available conflicting data and future direction of research. We discuss the key differences between the completed targeted therapy adjuvant trials, and highlight the importance of accurately identifying patients who are likely to benefit from adjuvant treatment. We also consider reasons why blinded independent radiology review and treatment dose may prove critical for adjuvant treatment success. The implications of using disease-free survival as a surrogate end point for overall survival from the patient perspective and measurement of health benefit have recently been brought into focus and are discussed. Finally, we discuss how the ongoing adjuvant trials with targeted therapies and checkpoint inhibitors may improve our understanding and ability to prevent tumor recurrence after nephrectomy in the future.

  3. 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.

  4. Comparing guidelines for adjuvant endocrine therapy in postmenopausal women with breast cancer: a coming of age.

    Science.gov (United States)

    Verma, Sunil; Jackisch, Christian

    2011-02-01

    Following surgery for early breast cancer, the standard of care for postmenopausal women is adjuvant therapy with any combination of radiation therapy, endocrine therapy, chemotherapy and/or targeted therapy. Clinicians rely on many tools, including guidelines, to make these treatment decisions. Such guidelines include the St Gallen consensus statement, the American Society of Clinical Oncology guidelines and the National Comprehensive Cancer Network guidelines, as well as various regional and national guidelines. Recommendations may vary, because different methods and criteria were used to assess the strength of supporting data. This article provides an overview of global guidelines for the adjuvant treatment of breast cancer and points out the major differences. Ongoing changes are highlighted, particularly those regarding the adjuvant endocrine treatment of postmenopausal women with breast cancer. While previous guidelines recommended tamoxifen alone, all major guidelines now recommend using third-generation aromatase inhibitors either in sequence with tamoxifen or as upfront treatment.

  5. Secondary malignancy among seminoma patients treated with adjuvant radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chao, Clifford K.S.; Lai, Peter P; Michalski, Jeff M; Perez, Carlos A

    1995-11-01

    interval, 1.22-11.63) than expected. The median duration for developing a second cancer was 11 years for tumors arising from tissues outside the irradiated field and 14 years for those within or near the irradiated area. Conclusions: The overall observed incidence of second nontesticular malignancy among patients with early-stage testicular seminoma treated with adjuvant radiation therapy was not significantly increased in comparison with the expected incidence. Clinical implications are discussed.

  6. Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

    International Nuclear Information System (INIS)

    Horowitz, David P.; Hsu, Charles C.; Wang Jingya; Makary, Martin A.; Winter, Jordan M.; Robinson, Ray; Schulick, Richard D.; Cameron, John L.; Pawlik, Timothy M.; Herman, Joseph M.

    2011-01-01

    Purpose: To evaluate the efficacy of adjuvant chemoradiation therapy (CRT) for pancreatic adenocarcinoma patients ≥75 years of age. Methods: The study group of 655 patients underwent pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma at the Johns Hopkins Hospital over a 12-year period (8/30/1993 to 2/28/2005). Demographic characteristics, comorbidities, intraoperative data, pathology data, and patient outcomes were collected and analyzed by adjuvant treatment status and age ≥75 years. Cox proportional hazards analysis determined clinical predictors of mortality and morbidity. Results: We identified 166 of 655 (25.3%) patients were ≥75 years of age and 489 of 655 patients (74.7%) were <75 years of age. Forty-nine patients in the elderly group (29.5%) received adjuvant CRT. For elderly patients, node-positive metastases (p = 0.008), poor/anaplastic differentiation (p = 0.012), and undergoing a total pancreatectomy (p = 0.010) predicted poor survival. The 2-year survival for elderly patients receiving adjuvant therapy was improved compared with surgery alone (49.0% vs. 31.6%, p = 0.013); however, 5-year survival was similar (11.7% vs. 19.8%, respectively, p = 0.310). After adjusting for major confounders, adjuvant therapy in elderly patients had a protective effect with respect to 2-year survival (relative risk [RR] 0.58, p = 0.044), but not 5-year survival (RR 0.80, p = 0.258). Among the nonelderly, CRT was significantly associated with 2-year survival (RR 0.60, p < 0.001) and 5-year survival (RR 0.69, p < 0.001), after adjusting for confounders. Conclusions: Adjuvant therapy after PD is significantly associated with increased 2-year but not 5-year survival in elderly patients. Additional studies are needed to select which elderly patients are likely to benefit from adjuvant CRT.

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

    Science.gov (United States)

    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.

  8. Optimization of Adjuvant Radiation in Breast Conservation Therapy: Can We Minimize without Compromise?

    International Nuclear Information System (INIS)

    Edwards-Bennett, S.M.; Correa, C.R.; Harris, E.E.

    2011-01-01

    Adjuvant breast radiation therapy after breast conservation surgery is recommended as it yields significant reduction in the risk of local recurrence, and confers a potential overall survival benefit. Although the standard breast radiation regimen has historically been delivered over 57 weeks; more novel, shorter courses of breast radiation are currently being employed, offering the advantage of more convenience and less time-commitment. Herein, we review the recent literature substantiating these abbreviated radiation treatment approaches and the methods of delivery thereof. In addition, we discuss imaged guided techniques currently being utilized to further refine the delivery of adjuvant breast radiation therapy

  9. Efficacy of Turmeric as Adjuvant Therapy in Type 2 Diabetic Patients

    OpenAIRE

    Maithili Karpaga Selvi, N.; Sridhar, M. G.; Swaminathan, R. P.; Sripradha, R.

    2014-01-01

    It is known that there is a significant interplay of insulin resistance, oxidative stress, dyslipidemia, and inflammation in type 2 diabetes mellitus (T2DM). The study was undertaken to investigate the effect of turmeric as an adjuvant to anti-diabetic therapy. Sixty diabetic subjects on metformin therapy were recruited and randomized into two groups (30 each). Group I received standard metformin treatment while group II was on standard metformin therapy with turmeric (2 g) supplements for 4 ...

  10. Pharmacological Therapy of Vascular Malformations of the Gastrointestinal Tract

    Directory of Open Access Journals (Sweden)

    Andrew Szilagyi

    2006-01-01

    Full Text Available Vascular malformation (AVM in the gastrointestinal tract is an uncommon, but not rare, cause of bleeding and iron deficiency anemia, especially in an aging population. While endoscopic coagulative therapy is the method of choice for controlling bleeding, a substantial number of cases require additional therapy. Adjunctive or even primary phamacotherapy may be indicated in recurrent bleeding. However, there is little evidence-based proof of efficacy for any agent. The bulk of support is derived from anecdotal reports or case series. The present review compares the outcome of AVM after no intervention, coagulative therapy or focus on pharmacological agents. Most of the literature encompasses two common AVMs, angiodysplasia and hereditary hemorrhagic telangiectasia. Similarly, the bulk of information evaluates two therapies, hormones (estrogen and progesterone and the somatostatin analogue octreotide. Of these, the former is the only therapy evaluated in randomized trials, and the results are conflicting without clear guidelines. The latter therapy has been reported only as case reports and case series without prospective trials. In addition, other anecdotally used medications are discussed.

  11. The pharmacology of neurokinin receptors in addiction: prospects for therapy

    Directory of Open Access Journals (Sweden)

    Sandweiss AJ

    2015-09-01

    Full Text Available Alexander J Sandweiss, Todd W VanderahDepartment of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USAAbstract: Addiction is a chronic disorder in which consumption of a substance or a habitual behavior becomes compulsive and often recurrent, despite adverse consequences. Substance p (SP is an undecapeptide and was the first neuropeptide of the neurokinin family to be discovered. The subsequent decades of research after its discovery implicated SP and its neurokinin relatives as neurotransmitters involved in the modulation of the reward pathway. Here, we review the neurokinin literature, giving a brief historical perspective of neurokinin pharmacology, localization in various brain regions involved in addictive behaviors, and the functional aspects of neurokinin pharmacology in relation to reward in preclinical models of addiction that have shaped the rational drug design of neurokinin antagonists that could translate into human research. Finally, we will cover the clinical investigations using neurokinin antagonists and discuss their potential as a therapy for drug abuse.Keywords: reward, substance p, alcohol, morphine, cocaine, dopamine

  12. Depression related to (neo)adjuvant hormonal therapy for prostate cancer

    International Nuclear Information System (INIS)

    Tol-Geerdink, Julia J. van; Leer, Jan Willem; Lin, Emile N.J.T. van; Schimmel, Erik C.; Stalmeier, Peep F.M.

    2011-01-01

    Background: We studied whether hormonal therapy, (neo)adjuvant to radiotherapy for localized prostate cancer, is related to an increase in depression and whether this is caused by the hormonal therapy itself or by the relatively poor prognosis of patients who get (neo)adjuvant hormonal therapy. Methods: Between 2002 and 2005, 288 patients, irradiated for prostate cancer (T1-3N0M0), were studied prospectively in two clinics. In one clinic almost all patients received (neo)adjuvant androgen deprivation (Bicalutamide + Gosereline). In a second clinic hormonal therapy was prescribed mainly for high risk patients. This allowed us to separate the effects of hormonal therapy and the patient's prognosis. Results: During the course of hormonal therapy, depression was significantly heightened by both hormone use (p < 0.001) and poor prognosis (p < 0.01). After completion of hormonal therapy, poor prognosis continued to affect the depression score (p < 0.01). The increase was, however, small. Conclusions: Depression was mildly increased in patients receiving hormonal therapy. The increase appeared to be related to both the hormone therapy itself and the high risk status of patients. High risk status, with the associated poor prognosis, had a more sustained effect on depression. The rise was statistically significant, but was too small, however, to bear clinical significance.

  13. Tabletted guar gum microspheres of piroxicam for targeted adjuvant therapy for colonic adenocarcinomas.

    Science.gov (United States)

    Vats, Anima; Pathak, Kamla

    2012-11-01

    In recent years, nonsteroidal anti-inflammatory drugs have been found to be cogent as an adjuvant therapeutic agent in mitigating colorectal cancer. Thus, this present investigation was aimed to formulate an oral, targeted tablet of piroxicam microspheres for sustained and targeted adjuvant therapy for colonic adenocarcinomas. Crosslinked guar gum microspheres of piroxicam were directly compressed into matrix tablet and coated with Eudragit S100. The optimized tablet that displayed 0% release in simulated gastric fluid, 15% in simulated intestinal fluid and 97.1% in simulated colonic fluid underwent roentgenographic study in rabbits to check its safe transit to the colon. x-ray images revealed intactness of the tablet until it reached the colon where the tablet matrix eroded. The designed, conceptual formulation emerged as potential carrier for targeted adjuvant therapy of piroxicam.

  14. The Pharmacological Basis of Cannabis Therapy for Epilepsy.

    Science.gov (United States)

    Reddy, Doodipala Samba; Golub, Victoria M

    2016-04-01

    Recently, cannabis has been suggested as a potential alternative therapy for refractory epilepsy, which affects 30% of epilepsy, both adults and children, who do not respond to current medications. There is a large unmet medical need for new antiepileptics that would not interfere with normal function in patients with refractory epilepsy and conditions associated with refractory seizures. The two chief cannabinoids are Δ-9-tetrahyrdrocannabinol, the major psychoactive component of marijuana, and cannabidiol (CBD), the major nonpsychoactive component of marijuana. Claims of clinical efficacy in epilepsy of CBD-predominant cannabis or medical marijuana come mostly from limited studies, surveys, or case reports. However, the mechanisms underlying the antiepileptic efficacy of cannabis remain unclear. This article highlights the pharmacological basis of cannabis therapy, with an emphasis on the endocannabinoid mechanisms underlying the emerging neurotherapeutics of CBD in epilepsy. CBD is anticonvulsant, but it has a low affinity for the cannabinoid receptors CB1 and CB2; therefore the exact mechanism by which it affects seizures remains poorly understood. A rigorous clinical evaluation of pharmaceutical CBD products is needed to establish the safety and efficacy of their use in the treatment of epilepsy. Identification of mechanisms underlying the anticonvulsant efficacy of CBD is also critical for identifying other potential treatment options. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

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

    International Nuclear Information System (INIS)

    McMillan, Matthew T.; Ojerholm, Eric; Roses, Robert E.; Plastaras, John P.; Metz, James M.; Mamtani, Ronac; Karakousis, Giorgos C.; Fraker, Douglas L.; Drebin, Jeffrey A.; Stripp, Diana; Ben-Josef, Edgar; Datta, Jashodeep

    2015-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    Showalter, Timothy N.; Ohri, Nitin; Teti, Kristopher G.; Foley, Kathleen A.; Keith, Scott W.; Trabulsi, Edouard J.; Lallas, Costas D.; Dicker, Adam P.; Hoffman-Censits, Jean; Pizzi, Laura T.; Gomella, Leonard G.

    2012-01-01

    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.

  19. Endodontic treatment of teeth with periapical lesion in one session with photodynamic therapy as an adjuvant: study "in vivo"

    OpenAIRE

    Supercilio Barros Filho

    2012-01-01

    Hypothesis of the study: It is assumed that the use of photodynamic therapy (PDT) as an adjuvant in root canal therapy can promote the repair of teeth with periapical lesions treated in one session. Objectives: This in vivo study was to evaluate the effects of photodynamic therapy as an adjuvant in root canal therapy in one session for the repair of periapical lesions. Method: Fourteen human teeth with mortification pulp and periapical lesions were randomly divided into two groups (n=7): G1- ...

  20. 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.

  1. Prognostic significance of adjuvant radiation therapy in adenocarcinoma of the cecum

    Science.gov (United States)

    Hosseini, Sare; Bananzadeh, Ali Mohammad; Mohammadianpanah, Mohammad; Salek, Roham; Taghizadeh-Kermani, Ali

    2018-01-01

    Purpose Local recurrence is a common failure pattern in adenocarcinoma of the cecum. This study aimed to investigate the potential role of adjuvant radiation therapy on oncologic outcomes of patients with adenocarcinoma of the cecum. Materials and Methods This retrospective study was carried out at three large tertiary university hospitals. We analyzed the characteristics, prognostic factors, and survival of 162 patients with adenocarcinoma of the cecum that were treated and followed up between 2000 and 2013. All the patients had undergone a right hemicolectomy and received chemotherapy with (n = 48) or without (n = 114) adjuvant radiation therapy. Results The subjects were 65 females and 97 males with a median age of 56 years (range, 17 to 90 years) at diagnosis. The 5-year local control (LC), disease free survival (DFS), and overall survival (OS) rates were 72.7%, 57.2%, and 62.6% respectively. In a multivariate analysis, age, tumor stage, node stage, and adjuvant radiation therapy were determined to be independent prognostic factors. Age more than 55 years (hazard ratio [HR] = 1.0; 95% confidence interval [CI], 0.06–0.32; p = 0.003], T4 stage (HR = 6.8; 95% CI, 3.07–15.36; p < 0.001), node positive disease (HR = 4.2; 95% CI, 1.94–9.13; p < 0.001), and the absence of adjuvant radiation therapy (HR = 3.0; 95% CI, 1.39–6.46; p = 0.005) had a negative influence on OS. Conclusion Adjuvant radiation therapy significantly improves DFS and OS in patients with adenocarcinoma of the cecum. PMID:29506326

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

    OpenAIRE

    Spugnini, Enrico P; Citro, Gennaro; Baldi, Alfonso

    2009-01-01

    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 complic...

  3. Pharmacological and Non-pharmacological Therapies of Cognitive Impairment in Multiple Sclerosis.

    Science.gov (United States)

    Miller, Elzbieta; Morel, Agnieszka; Redlicka, Justyna; Miller, Igor; Saluk, Joanna

    2018-01-01

    Cognitive impairment is one of the most important clinical features of neurodegenerative disorders including multiple sclerosis (MS). Conducted research shows that up to 65 percent of MS patients have cognitive deficits such as episodic memory, sustained attention, reduced verbal fluency; however, the cognitive MS domain is information processing speed. It is the first syndrome of cognitive dysfunction and the most widely affected in MS. Occasionally these impairments occur even before the appearance of physical symptoms. Therefore, this review focused on the current status of our knowledge about possible methods of treatment cognitive impairment in MS patients including novel strategies. Research and online content was performed using Medline and EMBASE databases. The most recent research suggests that cognitive impairment is correlated with brain lesion volume and brain atrophy. The examination of the cognitive impairment is usually based on particular neuropsychological batteries. However, it can be not enough to make a precise diagnosis. This creates a demand to find markers that might be useful for identifying patients with risk of cognitive impairment at an early stage of the disease. Currently the most promising methods consist of neuroimaging indicators, such as diffusion tensor imaging, the magnetization transfer ratio, and N-acetyl aspartate levels. Diagnosis problems are strictly connected with treatment procedures. There are two main cognitive therapies: pharmacological (disease modifying drugs (DMD), symptomatic treatments) and non-pharmacological interventions that are focused on psychological and physical rehabilitation. Some trials have shown a positive association between physical activity and the cognitive function. This article is an overview of the current state of knowledge related to cognition impairment treatment in MS. Additionally, novel strategies for cognitive impairments such as cryostimulation and other complementary methods are

  4. Gold glyconanoparticles coupled to listeriolysin O 91-99 peptide serve as adjuvant therapy against melanoma.

    Science.gov (United States)

    Calderon-Gonzalez, R; Terán-Navarro, H; García, I; Marradi, M; Salcines-Cuevas, D; Yañez-Diaz, S; Solis-Angulo, A; Frande-Cabanes, E; Fariñas, M C; Garcia-Castaño, A; Gomez-Roman, J; Penades, S; Rivera, F; Freire, J; Álvarez-Domínguez, C

    2017-08-03

    Dendritic cell-based (DC-based) vaccines are promising immunotherapies for cancer. However, several factors, such as the lack of efficient targeted delivery and the sources and types of DCs, have limited the efficacy of DCs and their clinical potential. We propose an alternative nanotechnology-based vaccine platform with antibacterial prophylactic abilities that uses gold glyconanoparticles coupled to listeriolysin O 91-99 peptide (GNP-LLO 91-99 ), which acts as a novel adjuvant for cancer therapy. GNP-LLO 91-99 , when used to vaccinate mice, exhibited dual antitumour activities, namely, the inhibition of tumour migration and growth and adjuvant activity for recruiting and activating DCs, including those from melanoma patients. GNP-LLO 91-99 nanoparticles caused tumour apoptosis and induced antigen- and melanoma-specific cytotoxic Th1 responses (P ≤ 0.5). We propose this adjuvant nanotherapy for preventing the progression of the first stages of melanoma.

  5. A cost-effectiveness analysis of adjuvant therapies for resected adenocarcinoma of the rectum

    International Nuclear Information System (INIS)

    Lee, Jason H.

    1997-01-01

    PURPOSE: Several prospective randomized trials have shown a significant survival advantage with adjuvant chemotherapy and radiation therapy following surgical resection of adenocarcinoma of the rectum. Recent and ongoing trials are evaluating the role of modulated and/or protracted venous infusion [PVI] chemotherapy with pelvic irradiation [PRT]. The economic implications of additional therapies compared with their incremental benefits have not been rigorously analyzed. This study attempts to assess the incremental cost effectiveness of adjuvant therapy over surgery alone, and secondly, adjuvant therapy with PVI delivery systems versus rapid infusion. METHODS: A Markov model was constructed to describe the natural history of rectal carcinoma [stage B2, C] following surgical resection in a hypothetical cohort of 60 year old patients. This model was used to perform two sets of comparisons: [1] surgery alone versus adjuvant bolus fluorouracil [5-FU] with PRT, and [2] bolus 5-FU with PRT versus PVI 5-FU with PRT. Relapse rates and overall survival were derived from an early GITSG trial for the first comparison and from the NCCTG 86-47-51 trial for the second comparison. Medicare reimbursement rates and reports from health maintenance organizations were used to obtain net medical costs of adjuvant treatments, routine follow-up, advanced recurrent disease, and terminal illness as a result of rectal carcinoma. Total years of life and medical costs were projected over an 8-year time horizon for the first comparison [GITSG data] and over a 5-year time horizon for the second comparison [NCCTG data]. Monetary and nonmonetary benefits were discounted at 5% per year. Adjustments for quality of life, costs of adverse effects from treatment, and indirect costs of disease or treatment were not included in this current analysis. RESULTS: The main survival and economic outcomes for each treatment arm in the two comparisons are reported in the table below. For the first comparison

  6. Efficacy of systemic adjuvant therapies administered to dogs after excision of oral malignant melanomas: 151 cases (2001-2012).

    Science.gov (United States)

    Boston, Sarah E; Lu, Xiaomin; Culp, William T N; Montinaro, Vincenzo; Romanelli, Giorgio; Dudley, Robert M; Liptak, Julius M; Mestrinho, Lisa A; Buracco, Paolo

    2014-08-15

    To determine prognostic factors for and compare outcome among dogs with oral malignant melanoma following excision with or without various systemic adjuvant therapies. Retrospective case series. 151 dogs with naturally occurring oral malignant melanomas treated by excision with or without adjuvant therapies from 2001 to 2012. Case accrual was solicited from Veterinary Society of Surgical Oncology members via an email list service. Information collected from case records included signalment, tumor staging, tumor characteristics, type of surgical excision, histologic diagnosis, adjuvant therapy, and survival time. The overall median survival time was 346 days. Results of multivariate analysis indicated that tumor size, patient age, and intralesional excision (vs marginal, wide, or radical excision) were considered poor prognostic indicators. All other demographic and clinical variables were not significantly associated with survival time after adjusting for the aforementioned 3 variables. A clear survival benefit was not evident with any systemic adjuvant therapy, including vaccination against melanoma or chemotherapy; however, the number of dogs in each treatment group was small. Ninety-eight dogs received no postoperative adjuvant therapy, and there was no difference in survival time between dogs that did (335 days) and did not (352 days) receive systemic adjuvant therapy. For dogs with oral malignant melanoma, increasing tumor size and age were negative prognostic factors. Complete excision of all macroscopic tumor burden improved survival time. Long-term survival was possible following surgery alone. Although systemic adjuvant therapy was not found to improve survival time, this could have been due to type II error.

  7. Calreticulin as cancer treatment adjuvant: combination with photodynamic therapy and photodynamic therapy-generated vaccines

    Directory of Open Access Journals (Sweden)

    Mladen eKorbelik

    2015-02-01

    Full Text Available Calreticulin is recognized as one of pivotal damage-associated molecular pattern (DAMP molecules alerting the host of the presence of distressed cells. In this role, calreticulin becomes exposed on the surface of tumor cells treated by several types of cancer therapy including photodynamic therapy (PDT. The goal of the present study was to examine the potential of externally added calreticulin for augmenting antitumor effect mediated by PDT. Recombinant calreticulin was found to bind to mouse SCCVII tumor cells treated by PDT. Compared to the outcome with PDT alone, cure-rates of SCCVII tumors grown in immunocompetent C3H/HeN mice were elevated when calreticulin (0.4 mg/mouse was injected peritumorally immediately after PDT. Such therapeutic gain with PDT plus calreticulin combination was not obtained with SCCVII tumors growing in immunodeficient NOD-scid mice. In PDT vaccine protocol, where PDT-treated SCCVII cells are used for vaccination of SCCVII tumor-bearing mice, adding recombinant calreticulin to cells before their injection produced improved therapeutic effect. The expression of calreticulin gene was reduced in PDT-treated cells, while no changes were observed with the expression of this gene in tumor, liver, and spleen tissues in PDT vaccine-treated mice. These findings reveal that externally added recombinant calreticulin can boost antitumor responses elicited by PDT or PDT-generated vaccines, and can thus serve as an effective adjuvant for cancer treatment with PDT and probably other cancer cell stress-inducing modalities.

  8. Adjuvant endocrine therapy for premenopausal women with hormone-responsive breast cancer.

    Science.gov (United States)

    Mathew, Aju; Davidson, Nancy E

    2015-11-01

    Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed and results have been presented over the last two years. These include tamoxifen for 5-10 years (ATLAS and aTTom), tamoxifen for 5 years followed by aromatase inhibitor (AI) for 5 years for women who have become postmenopausal (MA-17); ovarian ablation (OA) by surgery (EBCTCG overview); ovarian function suppression (OFS) by LHRH agonist (LHRH agonist meta-analysis); or combinations of approaches including OFS plus tamoxifen or AI (SOFT, TEXT, ABCSG 12 and E3193). Many of these trials have taken place in the backdrop of (neo)adjuvant chemotherapy which can confound interpretation because such therapy can suppress ovarian function either transiently or permanently. Nonetheless these trials suggest in aggregate that 10 years of tamoxifen are better than 5 years and that a program of extended adjuvant therapy of tamoxifen for 5 years followed by aromatase inhibitor for 5 years is effective for suitable candidates. The SOFT and E3193 trials do not show a major advantage for use of OFS + tamoxifen compared to tamoxifen alone. The joint SOFT/TEXT analysis and ABCGS12 trials both suggest that outcomes can be excellent with the use of combined endocrine therapy alone in properly selected patients but give conflicting results with regard to potential benefits for OFS + AI compared with OFS + tamoxifen. Further work will be needed to ascertain long-term outcomes, identify factors that predict who will benefit from extended adjuvant endocrine therapy, and assess role of OFS by medical or surgical means. It is clear, however, that endocrine therapy is a critical part of the adjuvant regimen for most premenopausal women with hormone-responsive breast cancer, and a subset of these women with luminal A-type tumors can be safely treated with endocrine therapy alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy.

    Science.gov (United States)

    Tate, Keisei; Yoshida, Hiroshi; Ishikawa, Mitsuya; Uehara, Takashi; Ikeda, Shun Ichi; Hiraoka, Nobuyoshi; Kato, Tomoyasu

    2018-05-01

    Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I-II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

  10. Intraperitoneal P-32 for adjuvant and consolidative therapy in ovarian carcinoma

    International Nuclear Information System (INIS)

    Condra, Kellie S.; Mendenhall, William M.; Morgan, Linda S.; Freeman, Debra E.; Marcus, Robert B.; Hagan, Michael P.

    1996-01-01

    Purpose/Objective: To determine the role of intraperitoneal radioactive chromic phosphate (P-32) in the treatment of patients with ovarian carcinoma. Survival results, patterns of recurrence, and treatment morbidity are reported for patients treated adjuvantly after primary surgery and for patients treated with the intent of consolidation after second-look laparotomy. Materials and Methods: Between 1976 and 1993, 25 patients with ovarian carcinoma were treated with 15 mCi P-32 as adjuvant therapy and 43 patients received P-32 as consolidation after second-look laparotomy. The majority of patients (13 of 19) treated adjuvantly had high-risk early-stage disease (IAG 3, IBG 2-3, IC) or more advanced stages (6 patients). Thirty-nine patients received consolidative P-32 after negative second-look laparotomy (35 Stage II-IV and 4 Stage I) and 4 Stage III patients were treated after positive second-look laparotomy. All patients had 2-year minimum follow-up (median, 7.9 years). Results: Ten-year abdominal control and cause-specific survival rates for adjuvant P-32 were 83% and 82%, respectively. For patients treated with consolidative P-32, 5-year abdominal control and cause-specific survival rates were 65% and 78%, respectively. The 5-year cause-specific survival rate for 35 patients with Stage II-IV disease treated with consolidative P-32 after negative second-look laparotomy was 81%. A component of peritoneal failure was the primary mode of recurrence (15 of 22 failures). Four patients required surgical intervention for small-bowel obstruction. No patients died of treatment-related complications. Conclusion: P-32 is well tolerated with acceptable toxicity. In comparing our results to the literature, adjuvant P-32 appears to offer improved cause-specific survival compared with observation alone and equivalent cause-specific survival compared with adjuvant chemotherapy. Consolidative P-32 after negative second-look laparotomy resulted in improved 5-year cause

  11. Pharmacologic Therapy in the Elderly with Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Shih-Huang Lee

    2008-03-01

    Full Text Available Atrial fibrillation (AF is the most common sustained arrhythmia, and its prevalence significantly increases with age. Morphologic changes in the atrial myocardium associated with AF may result from underlying cardiovascular disease and/or physiologic aging processes. Congestive heart failure, tachycardia-induced cardiomyopathy and thromboembolic events resulting from AF are more common in elderly patients. It is important to assess any comorbidity and potential triggers of AF before considering pharmacologic therapy for AF. Proper rate control should include control in response to exercise, together with an avoidance of bradycardias and symptomatic pauses in patients with AF. Digoxin, β-blockers and calcium channel blockers can all be effective in controlling ventricular rate in elderly patients with AF. In the elderly, amiodarone is probably the safest drug for short-term administration to exert chemical cardioversion, facilitate electrical cardioversion, and prevent recurrence of AF. Warfarin has been shown to be highly effective in preventing stroke in the elderly with AF; however, many studies also have documented underuse of warfarin, may be because of the increased risk of warfarin-induced hemorrhage in such patients. These findings have raised concerns regarding quality of care, physician adherence to guidelines, and translation of clinical trial results into real-world practice in anticoagulation therapy in the elderly with AF. [International Journal of Gerontology 2008; 2(1: 1–6

  12. Cough: neurophysiology, methods of research, pharmacological therapy and phonoaudiology

    Directory of Open Access Journals (Sweden)

    Balbani, Aracy Pereira Silveira

    2012-01-01

    Full Text Available Introduction: The cough is the more common respiratory symptom in children and adults. Objective: To present a revision on the neurophysiology and the methods for study of the consequence of the cough, as well as the pharmacotherapy and phonoaudiology therapy of the cough, based on the works published between 2005 and 2010 and indexed in the bases Medline, Lilacs and Library Cochrane under them to keywords "cough" or "anti-cough". Synthesis of the data: The consequence of the cough involves activation of receiving multiples becomes vacant in the aerial ways and of neural projections of the nucleus of the solitary treatment for other structures of the central nervous system. Experimental techniques allow studying the consequence of the cough to the cellular and molecular level to develop new anti-cough agents. It does not have evidences of that anti-cough exempt of medical lapsing they have superior effectiveness to the one of placebo for the relief of the cough. The phonoaudiology therapy can benefit patients with refractory chronic cough to the pharmacological treatment, over all when paradoxical movement of the vocal folds coexists. Final Comments: The boarding to multidiscipline has basic paper in the etiological diagnosis and treatment of the cough. The otolaryngologist must inform the patients on the risks of the anti-cough of free sales in order to prevent adverse poisonings and effect, especially in children.

  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. Adjuvant Therapy for Thymic Carcinoma--A Decade of Experience in a Taiwan National Teaching Hospital.

    Directory of Open Access Journals (Sweden)

    Yen-Han Tseng

    Full Text Available Thymic carcinomas are rare tumors for which surgical resection is the first treatment of choice. The role of adjuvant treatment after surgery is unknown because of limited available data. The present study evaluated the efficacy of post-surgery adjuvant chemotherapy or radiotherapy in patients with thymic carcinoma.To evaluate the role of adjuvant therapy in patients with thymic carcinoma, we retrospectively reviewed the records of patients with thymic carcinoma who were diagnosed and treated between 2004 and 2014.Among 78 patients with thymic carcinoma, 30 patients received surgical resection. Progression-free survival (PFS and overall survival (OS were significantly longer among these patients than among patients who received other treatments (PFS: 88.4 months vs 9.1 months, p<0.001; OS: 134.9 months vs 60.9 months; p = 0.003. Patients with stage III thymic carcinoma who received surgery had a longer OS than patients who did not receive surgery (70.1 months vs 23.9 months; p = 0.017, n = 11. Among 47 patients with stage IV carcinoma, 12 patients who received an extended thymothymectomy had a longer PFS than 35 patients who did not receive surgery (18.9 months vs 8.7 months; p = 0.029. Among 30 patients (with stage I- IV carcinoma who received primary lesion surgery, 19 patients received an R0 resection and 9 patients of the 19 patients received adjuvant radiotherapy. These patients had longer PFS (50.3 months than 2 patients who received adjuvant chemotherapy (5.9 months or 4 patients who received concurrent chemoradiotherapy (7.5 months after surgery (p = 0.003.Surgical resection should be considered for patients with thymic carcinoma, even for patients with locally advanced or stage IV carcinoma. Adjuvant radiotherapy resulted in a better PFS after R0 resection.

  15. Endoscopic Nd-YAG laser treatment and adjuvant therapy for metastatic lesions of airway

    Energy Technology Data Exchange (ETDEWEB)

    Okitsu, Hiroshi; Oho, Kenkichi; Naitoh, Jun; Tajika, Eishiro; Amemiya, Ryuta; Hayata, Yoshihiro [Tokyo Medical Coll. (Japan)

    1989-06-01

    Endoscopic Nd-YAG laser treatment and adjuvant therapy were performed in 44 cases with metastatic lesions of airway. The best results were obtained in 31 cases (93.9%) out of 33 cases complaining of ventilatory disturbance in which endoscopic Nd-YAG laser treatment was indicated as an emergency procedure. In most of these cases with metastatic lesions of airway consisted of respiratory tract invasion from mediastinal lymph nodes in cases of esophageal cancer or lung cancer. In these cases, after laser treatment for ventilatory disturbance, the patients condition improved to the extent that adjuvant therapy could be performed. Adjuvant therapy was performed in 38 cases, there were 7 cases treated surgically resection of the metastatic lesions of airway in 3 cases, tracheal tube stent operation in 4 cases 0, 28 radiotherapy in 28 cases Linac irradiation in 24 cases, /sup 60/Co intraluminal irradiation of the trachea in 4 cases 0, and 32 cases were treated with chemotherapy. Tracheal tube stent operation was useful for maintenance of the tracheal lumen following laser treatment, and /sup 60/Co intraluminal irradiation was effective for the residual intratracheal tumor. The 1-year survival rate of 44 cases with metastatic lesions of airway was 42% and the 2-year survival rate was 22%, so this result suggested endoscopic Nd-YAG laser treatment and adjuvant therapy for metastatic lesions of airway was useful to prolong survival time. However the main value of this modality is for the rapid relief of severe ventilatory disturbance due to obstructive airway lesions. (author).

  16. Adjuvant Medications That Improve Survival after Locoregional Therapy.

    Science.gov (United States)

    Boas, F Edward; Ziv, Etay; Yarmohammadi, Hooman; Brown, Karen T; Erinjeri, Joseph P; Sofocleous, Constantinos T; Harding, James J; Solomon, Stephen B

    2017-07-01

    To determine if outpatient medications taken at the time of liver tumor embolization or ablation affect survival. A retrospective review was done of 2,032 liver tumor embolization, radioembolization, and ablation procedures performed in 1,092 patients from June 2009 to April 2016. Pathology, hepatocellular carcinoma (HCC) stage (American Joint Committee on Cancer), neuroendocrine tumor (NET) grade, initial locoregional therapy, overall survival after initial locoregional therapy, Child-Pugh score, Eastern Cooperative Oncology Group performance status, Charlson Comorbidity Index, and outpatient medications taken at the time of locoregional therapy were analyzed for each patient. Kaplan-Meier survival curves were calculated for patients taking 29 medications or medication classes (including prescription and nonprescription medications) for reasons unrelated to their primary cancer diagnosis. Kaplan-Meier curves were compared using the log-rank test. For patients with HCC initially treated with embolization (n = 304 patients), the following medications were associated with improved survival when taken at the time of embolization: beta-blockers (P = .0007), aspirin (P = .0008) and other nonsteroidal antiinflammatory drugs (P = .009), proton pump inhibitors (P = .004), and antivirals for hepatitis B or C (P = .01). For colorectal liver metastases initially treated with ablation (n = 172 patients), beta-blockers were associated with improved survival when taken at the time of ablation (P = .02). Aspirin and beta-blockers are associated with significantly improved survival when taken at the time of embolization for HCC. Aspirin was not associated with survival differences after locoregional therapy for NET or colorectal liver metastases, suggesting an HCC-specific effect. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

  17. Bilateral lung irradiation as adjuvant therapy in osteogenic sarcoma

    International Nuclear Information System (INIS)

    Abbatucci, J.S.

    1982-01-01

    Bilateral lung irradiation as well as chemotherapy are still controversial in the ''prevention'' of pulmonary metastases from osteosarcomas. This paper presents theoretical and experimental evidence in support of such an irradiation. Doses which can be tolerated by the normal lung are recalled. Data from clinical experience is analyzed and the optimal modalities of irradiation are described. Confirmation of the presumptive effectiveness of radiation therapy can be obtained only through controlled trials such as the one which is ongoing at the EORTC [fr

  18. Oxygen carrying perfluorochemical emulsion as an adjuvant to radiation therapy

    International Nuclear Information System (INIS)

    Teicher, B.A.; Rose, C.M.

    1984-01-01

    The potential of a perfluorochemical emulsion which as an excellent carrying capacity for oxygen to enhance the ability of radiation therapy to delay the growth of Lewis lung tumor was examined. There was a highly significant effect produced by the addition of perfluorochemical emulsion and carbogen breathing in combination with irradiation. With single dose x-ray treatment the dose of perfluorochemical emulsion was varied from 0.05-0.6 ml addition to the blood volume of the animals. The dose response effect was very broad peaking at 0.3-0.4 ml which gave a dose modifying effect of 2.8 +- 0.6 with 1000 rad of x-rays. The addition of 0.3 ml of perfluorochemical free annex solution with carbogen breathing produced a small enhancement in tumor growth delay addition of the same volume of the complete emulsion increased the tumor growth delay time about 3-fold compared to the annex solution. When the perfluorochemical emulsion was added to a fractionated course of radiation therapy a dose modifying effect of 1.8 +- 0.3 was obtained. Oxygen carrying perfluorochemical emulsions may provide a nontoxic clinically useful means of increasing the effectiveness of radiation therapy and of certain chemotherapeutic agents

  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. Adjuvant radiation therapy for pancreatic cancer: a review of the old and the new.

    Science.gov (United States)

    Boyle, John; Czito, Brian; Willett, Christopher; Palta, Manisha

    2015-08-01

    Surgery represents the only potential curative treatment option for patients diagnosed with pancreatic adenocarcinoma. Despite aggressive surgical management for patients deemed to be resectable, rates of local recurrence and/or distant metastases remain high, resulting in poor long-term outcomes. In an effort to reduce recurrence rates and improve survival for patients having undergone resection, adjuvant therapies (ATs) including chemotherapy and chemoradiation therapy (CRT) have been explored. While adjuvant chemotherapy has been shown to consistently improve outcomes, the data regarding adjuvant radiation therapy (RT) is mixed. Although the ability of radiation to improve local control has been demonstrated, it has not always led to improved survival outcomes for patients. Early trials are flawed in their utilization of sub-optimal radiation techniques, limiting their generalizability. Recent and ongoing trials incorporate more optimized RT approaches and seek to clarify its role in treatment strategies. At the same time novel radiation techniques such as intensity modulated RT (IMRT) and stereotactic body RT (SBRT) are under active investigation. It is hoped that these efforts will lead to improved disease-related outcomes while reducing toxicity rates.

  1. Adjuvant Therapy for Revision Rhinoplasty of Contracted Nose Using Polydeoxyribonucleotide and Invasive Bipolar Radiofrequency

    Directory of Open Access Journals (Sweden)

    Tae Hwan Ahn, MD, PhD

    2018-01-01

    Full Text Available Summary:. Most cases of severely contracted nose require revision rhinoplasty and septoplasty, wherein preoperative and/or intraoperative expansion of nasal soft tissue is necessary for tension-free revision surgery. The present study aimed to evaluate the efficacy and safety of pre- and postoperative adjuvant therapy using polydeoxyribonucleotide (PDRN and invasive, pulsed-type, bipolar, alternating current radiofrequency (RF for revision surgery of a contracted nose. In total, 30 patients were treated with 16 sessions (8 preoperative sessions and 8 postoperative sessions of intralesional injection of PDRN and invasive RF treatment using microneedle electrodes at 1-week intervals. One week after the final combined pretreatment using PDRN and invasive bipolar RF, the skin of contracted noses was sufficiently softened, and nasal skin mobility was notably improved in all the patients. During revision rhinoplasty and septoplasty, the contracted nasal skin in each patient was adequately released for proper covering of the nasal tip without tension. Postoperatively, 8 sessions of adjuvant therapy elicited marked clinical improvements in persistent nasal tip dimpling and contracture, septal deviation, and warping from the incomplete recovery of nasal contracture after revision surgery. In conclusion, our pre- and postoperative adjuvant therapies using PDRN and invasive bipolar RF remarkably improved the therapeutic outcomes of revision rhinoplasty and septoplasty for contracted skin of the nose without major side effects.

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

    Science.gov (United States)

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

    2013-01-01

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

  3. 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.

  4. Computational prediction of multidisciplinary team decision-making for adjuvant breast cancer drug therapies: a machine learning approach.

    Science.gov (United States)

    Lin, Frank P Y; Pokorny, Adrian; Teng, Christina; Dear, Rachel; Epstein, Richard J

    2016-12-01

    Multidisciplinary team (MDT) meetings are used to optimise expert decision-making about treatment options, but such expertise is not digitally transferable between centres. To help standardise medical decision-making, we developed a machine learning model designed to predict MDT decisions about adjuvant breast cancer treatments. We analysed MDT decisions regarding adjuvant systemic therapy for 1065 breast cancer cases over eight years. Machine learning classifiers with and without bootstrap aggregation were correlated with MDT decisions (recommended, not recommended, or discussable) regarding adjuvant cytotoxic, endocrine and biologic/targeted therapies, then tested for predictability using stratified ten-fold cross-validations. The predictions so derived were duly compared with those based on published (ESMO and NCCN) cancer guidelines. Machine learning more accurately predicted adjuvant chemotherapy MDT decisions than did simple application of guidelines. No differences were found between MDT- vs. ESMO/NCCN- based decisions to prescribe either adjuvant endocrine (97%, p = 0.44/0.74) or biologic/targeted therapies (98%, p = 0.82/0.59). In contrast, significant discrepancies were evident between MDT- and guideline-based decisions to prescribe chemotherapy (87%, p machine learning models. A machine learning approach based on clinicopathologic characteristics can predict MDT decisions about adjuvant breast cancer drug therapies. The discrepancy between MDT- and guideline-based decisions regarding adjuvant chemotherapy implies that certain non-clincopathologic criteria, such as patient preference and resource availability, are factored into clinical decision-making by local experts but not captured by guidelines.

  5. 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.

  6. Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Clinical Practice Guideline Focused Update.

    Science.gov (United States)

    Denduluri, Neelima; Chavez-MacGregor, Mariana; Telli, Melinda L; Eisen, Andrea; Graff, Stephanie L; Hassett, Michael J; Holloway, Jamie N; Hurria, Arti; King, Tari A; Lyman, Gary H; Partridge, Ann H; Somerfield, Mark R; Trudeau, Maureen E; Wolff, Antonio C; Giordano, Sharon H

    2018-05-22

    Purpose To update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. Methods An Expert Panel conducted targeted systematic literature reviews guided by a signals approach to identify new, potentially practice-changing data that might translate to revised practice recommendations. Results The Expert Panel reviewed phase III trials that evaluated adjuvant capecitabine after completion of standard preoperative anthracycline- and taxane-based combination chemotherapy by patients with early-stage breast cancer HER2-negative breast cancer with residual invasive disease at surgery; the addition of 1 year of adjuvant pertuzumab to combination chemotherapy and trastuzumab for patients with early-stage, HER2-positive breast cancer; and the use of neratinib as extended adjuvant therapy for patients after combination chemotherapy and trastuzumab-based adjuvant therapy with early-stage, HER2-positive breast cancer. Recommendations Patients with early-stage HER2-negative breast cancer with pathologic, invasive residual disease at surgery following standard anthracycline- and taxane-based preoperative therapy may be offered up to six to eight cycles of adjuvant capecitabine. Clinicians may add 1 year of adjuvant pertuzumab to trastuzumab-based combination chemotherapy in patients with high-risk, early-stage, HER2-positive breast cancer. Clinicians may use extended adjuvant therapy with neratinib to follow trastuzumab in patients with early-stage, HER2-positive breast cancer. Neratinib causes substantial diarrhea, and diarrhea prophylaxis must be used. Additional information can be found at www.asco.org/breast-cancer-guidelines .

  7. 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.

  8. The results of radical retropubic prostatectomy and adjuvant therapy for pathologic stage C prostate cancer

    International Nuclear Information System (INIS)

    Schild, Steven E.; Wong, William W.; Grado, Gordon L.; Halyard, Michele Y.; Novicki, Donald E.; Swanson, Scott K.; Larson, Thayne R.; Ferrigni, Robert G.

    1996-01-01

    Purpose: The results of therapy in 288 men with pathologic Stage C prostate cancer who underwent radical retropubic prostatectomy (RRP) were analyzed to determine the effects of adjuvant therapy. Methods and Materials: Twenty-seven of the 288 patients received preoperative neoadjuvant hormonal therapy (leuprolide acetate). Postoperatively, 60 patients received adjuvant radiotherapy (RT) to the prostate bed. Follow-up ranged from 3 to 83 months (median = 32 months). Freedom from failure (FFF) was defined as maintaining a serum PSA level of ≤ 0.3 ng/ml. Results: The FFF was 61% at 3 years and 45% at 5 years for the entire group. The FFF following RRP plus RT was 75% at 3 years and 57% at 5 years as compared to 56% at 3 years and 40% at 5 years for RRP without RT (p = 0.049). The FFF following RRP plus neoadjuvant hormonal therapy was 58% at 3 years and 40% at 5 years as compared to 60% at 3 years and 45% at 5 years following RRP without hormonal therapy (p = 0.3). In patients without seminal vesicle (SV) invasion, the FFF was 81% at 3 and 5 years for RRP plus RT as compared to 61% at 3 years and 50% at 5 years for RRP without RT (p = 0.01). In patients with SV invasion, the FFF was 61% at 3 years and 36% at 5 years for RRP plus RT as compared to 44% at 3 years and 23% at 5 years for RRP without RT (p = 0.23). The projected local control rate was 83% at 5 years for those with RRP alone as compared to 100% for RRP plus RT (p = 0.02). Survival at 5 years was projected to be 92% and was not significantly altered by the administration of adjuvant therapies. Conclusions: Postoperative RT was associated with significantly improved local control and FFF rates, especially in patients with tumors which did not involve the seminal vesicles

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

    International Nuclear Information System (INIS)

    Lee, Kyung Ja; Moon, Hye Seong; Kim, Seung Cheol; Kim, Chong Il; Ahn, Jung Ja

    2003-01-01

    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

  10. Retroperitoneal liposarcoma; The role of adjuvant radiation therapy and the prognostic factors

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hong Seok; Yu, Jeong Il; Lim, Do Hoon; Kim, Sung Joo [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2016-09-15

    To evaluate the benefit of adjuvant radiation therapy (RT) for retroperitoneal liposarcoma (RPLS) following gross tumor removal. We reviewed 77 patients with primary RPLS surgically treated between January 2000 and December 2013. Cases with gross residual disease were excluded. Tumor grade was evaluated according to the French Federation of Cancer Centers Sarcoma Group (FNCLCC) system. Adjuvant RT was delivered to 32 patients (42%) using external beam RT alone. Median follow-up time was 36 months (range, 5 to 169). Among 77 patients, 33 (43%) presented with well-differentiated, 31 (40%) with de-differentiated, 8 (10%) with myxoid/round and 4 (5%) with pleomorphic morphology. The RT group included less well-differentiated subtype than surgery group (28% vs. 53%). During follow up, 34 patients (44%) showed local recurrence. Local recurrence rate was lower in the RT group (38%) compared to the surgery group (49%). The 3-year local control rate (LC) was 55.6%, and the 3-year overall survival (OS) was 82.1%. Tumor histology and FNCLCC grade were significantly associated with local recurrence. There was no statistical significance of adding adjuvant RT in LC (p = 0.312). However, patients with tumor histology other than well-differentiated subtype showed marginally decreased local recurrence rate after adjuvant RT (3-year LC, RT 43.9% vs. no RT 35.3%; p = 0.087). RPLS patients receiving RT experienced less local recurrence. We suggest that the addition of adjuvant RT may be related to improvement of LCs, especially in patients with non-favorable histologic subtypes.

  11. 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.

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

    International Nuclear Information System (INIS)

    Pinkham, Mark B.; Foote, Matthew C.; Burmeister, Elizabeth; Thomas, Janine; Meakin, Janelle; Smithers, B. Mark; Burmeister, Bryan H.

    2013-01-01

    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

  13. [Benefits of music therapy as therapy no pharmacology and rehabilitation moderate dementia].

    Science.gov (United States)

    Jiménez-Palomares, María; Rodríguez-Mansilla, Juan; González-López-Arza, María Victoria; Rodríguez-Domínguez, María Trinidad; Prieto-Tato, Marta

    2013-01-01

    An in-depth review is presented the possible benefits of music therapy in relation to the cognitive and/or behavioural level of elderly patients with dementia. We have carried out a systematic review of randomized controlled trials, case-control and pilot studies published from January 2000 to January 2012 using the Cochrane Database of Systematic Reviews, MEDLINE, Dialnet and CSIC. We focused on comparison of music therapy as non-pharmacological therapy, in patients over 65 years of age with moderate dementia, with regular therapeutic and occupational treatment. Ten articles were selected based on the inclusion criteria. The analysis of the results suggest that music Therapy influences the elderly people with dementia in a positive way by improving levels of behavioural and cognitive functioning and social participation. Copyright © 2012 SEGG. Published by Elsevier Espana. All rights reserved.

  14. Early MRI changes in glioblastoma in the period between surgery and adjuvant therapy.

    Science.gov (United States)

    Farace, Paolo; Amelio, Dante; Ricciardi, Giuseppe K; Zoccatelli, Giada; Magon, Stefano; Pizzini, Francesca; Alessandrini, Franco; Sbarbati, Andrea; Amichetti, Maurizio; Beltramello, Alberto

    2013-01-01

    To investigate the increase in MRI contrast enhancement (CE) occurring in glioblastoma during the period between surgery and initiation of chemo-radiotherapy, thirty-seven patients with newly diagnosed glioblastoma were analyzed by early post-operative magnetic resonance (EPMR) imaging within three days of surgery and by pre-adjuvant magnetic resonance (PAMR) examination before adjuvant therapy. Areas of new CE were investigated by use of EPMR diffusion-weighted imaging and PAMR perfusion imaging (by arterial spin-labeling). PAMR was acquired, on average, 29.9 days later than EPMR (range 20-37 days). During this period an increased area of CE was observed for 17/37 patients. For 3/17 patients these regions were confined to areas of reduced EPMR diffusion, suggesting postsurgical infarct. For the other 14/17 patients, these areas suggested progression. For 11/17 patients the co-occurrence of hyperperfusion in PAMR perfusion suggested progression. PAMR perfusion and EPMR diffusion did not give consistent results for 3/17 patients for whom small new areas of CE were observed, presumably because of the poor spatial resolution of perfusion imaging. Before initiation of adjuvant therapy, areas of new CE of resected glioblastomas are frequently observed. Most of these suggest tumor progression, according to EPMR diffusion and PAMR perfusion criteria.

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

    International Nuclear Information System (INIS)

    Narang, Amol K; Haddock, Michael G; Donohue, John H; Schulick, Richard D; Wolfgang, Christopher L; Cameron, John L; Herman, Joseph M; Miller, Robert C; Hsu, Charles C; Bhatia, Sumita; Pawlik, Timothy M; Laheru, Dan; Hruban, Ralph H; Zhou, Jessica; Winter, Jordan M

    2011-01-01

    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. 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 <60 days of follow-up, metastatic disease at surgery, or insufficient pathologic data were excluded. The final combined study consisted of 186 patients (n = 104 Johns Hopkins, n = 82 Mayo). Most patients received 5-FU based chemoradiation with conformal radiation. Cox proportional hazards models were used for survival analysis. 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 < 0.001), and poor histological grade (RR = 1.69, p = 0.011). Patients who received adjuvant chemoradiation (n = 66) vs. surgery alone (n = 120) showed a higher rate of T3/T4 stage disease (57.6% vs. 30.8%, P < 0.001), lymph node involvement (72.7% vs. 30.0%, P < 0.001), and close or positive margins (4.6% vs. 0.0%, P = 0.019). Five year survival rates among node negative and node positive patients were 58.7% and 18.4% respectively. When compared with surgery alone, use of adjuvant chemoradiation improved survival among node positive patients (mOS 32.1 vs. 15.7 mos, 5 yr OS: 27.5% vs. 5.9%; RR = 0.47, P = 0.004). After adjusting for adverse prognostic factors on multivariate analysis, patients treated with adjuvant chemoradiation demonstrated a significant survival benefit (RR = 0.40, P < 0.001). Disease relapse occurred in 37.1% of all patients, most commonly metastatic

  16. Adjuvant postoperative radiation therapy for resectable rectal cancer

    International Nuclear Information System (INIS)

    Minsky, B.D.; Cohen, A.M.; Enker, W.E.; Kelsen, D.; Kemeny, N.; Sigurdson, E.

    1991-01-01

    Following potentially curative surgery for resectable adenocarcinoma of the rectum, the incidence of local failure is 15% to 35% in stages T 3 N 0 and T 1 N 1-2 and 45% to 65% in stages T 4 N 0 , T 3 N 1-2 , and T 4 N 1-2 . In order to determine the impact of pelvic radiation therapy±chemotherapy on local failure and survival, we present a prospective analysis of our results of 25 patients treated with this approach. The median follow-up was 30 months (range: 10 to 48 months). For the total patients group the 3-year actuarial survival was 74%. In order to more accurately analyze the patterns of failure, actuarial calculations were performed. The actuarial incidence of local failure as a component of failure was 17%. For patients with node positive disesse (T 1-4 N 1-2 ), the overall survival was 80%, and the actuarial incidence of local failure as a component of failure was 15%. Complications were acceptable and the incidence of small bowel obstruction requiring surgery was 8%. (author)

  17. N-feruloylserotonin in preventive combination therapy with methotrexate reduced inflammation in adjuvant arthritis

    Czech Academy of Sciences Publication Activity Database

    Kuncírová, V.; Poništ, S.; Mihalová, D.; Dráfi, F.; Nosáľ, R.; Acquaviva, A.; Gardi, C.; Harmatha, Juraj; Hrádková, I.; Bauerová, K.

    2014-01-01

    Roč. 28, č. 6 (2014), s. 616-626 ISSN 0767-3981 Institutional support: RVO:61388963 Keywords : arthritis * inflammation * oxidative stress * combination therapy * methotrexate * N-feruloylserotonin Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 2.121, year: 2014

  18. Association between adjuvant regional radiotherapy and cognitive function in breast cancer patients treated with conservation therapy

    International Nuclear Information System (INIS)

    Shibayama, Osamu; Yoshiuchi, Kazuhiro; Inagaki, Masatoshi; Matsuoka, Yutaka; Yoshikawa, Eisho; Sugawara, Yuriko; Akechi, Tatsuo; Wada, Noriaki; Imoto, Shigeru; Murakami, Koji; Ogawa, Asao; Akabayashi, Akira; Uchitomi, Yosuke

    2014-01-01

    Although protracted cognitive impairment has been reported to occur after radiotherapy even when such therapy is not directed to brain areas, the mechanism remains unclear. This study investigated whether breast cancer patients exposed to local radiotherapy showed lower cognitive function mediated by higher plasma interleukin (IL)-6 levels than those unexposed. We performed the Wechsler Memory Scale-Revised (WMS-R) and measured plasma IL-6 levels for 105 breast cancer surgical patients within 1 year after the initial therapy. The group differences in each of the indices of WMS-R were investigated between cancer patients exposed to adjuvant regional radiotherapy (n = 51) and those unexposed (n = 54) using analysis of covariance. We further investigated a mediation effect by plasma IL-6 levels on the relationship between radiotherapy and the indices of WMS-R using the bootstrapping method. The radiotherapy group showed significantly lower Immediate Verbal Memory Index and Delayed Recall Index (P = 0.001, P = 0.008, respectively). Radiotherapy exerted an indirect effect on the lower Delayed Recall Index of WMS-R through elevation of plasma IL-6 levels (bootstrap 95% confidence interval = −2.6626 to −0.0402). This study showed that breast cancer patients exposed to adjuvant regional radiotherapy in conservation therapy might have cognitive impairment even several months after their treatment. The relationship between the therapy and the cognitive impairment could be partially mediated by elevation of plasma IL-6 levels

  19. Adjuvant Endocrine Therapy in Breast Cancer: Evolving Paradigms in Premenopausal Women.

    Science.gov (United States)

    Rossi, Lorenzo; Pagani, Olivia

    2017-05-01

    In the last few years, new adjuvant endocrine treatment options have become available in young women with early breast cancer, such as the addition of ovarian function suppression to tamoxifen or aromatase inhibitors. Treatment duration has been also adapted in the latest guidelines based on the individual risk of recurrence. The oncologist is therefore challenged to precisely assess the risk of recurrence according to currently available predictive and prognostic factors in order to offer the most appropriate therapeutic option to the individual patient, considering also potential side effects, quality of life, pregnancy planning and patients' preferences. The adjuvant treatment planning should always be discussed and agreed in a multidisciplinary context. Tamoxifen remains the standard of care in low-risk patients or in case of intolerance to combined treatment with pharmacological ovarian function suppression or aromatase inhibitors. Combination treatment is indicated in intermediate high-risk disease. The patient should always be considered an active partner in the treatment decision process, to improve treatment motivation and adherence. Finally, the therapeutic choice should take into account drug availability and pharmacoeconomic issues, which unfortunately may prevent, in many low-income countries, the provision of such effective treatments.

  20. 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

  1. 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.

  2. The impact of adjuvant radiation therapy on survival in women with uterine carcinosarcoma

    International Nuclear Information System (INIS)

    Clayton Smith, D.; Kenneth Macdonald, O.; Gaffney, David K.

    2008-01-01

    Background and purpose: Uterine carcinosarcoma is an aggressive neoplasm and the benefit of adjuvant radiation therapy (RT) is unclear. This retrospective study analyzes the influence of RT on survival using a large population database. Materials and methods: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program of the US National Cancer Institute. Women with uterine carcinosarcoma who underwent primary surgery were eligible. Survival rates and multivariate analyses were performed by standard methods. Results: Of the 2461 women in the analysis, 890 received adjuvant RT. Five-year rates of overall survival were 41.5% and 33.2% (P < 0.001) and uterine-specific survival were 56.0% and 50.8% (P = 0.005), for women receiving RT compared to those who did not. Women with stages I-III disease experienced a benefit in overall survival (HR 0.87, P = 0.03) while women with stage IV disease experienced benefits in overall (HR 0.63, P < 0.001) and uterine-specific survival (HR 0.63, P = 0.004) with RT. Conclusions: RT predicted for improved overall and disease specific survival in women with uterine carcinosarcoma within the SEER database. The benefit in disease specific survival was restricted to stage IV disease. These benefits may indicate a role for adjuvant RT in future prospective trials in the treatment of uterine carcinosarcoma

  3. Efficacy of Turmeric as Adjuvant Therapy in Type 2 Diabetic Patients.

    Science.gov (United States)

    Maithili Karpaga Selvi, N; Sridhar, M G; Swaminathan, R P; Sripradha, R

    2015-04-01

    It is known that there is a significant interplay of insulin resistance, oxidative stress, dyslipidemia, and inflammation in type 2 diabetes mellitus (T2DM). The study was undertaken to investigate the effect of turmeric as an adjuvant to anti-diabetic therapy. Sixty diabetic subjects on metformin therapy were recruited and randomized into two groups (30 each). Group I received standard metformin treatment while group II was on standard metformin therapy with turmeric (2 g) supplements for 4 weeks. The biochemical parameters were assessed at the time of recruitment for study and after 4 weeks of treatment. Turmeric supplementation in metformin treated type 2 diabetic patient significantly decreased fasting glucose (95 ± 11.4 mg/dl, P Turmeric administered group showed reduction in lipid peroxidation, MDA (0.51 ± 0.11 µmol/l, P Turmeric also exhibited beneficial effects on dyslipidemia LDL cholesterol (113.2 ± 15.3 mg/dl, P Turmeric supplementation as an adjuvant to T2DM on metformin treatment had a beneficial effect on blood glucose, oxidative stress and inflammation.

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

    Science.gov (United States)

    Al-Tonbary, Youssef; Al-Haggar, Mohammad; EL-Ashry, Rasha; EL-Dakroory, Sahar; Azzam, Hanan; Fouda, Ashraf

    2009-01-01

    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-α (TNF-α), 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. PMID:19960046

  6. 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.

  7. Does adjuvant systemic therapy contribute to decrease of breast recurrence after breast-conserving surgery?

    International Nuclear Information System (INIS)

    Nishimura, Reiki; Matsuda, Masakazu; Okazaki, Shinji; Kai, K.; Hiyoshi, Y.

    2005-01-01

    Preventing breast recurrence after breast-conserving surgery is an important issue. The main factors contributing to breast recurrences are positive margins and absence of radiotherapy. In late years a standard adjuvant treatment is widely used in Japan. We examined whether these standard treatments contributed to reduction of a breast recurrence. By March 2003, 845 patients were treated by breast-conserving surgery, and the cases were divided into two groups by operation period; 426 cases until 1998 (the first half group) and 202 patients with follow-up periods more than 2 years (the latter group). There were much positive margins and patients with radiotherapy in a latter group in background factor. An endocrine therapy for estrogen receptor (ER) positive was performed in 68.1% in first half period, and in contrast 94.2% in the latter period, and chemotherapy was performed in 87% (mainly Epirubicin) for ER negative in the latter period, and 77% (mainly oral agent) in the first half period. There was a significant difference of breast recurrence-free survival between 2 groups; an early recurrence was seen in 19 cases (4.5%) in the first half period and 2 cases (1.0%) in the latter group. In particular the difference was significant in patients with absence of radiotherapy or negative ER. Multivariate analysis revealed that the operation time was a significant factor for breast recurrence. In conclusion, an apparent reduction of breast recurrence may be brought by a standard adjuvant therapy. (authors)

  8. Assessment of adjuvant ademetionine therapy for the bilirubin metabolism and target organ function of neonatal jaundice

    Directory of Open Access Journals (Sweden)

    Fang Xu

    2017-11-01

    Full Text Available Objective: To study the effect of adjuvant ademetionine (SAMe therapy on the bilirubin metabolism and target organ function of neonatal jaundice. Methods: A total of 68 children who were diagnosed with neonatal jaundice in Hubei Jianghan Oilfield General Hospital between March 2015 and April 2017 were selected as the research subjects and randomly divided into the SAMe group who received ademetionine combined with blue ray irradiation and the control group who received blue ray irradiation. The serum contents of bilirubin metabolism indexes and target organ injury markers before treatment as well as 3 d and 7 d after treatment. Results: 3 d and 7 d after treatment, serum TBIL, ALT, AST, GGT, TBA, CK-MB, cTnT, MYO, HBDH, NSE, S100B and GFAP levels of both groups were lower than those before treatment, and serum TBIL, ALT, AST, GGT, TBA, CK-MB, cTnT, MYO, HBDH, NSE, S100B and GFAP levels of SAMe group were lower than those of control group. Conclusion: Adjuvant ademetionine therapy can improve the bilirubin metabolism of neonatal jaundice and reduce the central nerve, myocardial and liver injury.

  9. Postoperative radiation therapy and adjuvant chemoimmunotherapy in breast cancer. Aspects of timing and immune competence

    Energy Technology Data Exchange (ETDEWEB)

    Klefstroem, P.; Nuortio, L.; Taskinen, E.

    The effects of radiation therapy and adjuvant chemoimmunotherapy on the immune competence of patients with breast cancer were investigated. The tests performed included intradermal tuberculin tests, T- and B-lymphocyte counts, and lymphocyte blast transformation tests; phytohemagglutinin (PHA), concanavalin A (ConA) and pokeweed mitogen (PMW) were used as mitogens. Enhancement in lymphocyte proliferative response to mitogenic stimulation by PHA and PMW was seen in patients after 3 courses of chemotherapy + levamisole, whereas irradiation given after chemotherapy caused long-lasting depression in response to PHA and PWM (not significant). T-lymphocyte counts were also lower after irradiation than after chemoimmunotherapy. Clinically, the 16 patients treated with radiation therapy after chemotherapy exhibited a higher recurrence rate than the 24 patients treated first by irradiation. Enhanced reactivity to tuberculin tests occurred generally in patients receiving a planned treatment including irradiation, chemotherapy (5-fluorouracil, doxorubicin, cyclophosphamide) and levamisole. Enhancement of reactivity was seen more often in patients who had not relapsed.

  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. Bleomycin as adjuvant in radiation therapy of advanced squamous cell carcinoma in head and neck

    Energy Technology Data Exchange (ETDEWEB)

    Rygaard, J [Koepenhavn Amts. Sygehus, Herlev (Denmark). Dept. of oncology and Radiotherapy; Hansen, H S [Radium Centre, Copenhagen (Denmark)

    1979-09-01

    Since 1969, Bleomycin (BLM) has been used in three different ways at the Radium Centre in Copenhagen. First BLM given as the sole treatment led to complete regressions in 12% of 138 patients. Secondly BLM was used as simultaneous adjuvant in radiation therapy for 86 previously untreated patients, but 66% developed mucositis which disrupted the treatment. In a third period BLM was therefore combined sequentially with radiation, administered for 2 weeks prior to radiation therapy to 142 patients. The tumour shrinkage achieved with preirradiation BLM was very pronounced in 38 % of cases. 101 patients with T3 tumours have been observed for a minimum of 3 years. The prognostic value of the degree of shrinkage achieved with preirradiation BLM treatment is discussed.

  12. Acute treatment-related diarrhea during postoperative adjuvant therapy for high-risk rectal carcinoma

    International Nuclear Information System (INIS)

    Miller, Robert C.; Martenson, James A.; Sargent, Daniel J.; Kahn, Michael J.; Krook, James E.

    1998-01-01

    Purpose: The combination of pelvic radiotherapy and 5-fluorouracil-based chemotherapy is associated with an increase in acute gastrointestinal toxicity during rectal adjuvant therapy, most notably an increased incidence of diarrhea. Previous randomized, prospective studies have limited their analysis to presenting rates of severe and life-threatening diarrhea (Grade 3 or greater), and few data are available detailing the extent of mild to moderate diarrhea. To provide baseline data for future studies, we conducted a detailed analysis of diarrhea from a prior clinical trial of adjuvant therapy for rectal cancer. Methods and Materials: In a multiinstitutional clinical trial, 204 eligible patients with rectal carcinoma that either was deeply invasive (T3-T4) or involved regional lymph nodes were randomized to receive either postoperative pelvic radiotherapy alone (45 to 50.4 Gy) or pelvic radiotherapy and bolus 5-fluorouracil-based chemotherapy. Toxicity was assessed prospectively. Results: For the 99 eligible patients who received pelvic radiotherapy alone, rates of Grades 0, 1, 2, 3, and 4 diarrhea during treatment were 59, 20, 17, 4, and 0%, respectively. For the 96 eligible patients who received radiotherapy and 5-fluorouracil, the overall rates of grades 0, 1, 2, 3, and 4 diarrhea were 21, 34, 23, 20, and 2%, respectively. The increased rates of diarrhea during adjuvant rectal therapy were manifested across all toxicity levels for patients receiving chemotherapy and pelvic radiotherapy. Of primary clinical importance is the substantial increase in severe or life-threatening diarrhea (Grade 3 or more) (22 vs. 4%, p = 0.001) Additionally, increased rates of any diarrhea and also severe or life-threatening diarrhea were observed in patients who had a low anterior resection compared with those who had an abdominoperineal resection (p < 0.001 and p = 0.006, respectively). Conclusion: These results will be of value as a baseline for investigators who want to use

  13. Pharmacological therapy for analgesia and sedation in the newborn.

    Science.gov (United States)

    Anand, K J S; Hall, R W

    2006-11-01

    Rapid advances have been made in the use of pharmacological analgesia and sedation for newborns requiring neonatal intensive care. Practical considerations for the use of systemic analgesics (opioids, non-steroidal anti-inflammatory agents, other drugs), local and topical anaesthetics, and sedative or anaesthetic agents (benzodiazepines, barbiturates, other drugs) are summarised using an evidence-based medicine approach, while avoiding mention of the underlying basic physiology or pharmacology. These developments have inspired more humane approaches to neonatal intensive care. Despite these advances, little is known about the clinical effectiveness, immediate toxicity, effects on special patient populations, or long-term effects after neonatal exposure to analgesics or sedatives. The desired or adverse effects of drug combinations, interactions with non-pharmacological interventions or use for specific conditions also remain unknown. Despite the huge gaps in our knowledge, preliminary evidence for the use of neonatal analgesia and sedation is available, but must be combined with a clear definition of clinical goals, continuous physiological monitoring, evaluation of side effects or tolerance, and consideration of long-term clinical outcomes.

  14. 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.

  15. Adjuvant and Salvage Radiation Therapy After Prostatectomy: American Society for Radiation Oncology/American Urological Association Guidelines

    International Nuclear Information System (INIS)

    Valicenti, Richard K.; Thompson, Ian; Albertsen, Peter; Davis, Brian J.; Goldenberg, S. Larry; Wolf, J. Stuart; Sartor, Oliver; Klein, Eric; Hahn, Carol; Michalski, Jeff; Roach, Mack; Faraday, Martha M.

    2013-01-01

    Purpose: The purpose of this guideline was to provide a clinical framework for the use of radiation therapy after radical prostatectomy as adjuvant or salvage therapy. Methods and Materials: A systematic literature review using PubMed, Embase, and Cochrane database was conducted to identify peer-reviewed publications relevant to the use of radiation therapy after prostatectomy. The review yielded 294 articles; these publications were used to create the evidence-based guideline statements. Additional guidance is provided as Clinical Principles when insufficient evidence existed. Results: Guideline statements are provided for patient counseling, use of radiation therapy in the adjuvant and salvage contexts, defining biochemical recurrence, and conducting a restaging evaluation. Conclusions: Physicians should offer adjuvant radiation therapy to patients with adverse pathologic findings at prostatectomy (ie, seminal vesicle invastion, positive surgical margins, extraprostatic extension) and salvage radiation therapy to patients with prostate-specific antigen (PSA) or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiation therapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiation therapy as well as the potential benefits of preventing recurrence. The decision to administer radiation therapy should be made by the patient and the multidisciplinary treatment team with full consideration of the patient's history, values, preferences, quality of life, and functional status. The American Society for Radiation Oncology and American Urological Association websites show this guideline in its entirety, including the full literature review

  16. [Effectiveness of occupational therapy and other non-pharmacological therapies in cognitive impairment and Alzheimer's disease].

    Science.gov (United States)

    Matilla-Mora, Rosa; Martínez-Piédrola, Rosa María; Fernández Huete, Javier

    A review is presented on the existing knowledge about the usefulness of the occupational therapy in the non-pharmacological treatment of Alzheimer's disease. After conducting a literature search of the period 2010-2015, 25 articles that met the inclusion criteria were selected. The evidence obtained showed the efficiency and effectiveness of OT in delaying the progression of various disorders, especially when structured home OT programs are used. These programs should include aerobic and strengthening, sensory stimulation, and cognitive and memory training exercises based on learning without mistakes. These have shown benefits in the performance of activities of daily living, cognitive and emotional functioning. The importance is stressed of the combined and individual household level intervention and caregiver education. Finally, the need for more studies on the effectiveness of long-term sensory stimulation is highlighted. Copyright © 2015 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. 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

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

    International Nuclear Information System (INIS)

    Sher, David J.; Thotakura, Vijaya; Balboni, Tracy A.; Norris, Charles M.; Haddad, Robert I.; Posner, Marshall R.; Lorch, Jochen; Goguen, Laura A.; Annino, Donald J.; Tishler, Roy B.

    2011-01-01

    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

  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

    BACKGROUND: 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 w...

  20. Trade-off preferences regarding adjuvant endocrine therapy among women with estrogen receptor-positive breast cancer.

    NARCIS (Netherlands)

    Wouters, H.; Maatman, G.A.; Dijk, L. van; Bouvy, M.L.; Vree, R.; Geffen, E.C.G. van; Nortier, J.W.; Stiggelbout, A.M.

    2013-01-01

    Background: There is substantial nonadherence to effective adjuvant endocrine therapy for breast cancer prevention. We therefore examined patients' trade-offs between the efficacy, side-effects, and regimen duration, and whether trade-offs predicted nonadherence. Patients and methods: Trade-offs

  1. Trade-off preferences regarding adjuvant endocrine therapy among women with estrogen receptor-positive breast cancer

    NARCIS (Netherlands)

    Wouters, H; Maatman, G A; Van Dijk, L; Bouvy, M L; Vree, R; Van Geffen, E C G; Nortier, J W; Stiggelbout, A M

    BACKGROUND: There is substantial nonadherence to effective adjuvant endocrine therapy for breast cancer prevention. We therefore examined patients' trade-offs between the efficacy, side-effects, and regimen duration, and whether trade-offs predicted nonadherence. PATIENTS AND METHODS: Trade-offs

  2. Immunoendocrine Interactions during HIV-TB Coinfection: Implications for the Design of New Adjuvant Therapies

    Directory of Open Access Journals (Sweden)

    Guadalupe Veronica Suarez

    2015-01-01

    Full Text Available Worldwide, around 14 million individuals are coinfected with both tuberculosis (TB and human immunodeficiency virus (HIV. In coinfected individuals, both pathogens weaken immunological system synergistically through mechanisms that are not fully understood. During both HIV and TB infections, there is a chronic state of inflammation associated to dramatic changes in immune cytokine and endocrine hormone levels. Despite this, the relevance of immunoendocrine interaction on both the orchestration of an effective immune response against both pathogens and the control of the chronic inflammation induced during HIV, TB, or both infections is still controversial. The present study reviews immunoendocrine interactions occurring during HIV and TB infections. We also expose our own findings on immunoendocrine cross talk in HIV-TB coinfection. Finally, we evaluate the use of adrenal hormones and their derivatives in immune-therapy and discuss the use of some of these compounds like the adjuvant for the prevention and treatment of TB in HIV patients.

  3. Selective Thrombolysis in Acute Deep Vein Thrombosis: Evaluation of Adjuvant Therapy In Vivo

    International Nuclear Information System (INIS)

    Roy, Sumit; Brosstad, Frank; Sakariassen, Kjell S.

    1999-01-01

    Purpose: To evaluate in a porcine model of acute deep vein thrombosis (DVT) the efficacy of dalteparin and antithrombin with respect to heparin for local adjuvant therapy during selective thrombolysis, and the utility of nitroglycerin and iloprost as heparin supplements. Methods: DVT was induced in both hind limbs using a previously described technique (n = 20). Thirty minutes later, the animal was heparinized (2500 IU IV), and bilateral sequestrated thrombolysis was performed using 8 mg alteplase: both external iliac veins were endoluminally occluded with Swan-Ganz catheters, and a multi-sideport infusion wire coaxially introduced through each catheter and advanced into the ipsilateral popliteal vein. In the control limbs, tissue plasminogen activator (tPA) 8 mg was injected as 0.8-ml boluses at 3-min intervals for 2 hr as a 0.25-mg/ml solution containing heparin 50 IU/ml (n 20). On the contralateral side, heparin was substituted with either dalteparin 50 IU/ml (n = 5) or antithrombin 12.5 IU/ml (n = 5), or supplemented with either nitroglycerin 0.075 mg/ml (n = 5) or iloprost (150 ng/ml) (n = 5). Blood samples were taken at predetermined intervals to measure the activated partial thromboplastin time (aPTT), prothrombin time (PT), and fibrinogen concentration. At autopsy, the thrombus mass in the iliofemoral veins was measured, and the extent of residual thrombosis in the venous tributaries graded at four sites. Results: Bilateral thrombolysis was successfully completed in all animals. The median thrombus mass in the iliofemoral veins after thrombolysis was 0.48 g (range 0.06-1.58 g), 0.95 g (0.59-1.29 g), 0.74 g (0.52-0.96 g), and 0.29 g (0.0-0.77 g) for dalteparin, antithrombin, iloprost, and nitroglycerin respectively, as compared with 0.53 g (0.18-0.88 g) (p = 0.69), 0.97 g (0.46-1.15 g) (p = 0.69), 0.53 g (0.48-1.10 g) (p = 0.69), and 0.18 g (0.13-1.04 g) (p = 0.5) for the respective controls. Likewise, the severity of residual thrombosis in the venous

  4. 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.

  5. 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.

  6. Mapping the Decision-Making Process for Adjuvant Endocrine Therapy for Breast Cancer: The Role of Decisional Resolve.

    Science.gov (United States)

    Beryl, Louise L; Rendle, Katharine A S; Halley, Meghan C; Gillespie, Katherine A; May, Suepattra G; Glover, Jennifer; Yu, Peter; Chattopadhyay, Runi; Frosch, Dominick L

    2017-01-01

    Studies show adjuvant endocrine therapy increases survival and decreases risk of breast cancer recurrence for hormone receptor-positive tumors. Yet studies also suggest that adherence rates among women taking this therapy may be as low as 50% owing largely to adverse side effects. Despite these rates, research on longitudinal patient decision making regarding this therapy is scant. We sought to map the decision-making process for women considering and initiating adjuvant endocrine therapy, paying particular attention to patterns of uncertainty and decisional change over time. A longitudinal series of semistructured interviews conducted at a multispecialty health care organization in Northern California with 35 newly diagnosed patients eligible for adjuvant endocrine therapy were analyzed. Analysis led to the identification and indexing of 3 new decision-making constructs-decisional phase, decisional direction, and decisional resolve-which were then organized using a visual matrix and examined for patterns characterizing the decision-making process. Our data reveal that most patients do not make a single, discrete decision to take or not take hormone therapy but rather traverse multiple decisional states, characterized by 1) phase, 2) direction, and 3) strength of resolve. Our analysis tracks these decisional states longitudinally using a grayscale-coded matrix. Our data show that decisional resolve wavers not just when considering therapy, as the existing concept of decisional conflict suggests, but even after initiating it, which may signal future decisions to forgo therapy. Adjuvant endocrine therapy, like other chronic care decisions, has a longer decision-making process and implementation period. Thus, theoretical, empirical, and clinical approaches should consider further exploring the new concept and measurement of decisional resolve, as it may help to improve subsequent medication adherence. © The Author(s) 2016.

  7. Pharmacological Therapies for Autism Spectrum Disorder: A Review

    OpenAIRE

    LeClerc, Sheena; Easley, Deidra

    2015-01-01

    Medications are often added to behavioral therapy to help patients with autism spectrum disorder function successfully. This review discusses approved and off-label pharmacotherapeutic options for the various symptoms of the disorder.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  9. Adherence to adjuvant endocrine therapy: is it a factor for ethnic differences in breast cancer outcomes in New Zealand?

    Science.gov (United States)

    Seneviratne, Sanjeewa; Campbell, Ian; Scott, Nina; Kuper-Hommel, Marion; Kim, Boa; Pillai, Avinesh; Lawrenson, Ross

    2015-02-01

    Despite the benefits of adjuvant endocrine therapy for hormone receptor positive breast cancer, many women are non-adherent or discontinue endocrine treatment early. We studied differences in adherence to adjuvant endocrine therapy by ethnicity in a cohort of New Zealand women with breast cancer and its impact on breast cancer outcomes. We analysed data on women (n = 1149) with newly diagnosed hormone receptor positive, non-metastatic, invasive breast cancer who were treated with adjuvant endocrine therapy in the Waikato during 2005-2011. Linked data from the Waikato Breast Cancer Registry and National Pharmaceutical Database were examined to identify differences by ethnicity in adherence to adjuvant endocrine therapy and the effect of sub-optimal adherence on cancer recurrence and mortality. Overall, a high level of adherence of ≥80% was observed among 70.4% of women, which declined from 76.8% to 59.3% from the first to fifth year of treatment. Māori women were significantly more likely to be sub-optimally adherent (breast cancer mortality (HR = 1.77, 95% CI 1.05-2.99) and recurrence (HR = 2.14, 95% CI 1.46-3.14). Sub-optimal adherence to adjuvant endocrine therapy was a likely contributor for breast cancer mortality inequity between Māori and European women, and highlights the need for future research to identify effective ways to increase adherence in Māori women. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Adjuvant external beam radiation therapy with concurrent chemotherapy in the management of gallbladder carcinoma

    International Nuclear Information System (INIS)

    Kresl, John J.; Schild, Steven E.; Henning, George T.; Gunderson, Leonard L.; Donohue, John; Pitot, Henry; Haddock, Michael G.; Nagorney, David

    2002-01-01

    Purpose: This study was performed to evaluate the outcome of patients with gallbladder cancer who received postoperative concurrent chemotherapy and radiation therapy. Methods and Materials: Curative resection followed by adjuvant combined modality therapy with external beam radiation therapy (EBRT) and chemotherapy was attempted in 21 consecutive gallbladder carcinoma (GBC) patients at the Mayo Clinic from 1985 through 1997. All patients received concurrent 5-fluorouracil during EBRT. EBRT fields encompassed the tumor bed and regional lymph nodes (median dose of 54 Gy in 1.8-2.0-Gy fractions). One patient received 15 Gy intraoperatively after EBRT. A retrospective analysis was performed for the end points of local control, distant failure, and overall survival. Results: After maximal resection, 12 patients had no residual disease on pathologic evaluation, 5 had microscopic residual disease, and 4 had gross residual disease. One patient had Stage I disease, and 20 had Stage III-IV disease. With median follow-up of 5 years (range: 2.6-11.5 years), 5-year survival for the entire cohort was 33%. The 5-year survival rate of patients with Stage I-III disease was 65% vs. 0% for those with Stage IV disease (p 54 Gy (microscopic residual, 3 patients; gross residual, 1 patient; negative but narrow margins, 2 patients) vs. 65% for the 15 who received a lower dose (3, gross residual; 2, microresidual; 10, negative margins). Conclusion: Patients with completely resected (negative margins) GBC followed by adjuvant EBRT plus 5-fluorouracil chemotherapy had a relatively favorable prognosis, with a 5-year survival rate of 64%. These results seem to be superior to historical surgical controls from the Mayo Clinic and other institutions, which report 5-year survival rates of approximately 33% with complete resection alone. Both tumor stage and extent of resection seemed to influence survival and local control. More aggressive measures using current cancer therapies and integration

  11. Dexamethasone as adjuvant therapy in the treatment of invasive meningococcal diseases.

    Science.gov (United States)

    Tolaj, Ilir; Dreshaj, Shemsedin; Qehaja, Emine; Tolaj, Jasmina; Doda-Ejupi, Teuta; Mehmeti, Murat

    2010-01-01

    With this study we want to evaluate the role of dexamethasone adjuvant treatment in different clinical forms of invasive meningococcal diseases. WORK METHODS: This was a randomized, open label trial that was conducted in 147 individuals with meningococcal sepsis. All of the cases have been divided in two groups: (1) Cases with meningococcal disease and CNS infection, and (2) Cases with meningococcal disease and no affection of the CNS. Cases from both groups were treated with dexamethasone, 0.15 mg/kg, every 6 h, for 4 (four) days, as adjuvant therapy. Cases which were not treated with dexamethasone were used as control group. From overall number of cases, in 130 of them, the meningococcal disease was accompanied with meningitis; in other 17 cases only signs of sepsis were present. In both clinical forms, the dexamethasone was used in 92 cases. The higher mortality rate is registered among the cases without meningitis, 17.65%, compared with 6.92% which is registered among cases with meningitis. The overall mortality rate among all cases was 8.2%. The significant difference was recorded only on CSF sugar level between two groups (treated or not with dexamethasone) on the day 1-4 of the hospitalization. Our epidemiological data are in correlation with data from other epidemiological studies. Most of the cases 69.4%, were more than 12 hours sick at home before the hospitalization, 7.5 % of cases were hospitalized within 12 hours from the onset of the diseases, while 23.1% of cases data are missing. This is in correlation with similar data from other studies. Dexamethasone has a limited effect on outcome of the invasive meningococcal disease. Dexamethasone had some effect only during the days of administration in cases with clinical form of sepsis with meningitis, by normalizing the values of CSF sugar earlier.

  12. Triacetin-based acetate supplementation as a chemotherapeutic adjuvant therapy in glioma.

    Science.gov (United States)

    Tsen, Andrew R; Long, Patrick M; Driscoll, Heather E; Davies, Matthew T; Teasdale, Benjamin A; Penar, Paul L; Pendlebury, William W; Spees, Jeffrey L; Lawler, Sean E; Viapiano, Mariano S; Jaworski, Diane M

    2014-03-15

    Cancer is associated with epigenetic (i.e., histone hypoacetylation) and metabolic (i.e., aerobic glycolysis) alterations. Levels of N-acetyl-L-aspartate (NAA), the primary storage form of acetate in the brain, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis to generate acetate, are reduced in glioma; yet, few studies have investigated acetate as a potential therapeutic agent. This preclinical study sought to test the efficacy of the food additive Triacetin (glyceryl triacetate, GTA) as a novel therapy to increase acetate bioavailability in glioma cells. The growth-inhibitory effects of GTA, compared to the histone deacetylase inhibitor Vorinostat (SAHA), were assessed in established human glioma cell lines (HOG and Hs683 oligodendroglioma, U87 and U251 glioblastoma) and primary tumor-derived glioma stem-like cells (GSCs), relative to an oligodendrocyte progenitor line (Oli-Neu), normal astrocytes, and neural stem cells (NSCs) in vitro. GTA was also tested as a chemotherapeutic adjuvant with temozolomide (TMZ) in orthotopically grafted GSCs. GTA-induced cytostatic growth arrest in vitro comparable to Vorinostat, but, unlike Vorinostat, GTA did not alter astrocyte growth and promoted NSC expansion. GTA alone increased survival of mice engrafted with glioblastoma GSCs and potentiated TMZ to extend survival longer than TMZ alone. GTA was most effective on GSCs with a mesenchymal cell phenotype. Given that GTA has been chronically administered safely to infants with Canavan disease, a leukodystrophy due to ASPA mutation, GTA-mediated acetate supplementation may provide a novel, safe chemotherapeutic adjuvant to reduce the growth of glioma tumors, most notably the more rapidly proliferating, glycolytic and hypoacetylated mesenchymal glioma tumors. © 2013 UICC.

  13. Hyperbaric Oxygen Therapy as an Adjuvant Therapy for Comprehensive Treatment of Fournier's Gangrene.

    Science.gov (United States)

    Li, Chao; Zhou, Xu; Liu, Long-Fei; Qi, Fan; Chen, Jin-Bo; Zu, Xiong-Bing

    2015-01-01

    To compare simple conventional treatment with the addition of hyperbaric oxygen therapy (HBOT) to conventional therapies in the treatment of Fournier's gangrene (FG). A retrospective study of clinical data was performed by reviewing 28 cases of FG from January 2004 to December 2013 at Xiangya Hospital, Central South University. Among them, 12 patients were treated with the conventional therapy (non-HBOT group) and the other 16 cases were combined with hyperbaric oxygen therapy besides conventional therapy (HBOT group). All patients were followed up for 2 months to assess the therapeutic effect. The analyzed data included age, Fournier gangrene severity index (FGSI) score, number of surgical debridement, indwelling drainage tube time, length of stay (LOS), effective time, and curative time. The mortality rate was lower in the HBOT group at 12.5% (2/16) compared to the non-HBOT group, which was 33.3% (4/12). The difference in the number of surgical debridement, indwelling drainage tube time, and curative time between were significantly lower in the HBOT group compared to the non-HBOT group. Our preliminary research suggests that the effect of combining hyperbaric oxygen therapy with conventional therapy offers considerable advantage in the management of Fournier's gangrene. Multicenter studies with a larger sample size are required to confirm these observations. © 2015 S. Karger AG, Basel.

  14. 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.

  15. 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.)

  16. [Risk management of coronary artery disease--pharmacological therapy].

    Science.gov (United States)

    Hofmann, Thomas

    2004-06-01

    Treatment of coronary artery disease primarily aims at reducing the severity and frequency of cardiac symptoms and improving prognosis. Both goals can be achieved by the administration of beta-receptor blockers, which are now used as first-line therapy in these patients. Calcium channel blockers or nitrates should be given in the event of contraindications or severe intolerance to beta-receptor blocking therapy. Only long-acting calcium channel blockers should be used in this setting. Another indication for additional treatment with calcium channel blockers and nitrates is given when the efficacy of beta-blocker therapy is not sufficient to relieve symptoms. Nitroglycerin and nitrates are the drugs of choice for the treatment of the acute angina pectoris attack. Calcium channel blockers are used as first-line treatment in patients with vasospastic angina. In patients with syndrome X, nitrates as well as calcium channel blockers or beta-receptor blockers can be administered. In the absence of contraindications, every patient with coronary artery disease should be given aspirin. A daily dosage of 75 to 150 mg is sufficient to reduce the rate of future cardiac events. Clopidogrel should be given in every patient with intolerance or contraindications for aspirin. Increased plasma homocystein levels seem to be a risk factor for coronary artery disease. Homocystein levels can be reduced by dietary means as well as supplementation of folic acid or vitamin B complex. There is no evidence from controlled randomised studies that a decrease of homocystein is beneficial for the prognosis of patients with coronary artery disease.

  17. The endocrine pharmacology of testosterone therapy in men

    Science.gov (United States)

    Oettel, Michael

    The review starts off by outlining the history of the discovery of the male sex hormone testosterone and the historical background to the various, often dubious, approaches to the treatment of age-related endocrine disorders in older men. A discussion of congenital androgen deficiency in young men is followed by methods of diagnosing hypogonadism in older men. Among therapeutic options, the alternatives to direct testosterone replacement are discussed, although none of them have proved to be particularly successful in clinical practice. For testosterone replacement itself, various routes of administration and pharmaceutical formulations are now available, facilitating good monitoring and individualized therapy.

  18. 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.

  19. Adjuvant Hormone Therapy May Improve Survival in Epithelial Ovarian Cancer: Results of the AHT Randomized Trial.

    Science.gov (United States)

    Eeles, Rosalind A; Morden, James P; Gore, Martin; Mansi, Janine; Glees, John; Wenczl, Miklos; Williams, Christopher; Kitchener, Henry; Osborne, Richard; Guthrie, David; Harper, Peter; Bliss, Judith M

    2015-12-10

    To assess the effects of adjuvant hormone therapy (AHT) on survival and disease outcome in women with epithelial ovarian cancer. Participants were premenopausal and postmenopausal women who had been diagnosed with epithelial ovarian cancer (any International Federation of Gynecology and Obstetrics stage) 9 or fewer months previously. Ineligible patients included those with deliberately preserved ovarian function, with a history of a hormone-dependent malignancy, or with any contraindications to hormone-replacement therapy. Patients were centrally randomly assigned in a 1:1 ratio to either AHT for 5 years after random assignment or no AHT (control). Main outcome measures were overall survival (OS), defined as time from random assignment to death (any cause), and relapse-free survival, defined as time from random assignment to relapse or death (any cause). Patients who continued, alive and relapse free, were censored at their last known follow-up. A total of 150 patients (n = 75, AHT; n = 75, control) were randomly assigned from 1990 to 1995 from 19 centers in the United Kingdom, Spain, and Hungary; all patients were included in intention-to-treat analyses. The median follow-up in alive patients is currently 19.1 years. Of the 75 patients with AHT, 53 (71%) have died compared with 68 (91%) of 75 patients in the control group. OS was significantly improved in patients who were receiving AHT (hazard ratio, 0.63; 95% CI, 0.44 to 0.90; P = .011). A similar effect was seen for relapse-free survival (hazard ratio, 0.67; 95% CI, 0.47 to 0.97; P = .032). Effects remained after adjustment for known prognostic factors. These results show that women who have severe menopausal symptoms after ovarian cancer treatment can safely take hormone-replacement therapy, and this may, in fact, infer benefits in terms of OS in addition to known advantages in terms of quality of life. © 2015 by American Society of Clinical Oncology.

  20. An Archaeosome-Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination Significantly Enhances Protection from Murine Melanoma

    Directory of Open Access Journals (Sweden)

    Felicity C. Stark

    2017-10-01

    Full Text Available Archaeosomes constitute archaeal lipid vesicle vaccine adjuvants that evoke a strong CD8+ T cell response to antigenic cargo. Therapeutic treatment of murine B16-ovalbumin (B16-OVA melanoma with archaeosome-OVA eliminates small subcutaneous solid tumors; however, they eventually resurge despite an increased frequency of circulating and tumor infiltrating OVA-CD8+ T cells. Herein, a number of different approaches were evaluated to improve responses, including dose number, interval, and the combination of vaccine with checkpoint inhibitors. Firstly, we found that tumor protection could not be enhanced by repetitive and/or delayed boosting to maximize the CD8+ T cell number and/or phenotype. The in vivo cytotoxicity of vaccine-induced OVA-CD8+ T cells was impaired in tumor-bearing mice. Additionally, tumor-infiltrating OVA-CD8+ T cells had an increased expression of programmed cell death protein-1 (PD-1 compared to other organ compartments, suggesting impaired function. Combination therapy of tumor-bearing mice with the vaccine archaeosome-OVA, and α-CTLA-4 administered concurrently as well as α-PD-1 and an α-PD-L1 antibody administered starting 9 days after tumor challenge given on a Q3Dx4 schedule (days 9, 12, 15 and 18, significantly enhanced survival. Following multi-combination therapy ~70% of mice had rapid tumor recession, with no detectable tumor mass after >80 days in comparison to a median survival of 17–22 days for untreated or experimental groups receiving single therapies. Overall, archaeosomes offer a powerful platform for delivering cancer antigens when used in combination with checkpoint inhibitor immunotherapies.

  1. Pharmacologic Therapy in Men's Health: Hypogonadism, Erectile Dysfunction, and Benign Prostatic Hyperplasia.

    Science.gov (United States)

    Berkseth, Kathryn E; Thirumalai, Arthi; Amory, John K

    2016-07-01

    This article reviews current pharmacologic treatment options for 3 common men's health concerns: hypogonadism, erectile dysfunction (ED), and benign prostatic hyperplasia (BPH). Specific topics addressed include: management of male hypogonadism using testosterone replacement therapy, use of oral phosphodiesterase inhibitors as first-line therapy for men with ED and the utility of intraurethral and intrapenile alprostadil injections for patients who do not respond to oral medications, and the role of alpha1-adrenergic antagonists, 5-alpha-reductase inhibitors, anticholinergic agents, and herbal therapies in the management of BPH. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Does adjuvant therapy improve overall survival for stage IA/B pancreatic adenocarcinoma?

    Science.gov (United States)

    Ostapoff, Katherine T; Gabriel, Emmanuel; Attwood, Kristopher; Kuvshinoff, Boris W; Nurkin, Steven J; Hochwald, Steven N

    2017-07-01

    Current guidelines recommend adjuvant chemotherapy for resected pancreatic adenocarcinoma (PDAC). However, no studies have addressed its survival benefit for stage I patients as they comprise IA or IB PDAC were identified. Median OS was 60.3 months (mo) for stage IA and 36.9 mo for IB. 45.5% received adjuvant chemotherapy; 19.9% received adjuvant chemoradiation. There was OS benefit for both stage IA/IB patients with adjuvant chemotherapy (HR = 0.73 and 0.76 for IA and IB, respectively, p = 0.002 and IA disease (n = 1,477, 37.8%), age ≥70 (p < 0.001), higher grade (p < 0.001), ≤10 lymph nodes examined (p = 0.008), positive margins (p < 0.001), and receipt of adjuvant chemoradiation (p = 0.002) were associated with worse OS. For stage IB patients (n = 2,432, 62.2%), similar associations were observed with the exception of adjuvant chemoradiation whereby there was no significant association (p = 0.35). Adjuvant chemotherapy was associated with an OS benefit for patients with stage I PDAC; adjuvant chemoradiation was either of no benefit or associated with worse OS. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

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

    NARCIS (Netherlands)

    Visser, Annemiek; van de Ven, Eline M. W.; Ruczynski, Larissa I. A.; Blaisse, Reinoud J. B.; van Halteren, Henk K.; Aben, Katja; van Laarhoven, Hanneke W. M.

    2016-01-01

    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 trastuzumab treatment

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

    OpenAIRE

    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 attent...

  5. 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.

  6. Sibutramine as an adjuvant therapy in adolescents suffering from morbid obesity.

    Science.gov (United States)

    Reisler, Gad; Tauber, Tzvia; Afriat, Rachel; Bortnik, Oxana; Goldman, Michael

    2006-01-01

    The prevalence of morbid obesity is increasing rapidly. Weight reduction is very difficult using diet restriction and physical activity alone. Sibutramine has been shown to be effective and safe as an adjuvant therapy to diet restrictions. To describe our experience using sibutramine in weight reduction treatment of adolescents suffering from morbid obesity. The study group comprised 20 young persons (13 females, mean age 15 years 4 months, range 13-18 years) with morbid obesity (body mass index above the 95th percentile for age and/or > or =30 kg/m2) who were treated with sibutramine 10 mg once a day for 1 year. Mean BMI was 40 +/- 5.6 kg/m2 (range 30.1 - 49.5 kg/m2) at the beginning of treatment. Most patients showed an early weight reduction to mean BMI 39.3 +/- 4.9 and 35.9 +/- 5.7 at 3 and 6 months respectively, but stopped losing weight over the next 6 months. During the follow-up period 17 patients discontinued the treatment. The main reason for dropout was the slow rate of weight reduction after 6 months. Patients suffering from concomitant disorders (severe asthma, hypertension, sleep obstructive apnea) showed improvement after weight reduction. Adverse reactions from the treatment were transient, mild and well tolerated. Sibutramine may help in achieving weight reduction for a short period and in improving concomitant health problems, however its long-term effect is limited.

  7. 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.

  8. 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.

  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. PMID:25460731

  10. Pharmacologic Management of Type 2 Diabetes Mellitus: Available Therapies.

    Science.gov (United States)

    Thrasher, James

    2017-06-01

    Choices for the treatment of type 2 diabetes mellitus (T2DM) have multiplied as our understanding of the underlying pathophysiologic defects has evolved. Treatment should target multiple defects in T2DM and follow a patient-centered approach that considers factors beyond glycemic control, including cardiovascular risk reduction. The American Association of Clinical Endocrinologists/American College of Endocrinology and the American Diabetes Association recommend an initial approach consisting of lifestyle changes and monotherapy, preferably with metformin. Therapy choices are guided by glycemic efficacy, safety profiles, particularly effects on weight and hypoglycemia risk, tolerability, patient comorbidities, route of administration, patient preference, and cost. Balancing management of hyperglycemia with the risk of hypoglycemia and consideration of the effects of pharmacotherapy on weight figure prominently in US-based T2DM recommendations, whereas less emphasis has been placed on the ability of specific medications to affect cardiovascular outcomes. This is likely because, until recently, specific glucose-lowering agents have not been shown to affect cardiorenal outcomes. The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME), the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, and the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes 6 (SUSTAIN-6) recently showed a reduction in overall cardiovascular risk with empagliflozin, liraglutide, and semaglutide treatment, respectively. Moreover, empagliflozin has become the first glucose-lowering agent indicated to reduce the risk of cardiovascular death in adults with T2DM and established cardiovascular disease. Results from cardiovascular outcomes trials have prompted an update to the 2017 American Diabetes Association

  11. Pharmacologic Management of Type 2 Diabetes Mellitus: Available Therapies.

    Science.gov (United States)

    Thrasher, James

    2017-07-01

    Choices for the treatment of type 2 diabetes mellitus (T2DM) have multiplied as our understanding of the underlying pathophysiologic defects has evolved. Treatment should target multiple defects in T2DM and follow a patient-centered approach that considers factors beyond glycemic control, including cardiovascular risk reduction. The American Association of Clinical Endocrinologists/American College of Endocrinology and the American Diabetes Association recommend an initial approach consisting of lifestyle changes and monotherapy, preferably with metformin. Therapy choices are guided by glycemic efficacy, safety profiles, particularly effects on weight and hypoglycemia risk, tolerability, patient comorbidities, route of administration, patient preference, and cost. Balancing management of hyperglycemia with the risk of hypoglycemia and consideration of the effects of pharmacotherapy on weight figure prominently in US-based T2DM recommendations, whereas less emphasis has been placed on the ability of specific medications to affect cardiovascular outcomes. This is likely because, until recently, specific glucose-lowering agents have not been shown to affect cardiorenal outcomes. The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME), the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, and the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes 6 (SUSTAIN-6) recently showed a reduction in overall cardiovascular risk with empagliflozin, liraglutide, and semaglutide treatment, respectively. Moreover, empagliflozin has become the first glucose-lowering agent indicated to reduce the risk of cardiovascular death in adults with T2DM and established cardiovascular disease. Results from cardiovascular outcomes trials have prompted an update to the 2017 American Diabetes Association

  12. How does race/ethnicity influence pharmacological response to asthma therapies?

    Science.gov (United States)

    Cazzola, Mario; Calzetta, Luigino; Matera, Maria Gabriella; Hanania, Nicola A; Rogliani, Paola

    2018-04-01

    Our understanding of whether and/or how ethnicity influences pharmacological response to asthma therapies is still very scarce. A possible explanation for the increased asthma treatment failures observed in ethnic and racial minorities receiving asthma therapies is that some of these groups may have a pharmacogenomic predisposition to either nonresponse or to adverse response with a specific class of drugs. However, the effects of ethnicity on pharmacological response to asthma therapies are also, and mainly, determined by socioeconomic and environmental factors to a varying extent, depending on the ethnic groups. Areas covered: Genetic, socioeconomic and environmental factors that can affect the pharmacotherapeutic responses to asthma medications and their link(s) to race/ethnicity have been examined and critically discussed. Expert opinion: Differences in genetic ancestry are definitely non-modifiable factors, but socioeconomic and environmental disadvantages are all factors that can be modified. It is likely that improved outcomes may be achieved when tailored and multifaceted approaches that include home, school, and clinician-based interventions are implemented. Consequently, it is critical to determine if a clinical intervention programme combined with implementation strategies that attempt to reduce inequalities can reduce asthma disparities, including the influence of ethnicity and race on pharmacological response to asthma therapies.

  13. Gemcitabine-Based Combination Chemotherapy Followed by Radiation With Capecitabine as Adjuvant Therapy for Resected Pancreas Cancer

    International Nuclear Information System (INIS)

    Desai, Sameer; Ben-Josef, Edgar; Griffith, Kent A.; Simeone, Diane; Greenson, Joel K.; Francis, Isaac R.; Hampton, Janet; Colletti, Lisa; Chang, Alfred E.; Lawrence, Theodore S.; Zalupski, Mark M.

    2009-01-01

    Purpose: To report outcomes for patients with resected pancreas cancer treated with an adjuvant regimen consisting of gemcitabine-based combination chemotherapy followed by capecitabine and radiation. Patients and Methods: We performed a retrospective review of a series of patients treated at a single institution with a common postoperative adjuvant program. Between January 2002 and August 2006, 43 resected pancreas cancer patients were offered treatment consisting of 4, 21-day cycles of gemcitabine 1 g/m 2 intravenously over 30 min on Days 1 and 8, with either cisplatin 35 mg/m 2 intravenously on Days 1 and 8 or capecitabine 1500 mg/m 2 orally in divided doses on Days 1-14. After completion of combination chemotherapy, patients received a course of radiotherapy (54 Gy) with concurrent capecitabine (1330 mg/m 2 orally in divided doses) day 1 to treatment completion. Results: Forty-one patients were treated. Median progression-free survival for the entire group was 21.7 months (95% confidence interval 13.9-34.5 months), and median overall survival was 45.9 months. In multivariate analysis a postoperative CA 19-9 level of ≥180 U/mL predicted relapse and death. Toxicity was mild, with only two hospitalizations during adjuvant therapy. Conclusions: A postoperative adjuvant program using combination chemotherapy with gemcitabine and either cisplatin or capecitabine followed by radiotherapy with capecitabine is tolerable and efficacious and should be considered for Phase III testing in this group of patients.

  14. Bladder Cancer Patterns of Pelvic Failure: Implications for Adjuvant Radiation Therapy

    International Nuclear Information System (INIS)

    Baumann, Brian C.; Guzzo, Thomas J.; He Jiwei; Vaughn, David J.; Keefe, Stephen M.; Vapiwala, Neha; Deville, Curtiland; Bekelman, Justin E.; Tucker, Kai; Hwang, Wei-Ting; Malkowicz, S. Bruce; Christodouleas, John P.

    2013-01-01

    Purpose: Local-regional failures (LFs) after cystectomy with or without chemotherapy are common in locally advanced disease. Adjuvant radiation therapy (RT) could reduce LFs, but toxicity has discouraged its use. Modern RT techniques with improved normal tissue sparing have rekindled interest but require knowledge of pelvic failure patterns to design treatment volumes. Methods and Materials: Five-year LF rates after radical cystectomy plus pelvic node dissection with or without chemotherapy were determined for 8 pelvic sites among 442 urothelial bladder carcinoma patients. The impact of pathologic stage, margin status, nodal involvement, and extent of node dissection on failure patterns was assessed using competing risk analysis. We calculated the percentage of patients whose sites of LF would have been completely encompassed within various hypothetical clinical target volumes (CTVs) for postoperative radiation. Results: Compared with stage ≤pT2, stage ≥pT3 patients had higher 5-year LF rates in virtually all pelvic sites. Among stage ≥pT3 patients, margin status significantly altered the failure pattern whereas extent of node dissection and nodal positivity did not. In stage ≥pT3 patients with negative margins, failure occurred predominantly in the iliac/obturator nodes and uncommonly in the cystectomy bed and/or presacral nodes. Of these patients in whom failure subsequently occurred, 76% would have had all LF sites encompassed within CTVs covering only the iliac/obturator nodes. In stage ≥pT3 with positive margins, cystectomy bed and/or presacral nodal failures increased significantly. Only 57% of such patients had all LF sites within CTVs limited to the iliac/obturator nodes, but including the cystectomy bed and presacral nodes in the CTV when margins were positive increased the percentage of LFs encompassed to 91%. Conclusions: Patterns of failure within the pelvis are summarized to facilitate design of adjuvant RT protocols. These data suggest that

  15. Bladder Cancer Patterns of Pelvic Failure: Implications for Adjuvant Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Baumann, Brian C. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Guzzo, Thomas J. [Department of Urology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); He Jiwei [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Vaughn, David J.; Keefe, Stephen M. [Department of Medical Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Vapiwala, Neha; Deville, Curtiland; Bekelman, Justin E.; Tucker, Kai [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Hwang, Wei-Ting [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); 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)

    2013-02-01

    Purpose: Local-regional failures (LFs) after cystectomy with or without chemotherapy are common in locally advanced disease. Adjuvant radiation therapy (RT) could reduce LFs, but toxicity has discouraged its use. Modern RT techniques with improved normal tissue sparing have rekindled interest but require knowledge of pelvic failure patterns to design treatment volumes. Methods and Materials: Five-year LF rates after radical cystectomy plus pelvic node dissection with or without chemotherapy were determined for 8 pelvic sites among 442 urothelial bladder carcinoma patients. The impact of pathologic stage, margin status, nodal involvement, and extent of node dissection on failure patterns was assessed using competing risk analysis. We calculated the percentage of patients whose sites of LF would have been completely encompassed within various hypothetical clinical target volumes (CTVs) for postoperative radiation. Results: Compared with stage {<=}pT2, stage {>=}pT3 patients had higher 5-year LF rates in virtually all pelvic sites. Among stage {>=}pT3 patients, margin status significantly altered the failure pattern whereas extent of node dissection and nodal positivity did not. In stage {>=}pT3 patients with negative margins, failure occurred predominantly in the iliac/obturator nodes and uncommonly in the cystectomy bed and/or presacral nodes. Of these patients in whom failure subsequently occurred, 76% would have had all LF sites encompassed within CTVs covering only the iliac/obturator nodes. In stage {>=}pT3 with positive margins, cystectomy bed and/or presacral nodal failures increased significantly. Only 57% of such patients had all LF sites within CTVs limited to the iliac/obturator nodes, but including the cystectomy bed and presacral nodes in the CTV when margins were positive increased the percentage of LFs encompassed to 91%. Conclusions: Patterns of failure within the pelvis are summarized to facilitate design of adjuvant RT protocols. These data suggest

  16. Systematic review of evidence underpinning non-pharmacological therapies in dementia.

    Science.gov (United States)

    Olley, Richard; Morales, Andrea

    2017-05-15

    Objective Dementia is one of the most common illnesses worldwide, and is one of the most important causes of disability in older people. Currently, dementia affects over 35million people around the globe. It is expected that this number will increase to 65.7million by 2030. Early detection, diagnosis and treatment to control the principal behaviour symptoms may help reduce these numbers and delay the progression to more advanced and dangerous stages of this disorder with resultant increase quality of life for those affected. The main goal of the present systematic literature review was to examine contemporary evidence relating to non-pharmacological therapy in the treatment of dementia. Methods To achieve the study goal, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used. Results This study identified the five most common behaviours in patients with dementia as aggression, wandering, agitation, apathy and sleep disturbances. Two non-pharmacological therapies were the most studied treatment: music therapy and aromatherapy. Ten other non-pharmacological therapies were also identified, but these lack a sufficient evidence-base. Conclusion Although all the therapies identified could be used as part of the treatment of behavioural symptoms, there is insufficient evidence relating to the indications, appropriate use and effectiveness of these therapies to apply in each behavioural treatment. Thus, the present study has demonstrated a significant research gap. What is known about the topic? Despite the widespread use of many different types of therapies, there is limited evidence regarding the efficacy of non-pharmaceutical therapies deployed in the management of behaviours of concern manifested by some people who suffer with dementia in all its forms. What does this paper add? This systematic review examines contemporary evidence from the literature to determine whether there is an evidence base available that would

  17. CLINICAL-PHARMACOLOGICAL VALUE OF TREATMENT EFFICIENCY OF BHP-PATIENTS BY ANTITHROMBOTIC THERAPY

    Directory of Open Access Journals (Sweden)

    A.A. Svistunov

    2007-09-01

    Full Text Available Patients with BHP need in pharmacological treatment of thrombosis the most often in the first 3 cases because has dysfunctions of platelets and coagulation. According to results of analysis of efficiency antithrombotic therapy in BHP-patients confirmed clinical and biochemical influence antithrombotic therapy by Ticlid 250 mg twice on the day in comparison with Aspirin 100 mg and Dipiridomol 25 mg on the basic therapy of the BHP by Permixon 160 mg. The received results have had statistically meant differences. Manifestation of BHP and value QOL and others urodynamic complications most often appear on the basic specific monotherapy of BHP and lost after antithrombotic therapy for 1-3 months. The important complications of antithrombotic therapy of BHP-patients did not observe.

  18. Limited Advantages of Intensity-Modulated Radiotherapy Over 3D Conformal Radiation Therapy in the Adjuvant Management of Gastric Cancer

    International Nuclear Information System (INIS)

    Alani, Shlomo; Soyfer, Viacheslav; Strauss, Natan; Schifter, Dan; Corn, Benjamin W.

    2009-01-01

    Purpose: Although chemoradiotherapy was considered the standard adjuvant treatment for gastric cancer, a recent Phase III trial (Medical Research Council Adjuvant Gastric Infusional Chemotherapy [MAGIC]) did not include radiotherapy in the randomization scheme because it was considered expendable. Given radiotherapy's potential, efforts needed to be made to optimize its use for treating gastric cancer. We assessed whether intensity-modulated radiotherapy (IMRT) could improve upon our published results in patients treated with three-dimensional (3D) conformal therapy. Methods and Materials: Fourteen patients with adenocarcinoma of the stomach were treated with adjuvant chemoradiotherapy using a noncoplanar four-field arrangement. Subsequently, a nine-field IMRT plan was designed using a CMS Xio IMRT version 4.3.3 module. Two IMRT beam arrangements were evaluated: beam arrangement 1 consisted of gantry angles of 0 deg., 53 deg., 107 deg., 158 deg., 204 deg., 255 deg., and 306 deg.. Beam arrangement 2 consisted of gantry angles of 30 deg., 90 deg., 315 deg., and 345 deg.; a gantry angle of 320 deg./couch, 30 deg.; and a gantry angle of 35 o /couch, 312 o . Both the target volume coverage and the dose deposition in adjacent critical organs were assessed in the plans. Dose-volume histograms were generated for the clinical target volume, kidneys, spine, and liver. Results: Comparison of the clinical target volumes revealed satisfactory coverage by the 95% isodose envelope using either IMRT or 3D conformal therapy. However, IMRT was only marginally better than 3D conformal therapy at protecting the spine and kidneys from radiation. Conclusions: IMRT confers only a marginal benefit in the adjuvant treatment of gastric cancer and should be used only in the small subset of patients with risk factors for kidney disease or those with a preexisting nephropathy.

  19. Limited advantages of intensity-modulated radiotherapy over 3D conformal radiation therapy in the adjuvant management of gastric cancer.

    Science.gov (United States)

    Alani, Shlomo; Soyfer, Viacheslav; Strauss, Natan; Schifter, Dan; Corn, Benjamin W

    2009-06-01

    Although chemoradiotherapy was considered the standard adjuvant treatment for gastric cancer, a recent Phase III trial (Medical Research Council Adjuvant Gastric Infusional Chemotherapy [MAGIC]) did not include radiotherapy in the randomization scheme because it was considered expendable. Given radiotherapy's potential, efforts needed to be made to optimize its use for treating gastric cancer. We assessed whether intensity-modulated radiotherapy (IMRT) could improve upon our published results in patients treated with three-dimensional (3D) conformal therapy. Fourteen patients with adenocarcinoma of the stomach were treated with adjuvant chemoradiotherapy using a noncoplanar four-field arrangement. Subsequently, a nine-field IMRT plan was designed using a CMS Xio IMRT version 4.3.3 module. Two IMRT beam arrangements were evaluated: beam arrangement 1 consisted of gantry angles of 0 degrees , 53 degrees , 107 degrees , 158 degrees , 204 degrees , 255 degrees , and 306 degrees . Beam arrangement 2 consisted of gantry angles of 30 degrees , 90 degrees , 315 degrees , and 345 degrees ; a gantry angle of 320 degrees /couch, 30 degrees ; and a gantry angle of 35 degrees /couch, 312 degrees . Both the target volume coverage and the dose deposition in adjacent critical organs were assessed in the plans. Dose-volume histograms were generated for the clinical target volume, kidneys, spine, and liver. Comparison of the clinical target volumes revealed satisfactory coverage by the 95% isodose envelope using either IMRT or 3D conformal therapy. However, IMRT was only marginally better than 3D conformal therapy at protecting the spine and kidneys from radiation. IMRT confers only a marginal benefit in the adjuvant treatment of gastric cancer and should be used only in the small subset of patients with risk factors for kidney disease or those with a preexisting nephropathy.

  20. Effectiveness of massage therapy as co-adjuvant treatment to exercise in osteoarthritis of the knee: a randomized control trial.

    Science.gov (United States)

    Cortés Godoy, Virginia; Gallego Izquierdo, Tomás; Lázaro Navas, Irene; Pecos Martín, Daniel

    2014-01-01

    The effectiveness of exercise therapy in the treatment of osteoarthritis of the knee (KOA) is widely evidenced. The current study aims to compare the effectiveness of massage therapy as a co-adjuvant treatment for KOA. A blind, randomized controlled trial design was used. Eighteen women were randomly allocated to two different groups. Group A was treated with massage therapy and an exercise program, and Group B was treated with the exercise program alone. The intervention lasted for 6 weeks. Outcomes were assessed using a verbal analogue scale (VAS), the WOMAC index, and the Get-Up and Go test. Baseline, post-treatment, and 1- and 3- month follow-up data were collected. Values were considered statistically significant at a p massage therapy may lead to clinical improvement in patients with KOA. The use of massage therapy combined with exercise as a treatment for gonarthrosis does not seem to have any beneficial effects.

  1. FDG PET in non-pharmacological therapy in Alzheimer's disease; cerebral metabolic increase correlates with clinical improvement after cognitive therapy

    International Nuclear Information System (INIS)

    Na, Hae Ri; Kim, Yu Kyeong; Park, Seong Min; Lee, Seung Hyun; Park, Eun Kyung; Lee, Jung Seok; Kim, Sang Yun; Kim, Sang Eun

    2007-01-01

    In management of AD, pharmacological treatment alone using acetylcholinesterase inhibitor (AChEI) is general consensus, and provides beneficial effect to prolong their progression. Combined non-pharmacological therapy, especially cognitive therapy is recently having attention with expectation of improvement in cognitive ability. This study examined the effect of combined cognitive therapy in AD patients who were maintaining AChEI using FDG PET. Four patients (689 yrs) who diagnosed as probable Alzheimer's disease based on the NINCDS-ADRDA criteria participated in this study. 12-week cognitive therapy comprised seven fields to enhance orientation, memory, recall, visuo-motor organization, categorization and behavior modification/sequencing. They received 45-minute sessions twice per week with maintaining their previous medication. Clinical improvement was assessed by comprehensive neuropsychological tests. Two FDG PET studies were performed before cognitive therapy and in the middle of the therapy, and compared to evaluate the effect of cognitive therapy to cerebral metabolism. Two of 4 patients whose initial cognitive impairment was milder had clinical improvement after 12 weeks, the rest who were more severely impaired failed to have clinical improvement. Regional cerebral hypometabolism on initial PET was correlated with their functional status. Follow up PET of two responders demonstrated the increases in regional metabolism in the temporal and/or frontal cortex, which was associated their functional improvement. Cerebral metabolism in poor responders were minimally increased or no changed. This preliminary data suggests that cognitive therapy is potentially useful to stabilize or improve cognitive and functional performance in AD patients with relatively mild cognitive dysfunction. And FDG PET could demonstrate possible candidates for cognitive therapy and the effect of the therapy

  2. Stem cell therapy for cardiovascular disease: the demise of alchemy and rise of pharmacology.

    Science.gov (United States)

    Jadczyk, T; Faulkner, A; Madeddu, P

    2013-05-01

    Regenerative medicine holds great promise as a way of addressing the limitations of current treatments of ischaemic disease. In preclinical models, transplantation of different types of stem cells or progenitor cells results in improved recovery from ischaemia. Furthermore, experimental studies indicate that cell therapy influences a spectrum of processes, including neovascularization and cardiomyogenesis as well as inflammation, apoptosis and interstitial fibrosis. Thus, distinct strategies might be required for specific regenerative needs. Nonetheless, clinical studies have so far investigated a relatively small number of options, focusing mainly on the use of bone marrow-derived cells. Rapid clinical translation resulted in a number of small clinical trials that do not have sufficient power to address the therapeutic potential of the new approach. Moreover, full exploitation has been hindered so far by the absence of a solid theoretical framework and inadequate development plans. This article reviews the current knowledge on cell therapy and proposes a model theory for interpretation of experimental and clinical outcomes from a pharmacological perspective. Eventually, with an increased association between cell therapy and traditional pharmacotherapy, we will soon need to adopt a unified theory for understanding how the two practices additively interact for a patient's benefit. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

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

    International Nuclear Information System (INIS)

    Sabolch, Aaron; Else, Tobias; Griffith, Kent A.; Ben-Josef, Edgar; Williams, Andrew; Miller, Barbra S.; Worden, Francis; Hammer, Gary D.; Jolly, Shruti

    2015-01-01

    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

  4. 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.

  5. Effect of adjuvant levosimendan therapy on neuroendocrine hormones and cytokines in elderly patients with chronic heart failure

    Directory of Open Access Journals (Sweden)

    Li Lei

    2017-11-01

    Full Text Available Objective: To discuss the effect of adjuvant levosimendan therapy on neuroendocrine hormones and cytokines in elderly patients with chronic heart failure. Methods: A total of 100 elderly patients with chronic heart failure who were treated in the hospital between March 2014 and March 2017 were divided into control group and levosimendan group by random number table, each with 50 cases. Control group received clinical routine therapy for chronic heart failure, and levosimendan group received routine therapy combined with adjuvant levosimendan therapy. The differences in serum levels of RAAS indexes, thyroid hormones, myocardial damage indexes and endothelial function indexes were compared between the two groups before and after treatment. Results: At T0, there was no statistically significant difference in serum levels of RAAS indexes, thyroid hormones, myocardial damage indexes and endothelial function indexes between the two groups. At T1, serum RAAS indexes PRA, AngⅡ and ALD levels of levosimendan group were lower than those of control group; serum thyroid hormones TT3, TT4, FT3 and FT4 levels of levosimendan group were higher than those of control group; serum myocardial damage indexes cTnⅠ, H-FABP and NT-proBNP levels of levosimendan group were lower than those of control group; serum endothelial function index NO level of levosimendan group was higher than that of control group while ET-1 level was lower than that of control group. Conclusion: Adjuvant levosimendan therapy for elderly patients with chronic heart failure can effectively adjust the secretion of neuroendocrine hormones and reduce the myocardial and vascular endothelial damage.

  6. Adjuvant therapy for gastric cancer: what have we learned since INT0116?

    Science.gov (United States)

    Jácome, Alexandre A; Sankarankutty, Ajith K; dos Santos, José Sebastião

    2015-04-07

    Gastric cancer is one of the main cancer-related causes of death worldwide. The curative treatment of gastric cancer consists of tumor resection and lymphadenectomy. However, surgical treatment alone is associated with high recurrence rates. Adjuvant treatment strategies have been studied over the last decades, but there have been controversial results from the initial studies. The pivotal INT0116 study demonstrated that the use of adjuvant chemoradiotherapy with 5-fluorouracil increases relapse-free and overall survival, and it has been adopted across the Western world. The high toxicity of radiochemotherapy and suboptimal surgical treatment employed, with fewer than 10% of the patients submitted to D2 lymphadenectomy, were the main study limitations. Since its publication, other adjuvant treatment modalities have been studied, and radiochemotherapy is being refined to improve its efficacy and safety. A multimodal approach has been demonstrated to significantly increase relapse-free and overall survival, and it can be offered in the form of perioperative chemotherapy, adjuvant chemoradiotherapy or adjuvant chemotherapy, regardless of the extent of lymphadenectomy. The objective of the present review is to report the major advances obtained in the last decades in the adjuvant treatment of gastric cancer as well as the perspectives of treatment based on recent knowledge of the molecular biology of the disease.

  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. Anti-calmodulins and tricyclic adjuvants in pain therapy block the TRPV1 channel.

    Directory of Open Access Journals (Sweden)

    Zoltán Oláh

    2007-06-01

    Full Text Available Ca(2+-loaded calmodulin normally inhibits multiple Ca(2+-channels upon dangerous elevation of intracellular Ca(2+ and protects cells from Ca(2+-cytotoxicity, so blocking of calmodulin should theoretically lead to uncontrolled elevation of intracellular Ca(2+. Paradoxically, classical anti-psychotic, anti-calmodulin drugs were noted here to inhibit Ca(2+-uptake via the vanilloid inducible Ca(2+-channel/inflamatory pain receptor 1 (TRPV1, which suggests that calmodulin inhibitors may block pore formation and Ca(2+ entry. Functional assays on TRPV1 expressing cells support direct, dose-dependent inhibition of vanilloid-induced (45Ca(2+-uptake at microM concentrations: calmidazolium (broad range > or = trifluoperazine (narrow range chlorpromazine/amitriptyline>fluphenazine>>W-7 and W-13 (only partially. Most likely a short acidic domain at the pore loop of the channel orifice functions as binding site either for Ca(2+ or anti-calmodulin drugs. Camstatin, a selective peptide blocker of calmodulin, inhibits vanilloid-induced Ca(2+-uptake in intact TRPV1(+ cells, and suggests an extracellular site of inhibition. TRPV1(+, inflammatory pain-conferring nociceptive neurons from sensory ganglia, were blocked by various anti-psychotic and anti-calmodulin drugs. Among them, calmidazolium, the most effective calmodulin agonist, blocked Ca(2+-entry by a non-competitive kinetics, affecting the TRPV1 at a different site than the vanilloid binding pocket. Data suggest that various calmodulin antagonists dock to an extracellular site, not found in other Ca(2+-channels. Calmodulin antagonist-evoked inhibition of TRPV1 and NMDA receptors/Ca(2+-channels was validated by microiontophoresis of calmidazolium to laminectomised rat monitored with extracellular single unit recordings in vivo. These unexpected findings may explain empirically noted efficacy of clinical pain adjuvant therapy that justify efforts to develop hits into painkillers, selective to sensory Ca(2

  9. Local Failure in Resected N1 Lung Cancer: Implications for Adjuvant Therapy

    International Nuclear Information System (INIS)

    Higgins, Kristin A.; Chino, Junzo P.; Berry, Mark; Ready, Neal; Boyd, Jessamy; Yoo, David S.; Kelsey, Chris R.

    2012-01-01

    Purpose: To evaluate actuarial rates of local failure in patients with pathologic N1 non–small-cell lung cancer and to identify clinical and pathologic factors associated with an increased risk of local failure after resection. Methods and Materials: All patients who underwent surgery for non–small-cell lung cancer with pathologically confirmed N1 disease at Duke University Medical Center from 1995–2008 were identified. Patients receiving any preoperative therapy or postoperative radiotherapy or with positive surgical margins were excluded. Local failure was defined as disease recurrence within the ipsilateral hilum, mediastinum, or bronchial stump/staple line. Actuarial rates of local failure were calculated with the Kaplan-Meier method. A Cox multivariate analysis was used to identify factors independently associated with a higher risk of local recurrence. Results: Among 1,559 patients who underwent surgery during the time interval, 198 met the inclusion criteria. Of these patients, 50 (25%) received adjuvant chemotherapy. Actuarial (5-year) rates of local failure, distant failure, and overall survival were 40%, 55%, and 33%, respectively. On multivariate analysis, factors associated with an increased risk of local failure included a video-assisted thoracoscopic surgery approach (hazard ratio [HR], 2.5; p = 0.01), visceral pleural invasion (HR, 2.1; p = 0.04), and increasing number of positive N1 lymph nodes (HR, 1.3 per involved lymph node; p = 0.02). Chemotherapy was associated with a trend toward decreased risk of local failure that was not statistically significant (HR, 0.61; p = 0.2). Conclusions: Actuarial rates of local failure in pN1 disease are high. Further investigation of conformal postoperative radiotherapy may be warranted.

  10. Adjuvant therapy in the treatment of gallbladder cancer: a meta-analysis

    International Nuclear Information System (INIS)

    Ma, Ning; Cheng, Hui; Qin, Baodong; Zhong, Renqian; Wang, Bin

    2015-01-01

    The benefit of adjuvant therapy (AT) for gallbladder cancer (GBC) is unclear as evidenced by conflicting results from nonrandomized studies. Here we aimed to perform a meta-analysis to determine the impact of AT on overall survival (OS). We used data from MEDLINE, EMBASE and the Cochrane Collaboration Library and published between October 1967 and October 2014. Studies that evaluated AT compared with curative-intent surgery alone for resected GBC were included. Subgroup analyses of benefit based on node status, margins status, and American Joint Committee on Cancer (AJCC) staging were prespecified. Data were weighted and pooled using random-effect modeling. Ten retrospective studies involving 3,191 patients were analyzed. There was a nonsignificant improvement in OS with AT compared with surgery alone (hazard ratio [HR], 0.76; 95 % confidence interval [CI], 0.56–1.03). A significant improvement was observed in OS with chemotherapy (CT) compared with surgery alone (HR, 0.42; 95 % CI, 0.22–0.80) by sensitivity analysis. The greatest benefit for AT was also observed in those with R1 disease (HR, 0.33; 95 % CI, 0.19–0.59), LN-positive disease (HR, 0.71; 95 % CI, 0.63–0.81), and AJCC staging meeting or exceeding tumor Stage II (HR, 0.45; 95 % CI, 0.26–0.79), but not in those with LN-negative or R0 disease. Our results strongly support the use of CT as an AT in GBC. Moreover, patients with node positivity, margin positivity, or non-stage I disease are more likely to benefit from AT

  11. Local Failure in Resected N1 Lung Cancer: Implications for Adjuvant Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Higgins, Kristin A., E-mail: kristin.higgins@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Chino, Junzo P [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Berry, Mark [Department of Surgery, Division of Cardiovascular and Thoracic Surgery, Duke University Medical Center, Durham, NC (United States); Ready, Neal [Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, NC (United States); Boyd, Jessamy [US Oncology, Dallas, TX (United States); Yoo, David S; Kelsey, Chris R [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)

    2012-06-01

    Purpose: To evaluate actuarial rates of local failure in patients with pathologic N1 non-small-cell lung cancer and to identify clinical and pathologic factors associated with an increased risk of local failure after resection. Methods and Materials: All patients who underwent surgery for non-small-cell lung cancer with pathologically confirmed N1 disease at Duke University Medical Center from 1995-2008 were identified. Patients receiving any preoperative therapy or postoperative radiotherapy or with positive surgical margins were excluded. Local failure was defined as disease recurrence within the ipsilateral hilum, mediastinum, or bronchial stump/staple line. Actuarial rates of local failure were calculated with the Kaplan-Meier method. A Cox multivariate analysis was used to identify factors independently associated with a higher risk of local recurrence. Results: Among 1,559 patients who underwent surgery during the time interval, 198 met the inclusion criteria. Of these patients, 50 (25%) received adjuvant chemotherapy. Actuarial (5-year) rates of local failure, distant failure, and overall survival were 40%, 55%, and 33%, respectively. On multivariate analysis, factors associated with an increased risk of local failure included a video-assisted thoracoscopic surgery approach (hazard ratio [HR], 2.5; p = 0.01), visceral pleural invasion (HR, 2.1; p = 0.04), and increasing number of positive N1 lymph nodes (HR, 1.3 per involved lymph node; p = 0.02). Chemotherapy was associated with a trend toward decreased risk of local failure that was not statistically significant (HR, 0.61; p = 0.2). Conclusions: Actuarial rates of local failure in pN1 disease are high. Further investigation of conformal postoperative radiotherapy may be warranted.

  12. Safety and Feasibility of Carboplatin and Paclitaxel followed by Fluoropyrimidine Analogs and Radiation as Adjuvant Therapy for Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Mohammad Mobayed

    2009-11-01

    Full Text Available Background: Adjuvant 5-fluorouracil (5FU-based chemo-radiotherapy is currently considered a standard of care for the treatment of gastric cancer. The impact of 5FU-based adjuvant therapy on the rate of distant recurrence has been modest. In order to improve the systemic effects of adjuvant therapy, we have been treating patients with resected gastric cancer with carboplatin and paclitaxel followed by fluoropyrimidine analogue and radiation. Methods: We report on the outcomes of 21 consecutive gastric cancer patients treated off protocol with adjuvant carboplatin (area under the curve 5 mg/ml × min and paclitaxel (175–200 mg/m2 every 3 weeks, followed by concurrent pyrimidine analogs (either capecitabine 1,600–2,000 mg/m2/day in 17 patients, or 5FU 200 mg/m2/day in 4 patients and radiation (45–50.4 Gy. Patients received a total of 4–6 cycles of carboplatin and paclitaxel. Results: The median age at diagnosis was 60 years. Sixteen patients had stage 3 disease and 7 of them had positive surgical margins (6 with R1 and 1 with R2 resection, 3 patients were stage 2, and 2 patients were stage 1 (all had R0 resection. All patients had D1/D2 (4 had D2 and 17 had D1 lymph node dissection. The incidence of grade 3 or higher overall, hematologic, or gastrointestinal toxicity in the patients receiving carboplatin and paclitaxel was 57, 48 and 10%, respectively. No treatment-related deaths were observed. After adjuvant treatment 15 patients developed recurrent disease, 10 of whom had distant metastases. The median recurrence-free survival (RFS was 12.3 months. The median overall survival (OS was 16.0 months. Patients with R0 resection had significantly longer OS than did those with positive surgical margins (log-rank p = 0.0060. Median OS for the R0 resection group was 28.8 months. Conclusions: Carboplatin and paclitaxel added to radiation plus fluoropyrimidine analogs is a well-tolerated regimen in the adjuvant setting. The activity of this regimen

  13. Effectiveness of ketamine as an adjuvant to opioid-based therapy in decreasing pain associated with opioid tolerance in adults undergoing orthopedic surgery: a systematic review protocol.

    Science.gov (United States)

    Bennett, Marsha; Bonanno, Laura; Kuhn, William

    2016-10-01

    The objective of this systematic review is to examine the best available evidence on the clinical effectiveness of ketamine as an adjuvant to opioid-based therapy versus opioid-based therapy alone in decreasing perioperative pain associated with opioid tolerance in adult patients, aged 18-70 years, undergoing orthopedic surgical procedures.The following question guides the systematic review: does the administration of ketamine as an adjuvant to opioid-based therapy, compared to opioid-based therapy alone, improve perioperative pain relief in opioid-tolerant adult patients undergoing orthopedic surgical procedures?

  14. A Prospective Comparison of Younger and Older Patients' Preferences for Adjuvant Chemotherapy and Hormonal Therapy in Early Breast Cancer.

    Science.gov (United States)

    Hamelinck, Victoria C; Bastiaannet, Esther; Pieterse, Arwen H; de Glas, Nienke A; Portielje, Johanneke E A; Merkus, Jos W S; den Hoed, Irma D M; van de Velde, Cornelis J H; Liefers, Gerrit-Jan; Stiggelbout, Anne M

    2016-10-01

    It is unknown what minimal benefit in disease-free survival older patients with breast cancer require from adjuvant systemic therapy, and if this differs from that required by younger patients. We prospectively examined patients' preferences for adjuvant chemotherapy (aCT) and adjuvant hormonal therapy (aHT), factors related to minimally-required benefit, and patients' self-reported motivations. Fifty-two younger (40-64 years) and 29 older (≥ 65 years) women with a first primary, invasive tumor were interviewed post-surgery, prior to receiving aCT/aHT recommendation. The proportions of younger versus older participants who would accept, refuse, or were undecided about therapy were 92% versus 62%, 4% versus 24%, and 4% versus 14% for aCT, and 92% versus 59%, 8% versus 17%, and 0% versus 24% for aHT. The proportion of older participants who would refuse rather than accept aCT was larger than that of younger participants (P = .005). No significant difference was found for aHT (P = .12). Younger and older participants' minimally-required benefit, in terms of additional 10-year disease-free survival, to accept aCT (median, 5% vs. 4%; P = .13) or aHT (median, 10% vs. 8%; P = .15) did not differ. Being single/divorced/widowed (odds ratio [OR], 0.16; P = .005), presence of geriatric condition (inability to perform daily activities, incontinence, severe sensory impairment, depression, polypharmacy, difficulties with walking; OR, 0.27; P = .047), and having a preference to make the treatment decision either alone or after considering the clinician's opinion (active role; OR, 0.15; P = .012) were independently related to requiring larger benefits from aCT. The most frequent motivations for/against therapy included the wish to survive/avoid recurrence, clinician's recommendation, side effects, and treatment duration (only aHT). Whereas older participants were less willing to accept aCT than younger participants, no significant difference was found for aHT. However, a

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

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    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

  16. Adjuvant therapy of chronic gastroduodenitis in children with dysplasia of connective tissue

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    О. М. Mukvich

    2018-04-01

    Full Text Available Chronic gastroduodenitis (CGD hold one of main places among leading diseases of gastro-intestinal tract (GIT in childhood. A special category is children who have CGD against the background of connective tissue (CT dysplasia (DCT. CGD in such children is characterized by early appearance, aggressive, gradient course with frequent acute conditions and recurrences with evident symptoms of nonspecific intoxication manifestations. Defect of collagen synthesis leads to pronounced morphological changes of proximal GIT mucous membrane (MM and decline in its cytoptotecive abilities. Challenges related to the qualitative and quantitative local ecosystem changes can aggravate immune and metabolic local processes and enhance the destruction of proximal GIT mucous membrane. Aforesaid defines the need to include multiprobiotics into the treatment schemes of patient with CGD, associated with congenital fibrogenesis disorders, as adjuvant therapy with complex therapeutic action; they positively influence the CT metabolism, improve reparative processes in MM, normalize immune processes and maintain composition and functions of physiological microbiota. Purposes – improvement of CGD treatment efficiency in children with DCT through inclusion of the multiprobiotic Symbiter® forte-M into the treatment schemes. Materials and methods. There were examined 33 children with CGD on the background of DCT and 32 healthy children (control from 11 to 17 years old. The state of the mucous barrier was estimated by certain mucin constituents (fucose, glycosaminoglycans, sialic acids assessing, antimicrobial peptides (ß2-defencins, non-specific humoral factors of the local immunity (immunoglobulins, lysozyme in mucous secretions (saliva, coprofiltrate (CF before and after probiotic therapy. Results. Increased concentrations of ß2-defencins (psaliva = 0.03, pCF = 0.03, sialic acids (P = 0.04 and lysozyme (P = 0.01 and decreased of fucose level (P = 0.03 in mucous secretions

  17. Adjuvant endocrine therapy after breast cancer: a qualitative study of factors associated with adherence

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    Brett J

    2018-02-01

    Full Text Available Jo Brett,1 Mary Boulton,1 Debbie Fenlon,2 Nick J Hulbert-Williams,3 Fiona M Walter,4 Peter Donnelly,5 Bernadette A Lavery,6 Adrienne Morgan,7 Carolyn Morris,7 Eila K Watson1 1Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, 2College of Human and Health Sciences, Swansea University, Swansea, Wales, 3Department of Psychology, Chester Research Unit for the Psychology of Health, University of Chester, Chester, 4Department of Public Health and Primary Care, University of Cambridge, Cambridge, 5South Devon Healthcare NHS Foundation Trust, Torbay Hospital, Torquay, 6Cancer Services, Oxford University Hospitals Foundation NHS Trust, Oxford, 7Independent Cancer Patients’ Voice, London, UK Introduction: Despite evidence of the efficacy of adjuvant endocrine therapy (AET in reducing the risk of recurrence and mortality after treatment for primary breast cancer, adherence to AET is suboptimal. This study aimed to explore factors that influence adherence and nonadherence to AET following breast cancer to inform the development of supportive interventions.Methods: Interviews were conducted with 32 women who had been prescribed AET, 2–4 years following their diagnosis of breast cancer. Both adherers (n=19 and nonadherers (n=13 were recruited. The analysis was conducted using the Framework approach.Results: Factors associated with adherence were as follows: managing side effects including information and advice on side effects and taking control of side effects, supportive relationships, and personal influences. Factors associated with nonadherence were as follows: burden of side effects, feeling unsupported, concerns about long-term AET use, regaining normality, including valuing the quality of life over length of life, and risk perception.Conclusion: Provision of timely information to prepare women for the potential side effects of AET and education on medication management strategies are needed, including provision of timely and

  18. Mechanisms of, and Adjuvants for, Bone Pain.

    Science.gov (United States)

    Figura, Nicholas; Smith, Joshua; Yu, Hsiang-Hsuan Michael

    2018-06-01

    Metastatic bone pain is a complex, poorly understood process. Understanding the unique mechanisms causing cancer-induced bone pain may lead to potential therapeutic targets. This article discusses the effects of osteoclast overstimulation within the tumor microenvironment; the role of inflammatory factors at the tumor-nociceptor interface; the development of structural instability, causing mechanical nerve damage; and, ultimately, the neuroplastic changes in the setting of sustained pain. Several adjuvant therapies are available to attenuate metastatic bone pain. This article discusses the role of pharmacologic therapies, surgery, kyphoplasty, vertebroplasty, and radiofrequency ablation. Copyright © 2018 Elsevier Inc. All rights reserved.

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

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    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.

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

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    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.

  1. Adjuvant therapy decisions based on magnetic resonance imaging of extramural venous invasion and other prognostic factors in colorectal cancer

    Science.gov (United States)

    Swift, RI; Chau, I; Heald, RJ; Tekkis, PP; Brown, G

    2014-01-01

    Introduction There remains a lack of high quality randomised trial evidence for the use of adjuvant chemotherapy in stage II rectal cancer, particularly in the presence of high risk features such as extramural venous invasion (EMVI). The aim of this study was to explore this issue through a survey of colorectal surgeons and gastrointestinal oncologists. Methods An electronic survey was sent to a group of colorectal surgeons who were members of the Association of Coloproctology of Great Britain and Ireland. The survey was also sent to a group of gastrointestinal oncologists through the Pelican Cancer Foundation. Reminder emails were sent at 4 and 12 weeks. Results A total of 142 surgeons (54% response rate) and 99 oncologists (68% response rate) responded to the survey. The majority in both groups of clinicians thought EMVI was an important consideration in adjuvant treatment decision making and commented routinely on this in their multidisciplinary team meeting. Although both would consider treating patients on the basis of EMVI detected by magnetic resonance imaging, oncologists were more selective. Both surgeons and oncologists were prepared to offer patients with EMVI adjuvant chemotherapy but there was lack of consensus on the benefit. Conclusions This survey reinforces the evolution in thinking with regard to adjuvant therapy in stage II disease. Factors such as EMVI should be given due consideration and the prognostic information we offer patients must be more accurate. Historical data may not accurately reflect today’s practice and it may be time to consider an appropriately designed trial to address this contentious issue. PMID:25245736

  2. 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......-treatment sera from 460 patients with stage IIB-IIIC melanoma were analyzed for MMP-8. The patients were randomized after surgery to adjuvant IFN-α for 12 or 24 months (n = 313) or observation only (n = 147). The median serum MMP-8 level was used to classify the patients into a low MMP-8 (n = 232) and a high MMP......-8 (n = 228) group. In the high MMP-8 subgroup, IFN-α therapy significantly improved relapse-free survival (RFS). RFS was 36.8 months in patients with high MMP-8 levels receiving IFN-α therapy, whereas RFS for those with high MMP-8 levels with observation only was 10.6 months (P = 0.027). Median...

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

    International Nuclear Information System (INIS)

    Ost, Piet; Cozzarini, Cesare; De Meerleer, Gert; Fiorino, Claudio; De Potter, Bruno; Briganti, Alberto; Nagler, Evi V.T.; Montorsi, Francesco; Fonteyne, Valérie; Di Muzio, Nadia

    2012-01-01

    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.

  4. 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

  5. Adjuvant therapy of pancreatic carcinoma: the experience of Policlinico Umberto I, Università "Sapienza" Rome

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    De Felice F

    2013-08-01

    Full Text Available Francesca De Felice, Daniela Musio, Raffaele Cassese, Daria Masi, Vincenzo TomboliniDipartimento di Scienze Radiologiche Oncologiche e Anatomo-Patologiche, Cattedra di Radioterapia, Università degli Studi di Roma "Sapienza", Rome, ItalyBackground: Pancreatic cancer represents an unsolved oncological problem: only 10%–20% of patients have resectable disease at diagnosis. We describe our adjuvant treatment approach and our results of subsequent multidisciplinary care of resected pancreatic cancer patients.Materials and methods: Between January 2007 and May 2012, 17 patients with resected pancreatic cancer underwent adjuvant radiochemotherapy. Radiotherapy was delivered with a three-dimensional-conformational multiple field technique at a total dose of 50.4–54.0 Gy. Chemotherapy consisted of gemcitabine (200 mg/m2/week or fluorouracil (200 mg/m2/day.Results: 16 patients completed programmed treatment; one patient suspended planned adjuvant treatment because of hematological toxicity grade 3. He was the only case of toxicity grade 3. At a median follow-up of 17.7 months, nine patients are still disease-free survivors. The 2-year survival was 30%.Discussion: Our experience in resected pancreatic cancer patients treated with a radiochemotherapy regimen highlights the survival and toxicity profile benefits associated with concomitant treatment.Keywords: pancreatic cancer, adjuvant treatment, pancreas

  6. The Impact of Adjuvant Radiation Therapy for High-Grade Gliomas by Histology in the United States Population

    Energy Technology Data Exchange (ETDEWEB)

    Rusthoven, Chad G., E-mail: Chad.Rusthoven@ucdenver.edu [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Carlson, Julie A.; Waxweiler, Timothy V. [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Dally, Miranda J.; Barón, Anna E. [Department of Biostatistics and Informatics, University of Colorado School of Medicine, Aurora, Colorado (United States); Yeh, Norman; Gaspar, Laurie E.; Liu, Arthur K. [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Ney, Douglas E.; Damek, Denise M. [Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado (United States); Lillehei, Kevin O. [Department of Neurosurgery, University of Colorado School of Medicine, Aurora, Colorado (United States); Kavanagh, Brian D. [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States)

    2014-11-15

    Purpose: To compare the survival impact of adjuvant external beam radiation therapy (RT) for malignant gliomas of glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and mixed anaplastic oligoastrocytoma (AOA) histology. Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER) database was queried from 1998 to 2007 for patients aged ≥18 years with high-grade gliomas managed with upfront surgical resection, treated with and without adjuvant RT. Results: The primary analysis totaled 14,461 patients, with 12,115 cases of GBM (83.8%), 1312 AA (9.1%), 718 AO (4.9%), and 316 AOA (2.2%). On univariate analyses, adjuvant RT was associated with significantly improved overall survival (OS) for GBMs (2-year OS, 17% vs 7%, p<.001), AAs (5-year OS, 38% vs 24%, p<.001), and AOAs (5-year OS, 55% vs 44%, p=.026). No significant differences in OS were observed for AOs (5-year OS, with RT 50% vs 56% without RT, p=.277). In multivariate Cox proportional hazards models accounting for extent of resection, age, sex, race, year, marital status, and tumor registry, RT was associated with significantly improved OS for both GBMs (HR, 0.52; 95% CI, 0.50-0.55; P<.001) and AAs (HR, 0.57; 95% CI, 0.48-0.68; P<.001) but only a trend toward improved OS for AOAs (HR, 0.70; 95% CI, 0.45-1.09; P=.110). Due to the observation of nonproportional hazards, Cox regressions were not performed for AOs. A significant interaction was observed between the survival impact of RT and histology overall (interaction P<.001) and in a model limited to the anaplastic (WHO grade 3) histologies. (interaction P=.024), characterizing histology as a significant predictive factor for the impact of RT. Subgroup analyses demonstrated greater hazard reductions with RT among patients older than median age for both GBMs and AAs (all interaction P≤.001). No significant interactions were observed between RT and extent of resection. Identical patterns of significance were

  7. Inducers of Senescence, Toxic Compounds, and Senolytics: The Multiple Faces of Nrf2-Activating Phytochemicals in Cancer Adjuvant Therapy

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    Marco Malavolta

    2018-01-01

    Full Text Available The reactivation of senescence in cancer and the subsequent clearance of senescent cells are suggested as therapeutic intervention in the eradication of cancer. Several natural compounds that activate Nrf2 (nuclear factor erythroid-derived 2-related factor 2 pathway, which is involved in complex cytoprotective responses, have been paradoxically shown to induce cell death or senescence in cancer. Promoting the cytoprotective Nrf2 pathway may be desirable for chemoprevention, but it might be detrimental in later stages and advanced cancers. However, senolytic activity shown by some Nrf2-activating compounds could be used to target senescent cancer cells (particularly in aged immune-depressed organisms that escape immunosurveillance. We herein describe in vitro and in vivo effects of fifteen Nrf2-interacting natural compounds (tocotrienols, curcumin, epigallocatechin gallate, quercetin, genistein, resveratrol, silybin, phenethyl isothiocyanate, sulforaphane, triptolide, allicin, berberine, piperlongumine, fisetin, and phloretin on cellular senescence and discuss their use in adjuvant cancer therapy. In light of available literature, it can be concluded that the meaning and the potential of adjuvant therapy with natural compounds in humans remain unclear, also taking into account the existence of few clinical trials mostly characterized by uncertain results. Further studies are needed to investigate the therapeutic potential of those compounds that display senolytic activity.

  8. Effect of adjuvant acupuncture therapy on serum cytokines and neurotransmitters in patients with post-stroke depression

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    Wan Feng

    2017-07-01

    Full Text Available Objective: To study the effect of adjuvant acupuncture therapy on serum cytokines and neurotransmitters in patients with post-stroke depression. Methods: Patients with poststroke depression who were treated in Traditional Chinese Medicine Hospital of Yuyang District Yulin City between May 2014 and February 2017 were selected as the research subjects and divided into two groups by random number table, control group of patients received neurotrophy, rehabilitation exercise, antidepressant drugs and other symptomatic treatment, and the acupuncture group received auxiliary acupuncture treatment on the basis of symptomatic treatment. The serum levels of nerve cytokines, inflammatory cytokines and neurotransmitters were detected before treatment as well as 2 weeks and 4 weeks after treatment. Results: 2 weeks and 4 weeks after treatment, serum BDNF, NGF, IGF-1, FGF-2, NE, DA and 5-HT levels of both groups of patients were higher than those before treatment while HCY, IL- 1β, IL-2, sIL-2R, TNF-α levels were lower than those before treatment, and serum BDNF, NGF, IGF-1, FGF-2, NE, DA and 5-HT levels of acupuncture group were higher than those of control group while HCY, IL-1β, IL-2, sIL-2R, TNF-α levels were lower than those of control group. Conclusion: Adjuvant acupuncture therapy for post-stroke depression can increase the secretion of nerve cytokines, reduce the secretion of inflammatory cytokines and regulate the function of monoamine neurotransmitters.

  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. Survival benefit associated with adjuvant androgen deprivation therapy combined with radiotherapy for high- and low-risk patients with nonmetastatic prostate cancer

    International Nuclear Information System (INIS)

    Zeliadt, Steven B.; Potosky, Arnold L.; Penson, David F.; Etzioni, Ruth

    2006-01-01

    Background: The use of adjuvant androgen deprivation therapy (ADT) combined with radiotherapy has become common in low-risk patients, although clinical trials have focused primarily on high-risk patients. This study examines the effectiveness of adjuvant ADT combined with radiotherapy for a wide range of patients treated in the 1990s. Methods and Materials: Prostate cancer survival was examined in a population based cohort of 31,643 patients aged 65 to 85 years who were diagnosed with nonmetastatic prostate cancer and treated with external beam radiotherapy and/or brachytherapy. Instrumental variable analysis methods were used to control for selection bias. Results: Patients with stage T3/T4 disease who received adjuvant ADT experienced improved 5-year and 8-year survival. No survival advantage was observed for men with T1/T2 disease during this interval. Conclusion: High-risk patients who receive primary radiotherapy have benefited from adjuvant ADT, whereas low-risk patients with disease confined to the prostate have not yet benefited from adjuvant therapy within the first 8 years after treatment. These findings are consistent with practice guidelines, which recommend adjuvant ADT for patients with high-risk disease

  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. 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

  13. Improvement of sexual function in men with benign prostatic hyperplasia by pharmacologic therapy

    Directory of Open Access Journals (Sweden)

    Stojanović Nebojša

    2014-01-01

    Full Text Available Introduction. Benign prostatic hyperplasia (BPH causes disorders of voiding and sexual function. Pharmacologic therapy reduces symptoms of voiding thus impacting sexual function. Objective. To determine sex life status in men with BPH before and after pharmacologic treatment adapted to achieve satisfactory sexual function. Methods. We studied 117 sexually active BPH patients, not previously treated for BPH. After clinical examinations, symptoms of voiding, sexual and ejaculatory function were measured using standardized IPSS, IIEF and MSHQ-EjD questionnaires. After obtaining patients’ personal opinion about the importance of their sex life, therapy was chosen and possible side effects explained. Three groups of 39 patients each were formed. The first group was treated with alpha-blocker, tamsulosin, the second with 5-alpha reductase inhibitor, finasteride, while the third group was administered a combination therapy. The complete examination procedure was repeated after 3 and 6 months of therapy. Results. The average age of patients was 61.34±3.04 years. Eighty-seven percent reported that their sex life was important to a certain degree. Satisfaction with their sex life was reported by 47% of patients before treatment and by 67% of respondents 6 months after treatment. Questionnaire scores indicated general improvement of sexual function in all groups, which was statistically significant compared to baseline only in the group on tamsulosin alpha-blocker (2.95±7.81; p=0.028. The overall satisfaction with sex life as a component of sexual function, improved significantly in the group on the combined therapy (0.78±1.81; p=0.012. Conclusion. Before BPH treatment sexual function should be assessed and therapy customized to the patient’s expectations. Side effects of drugs should be presented especially to patients who emphasize the importance of sex life. In the manifested stages of the disease overall satisfaction with sex life may be

  14. 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.

  15. Does Adipose-derived Stromal Cell Adjuvant Therapy for Fragmented Medial Coronoid Process in Dogs Influence Outcome? A Pilot Project

    Directory of Open Access Journals (Sweden)

    Kristina M Kiefer

    2016-11-01

    Full Text Available Objective: The primary objective of this study was to identify adverse events associated with multiple intra-articular injections of adipose stromal cell (ASC therapy and secondarily to objectively assess the therapeutic effect of ASC therapy for treatment of fragmented medial coronoid process (FMCP in dogs when used as an adjuvant to standard of care (SOC treatment. Background: Preliminary trials assessing autologous ASC therapy to treat osteoarthritis indicate a positive impact on clinical signs, but assessment of donated, allogeneic ASC therapy is lacking.Evidentiary value: This prospective, randomised, controlled trial in dogs (n=30 provides objective evidence for clinical practitioners regarding ASC therapy in a naturally occurring osteoarthritic disease model.Methods: Dogs diagnosed with FMCP and osteoarthritis were enrolled. All dogs had arthroscopic fragment removal and proximal ulnar osteotomy (PUO and were assigned into three groups (n=10/group: 1 control group with no further treatment beyond the PUO and fragment removal (SOC, 2 PUO + autologous ASCs and 3 PUO+ allogeneic ASCs. Each dog had force platform gait analysis, Canine Brief Pain Inventory (CBPI questionnaires, and delayed gadolinium enhanced magnetic resonance imaging scores prior to and six months after therapeutic intervention.Results: No serious adverse events were reported in any participant. 3/10 dogs in the control group, 3/10 autologous ASC group and 7/10 allogeneic ASC group participants were assessed as successful outcomes.Conclusion: This study provides preliminary safety data for the use of intra-articular allogeneic ASC therapy to treat osteoarthritis, and justification for larger clinical studies.Application: Clinical practitioners considering ASC therapy within their practice are provided with additional evidence of autologous ASC therapy for osteoarthritis. Researchers committed to developing and generating effective ASC therapies are provided with safety

  16. New advances in amblyopia therapy I: binocular therapies and pharmacologic augmentation.

    Science.gov (United States)

    Kraus, Courtney L; Culican, Susan M

    2018-05-18

    Amblyopia therapy options have traditionally been limited to penalisation of the non-amblyopic eye with either patching or pharmaceutical penalisation. Solid evidence, mostly from the Pediatric Eye Disease Investigator Group, has validated both number of hours a day of patching and days per week of atropine use. The use of glasses alone has also been established as a good first-line therapy for both anisometropic and strabismic amblyopia. Unfortunately, visual acuity equalisation or even improvement is not always attainable with these methods. Additionally, non-compliance with prescribed therapies contributes to treatment failures, with data supporting difficulty adhering to full treatment sessions. Interest in alternative therapies for amblyopia treatment has long been a topic of interest among researchers and clinicians alike. Incorporating new technology with an understanding of the biological basis of amblyopia has led to enthusiasm for binocular treatment of amblyopia. Early work on perceptual learning as well as more recent enthusiasm for iPad-based dichoptic training have each generated interesting and promising data for vision improvement in amblyopes. Use of pharmaceutical augmentation of traditional therapies has also been investigated. Several different drugs with unique mechanisms of action are thought to be able to neurosensitise the brain and enhance responsiveness to amblyopia therapy. No new treatment has emerged from currently available evidence as superior to the traditional therapies in common practice today. But ongoing investigation into the use of both new technology and the understanding of the neural basis of amblyopia promises alternate or perhaps better cures in the future. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. Evaluation of resistance training to improve muscular strength and body composition in cancer patients undergoing neoadjuvant and adjuvant therapy: a meta-analysis.

    Science.gov (United States)

    Padilha, Camila S; Marinello, Poliana Camila; Galvão, Daniel A; Newton, Robert U; Borges, Fernando H; Frajacomo, Fernando; Deminice, Rafael

    2017-06-01

    Muscle atrophy and strength decline are two of the most prominent characteristics in cancer patients undergoing cancer therapy, leading to decreased functional ability and reduced quality of life. Therefore, the aim is to systematically review research evidence of the effects of resistance exercise (RE) on lower-limb muscular strength, lean body mass (LBM), and body fat (BF) in cancer patients undertaking neoadjuvant or adjuvant therapy. This research was conducted using the following online database: Clinical Trial Register, Cochrane Trial Register, PubMed, SPORT Discus, and SciELO, from September 2014 until May 2015. We used the following keywords in various combinations with a systematic search: "Cancer therapy," "Wasting muscle," "Muscle loss," "Muscle function," "Neoadjuvant therapy," "Adjuvant thera-py," "Resistance Training," "Weight training," and "Exercise." After selection of 272 full-text articles, 14 publications were included in this meta-analysis. Resistance exercise (RE) during neoadjuvant or adjuvant therapy increased lower-limb muscular strength (mean: 26.22 kg, 95% CI [16.01, 36.43], heterogeneity: P = body mass (LBM) increased (mean 0.8 kg, 95% CI [0.7, 0.9], heterogeneity: P = 0.99, I 2  = 0%, P body fat (BF) (mean: -1.3 kg, 95% CI [-1.5, 1.1], heterogeneity: P = 0.93, I 2  = 0%, P cancer patients undergoing neoadjuvant and adjuvant therapy regardless of the kind of treatment. RE increases muscle strength, maintains LBM, and reduces BF in cancer patients undergoing adjuvant and neoadjuvant therapies. Cancer patients and survivors should consider undertaking RE as an effective countermeasure for treatment-related adverse effects to the musculoskeletal system.

  18. Comparative Study of Multimodal and Pharmacological Therapy in Treating School Aged Children with ADHD

    Directory of Open Access Journals (Sweden)

    Susana Bogdana MILEA

    2012-09-01

    Full Text Available The attention deficit hyperactivity disorder (ADHD, one of the most commonly diagnosed psychiatric disorders among school aged children, continues to create disputes between specialists, upon the best treatment to be used. The herby study aims to bring forward some differences that may exist between the efficacy of the multimodal treatment compared to the drug treatment of ADHD. The novelty component of this study, unfolded February 2010-July 2012, is that the children, their parents and also their teachers were included in the multimodality treatment. The children included in this research (n=63, aged 6-14 and ADHD diagnosed, were randomly assigned in two groups. In the medication (Med group (n=32 the children only received the specific pharmacological treatment (Atomoxetine or Methylphenidate, and for the multimodality (MM group (n=31 the therapy included psychosocial interventions besides the drug therapy. All children were evaluated, both pre and post intervention, with the Achenbach System of Empirically Based Assessment – ASEBA, for the 6-18 aged category. We have compared the influence of therapy on the core symptoms, on the adaptive functionality and academic performance and on the competences and social functioning of the children in the two groups. The multimodal intervention proved to be more effective (p<0.05 than medication alone, firstly in ameliorating the child’s social behavior in both family and school environment, than in what concerns the main ADHD symptoms. The children’s academic performance was little impacted by either of the two therapies.

  19. 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

  20. Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis.

    Science.gov (United States)

    Mocellin, Simone; Pasquali, Sandro; Rossi, Carlo R; Nitti, Donato

    2010-04-07

    Based on previous meta-analyses of randomized controlled trials (RCTs), the use of interferon alpha (IFN-alpha) in the adjuvant setting improves disease-free survival (DFS) in patients with high-risk cutaneous melanoma. However, RCTs have yielded conflicting data on the effect of IFN-alpha on overall survival (OS). We conducted a systematic review and meta-analysis to examine the effect of IFN-alpha on DFS and OS in patients with high-risk cutaneous melanoma. The systematic review was performed by searching MEDLINE, EMBASE, Cancerlit, Cochrane, ISI Web of Science, and ASCO databases. The meta-analysis was performed using time-to-event data from which hazard ratios (HRs) and 95% confidence intervals (CIs) of DFS and OS were estimated. Subgroup and meta-regression analyses to investigate the effect of dose and treatment duration were also performed. Statistical tests were two-sided. The meta-analysis included 14 RCTs, published between 1990 and 2008, and involved 8122 patients, of which 4362 patients were allocated to the IFN-alpha arm. IFN-alpha alone was compared with observation in 12 of the 14 trials, and 17 comparisons (IFN-alpha vs comparator) were generated in total. IFN-alpha treatment was associated with a statistically significant improvement in DFS in 10 of the 17 comparisons (HR for disease recurrence = 0.82, 95% CI = 0.77 to 0.87; P < .001) and improved OS in four of the 14 comparisons (HR for death = 0.89, 95% CI = 0.83 to 0.96; P = .002). No between-study heterogeneity in either DFS or OS was observed. No optimal IFN-alpha dose and/or treatment duration or a subset of patients more responsive to adjuvant therapy was identified using subgroup analysis and meta-regression. In patients with high-risk cutaneous melanoma, IFN-alpha adjuvant treatment showed statistically significant improvement in both DFS and OS.

  1. Adjuvant therapy in stage I and stage II epithelial ovarian cancer. Results of two prospective randomized trials

    International Nuclear Information System (INIS)

    Young, R.C.; Walton, L.A.; Ellenberg, S.S.; Homesley, H.D.; Wilbanks, G.D.; Decker, D.G.; Miller, A.; Park, R.; Major, F. Jr.

    1990-01-01

    About a third of patients with ovarian cancer present with localized disease; despite surgical resection, up to half the tumors recur. Since it has not been established whether adjuvant treatment can benefit such patients, we conducted two prospective, randomized national cooperative trials of adjuvant therapy in patients with localized ovarian carcinoma. All patients underwent surgical resection plus comprehensive staging and, 18 months later, surgical re-exploration. In the first trial, 81 patients with well-differentiated or moderately well differentiated cancers confined to the ovaries (Stages Iai and Ibi) were assigned to receive either no chemotherapy or melphalan (0.2 mg per kilogram of body weight per day for five days, repeated every four to six weeks for up to 12 cycles). After a median follow-up of more than six years, there were no significant differences between the patients given no chemotherapy and those treated with melphalan with respect to either five-year disease-free survival or overall survival. In the second trial, 141 patients with poorly differentiated Stage I tumors or with cancer outside the ovaries but limited to the pelvis (Stage II) were randomly assigned to treatment with either melphalan (in the same regimen as above) or a single intraperitoneal dose of 32P (15 mCi) at the time of surgery. In this trial (median follow-up, greater than 6 years) the outcomes for the two treatment groups were similar with respect to five-year disease-free survival (80 percent in both groups) and overall survival (81 percent with melphalan vs. 78 percent with 32P; P = 0.48). We conclude that in patients with localized ovarian cancer, comprehensive staging at the time of surgical resection can serve to identify those patients (as defined by the first trial) who can be followed without adjuvant chemotherapy

  2. Progress on gene therapy, cell therapy, and pharmacological strategies toward the treatment of oculopharyngeal muscular dystrophy.

    Science.gov (United States)

    Harish, Pradeep; Malerba, Alberto; Dickson, George; Bachtarzi, Houria

    2015-05-01

    Oculopharyngeal muscular dystrophy (OPMD) is a muscle-specific, late-onset degenerative disorder whereby muscles of the eyes (causing ptosis), throat (leading to dysphagia), and limbs (causing proximal limb weakness) are mostly affected. The disease is characterized by a mutation in the poly(A)-binding protein nuclear-1 (PABPN1) gene, resulting in a short GCG expansion in the polyalanine tract of PABPN1 protein. Accumulation of filamentous intranuclear inclusions in affected skeletal muscle cells constitutes the pathological hallmark of OPMD. This review highlights the current translational research advances in the treatment of OPMD. In vitro and in vivo disease models are described. Conventional and experimental therapeutic approaches are discussed with emphasis on novel molecular therapies including the use of intrabodies, gene therapy, and myoblast transfer therapy.

  3. Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: first analysis of the early prostate cancer program

    DEFF Research Database (Denmark)

    See, William A; Wirth, Manfred P; McLeod, David G

    2002-01-01

    We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer.......We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer....

  4. End points for adjuvant therapy trials: has the time come to accept disease-free survival as a surrogate end point for overall survival?

    Science.gov (United States)

    Gill, Sharlene; Sargent, Daniel

    2006-06-01

    The intent of adjuvant therapy is to eradicate micro-metastatic residual disease following curative resection with the goal of preventing or delaying recurrence. The time-honored standard for demonstrating efficacy of new adjuvant therapies is an improvement in overall survival (OS). This typically requires phase III trials of large sample size with lengthy follow-up. With the intent of reducing the cost and time of completing such trials, there is considerable interest in developing alternative or surrogate end points. A surrogate end point may be employed as a substitute to directly assess the effects of an intervention on an already accepted clinical end point such as mortality. When used judiciously, surrogate end points can accelerate the evaluation of new therapies, resulting in the more timely dissemination of effective therapies to patients. The current review provides a perspective on the suitability and validity of disease-free survival (DFS) as an alternative end point for OS. Criteria for establishing surrogacy and the advantages and limitations associated with the use of DFS as a primary end point in adjuvant clinical trials and as the basis for approval of new adjuvant therapies are discussed.

  5. Effectiveness of high-frequency transcutaneous electrical nerve stimulation at tender points as adjuvant therapy for patients with fibromyalgia.

    Science.gov (United States)

    Carbonario, F; Matsutani, L A; Yuan, S L K; Marques, A P

    2013-04-01

    Fibromyalgia is a chronic pain syndrome associated with sleep disorders, fatigue and psychological symptoms. Combinations therapies, such as electrotherapy and therapeutic exercises have been used in the clinical practice. To assess the efficacy of high-frequency transcutaneous electrical nerve stimulation (TENS) as an adjuvant therapy to aerobic and stretching exercises, for the treatment of fibromyalgia. Controlled clinical trial. Unit of rehabilitation of a public hospital. Twenty-eight women aged 52.4±7.5 years, with fibromyalgia. A visual analogue scale measured pain intensity; tender points pain threshold, by dolorimetry; and quality of life, by the Fibromyalgia Impact Questionnaire. All subjects participated in an eight-week program consisting of aerobic exercises, followed by static stretching of muscle chains. In TENS group, high-frequency (150 Hz) was applied on bilateral tender points of trapezium and supraspinatus. TENS group had a greater pain reduction (mean change score=-2.0±2.9 cm) compared to Without TENS group (-0.7±3.7 cm). There was a difference between mean change scores of each group for pain threshold (right trapezium: 0.2±1 kg/cm² in TENS group and -0.2±1.2 kg/cm² in Without TENS group). In the evaluation of clinically important changes, patients receiving TENS had relevant improvement of pain, work performance, fatigue, stiffness, anxiety and depression compared to those not receiving TENS. It has suggested that high-frequency TENS as an adjuvant therapy is effective in relieving pain, anxiety, fatigue, stiffness, and in improving ability to work of patients with fibromyalgia. High-frequency TENS may be used as a short-term complementary treatment of fibromyalgia.

  6. The alterations of serum FGF-21 levels, metabolic and body composition in early breast cancer patients receiving adjuvant endocrine therapy.

    Science.gov (United States)

    Akyol, Murat; Alacacioglu, Ahmet; Demir, Leyla; Kucukzeybek, Yuksel; Yildiz, Yasar; Gumus, Zehra; Kara, Mete; Salman, Tarik; Varol, Umut; Taskaynatan, Halil; Oflazoglu, Utku; Bayoglu, Vedat; Tarhan, Mustafa Oktay

    2017-01-01

    In early breast cancer patients, the effects of hormonal therapy (tamoxifen and aromatase inhibitors) on plasma fibroblast growth factor 21 (FGF-21), lipid levels and body composition have not yet been investigated. Therefore, we aimed to analyze the relationship between FGF-21 and body composition as well as the effects of tamoxifen and aromatase inhibitors on plasma lipid levels, FGF-21, and body composition. A total of 72 patients were treated with either tamoxifen or aromatase inhibitors due to their menopausal status after adjuvant radiotherapy. Each patient was followed-up over a period of 1 year. Changes in body composition and serum lipid profile, glucose and FGF-21 levels were evaluated. We recorded the type of hormonal therapy, body mass index, waist-to-hip ratio, lipid profile, and FGF-21 levels both at the beginning and after 12 months. There was a statistically significant decrease in serum FGF-21 levels after 12 months of adjuvant endocrine therapy (46 ± 19.21 pg/ml vs. 30.99 ± 13.81 pg/ml, pbody water (pbody composition, glucose, lipid profile and FGF-21 were similar in tamoxifen and aromatase inhibitor groups. A positive correlation was found between basal weight, fat mass, fat-free mass and serum FGF-21 levels; however, the correlation was maintained only for the fat-free mass at the 12th month. As part of the present study, we suggest that both tamoxifen and aromatase inhibitors can reduce FGF-21 levels independently of body compositions, and these drugs can provide antihyperlipidemic, antidiabetic and cardio-protective effects. We also recommend that serum FGF-21 level can be utilized as a tumor biomarker in early-stage breast cancer and for monitoring purposes. FGF-21 levels may help physicians estimate prognosis, too. Further studies with larger populations may shed light on the role of FGF-21 in breast cancer.

  7. 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

    , 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......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...... 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...

  8. Fluorouracil and high-dose leucovorin with radiotherapy as adjuvant therapy for rectal cancer. Results of a phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Giralt, J. [Radiation Oncology Service, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Rubio, D. [Medical Oncology Service, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Maldonado, X. [Radiation Oncology Service, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Naval, J. [Dept. of Surgery, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Casado, S. [Medical Oncology Service, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Lara, F. [Dept. of Surgery, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Rosello, J.M. [Dept. of Preventive Medicine, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Armengol, M. [Dept. of Surgery, Hospital General Universitari Vall d`Hebron, Barcelona (Spain)

    1997-07-01

    The purpose of this phase II study was to evaluate the efficacy and toxicity of fluorouracil and high-dose leucovorin (5-FU/LV) with pelvic irradiation as adjuvant therapy for patients with macroscopical resected rectal or recto-sigmoid cancer. Following surgery for stages II-III primary (52) or recurrent rectal cancer (4), 56 patients received 8 cycles of 5-FU/LV and pelvic irradiation. 5-FU doses were 200 mgr/m{sup 2} for cycles 2-3 and 300 mgr/m{sup 2} for cycles 1 and 4-8. LV doses remained fixed at 200 mgr/m{sup 2}. Pelvic radiation was started in the third week, between the first and second cycle. The total dose was 50.4 Gy. No serve complications had been recorded. The incidence of grade 3 diarrhea was 19%. Three patients presented leukopenia grade 3 (5%). In 44 patients (78%) the planned treatment could be administered. The median follow-up was 40 months (range 22-66). Seven patients had a local relapse (13%) and 6 developed distant metastasis (10%). The 3-year disease-free survival was 72% and the overall survival was 76%. These preliminary results show that combined post-operative 5-FU/LV and pelvic radiotherapy are well tolerated and present a reasonable local control and survival rates. This adjuvant treatment should be evaluated in randomized trials. (orig.).

  9. Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients.

    Science.gov (United States)

    Dienstmann, Rodrigo; Salazar, Ramon; Tabernero, Josep

    2015-06-01

    For more than three decades, postoperative chemotherapy-initially fluoropyrimidines and more recently combinations with oxaliplatin-has reduced the risk of tumor recurrence and improved survival for patients with resected colon cancer. Although universally recommended for patients with stage III disease, there is no consensus about the survival benefit of postoperative chemotherapy in stage II colon cancer. The most recent adjuvant clinical trials have not shown any value for adding targeted agents, namely bevacizumab and cetuximab, to standard chemotherapies in stage III disease, despite improved outcomes in the metastatic setting. However, biomarker analyses of multiple studies strongly support the feasibility of refining risk stratification in colon cancer by factoring in molecular characteristics with pathologic tumor staging. In stage II disease, for example, microsatellite instability supports observation after surgery. Furthermore, the value of BRAF or KRAS mutations as additional risk factors in stage III disease is greater when microsatellite status and tumor location are taken into account. Validated predictive markers of adjuvant chemotherapy benefit for stage II or III colon cancer are lacking, but intensive research is ongoing. Recent advances in understanding the biologic hallmarks and drivers of early-stage disease as well as the micrometastatic environment are expected to translate into therapeutic strategies tailored to select patients. This review focuses on the pathologic, molecular, and gene expression characterizations of early-stage colon cancer; new insights into prognostication; and emerging predictive biomarkers that could ultimately help define the optimal adjuvant treatments for patients in routine clinical practice. © 2015 by American Society of Clinical Oncology.

  10. Pharmacological treatment and BBB-targeted genetic therapy for MCT8-dependent hypomyelination in zebrafish

    Directory of Open Access Journals (Sweden)

    David Zada

    2016-11-01

    Full Text Available Hypomyelination is a key symptom of Allan-Herndon-Dudley syndrome (AHDS, a psychomotor retardation associated with mutations in the thyroid-hormone (TH transporter MCT8 (monocarboxylate transporter 8. AHDS is characterized by severe intellectual deficiency, neuromuscular impairment and brain hypothyroidism. In order to understand the mechanism for TH-dependent hypomyelination, we developed an mct8 mutant (mct8−/− zebrafish model. The quantification of genetic markers for oligodendrocyte progenitor cells (OPCs and mature oligodendrocytes revealed reduced differentiation of OPCs into oligodendrocytes in mct8−/− larvae and adults. Live imaging of single glial cells showed that the number of oligodendrocytes and the length of their extensions are reduced, and the number of peripheral Schwann cells is increased, in mct8−/− larvae compared with wild type. Pharmacological analysis showed that TH analogs and clemastine partially rescued the hypomyelination in the CNS of mct8−/− larvae. Intriguingly, triiodothyronine (T3 treatment rescued hypomyelination in mct8−/− embryos before the maturation of the blood–brain barrier (BBB, but did not affect hypomyelination in older larvae. Thus, we expressed Mct8-tagRFP in the endothelial cells of the vascular system and showed that even relatively weak mosaic expression completely rescued hypomyelination in mct8−/− larvae. These results suggest potential pharmacological treatments and BBB-targeted gene therapy that can enhance myelination in AHDS and possibly in other TH-dependent brain disorders.

  11. 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.

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

    Science.gov (United States)

    Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol; Kim, Nam Kyu; Kim, Hyeong-Rok; Kang, Sung-Bum; Choi, Gyu-Seog; Lee, Kang Young; Kim, Seon-Hahn; Oh, Seung Taek; Lim, Seok-Byung; Kim, Jin Cheon; Oh, Jae Hwan; Kim, Sun Young; Lee, Woo Yong; Lee, Jung Bok; Yu, Chang Sik

    2015-07-01

    To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. 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. 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). 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. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol; Kim, Nam Kyu; Kim, Hyeong-Rok; Kang, Sung-Bum; Choi, Gyu-Seog; Lee, Kang Young; Kim, Seon-Hahn; Oh, Seung Taek; Lim, Seok-Byung; Kim, Jin Cheon; Oh, Jae Hwan; Kim, Sun Young; Lee, Woo Yong; Lee, Jung Bok; Yu, Chang Sik

    2015-01-01

    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

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

    International Nuclear Information System (INIS)

    Schmidt, Martina E.; Meynköhn, Anna; Habermann, Nina; Wiskemann, Joachim; Oelmann, Jan; Hof, Holger; Wessels, Sabine; Klassen, Oliver; Debus, Jürgen; Potthoff, Karin; Steindorf, Karen; Ulrich, Cornelia M.

    2016-01-01

    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"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

  15. 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

  16. Pharmacologic Treatment of Wet Type Age-related Macular Degeneration; Current and Evolving Therapies.

    Science.gov (United States)

    Shams Najafabadi, Hoda; Daftarian, Narsis; Ahmadieh, Hamid; Soheili, Zahra-Soheila

    2017-08-01

    Age-related macular degeneration as the major cause of blindness in the elderly population has remained at the epicenter of clinical research in ophthalmology. This retinal disorder is characterized by the photoreceptor and retinal pigment epithelial cells loss, occurring within the macula. The disease represents a spectrum of clinical manifestations. It is a multifactorial disease resulting from a combination of genetic predispositions and environmental risk factors. AMD is classified into two different types, dry and wet. Wet AMD is in close relation with angiogenesis and inflammatory processes.A variety of anti-angiogenesis and anti-inflammatory drugs have been proposed for the treatment of the disease. The purpose of this paper is to briefly review the pharmacological therapies of the wet form of AMD and focus on new drugs that are currently in different stages of research and development.

  17. Diabetic Macular Edema: Current Understanding, Pharmacologic Treatment Options, and Developing Therapies.

    Science.gov (United States)

    Miller, Kevin; Fortun, Jorge A

    2018-01-01

    Diabetic retinopathy and diabetic macular edema comprise a major source of visual disability throughout the developed world. The etiology and pathogenesis of macular edema is intricate and multifactorial, in which the hyperglycemic state in diabetes induces a microangiopathy. Through several inflammatory and vasogenic mediators, including vascular endothelial growth factor (VEGF) upregulation and inflammatory cytokines and chemokines, pathologic changes are induced in the vascular endothelium triggering breakdown of the blood retinal barrier, causing extravasation of fluid into the extracellular space and manifesting clinically as macular edema, resulting in visual loss. The advent of medications targeting the VEGF pathway has led to great clinical improvements compared with the previous standard of care of laser therapy alone, as shown in studies such as RISE, RIDE, VIVID, VISTA, and DRCR. However, analyses have shown that many patients have inadequate response or are nonresponders to anti-VEGF therapy, demonstrating the need for additional therapies to more comprehensively treat this disease. Although corticosteroid treatments and implants have demonstrated some efficacy in adjunctive and supplemental treatment, the need to more adequately treat macular edema remains. Our knowledge of diabetic macular edema continues to grow, leading to new currently available and emerging pharmacotherapies to further enhance our treatment and restore vision in those affected by diabetic macular edema. This review will discuss the pathogenesis of diabetic macular edema and the pharmacologic therapies available for its treatment, including anti-VEGF, steroids, and newer therapies still in development, such as angiopoietin antagonists, Tie2 agonists, kallikrein inhibitors, interleukin inhibitors, and others. Copyright 2018 Asia-Pacific Academy of Ophthalmology.

  18. Adjuvant postoperative radiation therapy following simple hysterectomy and radical hysterectomy in stage IB cancer of the cervix: Analysis of risk factors and patterns of failure

    International Nuclear Information System (INIS)

    Kim, R.Y.; Weppelmann, B.; Sanford, S.P.; Salter, M.M.; Brascho, D.J.

    1986-01-01

    Between 1969 and 1980, 242 cases of stage IB cancer of the cervix were referred to the department of radiation oncology for curative radiation therapy. In 186 cases treatment was with radiation therapy alone. In 56 cases treatment included adjuvant postoperative radiation therapy; a minimum follow-up of 5 years has been carried out in this group. In 17 cases radiation therapy followed a simple hysterectomy for an unexpected stage IB cancer of the cervix. In 39 cases radiation therapy was given after a radical hysterectomy for stage IB cancer of the cervix because of positive margins and/or positive pelvic lymph nodes

  19. Metachronous esophageal cancer which occurred after chemoradiotherapy as adjuvant therapy, report of two cases

    International Nuclear Information System (INIS)

    Fujiwara, Junko; Momma, Kumiko; Yoshida, Misao

    2007-01-01

    A 53-year-old male. We performed endoscopic mucosal resection (EMR) for squamous cell carcinoma of the esophagus in June, 2000 [SM1, ly (+), v (+)]. We performed chemoradiotherapy as adjuvant treatment. We diagnosed metachronous esophageal cancer six years later and performed EMR. Pathologically it was diagnosed as squamous cell carcinoma T1a-MM, ly0, v0. A 61-year-old male. We performed EMR for squamous cell carcinoma of the esophagus in November, 2000 [SM1, ly (-), v (+)]. We performed chemoradiotherapy as adjuvant treatment. We diagnosed metachronous esophageal cancer five years later, and performed EMR. Pathologically it was diagnosed as squamous cell carcinoma T1a-MM, ly1, v0. The two cases were diagnosed by six monthly endoscopic examination. The carcinoma were small, equal to less than 10 mm, but it was that their growth rate was fast, and it was noted that they were collapsed lesions whose circumference had swelled. In addition, both of the lesions had an invasion depth of T1a-MM. (author)

  20. Management of pegylated interferon alpha toxicity in adjuvant therapy of melanoma.

    Science.gov (United States)

    Daud, Adil; Soon, Christopher; Dummer, Reinhard; Eggermont, Alexander M M; Hwu, Wen-Jen; Grob, Jean Jacques; Garbe, Claus; Hauschild, Axel

    2012-08-01

    Both native IFNα2b and pegylated IFNα2b (PegIFNα2b) are approved for the adjuvant treatment of high-risk melanoma. This review compares the toxicity profiles of high-dose IFNα2b (HDI) and PegIFNα2b, and provides recommendations on the management of common PegIFNα2b-related toxicities, based on available clinical data and published literature. The toxicity profile of PegIFNα2b at the approved dose (6 μg/kg/week for 8 weeks then 3 μg/kg/week for up to 5 years) is qualitatively similar to HDI in melanoma. The most common adverse events (AEs) are fatigue, anorexia, hepatotoxicity, flu-like symptoms, injection site reactions and depression. However, fatigue and flu-like symptoms appear less severe with PegIFNα2b, and toxicity seems to occur earlier, whereas with HDI toxicity may increase with time. Most AEs can be managed effectively by dose modification and aggressive symptom control. Dosing to tolerance using a three-step dose reduction schedule to maintain an ECOG performance status of 0 - 1 may enable patients experiencing toxicity to remain on treatment; this can be applied readily in clinical practice. PegIFNα2b is therefore a valuable alternative option for adjuvant treatment in melanoma, with a toxicity profile similar to that of HDI overall but a more convenient administration schedule.

  1. Current Status of Intensified Neo-Adjuvant Systemic Therapy in Locally Advanced Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Engels, Benedikt; Gevaert, Thierry; Sermeus, Alexandra; De Ridder, Mark, E-mail: mark.deridder@uzbrussel.be [Department of Radiotherapy, UZ Brussel, Vrije Universiteit Brussel, Brussels (Belgium)

    2012-05-25

    The addition of 5-fluorouracil (5-FU) or its prodrug capecitabine to radiotherapy (RT) is a standard approach in the neo-adjuvant treatment of patients with rectal tumors extending beyond the muscularis propria (stage II) and/or with clinical evidence of regional lymph node metastases (stage III). According to European randomized trials, the combined treatment modality resulted in favorable local control rates as compared with radiotherapy (RT) alone, but no improvement was found regarding the occurrence of distant metastases or overall survival. In an effort to further enhance the response rates and to decrease the high incidence of distant metastases in locally advanced rectal cancer patients, the addition of other chemotherapeutical drugs and biologic agents as radiation sensitizers to neo-adjuvant 5-FU based chemoradiotherapy (CRT) has been recently investigated. The role of those agents is however questionable as first results from phase III data do not show improvement on pathologic complete remission and circumferential resection margin negative resection rates as compared to 5-FU based CRT, nevertheless an increased toxicity.

  2. Adjuvant and salvage therapy following radical prostatectomy for prostate cancer: effect of combined transient androgen deprivation and irradiation

    International Nuclear Information System (INIS)

    Eulau, Stephen M.; Tate, David J.; Cox, Richard S.; Bagshaw, Malcolm A.; Hancock, Steven L.

    1996-01-01

    Purpose: Adjuvant and salvage irradiation have been shown to improve local control after radical prostatectomy for prostatic cancer in patients with high risk pathologic features, rising PSA, or evidence of local failure. Transient androgen deprivation combined with primary irradiation has resulted in improved local control and biochemical disease free survival in patients with locally advanced, unresected, prostate cancer. This retrospective study evaluates whether transient androgen blockade improves the outcome from post-prostatectomy irradiation given as either adjuvant or salvage therapy. Methods: From August, 1985 to December, 1995, 105 patients were treated with radiotherapy to the prostatic fossa following radical prostatectomy for adenocarcinoma of the prostate. No patient had clinically or radiographically evident distant disease. Median follow-up was 4.6 years from the date of surgery and 3.2 years from completion of radiotherapy. Findings at prostatectomy included capsular penetration in 38 patients, seminal vesicle involvement in 42 patients, lymph node involvement in 15 patients, and positive surgical margins in 70 patients. Treatment was administered as adjuvant therapy for high risk pathologic features in 39 patients, for persistent or rising PSA in 52 patients, or for clinically evident local recurrence in 14 patients. Of the 105 patients, 32 received combined androgen deprivation/radiotherapy and 73 received radiotherapy alone. Both groups received 60-70 Gy in 2 Gy daily fractions to the prostatic fossa. Selected patients with poor prognostic features received pelvic irradiation to a median dose of 50 Gy. Androgen deprivation typically consisted of Lupron and Flutamide for 4 to 6 months before, during, and in selected cases, after irradiation. No patients received maintenance androgen deprivation or underwent orchiectomy. Tumor stage, lymph node status, Gleason sum, and indications for treatment did not differ significantly between the two groups

  3. 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; 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

  4. Prognostic value of Bcl-2 in two independent populations of estrogen receptor positive breast cancer patients treated with adjuvant endocrine therapy

    DEFF Research Database (Denmark)

    Larsen, Mathilde S; Bjerre, Karsten; Giobbie-Hurder, Anita

    2012-01-01

    Estrogen receptor (ER) status is not an optimal marker for response to adjuvant endocrine therapy since approximately 30% of patients with ER-positive tumors eventually relapse. Bcl-2 is regulated by ER and may thus be considered as an indicator of ER activity and a candidate supplementary marker...

  5. Effect of adjuvant low-molecular-weight heparin therapy on placental hypoxia and cell apoptosis in puerperae with severe preeclampsia

    Directory of Open Access Journals (Sweden)

    Miao Zhou1

    2017-04-01

    Full Text Available Objective: To study the effect of adjuvant low-molecular-weight heparin therapy on placental hypoxia and cell apoptosis in puerperae with severe preeclampsia. Methods: A total of 94 puerperae with severe preeclampsia who received treatment and safely gave birth in our hospital between May 2014 and May 2016 were selected as the research subjects and randomly divided into the LMWH group who received low-molecular-weight heparin combined with conventional symptomatic treatment and the control group who received conventional symptomatic treatment. Before and after treatment, serum was collected respectively to determine the levels of placental hypoxia-related cytokines, and after delivery, the placentas were collected to detect oxidative stress indexes and cell apoptosis indexes. Results: After treatment, serum PLGF and PAPP-A levels of both groups were significantly higher than those before treatment while sFlt-1 and sEng levels were significantly lower than those before treatment, and after treatment, serum PLGF and PAPP-A levels of LMWH group were significantly higher than those of control group while sFlt-1 and sEng levels were significantly lower than those of control group; ROS and RNS levels as well as Fas, FasL, caspase-3 and caspase-8 protein expression in placenta tissue of LMWH group were significantly lower than those of control group while GPx-1, SOD-1 and Trx levels as well as Survivin, XIAP and Bcl-2 protein expression were significantly higher than those of control group. Conclusion: Adjuvant low-molecular-weight heparin therapy can relieve the placental hypoxia, improve oxidative stress reaction and inhibit cell apoptosis in puerperae with severe preeclampsia.

  6. 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.

  7. Adjuvant therapy after resection of colorectal liver metastases: the predictive value of the MSKCC clinical risk score in the era of modern chemotherapy.

    Science.gov (United States)

    Rahbari, Nuh N; Reissfelder, Christoph; Schulze-Bergkamen, Henning; Jäger, Dirk; Büchler, Markus W; Weitz, Jürgen; Koch, Moritz

    2014-03-11

    Despite introduction of effective chemotherapy protocols, it has remained uncertain, if patients with colorectal cancer (CRC) liver metastases should receive adjuvant therapy. Clinical or molecular predictors may help to select patients at high risk for disease recurrence and death who obtain a survival advantage by adjuvant chemotherapy. A total of 297 patients with potentially curative resection of CRC liver metastases were analyzed. These patients had no neoadjuvant therapy, no extrahepatic disease and negative resection margins. The primary endpoint was overall survival. Patients' risk status was evaluated using the Memorial Sloan-Kettering Cancer Center clinical risk score (MSKCC-CRS). Multivariable analyses were performed using Cox proportional hazard models. A total of 137 (43%) patients had a MSKCC-CRS > 2. Adjuvant chemotherapy was administered to 116 (37%) patients. Patients who received adjuvant chemotherapy were of younger age (p = 0.03) with no significant difference in the presence of multiple metastases (p = 0.72) or bilobar metastases (p = 0.08). On multivariate analysis adjuvant chemotherapy was associated with improved survival in the entire cohort (Hazard ratio 0.69; 95% confidence interval 0.69-0.98). It improved survival markedly in high-risk patients with a MSKCC-CRS > 2 (HR 0.40; 95% CI 0.23-0.69), whereas it was of no benefit in patients with a MSKCC-CRS ≤ 2 (HR 0.90; 95% CI 0.57-1.43). The MSKCC-CRS offers a tool to select patients for adjuvant therapy after resection of CRC liver metastases. Validation in independent patient cohorts is required.

  8. Somato-Visceral Effects in the Treatment of Dysmenorrhea: Neuromuscular Manual Therapy and Standard Pharmacological Treatment.

    Science.gov (United States)

    Barassi, Giovanni; Bellomo, Rosa Grazia; Porreca, Annamaria; Di Felice, Piera Attilia; Prosperi, Loris; Saggini, Raoul

    2018-03-01

    This study aims to verify whether neuromuscular therapy (NMT) or pharmacology therapy (PT) is more effective for reducing symptoms in women affected by primary dysmenorrhea and the effects associated with each treatment. A controlled, randomized, single-blind clinical trial within the framework of the chair of physical medicine and rehabilitation of the University "G. d'Annunzio" of Chieti-Pescara. The study was conducted on a sample of 60 women suffering from primary dysmenorrhea. Subjects were randomly divided in two groups (A and B). Group A was treated with NMT and group B with PT. Group B was given ibuprofen or naproxen because they are considered the best painkillers for this condition. Group A was treated with 8 neuromuscular manual lumbosacral and abdominal therapy sessions twice per week for 4 weeks. Results were analyzed at the beginning (T0) and end (T1) of the study with a menstrual distress questionnaire, brief pain inventory, and visual analogue scale. Twenty patients from Group A were selected for evaluation of their maintenance of the eventual improvement that was detected in T1 at follow-up (T2). Both therapies had significant short-term effects in reducing the perception and duration of pain. However, NMT appears to give more improvements in the duration of pain. NMT had a long-term effect on perception of pain because patients conserved the positive effects of treatment after 4 weeks. NMT also had a long-term effect on duration of pain because patients conserved benefits of treatment, but this improvement started to decrease after 4 weeks. In the treatment of primary dysmenorrhea, NMT represents a valid therapeutic alternative method to PT. NMT is free from potential adverse effects of analgesics, is noninvasive, and is easy to perform.

  9. Combined influence of adjuvant therapy and interval after surgery on peripheral CD4+ T lymphocytes in patients with esophageal squamous cell carcinoma

    Science.gov (United States)

    LING, YANG; FAN, LIEYING; DONG, CHUNLEI; ZHU, JING; LIU, YONGPING; NI, YAN; ZHU, CHANGTAI; ZHANG, CHANGSONG

    2010-01-01

    The aim of this study was to investigate possible differences in cellular immunity between chemo- and/or radiotherapy groups during a long interval after surgery in esophageal squamous cell carcinoma (ESCC) patients. Cellular immunity was assessed as peripheral lymphocyte subsets in response to chemotherapy (CT), radiotherapy (RT) and CT+RT by flow cytometric analysis. There were 139 blood samples obtained at different time points relative to surgery from 73 patients with ESCC. The changes in the absolute and relative proportions of lymphocyte phenotypes were significant among the adjuvant therapy groups. There were significant differences in the absolute counts of CD4+ and CD8+ T cells among the interval groups, and a lower CD4/CD8 ratio was found in patients following a prolonged interval. RT alone had a profound effect on the absolute counts of CD3+, CD4+ and CD8+ T cells compared with the other groups. CD4+ T cells exhibited a decreasing trend during a long interval, leading to a prolonged T-cell imbalance after surgery. Univariate analysis revealed that the interaction of the type of adjuvant therapy and the interval after surgery was correlated only with the percentage of CD4+ T cells. The percentage of CD4+ T cells can be used as an indicator of the cellular immunity after surgery in ESCC patients. However, natural killer cells consistently remained suppressed in ESCC patients following adjuvant therapy after surgery. These findings confirm an interaction between adjuvant therapy and the interval after surgery on peripheral CD4+ T cells, and implies that adjuvant therapy may have selective influence on the cellular immunity of ESCC patients after surgery. PMID:23136603

  10. CD133 expression is not an independent prognostic factor in stage II and III colorectal cancer but may predict the better outcome in patients with adjuvant therapy

    International Nuclear Information System (INIS)

    Mia-Jan, Khalilullah; Jung, So Young; Kim, Ik-Yong; Oh, Sung Soo; Choi, EunHee; Chang, Sei Jin; Kang, Tae Young; Cho, Mee-Yon

    2013-01-01

    Cancer stem cells (CSCs) are notorious for their capacity of tumor progression, metastasis or resistance to chemo-radiotherapy. However, the undisputed role of cancer stem marker, CD133, in colorectal cancers (CRCs) is not clear yet. We assessed 271 surgically-resected stage II and III primary CRCs with (171) and without (100) adjuvant therapy after surgery. CD133 expression was analyzed by immunohistochemical (IHC) staining and real-time RT-PCR. CD133 promoter methylation was quantified by pyrosequencing. The CD133 IHC expression was significantly correlated with mRNA expression (p=0.0257) and inversely correlated with the promoter methylation (p=0.0001). CD133 was expressed more frequently in rectal cancer (p=0.0035), and in moderately differentiated tumors (p=0.0378). In survival analysis, CD133 expression was not significantly correlated with overall survival (OS) (p=0.9689) as well as disease-free survival (DFS) (p=0.2103). However, CD133+ tumors were significantly associated with better OS in patients with adjuvant therapy compared to those without adjuvant therapy (p<0.0001, HR 0.125, 95% CI 0.052-0.299). But the patients with CD133- tumors did not show any significant difference of survival according to adjuvant therapy (p=0.055, HR 0.500, 95% CI 0.247-1.015). In stage II and III CRCs, CD133 IHC expression may signify the benefit for adjuvant therapy although it is not an independent prognostic factor

  11. Pak1, adjuvant tamoxifen therapy, and breast cancer recurrence risk in a Danish population-based study

    DEFF Research Database (Denmark)

    Ahern, Thomas P; Cronin-Fenton, Deirdre P; Lash, Timothy L

    2016-01-01

    -/TAM - group. Pak1 cytoplasmic intensity was not associated with breast cancer recurrence in either group (ER+/TAM + ORadj for strong vs. no cytoplasmic staining = 0.91, 95% CI 0.57, 1.5; ER-/TAM - ORadj for strong vs. no cytoplasmic staining = 0.74, 95% CI 0.39, 1.4). Associations between Pak1 nuclear......Background Adjuvant tamoxifen therapy approximately halves the risk of estrogen receptor-positive (ER+) breast cancer recurrence, but many women do not respond to therapy. Observational studies nested in clinical trial populations suggest that overexpression or nuclear localization of p21-activated...... by immunohistochemical staining of primary breast tumors from recurrence cases and matched controls from two breast cancer populations; women diagnosed with ER-positive tumors who received at least one year of tamoxifen therapy (ER+/TAM+), and women diagnosed with ER-negative tumors who survived for at least one year...

  12. Influence of definitive radiation therapy for primary breast cancer on ability to deliver adjuvant chemotherapy

    International Nuclear Information System (INIS)

    Lippman, M.E.; Edwards, B.K.; Findlay, P.; Danforth, D.W. Jr.; MacDonald, H.; D'Angelo, T.; Gorrell, C.

    1986-01-01

    Primary radiotherapy as a means of managing stage I and II breast cancer is receiving increasing attention. In a prospectively randomized trial comparing modified radical mastectomy to lumpectomy followed by definitive radiotherapy, we evaluated whether radiotherapy has a deleterious effect on the ability to administer adjuvant doxorubicin and cyclophosphamide to patients with histologically positive axillary lymph nodes. All patients were treated with an identical regimen, and doses were escalated to the same degree until myelosuppression occurred. There were no significant differences in the amount of chemotherapy administered to either treatment group. Patients in both groups received approximately 100% of the predicted dose of doxorubicin and approximately 117% of the predicted dose of cyclophosphamide. At present, we have no evidence that there are differences in recurrence rates as a function of the quantity of drug received, although longer follow-up is required

  13. Systematic review of pharmacological therapies for the management of ischaemic pain in patients with non-reconstructable critical limb ischaemia.

    LENUS (Irish Health Repository)

    2017-08-23

    Critical limb ischaemia (CLI) is a severe manifestation of peripheral arterial disease, characterised by chronic ischaemic rest pain, ulcers or gangrene. Management of ischaemic pain is challenging in patients with no options for revascularisation and optimal pharmacological therapies have not been established.

  14. Brivaracetam: review of its pharmacology and potential use as adjunctive therapy in patients with partial onset seizures [Corrigendum

    OpenAIRE

    Russo, Emilio; Mumoli,Laura; Palleria,Caterina; Gasparini,Sara; Citraro,Rita; Labate,Angelo; Ferlazzo,Edoardo; Gambardella,Antonio; De Sarro,Giovambattista

    2015-01-01

    Brivaracetam: review of its pharmacology and potential use as adjunctive therapy in patients with partial onset seizures [Corrigendum] Mumoli L, Palleria C, Gasparini S, et al. Drug Des Devel Ther. 2015;9:5719–5725.   The authors advise several errors in the paper that are corrected in Corrigendum. View the original article by Mumoli et al.

  15. 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.

  16. 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).

  17. [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.

  18. Pharmacological/dynamic rehabilitative behavioural therapy for premature ejaculation: Results of a pilot study

    Directory of Open Access Journals (Sweden)

    Franco Mantovani

    2017-06-01

    Full Text Available Objectives: Premature ejaculation (PE is a sexual disorder characterised by excessive rapidity of orgasm. It is defined as either primary (60%, present since the onset of sexual activity, or secondary (40%, manifesting later in life. To date, dapoxetine is the only preparation approved for the on-demand treatment of PE. However, side effects, costs associated with the treatment of chronic PE, drug dependence and its variable effectiveness leads to a not insignificant drop-out rate. Dynamic rehabilitative/behavioural therapy may be a viable therapeutic option, working alongside pharmacological treatment, as long as the participation and involvement of both the individual and the couple is optimal. Materials and methods: 18 patients were enrolled, aged between 25 and 55 (mean: 40, all with primary PE, free of comorbidities and with their partners involved. Six patients were prescribed 30 mg dapoxetine two hours before sexual relations for 3 months (group A; 6 patients began the dynamic rehabilitative treatment (group B; 6 other couples were assigned to pharmacological treatment in association with dynamic rehabilitative behavioural treatment for 3 months (group C. Division of subjects was carried out by simple randomisation, excluding patients with a short frenulum, phimosis, ED, chronic prostatitis or experiencing results from previous treatment. Results: Outcomes of treatment were evaluated at the end of the 3 months of treatment and 3 months after discontinuing treatment. In Group A 75% of patients were cured at 3 months and 25% at 6 months. In Group B 25% patients were cured at 3 months and 25% at 6 months. In Group C 75% of patients were cured 3 months and 50% at 6 months. "Cured" means a Premature Ejaculation Diagnostic Tool (PEDT score reduced from an average of 12 to an average of 6 and Intravaginal Ejaculation Latency Time (IELT values from < 1 to > 6 minutes. Conclusions: the integration of pharmacological treatment with dynamic

  19. Comparison of Functional Capacity using Primary Percutaneous Coronary Intervention with Pharmacological Therapy on ST Elevation Acute Coronary Syndrome Patients

    Directory of Open Access Journals (Sweden)

    Andini Nurkusuma Wardhani

    2015-06-01

    Full Text Available Background: Acute Coronary Syndrome (ACS is a shift manifestations pattern of ischemic myocardium. Revascularization either with Primary Percutaneous Coronary Intervention (PCI or pharmacological therapy is an optional treatment for ST Elevation Acute Coronary Syndrome (STEACS patients. The aim of the study was to compare the functional capacity using six-minute walking test on STEACS patients who underwent Primary PCI or pharmacological therapy. Methods: A cross sectional study was conducted from September to October 2012 to 35 STEACS patients who were treated after two years. The samples were obtained from the list of patients at Dr. Hasan Sadikin General Hospital. Inclusion criteria consisted of patients diagnosed as STEACS, cooperative and not experiencing cognitive disturbance. The exclusion criteria were STEACS patients with unstable angina or myocardial infarct in the last month, stable exertional angina, and pregnant women. The patients underwent 6 minutes walking test,VO2max was measured using theCalahin and Cooper formula, then Metabolic Equation Task (METs was calculated. Data were analyzed by unpaired T-test. Results: There were 19 Primary PCI and 16 pharmacological therapy patients. The average of age between the two groups was distributed evenly. Most of the STEACS patients were male, had a college/academic degree and were retired. Patients treated with pharmacological therapy had higher average of VO2 max and METs than patients with Primary PCI. There was no significantly differences of METs between those groups (p>0.05 Conclusions: There were no significantly differences of functional capacity in STEACS patients treated with Primary PCI or Pharmacological therapy.

  20. Postoperative treatment of glioblastoma multiforme with radiation therapy plus concomitant and adjuvant temozolomide : A mono-institutional experience of 215 patients

    Directory of Open Access Journals (Sweden)

    Pramod Kumar Julka

    2013-01-01

    Full Text Available Objective: To study the clinical results and prognostic factors of patients with glioblastoma multiforme (GBM treated by postoperative radiation therapy (PORT and concomitant temozolomide followed by adjuvant temozolomide. Methods: From 2005 to 2008, 215 patients (median age 48 years with GBM were treated with PORT plus temozolomide chemotherapy. Radiation therapy (RT was employed with a dose of 60 Gy in 30 fractions over 6 weeks by conventional fractionation with concomitant temozolomide (75 mg/m 2 /day. Adjuvant therapy consisted of 6 cycles of temozolomide (150 mg/m 2 for 5 days, 28 days cycle. The primary end point of the study was overall survival (OS, and the secondary end points were progression free survival (PFS and toxicity. OS was determined with respect to different variables to study the prognostic significance. Results: Median follow up was 11 months (range 2-50 months. Median OS and PFS were 13 months and 11 months respectively. The 1-year and 2-year OS was 44% and 18% respectively. There was no statistical significant impact of age, sex, KP score, anatomical location and extent of surgery. Presentation without seizures (on univariate analysis and 6 cycles of adjuvant temozolomide therapy (on univariate as well as multivariate analysis were found significant prognostic factors. Sixteen patients developed grade III-IV neutropenia/thrombocytopenia during the course of RT. Conclusion: Our results authenticate the role of concomitant and adjuvant temozolomide chemotherapy in combination with PORT for the management of GBM patients. We strongly recommend complete 6 cycle of adjuvant temozolomide since it significantly improved the survival in our study.

  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. Does Adjuvant Radiation Therapy Improve Outcomes In pT1-3N0 Oral Cavity Cancer With Tumor-Free Margins and Perineural Invasion?

    International Nuclear Information System (INIS)

    Liao, C.-T.; Chang, J.T.-C.; Wang, H.-M.; Ng, S.-H.; Hsueh Chuen; Lee, L.-Y.; Lin, C.-H.

    2008-01-01

    Purpose: The criteria for administration of adjuvant radiation therapy (RT) in oral cavity squamous cell carcinoma (OSCC) remain controversial, and it is unclear whether patients with pT1-3N0 disease benefit from adjuvant radiation in the presence of free margins and perineural invasion. The goal of this report was to determine whether this group would benefit from adjuvant radiation therapy in terms of 5-year local control rate and overall survival rate. Methods and Materials: We retrospectively reviewed our case records from January 1996 to May 2005. In all, 460 pT1-3N0 OSCC patients had tumor-free margins, of whom 68 had perineural invasion. Postoperative adjuvant RT was performed in patients with pT4 tumors, positive lymph nodes, or close margins (≤4 mm). In addition, selected OSCC patients with large pT3 tumors or perineural invasion received postoperative adjuvant RT. Local control and overall survival rates were plotted by Kaplan-Meier analysis. Results: There were no significant differences in 5-year local control (p 0.1936) and overall survival (p = 0.5580) rates between patients with perineural invasion compared with those without. Among patients with perineural invasion, the addition of adjuvant radiotherapy did not significantly alter the 5-year local control rate (p = 0.3170) or the overall survival rate (p = 0.0935). Conclusion: Altogether, these data seem to indicate that radical surgical resection alone should be considered a sufficient treatment for OSCC patients with pT1-3N0 disease, even in the presence of perineural invasion

  3. Efficacy of l-ornithine-l-aspartate as an adjuvant therapy in cirrhotic patients with hepatic encephalopathy

    International Nuclear Information System (INIS)

    Abid, S.; Jafri, W.; Mumtaz, K.; Islam, M.; Abbas, Z.

    2011-01-01

    To evaluate the efficacy of L-ornithine-L-aspartate (LOLA) as an adjuvant therapy in cirrhotic patients with hepatic encephalopathy (HE). Study Design: Randomized placebo controlled study. Place and Duration of Study: The Aga Khan University Hospital, Karachi in the year 2003-2004. Methodology: Patients with HE were randomized to receive LOLA or placebo medicine as an adjuvant to treatment of HE. Number connection test-A (NCT-A), ammonia level, clinical grade of HE and duration of hospitalization were assessed. Results: Out of 120 patients, there were 62 males with mean age of 57 +- 11 years. Improvement in HE was higher (n=40, 66.7%) in LOLA group as compared to the placebo group (n=28, 46.7%, p=0.027). In patients with grade I or less encephalopathy, improvement was seen in 6 (35.3%) and 3 (20%) patients in LOLA and placebo groups respectively (p=0.667). Patients with HE grade II and above showed improvement in 34 (79.1%) and 25 (55.6%) cases in LOLA and placebo group respectively (p=0.019). On multivariate analysis patients with HE of grade II and above showed prothrombin time, creatinine level and use of LOLA influencing the outcome. Duration of hospitalization was 93.6 +- 25.7 hours and 135.2 +- 103.5 hours in LOLA and placebo groups respectively (p=0.025). No side effects were observed in either groups. Conclusion: In cirrhotic patients with advanced hepatic encephalopathy treatment with LOLA was safe and associated with relatively rapid improvement and shorter hospital stay. (author)

  4. 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.

  5. Eradication of breast cancer with bone metastasis by autologous formalin-fixed tumor vaccine (AFTV) combined with palliative radiation therapy and adjuvant chemotherapy: a case report.

    Science.gov (United States)

    Kuranishi, Fumito; Ohno, Tadao

    2013-06-04

    Skeletal metastasis of breast carcinoma is refractory to intensive chemo-radiation therapy and therefore is assumed impossible to cure. Here, we report an advanced case of breast cancer with vertebra-Th7 metastasis that showed complete response to combined treatments with formalin-fixed autologous tumor vaccine (AFTV), palliative radiation therapy with 36 Gy, and adjuvant chemotherapy with standardized CEF (cyclophosphamide, epirubicin, and 5FU), zoledronic acid, and aromatase inhibitors following mastectomy for the breast tumor. The patient has been disease-free for more than 4 years after the mammary surgery and remains well with no evidence of metastasis or local recurrence. Thus, a combination of AFTV, palliative radiation therapy, and adjuvant chemotherapy may be an effective treatment for this devastating disease.

  6. Adjuvant radiation therapy for bladder cancer: A dosimetric comparison of techniques

    Energy Technology Data Exchange (ETDEWEB)

    Baumann, Brian C.; Noa, Kate [Department of Radiation Oncology at the University of Pennsylvania, Philadelphia, PA (United States); Wileyto, E. Paul [Department of Biostatistics and Epidemiology at the University of Pennsylvania, Philadelphia, PA (United States); Bekelman, Justin E. [Department of Radiation Oncology at the University of Pennsylvania, Philadelphia, PA (United States); Deville, Curtiland [Department of Radiation Oncology and Molecular Radiation Sciences at Johns Hopkins University School of Medicine, Baltimore, MD (United States); Vapiwala, Neha; Kirk, Maura; Both, Stefan; Dolney, Derek; Kassaee, Ali [Department of Radiation Oncology at the University of Pennsylvania, Philadelphia, PA (United States); Christodouleas, John P., E-mail: christojo@uphs.upenn.edu [Department of Radiation Oncology at the University of Pennsylvania, Philadelphia, PA (United States)

    2015-01-01

    Trials of adjuvant radiation after cystectomy are under development. There are no studies comparing radiation techniques to inform trial design. This study assesses the effect on bowel and rectal dose of 3 different modalities treating 2 proposed alternative clinical target volumes (CTVs). Contours of the bowel, rectum, CTV-pelvic sidewall (common/internal/external iliac and obturator nodes), and CTV-comprehensive (CTV-pelvic sidewall plus cystectomy bed and presacral regions) were drawn on simulation images of 7 post-cystectomy patients. We optimized 3-dimensional conformal radiation (3-D), intensity-modulated radiation (IMRT), and single-field uniform dose (SFUD) scanning proton plans for each CTV. Mixed models regression was used to compare plans for bowel and rectal volumes exposed to 35% (V{sub 35%}), 65% (V{sub 65%}), and 95% (V{sub 95%}) of the prescribed dose. For any given treatment modality, treating the larger CTV-comprehensive volume compared with treating only the CTV-pelvic sidewall nodes significantly increased rectal dose (V{sub 35%} {sub rectum}, V{sub 65%} {sub rectum}, and V{sub 95%} {sub rectum}; p < 0.001 for all comparisons), but it did not produce significant differences in bowel dose (V{sub 95%} {sub bowel}, V{sub 65%} {sub bowel}, or V{sub 35%} {sub bowel}). The 3-D plans, compared with both the IMRT and the SFUD plans, had a significantly greater V{sub 65%} {sub bowel} and V{sub 95%} {sub bowel} for each proposed CTV (p < 0.001 for all comparisons). The effect of treatment modality on rectal dosimetry differed by CTV, but it generally favored the IMRT and the SFUD plans over the 3-D plans. Comparison of the IMRT plan vs the SFUD plan yielded mixed results with no consistent advantage for the SFUD plan over the IMRT plan. Targeting a CTV that spares the cystectomy bed and presacral region may marginally improve rectal toxicity but would not be expected to improve the bowel toxicity associated with any given modality of adjuvant radiation

  7. Systematic review and comparison of pharmacologic therapies for neuropathic pain associated with spinal cord injury

    Directory of Open Access Journals (Sweden)

    Snedecor SJ

    2013-07-01

    Full Text Available Sonya J Snedecor,1 Lavanya Sudharshan,1 Joseph C Cappelleri,2 Alesia Sadosky,3 Pooja Desai,4 Yash J Jalundhwala,5 Marc Botteman1 1Pharmerit International, Bethesda, MD, USA; 2Global Research and Development, Pfizer, Groton, CT, USA; 3Biostatistics, Pfizer, New York, NY, USA; 4College of Pharmacy, University of Texas at Austin, Austin, TX, USA; 5Pharmacy Administration, University of Illinois at Chicago, Chicago, IL, USA Background: Management of neuropathic pain (NeP associated with spinal cord injury (SCI is difficult. This report presents a systematic literature review and comparison of the efficacy and safety of pharmacologic therapies for treating SCI-associated NeP. Methods: Medline, Embase, Cochrane, and Database of Abstracts of Reviews of Effects were searched through December 2011 for randomized, blinded, and controlled clinical trials of SCI-associated NeP meeting predefined inclusion criteria. Efficacy outcomes of interest were pain reduction on the 11-point numeric rating scale (NRS or 100 mm visual analog scale and proportion of patients achieving ≥30% or ≥50% pain reduction. Discontinuations and adverse events (AEs were also assessed, for which Bayesian meta-analytic indirect comparisons were performed. Results: Of the nine studies included in the analysis, samples were <100 patients, except for one pregabalin study (n = 136. Standard errors for the NRS outcome were often not reported, precluding quantitative comparisons across treatments. Estimated 11-point NRS pain reduction relative to placebo was –1.72 for pregabalin, –1.65 for amitriptyline, –1.0 for duloxetine, –1 (median for levetiracetam, –0.27 for gabapentin, 1 (median for lamotrigine, and 2 for dronabinol. Risk ratios relative to placebo for 30% improvement were 0.71 for levetiracetam and 2.56 for pregabalin, and 0.94 and 2.91, respectively, for 50% improvement. Meta-analytic comparisons showed significantly more AEs with pregabalin and tramadol compared with

  8. Successful management of Churg-Strauss syndrome using omalizumab as adjuvant immunomodulatory therapy: first documented pediatric case.

    Science.gov (United States)

    Iglesias, E; Camacho Lovillo, M; Delgado Pecellín, I; Lirola Cruz, M J; Falcón Neyra, M D; Salazar Quero, J C; Bernabeu-Wittel, J; González Valencia, J P; Neth, O

    2014-03-01

    Churg-Strauss syndrome (CSS) is an anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis; it is extremely rare in childhood and defined according to the Chapel-Hill Consensus as an eosinophil-rich and granulomatous inflammation involving the respiratory tract and necrotizing vasculitis affecting small to medium-sized vessels. Children commonly have a history of asthma and sinusitis whilst clinical presentation typically involves pulmonary tract and less frequently skin, heart, gastrointestinal tract, and peripheral nerves. Cardiopulmonary disease is higher in children and prognosis is worse. It is associated with significant eosinophilia and raised serum IgE-levels. ANCA are only found in 25% of childhood cases. Here we report the case of a 10-year-old girl who presented to us with vomiting, abdominal pain, and weight loss, paresthesias of lower extremities and breathlessness as well as a history of asthma, sinusitis and allergic rhinitis. She was treated with corticosteroids, cyclophosphamide, intravenous immunoglobulin, mycophenolate mofetil (MMF), and rituximab. However, remission was only achieved after initiation of omalizumab therapy, a recombinant humanized anti-IgE antibody. To the best of our knowledge this is the first pediatric patient suffering from CSS successfully managed with adjuvant anti-IgE therapy resulting in the control of respiratory as well as gastrointestinal symptoms. © 2013 Wiley Periodicals, Inc.

  9. POSSIBILITY OF NATURAL RAW MATERIALS USE IN THE FORMULATION OF ADJUVANT THERAPY OF TUBERCULOSIS: EXPERIENCE OF FOLK MEDICINE, MODERN STATE OF STUDIES

    Directory of Open Access Journals (Sweden)

    M. E. Kim

    2017-01-01

    Full Text Available The signs of growth in the prevalence of multidrug-resistant tuberculosis, low effectiveness of therapy indicate the urgent need to solve problems aimed at the improvement of the effectiveness of treatment: the reduction of toxicity and side effects of anti-tuberculosis drugs, the provision of good tolerability and continuity of chemotherapy; the removal of symptoms of intoxication associated with the action of the pathogen on the body, the improvement of the quality of life of patients during therapy and remission.The aim of the investigation is to study the data of folk medicine, scientific research data concerning the use of raw materials of natural (vegetable, animal and mineral origin in the adjuvant therapy of tuberculosis.Materials and methods. The study was carried out using information retrieval and library databases (PubMed, eLIBRARY, Cyberleninka, technical information of manufacturers of dietary supplements to food, as well as site materials dedicated to the use of vegetable, animal and mineral raw materials in folk medicine.Results and discussion. The adjuvant therapy of tuberculosis includes remedies of natural origin: vegetable, animal and mineral ones. According to the research data, the use of phytotherapy is aimed at enhancing diuresis, which ensures the elimination of toxic substances and their metabolites, as well as the decrease of the overall level of toxins; the strengthening of the body’s antioxidant defense, and liver specificity, the compensation for the increased consumption of vitamins, amino acids and microelements by the liver, which actively metabolizes xenobiotics, as well as the increase of the body’s overall resistance. A long-term benefit of using natural mineral raw materials in adjuvant therapy of tuberculosis is also observed.Conclusion. Thus, adjuvant therapy of tuberculosis includes the use of raw materials of natural (vegetable, animal and mineral origin, the effectiveness of which is confirmed by

  10. Multimodal manual therapy vs. pharmacological care for management of tension type headache: A meta-analysis of randomized trials.

    Science.gov (United States)

    Mesa-Jiménez, Juan A; Lozano-López, Cristina; Angulo-Díaz-Parreño, Santiago; Rodríguez-Fernández, Ángel L; De-la-Hoz-Aizpurua, Jose L; Fernández-de-Las-Peñas, Cesar

    2015-12-01

    Manual therapies are generally requested by patients with tension type headache. To compare the efficacy of multimodal manual therapy vs. pharmacological care for the management of tension type headache pain by conducting a meta-analysis of randomized controlled trials. PubMed, MEDLINE, EMBASE, AMED, CINAHL, EBSCO, Cochrane Database of Systematic Reviews, Cochrane Collaboration Trials Register, PEDro and SCOPUS were searched from their inception until June 2014. All randomized controlled trials comparing any manual therapy vs. medication care for treating tension type headache adults were included. Data were extracted and methodological quality assessed independently by two reviewers. We pooled headache frequency as the main outcome and also intensity and duration. The weighted mean difference between manual therapy and pharmacological care was used to determine effect sizes. Five randomized controlled trials met our inclusion criteria and were included in the meta-analysis. Pooled analyses found that manual therapies were more effective than pharmacological care in reducing frequency (weighted mean difference -0.8036, 95% confidence interval -1.66 to -0.44; three trials), intensity (weighted mean difference -0.5974, 95% confidence interval -0.8875 to -0.3073; five trials) and duration (weighted mean difference -0.5558, 95% confidence interval -0.9124 to -0.1992; three trials) of the headache immediately after treatment. No differences were found at longer follow-up for headache intensity (weighted mean difference -0.3498, 95% confidence interval -1.106 to 0.407; three trials). Manual therapies were associated with moderate effectiveness at short term, but similar effectiveness at longer follow-up for reducing headache frequency, intensity and duration in tension type headache than pharmacological medical drug care. However, due to the heterogeneity of the interventions, these results should be considered with caution at this stage. © International Headache

  11. 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; P<0.00001), the required levodopa dose (-55.65 mg/day, CI -62.67 to -48.62; P<0.00001) and improved UPDRS scores (UPDRS ADL score

  12. Preliminary results of capecitabine metronomic chemotherapy in operable triple-negative breast cancer after standard adjuvant therapy - A singlearm phase II study

    International Nuclear Information System (INIS)

    Shawky, H.; Galal, S.

    2014-01-01

    Purpose: The aim of this study is to investigate efficacy and toxicity of 1 year of capecitabine metronomic therapy preceded by standard adjuvant chemotherapy in triple-negative breast cancer (TNBC) patients. Methods: Between June 2010 and February 2012, 19 women with pathologically proven operable TNBC, who had received standard adjuvant chemotherapy before were enrolled. Patients received 1 year of oral capecitabine metronomic therapy (650 mg/m2, twice every day), after standard adjuvant chemotherapy and radiotherapy if indicated. The primary endpoints of this study were disease-free survival rates (DFS) and safety profile. Secondary end point was overall survival (OS). Results: The maximal follow-up was 46.6 months with a median of 30.1 months ±11.525 (95% CI; 28.5-33.5 months). The median DFS was 41.7 months ±2.7 (95% CI; 36.5-46.9). No one developed locoregional recurrence. The actuarial rate of DFS was 88.8% and 82.05% at 2 and 3 years, respectively. At the time of the analyses, no patients had died and the median OS was not reached. Treatment-related adverse events were manageable with only 1 patient (5.3%) suffering from Grade 3/4 hand-foot syndrome and another 1 patient (5.3%) suffering from Grade 3 diarrhea. No Grade 3/4 hematologic toxicity was recorded. All patients received full doses of capecitabine throughout the study and dose reduction was not required in any of our patients. Conclusion: One year of capecitabine metronomic therapy preceded by standard adjuvant chemotherapy, is active and well-tolerated in TNBC patients previously treated with standard adjuvant chemotherapy.

  13. Preliminary results of capecitabine metronomic chemotherapy in operable triple-negative breast cancer after standard adjuvant therapy--a single-arm phase II study.

    Science.gov (United States)

    Shawky, Hanan; Galal, Samar

    2014-12-01

    The aim of this study is to investigate efficacy and toxicity of 1 year of capecitabine metronomic therapy preceded by standard adjuvant chemotherapy in triple-negative breast cancer (TNBC) patients. Between June 2010 and February 2012, 19 women with pathologically proven operable TNBC, who had received standard adjuvant chemotherapy before were enrolled. Patients received 1 year of oral capecitabine metronomic therapy (650 mg/m2, twice every day), after standard adjuvant chemotherapy and radiotherapy if indicated. The primary endpoints of this study were disease-free survival rates (DFS) and safety profile. Secondary end point was overall survival (OS). The maximal follow-up was 46.6 months with a median of 30.1 months±11.525 (95% CI; 28.5-33.5 months). The median DFS was 41.7 months±2.7 (95% CI; 36.5-46.9). No one developed locoregional recurrence. The actuarial rate of DFS was 88.8% and 82.05% at 2 and 3 years, respectively. At the time of the analyses, no patients had died and the median OS was not reached. Treatment-related adverse events were manageable with only 1 patient (5.3%) suffering from Grade 3/4 hand-foot syndrome and another 1 patient (5.3%) suffering from Grade 3 diarrhea. No Grade 3/4 hematologic toxicity was recorded. All patients received full doses of capecitabine throughout the study and dose reduction was not required in any of our patients. One year of capecitabine metronomic therapy preceded by standard adjuvant chemotherapy, is active and well-tolerated in TNBC patients previously treated with standard adjuvant chemotherapy. Copyright © 2014. Production and hosting by Elsevier B.V.

  14. The cerebrospinal fluid/serum leptin ratio during pharmacological therapy for obesity.

    Science.gov (United States)

    Rodrigues, Adriane Maria; Radominski, Rosana Bento; Suplicy, Henrique de Lacerda; De Almeida, Sergio Monteiro; Niclewicz, Patricia Artigas; Boguszewski, Cesar Luiz

    2002-04-01

    The aim of the present study was to evaluate the cerebrospinal fluid (CSF)/serum leptin ratio during pharmacological therapy for obesity with centrally and peripherally acting drugs. Thirty-one obese women (mean age, 32.3 +/- 10 yr; body mass index, 38.2 +/- 5.2 kg/m(2); body fat, 43.3 +/- 5.4%) were studied before and 2 months after a weight loss program consisting of a balanced diet (1200 kcal/d) plus drug therapy. The patients were randomly assigned into three study groups: group I, fenproporex 25 mg/d (n = 10); group II, sibutramine 10 mg/d (n = 10); and group III, orlistat 120 mg tid (n = 11). Body fat, measured by dual-energy x-ray absorptiometry, and serum and CSF concentrations of leptin were examined at baseline and 2 months after therapy. At baseline, clinical and biochemical characteristics of the groups were similar. All of the women lost weight, approximately 7.0% of their initial body weight, and the reduction was not different among the groups. Serum leptin fell significantly after 2 months in all groups, and the decline was proportional to the reduction in body fat, because leptin levels adjusted for body fat did not change after treatment. CSF leptin levels showed a significant decrease after 2 months in all groups, and this decline was higher on group III compared with group I (P = 0.006). After therapy, the CSF/serum leptin ratio did not change in group I (1.57 +/- 0.3 to 1.72 +/- 0.62%) and group II (1.78 +/- 1.01 to 1.69 +/- 1.27%), whereas it declined significantly in group III (1.65 +/- 0.43 to 1.09 +/- 0.47%; P obese women treated during 2 months with orlistat, whereas this ratio did not change in this period of time in obese women treated with fenproporex and sibutramine.

  15. 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.

  16. Where current pharmacological therapies fall short in COPD: symptom control is not enough

    Directory of Open Access Journals (Sweden)

    N. Roche

    2007-09-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is a common and progressive condition that is currently the fourth leading cause of death worldwide. There is now a large body of evidence indicating that both pulmonary and systemic inflammation are present in patients with stable COPD and may underlie both respiratory symptoms and common comorbidities of this disease. Smoking cessation and long-term oxygen therapy have been shown to change the course of COPD and recent results obtained with the combination of fluticasone and salmeterol have indicated that it could decrease mortality and slow the decline in lung function in patients with this disease. However, some pharmacological treatments can significantly improve dyspnoea, exercise tolerance, limitations in activity, rate of exacerbations and quality of life (e.g. long-acting bronchodilators and inhaled corticosteroids combined with a long-acting beta2-agonist. The ability of these agents to modify the rate of disease progression remains to be firmly established in large-scale, long-term trials. The concept of disease modification itself in COPD may need to be revisited and more precisely defined in terms of markers and clinical outcomes, including extrarespiratory manifestations: agents that durably affect symptoms, activities, exacerbations and quality of life should probably be considered as disease modifiers. It is also reasonable to suggest that early diagnosis and treatment of patients with COPD might be the first and potentially most important disease-modifying intervention. There is clearly a need for new therapies that directly target the specific inflammatory processes underlying chronic obstructive pulmonary disease and its pulmonary and extrapulmonary manifestations.

  17. Getting Innovative Therapies Faster to Patients at the Right Dose: Impact of Quantitative Pharmacology Towards First Registration and Expanding Therapeutic Use.

    Science.gov (United States)

    Nayak, Satyaprakash; Sander, Oliver; Al-Huniti, Nidal; de Alwis, Dinesh; Chain, Anne; Chenel, Marylore; Sunkaraneni, Soujanya; Agrawal, Shruti; Gupta, Neeraj; Visser, Sandra A G

    2018-03-01

    Quantitative pharmacology (QP) applications in translational medicine, drug-development, and therapeutic use were crowd-sourced by the ASCPT Impact and Influence initiative. Highlighted QP case studies demonstrated faster access to innovative therapies for patients through 1) rational dose selection for pivotal trials; 2) reduced trial-burden for vulnerable populations; or 3) simplified posology. Critical success factors were proactive stakeholder engagement, alignment on the value of model-informed approaches, and utilizing foundational clinical pharmacology understanding of the therapy. © 2018 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  18. Acute diarrhea during adjuvant therapy for rectal cancer: a detailed analysis from a randomized intergroup trial

    International Nuclear Information System (INIS)

    Miller, Robert C.; Sargent, Daniel J.; Martenson, James A.; Macdonald, John S.; Haller, Daniel; Mayer, Robert J.; Gunderson, Leonard L.; Rich, Tyvin A.; Cha, Stephen S.; O'Connell, Michael J.

    2002-01-01

    Purpose: During adjuvant radiotherapy (RT) for rectal cancer, patients receiving 5-fluorouracil (5-FU) by protracted venous infusion have a higher risk of diarrhea than have patients receiving bolus 5-FU. Toxicity from a previously reported randomized clinical trial was analyzed to quantify the difference in this risk. Additionally, the persistence of diarrhea after RT was analyzed. Methods and Materials: A total of 656 patients were eligible. Patients with T3-4 N0-2 M0 or T1-2 N1-2 M0 resected, high-risk rectal cancer were randomly allocated to receive 5-FU by either protracted venous infusion or bolus during RT (50.4-54.0 Gy). Two cycles of bolus 5-FU were given before and after RT. One-half of the first 445 patients were also randomly allocated to receive lomustine in conjunction with the bolus 5-FU. The incidence and severity of diarrhea in relation to patient and treatment characteristics were evaluated. Results: The rate of diarrhea was significantly greater in patients receiving 5-FU by protracted venous infusion than in patients receiving bolus 5-FU; the difference was most pronounced for Grade 3 (severe) diarrhea (21% versus 13%, p=0.007). The incidence and magnitude of diarrhea before and after RT were similar. Patients treated with an anterior resection had a higher rate of severe or life-threatening diarrhea than did patients treated with an abdominoperineal resection (31% vs. 12%, p<0.001). Conclusions: During pelvic RT, patients who receive 5-FU by protracted venous infusion rather than by bolus have a higher risk of severe or life-threatening diarrhea during RT. This risk does not appear to persist during chemotherapy after completion of pelvic RT

  19. Patterns of Failure After Radical Cystectomy for pT3-4 Bladder Cancer: Implications for Adjuvant Radiation Therapy

    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); Pariser, Joseph J.; Pearce, Shane M. [Section of Urology, Department of Surgery, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States); Weichselbaum, Ralph R. [Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States); Smith, Norm 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)

    2016-04-01

    Purpose: In patients with muscle-invasive bladder cancer, local-regional failure (LF) has been reported to occur in up to 20% of patients following radical cystectomy. The goals of this study were to describe patterns of LF, as well as assess factors associated with LF in a cohort of patients with pT3-4 bladder cancer. This information may have implications towards the use of adjuvant radiation therapy. Methods and Materials: Patients with pathologic T3-4 N0-1 bladder cancer were examined from an institutional radical cystectomy database. Preoperative demographics and pathologic characteristics were examined. Outcomes included overall survival and LF. Local-regional failures were defined using follow-up imaging reports and scans, and the locations of LF were characterized. Variables were tested by univariate and multivariate analysis for association with LF and overall survival. Results: A total of 334 patients had pT3-4 and N0-1 disease after radical cystectomy and bilateral pelvic lymph node dissection. Of these, 46% received perioperative chemotherapy. The median age was 71 years old, and median follow-up was 11 months. On univariate analysis, margin status, pT stage, and pN stage, were all associated with LF (P<.05), however, on multivariate analysis, only pT and pN stages were significantly associated with LF (P<.05). Three strata of risk were defined, including low-risk patients with pT3N0 disease, intermediate-risk patients with pT3N1 or pT4N0 disease, and high-risk patients with pT4N1 disease, who had a 2-year incidence of LF of 12%, 33%, and 72%, respectively. The most common sites of pelvic relapse included the external and internal iliac lymph nodes (LNs) and obturator LN regions. Notably, 34% of patients with LF had local-regional only disease at the time of recurrence. Conclusions: Patients with pT4 or N1 disease have a 2-year risk of LF that exceeds 30%. These patients may be the most likely to benefit from local adjuvant therapies.

  20. A prospective phase II study of adjuvant postoperative radiation therapy following nodal surgery in malignant melanoma-Trans Tasman Radiation Oncology Group (TROG) Study 96.06

    International Nuclear Information System (INIS)

    Burmeister, Bryan H.; Mark Smithers, B.; Burmeister, Elizabeth; Baumann, Kathryn; Davis, Sidney; Krawitz, Hedley; Johnson, Carol; Spry, Nigel

    2006-01-01

    Background: The role of adjuvant postoperative therapy after resection of localised malignant melanoma involving regional lymph nodes remains controversial. There are no randomised trials that confirm that postoperative radiation conveys a benefit in terms of regional control or survival. Methods: Two hundred and thirty-four patients with melanoma involving lymph nodes were registered on a prospective study to evaluate the effect of postoperative radiation therapy. The regimen consisted of 48 Gy in 20 fractions to the nodal basin using recommended treatment guidelines for each of the major node sites. The primary endpoints were regional in-field relapse and late toxicity. Secondary endpoints were adjacent relapse, distant relapse, overall survival, progression-free survival and time to in-field progression. Results: Adjuvant radiation therapy was well tolerated by all of the patients. As the first site of relapse, regional in-field relapses occurred in 16/234 patients (6.8%). The overall survival was 36% at 5 years. The progression-free survival and regional control rates were 27% and 91%, respectively, at 5 years. Patients with more than 2 nodes involved had a significantly worse outcome in terms of distant relapse, overall and progression-free survival. Conclusion: We believe that adjuvant radiation therapy following nodal surgery could offer a possible benefit in terms of regional control. These results require confirmation in a randomised trial

  1. Effects of processing adjuvants on traditional Chinese herbs

    Directory of Open Access Journals (Sweden)

    Lin-Lin Chen

    2018-04-01

    Full Text Available Processing of Chinese medicines is a pharmaceutical technique that transforms medicinal raw materials into decoction pieces for use in different therapies. Various adjuvants, such as vinegar, wine, honey, and brine, are used in the processing to enhance the efficacy and reduce the toxicity of crude drugs. Proper processing is essential to ensure the quality and safety of traditional Chinese medicines (TCMs. Therefore, sound knowledge of processing principles is crucial to the standardized use of these processing adjuvants and to facilitate the production and clinical use of decoction pieces. Many scientific reports have indicated the synergistic effects of processing mechanisms on the chemistry, pharmacology, and pharmacokinetics of the active ingredients in TCMs. Under certain conditions, adjuvants change the content of active or toxic components in drugs by chemical or physical transformation, increase or decrease drug dissolution, exert their own pharmacological effects, or alter drug pharmacokinetics. This review summarizes various processing methods adopted in the last two decades, and highlights current approaches to identify the effects of processing parameters on TCMs. Keywords: Adjuvant, Processing, Synergism, Traditional Chinese medicine

  2. 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.

  3. Association between Platelet Counts before and during Pharmacological Therapy for Patent Ductus Arteriosus and Treatment Failure in Preterm Infants

    Directory of Open Access Journals (Sweden)

    Hannes Sallmon

    2018-03-01

    Full Text Available BackgroundThe role of platelets for mediating closure of the ductus arteriosus in human preterm infants is controversial. Especially, the effect of low platelet counts on pharmacological treatment failure is still unclear.MethodsIn this retrospective study of 471 preterm infants [<1,500 g birth weight (BW], who were treated for a patent ductus arteriosus (PDA with indomethacin or ibuprofen, we investigated whether platelet counts before or during pharmacological treatment had an impact on the successful closure of a hemodynamically significant PDA. The effects of other factors, such as sepsis, preeclampsia, gestational age, BW, and gender, were also evaluated.ResultsPlatelet counts before initiation of pharmacological PDA treatment did not differ between infants with later treatment success or failure. However, we found significant associations between low platelet counts during pharmacological PDA therapy and treatment failure (p < 0.05. Receiver operating characteristic (ROC curve analysis showed that platelet counts after the first, and before and after the second cyclooxygenase inhibitor (COXI cycle were significantly associated with treatment failure (area under the curve of >0.6. However, ROC curve analysis did not reveal a specific platelet cutoff-value that could predict PDA treatment failure. Multivariate logistic regression analysis showed that lower platelet counts, a lower BW, and preeclampsia were independently associated with COXI treatment failure.ConclusionWe provide further evidence for an association between low platelet counts during pharmacological therapy for symptomatic PDA and treatment failure, while platelet counts before initiation of therapy did not affect treatment outcome.

  4. 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

  5. Lithium as adjuvant to radioiodine therapy in differentiated thyroid carcinoma: clinical and in vitro studies

    NARCIS (Netherlands)

    Liu, Y. Y.; van der Pluijm, G.; Karperien, M.; Stokkel, M. P. M.; Pereira, A. M.; Morreau, J.; Kievit, J.; Romijn, J. A.; Smit, J. W. A.

    2006-01-01

    Lithium has been reported to increase radioactive iodine (RaI) doses in benign thyroid disease and in differentiated thyroid carcinoma (DTC). It is not known whether lithium influences the outcome of RaI therapy in DTC. We therefore studied the clinical effects of RaI without and with lithium

  6. Adjuvant VHF therapy in locally recurrent and primary unresectable rectal cancer

    International Nuclear Information System (INIS)

    Trotter, J.M.; Lamb, M.H.; Bayliss, E.J.; Edis, A.J.; Blackwell, J.B.; Shepherd, J.M.; Cassidy, B.

    1996-01-01

    In a prospective randomized study, 434 MHz microwave therapy combined with external beam radiotherapy (VHF+RT) was compared with standard external beam radiotherapy (RT) in controlling locally recurrent or unresectable primary adenocarcinoma of the rectum. Independent assessors documented quality of life scores, performance status, toxicities local response to treatment, and systemic disease progression before treatment and after treatment and every 8 week thereafter. Of 75 patients randomized, 73 were eligible for inclusion in the study. Forty-three of these patients had local pelvic tumour recurrence only and 21 also had distant metastases. In addition, nine patients had primary inoperable carcinomas, two of whom also had metastases. Thirty-seven patients were randomized to RT and 36 to VHF+RT. Th median dose of radiation in the VHF+RT arm was 4275 cGy with a median fraction size of 150 cGy and median duration of therapy of 48.5 days versus 4500 cGy in the RT-only arm with a median fraction size of 180 cGy and median duration of therapy of 38 days. These doses are unlikely to be significantly different in biological effect. No significant difference between the two groups was observed in extent and duration of local control, measures of toxicity or quality of life scores. Additionally, survival and cumulative incidence of pelvic site of first progression did not differ significantly between the groups. It is concluded that VHF microwave therapy in conjunction with radiotherapy produces no therapeutic advantage over conventional radiation therapy alone in the treatment of locally recurrent rectal carcinoma. 35 refs., 8 tabs., 3 figs

  7. Sequence of Radiation Therapy and Chemotherapy as Adjuvant Treatment in Breast Cancer

    International Nuclear Information System (INIS)

    ABU-HAMAR, A.M.; BARAKAT, A.F.; NASEF, H.H.; ELGANTIRY, M.

    2010-01-01

    The aim of the work was to evaluate the prognostic importance of the sequence of radiotherapy (RT) and chemotherapy (CT) as adjuvant treatment in women with breast cancer who were treated with modified radical mastectomy or total mastectomy and their correlation also with other known prognostic factors. Methods: In this retrospective study, 200 women with breast cancer were evaluated. The age ranged from 25 to 73 years, with the mean age of 44 years; 125 patients had stage II and 75 had stage III disease. All were subjected to mastectomy. The influence of the following prognostic factors were evaluated: Age, histological grade, nodal status, number of positive nodes, tumor size, estrogen receptor status, menstrual status and as well as the sequence of radiotherapy and chemotherapy on 5-year locoregional disease free survival, 5-year systemic disease-free survival, and 5-year overall survival. Results: The 5-year locoregional disease free survival was 90.9% for the entire patient population. Nodal status, number of positive nodes and estrogen receptor status were prognostically significant for locoregional recurrence. The 5-year systemic disease-free survival was 67.6% for the whole group. On univariate analysis, the presence of positive axillary nodes, grade III tumor, ER-negative disease and radiotherapy first followed by chemotherapy, were independent poor risk factors for systemic recurrence. The 5-year overall survival was 71.8%. On univariate analysis, the presence of positive axillary nodes, grade III tumor, ER-negative disease and radiotherapy first followed by chemotherapy, were independent poor risk factors for death from breast cancer. Conclusions: In patients with breast cancer, a treatment protocol consisting of 6 cycles of CT followed by RT resulted in a better 5-year OS and DPS, and was easier to administer when compared with other treatment protocols. Ideal candidates are those with early-stage, age >35 years, low tumor grade, positive ER, and

  8. Association between Platelet Counts before and during Pharmacological Therapy for Patent Ductus Arteriosus and Treatment Failure in Preterm Infants.

    Science.gov (United States)

    Sallmon, Hannes; Weber, Sven C; Dirks, Juliane; Schiffer, Tamara; Klippstein, Tamara; Stein, Anja; Felderhoff-Müser, Ursula; Metze, Boris; Hansmann, Georg; Bührer, Christoph; Cremer, Malte; Koehne, Petra

    2018-01-01

    The role of platelets for mediating closure of the ductus arteriosus in human preterm infants is controversial. Especially, the effect of low platelet counts on pharmacological treatment failure is still unclear. In this retrospective study of 471 preterm infants [0.6). However, ROC curve analysis did not reveal a specific platelet cutoff-value that could predict PDA treatment failure. Multivariate logistic regression analysis showed that lower platelet counts, a lower BW, and preeclampsia were independently associated with COXI treatment failure. We provide further evidence for an association between low platelet counts during pharmacological therapy for symptomatic PDA and treatment failure, while platelet counts before initiation of therapy did not affect treatment outcome.

  9. 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

    2018-04-01

    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 group. Mitochondrial cristae appear collapsed, and Sertoli cells showed cytoplasmic vacuolations. HAART+VCO group showed improved ultrastructural details in Bm, and Sertoli cell and Leydig cells show abundant lipid droplets. Virgin coconut oil-treated group showed thinning of Bm with otherwise normal ultrastructural features of organelles. HAART-treated group showed significant increase (p Virgin coconut oil improved testicular morphology and reversed HAART-induced ultrastructural alterations. Further studies on putative mechanism are required. © 2017 Blackwell Verlag GmbH.

  10. Platelet-rich plasma, an adjuvant biological therapy to assist peripheral nerve repair

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    Mikel Sánchez

    2017-01-01

    Full Text Available Therapies such as direct tension-free microsurgical repair or transplantation of a nerve autograft, are nowadays used to treat traumatic peripheral nerve injuries (PNI, focused on the enhancement of the intrinsic regenerative potential of injured axons. However, these therapies fail to recreate the suitable cellular and molecular microenvironment of peripheral nerve repair and in some cases, the functional recovery of nerve injuries is incomplete. Thus, new biomedical engineering strategies based on tissue engineering approaches through molecular intervention and scaffolding offer promising outcomes on the field. In this sense, evidence is accumulating in both, preclinical and clinical settings, indicating that platelet-rich plasma products, and fibrin scaffold obtained from this technology, hold an important therapeutic potential as a neuroprotective, neurogenic and neuroinflammatory therapeutic modulator system, as well as enhancing the sensory and motor functional nerve muscle unit recovery.

  11. Brivaracetam: review of its pharmacology and potential use as adjunctive therapy in patients with partial onset seizures [Corrigendum

    Directory of Open Access Journals (Sweden)

    Mumoli L

    2015-12-01

    Full Text Available Brivaracetam: review of its pharmacology and potential use as adjunctive therapy in patients with partial onset seizures [Corrigendum] Mumoli L, Palleria C, Gasparini S, et al. Drug Des Devel Ther. 2015;9:5719–5725.   The authors advise several errors in the paper that are corrected in Corrigendum. View the original article by Mumoli et al.

  12. 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.

  13. Role of adjuvant therapy in the treatment of helicobacter pylori infection in children

    Directory of Open Access Journals (Sweden)

    Gerasymenko O.N.

    2014-06-01

    Full Text Available The aim was to study the effect of combined probiotic containing Lactobacillus acidophilus, Bifidobacterium infantis, Enterococcus faecium, on H.pylori eradication efficacy in the treatment of children with chronic H.pylori- associated gastroduodenitis in the scheme of "triple" therapy of H.pylori eradication. Determination of total serum Ig M , A, G protein to Ag SagA H. pylori, breathing "Helik" test, rapid urease "Helpil" test ; that of concentration of serum sCD14 was conducted. The study group included 20 children who received standard "triple" eradication therapy for 7 days and 1 caps. of probiotic 3 times a day for 4 weeks, control group (20 children – who received only standard eradication therapy. It is shown that combined use of probiotics in the treatment of Helicobacter pylori infection enhances effectiveness of eradication of H.pylori. In the basis of action of probiotic strains of the drug is an anti-inflammatory effect mediated by the impact on non-specific mechanisms of innate immunity, provided by molecular mechanism responsible for induction of sCD14 synthesis.

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

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    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.

  15. Predictors and rate of adjuvant radiation therapy following radical prostatectomy: A report from the Prostate Cancer Registry

    International Nuclear Information System (INIS)

    Daniels, Christopher P.; Millar, Jeremy L.; Spelman, Tim; Sengupta, Shomik; Evans, Sue M.

    2016-01-01

    Long-term data from three randomized trials have demonstrated that adjuvant radiation therapy (ART) reduces the rate of biochemical failure in high-risk men following radical prostatectomy (RP). One of these trials has shown a survival advantage. We investigated the rate of ART in Victoria and the predictors for this treatment. We analysed data from eligible patients who were notified to the Victorian Prostate Cancer Registry (PCR) by 37 Victorian hospitals between 1 August 2008 and 31 October 2011. We defined ART as radiation therapy (RT) delivered within 6 months of RP. Predictors of ART receipt were modelled using adjusted and unadjusted logistic regression. There were 4626 eligible cases from which 2018 underwent RP with recorded date of surgery. Of these eligible prostatectomy cases, a total of 89 received ART. A subgroup of 833 men had an adverse pathologic feature, of whom 78 received ART. In a multivariate model, pathologic tumour stage pT3a (odds ratio (OR) 2.64; 95% confidence interval (CI) 1.4–5.00; P = 0.003), pT3b (OR 4.58; 95% CI 2.12–9.89; P = 0.000), a positive surgical margin (OR 8.91; 95% CI 4.61–17.2; P = 0.000) and pathologic Gleason grade >7 (OR 7.18; 95% CI 1.54–33.6; P = 0.012) predicted receipt of ART. Adverse pathologic features and high pathologic Gleason score predict for receiving ART in Victorian men after RP, but overall, ART is not commonly prescribed. This finding is consistent with other published series and may reflect clinician scepticism regarding the benefit of ART over salvage RT and concern about toxicity and the risk of over treatment.

  16. Safety and efficacy of adjuvant therapy with oxaliplatin, leucovorin and 5-fluorouracil after mesorectal excision with lateral pelvic lymph node dissection for stage iii lower rectal cancer.

    Science.gov (United States)

    Iwasa, Satoru; Souda, Hiroaki; Yamazaki, Kentaro; Takahari, Daisuke; Miyamoto, Yuji; Takii, Yasumasa; Ikeda, Satoshi; Hamaguchi, Tetsuya; Kanemitsu, Yukihide; Shimada, Yasuhiro

    2015-03-01

    Preoperative chemoradiotherapy followed by total mesorectal excision (TME) is the standard treatment for stage III lower rectal cancer worldwide. However, in Japan, the standard treatment is TME with lateral pelvic lymph node dissection (LPLD) followed by adjuvant chemotherapy. We examined the safety and efficacy of adjuvant therapy with oxaliplatin, leucovorin, and 5-fluorouracil (modified FOLFOX6) after TME with LPLD. This retrospective study included 33 patients who received modified FOLFOX6 after TME with LPLD for stage III lower rectal cancer. The overall completion rate of 12 cycles of adjuvant modified FOLFOX6 was 76%. Grade 3 or 4 neutropenia was observed in eight patients (24%). Sensory neuropathy was observed in 32 patients (97%) with 4 (12%) having a grade 3 event. The disease-free survival (DFS) rate was 45% at 3 years. Adjuvant modified FOLFOX6 was feasible in patients with stage III lower rectal cancer after TME with LPLD. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  17. Racial differences in receipt of adjuvant hormonal therapy among Medicaid enrollees in South Carolina diagnosed with breast cancer

    Science.gov (United States)

    Felder, Tisha M.; Do, D. Phuong; Lu, Z. Kevin; Lal, Lincy S.; Heiney, Sue P.; Bennett, Charles L.

    2016-01-01

    Purpose Several factors contribute to the pervasive Black-White disparity in breast cancer mortality in the U.S., such as tumor biology, access to care and treatments received including adjuvant hormonal therapy (AHT), which significantly improves survival for hormone-receptor positive breast cancers (HR+). We analyzed South Carolina Central Cancer Registry-Medicaid linked data to determine if, in an equal access health care system, racial differences in the receipt of AHT exist. Methods We evaluated 494 study-eligible, Black (n=255) and White women (n=269) who were under 65 years old and diagnosed with stages I–III, HR+ breast cancers between 2004 and 2007. Bivariate and multivariate analyses were conducted to assess receipt of ≥ 1 AHT prescriptions at any point in time following (ever-use) or within 12 months of (early-use) breast cancer diagnosis. Results Seventy-two percent of the participants were ever-users (70% Black, 74% White) and 68% were early-users (65% Black, 71% White) of AHT. Neither ever-use (adjusted OR (AOR)=0.75, 95% CI: 0.48–1.17) nor early-use (AOR=0.70, 95% CI: 0.46–1.06) of AHT differed by race. However, receipt of other breast cancer-specific treatments was independently associated with ever-use and early-use of AHT [ever-use: receipt of surgery (AOR= 2.15, 95% CI: 1.35–3.44); chemotherapy (AOR=1.97, 95% CI: 1.22–3.20); radiation (AOR=2.33, 95% CI: 1.50–3.63); early-use: receipt of surgery (AOR=2.03, 95% CI: 1.30–3.17); chemotherapy (AOR=1.90, 95% CI: 1.20–3.03); radiation (AOR=1.73, 95% CI: 1.14–2.63)]. Conclusions No racial variations in use of AHT among women with HR+ breast cancers insured by Medicaid in South Carolina were identified, but overall rates of AHT use by these women is low. Strategies to improve overall use of AHT should include targeting breast cancer patients who do not receive adjuvant chemotherapy and/or radiation. PMID:27120468

  18. Microwave hyperthermia as an adjuvant to radiation therapy. Summary experience of 256 multifraction treatment cases

    International Nuclear Information System (INIS)

    Bicher, H.I.

    1985-01-01

    Analysis is presented of a series of 256 human tumors treated under multifraction protocol regimes with standard controlled hyperthermia parameters and increasing doses of radiation therapy. Air cooled microwave applicators intracavitary and interstitial antennae operating at 915 or 300 MHz were used in various sites. Temperatures were measured by micro-thermocouples. Minimum tumor temperatures of 42 0 C were maintained at 1 hour, twice weekly. Treatment included a radiation dose of 1600-1700 rads. Tumor response was 94% with 60% or more total response. Frequency and duration of total responses depended mainly on the radiation dose. Skin tumors, melanomas, chest wall recurrences responded better than head and neck or intrapelvic recurrences. Side effects observed were minor burns; proctitis or oesophagitis with intracavitary devices; ulcerations or fistulae due to rapid tumor regression; 4 cases of pleuritis treating chest wall. Overall toxicity was less than 5%. In conclusion: 1) Combination heat-low dose radiation offers good palliation. 2) Response depends on radiation dose. 3) Combination of full dose radiation therapy plus hyperthermia proves to be well tolerated

  19. Utilization pattern and survival outcomes of adjuvant therapies in high-grade nonretroperitoneal abdominal soft tissue sarcoma: A population-based study.

    Science.gov (United States)

    Green, William Ross; Chokshi, Ravi; Jabbour, Salma K; DeLaney, Thomas F; Mahmoud, Omar

    2018-02-01

    Nonretroperitoneal abdominal soft tissue sarcoma (NRA-STS) is a rare disease with limited data supporting its management. Our study aimed to reveal the utilization patterns of adjuvant therapy and its potential survival benefits using the National Cancer Data Base. The analysis included patients with resected high-grade NRA-STS. Chi-square analysis was used to evaluate distribution of patient and tumor-related factors within treatment groups. The Kaplan-Meier and Cox proportional hazards model were utilized to evaluate overall survival according to treatment approach. Multivariate analysis was used to determine the impact of these factors on patients' outcome. Matched propensity score analysis was implemented to control for imbalance of confounding variables. At median follow-up of 49 months, 5-year overall survival improved from 46% without adjuvant radiation therapy to 52% (P = 0.009) with radiotherapy delivery with a 30% reduction in hazard of death (95% confidence interval = 0.58-0.84). On multivariate analysis, age <50, tumor <8 cm, negative margins and radiotherapy delivery were significant predictors of improved survival. Chemotherapy was not associated with significant survival improvement (Hazard Ratios [HR]: 0.89, P = 0.28). Adjuvant radiotherapy was associated with improved survival in high-grade NRA-STS. Chemotherapy was not associated with a survival improvement; however, further studies are needed to refine treatment strategies. © 2017 John Wiley & Sons Australia, Ltd.

  20. An open-label, non-randomized comparison of venlafaxine and gabapentin as monotherapy or adjuvant therapy in the management of neuropathic pain in patients with peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    William Eardley

    2010-04-01

    Full Text Available William Eardley, Cory TothDepartment of Clinical Neurosciences and the University of Calgary, Calgary, AB, CanadaAbstract: Although many therapies are used in the management of neuropathic pain (NeP due to polyneuropathy (PN, few comparison studies exist. We performed a prospective, non-randomized, unblended, efficacy comparison of the serotonin-norepinephrine reuptake inhibitor venlafaxine, as either monotherapy or adjuvant therapy, with a first-line medication for NeP, gabapentin, in patients with PN-related NeP. VAS pain scores were assessed after 3 and 6 months in intervention groups and in a cohort of patients receiving no pharmacotherapy. In a total of 223 patients, we analyzed pain quantity and quality (visual analogue scale [VAS] score, Brief Pain Inventory [BPI], quality of life and health status measures [EuroQol 5 Domains, EQ-5D], Medical Outcomes Sleep Study Scale [MOSSS], Hospital Anxiety and Depression Scale [HADS] and Short Form 36 Health Survey [SF-36] after 6 months of therapy. Significant improvements in VAS pain scores occurred for all treatment groups after 6 months. Improvements in aspects of daily life and anxiety were identified in all treatment groups. Our data suggest that monotherapy or adjuvant therapy with venlafaxine is comparable to gabapentin for NeP management. We advocate for head-to-head, randomized, double-blinded studies of current NeP therapies.Keywords: peripheral neuropathy, neuropathic pain, pharmacotherapy, venlafaxine, gabapentin

  1. Clinical utility of gene expression profiling data for clinical decision-making regarding adjuvant therapy in early stage, node-negative breast cancer: a case report.

    Science.gov (United States)

    Schuster, Steven R; Pockaj, Barbara A; Bothe, Mary R; David, Paru S; Northfelt, Donald W

    2012-09-10

    Breast cancer is the most common malignancy among women in the United States with the second highest incidence of cancer-related death following lung cancer. The decision-making process regarding adjuvant therapy is a time intensive dialogue between the patient and her oncologist. There are multiple tools that help individualize the treatment options for a patient. Population-based analysis with Adjuvant! Online and genomic profiling with Oncotype DX are two commonly used tools in patients with early stage, node-negative breast cancer. This case report illustrates a situation in which the population-based prognostic and predictive information differed dramatically from that obtained from genomic profiling and affected the patient's decision. In light of this case, we discuss the benefits and limitations of these tools.

  2. Exploring the role of physician communication about adjuvant endocrine therapy among breast cancer patients on active treatment: a qualitative analysis.

    Science.gov (United States)

    Farias, Albert J; Ornelas, India J; Hohl, Sarah D; Zeliadt, Steven B; Hansen, Ryan N; Li, Christopher I; Thompson, Beti

    2017-01-01

    To better understand how physicians communicate with breast cancer patients about adjuvant endocrine therapy (AET), we explored, from the breast cancer patient's perspective, dimensions of the patient-provider communication among women who were on active AET treatment. Qualitative methods using semi-structured in-depth interviews were conducted with breast cancer patients (n = 22) who filled a prescription for AET in the previous 12 months. Interview questions aimed to elicit experiences with AET. We reviewed and coded interview transcripts using qualitative principles of inductive reasoning to identify concepts and themes from interview data. We grouped emergent themes into four major functions of physician-patient communication: (1) information exchange, (2) decision-making to take and continue AET, (3) enabling patient self-management and monitoring potential side effects, and (4) emotional support. Physicians exchanged information with patients in a way that they understood and enhanced patient's health literacy regarding the benefits and knowledge of AET. Physicians empowered patients to make decisions about their care. Patients expressed trust and confidence in their physician which helped them seek care when needed. Patients reported a high degree of self-efficacy to self-manage AET and were continuing treatment despite potential side effects. The results from our study suggest that women's interactions and communication with their physician may be an important factor that contributes to the continued use of AET. Physicians who can communicate information about AET treatment benefits, purpose, and expectations in a way that patients can understand is a critical aspect of care that needs to be further studied.

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

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

    International Nuclear Information System (INIS)

    Baumann, Brian C.; He, Jiwei; Hwang, Wei-Ting; Tucker, Kai N.; Bekelman, Justin E.; Herr, Harry W.; Lerner, Seth P.; Guzzo, Thomas J.; Malkowicz, S. Bruce; Christodouleas, John P.

    2016-01-01

    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 estimates.

  5. Effect of Hyperthermic Intraperitoneal Perfusion Chemotherapy in Combination with Intravenous Chemotherapy as Postoperative Adjuvant Therapy for Advanced Gastric Cancer.

    Science.gov (United States)

    Wu, Zhibing; Ma, Shenglin; Jing, Saisai; Deng, Qinghua; Zheng, Zhishuang; Wu, Kan; Li, Juan; Chen, Sumei; Tang, Rongjun; Li, Xiadong

    2014-06-01

    The aim is to evaluate the preliminary efficacy and side effects of paclitaxel, 5-fluorouracil, and leucovorin intravenous chemotherapy in combination with cisplatin hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) as postoperative adjuvant therapy for patients of locally advanced gastric cancer (GC) at high risk for recurrence after curative resection. Four GC patients who underwent radical gastrectomy with D2 lymphadenectomy were enrolled. All patients received paclitaxel 135 mg/m2 on day 1, 5-FU 500 mg/m2 on days 1-5, LV 200 mg/m2 on days 1-5 intravenous chemotherapy, cisplatin 75 mg/m2 on day 5, and HIPEC one month after surgery. It was repeated at 3 weeks intervals and at least two cycles administered. A total of 181 cycles of chemotherapy were administered (median, 4 cycles). The median disease free survival time of patients was 40.8 months. The median overall survival time was 48.0 months. The one-, two-, and three-year recurrence rates were 14.6%, 26.8%, and 46.3%, respectively. The main relapse patterns were remnant GC and metastases of retroperitoneal lymph nodes. The morbidity of grade 3 and 4 toxicities of myelosuppression, nausea/ vomiting were less than 10%. The side effects of grade 1 and 2 of hematologic toxicity, nausea and vomiting, abnormal function of liver, kidney or cardiac, fatigue and neurotoxicity were well tolerated. Cisplatin HIPEC combined with paclitaxel, 5-fluorouracil, and leucovorin intravenous chemotherapy regimen could improve the survival rate and decrease the postoperative recurrence of locally advanced GC.

  6. The benefit of a sentinel lymph node biopsy and adjuvant therapy in thick (>4 mm) melanoma: multicenter, retrospective study of 291 Japanese patients.

    Science.gov (United States)

    Fujisawa, Yasuhiro; Otsuka, Fujio

    2012-10-01

    The benefit of a sentinel lymph node (SLN) biopsy and adjuvant therapy for patients with thick (>4 mm) melanoma has not been well studied in the Asian population. We examined the benefit of an SLN biopsy and adjuvant therapy on prognosis in Japanese patients with thick melanoma. A review of the melanoma database collected from 26 institutions in Japan identified 291 patients with thick melanoma between 2005 and 2010. Univariate and multivariate analyses were performed to evaluate the factors predictive of the overall survival (OS) and the disease-free survival (DFS). Of the 242 patients with thick melanoma who underwent an SLN biopsy, the results for 96 (40%) were positive. On multivariate analysis, increased Breslow thickness (relative risk, 1.11; 95% confidence interval, 1.05-1.17; P=0.0002) and SLN metastasis (2.14; 1.04-4.43; P=0.040) were associated with a poor OS. Increased Breslow thickness (1.11; 1.04-1.18; P =0.0018), ulceration (3.11; 1.25-7.72; P=0.014), satellitosis (3.89; 1.62-9.31; P=0.0023), and SLN metastasis (2.24; 1.16-4.36; P=0.017) were associated with DFS. Adjuvant chemotherapy had no impact on either OS or DFS. Adjuvant use of a monthly dermal injection of interferon-β (IFN-β) was associated with a improvement in both OS (0.34; 0.17-0.67; P=0.0022) and DFS (0.42; 0.20-0.86; P=0.018). An SLN biopsy provided useful prognostic information and the adjuvant use of IFN-β improved both OS and DFS in Japanese patients with thick melanoma. These results were consistent with those of previous studies carried out on a white population. Therefore, we suggest that an SLN biopsy and adjuvant IFN should be considered for patients with thick melanoma irrespective of the Breslow thickness or ethnicity.

  7. The Effectiveness of Adjuvant Hyperbaric Oxygen Therapy in Adults who Underwent Hypospadias Surgery

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    Onder Kara

    2017-01-01

    Full Text Available Aim: To evaluate the role of hyperbaric oxygen therapy (HBO2T with buccal mucosal tube urethroplasty in adult patients with hypospadias. Material and Method: Sixteen adult patients with hypospadias were included in our study. Patients with a short urethra and penile curvature were treated in two stages (orthoplasty buccal mucosal tube urethroplasty. Buccal mucosa was taken and prepared for tube urethroplasty around a 16 French (Fr nelaton catheter and the urethral tube was introduced between the urethral meatus and glans penis. Beginning the 1st postoperative day (HBO2T was applied for 10 sessions during weekdays in 13 patients. Results: The mean age was 21 (±1.23 years and mean follow-up time was 10.1 (±2.1 months. In the group who received HBO2T postoperatively (n=13, a two-stage (orthoplasty buccal mucosal tube urethroplasty procedure was performed in 6 (46%, and the mean length of graft was 5.4 (±1.23 cm. In this group of 13 the success rate without any additional manipulations (urethrotomy intern, fistula repair was 54% (7/13. After additional manipulations, complete healing was achieved in 11 out of 13 patients (84.6%. In the group who did not receive HBO2T postoperatively (n=3, a two-stage procedure was performed in 1 patient (33%, and the mean length of graft was 8 (±5 cm. In this group of 3, complete healing was not achieved in any of these patients as a result of the hypospadias surgery. However, after the additional manipulations, complete healing was achieved in 1 patient (33%. Discussion: Given the promising rates of surgical success, postoperative HBO2T might be considered as a supportive treatment modality for adult patients with hypospadias who undergo buccal mucosal tube urethroplasty. Randomized controlled studies are needed.

  8. Intermediate doses of rituximab used as adjuvant therapy in refractory pemphigus

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    Pradnya J Londhe

    2014-01-01

    Full Text Available Background: Rituximab, a monoclonal anti-CD20 antibody, has been used with encouraging results in pemphigus. We describe herein refractory cases of pemphigus vulgaris (n = 23 and pemphigus foliaceus (n = 1 treated with rituximab in addition to steroids and immunosuppressants. Aims: To assess the response to treatment, the duration of clinical remission, serology of the response and adverse effects of rituximab in pemphigus patients. Methods: We recorded observations of 24 patients with pemphigus having either refractory disease in spite of high dose of steroids and immunosuppressants, corticosteroid-dependent disease, strong contraindications to corticosteroids, or severe disease. The patients were treated with infusions of one injection per week for three consecutive weeks of 375 mg of rituximab per m 2 of body-surface area. One similar infusion was repeated after 3 months of 3 rd dose. We observed the clinical outcome after 6 months of 3 rd dose of rituximab and looked for complete healing of cutaneous and mucosal lesions (complete remission. Observations: After follow-up of 7-24 months, five patients showed only partial improvement while 19 of 24 patients had a complete remission 3 months after rituximab. Of these 19 patients, 12 patients achieved complete remission and are off all systemic therapy, and the rest are continuing with no or low dose of steroids with immunosuppressants. Two patients relapsed after initial improvement; one was given moderate dose of oral steroids and immunosuppressant and the other was given repeat single dose of rituximab to control relapse. Conclusion: Rituximab is able to induce a prolonged clinical remission in pemphigus after a single course of four infusions. The high cost and limited knowledge of long term adverse effects are limitations to the use of this biologic agent.

  9. Effect of the adjuvant milrinone therapy on cardiac function, myocardial remodeling and RAAS system activity in patients with chronic heart failure

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    Jing Chen

    2017-09-01

    Full Text Available Objective: To explore the effect of the adjuvant milrinone therapy on cardiac function, myocardial remodeling and RAAS system activity in patients with chronic heart failure. Methods: A total of 110 patients with chronic heart failure who were treated in the hospital between January 2015 and January 2017 were divided into control group (n=55 and observation group (n=55 by random number table method. Control group received conventional therapy for chronic heart failure, and the observation group received milrinone on the basis of conventional therapy. The differences in ultrasound cardiac function and myocardial remodeling index levels as well as serum RAAS index contents were compared between the two groups before and after treatment. Results: Before treatment, the differences in ultrasound cardiac function and myocardial remodeling index levels as well as serum RAAS index contents were not statistically significant between the two groups. After treatment, CO and SV levels of both groups of patients were significantly higher than those before treatment while LADd, LVEDd, LVPWT, IVST and LVMI levels as well as serum PRA, AngⅡ and ALD contents were significantly lower than those before treatment, and CO and SV levels of observation group were significantly higher than those of control group while LADd, LVEDd, LVPWT, IVST and LVMI levels as well as serum PRA, AngⅡ and ALD contents were significantly lower than those of control group. Conclusion: Adjuvant milrinone therapy can effectively enhance the cardiac function, inhibit the myocardial remodeling and decrease the RAAS system activity in patients with chronic heart failure.

  10. A Comparison of Pharmacological (Amitriptyline HCL) and Nonpharmacological (Cognitive-Behavioral) Therapies for Chronic Tension Headaches.

    Science.gov (United States)

    Holroyd, Kenneth A.; And Others

    1991-01-01

    Randomly assigned 41 recurrent tension headache sufferers to either cognitive-behavioral therapy or to amitriptyline therapy. Both therapies yielded clinically significant improvements in headache activity. In instances where differences in treatment effectiveness were observed, cognitive-behavioral therapy yielded somewhat more positive outcomes…

  11. 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

  12. Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease

    DEFF Research Database (Denmark)

    Hughes, Derralynn A.; Nicholls, Kathleen; Shankar, Suma P.

    2017-01-01

    Background Fabry disease is an X-linked lysosomal storage disorder caused by GLA mutations, resulting in α-galactosidase (α-Gal) deficiency and accumulation of lysosomal substrates. Migalastat, an oral pharmacological chaperone being developed as an alternative to intravenous enzyme replacement t...

  13. Psychometric analysis of the Melancholia Scale in trials with non-pharmacological augmentation of patients with therapy-resistant depression

    DEFF Research Database (Denmark)

    Bech, Per; Lauritzen, Lise; Lunde, Marianne

    2014-01-01

    . Patients resistant to anti-depressant medication (therapy-resistant depression) have participated in our trials with non-pharmacological augmentation. On the basis of these trials, we have evaluated to what extent the neuropsychiatric subscale of the MES (concentration difficulties, fatigability, emotional...... of transferability, we have tested item ranks across the rating weeks. RESULTS: In the Mokken analysis, the coefficient of homogeneity was above 0.40 for both the HAM-D subscale and the apathia subscale at week 4. The numerical transferability across the weeks was statistically significant (p

  14. 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.

  15. 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.

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

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    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.

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

    International Nuclear Information System (INIS)

    Jebsen, Nina L.; Engellau, Jacob; Engström, Katarina; Bauer, Henrik C.; Monge, Odd R.; Muren, Ludvig P.; Eide, Geir E.; Trovik, Clement S.; Bruland, Øyvind S.

    2013-01-01

    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

  18. Short-term Effect of Radical Hysterectomy with or without Adjuvant Radiation Therapy on Urodynamic Parameters in Patients with Uterine Cervical Cancer

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    Jin Kyu Oh

    2012-06-01

    Full Text Available Purpose Lower urinary tract dysfunction is the most common complication after radical pelvic surgery. The aims of this study were to assess the effect of radical hysterectomy (RH on the storage function of the lower urinary tract and to evaluate the impact of radiation therapy (RT on postoperative urodynamic parameters. Methods This was a retrospective review of preoperative and postoperative urodynamic variables, which were prospectively collected. All women from 2006 to 2008, who underwent RH for uterine cervical cancer with a stage of 1A to 2B with or without adjuvant RT were enrolled. All patients were divided into two groups: group 1, without RT, and group 2, with adjuvant RT. Urodynamic studies were performed before, 10 days after, and 6 months after RH. Results A total of 42 patients with a mean (±standard error age of 51.9 (±12.3 years were analyzed. There were no significant differences in age, body mass index or clinical stage between the two groups. On the 10th postoperative day, all parameters were decreased except postvoid residual volume. In comparison with group 2 (n=14, group 1 (n=28 showed a significant increase in bladder compliance. At 6 months postoperatively, bladder compliance in group 1 had increased four times or more compared with that on postoperative 10 days. However, it had increased only 2.5 times in group 2 at the same time point (P<0.001. Conclusions The results of our study suggest that adjuvant RT after RH might result in a deterioration of bladder compliance. It is highly suggested that practitioners pay attention to low bladder compliance, especially in patients who have adjuvant RT after RH.

  19. 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.

  20. Randomized Adjuvant Chemotherapy of EGFR-Mutated Non-Small Cell Lung Cancer Patients with or without Icotinib Consolidation Therapy.

    Science.gov (United States)

    Feng, Siyang; Wang, Yuanyuan; Cai, Kaican; Wu, Hua; Xiong, Gang; Wang, Haofei; Zhang, Ziliang

    2015-01-01

    Epidermal growth factor receptor (EGFR) mutations occur in up to 50% of Asian patients with non-small cell lung cancer (NSCLC). Treatment of advanced NSCLC patients with EGFR-tyrosine kinase inhibitor (EGFR-TKI) confers a significant survival benefit. This study assessed the efficacy and safety of chemotherapy with or without icotinib in patients undergoing resection of stage IB to ⅢA EGFR-mutated NSCLC. Patients with surgically resected stage IB (with high risk factors) to ⅢA EGFR-mutated NSCLC were randomly assigned (1:1) to one of two treatment plans. One group received four cycles of platinum-based doublet chemotherapy every three weeks, and the other group received platinum-based chemotherapy supplemented with consolidation therapy of orally administered icotinib (125 mg thrice daily) two weeks after chemotherapy. The icotinib treatment continued for four to eight months, or until the occurrence of disease relapse, metastasis or unacceptable icotinib or chemotherapy toxicity. The primary endpoint was disease-free survival (DFS). 41 patients were enrolled between Feb 9, 2011 and Dec 17, 2012. 21 patients were assigned to the combined chemotherapy plus icotinib treatment group, while 20 patients received chemotherapy only. DFS at 12 months was 100% for icotinib-treated patients and 88.9% for chemotherapy-only patients (p = 0. 122). At 18 months DFS for icotinib-treated vs. chemotherapy-only patients was 95.2% vs. 83.3% (p = 0. 225), respectively, and at 24 months DFS was 90.5% vs. 66.7% (p = 0. 066). The adverse chemotherapy effects predominantly presented as gastrointestinal reactions and marrow suppression, and there was no significant difference between the two treatment groups. Patients in the chemotherapy plus icotinib treatment group showed favorable tolerance to oral icotinib. The results suggest that chemotherapy plus orally icotinib displayed better DFS compared with chemotherapy only, yet the difference in DFS was not significant. We would think

  1. Randomized Adjuvant Chemotherapy of EGFR-Mutated Non-Small Cell Lung Cancer Patients with or without Icotinib Consolidation Therapy.

    Directory of Open Access Journals (Sweden)

    Siyang Feng

    Full Text Available Epidermal growth factor receptor (EGFR mutations occur in up to 50% of Asian patients with non-small cell lung cancer (NSCLC. Treatment of advanced NSCLC patients with EGFR-tyrosine kinase inhibitor (EGFR-TKI confers a significant survival benefit. This study assessed the efficacy and safety of chemotherapy with or without icotinib in patients undergoing resection of stage IB to ⅢA EGFR-mutated NSCLC.Patients with surgically resected stage IB (with high risk factors to ⅢA EGFR-mutated NSCLC were randomly assigned (1:1 to one of two treatment plans. One group received four cycles of platinum-based doublet chemotherapy every three weeks, and the other group received platinum-based chemotherapy supplemented with consolidation therapy of orally administered icotinib (125 mg thrice daily two weeks after chemotherapy. The icotinib treatment continued for four to eight months, or until the occurrence of disease relapse, metastasis or unacceptable icotinib or chemotherapy toxicity. The primary endpoint was disease-free survival (DFS.41 patients were enrolled between Feb 9, 2011 and Dec 17, 2012. 21 patients were assigned to the combined chemotherapy plus icotinib treatment group, while 20 patients received chemotherapy only. DFS at 12 months was 100% for icotinib-treated patients and 88.9% for chemotherapy-only patients (p = 0. 122. At 18 months DFS for icotinib-treated vs. chemotherapy-only patients was 95.2% vs. 83.3% (p = 0. 225, respectively, and at 24 months DFS was 90.5% vs. 66.7% (p = 0. 066. The adverse chemotherapy effects predominantly presented as gastrointestinal reactions and marrow suppression, and there was no significant difference between the two treatment groups. Patients in the chemotherapy plus icotinib treatment group showed favorable tolerance to oral icotinib.The results suggest that chemotherapy plus orally icotinib displayed better DFS compared with chemotherapy only, yet the difference in DFS was not significant. We would

  2. Adjuvant radiation therapy versus surgery alone in operable breast cancer: long-term follow-up of a randomized clinical trial.

    Science.gov (United States)

    Rutqvist, L E; Pettersson, D; Johansson, H

    1993-02-01

    This paper presents long-term results from a randomized trial of pre- or postoperative megavoltage radiation therapy versus surgery alone in pre- and postmenopausal women with operable breast cancer. Treatment outcome after relapse among patients who developed loco-regional recurrences was also analyzed. A total of 960 patients were included in the trial. The mean follow-up was 16 years (range: 13-19 years). The radiation therapy was individually planned. It included the chest wall (and the breast in the preoperative cases) and the regional lymph nodes. The tumor dose was 45 Gy/5 weeks. No adjuvant systemic therapy was used. The results showed a significant benefit with radiation therapy in terms of recurrence-free survival during the entire follow-up period. There was also an overall survival difference-corresponding to a 16% reduction of deaths-in favor of the irradiated patients which, however, was not statistically significant (p = 0.09). Among those 169 patients who developed locoregional recurrences long-term control was only achieved in about one-third of the cases. This figure was similar among those who had received adjuvant radiation therapy (34%) compared to those initially treated with surgery alone (32%). This implied that the overall proportion of patients who eventually developed uncontrolled local disease was significantly higher among those initially allocated to surgery alone (16%) compared to those allocated to pre- or postoperative radiation therapy (6%, p < 0.01). These results suggest that local undertreatment may be deleterious in subgroups of patients.

  3. Opioid adjuvant strategy: improving opioid effectiveness.

    Science.gov (United States)

    Bihel, Frédéric

    2016-01-01

    Opioid analgesics continue to be the mainstay of pharmacologic treatment of moderate to severe pain. Many patients, particularly those suffering from chronic pain, require chronic high-dose analgesic therapy. Achieving clinical efficacy and tolerability of such treatment regimens is hampered by the appearance of opioid-induced side effects such as tolerance, hyperalgesia and withdrawal syndrome. Among the therapeutic options to improve the opioid effectiveness, this current review focuses on strategies combining opioids to other drugs that can modulate opioid-mediated effects. We will discuss about experimental evidences reported for several potential opioid adjuvants, including N-methyl-D-aspartate receptor antagonists, 5-HT7 agonists, sigma-1 antagonists, I2-R ligands, cholecystokinin antagonists, neuropeptide FF-R antagonists and toll-like receptor 4 antagonists.

  4. A selective review of glutamate pharmacological therapy in obsessive–compulsive and related disorders

    OpenAIRE

    Grados, Marco; Atkins,Elizabeth; Kovacikova,Gabriela Ika; McVicar,Erin

    2015-01-01

    Marco A Grados,1 Elizabeth B Atkins,2 Gabriela I Kovacikova,3 Erin McVicar4 1Division of Child and Adolescent Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, 2Department of Psychology, Smith College, Northampton, MA, 3Department of Psychology, Wellesley College, Wellesley, MA, 4Susquehanna University, Selinsgrove, PA, USA Abstract: Glutamate, an excitatory central nervous system neurotransmitter, is emerging as a potential alternative pharmacological treatment when co...

  5. Speech-language therapy program for mouth opening in patients with oral and oropharyngeal cancer undergoing adjuvant radiotherapy: a pilot study.

    Science.gov (United States)

    Marrafon, Caroline Somera; Matos, Leandro Luongo; Simões-Zenari, Marcia; Cernea, Claudio Roberto; Nemr, Katia

    2018-01-01

    Purpose Assess the effectiveness of an orofacial myofunctional therapeutic program in patients with oral or oropharyngeal cancer submitted to adjuvant radiotherapy through pre- and post-program comparison of maximum mandibular opening. Methods Prospective study involving five adult patients and five elderly patients postoperatively to oral cavity/oropharynx surgery who were awaiting the beginning of radiotherapy or had undergone fewer than five treatment sessions. The study participants had their maximum jaw opening measured using a sliding caliper at the beginning and end of the program. Two mobility exercises and three mandibular traction exercises were selected and weekly monitored presentially for 10 weeks. Descriptive data and pre- and post-therapy comparative measures were statistically analyzed using the Wilcoxon test. Results Ten patients (two women and eight men) with mean age of 58.4 years, median of 57.0 years, completed the therapeutic program. They presented mean maximum mandibular opening of 31.6 ± 11.7 and 36.4 ± 8.0 mm pre- and post-therapy, respectively (p =0.021). Conclusion The proposed orofacial myofunctional therapeutic program increased the maximum jaw opening of patients referred to adjuvant radiotherapy for oral cavity or oropharynx cancer treatment.

  6. A pilot randomized controlled trial of D-cycloserine and distributed practice as adjuvants to constraint-induced movement therapy after stroke.

    Science.gov (United States)

    Nadeau, Stephen E; Davis, Sandra E; Wu, Samuel S; Dai, Yunfeng; Richards, Lorie G

    2014-01-01

    Background. Phase III trials of rehabilitation of paresis after stroke have proven the effectiveness of intensive and extended task practice, but they have also shown that many patients do not qualify, because of severity of impairment, and that many of those who are treated are left with clinically significant deficits. Objective. To test the value of 2 potential adjuvants to normal learning processes engaged in constraint-induced movement therapy (CIMT): greater distribution of treatment over time and the coadministration of d-cycloserine, a competitive agonist at the glycine site of the N-methyl-D-aspartate glutamate receptor. Methods. A prospective randomized single-blind parallel-group trial of more versus less condensed therapy (2 vs 10 weeks) and d-cycloserine (50 mg) each treatment day versus placebo (in a 2 × 2 design), as potential adjuvants to 60 hours of CIMT. Results. Twenty-four participants entered the study, and 22 completed it and were assessed at the completion of treatment and 3 months later. Neither greater distribution of treatment nor treatment with d-cycloserine significantly augmented retention of gains achieved with CIMT. Conclusions. Greater distribution of practice and treatment with d-cycloserine do not appear to augment retention of gains achieved with CIMT. However, concentration of CIMT over 2 weeks ("massed practice") appears to confer no advantage either. © The Author(s) 2014.

  7. Effect of olanzapine for breast cancer patients resistant to triplet antiemetic therapy with nausea due to anthracycline-containing adjuvant chemotherapy.

    Science.gov (United States)

    Sato, Junya; Kashiwaba, Masahiro; Komatsu, Hideaki; Ishida, Kazushige; Nihei, Satoru; Kudo, Kenzo

    2016-05-01

    Triplet antiemetic therapy with neurokinin 1 receptor blocker, 5-hydroxytryptamine receptor blocker and steroids is commonly used in patients who are highly emetic after chemotherapy. However, an alternative antiemetic therapy for patients who are resistant to triplet antiemetic therapy is not established. Olanzapine is recommended in the guidelines as an optional antiemetic drug. However, the effectiveness of adding olanzapine to triplet antiemetic therapy is unknown. In this study, the effectiveness and safety of adding olanzapine to triplet antiemetic therapy with aprepitant, palonosetron and dexamethasone as highly emetic anthracycline-containing adjuvant chemotherapy for primary breast cancer patients were prospectively investigated. Forty-five patients with breast cancer who experienced >Grade 1 nausea or any vomiting after the first cycle of chemotherapy using both epirubicin and cyclophosphamide were included. Low-dose olanzapine (2.5 mg/day) was administered orally from the first day of chemotherapy for 4 days, and the number of episodes of vomiting, scale of nausea, dietary intake and somnolence were compared with the symptoms after the first cycle. As the primary endpoint, the nausea grade was significantly improved by adding olanzapine (P effectiveness and tolerability of adding low-dose olanzapine for patients with insufficient nausea relief with triplet antiemetic therapy consisting of palonosetron, steroid and aprepitant. Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  8. Adjuvant chemotherapy and cancer cure

    International Nuclear Information System (INIS)

    Bertino, J.R.

    1983-01-01

    The use of chemotherapy as an adjuvant to surgery and/or radiotherapy is well founded in experimental tumor systems and appears to be effective in patients in some circumstances. It is clear from both clinical and experimental studies that (1) the dose is important, (2) the earlier chemotherapy is started after primary therapy the better, and (3) combination chemotherapy may be more effective than single-agent treatment. The better the estimation of risk of recurrence, the better the assessment of the risk-benefit ratio with adjuvant therapy. Salvage therapy as well as relative risk of recurrence are considerations in the choice of patients to be treated. Finally, some evidence is presented to indicate that alkylating agents may not be necessary in combination regimens for adjuvant therapy if effective antimetabolite combinations are available

  9. Altered deoxyribonuclease activity in cancer cells and its role in non toxic adjuvant cancer therapy with mixed vitamins C and K3.

    Science.gov (United States)

    Taper, Henryk S

    2008-01-01

    The alterations of deoxyribonuclease DNase activity in cancer cells were the basis of the utilization of mixed vitamins C and K3 in a nontoxic, adjuvant cancer therapy. In order to localize exactly the altered activities of DNase in cancer cells, histochemical methods were utilized. The deficiency of alkaline and acid DNase activity appeared to be characteristic for non-necrotic cells of malignant human and animal tumors. This enzymatic deficiency appeared in experimental carcinogenesis before the phenotypic signs of malignancy. Tumor promoters directly reduced the activity of both DNases. The incidence of spontaneous malignant human and animal tumors appeared to be inversely proportional to the intensity of the activity of both DNases in normal cells and tissues from which these tumors were derived. The fact that alkaline and acid DNase activity was reactivated during the spontaneous and therapeutically induced necrosis of cancer cells suggests that this enzymatic deficiency of DNase activity in cancer cells was due to the action of specific inhibitors of DNases. Characteristic variations of serum alkaline DNase activity in positive responders to therapy, examined in more than 800 cancer-bearing patients, may be the basis for the development of a useful test for therapeutic prognosis and for monitoring of cancer bearing patients. Acid DNase was selectively reactivated in malignant tumor cells by vitamin C (sodium ascorbate), whereas alkaline DNase was reactivated by vitamin K3. Joint vitamin C and K3 administration produced in vitro and in vivo tumor growth inhibition, potentiation and sensitization of chemo- and/or radiotherapy and a decrease in the number of metastases in animals with experimental tumors. Joint vitamin C and K3 administration may be considered as a possible new, non-toxic, adjuvant cancer therapy, which can be easily introduced into the classic protocols of clinical cancer therapy without any supplementary risk for patients.

  10. Selecting postoperative adjuvant systemic therapy for early stage breast cancer: A critical assessment of commercially available gene expression assays

    Science.gov (United States)

    Schuur, Eric; Angel Aristizabal, Javier; Bargallo Rocha, Juan Enrique; Cabello, Cesar; Elizalde, Roberto; García‐Estévez, Laura; Gomez, Henry L.; Katz, Artur; Nuñez De Pierro, Aníbal

    2017-01-01

    Risk stratification of patients with early stage breast cancer may support adjuvant chemotherapy decision‐making. This review details the development and validation of six multi‐gene classifiers, each of which claims to provide useful prognostic and possibly predictive information for early stage breast cancer patients. A careful assessment is presented of each test's analytical validity, clinical validity, and clinical utility, as well as the quality of evidence supporting its use. PMID:28211064

  11. Combined adjuvant radiation and interferon-alpha 2B therapy in high-risk melanoma patients: the potential for increased radiation toxicity

    International Nuclear Information System (INIS)

    Hazard, Lisa J.; Sause, William T.; Noyes, R. Dirk

    2002-01-01

    Purpose: Surgically resected melanoma patients with high-risk features commonly receive adjuvant therapy with interferon-alpha 2b combined with radiation therapy; the purpose of our study was to evaluate the potential enhancement of radiation toxicity by interferon. Methods and Materials: Patients at LDS Hospital and the University of Utah Medical Center in Salt Lake City treated with interferon during radiotherapy or within 1 month of its completion were retrospectively identified, and their charts were reviewed. If possible, the patients were asked to return to the LDS Hospital radiation therapy department for follow-up. Results: Five of 10 patients receiving interferon-alpha 2b therapy during radiation therapy or within 1 month of its completion experienced severe subacute/late complications of therapy. Severe subacute/late complications included two patients with peripheral neuropathy, one patient with radiation necrosis in the brain, and two patients with radiation necrosis in the s.c. tissue. One patient with peripheral neuropathy and one patient with radiation necrosis also developed lymphedema. Conclusions: In vitro studies have identified a radiosensitizing effect by interferon-alpha on certain cell lines, which suggests the possibility that patients treated with interferon and radiation therapy may experience more severe radiation toxicities. We have observed severe subacute/late complications in five of 10 patients treated with interferon-alpha 2b during radiation therapy or within 1 month of its completion. Although an observational study of 10 patients lacks the statistic power to reach conclusions regarding the safety and complication rates of combined interferon and radiation therapy, it is sufficient to raise concerns and suggest the need for prospective studies

  12. Patient's adherence on pharmacological therapy for benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS) is different: is combination therapy better than monotherapy?

    Science.gov (United States)

    Cindolo, Luca; Pirozzi, Luisella; Sountoulides, Petros; Fanizza, Caterina; Romero, Marilena; Castellan, Pietro; Antonelli, Alessandro; Simeone, Claudio; Tubaro, Andrea; de Nunzio, Cosimo; Schips, Luigi

    2015-09-21

    Recent studies showed that the non-adherence to the pharmacological therapy of patients affected by BPH-associated LUTS increased the risk of clinical progression of BPH. We examined the patients adherence to pharmacological therapy and its clinical consequences in men with BPH-associated LUTS looking at the differences between drug classes comparing mono vs combination therapy. A retrospective, population-based cohort study, using prescription administrative database and hospital discharge codes from a total of 1.5 million Italian men. Patients ≥ 40 years, administered alpha-blockers (AB) and 5alpha-reductase inhibitors (5ARIs), alone or in combination (CT), for BPH-associated LUTS were analyzed. The 1-year and long term adherence together with the analyses of hospitalization rates for BPH and BPH-related surgery were examined using multivariable Cox proportional hazards regression model and Pearson chi square test. Patients exposed to at least 6 months of therapy had a 1-year overall adherence of 29 % (monotherapy AB 35 %, monotherapy 5ARI 18 %, CT 9 %). Patient adherence progressively declined to 15 %, 8 % and 3 % for AB, 5ARI, and CT, respectively at the fifth year of follow up. Patients on CT had a higher discontinuation rate along all the follow-up compared to those under monotherapy with ABs or 5ARIs (all p BPH-related surgery (HR 0.94; p BPH-associated LUTS is low and varies depending on drugs class. Patients under CT have a higher likelihood of discontinuing treatment for a number of reasons that should be better investigated. Our study suggests that new strategies aiming to increase patient's adherence to the prescribed treatment are necessary in order to prevent BPH progression.

  13. CLINICAL AND PHARMACOLOGICAL PECULIARITIES OF CETIRIZINE USE FOR THE THERAPY OF ALLERGIC DISEASES IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Yu. G. Levina

    2014-01-01

    Full Text Available The review is dedicated to treatment of allergic diseases in children, particularly to the use of the 2nd generation antihistamine. It demonstrates that mediator histamine has the crucial role in pathophysiology of the allergic reaction. Antihistamines block histamine action aimed at H1 receptors by way of competitive inhibition. The 2nd generation antihistamines are the drugs of choice for the treatment of allergic diseases due to the absence of sedative effect. The review presents clinical and pharmacological description of the selective 2nd generation antihistamine cetirizine, efficacy and safety of which have been appraised in numerous long-term clinical studies in children with allergic rhinitis, urticaria and atopic dermatitis. 

  14. Recurrent Obscure Gastrointestinal Bleeding: Dilemmas and Success with Pharmacological Therapies. Case Series and Review

    Directory of Open Access Journals (Sweden)

    Majid Almadi

    2009-01-01

    Full Text Available The present article describes three difficult cases of recurrent bleeding from obscure causes, followed by a review of the pitfalls and pharmacological management of obscure gastrointestinal bleeding. All three patients underwent multiple investigations. An intervening complicating diagnosis or antiplatelet drugs may have compounded long-term bleeding in two of the cases. A bleeding angiodysplasia was confirmed in one case but was aggravated by the need for anticoagulation. After multiple transfusions and several attempts at endoscopic management in some cases, long-acting octreotide was associated with decreased transfusion requirements and increased hemoglobin levels in all three cases, although other factors may have contributed in some. In the third case, however, the addition of low-dose thalidomide stopped bleeding for a period of at least 23 months.

  15. Phase I trial of aflibercept (VEGF trap) with radiation therapy and concomitant and adjuvant temozolomide in patients with high-grade gliomas.

    Science.gov (United States)

    Nayak, Lakshmi; de Groot, John; Wefel, Jeffrey S; Cloughesy, Timothy F; Lieberman, Frank; Chang, Susan M; Omuro, Antonio; Drappatz, Jan; Batchelor, Tracy T; DeAngelis, Lisa M; Gilbert, Mark R; Aldape, Kenneth D; Yung, Alfred W K; Fisher, Joy; Ye, Xiaobu; Chen, Alice; Grossman, Stuart; Prados, Michael; Wen, Patrick Y

    2017-03-01

    Anti-vascular endothelial growth factor (VEGF) therapy has shown promise in the treatment of high-grade gliomas (HGG). Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for VEGF-A, VEGF-B and placental growth factor, depleting circulating levels of these growth factors. The Adult Brain Tumor Consortium conducted a phase I trial of aflibercept and temozolomide (TMZ) in patients with newly diagnosed HGG with 2 dose levels and a 3+3 design. Three arms using aflibercept were examined; with radiation and concomitant temozolomide; with adjuvant temozolomide using the 5/28 regimen; and with adjuvant temozolomide using the 21/28 day regimen. Fifty-nine patients were enrolled, 21 in arm 1, 20 in arm 2 and 18 in arm 3. Median age was 56 years (24-69); median KPS 90 (60-100). The maximum tolerated dose (MTD) of aflibercept for all 3 arms was 4 mg/kg every 2 weeks. Dose limiting toxicities at the MTD were: Arm 1: 0/21 patients; Arm 2: 2/20 patients (G3 deep vein thrombosis, G4 neutropenia; Arm 3: 3/18 patients) (G4 biopsy-confirmed thrombotic microangiopathy, G3 rash, G4 thrombocytopenia). The median number of cycles of aflibercept was 5 (range, 1-16). All patients stopped treatment; 28 (47%) for disease progression, 21 (36%) for toxicities, 8 (14%) for other reasons, and 2 (3%) patients completed the full treatment course. This study met its primary endpoint and the MTD of aflibercept with radiation and concomitant and adjuvant temozolomide is 4 mg/kg every 2 weeks.

  16. Effect of speech therapy and pharmacological treatment in prosody of parkinsonians

    Directory of Open Access Journals (Sweden)

    Luciana Lemos de Azevedo

    2015-01-01

    Full Text Available Objective Parkinsonian patients usually present speech impairment. The aim of this study was to verify the influence of levodopa and of the adapted Lee Silverman Vocal Treatment® method on prosodic parameters employed by parkinsonian patients. Method Ten patients with idiopathic Parkinson's disease using levodopa underwent recording of utterances produced in four stages: expressing attitudes of certainty and doubt and declarative and interrogative modalities. The sentences were recorded under the effect of levodopa (on, without the effect of levodopa (off; before and after speech therapy during the on and off periods. Results The speech therapy and its association with drug treatment promoted the improvement of prosodic parameters: increase of fundamental frequency measures, reduction of measures of duration and greater intensity. Conclusion The association of speech therapy to medication treatment is of great value in improving the communication of parkinsonian patients.

  17. A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme.

    Science.gov (United States)

    Rosenfeld, Myrna R; Ye, Xiaobu; Supko, Jeffrey G; Desideri, Serena; Grossman, Stuart A; Brem, Steven; Mikkelson, Tom; Wang, Daniel; Chang, Yunyoung C; Hu, Janice; McAfee, Quentin; Fisher, Joy; Troxel, Andrea B; Piao, Shengfu; Heitjan, Daniel F; Tan, Kay-See; Pontiggia, Laura; O'Dwyer, Peter J; Davis, Lisa E; Amaravadi, Ravi K

    2014-08-01

    Preclinical studies indicate autophagy inhibition with hydroxychloroquine (HCQ) can augment the efficacy of DNA-damaging therapy. The primary objective of this trial was to determine the maximum tolerated dose (MTD) and efficacy of HCQ in combination with radiation therapy (RT) and temozolomide (TMZ) for newly diagnosed glioblastoma (GB). A 3 + 3 phase I trial design followed by a noncomparative phase II study was conducted in GB patients after initial resection. Patients received HCQ (200 to 800 mg oral daily) with RT and concurrent and adjuvant TMZ. Quantitative electron microscopy and immunoblotting were used to assess changes in autophagic vacuoles (AVs) in peripheral blood mononuclear cells (PBMC). Population pharmacokinetic (PK) modeling enabled PK-pharmacodynamic correlations. Sixteen phase I subjects were evaluable for dose-limiting toxicities. At 800 mg HCQ/d, 3/3 subjects experienced Grade 3 and 4 neutropenia and thrombocytopenia, 1 with sepsis. HCQ 600 mg/d was found to be the MTD in this combination. The phase II cohort (n = 76) had a median survival of 15.6 mos with survival rates at 12, 18, and 24 mo of 70%, 36%, and 25%. PK analysis indicated dose-proportional exposure for HCQ. Significant therapy-associated increases in AV and LC3-II were observed in PBMC and correlated with higher HCQ exposure. These data establish that autophagy inhibition is achievable with HCQ, but dose-limiting toxicity prevented escalation to higher doses of HCQ. At HCQ 600 mg/d, autophagy inhibition was not consistently achieved in patients treated with this regimen, and no significant improvement in overall survival was observed. Therefore, a definitive test of the role of autophagy inhibition in the adjuvant setting for glioma patients awaits the development of lower-toxicity compounds that can achieve more consistent inhibition of autophagy than HCQ.

  18. Role of vitamin C as an adjuvant therapy to different iron chelators in young β-thalassemia major patients: efficacy and safety in relation to tissue iron overload.

    Science.gov (United States)

    Elalfy, Mohsen S; Saber, Maha M; Adly, Amira Abdel Moneam; Ismail, Eman A; Tarif, Mohamed; Ibrahim, Fatma; Elalfy, Omar M

    2016-03-01

    Vitamin C, as antioxidant, increases the efficacy of deferoxamine (DFO). To investigate the effects of vitamin C as an adjuvant therapy to the three used iron chelators in moderately iron-overloaded young vitamin C-deficient patients with β-thalassemia major (β-TM) in relation to tissue iron overload. This randomized prospective trial that included 180 β-TM vitamin C-deficient patients were equally divided into three groups (n = 60) and received DFO, deferiprone (DFP), and deferasirox (DFX). Patients in each group were further randomized either to receive vitamin C supplementation (100 mg daily) or not (n = 30). All patients received vitamin C (group A) or no vitamin C (group B) were followed up for 1 yr with assessment of transfusion index, hemoglobin, iron profile, liver iron concentration (LIC) and cardiac magnetic resonance imaging (MRI) T2*. Baseline vitamin C was negatively correlated with transfusion index, serum ferritin (SF), and LIC. After vitamin C therapy, transfusion index, serum iron, SF, transferrin saturation (Tsat), and LIC were significantly decreased in group A patients, while hemoglobin and cardiac MRI T2* were elevated compared with baseline levels or those in group B without vitamin C. The same improvement was found among DFO-treated patients post-vitamin C compared with baseline data. DFO-treated patients had the highest hemoglobin with the lowest iron, SF, and Tsat compared with DFP or DFX subgroups. Vitamin C as an adjuvant therapy possibly potentiates the efficacy of DFO more than DFP and DFX in reducing iron burden in the moderately iron-overloaded vitamin C-deficient patients with β-TM, with no adverse events. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Brivaracetam: review of its pharmacology and potential use as adjunctive therapy in patients with partial onset seizures

    Directory of Open Access Journals (Sweden)

    Mumoli L

    2015-10-01

    Full Text Available Laura Mumoli,1 Caterina Palleria,2 Sara Gasparini,1 Rita Citraro,2 Angelo Labate,1 Edoardo Ferlazzo,1 Antonio Gambardella,1 Giovambattista De Sarro,2 Emilio Russo2 1Institute of Neurology, 2Institute of Pharmacology, University Magna Græcia, Catanzaro, Italy Abstract: Brivaracetam (BRV, a high-affinity synaptic vesicle protein 2A ligand, reported to be 10–30-fold more potent than levetiracetam (LEV, is highly effective in a wide range of experimental models of focal and generalized seizures. BRV and LEV similarly bind to synaptic vesicle protein 2A, while differentiating for other pharmacological effects; in fact, BRV does not inhibit high voltage Ca2+ channels and AMPA receptors as LEV. Furthermore, BRV apparently exhibits inhibitory activity on neuronal voltage-gated sodium channels playing a role as a partial antagonist. BRV is currently waiting for approval both in the United States and the European Union as adjunctive therapy for patients with partial seizures. In patients with photosensitive epilepsy, BRV showed a dose-dependent effect in suppressing or attenuating the photoparoxysmal response. In well-controlled trials conducted to date, adjunctive BRV demonstrated efficacy and good tolerability in patients with focal epilepsy. BRV has a linear pharmacokinetic profile. BRV is extensively metabolized and excreted by urine (only 8%–11% unchanged. The metabolites of BRV are inactive, and hydrolysis of the acetamide group is the mainly involved metabolic pathway; hepatic impairment probably requires dose adjustment. BRV does not seem to influence other antiepileptic drug plasma levels. Six clinical trials have so far been completed indicating that BRV is effective in controlling seizures when used at doses between 50 and 200 mg/d. The drug is generally well-tolerated with only mild-to-moderate side effects; this is confirmed by the low discontinuation rate observed in these clinical studies. The most common side effects are related to

  20. Comparison of Efficacy and Side Effects of Oral Baclofen Versus Tizanidine Therapy with Adjuvant Botulinum Toxin Type A in Children With Cerebral Palsy and Spastic Equinus Foot Deformity.

    Science.gov (United States)

    Dai, Alper I; Aksoy, Sefika N; Demiryürek, Abdullah T

    2016-02-01

    This retrospective study aimed to compare the therapeutic response, including side effects, for oral baclofen versus oral tizanidine therapy with adjuvant botulinum toxin type A in a group of 64 pediatric patients diagnosed with static encephalopathy and spastic equinus foot deformity. Following botulinum toxin A treatment, clinical improvement led to the gradual reduction of baclofen or tizanidine dosing to one-third of the former dose. Gross Motor Functional Measure and Caregiver Health Questionnaire scores were markedly elevated post-botulinum toxin A treatment, with scores for the tizanidine (Gross Motor Functional Measure: 74.45 ± 3.72; Caregiver Health Questionnaire: 72.43 ± 4.29) group significantly higher than for the baclofen group (Gross Motor Functional Measure: 68.23 ± 2.66; Caregiver Health Questionnaire: 67.53 ± 2.67, P botulinum toxin A and a low dose of tizanidine in treating children with cerebral palsy appears to be more effective and has fewer side effects versus baclofen with adjuvant botulinum toxin A. © The Author(s) 2015.

  1. 21-Gene Recurrence Score for prognosis and prediction of taxane benefit after adjuvant chemotherapy plus endocrine therapy: results from NSABP B-28/NRG Oncology.

    Science.gov (United States)

    Mamounas, Eleftherios P; Tang, Gong; Paik, Soonmyung; Baehner, Frederick L; Liu, Qing; Jeong, Jong-Hyeon; Kim, S Rim; Butler, Steven M; Jamshidian, Farid; Cherbavaz, Diana B; Sing, Amy P; Shak, Steven; Julian, Thomas B; Lembersky, Barry C; Wickerham, D Lawrence; Costantino, Joseph P; Wolmark, Norman

    2018-02-01

    The 21-gene recurrence score (RS) predicts outcome and benefit from adjuvant chemotherapy benefit in breast cancer patients treated with adjuvant endocrine therapy. In the NSABP B-28 study, we evaluated the 21-gene RS for its prognostic impact and its ability to predict benefit from paclitaxel (P) in node-positive, estrogen receptor-positive (ER+) breast cancer patients treated with adjuvant chemotherapy plus tamoxifen. The B-28 trial compared doxorubicin/cyclophosphamide (AC) with AC followed by P in 3060 patients. Tamoxifen for 5 years was also given to patients > 50 years and those < 50 years with ER+ and/or progesterone receptor-positive (PR+) tumors. The present study includes 1065 ER-positive, tamoxifen-treated patients with RS assessment. Median follow-up time was 11.2 years. In univariate analyses, RS was a significant predictor of outcome. In multivariate analyses, RS remained a significant independent predictor of outcome beyond clinico-pathologic factors, age, and type of surgery (p < 0.001). In the study population (n = 1065), the disease-free survival (DFS) hazard ratio (HR) with adding P to AC was 0.87 (95% CI 0.72-1.05; p = 0.14). RS was not a significant predictor of P benefit: for DFS, HRs for adding P to AC in RS low, intermediate, and high subgroups were 1.01 (95% CI 0.69-1.47; p = 0.99), 0.84 (95% CI 0.62-1.14; p = 0.26), and 0.81 (95% CI 0.60-1.10; p = 0.21), respectively (interaction p = 0.64). Similar findings were observed for the other study endpoints. RS maintains significant prognostic impact in ER-positive, node-positive patients treated with adjuvant chemotherapy plus tamoxifen. However, RS did not significantly predict benefit from adding paclitaxel to AC chemotherapy. (Trial Registration: PDQ: NSABP-B-28).

  2. Selecting Infants With Cryptorchidism and High Risk of Infertility for Optional Adjuvant Hormonal Therapy and Cryopreservation of Germ Cells: Experience From a Pilot Study

    Directory of Open Access Journals (Sweden)

    Jorgen Thorup

    2018-06-01

    Full Text Available IntroductionOrchiopexy for congenital cryptorchid testes is recommended between ½ and 1 year of age to preserve testicular germ cell maturation. Early operation is not enough to preserve fertility in 22 and 36% of cases. Aim of this study was to set up a protocol for optional adjuvant hormonal therapy after orchiopexy and thereafter cryopreservation of testicular biopsies from infants with bilateral cryptorchidism and high infertility risk.Materials and methodsWe included 17 boys with bilateral cryptorchidism, normal FSH, and impaired germ cell number per tubular transverse section (G/T in testicular biopsies at orchiopexy, 7 months to 3½ years old. Postoperatively, optional adjuvant LHRH (kryptocur® 0.2 mg/0.1 mL 2× every second day in 16 weeks were offered. Ten boys were applicable for age matching according to parent’s choice of treatment regime and G/T. Five of them had kryptocur®, and five were controls. Repeat bilateral testicular biopsy evaluation and cryopreservation were offered to all boys 12 months after primary orchiopexy. For cryopreservation, tissue pieces were incubated with a cryoprotectant with a slow program freezing.ResultsTwo out of five kryptorcur®-treated boys normalized both the average G/T and the number of adult dark spermatogonia (Ad-S. Another kryptocur®-treated boy with initial low G/T and no Ad-S increased the G/T and achieved normal number of Ad-S at time of cryopreservation. In the control group, two patients reached only normal lower range regarding the G/T and the number of Ad-S. None of boys with less than average 0.2 G/T improved significantly, whether they were kryptocur®-treated or not.ConclusionBased on literature and the present results, we recommend adjuvant LHRH treatment to boys with cryptorchidism and insufficient genuine gonadotropin stimulation at time of surgery, as these patients have high infertility risk. Cryopreservation should be an option in case of treatment failure

  3. Current strategies for non-pharmacological therapy of long-standing persistent atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Teiichi Yamane, MD, PhD

    2012-06-01

    Full Text Available Non-pharmacological rhythm control of atrial fibrillation (AF is becoming increasingly important in our aging society. Advancement of catheter ablation techniques in the last decade has provided a cure for AF patients, with a nearly established efficiency for paroxysmal cases. However, since ablation of persistent/chronic AF cases is still challenging, early treatment of paroxysmal AF before transformation to the persistent/chronic form is mandatory. Although there is a consensus that pulmonary vein isolation is the first-line approach for ablation of long-standing persistent AF, similar to that for paroxysmal AF, there are still wide variations in the adjunctive approach to modify the atrial substrate of persistent AF (anatomical linear ablation, electrogram-based complex fractionated atrial electrogram ablation, ganglionated plexus ablation, etc.. Since data comparing the effectiveness of these adjunctive approaches are still lacking, large-scale controlled trials evaluating the effect of catheter ablation in diverse patient populations on a long-term basis are needed to establish the appropriate approach for long-standing persistent AF. Furthermore, the development of de novo ablation methods (new energies, new targets, etc. is expected to improve ablation outcome in patients with long-standing persistent AF.

  4. The diversity of abnormal hormone receptors in adrenal Cushing's syndrome allows novel pharmacological therapies

    Directory of Open Access Journals (Sweden)

    Lacroix A.

    2000-01-01

    Full Text Available Recent studies from several groups have indicated that abnormal or ectopic expression and function of adrenal receptors for various hormones may regulate cortisol production in ACTH-independent hypercortisolism. Gastric inhibitory polypeptide (GIP-dependent Cushing's syndrome has been described in patients with either unilateral adenoma or bilateral macronodular adrenal hyperplasia; this syndrome results from the large adrenal overexpression of the GIP receptor without any activating mutation. We have conducted a systematic in vivo evaluation of patients with adrenal Cushing's syndrome in order to identify the presence of abnormal hormone receptors. In macronodular adrenal hyperplasia, we have identified, in addition to GIP-dependent Cushing's syndrome, other patients in whom cortisol production was regulated abnormally by vasopressin, ß-adrenergic receptor agonists, hCG/LH, or serotonin 5HT-4 receptor agonists. In patients with unilateral adrenal adenoma, the abnormal expression or function of GIP or vasopressin receptor has been found, but the presence of ectopic or abnormal hormone receptors appears to be less prevalent than in macronodular adrenal hyperplasia. The identification of the presence of an abnormal adrenal receptor offers the possibility of a new pharmacological approach to control hypercortisolism by suppressing the endogenous ligands or by using specific antagonists for the abnormal receptors.

  5. Clipping of tumour resection margins allows accurate target volume delineation in head and neck cancer adjuvant radiation therapy

    International Nuclear Information System (INIS)

    Bittermann, Gido; Wiedenmann, Nicole; Bunea, Andrei; Schwarz, Steffen J.; Grosu, Anca-L.; Schmelzeisen, Rainer; Metzger, Marc C.

    2015-01-01

    Background: Accurate tumour bed localisation is a key requirement for adjuvant radiotherapy. A new procedure is described for head and neck cancer treatment that improves tumour bed localisation using titanium clips. Materials and methods: Following complete local excision of the primary tumour, the tumour bed was marked with titanium clips. Preoperative gross target volume (GTV) and postoperative tumour bed were examined and the distances between the centres of gravity were evaluated. Results: 49 patients with squamous cell carcinoma of the oral cavity were prospectively enrolled in this study. All patients underwent tumour resection, neck lymph node dissection and defect reconstruction in one stage. During surgery, 7–49 clips were placed in the resection cavity. Surgical clip insertion was successful in 88% (n = 43). Clip identification and tumour bed delineation was successful in all 43 patients. The overall distance between the centres of gravity of the preoperative tumour extension to the tumour bed was 0.9 cm. A significant relationship between the preoperative tumour extension and the postoperative tumour bed volume could be demonstrated. Conclusion: We demonstrate a precise delineation of the former tumour cavity. Improvements in tumour bed delineation allow an increase of accuracy for adjuvant treatment

  6. Effect of botanical immunomodulators on human CYP3A4 inhibition: implications for concurrent use as adjuvants in cancer therapy.

    Science.gov (United States)

    Patil, Dada; Gautam, Manish; Gairola, Sunil; Jadhav, Suresh; Patwardhan, Bhushan

    2014-03-01

    Many botanical immunomodulators are used as adjuvants along with cancer chemotherapy. However, information on the impact of concurrent administration of such botanicals on pharmacokinetics of chemotherapy agents is inadequate. This study investigates inhibitory activities of 3 popular botanical adjuvants: ASPARAGUS RACEMOSU: (root aqueous extract; ARE), WITHANIA SOMNIFER: (root aqueous extract; WSE), and TINOSPORA CORDIFOLI: (stem aqueous extract, TCE) on human CYP3A4 isoenzyme, responsible for metabolism of several chemotherapy agents. . Testosterone 6-β hydroxylation was monitored using high-performance liquid chromatography as an indicator of CYP3A4 catalytic activities. Ketoconazole (positive control) and extracts were studied at their in vivo-relevant concentrations. TCE showed mild inhibition while no significant inhibitory activities were observed in WSE and ARE. TCE was further fractionated to obtain polar and nonpolar fractions. The nonpolar fraction showed significant CYP3A4 inhibition with IC50 13.06 ± 1.38 µg/mL. Major constituents of nonpolar fraction were identified using HPLC-DAD-MS profiling as berberine, jatrorrhizine, and palmatine, which showed IC50 values as 6.25 ± 0.30, 15.18 ± 1.59, and 15.53 ± 1.89 µg/mL, respectively. Our findings suggest that constituents of TCE extract especially protoberberine alkaloids have the potential to interact with cancer chemotherapy agents that are metabolized by CYP3A4 in vivo.

  7. 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

  8. 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....

  9. Reversible, PET-positive, generalized lymphadenopathy and splenomegaly during high-dose interferon-alpha-2b adjuvant therapy for melanoma.

    Science.gov (United States)

    Ridolfi, Laura; Cangini, Delia; Galassi, Riccardo; Passardi, Alessandro; Marzullo, Annamaria; Moretti, Andrea; Framarini, Massimo; Tauceri, Francesca; Serra, Luigi; Chiarion-Sileni, Vanna; Ridolfi, Ruggero

    2008-09-01

    A patient with resected stage III nodular melanoma treated with high-dose interferon-alpha-b2 adjuvant therapy went on to develop generalized lymphadenopathy and splenomegaly. The total body positron emission tomography showed a high F-fluorodeoxyglucose uptake (standardized uptake values >9), indicating possible lymph node and spleen malignancies. Histologic examinations of an axillary lymph node biopsy and an osteomedullar biopsy were negative, excluding both melanoma metastases and hematopoietic tumors. The symptoms completely regressed after suspension of treatment and a follow-up positron emission tomography was negative. It remains to be seen whether this unusual event can be ascribed to an autoimmune phenomenon linked to potential treatment efficacy and survival.

  10. Chemokines as Cancer Vaccine Adjuvants

    Directory of Open Access Journals (Sweden)

    Agne Petrosiute

    2013-10-01

    Full Text Available We are witnessing a new era of immune-mediated cancer therapies and vaccine development. As the field of cancer vaccines advances into clinical trials, overcoming low immunogenicity is a limiting step in achieving full success of this therapeutic approach. Recent discoveries in the many biological roles of chemokines in tumor immunology allow their exploitation in enhancing recruitment of antigen presenting cells (APCs and effector cells to appropriate anatomical sites. This knowledge, combined with advances in gene therapy and virology, allows researchers to employ chemokines as potential vaccine adjuvants. This review will focus on recent murine and human studies that use chemokines as therapeutic anti-cancer vaccine adjuvants.

  11. Prognostic role of a multigene reverse transcriptase-PCR assay in patients with node-negative breast cancer not receiving adjuvant systemic therapy.

    Science.gov (United States)

    Esteva, Francisco J; Sahin, Aysegul A; Cristofanilli, Massimo; Coombes, Kevin; Lee, Sang-Joon; Baker, Joffre; Cronin, Maureen; Walker, Michael; Watson, Drew; Shak, Steven; Hortobagyi, Gabriel N

    2005-05-01

    To test the ability of a reverse transcriptase-PCR (RT-PCR) assay, based on gene expression profiles, to accurately determine the risk of recurrence in patients with node-negative breast cancer who did not receive systemic therapy using formalin-fixed, paraffin-embedded tissue. A secondary objective was to determine whether the quantitative RT-PCR data correlated with immunohistochemistry assay data regarding estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status. We obtained archival paraffin-embedded tissue from patients with invasive breast cancer but no axillary lymph node involvement who had received no adjuvant systemic therapy and been followed for at least 5 years. RNA was extracted from three 10-microm-thick sections. The expression of 16 cancer-related genes and 5 reference genes was quantified using RT-PCR. A gene expression algorithm was used to calculate a recurrence score for each patient. We then assessed the ability of the test to accurately predict distant recurrence-free survival in this population. We identified 149 eligible patients. Median age at diagnosis was 59 years; mean tumor diameter was 2 cm; and 69% of tumors were estrogen receptor positive. Median follow-up was 18 years. The 5-year disease-free survival rate for the group was 80%. The 21 gene-based recurrence score was not predictive of distant disease recurrence. However, a high concordance between RT-PCR and immunohistochemical assays for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status was noted. RT-PCR can be done on paraffin-embedded tissue to validate the large numbers of genes associated with breast cancer recurrence. However, further work needs to be done to develop an assay to identify the likelihood of recurrent disease in patients with node-negative breast cancer who do not receive adjuvant tamoxifen or chemotherapy.

  12. Brivaracetam: review of its pharmacology and potential use as adjunctive therapy in patients with partial onset seizures.

    Science.gov (United States)

    Mumoli, Laura; Palleria, Caterina; Gasparini, Sara; Citraro, Rita; Labate, Angelo; Ferlazzo, Edoardo; Gambardella, Antonio; De Sarro, Giovambattista; Russo, Emilio

    2015-01-01

    Brivaracetam (BRV), a high-affinity synaptic vesicle protein 2A ligand, reported to be 10-30-fold more potent than levetiracetam (LEV), is highly effective in a wide range of experimental models of focal and generalized seizures. BRV and LEV similarly bind to synaptic vesicle protein 2A, while differentiating for other pharmacological effects; in fact, BRV does not inhibit high voltage Ca(2+) channels and AMPA receptors as LEV. Furthermore, BRV apparently exhibits inhibitory activity on neuronal voltage-gated sodium channels playing a role as a partial antagonist. BRV is currently waiting for approval both in the United States and the European Union as adjunctive therapy for patients with partial seizures. In patients with photosensitive epilepsy, BRV showed a dose-dependent effect in suppressing or attenuating the photoparoxysmal response. In well-controlled trials conducted to date, adjunctive BRV demonstrated efficacy and good tolerability in patients with focal epilepsy. BRV has a linear pharmacokinetic profile. BRV is extensively metabolized and excreted by urine (only 8%-11% unchanged). The metabolites of BRV are inactive, and hydrolysis of the acetamide group is the mainly involved metabolic pathway; hepatic impairment probably requires dose adjustment. BRV does not seem to influence other antiepileptic drug plasma levels. Six clinical trials have so far been completed indicating that BRV is effective in controlling seizures when used at doses between 50 and 200 mg/d. The drug is generally well-tolerated with only mild-to-moderate side effects; this is confirmed by the low discontinuation rate observed in these clinical studies. The most common side effects are related to central nervous system and include fatigue, dizziness, and somnolence; these apparently disappear during treatment. In this review, we analyzed BRV, focusing on the current evidences from experimental animal models to clinical studies with particular interest on potential use in clinical

  13. Pharmacological treatment of severe, therapy-resistant asthma in children: what can we learn from where?

    DEFF Research Database (Denmark)

    Bush, A; Pedersen, S; Hedlin, G

    2011-01-01

    There is a lack of high-quality evidence on what treatment should be used in children with properly characterised severe, therapy-resistant asthma. Data have to be largely extrapolated from trials in children with mild asthma, and adults with severe asthma. Therapeutic options can be divided......, particularly in the context of good baseline asthma control, are particularly difficult to treat; baseline control and lung function must be optimised with the lowest possible dose of ICS, and allergen triggers and exposures minimised. The use of high-dose ICS, leukotriene receptor antagonists or both...

  14. [Clinical and pharmacological aspects of rifaximin, local antibiotic therapy in intestinal disorders].

    Science.gov (United States)

    Gasztonyi, Beáta; Hunyady, Béla

    2004-10-24

    The authors report pharmacokinetics and indications of rifaximin and the results of clinical studies. Rifaximin has a large antibacterial spectrum with a good therapeutic effect on both gram positive and gram negative aerob and anaerob bacteria. Practically there is no absorption (< 1%) following oral administration with a high concentration in gastrointestinal mucosa (8000 microg/g). No increase in absorption can be detected in intestinal damage caused by inflammatory bowel disease. The remarkable safety profile of rifaximin is due to its negligible quality of absorption. According to the clinical studies rifaximin could be an adequate therapeutic approach in all gastrointestinal diseases and interventions when antibacterial therapy is needed.

  15. [Pharmacological therapy of age-related macular degeneration based on etiopathogenesis].

    Science.gov (United States)

    Fischer, Tamás

    2015-11-15

    It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator-activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl-cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors

  16. [Consensus for pharmacologic treatment of atherogenic dyslipidemia with statin-fenofibrate combined therapy].

    Science.gov (United States)

    2016-01-01

    LDLc levels are associated with increase of cardiovascular risk, and statins are currently used for their control. Nevertheless, a despite of LDLc levels at goal, a residual risk is persistent, commonly associated with persistent lipids modifications (high triglycerides and low HDLc). So, it is necessary to evaluate triglycerides and HDL to assessment cardiovascular risk. Clinical data are consistent with efficacy and safety of combination therapy with statin and other lipid lowering drugs, for instance fenofibrate. Patients with hipertriglyceridemia and low HDLc are the group with most potential improve. In that patients with atherogenic dyslipidemia, the target for therapeutic objectives related with non-HDL-cholesterol is a priority, because non-HDL-cholesterol is considered as a more accuracy measure to assessment cardiovascular risk. Copyright © 2015. Published by Elsevier España.

  17. Modeling Pharmacological Inhibition of Mast Cell Degranulation as a Therapy for Insulinoma

    Directory of Open Access Journals (Sweden)

    Laura Soucek

    2011-11-01

    Full Text Available Myc, a pleiotropic transcription factor that is deregulated and/or overexpressed in most human cancers, instructs multiple extracellular programs that are required to sustain the complex microenvironment needed for tumor maintenance, including remodeling of tumor stroma, angiogenesis, and inflammation. We previously showed in a model of pancreatic β-cell tumorigenesis that acute Myc activation in vivo triggers rapid recruitment of mast cells to the tumor site and that this is absolutely required for angiogenesis and macroscopic tumor expansion. More-over, systemic inhibition of mast cell degranulation with sodium cromoglycate induced death of tumor and endothelial cells in established tumors. Hence, mast cells are required both to establish and to maintain the tumors. Whereas this intimates that selective inhibition of mast cell function could be therapeutically efficacious, cromoglycate is not a practical drug for systemic delivery in humans, and no other systemic inhibitor of mast cell degranulation has hitherto been available. PCI-32765 is a novel inhibitor of Bruton tyrosine kinase (Btk that blocks mast cell degranulation and is currently in clinical trial as a therapy for B-cell non–Hodgkin lymphoma. Here, we show that systemic treatment of insulinoma-bearing mice with PCI-32765 efficiently inhibits Btk, blocks mast cell degranulation, and triggers collapse of tumor vasculature and tumor regression. These data reinforce the notion that mast cell function is required for maintenance of certain tumor types and indicate that the Btk inhibitor PCI-32765 may be useful in treating such diseases.

  18. Mature Results of a Prospective Randomized Trial Comparing 5-Flourouracil with Leucovorin to 5-Flourouracil with Levamisole as Adjuvant Therapy of Stage II and III Colorectal Cancer- The Israel Cooperative Oncology Group (ICOG Study

    Directory of Open Access Journals (Sweden)

    Arie Figer, Aviram Nissan, Adi Shani, Riva Borovick, Mariana Stiener, Mario Baras, Herbert R. Freund, Aaron Sulkes, Alexander Stojadinovic, Tamar Peretz

    2011-01-01

    Full Text Available Objective: Survival benefit with adjuvant therapy was shown in patients with Stage III colorectal cancer (CRC. This study evaluates long-term (10-year outcome in patients with CRC randomly assigned to adjuvant 5-Fluorouracil/Leucovorin (5FU+LV or 5-FU/Levamisole (5FU+LEV.Methods: Between 1990 and 1995, 398 patients with curatively resected Stage II-III CRC were randomly assigned to adjuvant 5FU+LV or 5FU+LEV for 12 months.Results: No difference was evident in 10-year relapse-free or overall survival between study groups. Grade III toxicity was similar between groups; however, neurotoxicity was significantly greater with 5FU+LEV (p=0.02 and gastrointestinal toxicity with 5FU+LV (p=0.03. Female patients treated with 5FU+LEV had improved overall survival.Conclusions: Adjuvant treatment of CRC is still based on leucovorin modulated fluorouracil. The long-term follow-up results of this trial indicate that the adjuvant treatment of Stage II-III CRC with 5FU+LV or 5FU+LEV is equally effective. The finding of improved survival in female subjects treated with 5FU+LEV warrants further study to determine if Levamisole is a better modulator of 5-FU than Leucovorin in this patient subset.

  19. Delafloxacin: Place in Therapy and Review of Microbiologic, Clinical and Pharmacologic Properties.

    Science.gov (United States)

    Jorgensen, Sarah C J; Mercuro, Nicholas J; Davis, Susan L; Rybak, Michael J

    2018-03-31

    Delafloxacin (formerly WQ-3034, ABT492, RX-3341) is a novel fluoroquinolone chemically distinct from currently marketed fluoroquinolones with the absence of a protonatable substituent conferring a weakly acidic character to the molecule. This property results in increased intracellular penetration and enhanced bactericidal activity under acidic conditions that characterize the infectious milieu at a number of sites. The enhanced potency and penetration in low pH environments contrast what has been observed for other zwitterionic fluoroquinolones, which tend to lose antibacterial potency under acidic conditions, and may be particularly advantageous against methicillin-resistant Staphylococcus aureus, for which the significance of the intracellular mode of survival is increasingly being recognized. Delafloxacin is also unique in its balanced target enzyme inhibition, a property that likely explains the very low frequencies of spontaneous mutations in vitro. Delafloxacin recently received US Food and Drug Administration approval for the treatment of acute bacterial skin and skin structure infections and is currently being evaluated in a phase 3 trial among patients with community-acquired pneumonia. In the current era of a heightened awareness pertaining to collateral ecologic damage, safety issues and antimicrobial stewardship principles, it is critical to describe the unique properties of delafloxacin and define its potential role in therapy. The purpose of this article is to review available data pertaining to delafloxacin's biochemistry, pharmacokinetic/pharmacodynamics characteristics, in vitro activity and potential for resistance selection as well as current progress in clinical trials to ultimately assist clinicians in selecting patients who will benefit most from the distinctive properties of this agent.

  20. 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.

  1. Study of new ways of supplementary and combinatory therapy of rheumatoid arthritis with immunomodulators. Glucomannan and Imunoglukán in adjuvant arthritis.

    Science.gov (United States)

    Bauerová, K; Paulovicová, E; Mihalová, D; Svík, K; Ponist, S

    2009-01-01

    We studied the anti-arthritic activity of glucomannan (GM) isolated from Candida utilis and of Imunoglukán, a beta-(1,3/1,6)-D-glucan (IMG) isolated from Pleurotus ostreatus. Adjuvant arthritis (AA) was induced intradermally by the injection of Mycobacterium butyricum in incomplete Freund's adjuvant to Lewis rats. Blood for biochemical and immunological analysis was collected on experimental days 1, 14, 21, and 28. A clinical parameter--hind paw volume (HPV)--was also measured. The detection of IL-1 alpha, IL-4, TNF alpha, and MCP-1 was done by immunoflowcytometry. On day 28--the end of the experiment--we determined spectrophotometrically: the total anti-oxidant status (TAS) of plasma samples along with thiobarbituric acid-reacting substances (TBARS) levels in plasma and we assessed the activity of gamma-glutamyl transferase (GGT) in hind paw joint homogenate. The experiments included healthy animals, arthritic animals without treatment, and arthritic animals with administration of glucomannan (GM-AA) in the oral daily dose of 15 mg/kg b.w. and of IMG (IMG-AA) in the oral daily dose of 2 mg/kg b.w. The progress of AA was manifested by all parameters monitored. Both substances had beneficial effects on HPV, TBARS levels, GGT activity, and TAS levels. For cytokine assessment, only IMG-AA samples were selected, considering the significant HPV improvement accompanied with the observed anti-oxidant action. IMG administration had a positive immunomodulating effect on all cytokine plasma levels measured, changed markedly due to arthritis progression. Thus, IMG may be considered as a candidate for combinatorial therapy of rheumatoid arthritis.

  2. Efficacy, tolerability, and safety of non-pharmacological therapies for chronic pain: An umbrella review on various CAM approaches.

    Science.gov (United States)

    Houzé, Bérengère; El-Khatib, Héjar; Arbour, Caroline

    2017-10-03

    Complementary and alternative medicine (CAM) therapies may be used as a non-pharmacological approach to chronic pain management. While hundreds of trials about individual CAM modality have been conducted, a comprehensive overview of their results is currently lacking for pain clinicians and researchers. This umbrella review synthesized the quality of meta-analytic evidence supporting the efficacy, tolerability and safety of CAM therapies for the management of chronic pain. MEDLINE, EMBASE, CINAHL, and CENTRAL were searched from October 1991 to November 2016. Reviews of clinical trials (randomized and non-randomized) with meta-analysis investigating the utility of any CAM modality for chronic pain were eligible. Pain relief post-intervention was the main outcome and secondary outcomes included patients' adherence and incidence of adverse effects during CAM protocol. Twenty-six reviews (207 clinical trials, >12,000 participants) about 18 CAM modalities, falling under natural products, mind and body practices or other complementary health approaches were included. Inhaled cannabis, graded motor imagery, and Compound Kushen injection (a form of Chinese medicine) were found the most efficient (with moderate-to-high effect sizes and low heterogeneity) and tolerable (≥80% of adherence to study protocols) for chronic pain relief. When reported, adverse effects related to these CAM were minor. Although several CAM were found effective for chronic pain relief, it remains unclear when these modalities are a reasonable choice against or in conjunction with mainstream treatments. In that sense, future research with a clear emphasis on concurrent evaluation of CAM overall efficacy and patient adherence/tolerance is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. 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

    Energy Technology Data Exchange (ETDEWEB)

    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

  4. 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.

  5. Higher utilization of the pharmacologic and non-pharmacologic therapies in patients with chronic low back pain in a developing country than in the USA: Treatment of chronic low back pain

    Directory of Open Access Journals (Sweden)

    Jovičić Jelena

    2016-01-01

    therapy (52.2 ± 4.9%, massage (50.8 ± 4.8%, chiropractic manipulation (69.1 ± 10.4% and acupuncture treatment (50 ± 11.6%. All patients used NSAIDs, with the average duration of therapy 24.2 ± 11.9 months, and the average effectiveness 61.6 ± 2.8%. These patients used compounding topical creams for 7.5 ± 2.3 months on average with effectiveness of 41.1 ± 3.5%. None of the patients used opioids. Majority of them - 72.8% never missed any day of work while 8.6% missed 10-30 days, and only 4.3% missed more than 30 days of work even though 79.6% patients had an active type of job (walking, bending, heavy lifting, etc. Discussion: Administration of opioids, epidural steroid injection, facet joint block in the treatment of chronic low back pain became extremly frequent in the USA in the last 15 years. Multimodal therapy approach of back pain is the main characteristic of the treatment strategies in the USA. Opposite to the USA, European strategy concern non-invasive, non-pharmacologic and pharmacologic approaches. Conclusion: Results of this study showed higher utilization of pharmacologic and non-pharmacological therapies in patients with chronic low back pain prior to opioids and interventional procedures than in the USA.

  6. Radiation Therapy-First Strategy After Surgery With or Without Adjuvant Chemotherapy in Stage IIIA-N2 Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Lee, Hyun Woo; Noh, O Kyu; Oh, Young-Taek; Choi, Jin-Hyuk; Chun, Mison; Kim, Hwan-Ik; Heo, Jaesung; Ahn, Mi Sun; Park, Seong Yong; Park, Rae Woong; Yoon, Dukyong

    2016-03-01

    Postoperative radiation therapy (PORT) and postoperative chemotherapy (POCT) can be administered as adjuvant therapies in patients with non-small cell lung cancer (NSCLC). The aim of this study was to present the clinical outcomes in patients treated with PORT-first with or without subsequent POCT in stage IIIA-N2 NSCLC. From January 2002 to November 2014, the conditions of 105 patients with stage IIIA-N2 NSCLC who received PORT-first with or without subsequent POCT were analyzed. PORT was initiated within 4 to 6 weeks after surgical resection. Platinum-based POCT was administered 3 to 4 weeks after the completion of PORT. We analyzed the outcomes and the clinical factors affecting survival. Of 105 patients, 43 (41.0%) received POCT with a median of 4 cycles (range, 2-6 cycles). The follow-up times ranged from 3 to 123 months (median, 30 months), and the 5-year overall survival (OS) was 40.2%. The 5-year OS of patients treated with PORT and POCT was significantly higher than that of patients with PORT (61.3% vs 29.2%, Ptreatment of stage IIIA-N2 NSCLC. The benefit of POCT on OS was preserved even in the PORT-first setting. Further studies are warranted to compare the sequencing of PORT and POCT, guaranteeing the proper use of POCT. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. 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.

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

    International Nuclear Information System (INIS)

    Roberts, Kenneth B.; Soulos, Pamela R.; Herrin, Jeph; Yu, James B.; Long, Jessica B.; Dostaler, Edward

    2013-01-01

    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

  9. Marketed Drugs Can Inhibit Cytochrome P450 27A1, a Potential New Target for Breast Cancer Adjuvant Therapy.

    Science.gov (United States)

    Mast, Natalia; Lin, Joseph B; Pikuleva, Irina A

    2015-09-01

    Cytochrome P450 CYP27A1 is the only enzyme in humans converting cholesterol to 27-hydroxycholesterol, an oxysterol of multiple functions, including tissue-specific modulation of estrogen and liver X receptors. Both receptors seem to mediate adverse effects of 27-hydroxycholesterol in breast cancer when the levels of this oxysterol are elevated. The present work assessed druggability of CYP27A1 as a potential antibreast cancer target. We selected 26 anticancer and noncancer medications, most approved by the Food and Drug Administration, and evaluated them first in vitro for inhibition of purified recombinant CYP27A1 and binding to the enzyme active site. Six strong CYP27A1 inhibitors/binders were identified. These were the two antibreast cancer pharmaceuticals anastrozole and fadrozole, antiprostate cancer drug bicalutamide, sedative dexmedetomidine, and two antifungals ravuconazole and posaconazole. Anastrozole was then tested in vivo on mice, which received subcutaneous drug injections for 1 week. Mouse plasma and hepatic 27-hydroxycholesterol levels were decreased 2.6- and 1.6-fold, respectively, whereas plasma and hepatic cholesterol content remained unchanged. Thus, pharmacologic CYP27A1 inhibition is possible in the whole body and individual organs, but does not negatively affect cholesterol elimination. Our results enhance the potential of CYP27A1 as an antibreast cancer target, could be of importance for the interpretation of Femara versus Anastrozole Clinical Evaluation Trial, and bring attention to posaconazole as a potential complementary anti-breast cancer medication. More medications on the US market may have unanticipated off-target inhibition of CYP27A1, and we propose strategies for their identification. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  10. 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.

  11. Colonic healing: the effect of irradiation and chemotherapy - an experimental study, resembling adjuvant therapy for colorectal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Weiber, S.

    1993-08-01

    Adjuvant treatment of colon and rectal carcinoma is of major interest. Irradiation and chemotherapy are modalities used widely. The purpose of this study was to evaluate the effect of preoperative irradiation and postoperative intraperitoneal 5-fluorouracil treatment on colonic healing. In rats preoperative irradiation of the lower abdominal region by 10 + 10 Gy four days apart caused inflammatory reaction in the colon as evaluated by histology and determination of myeloperoxidase activity. The inflammatory reaction reached its peek within a week of the second irradiation. When standard used colonic resections and anastomes were performed within the irradiate part of the colon the anastomotic healing was not affected during the first week after operation as judged by complications and breaking strength. A lower breaking strength and an increase in myeloperoxidase activity two months after operation may indicate late changes within the intestinal wall. Intraperitoneal 5-fluorouracil in rat given immediately after colonic resection and repeated as daily injections caused a weight loss and marked reduction in breaking strength of the anastomosis as well as in the abdominal skin wound. A reduction in 5-fluorouracil concentration did not alter the negative wound healing effect of the chemotherapy. In a group of rats subjected to nutritional depletion, mimicking the weight curve of 5-fluorouracil treated animals, anastomotic breaking strength was not compromised to the same extent as when 5-fluorouracil was given. This indicated a direct toxic effect rather than an effect of reduced food intake caused by 5-FU treatment. Collagen synthesis and the formation of new tissue in the wound gap was reduced in 5-fluorouracil treated animals compared to controls as judged by in vivo incorporation of {sup 3}H-proline in the anastomotic segment and determination of anastomotic breaking strength after removal of sutures. 108 refs.

  12. Colonic healing: the effect of irradiation and chemotherapy - an experimental study, resembling adjuvant therapy for colorectal carcinoma

    International Nuclear Information System (INIS)

    Weiber, S.

    1993-08-01

    Adjuvant treatment of colon and rectal carcinoma is of major interest. Irradiation and chemotherapy are modalities used widely. The purpose of this study was to evaluate the effect of preoperative irradiation and postoperative intraperitoneal 5-fluorouracil treatment on colonic healing. In rats preoperative irradiation of the lower abdominal region by 10 + 10 Gy four days apart caused inflammatory reaction in the colon as evaluated by histology and determination of myeloperoxidase activity. The inflammatory reaction reached its peek within a week of the second irradiation. When standard used colonic resections and anastomes were performed within the irradiate part of the colon the anastomotic healing was not affected during the first week after operation as judged by complications and breaking strength. A lower breaking strength and an increase in myeloperoxidase activity two months after operation may indicate late changes within the intestinal wall. Intraperitoneal 5-fluorouracil in rat given immediately after colonic resection and repeated as daily injections caused a weight loss and marked reduction in breaking strength of the anastomosis as well as in the abdominal skin wound. A reduction in 5-fluorouracil concentration did not alter the negative wound healing effect of the chemotherapy. In a group of rats subjected to nutritional depletion, mimicking the weight curve of 5-fluorouracil treated animals, anastomotic breaking strength was not compromised to the same extent as when 5-fluorouracil was given. This indicated a direct toxic effect rather than an effect of reduced food intake caused by 5-FU treatment. Collagen synthesis and the formation of new tissue in the wound gap was reduced in 5-fluorouracil treated animals compared to controls as judged by in vivo incorporation of 3 H-proline in the anastomotic segment and determination of anastomotic breaking strength after removal of sutures. 108 refs

  13. Adjuvant chemo- and radiotherapy in gastrointestinal tumors

    International Nuclear Information System (INIS)

    Sendler, A.; Feldmann, H.J.; Fink, U.; Molls, M.; Siewert, J.R.

    1995-01-01

    In modern surgical oncology, adjuvant therapies are important complementary strategies. In local advanced carcinomas of the gastrointestinal tract, 5-year survival data are still disappointing despite standardized surgery. In this context, it has to be differentiated between adjuvant therapy following complete tumor exstirpation (so-called UICC R 0 resection) and additive therapies following incomplete tumor resections (UICC R 1 or R 2 resection). Modalities in the adjuvant setting are chemotherapy, radiotherapy or the combined radio-/chemotherapy. In esophageal and gastric cancer there is up to now no benefit of postoperative adjuvant therapy. In pancreatic cancer, there are studies indicating a benefit of combined radio-/chemotherapy after complete tumor resection. A standard adjuvant chemotherapeutic treatment is proven in colon cancer stage III (Dukes C) with levamisole and 5-FU. Completely resected rectal carcinoma should be treated postoperatively with combined radio-/chemotherapy. In the common clinical or practical setting, adjuvant therapy is indicated only in locally advanced gastrointestinal tumors following R 0 resection. Postoperative therapy following incomplete tumor resection has its reason only in a palliative intention. (orig.) [de

  14. 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

  15. Overexpression of nuclear AR-V7 protein in primary prostate cancer is an independent negative prognostic marker in men with high-risk disease receiving adjuvant therapy.

    Science.gov (United States)

    Chen, Xin; Bernemann, Christof; Tolkach, Yuri; Heller, Martina; Nientiedt, Cathleen; Falkenstein, Michael; Herpel, Esther; Jenzer, Maximilian; Grüllich, Carsten; Jäger, Dirk; Sültmann, Holger; Duensing, Anette; Perner, Sven; Cronauer, Marcus V; Stephan, Carsten; Debus, Jürgen; Schrader, Andres Jan; Kristiansen, Glen; Hohenfellner, Markus; Duensing, Stefan

    2018-04-01

    Overexpression of the androgen receptor (AR) splice variant 7 (AR-V7) has recently been reported to be associated with resistance to antihormonal therapy. Herein, we address the question whether tumor cells with AR-V7 expression can be detected at the time of radical prostatectomy, that is, before long-term hormonal manipulation and castration resistance, and what the potential prognostic impact on the biochemical recurrence (BCR)-free survival may be. An anti-AR-V7 antibody was first validated in a training set of prostate cancer specimens by a comparison of AR-V7 protein to AR-V7 mRNA expression. We then analyzed nuclear AR-V7 protein expression in the primary tumors and lymph node metastases from 163 predominantly high-risk patients (cohort I) as well as the primary tumors from patients of a second, consecutive patient cohort (n = 238, cohort II) not selected for any clinicopathological features. Staining results were correlated to patient characteristics and BCR-free patient survival. High nuclear AR-V7 protein expression was detected in approximately 30%-40% of patients in cohort I and II at the time of radical prostatectomy. High baseline expression of nuclear AR-V7 protein was associated with an unfavorable BCR-free survival in the high-risk patient cohort I but not in the unselected consecutive cohort II. Remarkably, AR-V7 was an independent negative prognostic factor in high-risk prostate cancer patients of cohort I who were selected to receive adjuvant treatment. Prostate cancer cells with high nuclear AR-V7 protein expression can be detected in a substantial proportion of tumors at the time of radical prostatectomy. The presence of AR-V7-positive tumor cells is associated with an unfavorable prognosis for BCR-free survival in a high-risk patient cohort including a subgroup of patients selected to receive adjuvant therapy, in which AR-V7 was an independent negative prognosticator. Overexpression of nuclear AR-V7 protein hence identifies a subset of tumors

  16. The use of Chinese herbal medicine as an adjuvant therapy to reduce incidence of chronic hepatitis in colon cancer patients: A Taiwanese population-based cohort study.

    Science.gov (United States)

    Lin, Tsai-Hui; Yen, Hung-Rong; Chiang, Jen-Huai; Sun, Mao-Feng; Chang, Hen-Hong; Huang, Sheng-Teng

    2017-04-18

    There is a decided lack of in-depth studies to evaluate the effectiveness of Chinese Herbal Medicine (CHM) as an adjuvant therapy on the incidence of chronic hepatitis in patients with colon cancer. The aim of this study is to assess whether CHM treatment decreased the incidence of chronic hepatitis in colon cancer patients who received conventional Western medical treatment. A Taiwanese nationwide population-based study of colon cancer patients receiving Western medicine treatment in conjunction with CHM treatment, using data provided by the National Health Insurance (NHI) Research Database, was conducted. A total of 61676 patients were diagnosed with colon cancer in Taiwan within the defined study period, from 1997 to 2010. After randomly equal matching for age, sex, excluding patients younger than 18 years of age, chronic hepatitis before colon cancer diagnosis date, receiving acupuncture and/or moxibustion and taking CHM for less than 30 days, data from 155 patients were analyzed. Hazard ratios of incidence rate of chronic hepatitis were used to determine the influence of CHM and the therapeutic potential of herbal products in treating patients with colon cancer. CHM used for patients with colon cancer exhibited significantly decreased incidence rates of chronic hepatitis [hazard ratio (HR)=0.53; 95% confidence interval (CI):0.38-0.74], with multivariate adjustment, compared to those without CHM use. The protective effect of CHM treatment with statistical significance across the stratification of age, gender, co-morbidity and treatment modality was noted. The cumulative incidence of chronic hepatitis was also reduced in patients with colon cancer receiving CHM treatment during a five-year period. In this study, we provide the ten most used single herbs and herbal formulas that were prescribed for patients with colon cancer; moreover, we identify the eight single herbs and five formulas used in CHM treatment which significantly decreased incidence of chronic

  17. Photobiomodulation therapy for the management of radiation-induced dermatitis. A single-institution experience of adjuvant radiotherapy in breast cancer patients after breast conserving surgery

    International Nuclear Information System (INIS)

    Strouthos, Iosif; Chatzikonstantinou, Georgios; Tselis, Nikolaos; Bon, Dimitra; Karagiannis, Efstratios; Zoga, Eleni; Ferentinos, Konstantinos; Maximenko, Julia; Nikolettou-Fischer, Vassiliki; Zamboglou, Nikolaos

    2017-01-01

    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. (orig.) [de

  18. Understanding discontinuation of oral adjuvant endocrine therapy by women with hormone receptor-positive invasive breast cancer nearly 4 years from diagnosis.

    Science.gov (United States)

    Bell, Robin J; Fradkin, Pamela; Schwarz, Max; Davis, Susan R

    2013-01-01

    The aim of this study was to investigate the extent of discontinuation of oral adjuvant endocrine therapy (OAET) in women nearly 4 years from the diagnosis of their first episode of invasive breast cancer and the reasons for such discontinuation. We used a large, prospective cohort study of women who had been diagnosed with their first episode of invasive breast cancer between 2004 and 2006, recruited through a state-based cancer registry. All participants completed an enrollment questionnaire (EQ) within 12 months of diagnosis and annual follow-up questionnaires (FQs) thereafter. The data in this report were obtained from the EQ and the first three FQs. A total of 1,370 women with hormone receptor-positive disease completed the EQ. At the completion of the third FQ nearly 4 years from diagnosis, 1,193 women remained in the study. Use of OAET peaked by 2 years postdiagnosis. At nearly 4 years from diagnosis, 18% of the 1,193 women remaining in the study were not taking OAET. Of these women, just more than half had ceased therapy mainly owing to a range of adverse effects, predominantly estrogen deficiency symptoms, but the remainder (8% of women remaining in the study) had never used OAET. Our study confirms that early discontinuation of OAET due to estrogen deficiency symptoms remains an important issue despite calls for strategies to address this problem. The number of women potentially suitable for OAET but not receiving it was almost as great as the number of those who have discontinued therapy.

  19. The impact of different definitions and reference groups on the prevalence of cognitive impairment: a study in postmenopausal breast cancer patients before the start of adjuvant systemic therapy.

    Science.gov (United States)

    Schilder, Christina M; Seynaeve, Caroline; Linn, Sabine C; Boogerd, Willem; Gundy, Chad M; Beex, Louk V; van Dam, Frits S; Schagen, Sanne B

    2010-04-01

    Several prospective studies into the effects of adjuvant systemic therapy on cognitive functioning suggest that a proportion of breast cancer patients show cognitive deficits already before the start of systemic therapy. Owing to, among others, methodological inconsistency, studies report different rates of this pre-treatment cognitive impairment. We examined the impact of four different criteria of cognitive impairment and two types of reference groups (a study-specific healthy reference group versus published normative data) on the prevalence of cognitive impairment. Two hundred and five postmenopausal breast cancer patients underwent a battery of neuropsychological tests before the start of endocrine therapy, 124 healthy subjects underwent the same tests. Proportions of cognitive impaired patients were calculated for each of four criteria for cognitive impairment, using (1) study-specific healthy controls and (2) published norms of healthy controls as reference groups. The prevalence of cognitive impairment varied greatly with the strictness of the criterion, as expected, but also was dependent on the reference group used. Cognitive impairment, relative to published norms, ranged from 1% for the strictest to 36.6% for the less strict criterion, cognitive impairment relative to study-specific healthy controls, ranged from 13.7 to 45.4% for the same criteria. This study highlights contrasting proportions of cognitive impairment by using different criteria for cognitive impairment and different reference groups. (Dis)advantages of the methods using a criterion for cognitive impairment, and of the use of published norms versus a study-specific reference group are discussed. Copyright 2009 John Wiley & Sons, Ltd.

  20. Preliminary results of the use of photon-magnetic therapy in prevention and treatment of skin radiation reactions of patients with breast cancer with adjuvant radiation therapy

    International Nuclear Information System (INIS)

    Syimonova, L.Yi.; Gertman, V.Z.; Byilogurova, L.V.; Kulyinyich, G.V.; Lavrik, V.P.

    2012-01-01

    The authors report preliminary findings of the investigation of the effect of combination photon-magnetic therapy with successive application of red and blue light to the skin of breast cancer patients during the course of post-operative radiation therapy. It was established that photonmagnetic therapy positively influenced the state of the skin in the irradiated areas. Addition of the magnetic factor significantly improved the efficacy of phototherapy. The patients receiving photon-magnetic therapy finished the course of radiation therapy with almost unchanged skin.

  1. Acupuncture as a complementary therapy to the pharmacological treatment of osteoarthritis of the knee: randomised controlled trial

    Science.gov (United States)

    Vas, Jorge; Méndez, Camila; Perea-Milla, Emilio; Vega, Evelia; Panadero, María Dolores; León, José María; Borge, Miguel Ángel; Gaspar, Olga; Sánchez-Rodríguez, Francisco; Aguilar, Inmaculada; Jurado, Rosario

    2004-01-01

    Objectives To analyse the efficacy of acupuncture as a complementary therapy to the pharmacological treatment of osteoarthritis of the knee, with respect to pain relief, reduction of stiffness, and increased physical function during treatment; modifications in the consumption of diclofenac during treatment; and changes in the patient's quality of life. Design Randomised, controlled, single blind trial, with blinded evaluation and statistical analysis of results. Setting Pain management unit in a public primary care centre in southern Spain, over a period of two years. Participants 97 outpatients presenting with osteoarthritis of the knee. Interventions Patients were randomly separated into two groups, one receiving acupuncture plus diclofenac (n = 48) and the other placebo acupuncture plus diclofenac (n = 49). Main outcome measures The clinical variables examined included intensity of pain as measured by a visual analogue scale; pain, stiffness, and physical function subscales of the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index; dosage of diclofenac taken during treatment; and the profile of quality of life in the chronically ill (PQLC) instrument, evaluated before and after the treatment programme. Results 88 patients completed the trial. In the intention to treat analysis, the WOMAC index presented a greater reduction in the intervention group than in the control group (mean difference 23.9, 95% confidence interval 15.0 to 32.8) The reduction was greater in the subscale of functional activity. The same result was observed in the pain visual analogue scale, with a reduction of 26.6 (18.5 to 34.8). The PQLC results indicate that acupuncture treatment produces significant changes in physical capability (P = 0.021) and psychological functioning (P = 0.046). Three patients reported bruising after the acupuncture sessions. Conclusions Acupuncture plus diclofenac is more effective than placebo acupuncture plus diclofenac for the symptomatic

  2. Limb sparing approach: Adjuvant radiation therapy in adults with intermediate or high-grade limb soft tissue sarcoma

    International Nuclear Information System (INIS)

    Merimsky, Ofer; Soyfer, Vjacheslav; Kovner, Felix; Bickels, Jacob; Issakov, Josephine; Flusser, Gideon; Meller, Isaac; Ofer, Oded; Kollender, Yehuda

    2005-01-01

    Background: Limb soft tissue sarcomas (STS) are currently treated with limb sparing surgery (LSS) followed by radiation therapy (RT). Patients and methods: Between October 1994 and October 2002, 133 adult patients with intermediate or high-grade limb STS were approached by LSS+RT. Results: RT related toxicity was manageable, with a low rate of severe effects. At 4-year median follow-up, there were 48 recurrences of any type, 23 of isolated local failure, and 35 of systemic spread w/o local failure. DFS and OS were influenced by disease stage II vs I, primary site in the upper limb vs lower limb, MPNST vs other types, induction therapy vs no induction, adequate resection vs marginal resection or involved margins, and good response to induction therapy vs bad response. DFS and OS were Patient's age and sex, tumor depth, acute or late toxicity of RT, or the interval of time between the date of definitive surgery and the start of RT did not affect DFS and or OS. Conclusions: The RT protocol is applicable in the era of complicated, expensive and time-consuming 3D therapy. Our results of LSS+RT in adults with limb HG STS are satisfactory

  3. The Effect of Reflexology on the Pain-Insomnia-Fatigue Disturbance Cluster of Breast Cancer Patients During Adjuvant Radiation Therapy.

    Science.gov (United States)

    Tarrasch, Ricardo; Carmel-Neiderman, Narin N; Ben-Ami, Sarah; Kaufman, Bella; Pfeffer, Raphi; Ben-David, Merav; Gamus, Dorit

    2018-01-01

    To evaluate the effects of reflexology treatment on quality of life, sleep disturbances, and fatigue in breast cancer patients during radiation therapy. A total of 72 women with breast cancer (stages 1-3) scheduled for radiation therapy were recruited. Women were allocated upon their preference either to the group receiving reflexology treatments once a week concurrently with radiotherapy and continued for 10 weeks or to the control group (usual care). The Lee Fatigue Scale, General Sleep Disturbance Scale, and Multidimensional Quality of Life Scale Cancer were completed by each patient in both arms at the beginning of the radiation treatment, after 5 weeks, and after 10 weeks of reflexology treatment. The final analysis included 58 women. The reflexology treated group demonstrated statistically significant lower levels of fatigue after 5 weeks of radiation therapy (p fatigue, quality of sleep, pain, and quality of life in breast cancer patients during radiation therapy. Reflexology prevented the decline in quality of life and significantly ameliorated the fatigue and quality of sleep of these patients. An encouraging trend was also noted in amelioration of pain levels.

  4. 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

  5. Report of the ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases: definitions, frequency and pharmacological aspects

    DEFF Research Database (Denmark)

    Allez, Matthieu; Karmiris, Konstantinos; Louis, Edouard

    2010-01-01

    The first ECCO pathogenesis workshop focused on anti-TNF therapy failures in inflammatory bowel diseases (IBDs). The overall objective was to better understand and explore primary non response and loss of response to anti-TNF agents in IBD. The outcome of this workshop is presented into two parts....... This first section addresses definitions, frequency and pharmacological aspects of anti-TNF therapy failure, including pharmacokinetics of anti-TNF monoclonal antibodies and immune and non-immune mediated clearance of anti-TNF mAbs. The second section concerns the biological roles of TNF and TNF antagonists...

  6. Monitoring the response of breast cancer to radiotherapy and adjuvant therapy using breast cancer antigen CA 15-3

    International Nuclear Information System (INIS)

    Bafarag, Saeed Mohamed Ibrahim

    2001-05-01

    In this study 35 breast cancer patients were followed during their treatment in Radiation and Isotope Center of Khartoum (RICK) using breast cancer antigen CA 15-3 as an indicator of tumor marker. They were classified into three categories of CA 15-3 concentration level as stated by Colomer and Genolla (1989) as follows: normal level less than 40 UI/ml, moderate level more than 40 UI/ml and less than 60 UI/ml, and high level, more than 60 UI/ml to 3000 UI/ml. A 5 ml of venous blood samples' were collected using sterile syringes from patients with different stage of breast cancer. The sample size were thirty-five cases, one of the cases is rejected because the patient discontinued the treatment. The blood samples were collected as follows: before starting the treatment course, at the mid time of treatment course, after completion the treatment course, and after one month of completion of the treatment course. The patients classified into two groups according to their treatment protocol. The first group received only external radiation therapy treatment and those were 18 patients out of 35, while the second group received combined therapy and those were 16 patients out of 35. For those whom received external radiation radiation therapy only, the results showed that the mean value of CA 15-3 concentration level decreased at the mid of the treatment as follows: 26±3 UI/ml, 24±3 UI/ml, 22±3 UI/ml respectively, while the mean value of CA 15-3 concentration level before starting the treatment was found to be 46±14 UI/ml. The number of the patients in the normal concentration level of CA 15-3 increased by 11% at the mid of external radiotherapy treatment and by 13% at the mid combined therapy, while the moderate level decreased by 6% for both external radiotherapy and combined therapy, while the number of patients within the high level decreased by 5% for external radiotherapy and 7% for combined therapy. After completion and after one month of completion of external

  7. Sexual Functioning Among Endometrial Cancer Patients Treated With Adjuvant High-Dose-Rate Intra-Vaginal Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. Sexual Functioning Among Endometrial Cancer Patients Treated With Adjuvant High-Dose-Rate Intra-Vaginal Radiation Therapy

    International Nuclear Information System (INIS)

    Damast, Shari; Alektiar, Kaled M.; Goldfarb, Shari; Eaton, Anne; Patil, Sujata; Mosenkis, Jeffrey; Bennett, Antonia; Atkinson, Thomas; Jewell, Elizabeth; Leitao, Mario; Barakat, Richard; Carter, Jeanne; Basch, Ethan

    2012-01-01

    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 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.

  9. Personal and clinical social support and adherence to adjuvant endocrine therapy among hormone receptor-positive breast cancer patients in an integrated health care system.

    Science.gov (United States)

    Kroenke, Candyce H; Hershman, Dawn L; Gomez, Scarlett L; Adams, Sara R; Eldridge, Elizabeth H; Kwan, Marilyn L; Ergas, Isaac J; Kubo, Ai; Kushi, Lawrence H

    2018-04-18

    We evaluated associations between personal and clinical social support and non-adherence to adjuvant endocrine therapy (AET) in a large, Northern California breast cancer (BC) cohort from an integrated healthcare network. This study included 3382 women from the Pathways Study diagnosed from 2005 to 2013 with stages I-III hormone receptor-positive BC and who responded to the Medical Outcomes Study Social Support and Interpersonal Processes of Care surveys, approximately 2 months post-diagnosis. We used logistic regression to evaluate associations between tertiles of social support and non-initiation (social support (P trend = 0.02). Women with moderate (HR 1.20, 95% CI 0.99-1.45) or low (HR 1.32, 95% CI 1.09-1.60) personal social support were also more likely to discontinue treatment (P trend = 0.01). Furthermore, women with moderate (HR 1.25, 95% CI 1.02-1.53) or low (HR 1.38, 95% CI 1.12-1.70) personal social support had higher non-adherence (P trend = 0.007). Associations with clinical social support and outcomes were similar. Notably, high clinical social support mitigated the risk of discontinuation when patients' personal support was moderate or low (P value = 0.04). Women with low personal or clinical social support had higher AET non-adherence. Clinician teams may need to fill support gaps that compromise treatment adherence.

  10. The Role of Postoperative Adjuvant Radiation Therapy in the Management of Adenocarcinoma of the Colon-A review of 21 Patients

    International Nuclear Information System (INIS)

    Park, Kyung Ho; Kim, Dong Won; Loh, John J. K.; Suh, Chang Ok

    1989-01-01

    From March 1970 to December 1984, treatment results of 21 patients treated initially with curative surgery for adenocarcinoma of the colon and referred to the Department of Radiation Oncology, College of Medicine, Yonsei University, were analyzed retrospectively. Thirteen of 21 patients who were considered to be at high risk (i.e, stage B2 or above), received postoperative adjuvant radiation therapy. However, 2 of 13 patients did not complete their courses of radiotherapy as planned because of poor tolerance to radiotherapy or patient refusal and were excluded from this study. Remaining 8 of 21 patients who did not receive postoperative radiotherapy, presented with recurrence at the time of referral and treated for palliation. In 11 patients who finished postoperativc radiotherapy, overall local failure rate was 9%(1/11) and the 5 year actuarial survival rate was 55%. Local failure rates by stage were 0(0/4), 14%(1/7) for stage B2+B3, C1+C2+C3 respectively and 0(0/2), 17%(1/6), 0(0/3) for stage C1, B2+C2, B3+C3 respectively

  11. Therapeutic treatments potentially mediated by melatonin receptors: potential clinical uses in the prevention of osteoporosis, cancer and as an adjuvant therapy.

    Science.gov (United States)

    Witt-Enderby, Paula A; Radio, Nicholas M; Doctor, John S; Davis, Vicki L

    2006-11-01

    Melatonin's therapeutic potential is grossly underestimated because its functional roles are diverse and its mechanism(s) of action are complex and varied. Melatonin produces cellular effects via a variety of mechanisms in a receptor independent and dependent manner. In addition, melatonin is a chronobiotic agent secreted from the pineal gland during the hours of darkness. This diurnal release of melatonin impacts the sensitivity of melatonin receptors throughout a 24-hr period. This changing sensitivity probably contributes to the narrow therapeutic window for use of melatonin in treating sleep disorders, that is, at the light-to-dark (dusk) or dark-to-light (dawn) transition states. In addition to the cyclic changes in melatonin receptors, many genes cycle over the 24-hr period, independent or dependent upon the light/dark cycle. Interestingly, many of these genes support a role for melatonin in modulating metabolic and cardiovascular physiology as well as bone metabolism and immune function and detoxification of chemical agents and cancer reduction. Melatonin also enhances the actions of a variety of drugs or hormones; however, the role of melatonin receptors in modulating these processes is not known. The goal of this review is to summarize the evidence related to the utility of melatonin as a therapeutic agent by focusing on its other potential uses besides sleep disorders. In particular, its use in cancer prevention, osteoporosis and, as an adjuvant to other therapies are discussed. Also, the role that melatonin and, particularly, its receptors play in these processes are highlighted.

  12. Women’s Beliefs on Early Adherence to Adjuvant Endocrine Therapy for Breast Cancer: A Theory-Based Qualitative Study to Guide the Development of Community Pharmacist Interventions

    Directory of Open Access Journals (Sweden)

    Brittany Humphries

    2018-06-01

    Full Text Available Adjuvant endocrine therapy (AET taken for a minimum of five years reduces the recurrence and mortality risks among women with hormone-sensitive breast cancer. However, adherence to AET is suboptimal. To guide the development of theory-based interventions to enhance AET adherence, we conducted a study to explore beliefs regarding early adherence to AET. This qualitative study was guided by the Theory of Planned Behavior (TPB. We conducted focus groups and individual interviews among women prescribed AET in the last two years (n = 43. The topic guide explored attitudinal (perceived advantages and disadvantages, normative (perception of approval or disapproval, and control beliefs (barriers and facilitating factors towards adhering to AET. Thematic analysis was conducted. Most women had a positive attitude towards AET regardless of their medication-taking behavior. The principal perceived advantage was protection against a recurrence while the principal inconvenience was side effects. Almost everyone approved of the woman taking her medication. The women mentioned facilitating factors to encourage medication-taking behaviors and cope with side effects. For adherent women, having trouble establishing a routine was their main barrier to taking medication. For non-adherent women, it was side effects affecting their quality of life. These findings could inform the development of community pharmacy-based adherence interventions.

  13. Adjuvant radiation therapy in uterine carcinosarcoma: A population-based analysis of patient demographic and clinical characteristics, patterns of care and outcomes.

    Science.gov (United States)

    Manzerova, Julia; Sison, Cristina P; Gupta, Divya; Holcomb, Kevin; Caputo, Thomas A; Parashar, Bhupesh; Nori, Dattatreyudu; Wernicke, A Gabriella

    2016-05-01

    To examine clinical and demographic characteristics of a population-based cohort of patients with uterine carcinosarcoma (UCS), to assess access to treatment and survival patterns. Surveillance, Epidemiology and End Results database was queried for patients diagnosed in 1999-2010 and treated with surgery with or without adjuvant radiation therapy (aRT). The Kaplan-Meier method was used to estimate survival functions, and Cox proportional hazards regression - to analyze the effect of covariates on survival. 2342 patients were eligible. African Americans presented with more advanced AJCC stages than other races (35.4% vs. 29.1%; pAfrican Americans vs. others, and women diagnosed in 1999-2004 vs. in 2005-2010, received aRT at a similar rate: 36.5% vs. 39.9% (p=NS), and 39.5% vs. 38.9% (p=NS), respectively. There was a trend towards higher aRT utilization among patients younger than 65 vs. older (41.4% vs. 37.5%; paRT group: 42 vs. 22 (paRT group. African Americans were more likely to present with later stage disease and die of UCS than non-African Americans. Age and stage, but not race, influenced receipt of aRT. Patients treated more recently survived longer. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Cardiovascular event-free survival after adjuvant radiation therapy in breast cancer patients stratified by cardiovascular risk

    International Nuclear Information System (INIS)

    Onwudiwe, Nneka C; Kwok, Young; Onukwugha, Eberechukwu; Sorkin, John D; Zuckerman, Ilene H; Shaya, Fadia T; Daniel Mullins, C

    2014-01-01

    The objective of this study was to estimate the risk of a cardiovascular event or death associated with modern radiation in a population of elderly female breast cancer patients with varying baseline cardiovascular risk. The data used for this analysis are from the linked Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. The retrospective cohort study included women aged 66 years and older with stage 0–III breast cancer diagnosed between 2000 and 2005. Women were grouped as low, intermediate, or high cardiovascular risk based on the presence of certain clinical diagnoses. The risk for the combined outcome of a hospitalization for a cardiovascular event or death within 6 months and 24 months of diagnosis was estimated using a multivariable Cox model. The median follow-up time was 24 months. Among the 91,612 women with American Joint Committee on Cancer (AJCC) stage 0–III breast cancer: 39,555 (43.2%) were treated with radiation therapy and 52,057 (56.8%) were not. The receipt of radiation therapy in the first 6 months was associated with a statistically significant increased risk for the combined outcome in women categorized as high risk (HR = 1.510; 95% CI, 1.396–1.634) or intermediate risk (HR = 1.415; 95% CI, 1.188–1.686) but not low risk (HR = 1.027; 95% CI, 0.798–1.321). Women with a prior medical history of cardiovascular disease treated with radiation therapy are at increased risk for an event and should be monitored for at least 6 months following treatment with radiation therapy

  15. Breast and other cancer dormancy as a therapeutic endpoint: speculative recombinant T cell receptor ligand (RTL) adjuvant therapy worth considering?

    International Nuclear Information System (INIS)

    Bakács, Tibor; Mehrishi, Jitendra N

    2010-01-01

    Most individuals who died of trauma were found to harbour microscopic primary cancers at autopsies. Surgical excision of the primary tumour, unfortunately, seems to disturb tumour dormancy in over half of all metastatic relapses. A recently developed immune model suggested that the evolutionary pressure driving the creation of a T cell receptor repertoire was primarily the homeostatic surveillance of the genome. The model is based on the homeostatic role of T cells, suggesting that molecular complementarity between the positively selected T cell receptors and the self peptide-presenting major histocompatibility complex molecules establishes and regulates homeostasis, strictly limiting variations of its components. The repertoire is maintained by continuous peripheral stimulation via soluble forms of self-peptide-presenting major histocompatibility complex molecules governed by the law of mass action. The model states that foreign peptides inhibit the complementary interactions between the major histocompatibility complexes and T cell receptors. Since the vast majority of clinically detected cancers present self-peptides the model assumes that tumour cells are, paradoxically, under homeostatic T cell control. The novelty of our hypothesis therefore is that resection of the primary tumour mass is perceived as loss of 'normal' tissue cells. Consequently, T cells striving to reconstitute homeostasis stimulate rather than inhibit the growth of dormant tumour cells and avascular micrometastases. Here we suggest that such kick-start growths could be prevented by a recombinant T cell receptor ligand therapy that modifies T cell behaviour through a partial activation mechanism. The homeostatic T cell regulation of tumours can be tested in a tri-transgenic mice model engineered to express potent oncogenes in a doxycycline-dependent manner. We suggest seeding dissociated, untransformed mammary cells from doxycycline naïve mice into the lungs of two mice groups: one

  16. Efficacy of post operative adjuvant therapy with human interferon beta, MCNU and radiation (IMR) for malignant glioma: comparison among three protocols

    International Nuclear Information System (INIS)

    Hatano, N.; Wakabayashi, T.; Kajita, Y.; Mizuno, M.; Ohno, T.; Nakayashiki, N.; Takemura, A.; Yoshida, J.

    2000-01-01

    In order to develop ultimate adjuvant therapy for malignant gliomas, we analyzed 77 patients with malignant gliomas (29 anaplastic astrocytomas (AAs) and 48 glioblastoma multiformes (GMs)) treated by three protocols of IMR therapy (human interferon-beta (HuIFN-β), MCNU and radiation). In protocol 1 (n = 45 : AA = 13, GM = 32), 1 x 10 6 IU of HuIFN-β was administrated intravenously once a day for 7 days. On day 2, MCNU was administrated at a dose of 2 mg/kg b.w. intravenously and from day 3, radiation was started in five weekly fractions of 2 Gy for 6 weeks. Total dose was 60 Gy. Protocol 2 (n = 19 : AA = 11, GM = 8) was comparable with protocol 1 except HuIFN-β was administrated twice a day at a dose of 1 x 10 6 IU each. Protocol 3 (n = 13 : AA = 5, GM = 8) differed from protocol 2 only in a high dose-hyperfractionated radiation which was given twice a day at a dose of 1.5 Gy each and for a total dose of 66 Gy. Antitumor effects were evaluated by survival and response rate determined by decrease of tumor size. Significant improvement was obtained in patients with AAs by protocol 2 and 3. Response rates of patients with AAs and GMs were 46.2 % and 50 % in protocol 1, 63.6 % and 50 % in protocol 2, and 80 % and 50 % in protocol 3, respectively. One and two year survival rates in AAs were 46.4 % and 34.8 % in protocol 1, both 75 % in protocol 2, and both 100 % in protocol 3. Survival rates in GMs were not different among them. Except of radiation necrosis, which was observed in 38.5 % of the patients under protocol 3, there was no significant difference in the adverse effects among the three protocols. In the present study, the efficacy of IMR therapy for patients with malignant gliomas, especially for AAs, was confirmed. We conclude that twice a day administrations of HuIFN-β in combination with a high dose-hyperfractionated radiation provide increased efficacy in IMR therapy. (author)

  17. 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.

  18. One-Year Follow-Up of Natural Killer Cell Activity in Multiple Myeloma Patients Treated With Adjuvant Lenalidomide Therapy

    Directory of Open Access Journals (Sweden)

    Laurie Besson

    2018-04-01

    Full Text Available Multiple myeloma (MM is a proliferation of tumoral plasma B cells that is still incurable. Natural killer (NK cells can recognize and kill MM cells in vitro and can limit MM growth in vivo. Previous reports have shown that NK cell function is impaired during MM progression and suggested that treatment with immunomodulatory drugs (IMIDs such as lenalidomide (LEN could enhance it. However, the effects of IMIDs on NK cells have been tested mostly in vitro or in preclinical models and supporting evidence of their effect in vivo in patients is lacking. Here, we monitored NK cell activity in blood samples from 10 MM patients starting after frontline induction chemotherapy (CTX consisting either of association of bortezomib–lenalidomide–dexamethasone (Velcade Revlimid Dexamethasone or autologous stem-cell transplantation (SCT. We also monitored NK cell activity longitudinally each month during 1 year, after maintenance therapy with LEN. Following frontline chemotherapy, peripheral NK cells displayed a very immature phenotype and retained poor reactivity toward target cells ex vivo. Upon maintenance treatment with LEN, we observed a progressive normalization of NK cell maturation, likely caused by discontinuation of chemotherapy. However, LEN treatment neither activated NK cells nor improved their capacity to degranulate or to secrete IFN-γ or MIP1-β following stimulation with MHC-I-deficient or antibody-coated target cells. Upon LEN discontinuation, there was no reduction of NK cell effector function either. These results caution against the use of LEN as single therapy to improve NK cell activity in patients with cancer and call for more preclinical assessments of the potential of IMIDs in NK cell activation.

  19. 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

  20. 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.

  1. 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

    DEFF Research Database (Denmark)

    Martin, Miguel; Holmes, Frankie A; Ejlertsen, Bent

    2017-01-01

    BACKGROUND: 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...... 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....../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...

  2. 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.

  3. Health-Related Quality of Life in Elderly Patients With Newly Diagnosed Glioblastoma Treated With Short-Course Radiation Therapy Plus Concomitant and Adjuvant Temozolomide

    International Nuclear Information System (INIS)

    Minniti, Giuseppe; Scaringi, Claudia; Baldoni, Alessandra; Lanzetta, Gaetano; De Sanctis, Vitaliana; Esposito, Vincenzo; Enrici, Riccardo Maurizi

    2013-01-01

    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

  4. Determinants of Weight Gain During Adjuvant Endocrine Therapy and Association of Such Weight Gain With Recurrence in Long-term Breast Cancer Survivors.

    Science.gov (United States)

    Raghavendra, Akshara; Sinha, Arup K; Valle-Goffin, Janeiro; Shen, Yu; Tripathy, Debu; Barcenas, Carlos H

    2018-02-01

    Weight gain is a negative prognostic factor in breast cancer (BC) patients. The risk factors for weight gain during adjuvant endocrine therapy (ET) and the extent to which such weight gain is associated with disease recurrence remain unclear. We retrospectively identified a cohort of women with a diagnosis of stage I-III, hormone receptor-positive, human epidermal growth factor receptor 2-negative BC from January 1997 to August 2008, who had received initial treatment at the MD Anderson Cancer Center, had completed 5 years of ET, and had remained free of locoregional or distant relapse or contralateral BC for ≥ 5 years after diagnosis. The weight change at the end of 5 years of ET was measured as the percentage of the change in weight from the start of ET, with a weight gain of > 5% considered clinically significant. Multivariable logistic regression and Cox proportional hazards models were used to assess the determinants of such weight gain and the risk of recurrence after 5 years. Of 1282 long-term BC survivors, 432 (33.7%) had a weight gain of > 5% after 5 years of ET. Women who were premenopausal at diagnosis were 1.40 times more likely than women who were postmenopausal at diagnosis to have a weight gain of > 5%. Asian women had the lowest risk of gaining weight. The recurrence risks of patients who had gained weight and those who had not were not significantly different. Premenopausal BC patients had an increased risk of weight gain after 5 years of ET; however, BC patients with a weight gain of > 5% did not have an increased risk of disease recurrence. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Ultrasound-guided stellate ganglion blocks combined with pharmacological and occupational therapy in Complex Regional Pain Syndrome (CRPS): a pilot case series ad interim.

    Science.gov (United States)

    Wei, Karin; Feldmann, Robert E; Brascher, Anne-Kathrin; Benrath, Justus

    2014-12-01

    This preliminary and retrospective pilot case series examines a treatment concept consisting of ultrasound-guided stellate ganglion blocks (SGBs) combined with pharmacological and occupational therapy in patients with complex regional pain syndrome (CRPS) of the hand. Efficacy of combined treatment concepts and safety of ultrasound-guided SGB have not been sufficiently investigated yet. A total number of 156 blocks were evaluated in 16 patients with CRPS in a retrospective analysis. All patients received pharmacotherapy and a standard regimen of occupational therapy offered simultaneously to the SGBs. Changes in both spontaneous and evoked pain levels were assessed by numerical pain rating score before and after the last blockade of a series. Side effects were documented. The overall mean pain reduction was 63.2% regarding spontaneous and 45.3% regarding evoked pain. Mild complications, such as hoarseness or dysphagia, occurred in 13.5% of the blocks (21 SGBs). Serious complications, such as plexus paresis or accidental puncture of vessels or other structures, did not occur. Time between symptom onset and start of treatment did not affect the extent of pain reduction. The combination of ultrasound-guided SGB and simultaneous pharmacological and occupational therapy showed encouraging treatment results under conditions of this pilot case series. Assessment of efficacy of this combined treatment concept and safety of ultrasound-guided SGB require further prospective clinical studies with larger number of participants. Wiley Periodicals, Inc.

  6. Survival Impact of Adjuvant Radiation Therapy in Masaoka Stage II to IV Thymomas: A Systematic Review and Meta-analysis

    International Nuclear Information System (INIS)

    Lim, Yu Jin; Kim, Eunji; Kim, Hak Jae; Wu, Hong-Gyun; Yan, Jinchun; Liu, Qin; Patel, Shilpen

    2016-01-01

    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.

  7. The Effect of Adjuvant Zinc Therapy on Recovery from Pneumonia in Hospitalized Children: A Double-Blind Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Mohammad Javad Qasemzadeh

    2014-01-01

    Full Text Available Objectives. Pneumonia is one of the common mortality causes in young children. Some studies have shown beneficial effect of zinc supplements on treatment of pneumonia. The present study aimed to investigate the effects of short courses of zinc administration on recovery from this disease in hospitalized children. Methods. In a parallel Double-Blind Randomized Controlled Trial at Ayatollah Golpaygani Hospital in Qom, 120 children aged 3–60 months with pneumonia were randomly assigned 1 : 1 to receive zinc or placebo (5 mL every 12 hours along with the common antibiotic treatments until discharge. Primary outcome was recovery from pneumonia which included the incidence and resolving clinical symptoms and duration of hospitalization. Results. The difference between two groups in all clinical symptoms at admittance and the variables affecting the disease such as age and sex were not statistically significant (P<0.05 at baseline. Compared to the placebo group, the treatment group showed a statistically significant decrease in duration of clinical symptoms (P=0.044 and hospitalization (P=0.004. Conclusions. Supplemental administration of zinc can expedite the healing process and results in faster resolution of clinical symptoms in children with pneumonia. In general, zinc administration, along with common antibiotic treatments, is recommended in this group of children. It can also reduce the drug resistance caused by multiple antibiotic therapies. This trial is approved by Medical Ethic Committee of Islamic Azad University in Iran (ID Number: 8579622-Q. This study is also registered in AEARCTR (The American Economic Association's Registry for Randomized Controlled Trials. This trial is registered with RCT ID: AEARCTR-0000187.

  8. 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.

  9. A pilot randomized trial to prevent sexual dysfunction in postmenopausal breast cancer survivors starting adjuvant aromatase inhibitor therapy.

    Science.gov (United States)

    Advani, Pragati; Brewster, Abenaa M; Baum, George P; Schover, Leslie R

    2017-08-01

    A randomized pilot trial evaluated the hypothesis that early intervention lessens sexual dysfunction in the first year on aromatase inhibitors. A secondary aim was comparing the efficacy of two vaginal moisturizers. Fifty-seven postmenopausal women with early stage breast cancer starting aromatase inhibitors were randomized to three treatment groups. All received a handout on managing sexual and other side effects. The Usual Care group received no additional therapy. The Active Treatment groups received a 6-month supply of a vaginal moisturizer (hyaluronic acid-based in Active Group-H and prebiotic in Active Group-P) and a vaginal lubricant and dilator, plus access to an educational website and phone coaching. Questionnaires completed at baseline, 6, and 12 months included the Female Sexual Function Index (FSFI), Menopausal Sexual Interest Questionnaire (MSIQ), Female Sexual Distress Scale-Revised (FSDS-R), and a menopausal symptom scale. Forty-nine women (86%) provided follow-up data. Mean age was 59 and 77% were non-Hispanic Caucasian. Sexual function was impaired at baseline, but remained stable over 12 months for all groups. The combined active treatment group had less dyspareunia (P = 0.07) and sexual distress (P = 0.02) at 6 months than the Usual Care group. At 6 months, the Active-H group improved significantly more than the Active-P group on FSFI total score (P = 0.04). Sexual counseling helped women maintain stable sexual function on aromatase inhibitors. Active intervention resulted in better outcomes at 6 months. This promising pilot trial suggests a need for more research on preventive counseling to maintain sexual function during aromatase inhibitor treatment.

  10. Patterns and Predictors of Early Biochemical Recurrence After Radical Prostatectomy and Adjuvant Radiation Therapy in Men With pT3N0 Prostate Cancer: Implications for Multimodal Therapies

    International Nuclear Information System (INIS)

    Briganti, Alberto; Joniau, Steven; Gandaglia, Giorgio; Cozzarini, Cesare; Sun, Maxine; Tombal, Bertrand; Haustermans, Karin; Hinkelbein, Wolfgang; Shariat, Shahrokh F.; Karakiewicz, Pierre I.; Montorsi, Francesco; Van Poppel, Hein; Wiegel, Thomas

    2013-01-01

    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 3 N 0 prostate cancer (PCa) receiving RP and aRT at 6 European centers between 1993 and 2006. Patients who were free from BCR at 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 3 N 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 aRT, delivered to the prostatic bed

  11. 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

  12. 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

  13. CpG island methylator phenotype is associated with response to adjuvant irinotecan-based therapy for stage III 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

    2014-09-01

    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). We analyzed data from patients with stage III colon adenocarcinoma randomly assigned to groups given fluorouracil and leucovorin or IFL after surgery, from April 1999 through April 2001. The primary end point of the trial was overall survival and the secondary end point 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. 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 = 1.36; 95% confidence interval: 1.01-1.84). Treatment with IFL showed a trend toward increased overall survival for patients with CIMP-positive tumors, compared with treatment with fluorouracil and leucovorin (hazard ratio = 0.62; 95% CI: 0.37-1.05; P = .07), but not for patients with CIMP-negative tumors (hazard ratio = 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

  14. Uso da terapia não farmacológica, medicina alternativa e complementar na fibromialgia Non-pharmacological therapy and complementary and alternative medicine in fibromyalgia

    Directory of Open Access Journals (Sweden)

    Alessandra de Sousa Braz

    2011-06-01

    multifactorial pathogenesis, its ideal treatment requires a multidisciplinary approach including the association of pharmacological and non-pharmacological therapies. The pharmacological therapy currently recommended for the syndrome includes antidepressants, calcium-channel modulators, muscle relaxants, and analgesics. In most cases, the non-pharmacological treatment consists of patient education, supervised aerobic physical activity, and cognitive-behavioral therapy. However, many patients do not respond satisfactorily, or have side effects associated with the long-term use of drugs, in addition to reporting difficulties in adhering to a therapy based on exercises and physical medicine. Thus, physicians and patients are increasingly interested in an alternative and complementary therapy for fibromyalgia. This review approaches the different therapeutic modalities used in fibromyalgia, emphasizing the evidence of non-pharmacological therapy and use of alternative and complementary medicine for these patients.

  15. Brivaracetam: review of its pharmacology and potential use as adjunctive therapy in patients with partial onset seizures

    OpenAIRE

    Russo, Emilio; Mumoli,Laura; Palleria,Caterina; Gasparini,Sara; Citraro,Rita; Labate,Angelo; Ferlazzo,Edoardo; Gambardella,Antonio; De Sarro,Giovambattista

    2015-01-01

    Laura Mumoli,1 Caterina Palleria,2 Sara Gasparini,1 Rita Citraro,2 Angelo Labate,1 Edoardo Ferlazzo,1 Antonio Gambardella,1 Giovambattista De Sarro,2 Emilio Russo2 1Institute of Neurology, 2Institute of Pharmacology, University Magna Græcia, Catanzaro, Italy Abstract: Brivaracetam (BRV), a high-affinity synaptic vesicle protein 2A ligand, reported to be 10–30-fold more potent than levetiracetam (LEV), is highly effective in a wide range of experimental models of focal an...

  16. [Non-pharmacologic therapy of age-related macular degeneration, based on the etiopathogenesis of the disease].

    Science.gov (United States)

    Fischer, Tamás

    2015-07-12

    It has a great therapeutic significance that the disorder of the vascular endothelium, which supplies the affected ocular structures, plays a major role in the development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfuncition and age-related macular degeneration is accompanied by a general inflammatory response. The vascular wall including those in chorioids may be activated by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic and genetic factors causing a protracted host defence response with a consequent vascular damage, which leads to age-related macular degeneration. Based on this concept, age-related macular degeneration is a local manifestation of the systemic vascular disease. This recognition should have therapeutic implications because restoration of endothelial dysfunction can stabilize the condition of chronic vascular disease including age-related macular degeneration, as well. Restoration of endothelial dysfunction by non-pharmacological or pharmacological interventions may prevent the development or improve endothelial dysfunction resulting in prevention or improvement of age-related macular degeneration. Non-pharmacological interventions which may have beneficial effect in endothelial dysfunction include (1) smoking cessation; (2) reduction of increased body weight; (3) adequate physical activity; (4) appropriate diet (a) proper dose of flavonoids, polyphenols and kurcumin; (b) omega-3 long-chain polyunsaturated fatty acids: docosahexaenoic acid and eicosapentaenoic acid; (c) carotenoids, lutein and zeaxanthins), (d) management of dietary glycemic index, (e) caloric restriction, and (5) elimination of stressful lifestyle. Non-pharmacological interventions should be preferable even if medicaments are also used for the treatment of endothelial dysfunction.

  17. Lobular breast cancers lack the inverse relationship between ER/PR status and cell growth rate characteristic of ductal cancers in two independent patient cohorts: implications for tumor biology and adjuvant therapy.

    Science.gov (United States)

    Wong, Hilda; Lau, Silvia; Cheung, Polly; Wong, Ting Ting; Parker, Andrew; Yau, Thomas; Epstein, Richard J

    2014-11-10

    Although invasive lobular carcinoma (ILC) of the breast differs from invasive ductal carcinoma (IDC) in numerous respects - including its genetics, clinical phenotype, metastatic pattern, and chemosensitivity - most experts continue to manage ILC and IDC identically in the adjuvant setting. Here we address this discrepancy by comparing early-stage ILC and IDC in two breast cancer patient cohorts of differing nationality and ethnicity. The clinicopathologic features of 2029 consecutive breast cancer patients diagnosed in Hong Kong (HK) and Australia (AUS) were compared. Interrelationships between tumor histology and other clinicopathologic variables, including ER/PR and Ki67, were analysed. Two hundred thirty-nine patients were identified with ILC (11.8%) and 1790 patients with IDC. AUS patients were older (p patients. As expected, ILC tumors were lower in grade and proliferative rate, and more often ER-positive and HER2-negative, than IDC (p 0.7). Moreover, whereas IDC tumors exhibited a strongly negative relationship between ER/PR and Ki67 status (p 0.6). These data imply that the primary adhesion defect in ILC underlies a secondary stromal-epithelial disconnect between hormonal signaling and tumor growth, suggesting in turn that this peritumoral feedback defect could reduce both the antimetastatic (adjuvant) and tumorilytic (palliative) efficacy of cytotoxic therapies for such tumors. Hence, we caution against assuming similar adjuvant chemotherapeutic survival benefits for ILC and IDC tumors with similar ER and Ki67, whether based on immunohistochemical or gene expression assays.

  18. The Role of Wnt Signal in Glioblastoma Development and Progression: A Possible New Pharmacological Target for the Therapy of This Tumor.

    Science.gov (United States)

    Zuccarini, Mariachiara; Giuliani, Patricia; Ziberi, Sihana; Carluccio, Marzia; Iorio, Patrizia Di; Caciagli, Francesco; Ciccarelli, Renata

    2018-02-17

    Wnt is a complex signaling pathway involved in the regulation of crucial biological functions such as development, proliferation, differentiation and migration of cells, mainly stem cells, which are virtually present in all embryonic and adult tissues. Conversely, dysregulation of Wnt signal is implicated in development/progression/invasiveness of different kinds of tumors, wherein a certain number of multipotent cells, namely "cancer stem cells", are characterized by high self-renewal and aggressiveness. Hence, the pharmacological modulation of Wnt pathway could be of particular interest, especially in tumors for which the current standard therapy results to be unsuccessful. This might be the case of glioblastoma multiforme (GBM), one of the most lethal, aggressive and recurrent brain cancers, probably due to the presence of highly malignant GBM stem cells (GSCs) as well as to a dysregulation of Wnt system. By examining the most recent literature, here we point out several factors in the Wnt pathway that are altered in human GBM and derived GSCs, as well as new molecular strategies or experimental drugs able to modulate/inhibit aberrant Wnt signal. Altogether, these aspects serve to emphasize the existence of alternative pharmacological targets that may be useful to develop novel therapies for GBM.

  19. Developmental paediatric anaesthetic pharmacology

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing

    2015-01-01

    Safe and effective drug therapy in neonates, infants and children require detailed knowledge about the ontogeny of drug disposition and action as well how these interact with genetics and co-morbidity of children. Recent advances in developmental pharmacology in children follow the increased...

  20. 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?

    Science.gov (United States)

    Delishaj, Durim; Fabrini, Maria Grazia; Gonnelli, Alessandra; Morganti, Riccardo; Perrone, Franco; Tana, Roberta; Paiar, Fabiola; Gadducci, Angiolo

    2016-01-01

    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. PMID:28115957

  1. Preferences of German melanoma patients for interferon (IFN) α-2b toxicities (the DeCOG "GERMELATOX survey") versus melanoma recurrence to quantify patients' relative values for adjuvant therapy.

    Science.gov (United States)

    Kaehler, Katharina C; Blome, Christine; Forschner, Andrea; Gutzmer, Ralf; Haalck, Thomas; Heinzerling, Lucie; Kornek, Thomas; Livingstone, Elisabeth; Loquai, Carmen; Maul, Lara Valeska; Lang, Berenice M; Schadendorf, Dirk; Stade, Barbara; Terheyden, Patrick; Utikal, Jochen; Wagner, Tobias; Hauschild, Axel; Garbe, Claus; Augustin, Matthias

    2016-11-01

    Currently interferon alfa-2b (IFNα-2b) is an approved adjuvant drug for high-risk melanoma patients that leads to an improvement in disease-free survival (DFS). However, it is unclear whether it also impacts overall survival. Widespread use of adjuvant high-dose IFNα has been tempered by its significant toxicity and its limited efficacy. Current therapeutic strategies like immune checkpoint blockade or targeted therapy may also be useful in the adjuvant setting. Therefore, it is important to weigh the trade-offs between possible side effects and therapeutic benefit.We assessed patient utilities for health states associated with IFN therapy. Utilities are measures of preference for a specific health state on a scale of 0 (death) to 1 (perfect health).Utilities were determined for health states associated with adjuvant IFN among 130 German low-risk melanoma patients using the standard gamble technique. Four IFNα-2b toxicity scenarios and the following 3 posttreatment outcomes were assessed: disease-free health and melanoma recurrence (with or without previous use of IFNα-2b) resulting in cancer death. Patients were asked to trade-off the improvement in 5-year DFS and the IFN-related side effects.Utilities for melanoma recurrence (mean 0.60) were significantly lower than for all IFNα-2b toxicity scenarios (mean 0.81-0.90). Patients were willing to tolerate mild-to-moderate and severe toxicity for a 50% and 75% chance of 5-year DFS, respectively. Both utilities and threshold benefits were mostly independent from patient characteristics like gender, income, and social situation. Significant impact was only observed by age and previous personal experience with cancer.On average, German patients were willing to trade even severe IFNα-2b toxicity for reducing the rate of melanoma recurrence. This result points out the importance of a relapse-free survival for melanoma patients. The utilities measured in our study can be applied to decision-making processes in

  2. Second Malignancies After Adjuvant Radiation Therapy for Early Stage Breast Cancer: Is There Increased Risk With Addition of Regional Radiation to Local Radiation?

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, Sarah Nicole [Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia (Canada); Tyldesley, Scott, E-mail: styldesl@bccancer.bc.ca [Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia (Canada); Li, Dongdong [Cancer Control Research Department, British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia (Canada); Olson, Robert [Department of Radiation Oncology, British Columbia Cancer Agency-Centre for the North, Prince George, British Columbia (Canada); McBride, Mary [Cancer Control Research Department, British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia (Canada)

    2015-04-01

    Purpose: This study was undertaken to determine whether there was an increased risk of second malignancies (SM), particularly lung cancer, in early stage breast cancer patients treated with the addition of nodal fields to breast and/or chest wall radiation therapy (RT). Materials and Methods: Subjects were stage I/II female breast cancer patients 20 to 79 years of age, diagnosed between 1989 and 2005 and treated with adjuvant RT at our institution. Patients were included if they survived and did not have SM within 3 years of diagnosis. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated to compare SM incidence to cancer incidence in the general sex- and age-matched populations. Secondary malignancy risks in patients treated with local RT (LRT) to the breast/chest wall were compared to those in patients treated with locoregional RT (LRRT) to the breast/chest wall and regional nodes, using multivariate regression analysis (MVA) to account for covariates. Results: The cohort included 12,836 patients with a median follow-up of 8.4 years. LRRT was used in 18% of patients. The SIR comparing patients treated with LRT to the general population was 1.29 (CI: 1.21-1.38). No statistically significant increased incidence of in-field malignancies (SIR, 1.04; CI: 0.87-1.23) and lung cancers (SIR, 1.06; CI: 0.88-1.26) was detected. The SIR comparing patients treated with LRRT to the general population was 1.39 (CI: 1.17-1.64). No statistically significant increased incidence of in-field malignancies (SIR, 1.26; CI: 0.77-1.94) and lung cancers (SIR, 1.27; CI: 0.76-1.98) was detected. On MVA comparing LRRT to LRT, the adjusted hazard ratio was 1.20 for in-field malignancies (CI: 0.68-2.16) and 1.26 for lung cancer (CI: 0.67-2.36). The excess attributable risk (EAR) to regional RT was 3.1 per 10,000 person years (CI: −8.7 to 9.9). Conclusions: No statistically significant increased risk of second malignancy was detected after LRRT relative to

  3. Apego al tratamiento farmacológico en pacientes con diagnóstico de diabetes mellitus tipo 2 Pharmacological therapy compliance in diabetes

    Directory of Open Access Journals (Sweden)

    Blanca Rosa Durán-Varela

    2001-06-01

    Full Text Available Objetivos. Establecer la frecuencia de apego al tratamiento farmacológico en pacientes diabéticos tipo 2, relacionarla con el control metabólico e identificar factores que influyen para el no apego. Material y métodos. Estudio transversal comparativo, efectuado en 150 pacientes con diabetes mellitus tipo 2 de la unidad de medicina familiar No. 33 del Instituto Mexicano del Seguro Social de Chihuahua, Chih., México, hecho entre 1997 y 1998. Se midió el apego con cuenta de tabletas en su domicilio. El control metabólico se midió con hemoglobina glucosilada. Un cuestionario investigó factores relacionados. Se utilizó estadística descriptiva, t de Student y razón de momios. Resultados. El apego correspondió a 54.2%. Los factores asociados al no apego fueron la escolaridad primaria y la falta de información sobre la enfermedad (phttp://www.insp.mx/salud/index.htmlObjective. To establish the frequency of compliance to pharmacological therapy, and to identify non-compliance factors, in relation to metabolic control on patients with type-II diabetes mellitus. Material and methods. A comparative cross-sectional study was conducted between 1997 and 1998, among 150 type-II diabetic patients, at the Family Medicine Unit No. 33, of the Mexican Institute of Social Security, in Chihuahua, Mexico. Compliance to drug therapy was measured by counting tablets at home. Metabolic control was measured through glycosilated hemoglobin. A questionnaire was given to collect data on factors related to compliance. Statistical analysis consisted of descriptive statistics, Student's t and odds ratios. Results. Pharmacological therapy compliance was 54.2%. Factors associated with non-compliance were elementary schooling and lack of information about the disease. Conclusions. Pharmacological therapy compliance was low. Factors related to non-compliance can be modified through education. The English version of this paper is available at: http://www.insp.mx/salud/index.html

  4. Anesthetic pharmacology

    National Research Council Canada - National Science Library

    Evers, Alex S; Maze, M; Kharasch, Evan D

    2011-01-01

    ...: Section 1 introduces the principles of drug action, Section 2 presents the molecular, cellular and integrated physiology of the target organ/functional system and Section 3 reviews the pharmacology...

  5. Impact of pharmacologic therapy for benign prostatic hyperplasia on prostate volume and free testosterone and consequently on urinary parameters and sexual desire in men

    Directory of Open Access Journals (Sweden)

    Stojanović Nebojša

    2017-01-01

    Full Text Available Background/Aim. Pharmacologic therapy for benign prostatic hyperplasia (BPH relieves disease progression and affects the androgen hormone status. A decrease in the level of free testosterone (freeT within total testosterone (totalT leads to symptoms of sexual dysfunction. The aim of this study was to show the impact of pharmacological treatment for BPH on prostate volume (PV and levels of freeT and, consequently, on urinary parameters and sexual desire in men during 6 months of administration. Methods. This clinical prospective study included 156 BPH patients with moderate urinary symptoms – International Prostate Symptom Score (IPSS 30 mL and prostate specific antigen (PSA value < 4 ng/mL. The average age of patients was 61.16 ± 2.97 years. The performed tests included determination of tumor markers (PSA, free PSA, hormones (totalT, freeT, freeT/totalT ratio, trans abdominal ultrasonography and uroflowmetry. Urinary symptoms were measured by IPSS and the Quality of Life (QoL questionnaire while the changes in sexual desire were measured using the International Index of Erectile Function (IIEF questionnaire. Four groups were formed, 39 patients each. The group 1 received alpha1- blocker (AB tamsulosin, the group 2, 5 alpha-reductase inhibitor (5-ARI finasteride, the group 3, combined therapy of both drugs (tamsulosin and finasteride, while the group 4 (control group had no therapy. Follow-ups were performed every three and six months during therapy administration. Results. Prostate volume significantly decreased in the patients on combined therapy (-6.95 ± 2.00; p < 0.001 and finasteride (-6.67 ± 3.35. In the finasteride group, the levels of freeT (-4.23 ± 5.2; p < 0.001 and freeT/totalT ratio (-0.12 0.08; p < 0.001 significantly decreased as did the freeT (-2.64 ± 7.81 and freeT/totalT ratio (-0.09 ± 0.13 in the combined therapy group. Uroflowmetry showed a significant improvement in all parameters and all the therapy groups. Combined

  6. Association Between Facility-Level Utilization of Non-pharmacologic Chronic Pain Treatment and Subsequent Initiation of Long-Term Opioid Therapy.

    Science.gov (United States)

    Carey, Evan P; Nolan, Charlotte; Kerns, Robert D; Ho, P Michael; Frank, Joseph W

    2018-05-01

    Expert guidelines recommend non-pharmacologic treatments and non-opioid medications for chronic pain and recommend against initiating long-term opioid therapy (LTOT). We examined whether veterans with incident chronic pain receiving care at facilities with greater utilization of non-pharmacologic treatments and non-opioid medications are less likely to initiate LTOT. Retrospective cohort study PARTICIPANTS: Veterans receiving primary care from a Veterans Health Administration facility with incident chronic pain between 1/1/2010 and 12/31/2015 based on either of 2 criteria: (1) persistent moderate-to-severe patient-reported pain and (2) diagnoses "likely to represent" chronic pain. The independent variable was facility-level utilization of pain-related treatment modalities (non-pharmacologic, non-opioid medications, LTOT) in the prior calendar year. The dependent variable was patient-level initiation of LTOT (≥ 90 days within 365 days) in the subsequent year, adjusting for patient characteristics. Among 1,094,569 veterans with incident chronic pain from 2010 to 2015, there was wide facility-level variation in utilization of 10 pain-related treatment modalities, including initiation of LTOT (median, 16%; range, 5-32%). Veterans receiving care at facilities with greater utilization of non-pharmacologic treatments were less likely to initiate LTOT in the year following incident chronic pain. Conversely, veterans receiving care at facilities with greater non-opioid and opioid medication utilization were more likely to initiate LTOT; this association was strongest for past year facility-level LTOT initiation (adjusted rate ratio, 2.10; 95% confidence interval, 2.06-2.15, top vs. bottom quartile of facility-level LTOT initiation in prior calendar year). Facility-level utilization patterns of non-pharmacologic, non-opioid, and opioid treatments for chronic pain are associated with subsequent patient-level initiation of LTOT among veterans with incident chronic pain

  7. 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....

  8. Feasibility of a dose-intensive CMF regimen with granulocyte colony-stimulating factor as adjuvant therapy in premenopausal patients with node-positive breast cancer

    NARCIS (Netherlands)

    Bos, AME; de Graaf, H; de Vries, EGE; Piersma, H; Willemse, PHB

    Our aim was to study the feasibility of an intensified intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) schedule with the aim to escalate dose intensity (DI). Twenty-three premenopausal breast cancer patients received 6 cycles of adjuvant CMF intravenously on days 1. and 8 every 3

  9. Targeting Adenosine Signaling in Parkinson's Disease: From Pharmacological to Non-pharmacological Approaches

    Directory of Open Access Journals (Sweden)

    Luiza R. Nazario

    2017-11-01

    Full Text Available Parkinson's disease (PD is one of the most prevalent neurodegenerative disease displaying negative impacts on both the health and social ability of patients and considerable economical costs. The classical anti-parkinsonian drugs based in dopaminergic replacement are the standard treatment, but several motor side effects emerge during long-term use. This mini-review presents the rationale to several efforts from pre-clinical and clinical studies using adenosine receptor antagonists as a non-dopaminergic therapy. As several studies have indicated that the monotherapy with adenosine receptor antagonists reaches limited efficacy, the usage as a co-adjuvant appeared to be a promising strategy. The formulation of multi-targeted drugs, using adenosine receptor antagonists and other neurotransmitter systems than the dopaminergic one as targets, have been receiving attention since Parkinson's disease presents a complex biological impact. While pharmacological approaches to cure or ameliorate the conditions of PD are the leading strategy in this area, emerging positive aspects have arisen from non-pharmacological approaches and adenosine function inhibition appears to improve both strategies.

  10. The relationship between right-sided tumour location, tumour microenvironment, systemic inflammation, adjuvant therapy and survival in patients undergoing surgery for colon and rectal cancer.

    Science.gov (United States)

    Patel, Meera; McSorley, Stephen T; Park, James H; Roxburgh, Campbell S D; Edwards, Joann; Horgan, Paul G; McMillan, Donald C

    2018-03-06

    There has been an increasing interest in the role of tumour location in the treatment and prognosis of patients with colorectal cancer (CRC), specifically in the adjuvant setting. Together with genomic data, this has led to the proposal that right-sided and left-sided tumours should be considered as distinct biological and clinical entities. The aim of the present study was to examine the relationship between tumour location, tumour microenvironment, systemic inflammatory response (SIR), adjuvant chemotherapy and survival in patients undergoing potentially curative surgery for stage I-III colon and rectal cancer. Clinicopathological characteristics were extracted from a prospective database. MMR and BRAF status was determined using immunohistochemistry. The tumour microenvironment was assessed using routine H&E pathological sections. SIR was assessed using modified Glasgow Prognostic Score (mGPS), neutrophil:lymphocyte ratio (NLR), neutrophil:platelet score (NPS) and lymphocyte:monocyte ratio (LMR). Overall, 972 patients were included. The majority were over 65 years (68%), male (55%), TNM stage II/III (82%). In all, 40% of patients had right-sided tumours and 31% had rectal cancers. Right-sided tumour location was associated with older age (P=0.001), deficient MMR (P=0.005), higher T stage (Plocation was consistently associated with a high SIR, mGPS (Plocation, adjuvant chemotherapy (P=0.632) or cancer-specific survival (CSS; P=0.377). In those 275 patients who received adjuvant chemotherapy, right-sided location was not associated with the MMR status (P=0.509) but was associated with higher T stage (P=0.001), venous invasion (P=0.036), CD3 + at the invasive margin (P=0.033) and CD3 + within cancer nests (P=0.012). There was no relationship between tumour location, SIR or CSS in the adjuvant group. Right-sided tumour location was associated with an elevated tumour lymphocytic infiltrate and an elevated SIR. There was no association between tumour location and

  11. 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; p1). There was a trend towards hypoglycemia from baseline to month 3 post addition of exenatide ER (0.33 events vs. 1.33 events; p=0.055). In patients treated with regular U-500 insulin, 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.

  12. A pan-inhibitor of DASH family enzymes induces immune-mediated regression of murine sarcoma and is a potent adjuvant to dendritic cell vaccination and adoptive T-cell therapy.

    Science.gov (United States)

    Duncan, Brynn B; Highfill, Steven L; Qin, Haiying; Bouchkouj, Najat; Larabee, Shannon; Zhao, Peng; Woznica, Iwona; Liu, Yuxin; Li, Youhua; Wu, Wengen; Lai, Jack H; Jones, Barry; Mackall, Crystal L; Bachovchin, William W; Fry, Terry J

    2013-10-01

    Multimodality therapy consisting of surgery, chemotherapy, and radiation will fail in approximately 40% of patients with pediatric sarcomas and result in substantial long-term morbidity in those who are cured. Immunotherapeutic regimens for the treatment of solid tumors typically generate antigen-specific responses too weak to overcome considerable tumor burden and tumor suppressive mechanisms and are in need of adjuvant assistance. Previous work suggests that inhibitors of DASH (dipeptidyl peptidase IV activity and/or structural homologs) enzymes can mediate tumor regression by immune-mediated mechanisms. Herein, we demonstrate that the DASH inhibitor, ARI-4175, can induce regression and eradication of well-established solid tumors, both as a single agent and as an adjuvant to a dendritic cell (DC) vaccine and adoptive cell therapy (ACT) in mice implanted with the M3-9-M rhabdomyosarcoma cell line. Treatment with effective doses of ARI-4175 correlated with recruitment of myeloid (CD11b) cells, particularly myeloid DCs, to secondary lymphoid tissues and with reduced frequency of intratumoral monocytic (CD11bLy6-CLy6-G) myeloid-derived suppressor cells. In immunocompetent mice, combining ARI-4175 with a DC vaccine or ACT with tumor-primed T cells produced significant improvements in tumor responses against well-established M3-9-M tumors. In M3-9-M-bearing immunodeficient (Rag1) mice, ACT combined with ARI-4175 produced greater tumor responses and significantly improved survival compared with either treatment alone. These studies warrant the clinical investigation of ARI-4175 for treatment of sarcomas and other malignancies, particularly as an adjuvant to tumor vaccines and ACT.

  13. SUPREMO (Selective Use of Postoperative Radiotherapy aftEr MastectOmy) - a phase III randomised trial assessing the role of postmastectomy chest wall irradiation in 'intermediate risk' women with operable breast cancer receiving adjuvant systemic therapy

    International Nuclear Information System (INIS)

    Kunkler, I.H.; Price, A.; Dixon, M.; Canney, P.; Prescott, R.; Sainsbury, R.; Aird, E.

    2003-01-01

    Danish and Canadian randomised trials of postmastectomy radiotherapy (PMRT) have shown the importance of loco-regional control to survival in 'high risk' pre and postmenopausal women receiving adjuvant systemic therapy. The effects of radiotherapy (RT) in terms of improving survival are similar to those of systemic therapy. International consensus now supports the use of postmastectomy chest wall irradiation in women with 4 or more involved axillary nodes or primary tumour size=/> 5cm. The role of PMRT in women at intermediate risk' with 1-3 involved nodes or node negative with other risk factors is controversial. The absolute reduction in risk of loco-regional recurrence varies widely (3-23%) in trials of PMRT in women with 1-3 involved nodes receiving systemic therapy. A UK survey of clinical oncologists (Kunkler et al,The Breast 1999;8:235) showed wide variations in opinion on the use of radiotherapy in these subgroups. It is possible that while RT may confer most benefit in loco-regional control, a greater survival benefit might accrue in patients with smaller tumours and fewer involved nodes. The 2000 Oxford overview of randomised trials of postoperative RT identifies non breast cancer deaths from RT related vascular morbidity as counterbalancing the benefits of RT in reducing breast cancer mortality. With the more extensive use of potentially cardiotoxic anthracycline containing adjuvant systemic therapy there are concerns about greater cardiac morbidity in patients receiving PMRT in addition. A large randomised international trial (SUPREMO) is proposed to recruit 3500 patients with (a) 1-3 involved axillary nodes or (b) node negative with other risk factors (grade 3 or lymphovascular invasion) treated by mastectomy, axillary clearance and appropriate systemic therapy for T0-3,N0-1,MO breast cancer. The primary endpoint is overall survival. Secondary endpoints are disease free survival, quality of life, morbidity (including cardiac), cost per life year saved

  14. Tratamiento no farmacológico de la hipertensión arterial Non-pharmacologic therapy for hypertension: a review

    Directory of Open Access Journals (Sweden)

    Iván Villegas

    1992-01-01

    Full Text Available

    El manejo no farmacológico se recomienda como terapia inicial en todo paciente con hipertensión arterial pero ha sido ampliamente desplazado por el tratamiento farmacológico. Los avances recientes permiten concluir que la reducción de peso, la restricción moderada de sal y el ejercicio son las modalidades que mayores beneficios producen en el hipertenso. Los resultados del manejo del estrés, de la modificación de la dieta y de los suplementos de calcio, magnesio, potasio, vitamina D y ácido gama amino Iinolénico son más controvertidos.

    Despite the fact that non-pharmacologic therapy has been recommended as the initial step in hypertension treatment, it has been largely displaced by the pharmacologic approach. Recent findings of hypertension research show that weight reduction, moderate salt restriction and exercise are the most beneficial modalities for the hypertensive patient. Measures Iike stress management, diet modification and dietary supplementation of calcium, potassium, magnesium, vitamin D or gamma-amino- Iinolenic acid provide controversial results. 

  15. Prognostic and predictive importance of the estrogen receptor coactivator AIB1 in a randomized trial comparing adjuvant letrozole and tamoxifen therapy in postmenopausal breast cancer

    DEFF Research Database (Denmark)

    Alkner, S; Jensen, Maj-Britt Raaby; Rasmussen, B B

    2017-01-01

    PURPOSE: To evaluate the estrogen receptor coactivator amplified in breast cancer 1 (AIB1) as a prognostic marker, as well as a predictive marker for response to adjuvant tamoxifen and/or aromatase inhibitors, in early estrogen receptor-positive breast cancer. METHOD: AIB1 was analyzed...... with immunohistochemistry in tissue microarrays of the Danish subcohort (N = 1396) of the International Breast Cancer Study Group's trial BIG 1-98 (randomization between adjuvant tamoxifen versus letrozole versus the sequence of the two drugs). RESULTS: Forty-six percent of the tumors had a high AIB1 expression. In line...... with previous studies, AIB1 correlated to a more aggressive tumor-phenotype (HER2 amplification and a high malignancy grade). High AIB1 also correlated to higher estrogen receptor expression (80-100 vs. 1-79%), and ductal histological type. High AIB1 expression was associated with a poor disease-free survival...

  16. Adjuvant Radiation Therapy for Margin-Positive Vulvar Squamous Cell Carcinoma: Defining the Ideal Dose-Response Using the National Cancer Data Base

    International Nuclear Information System (INIS)

    Chapman, Bhavana V.; Gill, Beant S.; Viswanathan, Akila N.; Balasubramani, Goundappa K.; Sukumvanich, Paniti; Beriwal, Sushil

    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

  17. Sequential psychological and pharmacological therapies for comorbid and primary insomnia: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Morin, Charles M; Edinger, Jack D; Krystal, Andrew D; Buysse, Daniel J; Beaulieu-Bonneau, Simon; Ivers, Hans

    2016-03-03

    Chronic insomnia is a prevalent disorder associated with significant psychosocial, health, and economic impacts. Cognitive behavioral therapies (CBTs) and benzodiazepine receptor agonist (BzRA) medications are the most widely supported therapeutic approaches for insomnia management. However, few investigations have directly compared their relative and combined benefits, and even fewer have tested the benefits of sequential treatment for those who do not respond to initial insomnia therapy. Moreover, insomnia treatment studies have been limited by small, highly screened study samples, fixed-dose, and fixed-agent pharmacotherapy strategies that do not represent usual clinical practices. This study will address these limitations. This is a two-site randomized controlled trial, which will enroll 224 adults who meet the criteria for a chronic insomnia disorder with or without comorbid psychiatric disorders. Prospective participants will complete clinical assessments and polysomnography and then will be randomly assigned to first-stage therapy involving either behavioral therapy (BT) or zolpidem. Treatment outcomes will be assessed after 6 weeks, and treatment remitters will be followed for the next 12 months on maintenance therapy. Those not achieving remission will be offered randomization to a second, 6-week treatment, again involving either pharmacotherapy (zolpidem or trazodone) or psychological therapy (BT or cognitive therapy (CT)). All participants will be re-evaluated 12 weeks after the protocol initiation and at 3-, 6-, 9-, and 12-month follow-ups. Insomnia remission, defined categorically as a score Insomnia Severity Index, a patient-reported outcome, will serve as the primary endpoint for treatment comparisons. Secondary outcomes will include sleep parameters derived from daily sleep diaries and from polysomnography, subjective measures of fatigue, mood, quality of life, and functional impairments; and measures of adverse events; dropout rates; and treatment

  18. Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy

    Directory of Open Access Journals (Sweden)

    Claire M. Doskey

    2016-12-01

    Full Text Available Ascorbate (AscH− functions as a versatile reducing agent. At pharmacological doses (P-AscH−; [plasma AscH−] ≥≈20 mM, achievable through intravenous delivery, oxidation of P-AscH− can produce a high flux of H2O2 in tumors. Catalase is the major enzyme for detoxifying high concentrations of H2O2. We hypothesize that sensitivity of tumor cells to P-AscH− compared to normal cells is due to their lower capacity to metabolize H2O2. Rate constants for removal of H2O2 (kcell and catalase activities were determined for 15 tumor and 10 normal cell lines of various tissue types. A differential in the capacity of cells to remove H2O2 was revealed, with the average kcell for normal cells being twice that of tumor cells. The ED50 (50% clonogenic survival of P-AscH− correlated directly with kcell and catalase activity. Catalase activity could present a promising indicator of which tumors may respond to P-AscH−.

  19. In question: the scientific value of preclinical safety pharmacology and toxicology studies with cell-based therapies

    Directory of Open Access Journals (Sweden)

    Christiane Broichhausen

    2014-01-01

    Full Text Available A new cell-based medicinal product containing human regulatory macrophages, known as Mreg_UKR, has been developed and conforms to expectations of a therapeutic drug. Here, Mreg_UKR was subjected to pharmacokinetic, safety