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Sample records for adjuvant treatment strategies

  1. Adjuvant treatment

    PubMed Central

    Sultana, Asma; Neoptolemos, John

    2006-01-01

    Exocrine pancreatic cancer (pancreatic ductal adenocarcinoma) is one of the leading causes of cancer deaths in the western world, accounting for 5% of all cancer-related deaths. Only a small percentage of patients with pancreatic cancer are able to undergo potentially curative resection, even in specialized centres, and prognosis remains poor after successful surgery. Over the last few years efforts have been directed towards the development of adjuvant therapies in attempts to improve outcome. The main trials of adjuvant chemotherapy, chemoradiotherapy and chemoradiotherapy with follow-on chemotherapy are described in this paper, followed by the results of the ESPAC-1 trial and the status of ESPAC-2 and -3 trials. PMID:18333088

  2. Adjuvant treatment for pancreatic cancer.

    PubMed

    Daoud, Vladimir; Saif, Muhammad Wasif; Goodman, Martin

    2014-07-01

    Pancreatic cancer is the fourth leading cause of cancer deaths in both men and women. Surgical resection has been shown to be the only curable treatment available. Unfortunately only 20% of all patients diagnosed with pancreatic cancer are surgical candidates due to the aggressive biology of this disease. There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. Chemoradiation is the favored treatment modality by many in the United States while gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free intervals and in some studies overall survival. The survival of these patients, even status post resection and adjuvant therapy, remains poor and therefore the need for alternative adjuvant therapies is needed. We will therefore discuss Abstracts #4124, #TPS4162, #4120 and #E15191 in this paper which are relevant to the issues described above. PMID:25076340

  3. Current strategies for surgical management and adjuvant treatment of childhood papillary thyroid carcinoma.

    PubMed

    Thompson, Geoffrey B; Hay, Ian D

    2004-12-01

    Childhood papillary thyroid carcinoma is associated with more locally aggressive and more frequent distant disease than its adult counterpart. Recurrence rates tend to be higher in children, but cause-specific mortality remains low. Optimal initial treatment of childhood papillary thyroid carcinoma should include total or near-total thyroidectomy and central compartment node clearance. Modified neck dissections should be performed for biopsy-proven lateral neck disease. Every effort should be made to maintain parathyroid and laryngeal nerve function. Radical neck dissections are to be avoided. Radioiodine remnant ablation (RRA), appropriate thyroid hormone suppressive therapy (THST), and judicious use of therapeutic doses of (131)I are applied to achieve a disease-free status, which is most often confirmed by negative neck ultrasonography, negative whole-body scan (either withdrawal or recombinant human thyroid-stimulating hormone-stimulated), and extremely low levels of serum thyroglobulin. Appropriate utilization of (131)I, THST, repeat surgery, external beam radiotherapy, and rarely chemotherapy may provide long-term palliation and some cures in patients with recurrent/persistent disease. Follow-up should be lifelong, and the care of children after age 17 should subsequently be transferred to adult-care endocrinologists with expertise in managing thyroid neoplasia. Optimal surgical management can be achieved if adequate operations are routinely carried out by "high-volume" thyroid surgeons with expertise in the care of children. Nowhere is a multidisciplinary approach (endocrinologists, surgeons, nuclear medicine physicians, pediatricians, pathologists, oncologists) more critical than in the long-term management of papillary thyroid carcinoma that presents during childhood. PMID:15517490

  4. [Adjuvant treatment of diabetic foot].

    PubMed

    Lo Pardo, Dante; Pezzuti, Gabriela; Selleri, Carmine; Pepe, Stefano; Esposito, Silvano

    2012-01-01

    A diabetic infected foot with erythema and fluctuation can suspect that the infection has passed the fascial compartmental, a condition that requires surgical drainage. Elective amputation may be considered for patients who have recurrent ulcers, irreversible loss of function or injuries that require long-term treatment in the hospital. If the diabetic infected foot appears ischemic it requires a treatment of revascularization. The outcome of revascularization is related with the extension of the damaged artery. The debridement removes the bacterial colonies, promotes granulation tissue and its reepithelialization, also facilitates the collection of samples for microbiological analyses. This procedure can be performed with the classic sharp instruments or with advanced autolytic dressings, maggots or ultrasonic equipment. The use of hyperbaric oxygen therapy in the treatment of infected diabetic foot is controversial because studies in this area are few and methodologically questionable. The same conclusion was reached also for the use of growth factors and skin substitutes. PMID:22982696

  5. Adjuvant and neoadjuvant treatment in pancreatic cancer

    PubMed Central

    Herreros-Villanueva, Marta; Hijona, Elizabeth; Cosme, Angel; Bujanda, Luis

    2012-01-01

    Pancreatic adenocarcinoma is one of the most aggressive human malignancies, ranking 4th among causes for cancer-related death in the Western world including the United States. Surgical resection offers the only chance of cure, but only 15 to 20 percent of cases are potentially resectable at presentation. Different studies demonstrate and confirm that advanced pancreatic cancer is among the most complex cancers to treat and that these tumors are relatively resistant to chemotherapy and radiotherapy. Currently there is no consensus around the world on what constitutes “standard” adjuvant therapy for pancreatic cancer. This controversy derives from several studies, each fraught with its own limitations. Standards of care also vary somewhat with regard to geography and economy, for instance chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America while chemotherapy alone is the current standard in Europe. Regardless of the efforts in adjuvant and neoadjuvant improved therapy, the major goal to combat pancreatic cancer is to find diagnostic markers, identifying the disease in a pre-metastatic stage and making a curative treatment accessible to more patients. In this review, authors examined the different therapy options for advanced pancreatic patients in recent years and the future directions in adjuvant and neoadjuvant treatments for these patients. PMID:22529684

  6. Resectable Cholangiocarcinoma: Reviewing the Role of Adjuvant Strategies

    PubMed Central

    Cidon, E. Una

    2016-01-01

    Cholangiocarcinoma is a very heterogeneous and rare group of neoplasms originating from the perihilar, intra-, or extrahepatic bile duct epithelium. It represents only 3% of gastrointestinal cancers, although their incidence is increasing as its mortality increases. Surgical resection is the only potentially curative option, but unfortunately the resectability rate is low. Overall, these malignancies have got a very poor prognosis with a five-year survival rate of 5–10%. Although the five-year survival rate increases to 25–30% in the cases amenable to surgery, only 10–40% of patients present with resectable disease. Therefore, it is necessary to optimize the benefit of adjuvant strategies after surgery to increase the rate of curability. This study reviewed the role of adjuvant chemotherapy in resectable bile duct cancers. PMID:27199577

  7. Current treatment of early breast cancer: adjuvant and neoadjuvant therapy

    PubMed Central

    Miller, Elizabeth; Lee, Hee Jin; Lulla, Amriti; Hernandez, Liz; Gokare, Prashanth; Lim, Bora

    2014-01-01

    Breast cancer is the most commonly diagnosed cancer in women. The latest world cancer statistics calculated by the International Agency for Research on Cancer (IARC) revealed that 1,677,000 women were diagnosed with breast cancer in 2012 and 577,000 died. The TNM classification of malignant tumor (TNM) is the most commonly used staging system for breast cancer. Breast cancer is a group of very heterogeneous diseases. The molecular subtype of breast cancer carries important predictive and prognostic values, and thus has been incorporated in the basic initial process of breast cancer assessment/diagnosis. Molecular subtypes of breast cancers are divided into human epidermal growth factor receptor 2 positive (HER2 +), hormone receptor positive (estrogen or progesterone +), both positive, and triple negative breast cancer. By virtue of early detection via mammogram, the majority of breast cancers in developed parts of world are diagnosed in the early stage of the disease. Early stage breast cancers can be completely resected by surgery. Over time however, the disease may come back even after complete resection, which has prompted the development of an adjuvant therapy. Surgery followed by adjuvant treatment has been the gold standard for breast cancer treatment for a long time. More recently, neoadjuvant treatment has been recognized as an important strategy in biomarker and target evaluation. It is clinically indicated for patients with large tumor size, high nodal involvement, an inflammatory component, or for those wish to preserve remnant breast tissue. Here we review the most up to date conventional and developing treatments for different subtypes of early stage breast cancer. PMID:25400908

  8. Examples of adjuvant treatment enhancing the antitumor effect of photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Cecic, Ivana; Sun, Jinghai; Chaplin, David J.

    1999-07-01

    Strategies for improving the clinical efficacy of photodynamic therapy (PDT) in treatment of solid cancers include applications of different types of adjuvant treatments in addition to this modality that may result in superior therapeutic outcome. Examples of such an approach investigated using mouse tumor models are presented in this report. It is shown that the cures of PDT treated subcutaneous tumors can be substantially improved by adjuvant therapy with: metoclopramide (enhancement of cancer cell apoptosis), combretastatin A-4 (selective destruction of tumor neovasculature), Roussin's Black Salt (light activated tumor localized release of nitric oxide), or dendritic cell-based adoptive immunotherapy (immune rejection of treated tumor).

  9. Who benefits most from adjuvant interferon treatment for melanoma?

    PubMed

    Gogas, Helen; Abali, Huseyin; Ascierto, Paolo A; Demidov, Lev; Pehamberger, Hubert; Robert, Caroline; Schachter, Jacob; Eggermont, Alexander M M; Hauschild, Axel; Espinosa, Enrique

    2015-01-01

    Metastatic melanoma has a poor prognosis; the median survival for patients with stage IV melanoma ranges from 8 to 18 months after diagnosis. Interferon-α provides significant improvement in disease-free survival at the cost of poor tolerability. Identifying patients who benefit the most may improve the cost:benefit ratio. In addition, no data exist for the role of adjuvant therapy in noncutaneous melanoma. Molecular profiles may help to identify patients who benefit the most from adjuvant interferon therapy. In this review, the American Joint Commission on Cancer 2009 staging criteria and emerging biomarker data to guide adjuvant treatment decisions will be discussed. Several criteria to guide selection of patients are discussed in detail. These include Breslow thickness, number of positive lymph nodes, whether or not the primary lesion has ulcerated, immunologic markers, and cytokine profiles. Substantial progress has been made in deciding which patients benefit from interferon-α adjuvant therapy. Interferon-α is the only agent currently approved for the adjuvant treatment of this deadly disease, despite its side effect profile. More effective drugs with better tolerability are needed. PMID:24176884

  10. [Adjuvant treatment of colon cancer MOSAIC study's main results].

    PubMed

    André, Thierry; Tournigand, Christophe; Achille, Emmanuel; Tubiana-Mathieu, Nicole; Lledo, Gérard; Raoul, Yves; Carola, Elisabeth; Flesch, Michel; Muron, Thierry; Boutan-Laroze, Arnaud; Guérin Meyer, Véronique; Boaziz, Catherine; Maigre, Michel; Ganem, Gérard; Mousseau, Mireille; Mounedji-Boudiaf, Lamia; de Gramont, Aimery

    2006-02-01

    Oxaliplatin in combination with 5-fluorouracil/leucovorin (LV5FU) improves the response rate and survival of patients with metastatic colorectal cancer. The objective of the Mosaic study was to evaluate the efficacy of this association in the adjuvant treatment of stage II and III colon cancer. This international study, including 2,246 patients, compared the efficacy of standard treatment with LV5FU2 alone to that of oxaliplatin-LV5FU (Folfox4 regimen) following R0 resection of the primary tumour. Both treatments were administered every two weeks for six months. At 3-year follow-up, the risk of relapse was decreased by 23% in the Folfox4 group (p = 0.002). The protocol was well tolerated, with an identical overall mortality during treatment (0.5%) in both groups. The main specific complication, peripheral sensory neuropathy was reversible in the great majority of cases. A new analysis at 4-year follow-up (median 48.6 months) confirmed the superior efficacy of the Folfox4 regimen compared to the standard treatment, the reduction in relapse risk being 24% (p = 0.0008). On the strength of these results, oxaliplatin was granted a marketing authorization for the indication adjuvant treatment of stage III colon cancer. Based on the data currently available, physicians should consider adjuvant treatment for stage II patients, making each individual decision for treatment on a case-by-case basis. PMID:16483940

  11. Strategies for treatment of dystonia.

    PubMed

    Dressler, Dirk; Altenmueller, Eckart; Bhidayasiri, Roongroj; Bohlega, Saeed; Chana, Pedro; Chung, Tae Mo; Frucht, Steven; Garcia-Ruiz, Pedro J; Kaelin, Alain; Kaji, Ryuji; Kanovsky, Petr; Laskawi, Rainer; Micheli, Federico; Orlova, Olga; Relja, Maja; Rosales, Raymond; Slawek, Jaroslaw; Timerbaeva, Sofia; Warner, Thomas T; Saberi, Fereshte Adib

    2016-03-01

    Treatment of dystonias is generally symptomatic. To produce sufficient therapy effects, therefore, frequently a multimodal and interdisciplinary therapeutic approach becomes necessary, combining botulinum toxin therapy, deep brain stimulation, oral antidystonic drugs, adjuvant drugs and rehabilitation therapy including physiotherapy, occupational therapy, re-training, speech therapy, psychotherapy and sociotherapy. This review presents the recommendations of the IAB-Interdisciplinary Working Group for Movement Disorders Special Task Force on Interdisciplinary Treatment of Dystonia. It reviews the different therapeutic modalities and outlines a strategy to adapt them to the dystonia localisation and severity of the individual patient. Hints to emerging and future therapies will be given. PMID:26370676

  12. Adjuvant brachytherapy in the treatment of soft-tissue sarcomas.

    PubMed

    Crownover, R L; Marks, K E

    1999-06-01

    For many patients with STS, administering adjuvant radiation treatments in the form of interstitial brachytherapy provides an excellent alternative to a protracted course of EBRT. Ideal patients are those with intermediate- or high-grade tumors amenable to en bloc resection. Attractive features of this approach include an untainted pathologic specimen, expeditious completion of treatment, reduction in wound complications, and improved functional outcome. Brachytherapy can permit definitive reirradiation by tightly localizing the high dose radiation exposure. It is also useful in patients who are known to have or be at high risk of metastatic disease, for whom the rapid completion of local treatment allows systemic therapy to begin quickly. Introduction of HDR techniques has shifted the delivery of brachytherapy from inpatient solitary confinement to an outpatient setting. Early reports using HDR brachytherapy for treatment of adult and pediatric STS are quite encouraging. The clinical equivalence between hyperfractionated HDR schedules and traditional LDR techniques is gaining acceptance. PMID:10432432

  13. Using antimicrobial adjuvant therapy in cancer treatment: a review

    PubMed Central

    2012-01-01

    Recent clinical and pre-clinical data demonstrate that adjuvant antimicrobial therapy is beneficial in cancer treatment. There could be several reasons for this effect, which include treating cancer associated bacteria and viruses, prophylaxis of post-chemotherapy infections due to immunosuppression, and antiproliferative effect of certain antimicrobials. Targeting cancer associated viruses and bacteria with antimicrobial agents is currently used for gastric, cervical, hematopoietic, liver and brain cancer. However this treatment is effective only in combination with conventional therapies. Antimicrobials can also have a direct antiproliferative and cytotoxic effect, and can cause apoptosis. Moreover, some antimicrobials are known to be helpful in overcoming side effects of drugs commonly used in cancer treatment. Chemotherapy related bacteremia and neutropenia can be overcome by the appropriately timed use of antimicrobials. This review summarizes the data on the effects of antivirals and antibiotics on cancer treatment and describes their mechanisms. PMID:23164412

  14. Uncaria tomentosa-Adjuvant Treatment for Breast Cancer: Clinical Trial.

    PubMed

    Santos Araújo, Maria do Carmo; Farias, Iria Luiza; Gutierres, Jessie; Dalmora, Sergio L; Flores, Nélia; Farias, Julia; de Cruz, Ivana; Chiesa, Juarez; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa

    2012-01-01

    Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma-Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer. PMID:22811748

  15. Uncaria tomentosa—Adjuvant Treatment for Breast Cancer: Clinical Trial

    PubMed Central

    Santos Araújo, Maria do Carmo; Farias, Iria Luiza; Gutierres, Jessie; Dalmora, Sergio L.; Flores, Nélia; Farias, Julia; de Cruz, Ivana; Chiesa, Juarez; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa

    2012-01-01

    Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma—Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer. PMID:22811748

  16. Comparable quality attributes of hepatitis E vaccine antigen with and without adjuvant adsorption-dissolution treatment

    PubMed Central

    Zhang, Yue; Li, Min; Yang, Fan; Li, Yufang; Zheng, Zizheng; Zhang, Xiao; Lin, Qingshan; Wang, Ying; Li, Shaowei; Xia, Ningshao; Zhang, Jun; Zhao, Qinjian

    2015-01-01

    Most vaccines require adjuvants for antigen stabilization and immune potentiation. Aluminum-based adjuvants are the most widely used adjuvants for human vaccines. Previous reports demonstrated the preservation of antigen conformation and other antigen characteristics after recovery from adjuvanted Hepatitis B and human papillomavirus vaccines. In this study, we used a combination of various physiochemical and immunochemical methods to analyze hepatitis E vaccine antigen quality attributes after recovery from adjuvants. All biochemical and biophysical methods showed similar characteristics of the p239 protein after recovery from adjuvanted vaccine formulation compared to the antigen in solution which never experienced adsorption/desorption process. Most importantly, we demonstrated full preservation of key antigen epitopes post-recovery from adjuvanted vaccine using a panel of murine monoclonal antibodies as exquisite probes. Antigenicity of p239 was probed with a panel of 9 mAbs using competition/blocking ELISA, surface plasmon resonance and sandwich ELISA methods. These multifaceted analyses demonstrated the preservation of antigen key epitopes and comparable protein thermal stability when adsorbed on adjuvants or of the recovered antigen post-dissolution treatment. A better understanding of the antigen conformation in adjuvanted vaccine will enhanced our knowledge of antigen-adjuvant interactions and facilitate an improved process control and development of stable vaccine formulation. PMID:26018442

  17. Antibiotic adjuvants: diverse strategies for controlling drug-resistant pathogens.

    PubMed

    Gill, Erin E; Franco, Octavio L; Hancock, Robert E W

    2015-01-01

    The growing number of bacterial pathogens that are resistant to numerous antibiotics is a cause for concern around the globe. There have been no new broad-spectrum antibiotics developed in the last 40 years, and the drugs we have currently are quickly becoming ineffective. In this article, we explore a range of therapeutic strategies that could be employed in conjunction with antibiotics and may help to prolong the life span of these life-saving drugs. Discussed topics include antiresistance drugs, which are administered to potentiate the effects of current antimicrobials in bacteria where they are no longer (or never were) effective; antivirulence drugs, which are directed against bacterial virulence factors; host-directed therapies, which modulate the host's immune system to facilitate infection clearance; and alternative treatments, which include such therapies as oral rehydration for diarrhea, phage therapy, and probiotics. All of these avenues show promise for the treatment of bacterial infections and should be further investigated to explore their full potential in the face of a postantibiotic era. PMID:25393203

  18. Antibiotic Adjuvants: Diverse Strategies for Controlling Drug-Resistant Pathogens

    PubMed Central

    Gill, Erin E; Franco, Octavio L; Hancock, Robert E W

    2015-01-01

    The growing number of bacterial pathogens that are resistant to numerous antibiotics is a cause for concern around the globe. There have been no new broad-spectrum antibiotics developed in the last 40 years, and the drugs we have currently are quickly becoming ineffective. In this article, we explore a range of therapeutic strategies that could be employed in conjunction with antibiotics and may help to prolong the life span of these life-saving drugs. Discussed topics include antiresistance drugs, which are administered to potentiate the effects of current antimicrobials in bacteria where they are no longer (or never were) effective; antivirulence drugs, which are directed against bacterial virulence factors; host-directed therapies, which modulate the host's immune system to facilitate infection clearance; and alternative treatments, which include such therapies as oral rehydration for diarrhea, phage therapy, and probiotics. All of these avenues show promise for the treatment of bacterial infections and should be further investigated to explore their full potential in the face of a postantibiotic era. PMID:25393203

  19. Current adjuvant treatment modalities for gastric cancer: From history to the future.

    PubMed

    Kilic, Leyla; Ordu, Cetin; Yildiz, Ibrahim; Sen, Fatma; Keskin, Serkan; Ciftci, Rumeysa; Pilanci, Kezban Nur

    2016-05-15

    The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world. The adjuvant treatment recommendation is generally chemoradiotherapy in the United States, perioperative chemotherapy in the United Kingdom and parts of Europe, and chemotherapy in Asia. These options mainly rely on the United States Intergroup-0116, United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy, and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials. However, the benefits were evident for only certain patients, which were not very homogeneous regarding the type of surgery, chemotherapy regimens, and stage of disease. Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate. Regardless of the extent of surgery, multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement. Moreover, in the era of individualized treatment for most of the other cancer types, identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation. The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients. PMID:27190583

  20. Current adjuvant treatment modalities for gastric cancer: From history to the future

    PubMed Central

    Kilic, Leyla; Ordu, Cetin; Yildiz, Ibrahim; Sen, Fatma; Keskin, Serkan; Ciftci, Rumeysa; Pilanci, Kezban Nur

    2016-01-01

    The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world. The adjuvant treatment recommendation is generally chemoradiotherapy in the United States, perioperative chemotherapy in the United Kingdom and parts of Europe, and chemotherapy in Asia. These options mainly rely on the United States Intergroup-0116, United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy, and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials. However, the benefits were evident for only certain patients, which were not very homogeneous regarding the type of surgery, chemotherapy regimens, and stage of disease. Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate. Regardless of the extent of surgery, multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement. Moreover, in the era of individualized treatment for most of the other cancer types, identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation. The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients. PMID:27190583

  1. Versatile strategy for the divergent synthesis of linear oligosaccharide domain variants of Quillaja saponin vaccine adjuvants.

    PubMed

    Fernández-Tejada, Alberto; Tan, Derek S; Gin, David Y

    2015-09-21

    We describe a new, versatile synthetic approach to Quillaja saponin variants based on the natural product immunoadjuvant QS-21. This modular, divergent strategy provides efficient access to linear oligosaccharide domain variants with modified sugars and regiochemistries. This new synthetic approach opens the door to the rapid generation of diverse analogues to identify novel saponin adjuvants with improved synthetic accessibility. PMID:26243268

  2. Ovarian hyperstimulation in premenopausal women during adjuvant tamoxifen treatment for endocrine-dependent breast cancer: A report of two cases

    PubMed Central

    MADEDDU, CLELIA; GRAMIGNANO, GIULIA; KOTSONIS, PARASKEVAS; PARIBELLO, FRANCESCO; MACCIÒ, ANTONIO

    2014-01-01

    Adjuvant endocrine therapy is an integral component of care for endocrine-dependent breast cancer. The aim of this type of therapy is to counteract the production and the action of estrogens. The ovary is the primary site of estrogen production in premenopausal women, whereas, in postmenopausal women, the main source of estrogens is adipose tissue. Therefore, ovarian function suppression is an effective adjuvant strategy in premenopausal estrogen-dependent breast cancer. Similarly, the inhibition of estrogen action at the receptor site by tamoxifen has proven to be effective. To date, international consensus statements recommend tamoxifen (20 mg/day) for five years as the standard adjuvant endocrine therapy for premenopausal women. It should be noted that tamoxifen is a potent inducer of ovarian function and consequent hyperestrogenism in premenopausal women. In the present study, we report two cases of ovarian cyst formation with very high estrogen levels and endometrial hyperplasia during the administration of tamoxifen alone as adjuvant treatment for estrogen receptor-positive breast cancer in premenopausal women. These cases suggest that in young premenopausal patients with estrogen-dependent breast cancer, ovarian suppression is an essential prerequisite for an adjuvant endocrine therapy with tamoxifen. In this context, luteinizing hormone-releasing hormone agonist treatment by suppressing effective ovarian function may lead to a hypoestrogenic status that may positively impact breast cancer prognosis and prevent the effects of tamoxifen at the gynecological level. It is important to reconsider the action of tamoxifen on ovarian function and include these specific effects of tamoxifen in the informed consent of premenopausal patients who are candidates for tamoxifen alone as adjuvant endocrine treatment. PMID:25120706

  3. Radioimmunotherapy of micrometastases: Theoretical evaluation of adjuvant treatment

    SciTech Connect

    Sgouros, G.; Yorke, E.D.; Willins, J.D.

    1994-05-01

    Failure of current cancer treatment modalities is generally associated with the inability to control distant metastatic disease. This work examines the adjuvant use of radiolabeled antibodies for targeting micrometastases. A Monte Carlo program is used to estimate the number and size distribution of metastases that are present in a given (node-negative) prostate cancer patient population at the time of diagnosis. These results are used in a second program that solves the equations associated with antibody (Ab) diffusion, binding, and dissociation to yield the kinetics of Ab penetration within pre-vascularized micrometastases. These simulated kinetic data are then micrometastasis. Using a two-compartment macroscopic model of Ab distribution, the red marrow dose is also calculated. Calculations are performed for I-123 and for I-131-labeled antibody. With these results, the fraction of the patient population that would benefit from radioimmunotherapy is estimated. The analysis suggests that a single administration of radioimmunotherapy following surgery or external beam radiotherapy will yield a potentially lethal dose ({ge} 20 Gy for I-123 and {ge} 38 Gy for I-131) to 23% of micrometastases present at the time of initial diagnosis without inducing prohibitive red marrow morbidity (absorbed dose {le}2.5 Gy). Multiple courses of radioimmunotherapy, designed to target micrometastases that are initially too small but that eventually reach a targetable size (i.e., 20 {mu}m {le} micromet. radius {le}200{mu}m), will yield a potentially lethal results suggest that approximately 25% of high risk prostate cancer patients (i.e., patients with occult metastases at the time of diagnosis) could benefit from single course of radioimmunotherapy; multiple courses of radioimmunotherapy could benefit 75% of high risk prostate cancer patients.

  4. Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

    PubMed Central

    Tandrup Schmidt, Signe; Foged, Camilla; Smith Korsholm, Karen; Rades, Thomas; Christensen, Dennis

    2016-01-01

    The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens for which no effective vaccines exist. The subunit vaccine technology exploits pathogen subunits as antigens, e.g., recombinant proteins or synthetic peptides, allowing for highly specific immune responses against the pathogens. However, such antigens are usually not sufficiently immunogenic to induce protective immunity, and they are often combined with adjuvants to ensure robust immune responses. Adjuvants are capable of enhancing and/or modulating immune responses by exposing antigens to antigen-presenting cells (APCs) concomitantly with conferring immune activation signals. Few adjuvant systems have been licensed for use in human vaccines, and they mainly stimulate humoral immunity. Thus, there is an unmet demand for the development of safe and efficient adjuvant systems that can also stimulate cell-mediated immunity (CMI). Adjuvants constitute a heterogeneous group of compounds, which can broadly be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode. Immunostimulators represent highly diverse classes of molecules, e.g., lipids, nucleic acids, proteins and peptides, and they are ligands for pattern-recognition receptors (PRRs), which are differentially expressed on APC subsets. Different formulation strategies might thus be required for incorporation of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the specific PRR

  5. Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators.

    PubMed

    Tandrup Schmidt, Signe; Foged, Camilla; Korsholm, Karen Smith; Rades, Thomas; Christensen, Dennis

    2016-01-01

    The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens for which no effective vaccines exist. The subunit vaccine technology exploits pathogen subunits as antigens, e.g., recombinant proteins or synthetic peptides, allowing for highly specific immune responses against the pathogens. However, such antigens are usually not sufficiently immunogenic to induce protective immunity, and they are often combined with adjuvants to ensure robust immune responses. Adjuvants are capable of enhancing and/or modulating immune responses by exposing antigens to antigen-presenting cells (APCs) concomitantly with conferring immune activation signals. Few adjuvant systems have been licensed for use in human vaccines, and they mainly stimulate humoral immunity. Thus, there is an unmet demand for the development of safe and efficient adjuvant systems that can also stimulate cell-mediated immunity (CMI). Adjuvants constitute a heterogeneous group of compounds, which can broadly be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode. Immunostimulators represent highly diverse classes of molecules, e.g., lipids, nucleic acids, proteins and peptides, and they are ligands for pattern-recognition receptors (PRRs), which are differentially expressed on APC subsets. Different formulation strategies might thus be required for incorporation of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the specific PRR

  6. Early adjuvant radiotherapy in the treatment of atypical meningioma.

    PubMed

    Jenkinson, Michael D; Waqar, Mueez; Farah, Jibril Osman; Farrell, Michael; Barbagallo, Giuseppe M V; McManus, Robin; Looby, Seamus; Hussey, Deirdre; Fitzpatrick, David; Certo, Francesco; Javadpour, Mohsen

    2016-06-01

    Atypical meningiomas have a greater propensity to recur than benign meningiomas and the benefits of early adjuvant radiotherapy are unclear. Existing studies report conflicting results. This retrospective cohort study evaluated the role of early adjuvant radiotherapy following surgical resection of atypical meningioma. A triple center case-note review of adults with newly-diagnosed atypical meningiomas between 2001 and 2010 was performed. Pathology diagnosis was made according to the World Health Organization classification in use at the time of surgery. Patients with multiple meningiomas, neurofibromatosis type 2 and radiation-induced meningiomas were excluded. Extent of resection was defined as gross total resection (GTR; Simpson Grade I-III) or subtotal resection (STR; Simpson Grade IV-V). Survival analysis was performed using the Kaplan-Meier method. One hundred thirty-three patients were identified with a median age of 62years (range 22-86years) and median follow-up of 57.4months (range 0.1-152.2months). Tumors were mostly located in the convexity (50.4%) or falcine/parasagittal regions (27.1%). GTR (achieved in 85%) was associated with longer progression free survival (PFS) (5year PFS 81.2% versus 40.08%, log-rank=11.117, p=0.001) but not overall survival (OS) (5year OS 76.6% versus 39.7%, log-rank=3.652, p=0.056). Following GTR, early adjuvant radiotherapy was administered to 28.3% of patients and did not influence OS (5year OS 77.0% versus 75.7%, log-rank=0.075, p=0.784) or PFS (5year PFS 82.0% versus 79.3%, log-rank=0.059, p=0.808). Although extent of resection emerged as an important prognostic variable, early adjuvant radiotherapy did not influence outcome following GTR of atypical meningiomas. Prospective randomized controlled trials are planned. PMID:26775147

  7. Zingiber officinale Roscoe (ginger) as an adjuvant in cancer treatment: a review.

    PubMed

    Pereira, M M; Haniadka, R; Chacko, P P; Palatty, P L; Baliga, M S

    2011-01-01

    Despite acquiring a strong understanding of the molecular basis and advances in treatment, cancer is the second major cause of death in the world. In clinics, the stagedependent treatment strategies may include surgery, radiotherapy and systemic treatments like hormonotherapy and chemotherapy, which are associated with side effects. The use of traditional herbal medicine in cancer patients is on a rise, as it is believed that these medications are non toxic and alleviate the symptoms of cancer, boost the immune system, or may tackle the cancer itself. Since antiquity the rhizome of Zingiber officinale Roscoe commonly known as ginger (family Zingiberaceae) have widely been used as a spice and condiment in different societies. Additionally, ginger also has a long history of medicinal use in various cultures for treating common colds, fever, to aid digestion, treat stomach upset, diarrhoea, nausea, rheumatic disorders, gastrointestinal complications and dizziness. Preclinical studies have also shown that ginger possesses chemopreventive and antineoplastic properties. It is also reported to be effective in ameliorating the side effects of γ-radiation and of doxorubicin and cisplatin; to inhibit the efflux of anticancer drugs by P-glycoprotein (P-gp) and to possess chemosensitizing effects in certain neoplastic cells in vitro and in vivo. The objective of this review is to address observations on the role of ginger as adjuvant to treatment modalities of cancer. Emphasis is also placed on the drawbacks and on future directions for research that will have a consequential effect on cancer treatment and cure. PMID:22006742

  8. Adjuvant treatments for Henoch-Schönlein purpura nephritis in children: A systematic review

    PubMed Central

    Zaffanello, Marco; Brugnara, Milena; Franchini, Massimo; Fanos, Vassilios

    2009-01-01

    Background: The management of Henoch-Schönlein purpura nephritis (HSPN) in childhood is controversial. Adjuvant therapies such as immunoglobulin, anticoagulants, and vitamins have been used with conventional treatments despite a lack of evidence of their efficacy. Objective: The aim of this study was to review the scientific literature regarding adjuvant treatments administered with conventional drugs in the treatment of childhood HSPN. Methods: Published articles were identified from the MEDLINE and EMBASE databases (1988–December 2008; key words: Henoch-Schönlein nephritis and Henoch-Schönlein purpura). The search was limited to published English-language studies on therapeutic options for HSPN in children. Results: A total of 12 studies were identified and included in this review; most (n = 8) were case series or retrospective studies. Studies of conventional therapy combined with adjuvant treatment should be interpreted with caution. In particular, factor XIII administration was reported to improve kidney symptoms in 1 study. Based on the results from 9 studies, no convincing evidence on intravenous immunoglobu-lin, urokinase, or anticoagulants was identified. No substantial information was available on the benefit of antiplatelet agents or heparin in treating HSPN. Integrating treatment with vitamin E was not recommended based on the results from 1 randomized controlled trial. Fish oil was reported to be effective in 1 case series. Conclusions: Studies concerning the treatment of HSPN in children with adjuvant therapies were retrospective and recommendations were drawn from level IV evidence. One randomized controlled trial on the use of tocopherol as adjuvant treatment was identified; however, no clinical utility was reported. At present, there is no strong evidence supporting benefits with the use of adjuvant treatments. PMID:24683235

  9. Adjuvant Treatment after Surgery in Stage IIIA Endometrial Adenocarcinoma

    PubMed Central

    Yoon, Mee Sun; Huh, Seung Jae; Kim, Hak Jae; Kim, Young Seok; Kim, Yong Bae; Kim, Joo-Young; Lee, Jong-Hoon; Kim, Hun Jung; Cha, Jihye; Kim, Jin Hee; Kim, Juree; Yoon, Won Sup; Choi, Jin Hwa; Chun, Mison; Choi, Youngmin; Lee, Kang Kyoo; Kim, Myungsoo; Jeong, Jae-Uk; Chang, Sei Kyung; Park, Won

    2016-01-01

    Purpose We evaluated the role of adjuvant therapy in stage IIIA endometrioid adenocarcinoma patients who underwent surgery followed by radiotherapy (RT) alone or chemoradiotherapy (CTRT) according to risk group. Materials and Methods A multicenter retrospective study was conducted including patients with surgical stage IIIA endometrial cancertreated by radical surgery and adjuvant RT or CTRT. Disease-free survival (DFS) and overall survival (OS) were analyzed. Results Ninety-three patients with stage IIIA disease were identified. Nineteen patients (20.4%) experienced recurrence, mostly distant metastasis (17.2%). Combined CTRT did not affect DFS (74.1% vs. 82.4%, p=0.130) or OS (96.3% vs. 91.9%, p=0.262) in stage IIIA disease compared with RT alone. Patients with age ≥ 60 years, grade G2/3, and lymphovascular space involvement had a significantly worse DFS and those variables were defined as risk factors. The high-risk group showed a significant reduction in 5-year DFS (≥ 2 risk factors) (49.0% vs. 88.0%, p < 0.001) compared with the low-risk group (< 2). Multivariate analysis confirmed that more than one risk factor was the only predictor of worse DFS (hazard ratio, 5.45; 95% confidence interval, 2.12 to 13.98; p < 0.001). Of patients with no risk factors, a subset treated with RT alone showed an excellent 5-year DFS and OS (93.8% and 100%, respectively). Conclusion We identified a low-risk subset of stage IIIA endometrioid adenocarcinoma patients who might be reasonable candidates for adjuvant RT alone. Further randomized studies are needed to determine which subset might benefit from combined CTRT. PMID:26511800

  10. Stage III Colon Cancer: The Individualized Strategy of Adjuvant Chemotherapy for Aged Under and Over 70

    PubMed Central

    Lu, Chieh-Sheng; Chang, Ping-Ying; Chen, Yu-Guang; Chen, Jia-Hong; Wu, Yi-Ying; Ho, Ching-Liang

    2015-01-01

    advantage in the old patients when they received intensive therapies or even oxaliplatin-contained regimens. Prolonged cycles of adjuvant therapy resulted in no significant benefit to survival rates regardless of ages. Conclusions The adequate individualized therapeutic strategy plays an important role for stage III colon cancer. Our findings suggested that benefit of oxaliplatin-contained therapy is limited to patients aged under 70 and oral fluoropyrimidines may be an effective option for old patients. In addition, prolonged adjuvant setting is suggested to be unbeneficial for managing stage III colon cancer. PMID:26382962

  11. Adjuvant radiotherapy in the treatment of gall bladder carcinoma: What is the current evidence.

    PubMed

    Mallick, Supriya; Benson, Rony; Haresh, K P; Julka, P K; Rath, G K

    2016-03-01

    Gall bladder carcinoma (GBC) is considered the fifth most common one of the most aggressive gastro intestinal tract malignancies. Owing to their large incidence randomised controlled trials have hardly been conducted to look into their optimum treatment. Over the years surgical resection has been considered the only curative treatment of these tumors. However, the outcome still remains guarded. The predominant pattern of failure is loco-regional followed by systemic. Hence, local adjuvant radiation has been used by different institutes with concurrent and adjuvant chemotherapy. The large retrospective series with their limitations showed improved survival in patients with regional spread or tumors infiltrating the liver when treated with adjuvant radiotherapy. In the present era with modern radiation techniques and target delineation radiation may further improve upon the impact without adding to the toxicity profile. Hence, radiation in gall bladder cancer needs a relook to optimize treatment outcome of such aggressive disease. PMID:26265290

  12. EGFR-TKIs in adjuvant treatment of lung cancer: to give or not to give?

    PubMed Central

    Milovancev, Aleksandar; Stojsic, Vladimir; Zaric, Bojan; Kovacevic, Tomi; Sarcev, Tatjana; Perin, Branislav; Zarogoulidis, Konstantinos; Tsirgogianni, Katerina; Freitag, Lutz; Darwiche, Kaid; Tsavlis, Drosos; Zissimopoulos, Athanasios; Stratakos, Grigoris; Zarogoulidis, Paul

    2015-01-01

    Epidermal growth factor receptor-tyrosine-kinase inhibitors (EGFR-TKIs) brought a significant revolution in the treatment of non-small-cell lung cancer (NSCLC). In a short period of time, EGFR-TKIs became the standard of treatment for mutation-positive, advanced stage non-squamous NSCLC. In recent years, second- and third-generation EGFR-TKIs are emerging, further widening the clinical use. However, the question of EGFR-TKIs efficiency in the treatment of early stage NSCLC still remains open. Early clinical trials failed to approve the use of EGFR-TKIs in adjuvant setting. The majority of these early trials were performed in unselected NSCLC populations and without standardized biomarker identification. One should certainly not rely solely on these results and dismiss the use of EGFR-TKIs as adjuvant therapy. Many important questions are still unanswered. Most important issues such as stage heterogeneity (IA–IIIA), timing (after or concomitantly with chemotherapy), and type of administration (monotherapy or combination) need to be answered in near future. Adjuvant TKIs in the treatment of lung cancer might offer significant number of advancements. Having in mind the significant duration of response observed in advance disease setting, there could be place for prolongation of response in adjuvant setting potentially, leading to improvement in survival. TKIs could offer less-toxic adjuvant treatment with better efficiency than chemotherapy. However, there is a chronic lack of randomized controlled trials in this field, leading to inability to draw any scientifically sound conclusion with regard to the adjuvant treatment. For now, the use of EGFR-TKIs outside clinical trial setting is not recommended. The purpose of this review is to evaluate current and available data. PMID:26508876

  13. Potential pleiotropic beneficial effects of adjuvant melatonergic treatment in posttraumatic stress disorder.

    PubMed

    Agorastos, Agorastos; Linthorst, Astrid C E

    2016-08-01

    Loss of circadian rhythmicity fundamentally affects the neuroendocrine, immune, and autonomic system, similar to chronic stress and may play a central role in the development of stress-related disorders. Recent articles have focused on the role of sleep and circadian disruption in the pathophysiology of posttraumatic stress disorder (PTSD), suggesting that chronodisruption plays a causal role in PTSD development. Direct and indirect human and animal PTSD research suggests circadian system-linked neuroendocrine, immune, metabolic and autonomic dysregulation, linking circadian misalignment to PTSD pathophysiology. Recent experimental findings also support a specific role of the fundamental synchronizing pineal hormone melatonin in mechanisms of sleep, cognition and memory, metabolism, pain, neuroimmunomodulation, stress endocrinology and physiology, circadian gene expression, oxidative stress and epigenetics, all processes affected in PTSD. In the current paper, we review available literature underpinning a potentially beneficiary role of an add-on melatonergic treatment in PTSD pathophysiology and PTSD-related symptoms. The literature is presented as a narrative review, providing an overview on the most important and clinically relevant publications. We conclude that adjuvant melatonergic treatment could provide a potentially promising treatment strategy in the management of PTSD and especially PTSD-related syndromes and comorbidities. Rigorous preclinical and clinical studies are needed to validate this hypothesis. PMID:27061919

  14. Surgical adjuvant treatment of locally advanced breast cancer.

    PubMed Central

    Townsend, C M; Abston, S; Fish, J C

    1985-01-01

    The reported incidence of local recurrence after mastectomy for locally advanced breast cancer (TNM Stage III and IV) is between 30% and 50%. The purpose of this study was to evaluate the effect of radiation therapy (XRT) followed by total mastectomy on the incidence of local recurrence in patients with locally advanced breast cancer. Fifty-three patients who presented with locally advanced breast cancer, without distant metastases, were treated with XRT (4500-5000 R) to the breast, chest wall, and regional lymph nodes. Five weeks after completion of XRT, total mastectomy was performed. There were no operative deaths. The complications that occurred in 22 patients after surgery were flap necrosis, wound infection, and seroma. Patients have been followed from 3 to 134 months. Twenty-five patients are alive (3-134 months), 12 free of disease; 28 patients have died with distant metastases (6-67 months). Isolated local recurrence occurred in only two patients. Four patients had local and distant recurrence (total local recurrence is 6/53). The remaining patients all developed distant metastases. We have devised a treatment strategy which significantly decreases the incidence of local recurrence in patients with locally advanced breast cancer. However, the rapid appearance of distant metastases emphasizes the need for systemically active therapy in patients with locally advanced breast cancer. PMID:3994434

  15. Radiation Therapy Is Associated With Improved Survival in the Adjuvant and Definitive Treatment of Intrahepatic Cholangiocarcinoma

    SciTech Connect

    Shinohara, Eric T. Mitra, Nandita; Guo Mengye; Metz, James M.

    2008-12-01

    Purpose: Intrahepatic cholangiocarcinomas (IHC) are rare tumors for which large randomized studies regarding the use of radiation are not available. The purpose of this study was to examine the role of adjuvant and definitive radiation therapy in the treatment of IHC in a large group of patients. Methods and Materials: This is a retrospective analysis of 3,839 patients with IHC collected from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was overall survival (OS). Results: Patients received either surgery alone (25%), radiation therapy alone (10%), surgery and adjuvant radiation therapy (7%) or no treatment (58%). The median age of the patient population was 73 years (range, 22-102 years); 52% of patients were male and 81% were Caucasian. Median OS was 11 (95% confidence interval [CI], 9-13), 6 (95% CI, 5-6), 7 (95% CI, 6-8), and 3 months for surgery and adjuvant radiation therapy, sugery alone, radiation therapy alone, and no treatment, respectively. The OS was significantly different between surgery alone and surgery and adjuvant radiation therapy (p = 0.014) and radiation therapy alone and no treatment (p < 0.0001). Use of surgery and adjuvant radiation therapy conferred the greatest benefit on OS (HR = 0.40; 95% CI, 0.34-0.47), followed by surgery alone (hazard ratio [HR], 0.49; 95% CI, 0.44-0.54) and radiation therapy alone (HR, 0.68; 95% CI, 0.59-0.77) compared with no treatment, on multivariate analysis. Propensity score adjusted hazard ratios (controlling for age, race/ethnicity, stage, and year of diagnosis) were also significant (surgery and adjuvant radiation therapy vs. surgery alone (HR, 0.82; 95% CI, 0.70-0.96); radiation therapy alone vs. no treatment (HR, 0.67; 95% CI, 0.58-0.76)). Conclusions: The study results suggest that adjuvant and definitive radiation treatment prolong survival, although cure rates remain low. Future studies should evaluate the addition of chemotherapy and biologics to the treatment of

  16. Docetaxel as adjuvant and neoadjuvant treatment for patients with breast cancer.

    PubMed

    Heys, Steven D; Sarkar, Tarun; Hutcheon, Andrew W

    2004-10-01

    Developments in the role of adjuvant and neoadjuvant chemotherapy for the treatment of patients with breast cancer have focused on the taxes, in particular, docetaxel. This paper discusses the rationale for the introduction of docetaxel into the management of patients following surgery and also its role in those patients with locally-advanced disease, focussing on key clinical trials. The addition of docetaxel to standard adjuvant chemotherapeutic regimens does seem to result in an increased survival in some patients with early-stage disease. In the neoadjuvant setting, the addition of docetaxel to standard regimens does increase pathological response rates, which is a surrogate marker of eventual outcome. PMID:15461550

  17. A Preliminary Evaluation of Fast ForWord-Language as an Adjuvant Treatment in Language Intervention

    ERIC Educational Resources Information Center

    Fey, Marc E.; Finestack, Lizbeth H.; Gajewski, Byron J.; Popescu, Mihai; Lewine, Jeffrey D.

    2010-01-01

    Purpose: Fast ForWord-Language (FFW-L) is designed to enhance children's processing of auditory-verbal signals and, thus, their ability to learn language. As a preliminary evaluation of this claim, we examined the effects of a 5-week course of FFW-L as an adjuvant treatment with a subsequent 5-week conventional narrative-based language…

  18. Arthritis associated with adjuvant mycobacterial treatment for carcinoma of the bladder.

    PubMed Central

    Hughes, R A; Allard, S A; Maini, R N

    1989-01-01

    A patient who developed an inflammatory polyarthritis following intravesical administration of bacillus Calmette-Guérin (BCG) used in the treatment of bladder cancer is described. An inflammatory synovitis comprising predominantly T lymphocytes was demonstrated on synovial biopsy. The synovitis resolved spontaneously within 14 days in this 'human model' of adjuvant arthritis. Images PMID:2786389

  19. Improvements in breast cancer survival between 1995 and 2012 in Denmark: The importance of earlier diagnosis and adjuvant treatment.

    PubMed

    Jensen, Maj-Britt; Ejlertsen, Bent; Mouridsen, Henning T; Christiansen, Peer

    2016-06-01

    Background Breast cancer mortality has declined from 1995 through 2012 which may be attributed to earlier diagnosis, changes in lifestyle risk factors, and improved treatments. To a large extent the relative contribution of these modalities are unknown. Mammography screening was introduced late in Denmark; in 1995 around 20% of the Danish female population aged 50-69 was covered by population-based screening, and this was in 2008 extended to the entire population. Breast conserving surgery gradually replaced mastectomy, and sentinel node biopsy was introduced. In the same period adjuvant treatment was extended considerable. Methods A population-based study of 68 842 breast cancer patients registered in the clinical database of the Danish Breast Cancer Cooperative Group in 1995-2012. Comprehensive data on prognostic factors, comorbidity and treatment together with complete follow-up for survival were used to evaluate improvements in mortality and standardized mortality rate in successive time periods. Results The results from this study demonstrated a significant improvement in prognosis in successive time periods covering 1995-2012. Apart from patients with a high Charlson Comorbidity Index (CCI) improvements were seen in all subgroups of patients. Prognostic factors were more favorable in the latest time period accordingly to the introduction of nationwide screening. In the study period adjuvant treatment was extended considerable. Conclusion The impact of screening was by nature of limited magnitude. The modified treatment strategies implemented by the use of nationwide guidelines seemed to have a major impact on the substantial survival improvements. PMID:26797010

  20. What make differences in the outcome of adjuvant treatments for resected gastric cancer?

    PubMed Central

    Nakajima, Toshifusa; Fujii, Masashi

    2014-01-01

    After a long history of Dark Age of adjuvant chemotherapy for gastric cancer, definite evidences of survival benefit from adjuvant treatment have been reported since 2000s. These survival benefits are likely attributed to something new approach different from pervious studies. In 2001, South West Oncology Group INT0116 trial yielded survival benefit in curatively resected gastric cancer patients with postoperative chemoradiotherapy [5-fluorouracil (5-FU) + Leucovorin + radiotherapy], followed by positive result by MAGIC Trial, employing peri-operative(pre- and postoperative chemotherapy with Epirubicin, cisplatin (CDDP), 5-fluorouracil (ECF) regimen in patients with curative resection. A novel drug [S1: ACTS-GC (Adjuvant chemotherapy trial of TS-1 for gastric cancer) in 2007], or new drug combination chemotherapys [CDDP + 5-FU: FNCLCC/FFCD (Federation Nationale des Centres de Lutte contre le cancer/Federation Francophone de Cancerologie Digestive) in 2011, Capecitabine + Oxaliplatin: CLASSIC in 2012] also produced positive results in terms of improved prognosis. Neoadjuvant or perioperative chemotherapy, novel anti-cancer drugs, and chemoradiotherapy might be the key words to develop further improvement in the adjuvant treatment of resectable gastric cancer. Moreover, it is not new but still true to stress the importance of D2 surgery as the baseline treatment in order to minimize the amount of residual tumor after surgery. PMID:25206264

  1. Adjuvant Stereotactic Radiosurgery and Radiation Therapy for the Treatment of Intracranial Chordomas.

    PubMed

    Choy, Winward; Terterov, Sergei; Ung, Nolan; Kaprealian, Tania; Trang, Andy; DeSalles, Antonio; Chung, Lawrance K; Martin, Neil; Selch, Michael; Bergsneider, Marvin; Yong, William; Yang, Isaac

    2016-02-01

    Objective Chordomas are locally aggressive, highly recurrent tumors requiring adjuvant radiotherapy following resection for successful management. We retrospectively reviewed patients treated for intracranial chordomas with adjuvant stereotactic radiosurgery (SRS) and stereotactic radiation therapy (SRT). Methods A total of 57 patients underwent 83 treatments at the UCLA Medical Center between February 1990 and August 2011. Mean follow-up was 57.8 months. Mean tumor diameter was 3.36 cm. Overall, 8 and 34 patients received adjuvant SRS and SRT, and the mean maximal dose of radiation therapy was 1783.3 cGy and 6339 cGy, respectively. Results Overall rate of recurrence was 51.8%, and 1- and 5-year progression-free survival (PFS) was 88.2% and 35.2%, respectively. Gross total resection was achieved in 30.9% of patients. Adjuvant radiotherapy improved outcomes following subtotal resection (5-year PFS 62.5% versus 20.1%; p = 0.036). SRS and SRT produced comparable rates of tumor control (p = 0.28). Higher dose SRT (> 6,000 cGy) (p = 0.013) and younger age (< 45 years) (p = 0.03) was associated with improved rates of tumor control. Conclusion Adjuvant radiotherapy is critical following subtotal resection of intracranial chordomas. Adjuvant SRT and SRS were safe and improved PFS following subtotal resection. Higher total doses of SRT and younger patient age were associated with improved rates of tumor control. PMID:26949587

  2. Is Radiotherapy a Good Adjuvant Strategy for Men With a History of Cryptorchism and Stage I Seminoma?

    SciTech Connect

    Martin, Jarad M.; Gorayski, Peter; Zwahlen, Daniel; Fay, Michael; Keller, Jacqui; Millar, Jeremy

    2010-01-15

    Purpose: Men with cryptorchism can have aberrant abdominopelvic lymph node (LN) drainage or a different natural history if they develop Stage I seminoma. If so, the nodal echelons for metastases will not be reliable, and adjuvant radiotherapy (RT) would not be an ideal strategy. Methodsand Materials: Two prospectively maintained oncology databases were reviewed for men with a history of testicular seminoma and cryptorchidism. The primary endpoint was the 5-year relapse-free rate. Results: A total of 23 men were identified, most (n = 13) had had a tumor in a scrotal location after orchiopexy. After orchiectomy, 5 men were managed with surveillance, and 18 underwent RT to a median dose of 25 Gy (range, 20-30 Gy). All the radiation fields included the para-aortic LNs, and 13 included the ipsilateral pelvic LNs. After a median follow-up of 64 months (range, 2-148), 2 patients developed a relapse. One did so 4 months into a surveillance program in the para-aortic and ipsilateral pelvic LNs, sites that would have been treated had he undergone RT. The other patient developed a relapse in the contralateral testis 46 months after having undergone RT. It is likely that the latter patient had a metachronous primary rather than a relapse; hence, the 5-year relapse-free rate was 80% for surveillance and 100% for RT. Both patients underwent successful salvage treatment, and all patients were disease free and alive at the last follow-up visit. Conclusion: A history of cryptorchism does not appear to confer a greater risk of relapse for men with Stage I seminoma managed with radiotherapy. RT, surveillance, and adjuvant carboplatin chemotherapy are treatment options for these patients.

  3. Adjuvant imatinib treatment in gastrointestinal stromal tumor: which risk stratification criteria and for how long? A case report.

    PubMed

    Blay, Jean-Yves; Levard, Alice

    2016-01-01

    Imatinib mesylate is approved for the adjuvant treatment of KIT-positive gastrointestinal stromal tumor (GIST) following surgical resection. However, uncertainty remains in terms of patient eligibility for adjuvant treatment and the optimal duration of treatment. Here, we present two challenging patient cases encountered in clinical practice that highlight the ambiguity in the current recommendations for adjuvant imatinib in GIST and discuss our approaches and rationales for treatment. The first case involves a 36-year-old man with a 7 cm duodenal GIST and possible tumor rupture during surgical resection. This patient's risk of GIST recurrence was either intermediate or high depending on which risk stratification criteria were used. The patient was treated with adjuvant imatinib for 3 years and experienced disease recurrence 14 months after the completion of treatment. Imatinib treatment was reintroduced, and the patient is in partial response 17 months later. The second case involves a 46-year-old woman at high risk of recurrence following surgical resection. Adjuvant treatment with imatinib was initiated. After considering the patient's initial high risk and good side-effect profile, the decision was made to continue adjuvant imatinib treatment for 5 years. As of May 2013, the patient has been receiving continuous imatinib treatment for 52 months, with no sign of progression. These reports exemplify the challenges faced in clinical practice because of uncertainties in optimal risk stratification criteria and duration of treatment. They stress the importance of individualized treatment and shared decision making between the physician and the patient. PMID:26457546

  4. Antihormonal treatment associated musculoskeletal pain in women with breast cancer in the adjuvant setting

    PubMed Central

    Seber, Selcuk; Solmaz, Dilek; Yetisyigit, Tarkan

    2016-01-01

    Purpose Antihormonal treatment is an effective therapy in the adjuvant setting. However, musculoskeletal pain is a common adverse effect encountered in patients receiving this treatment. We aimed to evaluate the risk factors for the development of antihormonal treatment-associated musculoskeletal pain (AHAMP) and its impact on the health-related quality of life (HRQOL). Patients and methods A cross-sectional survey of 78 consecutive breast cancer patients receiving adjuvant antihormonal treatment for early-stage breast cancer in an academic medical oncology clinic was conducted. AHAMP was assessed by Health Assessment Questionnaire (HAQ) and 10 cm visual analog scale (VAS). HRQOL was assessed by self-administered short form 36 and Functional Assessment of Cancer Therapy-Breast subscale surveys. Results AHAMP was found to be present in 37 (47.7%) patients. In multivariate regression analysis, having a normal body mass index (<30 kg/m2), cigarette smoking, and low serum vitamin D level (20 ng/mL) were found to be independent risk factors. In HRQOL assessment, physical and mental scores were found to be significantly lower in patients with joint arthralgia. Conclusion AHAMP has an adverse effect on the quality of life of breast cancer patients receiving adjuvant antihormonal treatment, and assessment of predictive factors is important for identification of patient groups at risk of developing this condition. PMID:27563249

  5. Successful treatment of gallbladder mixed adenoneuroendocrine carcinoma with neo-adjuvant chemotherapy

    PubMed Central

    2012-01-01

    Mixed adenoneuroendocrine carcinoma (MANEC) carcinomas rarely occur in the gallbladder. Here we reported a case of giant gallbladder unresectable mass with local liver invasion and omentum metastasis, which proved to be neuroendocrine carcinoma (NEC) by biopsy, received successful radical operation after neo-adjuvant chemotherapy plus somatostatin treatment. The patient showed good response as the neoplasm diminished dramatically and showed clear margin after 6 courses of treatment. A radical operation including cholecystectomy, hepatic wedge resection of the gallbladder fossa segment and lymph node of group 8a and 8p resection was performed successfully. Postoperative histopathological examination revealed neuroendocrine carcinoma mixed with adenocarcinoma in the gallbladder wall. Followed up showed no evidence of recurrence after 7 months of the operation. We suggest that neo-adjuvant chemotherapy may be beneficial to gallbladder mixed neuroendocrine carcinomas in an advanced stage which could also be advantageous to NEC of other organs. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/2731892837743787 PMID:23186166

  6. Quercetin: a potential natural drug for adjuvant treatment of rheumatoid arthritis.

    PubMed

    Ji, Jian-Jun; Lin, Yuan; Huang, Shan-Shan; Zhang, Hou-Li; Diao, Yun-Peng; Li, Kun

    2013-01-01

    Rheumatoid arthritis (RA) is the rheumatism mainly manifested as disabling joint disease and mainly involves hands, wrists, feet and other small joints. Recurrent arthritis attacks, synovial cell hypertrophy and hyperplasia and bone and cartilage damages eventually lead to joint dysfunction and other complications, and there is no cure. Quercetin (QU) is a kind of natural flavonoids, with lipid-lowering, anti-inflammatory and other pharmacological activities, and minor toxic side effects. Thus, we assume that QU may be an adjuvant natural drug for treatment of RA. The possible mechanism is through regulation of NF-κB, to inhibit the transcription of joint synovitis factors, hinder the generation of inflammatory factors, and inhibit the inflammatory reaction; through inhibiting the activities of VEGF, bFGF, MMP-2 and other cytokines, to inhibit angiogenesis in multiple links and inhibit synovial pannus formation. QU may be an adjuvant natural drug for treatment of RA. PMID:24146468

  7. The neo-adjuvant treatment in gastrointestinal stromal tumor.

    PubMed

    Catania, V; Consoli, A; Cavallaro, A; Liardo, R L E; Malaguarnera, M

    2010-08-01

    Gastrointestinal Stromal Tumor (GIST) is a rare intra-abdominal tumor, characterized by a specific histological and immunohistochemical pattern. These tumors affect with higher frequency stomach and small bowel and occur at a median age of 60 years with a slight male predominance. An early stage of GIST often don't cause any symptoms, so most GISTs are diagnosed in later stages of the disease. We report a case of GIST diagnosed only with clinical data and positron emission tomography (PET). We demonstrate the usefulness of neoadjuvant treatment with Imatinib mesylate, a newly developed tyrosine kinase receptor inhibitor. The neoadjuvant treatment with Imatinib reduced the mass size and vascularization, making possible a surgical approach. PMID:20707293

  8. Tuberculosis axillary lymph node coexistent breast cancer in adjuvant treatment: case report

    PubMed Central

    Bromberg, Silvio Eduardo; do Amaral, Paulo Gustavo Tenório

    2015-01-01

    Coexistence of breast cancer and tuberculosis is rare. In most cases, involvement by tuberculosis occurs in axillary lymph nodes. We report a case of a 43-years-old patient who had undergone adenomastectomy and left sentinel lymph node biopsy due to a triple negative ductal carcinoma. At the end of adjuvant treatment, the patient had an atypical lymph node in the left axilla. Lymph node was excised, and after laboratory analysis, the diagnosis was ganglion tuberculosis. The patient underwent treatment for primary tuberculosis. The development of these two pathologies can lead to problems in diagnosis and treatment. An accurate diagnosis is important to avoid unnecessary surgical procedures. PMID:26018148

  9. EPO-R expression patterns in resected gastric adenocarcinoma followed by adjuvant chemoradiation treatment.

    PubMed

    Sereno, Maria; De Castro, Javier; Belda-Iniesta, Cristóbal; Garcia-Cabezas, Miguel Angel; Cejas, Paloma; Casado, Enrique; Barriuso, Jorge; Feliu, Jaime; Larrauri, Javier

    2009-03-01

    The primary aim was to determine whether Epo-R immunohistochemical expression is related to disease free survival (DFS) in specimens of GC from patients who underwent adjuvant chemoradiation. Specimens of gastric adenocarcinomas obtained from 44 patients who had undergone curative gastrectomy and adjuvant treatment were investigated immunohistochemically expression of Epo-R. Three patterns for Epo-R staining were defined: Pattern A (secretory cells-like staining), Pattern B (parietal-like staining) and Pattern C (chief-like staining). Median DFS was 38 months (CI 95%: 33-43) and 15 months (IC 95%: 3-27) in the pattern B and C, respectively, but it was not reached in the pattern A (p = 0.06). Our findings suggest that there may be a relationship between Epo-R expression and DFS in the patients with GC resected. PMID:19002606

  10. Endometrial cancer - reduce to the minimum. A new paradigm for adjuvant treatments?

    PubMed Central

    2011-01-01

    Background Up to now, the role of adjuvant radiation therapy and the extent of lymph node dissection for early stage endometrial cancer are controversial. In order to clarify the current position of the given adjuvant treatment options, a systematic review was performed. Materials and methods Both, Pubmed and ISI Web of Knowledge database were searched using the following keywords and MESH headings: "Endometrial cancer", "Endometrial Neoplasms", "Endometrial Neoplasms/radiotherapy", "External beam radiation therapy", "Brachytherapy" and adequate combinations. Conclusion Recent data from randomized trials indicate that external beam radiation therapy - particularly in combination with extended lymph node dissection - or radical lymph node dissection increases toxicity without any improvement of overall survival rates. Thus, reduced surgical aggressiveness and limitation of radiotherapy to vaginal-vault-brachytherapy only is sufficient for most cases of early stage endometrial cancer. PMID:22118369

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

    SciTech Connect

    McMillan, Matthew T.; Ojerholm, Eric; Roses, Robert E.; Plastaras, John P.; Metz, James M.; Mamtani, Ronac; Stripp, Diana; Ben-Josef, Edgar; Datta, Jashodeep

    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.

  12. Iodine and doxorubicin, a good combination for mammary cancer treatment: antineoplastic adjuvancy, chemoresistance inhibition, and cardioprotection

    PubMed Central

    2013-01-01

    Background Although mammary cancer (MC) is the most common malignant neoplasia in women, the mortality for this cancer has decreased principally because of early detection and the use of neoadjuvant chemotherapy. Of several preparations that cause MC regression, doxorubicin (DOX) is the most active, first-line monotherapeutic. Nevertheless, its use is limited due to the rapid development of chemoresistance and to the cardiotoxicity caused by free radicals. In previous studies we have shown that supplementation with molecular iodine (I2) has a powerful antineoplastic effect in methylnitrosourea (MNU)-induced experimental models of MC. These studies also showed a consistent antioxidant effect of I2 in normal and tumoral tissues. Methods Here, we analyzed the effect of I2 in combination with DOX treatment in female Sprague Dawley rats with MNU-induced MC. In the first experiment (short) animals were treated with the therapeutic DOX dose (16 mg/kg) or with lower doses (8 and 4 mg/Kg), in each case with and without 0.05% I2 in drinking water. Iodine treatment began on day 0, a single dose of DOX was injected (ip) on day 2, and the analysis was carried out on day 7. In the second experiment (long) animals with and without iodine supplement were treated with one or two injections of 4 mg/kg DOX (on days 0 and 14) and were analyzed on day 56. Results At all DOX doses, the short I2 treatment induced adjuvant antineoplastic effects (decreased tumor size and proliferating cell nuclear antigen level) with significant protection against body weight loss and cardiotoxicity (creatine kinase MB, cardiac lipoperoxidation, and heart damage). With long-term I2, mammary tumor tissue became more sensitive to DOX, since a single injection of the lowest dose of DOX (4 mg/Kg) was enough to stop tumor progression and a second DOX4 injection on day 14 caused a significant and rapid decrease in tumor size, decreased the expression of chemoresistance markers (Bcl2 and survivin), and increased

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

    SciTech Connect

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

    2006-08-01

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

  14. Chinese herbal medicines as adjuvant treatment during chemo- or radio-therapy for cancer.

    PubMed

    Qi, Fanghua; Li, Anyuan; Inagaki, Yoshinori; Gao, Jianjun; Li, Jijun; Kokudo, Norihiro; Li, Xiao-Kang; Tang, Wei

    2010-12-01

    Numerous studies have indicated that in cancer treatment Chinese herbal medicines in combination with chemo- or radio-therapy can be used to enhance the efficacy of and diminish the side effects and complications caused by chemo- and radio-therapy. Therefore, an understanding of Chinese herbal medicines is needed by physicians and other health care providers. This review provides evidence for use of Chinese herbal medicines as adjuvant cancer treatment during chemo- or radio-therapy. First, Chinese herbal medicines (e.g. Astragalus, Turmeric, Ginseng, TJ-41, PHY906, Huachansu injection, and Kanglaite injection) that are commonly used by cancer patients for treating the cancer and/or reducing the toxicity induced by chemo- or radio-therapy are discussed. Preclinical and clinical studies have shown that these Chinese herbal medicines possess great advantages in terms of suppressing tumor progression, increasing the sensitivity of chemo- and radio-therapeutics, improving an organism's immune system function, and lessening the damage caused by chemo- and radio-therapeutics. Second, clinical trials of Chinese herbal medicines as adjuvant cancer treatment are reviewed. By reducing side effects and complications during chemo- and radio-therapy, these Chinese herbal medicines have a significant effect on reducing cancer-related fatigue and pain, improving respiratory tract infections and gastrointestinal side effects including diarrhea, nausea, and vomiting, protecting liver function, and even ameliorating the symptoms of cachexia. This review should contribute to an understanding of Chinese herbal medicines as adjuvant treatment for cancer and provide useful information for the development of more effective anti-cancer drugs. PMID:21248427

  15. Newer antiatherosclerosis treatment strategies

    PubMed Central

    Aggarwal, Amitesh; Singh, Safal

    2011-01-01

    Atherosclerosis has been a target of much clinical and molecular research. As a result of this extensive research, it is amply clear that atherogenesis is a multifactorial process involving an interplay of metabolic, immune and inflammatory mechanisms. Antiatherosclerotic strategies are today aiming for a multipronged approach targeting each arm of this multifactorial process. The newer agents under development can be divided into three broad categories: anti-inflammatory agents, modulators of intermediary metabolism and antiatherosclerosis vaccines. Potential targets for anti-inflammatory agents include inhibition of conversion of low-density lipoprotein (LDL) to oxidised LDL, blocking or downregulation of cell adhesion molecules, chemokine modulation and macrophage receptor blockade. Beyond inhibition of plaque formation, efforts are also ongoing to develop agents which stabilise the plaque by increasing its fibrous content and inhibiting its disruption. So far as research in the sphere of intermediary metabolism is concerned, the focus is now primarily on raising high-density lipoprotein and promoting reverse cholesterol transport; potential targets include cholesteryl ester transfer protein, liver X-receptor, lecithin cholesterol acyltransferase and high-density lipoprotein mimetics. Acyl-coenzymeA: cholesterol acyltransferase is another enzyme whose selective and differential inhibition is under active investigation. The concept of immunisation against a non-communicable disease such as atherosclerosis is still in its nascent stages. However, with increasing evidence to suggest the role of antigen-specific T-cell-mediated immunity in atherogenesis, this approach is potentially promising. Possible antigens under evaluation include oxidised LDL and its subparticles, heat-shock proteins and cholesteryl ester transfer protein. With cardiovascular disease being the single leading cause of death worldwide, the development of a safe and successful antiatherosclerosis

  16. Adjuvant bisphosphonate treatment for breast cancer: Where are we heading and can the pre-clinical literature help us get there?

    PubMed Central

    Russell, Kent; Clemons, Mark; Costa, Luis; Addison, Christina L.

    2012-01-01

    Bisphosphonates have demonstrated anti-tumour activity in preclinical studies of bone metastatic disease, thus it was natural to transition these agents into the adjuvant cancer therapy setting. Surprisingly, the results of adjuvant breast cancer trials have shown either modest to no benefit or even harm. We sought to explore whether the preclinical results supporting bisphosphonate use provided clues to help explain the current clinical data. Interestingly, the majority of preclinical data suggested that bisphosphonate treatment was more efficacious when administered after the establishment of osseous metastases. This is similar to the findings of one clinical study whereby patients with biopsy evidence of osseous micrometastases derive greater survival benefit from bisphosphonate treatment. Another clinical study found bisphosphonates were associated with increased incidence of visceral metastases, similar to what has been previously published in preclinical models using “preventative” dosing strategies. While the current clinical data suggest bisphosphonates may be more efficacious in post-menopausal or oestrogen depleted patients, or those with hormone receptor positive tumours, to date no appropriately designed preclinical studies have evaluated these effects. Furthermore, putative mechanisms that regulate response to bisphosphonates in other tumour types remain to be evaluated in breast cancer. Despite the initial optimism regarding adjuvant bisphosphonate therapy, the conflicting clinical results from large trials suggest that we should return to the bench to further investigate factors that may influence response to bisphosphonate treatment or identify appropriate characteristics that would indicate the sub-groups of patients most likely to benefit from bisphosphonate treatment. PMID:26909249

  17. Adjuvant treatment modalities to control macular edema in diabetic patients undergoing cataract surgery.

    PubMed

    Cetin, Ebru Nevin; Yıldırım, Cem

    2013-10-01

    Cataract surgical outcomes in diabetic patients has been subject to changes with the advances in the surgical techniques. Recent studies suggest that cataract surgery does not cause the progression of diabetic retinopathy and intravitreal bevacizumab and/or triamcinolone injections combined with cataract surgery may contribute in short term improvement of macular edema in diabetic patients. This article reviews the progression of diabetic retinopathy after cataract surgery with phacoemulsification and the use of adjuvant intravitreal treatments combined with phacoemusification in diabetic patients undergoing cataract surgery. PMID:23248073

  18. Dual HER2 blockade in the neoadjuvant and adjuvant treatment of HER2-positive breast cancer

    PubMed Central

    Advani, Pooja; Cornell, Lauren; Chumsri, Saranya; Moreno-Aspitia, Alvaro

    2015-01-01

    Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase transmembrane receptor that is overexpressed on the surface of 15%–20% of breast tumors and has been associated with poor prognosis. Consistently improved pathologic response and survival rates have been demonstrated with use of trastuzumab in combination with standard chemotherapy in both early and advanced breast cancer. However, resistance to trastuzumab may pose a major problem in the effective treatment of HER2-positive breast cancer. Dual HER2 blockade, using agents that work in a complimentary fashion to trastuzumab, has more recently been explored to evade resistance in both the preoperative (neoadjuvant) and adjuvant settings. Increased effectiveness of dual anti-HER2 agents over single blockade has been recently reported in clinical studies. Pertuzumab in combination with trastuzumab and taxane is currently approved in the metastatic and neoadjuvant treatment of HER2-positive breast cancer. Various biomarkers have also been investigated to identify subsets of patients with HER2-positive tumors who would likely respond best to these targeted therapy combinations. In this article, available trial data regarding efficacy and toxicity of treatment with combination HER2 agents in the neoadjuvant and adjuvant setting have been reviewed, and relevant correlative biomarker data from these trials have been discussed. PMID:26451122

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

    SciTech Connect

    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.

    2011-11-15

    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

  20. Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma.

    PubMed

    Finocchiaro, L M E; Glikin, G C

    2008-02-01

    We evaluated the safety, efficacy and anti-tumor effects of a surgery adjuvant treatment on canine patients with malignant melanoma. This approach combined suicide gene therapy with a subcutaneous vaccine composed by formolized tumor cells and irradiated xenogeneic cells producing human interleukin-2 and granulocyte-macrophage colony-stimulating factor. The post-surgical margin of the cavity was infiltrated with lipid-complexed thymidine kinase suicide gene coadministrated with ganciclovir. Toxicity was minimal or absent in all patients. With respect to surgery-treated controls (SC), this combined treatment (CT) significantly increased the fraction of patients local disease-free from 6 to 58% and distant metastases-free from 43 to 78% (Fisher's Exact test). In addition, CT significantly improved both SC overall 78 (23-540) and metastasis-free survival 112 (0-467) days to more than 1312 days (respective ranges: 43-1312 and 0-1312) (Kaplan-Meier analysis). In those patients subjected to partial surgery or presenting local recurrence, the efficacy of CT was verified by a 49% of objective responses that averaged 85% of tumor mass loss, while 22% displayed tumor progression as 94% of SC did. Therefore, surgery adjuvant CT controlled tumor growth, delaying or preventing post-surgical recurrence and distant metastasis, significantly extending survival and recovering the quality of life. PMID:18033308

  1. [Glioma treatment strategies using mesenchymal stem cells].

    PubMed

    Namba, Hiroki

    2010-10-01

    Because of the growth characteristics of malignant gliomas that are highly invasive and deeply infiltrate the surrounding brain area; the surgical resection of these gliomas with preservation of neural functions is almost always noncurative. The residual tumor cells are usually resistant to standard adjuvant radiochemotherapy, and therefore, the tumors inevitably recur after a certain period and finally cause the death of the patients. Neural and mesenchymal stem cells have been extensively studied for the development of new strategies for treating malignant gliomas because of these cells possess the intrinsic property of homing toward tumor cells. By using neural and mesenchymal stem cells as vehicles for drug carriers, it is possible to deliver anticancer drugs to the tumor cells that infiltrate functioning normal brain tissue and are difficult to remove. Several cytokines and suicide genes have been tested, and promising results have been reported in animal brain tumor models. However, further studies involving safety issues such as secondary cancer formation are required before human trials of stem cell therapies. In the present paper, the author has reviewed the recent concepts involved in the treatment of malignant gliomas with stem cells, especially mesenchymal stem cells that are much easier to obtain from the patients themselves. PMID:20940507

  2. The role of neoadjuvant and adjuvant treatment for adenocarcinoma of the upper gastrointestinal tract

    PubMed Central

    2011-01-01

    Both locally advanced adenocarcinoma of the stomach and gastro-esophageal junction are associated with poor prognosis due to the lack of effective treatment. Recently multimodal treatment consisting of neoadjuvant chemotherapy in combination with radiotherapy is reported to improve survival when compared to surgery alone. Neoadjuvant therapy in these locally advanced tumors allows for early tumor responses and the extent of tumor regression that can be achieved is considered a significant prognostic factor. This, in turn, increases the resectability of these tumors. Also due to the high frequency of lymph node metastasis, patients with locally advanced adenocarcinoma should undergo a D2 lymphadenectomy. Postoperative chemoradiation and perioperative chemotherapy have been studied in gastric adenocarcinomas and showed a survival benefit. However, the surgical techniques used in these trials are no longer considered to be standard by today's surgical practice. In addition, there are no standard recommendations for adjuvant chemotherapy or chemoradiation after R0 resection and adequate lymph node dissection. PMID:21810561

  3. Curative effect of the recent photofrin photodynamic adjuvant treatment on young patients with advanced colorectal cancer

    PubMed Central

    SUN, BO; LI, WEI; LIU, NING

    2016-01-01

    Advanced colorectal cancer has a high mortality rate and conventional treatments have poor therapeutic effects. The aim of the present study was to analyze the recent curative effect and adverse reaction of photofrin photodynamic adjuvant treatment on young patients with advanced colorectal cancer. A total of 23 patients with advanced colorectal cancer who had accepted semiconductor laser photodynamic adjuvant treatment were selected as the observation group. In addition, 30 patients who had accepted concurrent radiotherapy and chemotherapy during the same period served as the control group. The observation group received photofrin (2 mg/kg) intravenously in 100 ml of 5% glucose, followed by the introduction of the endoscopic optical fiber to deliver laser radiation with an intensity of 630 nm wavelength pulse power. After 2 days, necrotic tissues were removed and irradiation of the original or new tumor lesions was performed and necrotic tissues were removed. The total effective rate and survival time was higher and the length of hospital stay was shorter in the observation group in comparison with the control group. The differences were statistically significant (P<0.05). The number of patients in the control and observation groups with symptoms of hematochezia, change in bowel habit, intestinal stimulation and incomplete intestinal obstruction were reduced. Additionally, the reduced ratio of the observation group was significantly increased in comparison with the control group (P<0.05). The adverse reaction rate of the observation group was lower than that of the control group and this difference was also statistically significant (P<0.05). In conclusion, use of photodynamic treatment for young patients with advanced colorectal cancer can effectively improve the clinical symptoms and reduce complications. PMID:26998124

  4. A randomized trial comparing adjuvant fluorouracil, epirubicin, and mitomycin with no treatment in operable gastric cancer.

    PubMed

    Tsavaris, N; Tentas, K; Kosmidis, P; Mylonakis, N; Sakelaropoulos, N; Kosmas, C; Lisaios, B; Soumilas, A; Mandrekas, D; Tsetis, A; Klonaris, C

    1996-01-01

    Combination chemotherapy (CT) has, in some groups of patients with gastric cancer (GC), who are at a high risk for relapse, resulted in a small but measurable improvement in palliation and patient survival not reaching statistical significance and therefore remaining applicable in an investigational setting. Based on the above data, we studied adjuvant CT with FEM (5-fluorouracil (5-FU), epirubicin, mitomycin C) in a randomized study of patients with completely resected stage III GC and patients with stages T1-3 with a low histologic grade. CT was started 2-3 weeks after surgery. From August 1988 until February 1994, 84 patients with completely resected tumors and lymph nodes were randomized to either group A (FEM) or group B (no treatment). Patients were eligible for randomization if they had a Karnofsky score > 60, no postoperative evidence of residual tumor, and normal cardiac, hepatic and renal functions. Forty-two patients were randomized to each group, with no significant differences regarding: age distribution, group A 53 years (41-65), group B 57 years (35-66); sex, group A 32/10, group B 25/17 (men/women); site of primary tumor, group A 22/20, group B 25/17 (pylorus/antrum); histologic grade, group A 0/19/23, group B 0/25/17 (grades I/II/III); lymph node metastases, group A 30, group B 32, and surgical procedure, group A 33/9/6, group B 35/7/9 (total gastrectomy/partial gastrectomy/splenectomy). Group A received 5-FU 600 mg/m2/day i.v. on days 1, 8, 29 and 36, epirubicin 45 mg/m2/day i.v. on days 1 and 29, and mitomycin C 10 mg/m2 i.v. on day 1. The schedule was repeated every 56 days for 3 cycles. Group B received no treatment odd was only subjected to the regular follow-up. At the last follow-up at 66 months, 27/42 patients in group A (64%) had relapsed or died, compared to 34/42 patients in group B (81%). The differences in the relapse and the disease-free and the overall survival rates were not statistically significant. Only the subgroup of patients

  5. Treatment strategy for Boerhaave's syndrome.

    PubMed

    Ochiai, T; Hiranuma, S; Takiguchi, N; Ito, K; Maruyama, M; Nagahama, T; Kawano, T; Nagai, K; Nishikage, T; Noguchi, N; Takamatsu, S; Kawamura, T; Teramoto, K; Iwai, T; Arii, S

    2004-01-01

    Esophageal rupture is a potentially mortal condition. Rapid and correct diagnosis, and urgent surgical treatment with esophagectomy is indicated, but conservative and other surgical treatments have also been reported recently. The treatment strategies for esophageal rupture are discussed here, based on our experiences with four cases during the last 10 years. They were admitted urgently and each was treated by a different method. Three of them underwent emergency operations, one undergoing primary closure of the ruptured esophagus, another received a T-tube insertion from the ruptured site with omental flap, and the third an esophagogastrectomy. The fourth case was treated conservatively. All patients survived and were discharged 36-144 days post treatment. One of them was readmitted for debridement of necrotic rib. In conclusion, the prompt and accurate diagnosis of esophageal rupture is crucial for a subsequent successful treatment. Conservative treatment or operation including esophagectomy will be determined by the severity of the condition. PMID:15209751

  6. The Prognostic Impact of NK/NKT Cell Density in Periampullary Adenocarcinoma Differs by Morphological Type and Adjuvant Treatment

    PubMed Central

    Warfvinge, Carl Fredrik; Elebro, Jacob; Heby, Margareta; Nodin, Björn; Krzyzanowska, Agnieszka; Bjartell, Anders; Leandersson, Karin; Eberhard, Jakob; Jirström, Karin

    2016-01-01

    Background Natural killer (NK) cells and NK T cells (NKT) are vital parts of tumour immunosurveillance. However, their impact on prognosis and chemotherapy response in periampullary adenocarcinoma, including pancreatic cancer, has not yet been described. Methods Immune cell-specific expression of CD56, CD3, CD68 and CD1a was analysed by immunohistochemistry on tissue microarrays with tumours from 175 consecutive cases of periampullary adenocarcinoma, 110 of pancreatobiliary type (PB-type) and 65 of intestinal type (I-type) morphology. Kaplan-Meier and Cox regression analysis were applied to determine the impact of CD56+ NK/NKT cells on 5-year overall survival (OS). Results High density of CD56+ NK/NKT cells correlated with low N-stage and lack of perineural, lymphatic vessel and peripancreatic fat invasion. High density of CD56+ NK/NKT cells was associated with prolonged OS in Kaplan-Meier analysis (p = 0.003), and in adjusted Cox regression analysis (HR = 0.49; 95% CI 0.29–0.86). The prognostic effect of high CD56+ NK/NKT cell infiltration was only evident in cases not receiving adjuvant chemotherapy in PB-type tumours (p for interaction = 0.014). Conclusion This study demonstrates that abundant infiltration of CD56+ NK/NKT cells is associated with a prolonged survival in periampullary adenocarcinoma. However, the negative interaction with adjuvant treatment is noteworthy. NK cell enhancing strategies may prove to be successful in the management of these cancers. PMID:27275582

  7. Future treatment strategies in phenylketonuria.

    PubMed

    van Spronsen, Francjan J; Enns, Gregory M

    2010-01-01

    Phenylketonuria (PKU) was the first inherited metabolic disease in which treatment was found to prevent clinical features of the disorder; dietary management was established almost 60 years ago. The institution of a low-phenylalanine (Phe) diet in the first few weeks of life was made possible by Guthrie neonatal screening, which further increased effectiveness of therapy. Indeed, neonatal diagnosis of PKU followed by institution of a low-Phe diet has been a remarkable success in preventing the devastating brain damage associated with untreated PKU. Nevertheless, significant difficulties exist in caring for PKU patients, including problems with adhering to the prescribed dietary regimen and the presence of neurocognitive deficits despite therapy. During the past few years, several ideas for new treatment strategies have emerged. This review aims to address these treatment strategies based on theoretical considerations of the biochemistry and pathogenesis of PKU. Recent times have seen the introduction of a wide array of novel treatments currently in clinical use, including more palatable medical foods, glycomacropeptide, large neutral amino acids, and tetrahydrobiopterin. Human trials are underway using an enzymatic therapeutic approach, while preclinical work continues in the fields of gene and cellular therapy. These therapeutic strategies propose to treat PKU at various levels, including nutritional intake, gut, liver, and blood-brain barrier, and have the potential to further improve outcome in PKU. PMID:20123478

  8. Adjuvant systemic treatment for individual patients with triple negative breast cancer.

    PubMed

    Oakman, Catherine; Moretti, Erica; Galardi, Francesca; Biagioni, Chiara; Santarpia, Libero; Biganzoli, Laura; Di Leo, Angelo

    2011-10-01

    Chemotherapy is the only evidence based adjuvant systemic treatment option in triple negative breast cancer (TNBC). Despite emerging results for targeted biological therapies for this subpopulation, lack of robust results does not currently support their use beyond the confines of a clinical trial. Conventional systemic chemotherapy remains the standard of care and is curative in a minority of patients. There is no defined standard chemotherapy and there is currently no robust, prospective, randomized data to advise different use of specific chemotherapy agents in TNBC as compared to non-TNBC. Data suggest high sensitivity to chemotherapy, however it is yet to be determined whether this increased sensitivity is agent/regimen specific or whether it reflects general chemosensitivity. This review will focus on systemic chemotherapy in early TNBC, particularly anthracyclines and platinums, and potential predictive tools to guide chemotherapy use. PMID:22015281

  9. Radiation Therapy Field Extent for Adjuvant Treatment of Axillary Metastases From Malignant Melanoma

    SciTech Connect

    Beadle, Beth M.; Guadagnolo, B. Ashleigh Ballo, Matthew T.; Lee, Jeffrey E.; Gershenwald, Jeffrey E.; Cormier, Janice N.; Mansfield, Paul F.; Ross, Merrick I.; Zagars, Gunar K.

    2009-04-01

    Purpose: To compare treatment-related outcomes and toxicity for patients with axillary lymph node metastases from malignant melanoma treated with postoperative radiation therapy (RT) to either the axilla only or both the axilla and supraclavicular fossa (extended field [EF]). Methods and Materials: The medical records of 200 consecutive patients treated with postoperative RT for axillary lymph node metastases from malignant melanoma were retrospectively reviewed. All patients received postoperative hypofractionated RT for high-risk features; 95 patients (48%) received RT to the axilla only and 105 patients (52%) to the EF. Results: At a median follow-up of 59 months, 111 patients (56%) had sustained relapse, and 99 patients (50%) had died. The 5-year overall survival, disease-free survival, and distant metastasis-free survival rates were 51%, 43%, and 46%, respectively. The 5-year axillary control rate was 88%. There was no difference in axillary control rates on the basis of the treated field (89% for axilla only vs. 86% for EF; p = 0.4). Forty-seven patients (24%) developed treatment-related complications. On both univariate and multivariate analyses, only treatment with EF irradiation was significantly associated with increased treatment-related complications. Conclusions: Adjuvant hypofractionated RT to the axilla only for metastatic malignant melanoma with high-risk features is an effective method to control axillary disease. Limiting the radiation field to the axilla only produced equivalent axillary control rates to EF and resulted in lower treatment-related complication rates.

  10. Breast cancer follow-up strategies in randomized phase III adjuvant clinical trials: a systematic review

    PubMed Central

    2013-01-01

    The effectiveness of different breast cancer follow-up procedures to decrease breast cancer mortality are still an object of debate, even if intensive follow-up by imaging modalities is not recommended by international guidelines since 1997. We conducted a systematic review of surveillance procedures utilized, in the last ten years, in phase III randomized trials (RCTs) of adjuvant treatments in early stage breast cancer with disease free survival as primary endpoint of the study, in order to verify if a similar variance exists in the scientific world. Follow-up modalities were reported in 66 RCTs, and among them, minimal and intensive approaches were equally represented, each being followed by 33 (50%) trials. The minimal surveillance regimen is preferred by international and North American RCTs (P = 0.001) and by trials involving more than one country (P = 0.004), with no relationship with the number of participating centers (P = 0.173), with pharmaceutical industry sponsorship (P = 0.80) and with trials enrolling > 1000 patients (P = 0.14). At multivariate regression analysis, only geographic location of the trial was predictive for a distinct follow-up methodology (P = 0.008): Western European (P = 0.004) and East Asian studies (P = 0.010) use intensive follow-up procedures with a significantly higher frequency than international RCTs, while no differences have been detected between North American and international RCTs. Stratifying the studies according to the date of beginning of patients enrollment, before or after 1998, in more recent RCTs the minimal approach is more frequently followed by international and North American RCTs (P = 0.01), by trials involving more than one country (P = 0.01) and with more than 50 participating centers (P = 0.02). It would be highly desirable that in the near future breast cancer follow-up procedures will be homogeneous in RCTs and everyday clinical settings. PMID:24438135

  11. A novel adjuvanted capsule based strategy for oral vaccination against infectious diarrhoeal pathogens.

    PubMed

    Davitt, Christopher J H; McNeela, Edel A; Longet, Stephanie; Tobias, Joshua; Aversa, Vincenzo; McEntee, Craig P; Rosa, Monica; Coulter, Ivan S; Holmgren, Jan; Lavelle, Ed C

    2016-07-10

    Diarrhoeal infections are a major cause of morbidity and mortality with enterotoxigenic Escherichia coli (ETEC) and cholera imposing a significant global burden. There is currently no licensed vaccine for ETEC. Development of new nonliving oral vaccines has proven difficult due to the physicochemical and immunological challenges associated with the oral route. This demands innovative delivery solutions to protect antigens, control their release and build in immune-stimulatory activity. We describe the Single Multiple Pill® (SmPill®) vaccine formulation which combines the benefits of enteric polymer coating to protect against low gastric pH, a dispersed phase to control release and aid the solubility of non-polar components and an optimized combination of adjuvant and antigen to promote mucosal immunity. We demonstrate the effectiveness of this system with whole cell killed E. coli overexpressing colonization factor antigen I (CFA/I), JT-49. Alpha-galactosylceramide was identified as a potent adjuvant within SmPill® that enhanced the immunogenicity of JT-49. The bacteria associated with the dispersed phase were retained within the capsules at gastric pH but released at intestinal pH. Vaccination with an optimized SmPill® formulation promoted CFA/I-specific immunoglobulin A (IgA) responses in the intestinal mucosa in addition to serum IgG and a solubilized adjuvant was indispensable for efficacy. PMID:27157995

  12. Adjuvants and immunization strategies to induce influenza virus hemagglutinin stalk antibodies.

    PubMed

    Goff, Peter H; Eggink, Dirk; Seibert, Christopher W; Hai, Rong; Martínez-Gil, Luis; Krammer, Florian; Palese, Peter

    2013-01-01

    The global population remains vulnerable in the face of the next pandemic influenza virus outbreak, and reformulated vaccinations are administered annually to manage seasonal epidemics. Therefore, development of a new generation of vaccines is needed to generate broad and persistent immunity to influenza viruses. Here, we describe three adjuvants that enhance the induction of stalk-directed antibodies against heterologous and heterosubtypic influenza viruses when administered with chimeric HA proteins. Addavax, an MF59-like nanoemulsion, poly(I:C), and an RNA hairpin derived from Sendai virus (SeV) Cantell were efficacious intramuscularly. The SeV RNA and poly(I:C) also proved to be effective respiratory mucosal adjuvants. Although the quantity and quality of antibodies induced by the adjuvants varied, immunized mice demonstrated comparable levels of protection against challenge with influenza A viruses on the basis of HA stalk reactivity. Finally, we present that intranasally, but not intramuscularly, administered chimeric HA proteins induce mucosal IgA antibodies directed at the HA stalk. PMID:24223176

  13. A Preliminary Evaluation of Fast ForWord-Language as an Adjuvant Treatment in Language Intervention

    PubMed Central

    Fey, Marc E.; Finestack, Lizbeth H.; Gajewski, Byron J.; Popescu, Mihai; Lewine, Jeffrey D.

    2010-01-01

    Purpose Fast ForWord-Language (FFW-L) is designed to enhance children's processing of auditory–verbal signals and, thus, their ability to learn language. As a preliminary evaluation of this claim, we examined the effects of a 5-week course of FFW-L as an adjuvant treatment with a subsequent 5-week conventional narrative-based language intervention (NBLI) that targeted narrative comprehension and production and grammatical output. Method Twenty-three children 6–8 years of age with language impairments were assigned randomly to 1 of 3 intervention sequences: (a) FFW-L/NBLI, (b) NBLI/FFW-L, or (c) wait/NBLI. We predicted that after both treatment periods, the FFW-L/NBLI group would show greater gains on measures of narrative ability, conversational grammar, and nonword repetition than the other groups. Results After the first 5-week study period, the intervention groups, taken together (i.e., FFW-L/NBLI and NBLI/FFW-L), significantly outperformed the no-treatment wait/NBLI group on 2 narrative measures. At the final test period, all 3 groups displayed significant time-related effects on measures of narrative ability, but there were no statistically significant between-groups effects of intervention sequence. Conclusions This preliminary study provides no evidence to support the claim that FFW-L enhances children's response to a conventional language intervention. PMID:19696435

  14. Trastuzumab re-treatment following adjuvant trastuzumab and the importance of distant disease-free interval: the HERA trial experience.

    PubMed

    Metzger-Filho, Otto; de Azambuja, Evandro; Procter, Marion; Krieguer, Magalie; Smith, Ian; Baselga, Jose; Cameron, David; Untch, Michael; Jackisch, Christian; Bell, Richard; Gianni, Luca; Goldhirsch, Aron; Piccart, Martine; Gelber, Richard D

    2016-01-01

    This retrospective analysis conducted using data from patients enrolled onto the Herceptin Adjuvant has two objectives: The first is to evaluate the impact of the time interval between the end of adjuvant trastuzumab and distant recurrence (TDRI) upon overall survival (OS). The second is to describe the duration of trastuzumab-based regimens in the metastatic setting for patients previously treated with adjuvant trastuzumab. The first objective included 187 patients treated with adjuvant trastuzumab and diagnosed with distant recurrence at 4-year median follow-up. The second objective included data from questionnaires sent to investigators retreating patients with trastuzumab upon distant recurrence: 144 of 156 questionnaires were returned (93 %), and 90 patients were selected based on available clinical information and consent for subsequent studies. There was no statistically significant relationship between TDRI following 1 year of adjuvant trastuzumab and OS from distant recurrence: hazard ratio 0.991, p = 0.46. The median OS from distant recurrence was numerically longer among patients with a TDRI of ≥12 months (n = 103) than <12 months (n = 84) but not statistically significant (23.7 vs. 17.8 months, p = 0.47). The median duration of first-line trastuzumab-based regimens for patients previously treated with adjuvant trastuzumab and diagnosed with distant disease recurrence was 8.8 months (n = 88). This retrospective, exploratory study suggests that TDRI did not impact on OS measured from distant recurrence. We argue that prospective collection of treatment information beyond disease progression should be included in future clinical studies. PMID:26708471

  15. Multimedia strategy considers waste treatment

    SciTech Connect

    Phillips, J.B.

    1995-05-01

    The advent of multimedia pollution prevention programs has raised some interesting and challenging questions on the subject of facility operations. First and foremost is the goal of a multimedia pollution prevention program: how can industrial streams in an operating facility be treated to prevent pollutants from escaping in a particular effluent or waste streams without transferring the same pollutants to another medium? Once this is resolved, the next issue to be addressed is the fate of pollutants removed from effluent streams. EPA is moving toward discouraging destruction as an acceptable means of waste treatment. The strategies are presented for handling pollutants from one media without contaminating another.

  16. Influence of Patient and Treatment Factors on Adherence to Adjuvant Endocrine Therapy in Breast Cancer

    PubMed Central

    Bender, Catherine M.; Gentry, Amanda L.; Brufsky, Adam M.; Casillo, Frances E.; Cohen, Susan M.; Dailey, Meredith M.; Donovan, Heidi S.; Dunbar-Jacob, Jacqueline; Jankowitz, Rachel C.; Rosenzweig, Margaret Q.; Sherwood, Paula R.; Sereika, Susan M.

    2014-01-01

    Purpose/Objectives To comprehensively assess the patient and illness or treatment factors that may predict nonadherence to adjuvant endocrine therapy and to explore whether an interaction occurs between these factors in women with breast cancer. Design Repeated-measures design. Setting The Outpatient Services of the Women's Cancer Program at the University of Pittsburgh Cancer Institute and participants' homes. Sample 91 women with early-stage breast cancer who received endocrine therapy. Methods Adherence was assessed continuously for the first 18 months of endocrine therapy. Patient and illness or treatment factors were assessed at four time points (Time 1 to Time 4). Time 1 (baseline) was within two weeks prior to the initiation of endocrine therapy. Times 2–4 occurred at six-month intervals, as many as 18 months after Time 1. Main Research Variables Adherence, patient factors, and illness or treatment factors. Findings Adherence to endocrine therapy declined significantly during the first 18 months of treatment in women with breast cancer. The presence of negative mood and symptoms before starting treatment predicted nonadherence to endocrine therapy over time. Perceptions of financial hardship, symptoms, disease stage, and more complex medication regimens intensified the effect of negative mood on adherence over time. Conclusions Women with breast cancer may be at risk for nonadherence to prescribed endocrine therapy if they experience depression or anxiety and symptoms prior to initiating therapy. Implications for Nursing Oncology nurses should be alert to women with breast cancer who are depressed or anxious or who are experiencing symptoms. Management of negative mood and symptoms may result in better adherence. PMID:24769592

  17. Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen.

    PubMed

    Markopoulos, Christos; Kykalos, Stylianos; Mantas, Dimitrios

    2014-08-10

    Biotransformation of tamoxifen to the potent antiestrogen endoxifen is performed by cytochrome P450 (CYP) enzymes, in particular the CYP2D6 isoform. CYP2D6*4 is one of the most frequent alleles associated with loss of enzymatic activity. The incidence of CYP2D6*4 among Caucasians is estimated up to 27%, while it is present in up to 90% of all poor metabolizers within the Caucasian population. The hypothesis under question is whether the presence of one or two non-functioning (null) alleles predicts an inferior outcome in postmenopausal women with breast cancer receiving adjuvant treatment with tamoxifen. The numerous existing studies investigating the association of CYP2D6 with treatment failure in breast cancer are inconsistent and give rather conflicting results. Currently, routine CYP2D6 testing among women with breast cancer is not recommended and the significance of CYP2D6 phenotype in decision making regarding the administration of tamoxifen is unclear. The present study summarizes current literature regarding clinical studies on CYP2D6*4, particularly in terms of response to tamoxifen therapy and breast cancer outcome. PMID:25114852

  18. Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen

    PubMed Central

    Markopoulos, Christos; Kykalos, Stylianos; Mantas, Dimitrios

    2014-01-01

    Biotransformation of tamoxifen to the potent antiestrogen endoxifen is performed by cytochrome P450 (CYP) enzymes, in particular the CYP2D6 isoform. CYP2D6*4 is one of the most frequent alleles associated with loss of enzymatic activity. The incidence of CYP2D6*4 among Caucasians is estimated up to 27%, while it is present in up to 90% of all poor metabolizers within the Caucasian population. The hypothesis under question is whether the presence of one or two non-functioning (null) alleles predicts an inferior outcome in postmenopausal women with breast cancer receiving adjuvant treatment with tamoxifen. The numerous existing studies investigating the association of CYP2D6 with treatment failure in breast cancer are inconsistent and give rather conflicting results. Currently, routine CYP2D6 testing among women with breast cancer is not recommended and the significance of CYP2D6 phenotype in decision making regarding the administration of tamoxifen is unclear. The present study summarizes current literature regarding clinical studies on CYP2D6*4, particularly in terms of response to tamoxifen therapy and breast cancer outcome. PMID:25114852

  19. Weight gain during adjuvant endocrine treatment for early-stage breast cancer: What is the evidence?

    PubMed

    Nyrop, K A; Williams, G R; Muss, H B; Shachar, S S

    2016-07-01

    Most breast cancer (BC) tumors are early stage and hormone receptor positive, where treatment generally includes adjuvant endocrine treatment (ET). Oncology providers and women about to start ET want to know about side effects, including potential weight gain. The aim of this study was a literature review to identify the independent effect of ET on post-diagnosis weight gain. Weight gain is of concern with regard to potential associations with BC recurrence, mortality, and quality of life in survivorship. We conducted a targeted review of the literature. Thirty-eight studies met our inclusion criteria. Patient-reported weight gain ranged widely from 18 to 52 % of patients in Year 1 and from 7 to 55 % in Year 5. Some studies reported categories of weight change: lost weight (9-17 %), stable weight (47-64 %), and gained weight (27-36 %). Most studies comparing ET with placebo or tamoxifen with AI reported no significant difference between the two groups. Wide-ranging and inconsistent results point to the need for further research to clarify annual weight change (loss, gain, stability) from BC diagnosis through 5 years of ET and beyond. There is also a need to explore weight change by type of ET and to explore risk factors for weight gain in women on ET, including tumor type, sociodemographic characteristics, and health behaviors. More specific information is needed to identify high-risk BC patients who could be targeted for weight management interventions. PMID:27342454

  20. Axillary radiotherapy: an alternative treatment option for adjuvant axillary management of breast cancer

    PubMed Central

    Zhang, Jie; Wang, Chuan

    2016-01-01

    Axillary lymph node dissection is standard management of axilla in invasive breast cancer. Radiotherapy also is important in local treatment. It is controversial as to whether axillary radiotherapy can displace axillary lymph node dissection. We performed a meta-analysis comparing axillary radiotherapy with axillary dissection. No significant difference was observed for disease free survival and overall survival between the radiation group and the dissection group. There was also no significant difference in either the axillary recurrence or the local recurrence between the two groups. But the axillary relapse rate in the radiation group was higher than in the surgery group at five-year follow-up while the local recurrence rate in the surgery group was higher than in the radiation group. A subgroup analysis showed that the difference in the axillary recurrence rate (RR = 0.20, P = 0.01) and local recurrence rate (RR = 4.7, P = 0.01) mainly appeared in the clinical node-positive subgroup. The edema rate in the surgery group was higher than in the radiation group (RR = 2.08, 95%: 1.71–2.54, P < 0.0001). We concluded that radiotherapy may be an alternative treatment option for adjuvant management of the axilla in selected sub-groups of patients. PMID:27212421

  1. Adjuvant chemotherapy for early-stage cervical cancer

    PubMed Central

    Asano, Hiroshi; Todo, Yukiharu; Watari, Hidemichi

    2016-01-01

    The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery (RS) has not yet been established, and radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life (QOL) or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival (OS) with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin (TP) regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group (GOG), had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial (RCT) of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable

  2. Treatment strategies for atopic dermatitis: optimizing the available therapeutic options.

    PubMed

    Paller, Amy S; Simpson, Eric L; Eichenfield, Lawrence F; Ellis, Charles N; Mancini, Anthony J

    2012-09-01

    Bathing and moisturization to control dryness, applications of topical anti-inflammatory agents (including corticosteroids and calcineurin inhibitors [TCIs]) to control flares, minimization of the risk for infection, and relief of pruritus are the cornerstones of effective therapy for atopic dermatitis. Education of parents and patients is crucial to enhance adherence. Strategies for reduced Staphylococcus aureus colonization may help control re-emergence of flares following cessation of antimicrobial treatment for infection; these include dilute bleach baths and minimizing the risk for contamination of topical agents. In severe, refractory cases, more aggressive therapy with systemic immunosuppressants may be considered, but appropriate laboratory testing must be included as part of patient monitoring during treatment. The value of adjuvant therapy with wet wraps to "cool down" particularly erythematous and pruritic flares is becoming increasingly recognized. PMID:23021780

  3. Hybrid curcumin compounds: a new strategy for cancer treatment.

    PubMed

    Teiten, Marie-Hélène; Dicato, Mario; Diederich, Marc

    2014-01-01

    Cancer is a multifactorial disease that requires treatments able to target multiple intracellular components and signaling pathways. The natural compound, curcumin, was already described as a promising anticancer agent due to its multipotent properties and huge amount of molecular targets in vitro. Its translation to the clinic is, however, limited by its reduced solubility and bioavailability in patients. In order to overcome these pharmacokinetic deficits of curcumin, several strategies, such as the design of synthetic analogs, the combination with specific adjuvants or nano-formulations, have been developed. By taking into account the risk-benefit profile of drug combinations, as well as the knowledge about curcumin's structure-activity relationship, a new concept for the combination of curcumin with scaffolds from different natural products or components has emerged. The concept of a hybrid curcumin molecule is based on the incorporation or combination of curcumin with specific antibodies, adjuvants or other natural products already used or not in conventional chemotherapy, in one single molecule. The high diversity of such conjugations enhances the selectivity and inherent biological activities and properties, as well as the efficacy of the parental compound, with particular emphasis on improving the efficacy of curcumin for future clinical treatments. PMID:25514225

  4. Autophagy and mitochondrial dysfunction in adjuvant-arthritis rats treatment with resveratrol

    PubMed Central

    Zhang, Junqiang; Song, Xianbin; Cao, Wei; Lu, Jinseng; Wang, Xiaoqing; Wang, Gaoyuan; Wang, Zhicheng; Chen, Xiaoyu

    2016-01-01

    Resveratrol is a polyphenol derivatives which exhibits a pro-apoptotic effect in a variety of human cancers by triggering mitochondria apoptosis pathway and autophagy. However, there are scarcely reports on its apoptosis-promoting effect in abnormal proliferation fibroblast-like synoviocytes (FLSs). In this study, we investigated the underlying mechanism and apoptosis-inducing effects of resveratrol on the abnormal proliferation of FLSs in adjuvant-arthritis (AA) rats. Since using resveratrol for 12 days resulted in a significant decreasing the swelling degree of the paw, reducing malondialdehyde (MDA) content and enhancing superoxide dismutase (SOD) activity, antioxidant capacity, glutathione peroxidase and glutathione reductase ratio in AA rats. Moreover, we found that 5 μMH2O2 could increase cells viability, Beclin1, LC3A/B, MnSOD, SIRT3 protein expression in FLSs. But, resveratrol could reverse these effects by changing mitochondrial membrane potential (Δψm) to promote mitochondrial reactive oxygen species (mtROS) generation in 5 μMH2O2-treatment FLSs. These results suggest that oxidative stress existed in AA rats. Resveratrol could suppress oxidative stress in AA rats and increase mtROS production by reducing autophagy protein Beclin1, LC3A/B and oxidative stress protein MnSOD to promoted the apoptosis of FLSs. Thus, targeting of mtROS may be a crucial mechanism of resveratrol confers patients with rheumatoid arthritis. PMID:27611176

  5. A Phase I study of concurrent radiotherapy and capecitabine as adjuvant treatment for operable rectal cancer

    SciTech Connect

    Jin Jing

    2006-03-01

    Purpose: To determine the maximum tolerated dose and the dose-limiting toxicity of capecitabine with standard radiotherapy (RT) as adjuvant treatment in patients with rectal cancer. Methods and Materials: Patients with Stage II/III rectal cancer after surgery were eligible. Total RT dose was delivered as DT 50 Gy in fractions of 2.0 Gy/day for 5 weeks to the pelvic area. Capecitabine was administered concurrently with RT in escalating doses, twice daily with a 12-h interval, for two cycles of 14 days separated by a 7-day rest. Dose-limiting toxicity included Grade 3 or Grade 4 hematologic and nonhematologic toxicity. Results: Twenty-four patients were enrolled at the following dose levels: 1,000 (3 patients), 1,200 (3 patients), 1,400 (3 patients), 1,500 (3 patients), 1,600 (6 patients), and 1,700 mg/m{sup 2}/day (6 patients). Dose-limiting toxicity was observed in 1 patient at 1,600 mg/m{sup 2}/day (Grade 3 diarrhea) and in 2 patients at 1,700 mg/m{sup 2}/day (1 patient had Grade 3 and 1 Grade 4 diarrhea). Conclusion: The maximum tolerated dose (MTD) of capecitabine given concurrently with RT was 1,600 mg/m{sup 2}, daily from the 1st to the 14th day, with a 7-day rest, for two cycles.

  6. Autophagy and mitochondrial dysfunction in adjuvant-arthritis rats treatment with resveratrol.

    PubMed

    Zhang, Junqiang; Song, Xianbin; Cao, Wei; Lu, Jinseng; Wang, Xiaoqing; Wang, Gaoyuan; Wang, Zhicheng; Chen, Xiaoyu

    2016-01-01

    Resveratrol is a polyphenol derivatives which exhibits a pro-apoptotic effect in a variety of human cancers by triggering mitochondria apoptosis pathway and autophagy. However, there are scarcely reports on its apoptosis-promoting effect in abnormal proliferation fibroblast-like synoviocytes (FLSs). In this study, we investigated the underlying mechanism and apoptosis-inducing effects of resveratrol on the abnormal proliferation of FLSs in adjuvant-arthritis (AA) rats. Since using resveratrol for 12 days resulted in a significant decreasing the swelling degree of the paw, reducing malondialdehyde (MDA) content and enhancing superoxide dismutase (SOD) activity, antioxidant capacity, glutathione peroxidase and glutathione reductase ratio in AA rats. Moreover, we found that 5 μMH2O2 could increase cells viability, Beclin1, LC3A/B, MnSOD, SIRT3 protein expression in FLSs. But, resveratrol could reverse these effects by changing mitochondrial membrane potential (Δψm) to promote mitochondrial reactive oxygen species (mtROS) generation in 5 μMH2O2-treatment FLSs. These results suggest that oxidative stress existed in AA rats. Resveratrol could suppress oxidative stress in AA rats and increase mtROS production by reducing autophagy protein Beclin1, LC3A/B and oxidative stress protein MnSOD to promoted the apoptosis of FLSs. Thus, targeting of mtROS may be a crucial mechanism of resveratrol confers patients with rheumatoid arthritis. PMID:27611176

  7. Efficacy and Interaction of Antioxidant Supplements as Adjuvant Therapy in Cancer Treatment: A Systematic Review.

    PubMed

    Yasueda, Asuka; Urushima, Hayato; Ito, Toshinori

    2016-03-01

    Oxidative stress is a key component in carcinogenesis. Although radiation produces reactive oxygen species, some anticancer agents such as alkylating agents, platinum and antitumor antibiotics exert cytotoxicity by generating free radicals. Nonenzymatic exogenous antioxidants such as vitamins, minerals, and polyphenols can quench ROS activity. However, whether antioxidants alter antitumor effects during radiotherapy and some types of chemotherapy remains unclear. In the present study, we reviewed antioxidants as an adjuvant therapy for cancer patients during chemotherapy or radiotherapy. Electronic literature searches were performed to select all randomized controlled clinical trials (RCTs) in which antioxidants were administered to cancer patients along with chemotherapy or radiotherapy. Articles or abstracts written in English were included. In total, 399 reports received primary screening. Duplicated articles and those meeting the exclusion criteria (not RCT, not human, and no oral administration) were excluded. Finally, 49 reports matching the inclusion criteria were included. It was difficult to determine whether antioxidants affect treatment outcomes or whether antioxidants ameliorate adverse effects induced by chemotherapy and radiotherapy. It is desirable to use an evidence-based method to select supplements best suited to cancer patients. Although there are many opinions about risks or benefits of antioxidant supplementation, we could mostly conclude that the harm caused by antioxidant supplementation remains unclear for patients during cancer therapy, except for smokers undergoing radiotherapy. PMID:26503419

  8. Economic comparison of capecitabine + oxaliplatin and 5-fluorouracil + oxaliplatin in the adjuvant treatment of colon cancer

    PubMed Central

    Aitini, Enrico; Rossi, Anna; Morselli, Patrizia; Vivorio, Beatrice; Bruschi, Alessandra; Bottura, Chiara; Colombo, Giorgio L

    2012-01-01

    Background Colorectal cancer is one of the most frequent and lethal cancers. The aim of this study was to analyze the costs relating to treatment of colorectal cancer between Xelox and Folfox-4 at a regional level according to the clinical experience at an Italian hospital in Lombardy. Methods A cost analysis was carried out regarding resource consumption by patients suffering from colorectal cancer based on data collected over a 12-month period between 2010 and 2011. The analysis involved 40 patients who attended the Department of Medical Oncology and Hematology at Carlo Poma Hospital to undergo adjuvant therapy for colorectal cancer. A chart was created for each patient containing their medical history, their pharmacological therapy indicating the number and duration of chemotherapy cycles, dose in mg administered for each cycle, number of day hospital visits for each cycle, number of days spent in hospital to position the central vein catheter, type of infusion pump used, any subsequent supportive therapy, and any side effects and outpatient visits connected with side effects. Results The cost analysis shows the savings involved in using Xelox for a single cycle of treatment, ie, approximately €1414.00 per patient (53% compared with Folfox-4). For each single cycle of treatment, the savings generated by using capecitabine compared with 5-FU can be attributed mostly to the fact that oral administration of chemotherapy requires fewer resources and does not require use of a central vein catheter (approximately 70% of overall cost) which amply compensates for the higher cost of capecitabine compared with 5-FU-LV. Sensibility analysis confirms the results of the base-case scenario. Conclusion The results of our study indicate that infusion via a central vein catheter represents a significant cost, and that substitution with an oral therapy, even when associated with drugs administered intravenously, represents a consistent saving of hospital resources. PMID

  9. Surgical Excision with Adjuvant Irradiation for Treatment of Keloid Scars: A Systematic Review

    PubMed Central

    Stokmans, Suzanne C.; Bulstra, Anne Eva J.; Meijer, Otto W. M.; Heymans, Martijn W.; Ket, Johannes C. F.; Ritt, Marco J. P. F.; van Leeuwen, Paul A. M.; Niessen, Frank B.

    2015-01-01

    Background: Excision followed by adjuvant irradiation is considered safe and most efficacious for treatment of keloid scars. Recently, different authors published successful treatment protocols and recommended the following: (1) the use of high-dose-rate brachytherapy instead of low-dose-rate brachytherapy or external radiation; (2) a short-time interval between operation and irradiation; (3) single fraction instead of multifraction irradiation; and (4) a minimum of 12- to 24-month follow-up post treatment. Methods: This study evaluates the above recommendations with a systematic review of the English-language literature, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Both PubMed and EMBASE were searched. Studies were graded according to the American Society of Plastic Surgeons Rating Levels of Evidence. Results: Thirty-three studies were selected. Six studies were graded as level of evidence type II studies and 27 as type III. High-dose-rate brachytherapy showed lower recurrence rates compared with low-dose-rate brachytherapy and external radiation. A short-time (<7 hours) interval between scar excision and irradiation results in a lower recurrence rate compared with long-time intervals (>24 hours). Single-fraction irradiation showed promising results in terms of recurrence rate and patient convenience. Finally, scar recurrences were seen between 2 and 36 months, with a mean of 15 months. Conclusions: Based on this systematic review of the literature, the evidence confirms the recommendations stated by authors in the recent years. However, due to the lack of high-quality randomized studies, the quality of this evidence is limited. More randomized studies will generate stronger recommendations. PMID:26301129

  10. Adjuvant chemotherapy after primary treatments for cervical cancer: a critical point of view and review of the literature.

    PubMed

    Angioli, Roberto; Luvero, Daniela; Aloisi, Alessia; Capriglione, Stella; Gennari, Paolo; Linciano, Francesca; Li Destri, Marta; Scaletta, Giuseppe; Montera, Roberto; Plotti, Francesco

    2014-04-01

    Cervical cancer is the second most frequent female malignancy worldwide. Concurrent chemoradiotherapy represents the standard of care for patients with advanced stage cervical cancer, while radical surgery (RS) and radiotherapy is widely used for treating early stage cervical cancer. However, the poor control of micrometastasis, declining operability, the lack of radiotherapy departments and the high incidence of long-term complications due to radiotherapy have brought about the development of different therapeutic approaches such as neoadjuvant chemotherapy followed by RS. Unfortunately, treatment results are still unsatisfactory due to a high recurrence rate and several authors have studied the possibility to add an adjuvant treatment to primary therapy. We reviewed the literature concerning the role of adjuvant chemotherapy in advanced cervical cancer after neoadjuvant chemotherapy followed by RS and after chemoradiotherapy. PMID:24483847

  11. Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100- Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies

    PubMed Central

    Liu, Heng; Patil, Harshad P.; de Vries-Idema, Jacqueline; Wilschut, Jan; Huckriede, Anke

    2013-01-01

    Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN) or the intrapulmonary (IPL) route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses. PMID:23936066

  12. Trends in vaccine adjuvants.

    PubMed

    Schijns, Virgil E J C; Lavelle, Ed C

    2011-04-01

    Adjuvants are essential components of most clinically used vaccines. This is because the majority of nonliving vaccines are relatively poor inducers of adaptive immunity unless effective adjuvants are co-administered. Aluminum salts (alum) have been used as adjuvants with great success for almost a century and have been particularly effective at promoting protective humoral immunity. However, alum is not optimally effective for diseases where cell-mediated immunity is required for protection. Furthermore, adjuvants including oil-in-water emulsions have shown improved efficacy for avian influenza protection suggesting that even for diseases where humoral immunity can confer protection, there is scope for developing improved adjuvants. There have been major developments in antigen discovery over the past decade, which has accelerated the vaccine development process for new indications and this demands a new generation of adjuvants that can drive and specifically direct the desired immune responses. A number of systems are under investigation that combine different types of adjuvants into specific formulations with greater activity. Additionally, targeting of vaccines to specific immune cells shows great promise. In the case of cancer and chronic infectious diseases, it may be difficult to develop effective vaccines without blocking immune regulatory pathways, which impede cell-mediated responses. However, increased understanding of immunology and particularly the innate immune system is informing vaccine adjuvant research and consequently driving the development of novel and specifically directed vaccine adjuvant strategies. In this article we address the importance of adjuvants in vaccine development, the known mode of action of specific adjuvants and recent developments in this important field. PMID:21506650

  13. Splenomegaly and Its Associations with Genetic Polymorphisms and Treatment Outcome in Colorectal Cancer Patients Treated with Adjuvant FOLFOX

    PubMed Central

    Kim, Mi-Jung; Han, Sae-Won; Lee, Dae-Won; Cha, Yongjun; Lee, Kyung-Hun; Kim, Tae-Yong; Oh, Do-Youn; Kim, Se Hyung; Im, Seock-Ah; Bang, Yung-Jue; Kim, Tae-You

    2016-01-01

    Purpose Splenomegaly is a clinical surrogate of oxaliplatin-induced sinusoidal obstruction syndrome (SOS). We investigated development of splenomegaly and its association with treatment outcome and genetic polymorphisms following adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in colorectal cancer (CRC) patients. Materials and Methods Splenomegaly was determined by spleen volumetry using computed tomography images obtained before initiation of chemotherapy and after completion of adjuvant FOLFOX in CRC patients. Ten genetic polymorphisms in 4 SOS-related genes (VEGFA, MMP9, NOS3, and GSTP1) were analyzed using DNA from peripheral blood mononuclear cells. Results Of 124 patients included, increase in spleen size was observed in 109 (87.9%). Median change was 31% (range, –42% to 168%). Patients with splenomegaly had more severe thrombocytopenia compared to patients without splenomegaly during the chemotherapy period (p < 0.0001). The cumulative dose of oxaliplatin and the lowest platelet count during the chemotherapy period were clinical factors associated with splenomegaly. However, no significant associations were found between genetic polymorphisms and development of splenomegaly. Disease-free survival was similar regardless of the development of splenomegaly. Conclusion Splenomegaly was frequently observed in patients receiving adjuvant FOLFOX and resulted in more severe thrombocytopenia but did not influence treatment outcome. Examined genetic polymorphisms did not predict development of splenomegaly. PMID:26790967

  14. Oral clodronate for adjuvant treatment of operable breast cancer (National Surgical Adjuvant Breast and Bowel Project protocol B-34): a multicentre, placebo-controlled, randomised trial

    PubMed Central

    Paterson, Alexander H G; Anderson, Stewart J; Lembersky, Barry C; Fehrenbacher, Louis; Falkson, Carla I; King, Karen M; Weir, Lorna M; Brufsky, Adam M; Dakhil, Shaker; Lad, Thomas; Baez-Diaz, Luis; Gralow, Julie R; Robidoux, André; Perez, Edith A; Zheng, Ping; Geyer, Charles E; Swain, Sandra M; Costantino, Joseph P; Mamounas, Eleftherios P; Wolmark, Norman

    2016-01-01

    Summary Background Bisphosphonates are thought to act through the osteoclast by changing bone microenvironment. Previous findings of adjuvant clodronate trials in different populations with operable breast cancer have been mixed. The National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-34 aims to ascertain whether oral clodronate can improve outcomes in women with primary breast cancer. Methods NSABP B-34 is a multicentre, randomised, double-blind, placebo-controlled study in 3323 women with stage 1–3 breast cancer. After surgery to remove the tumour, patients were stratified by age, axillary nodes, and oestrogen and progesterone receptor status and randomly assigned in a 1:1 ratio to either oral clodronate 1600 mg daily for 3 years (n=1662) or placebo (1661). The primary endpoint was disease-free survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00009945. Findings Median follow-up was 90·7 months (IQR 82·7–100·0) and 3311 patients had data for this period. Disease-free survival did not differ between groups (286 events in the clodronate group vs 312 in the placebo group; hazard ratio 0·91, 95% CI 0·78–1·07; p=0·27). Moreover, no differences were recorded for overall survival (0·84, 0·67–1·05; p=0·13), recurrence-free interval (0·83, 0·67–1·04; p=0·10), or bone metastasis-free interval (0·77, 0·55–1·07; p=0·12). Non-bone metastasis-free interval was slightly increased with clodronate (0·74, 0·55–1·00; p=0·047). Analyses in women age 50 years or older on study entry showed benefits of clodronate for recurrence-free interval (0·75, 0·57–0·99; p=0·045), bone metastasis-free interval (0·62, 0·40–0·95; p=0·027), and non-bone metastasis-free interval (0·63, 0·43–0·91; p=0·014), but not for overall survival (0·80, 0·61–1·04, p=0·094). Adherence to treatment at 3 years was 56% for the clodronate group and 60% for the placebo group. Grade 3 or

  15. Oral Zinc Sulfate as Adjuvant Treatment in Children With Nephrolithiasis: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial

    PubMed Central

    Yousefichaijan, Parsa; Cyrus, Ali; Dorreh, Fatemeh; Rafeie, Mohammad; Sharafkhah, Mojtaba; Frohar, Faryar; Safi, Fatemeh

    2015-01-01

    Background: Nephrolithiasis in children is associated with a high rate of complications and recurrence. Objectives: Since some evidences reported that zinc has an important place amongst inhibitors of crystallization and crystal growth, we decided to assess the effectiveness of oral zinc sulfate as adjuvant treatment in children with nephrolithiasis. Patients and Methods: This was a randomized, double-blind, placebo-controlled clinical trial. 102 children in the age range 1 month to 11 years with first nephrolithiasis were recruited. Patients were randomly divided into two equal groups (intervention and control groups). Intervention group received conservative measures for stones and 1 mg/kg/day (maximum 20 mg/day) oral zinc sulfate syrup for 3 months. Control group received placebo in addition to conservative measures, also for 3 months. Patients were followed up by ultrasonography for 9 months, in 5 steps (at the end of 1st, 2nd, 3rd, 6th and 9th month after treatment) assessing size and number of stones in the kidneys. Results: Only at the end of the first month, the average number (intervention: 1.15 ± 3.78, control: 1.3 ± 2.84) (P = 0.001) and size (cm) (intervention: 0.51 ± 1.76, control: 0.62 ± 1.39) (P = 0.001) of stones was significantly lower in the intervention group, and in other points there was no significant therapeutic efficacy in oral zinc adjuvant treatment compared to conservative treatment alone. Also, during the 9-month follow-up, the number and size of stones in both groups decreased significantly (both: P < 0.0001) in a way that the decrease in the intervention group showed no difference with the control group. Conclusions: Adjuvant treatment with zinc is not more effective than consecutive treatment in children with nephrolithiasis. However, further studies are recommended due to the lack of clinical evidence in this field. PMID:26635934

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

    PubMed Central

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

    2014-01-01

    Background: The beneficial role of cabergoline as a prophylactic agent to prevent ovarian hyper stimulation syndrome (OHSS) among high-risk patients has been demonstrated in previous studies. But data for its role as a treatment for established severe OHSS is still limited. We represent the treatment results of high dose oral cabergoline in management of six patients after the syndrome is established. Case: High-dose oral cabergoline (1 mg daily for eight days) was prescribed as an adjuvant to symptomatic treatment for six hospitalized patients with established severe OHSS following infertility treatment cycles. In two cases OHSS resolved rapidly despite the occurrence of ongoing pregnancy. Conclusion: Considering the treatment outcomes of our patients, high dose cabergoline did not eliminate the need for traditional treatments, but it was a relatively effective and safe therapy in management of established severe OHSS, and prevented the increase in its severity following the occurrence of pregnancy. PMID:25469130

  17. Systemic adjuvant therapies in renal cell carcinoma.

    PubMed

    Buti, Sebastiano; Bersanelli, Melissa; Donini, Maddalena; Ardizzoni, Andrea

    2012-10-01

    Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC. PMID:25992216

  18. Eugenia punicifolia (Kunth) DC. as an adjuvant treatment for type-2 diabetes mellitus: a non-controlled, pilot study.

    PubMed

    Sales, Débora Simone; Carmona, Fabio; de Azevedo, Bruna Cestari; Taleb-Contini, Silvia Helena; Bartolomeu, Ana Carolina Duó; Honorato, Fernando B; Martinez, Edson Z; Pereira, Ana Maria Soares

    2014-12-01

    Type-2 diabetes mellitus (DM) is a highly prevalent disease with significant morbidity and mortality around the world. However, there is no universally effective treatment, because response to different treatment regimens can vary widely among patients. In this study, we aimed to investigate whether the use of the powdered dried leaves of Eugenia punicifolia (Kunth) DC. (Myrtaceae) is effective as an adjuvant to the treatment of patients with type-2 DM. Fifteen patients were enrolled in a pilot, non-controlled study, and received E. punicifolia for 3 months. After treatment, we observed a significant decrease in glycosylated hemoglobin, basal insulin, thyroid-stimulating hormone, C-reactive protein, and both systolic and diastolic blood pressure. There were no changes in fasting and postprandial glycemia. The compounds myricetin-3-O-rhamnoside, quercetin-3-O-galactoside, quercetin-3-O-xyloside, quercetin-3-O-rhamnoside, kaempferol-3-O-rhamnoside, phytol, gallic acid, and trans-caryophyllene present in the powdered dried leaves of E. punicifolia may be responsible for the therapeutic effect. In conclusion, the powdered leaves of E. punicifolia are promising as an adjuvant in the treatment of type-2 DM and deserve further investigation. PMID:25132112

  19. Improved Survival Endpoints With Adjuvant Radiation Treatment in Patients With High-Risk Early-Stage Endometrial Carcinoma

    SciTech Connect

    Elshaikh, Mohamed A.; Vance, Sean; Suri, Jaipreet S.; Mahan, Meredith; Munkarah, Adnan

    2014-02-01

    Purpose/Objective(s): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. Methods and Materials: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. Results: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years. All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. Conclusion: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial carcinoma

  20. The effects of postoperative adjuvant chemotherapy and radiotherapy on testicular function in men undergoing treatment for soft tissue sarcoma

    SciTech Connect

    Shamberger, R.C.; Sherins, R.J.; Rosenberg, S.A.

    1981-05-15

    Testicular function was studied in 26 men with sarcoma who received adjuvant treatment with doxorubicin, cyclophosphamide, and high-dose methotrexate (with or without radiotherapy). Testicular size, sperm output, and serum FSH, LH and testosterone levels were assessed after treatment. Five of 17 men who received chemotherapy or chemotherapy with radiotherapy to the neck, arm, chest, or leg, had normal testicular function. Eight of the remaining 12 men who provided ejaculates were oligospermic or azoospermic and serum FSH was increased threefold and LH twofold; testosterone levels were normal. In the five men with normal testicular function, FSH was increased fourfold during therapy but returned to normal six to 21 months after treatment. In men less than 40 years old, the mean FSH was less than that of men over 40 years of age (P . to 0.05), suggesting that recovery from the injury was age-related. By contrast, all nine men who received chemotherapy plus radiotherapy to the abdomen or thigh had decreased testicular size, azoospermia, fourfold increase in FSH, and twofold increase in LH levels; but testosterone concentration was normal. These data increase in FSH, and reversible testicular injury occurs after treatment with doxorubicin, cyclophosphamide, and high-dose methotrexate; recovery is age-related. However, these agents in combination with use of adjuvant radiotherapy to the thigh or abdomen may produce permanent testicular injury even in young patients.

  1. Meta-analysis of trials comparing anastrozole and tamoxifen for adjuvant treatment of postmenopausal women with early breast cancer

    PubMed Central

    Aydiner, Adnan; Tas, Faruk

    2008-01-01

    Objective It was aimed to review the literature and make a meta-analysis of the trials on both upfront, switching, and sequencing anastrozole in the adjuvant treatment of early breast cancer. Methods The PubMed, ClinicalTrials.gov and Cochrane databases were systematically reviewed for randomized-controlled trials comparing anastrozole with tamoxifen in the adjuvant treatment of early breast cancer. Results The combined hazard rate of 4 trials for event-free survival (EFS) was 0.77 (95%CI: 0.70–0.85) (P < 0.0001) for patients treated with anastrozole compared with tamoxifen. In the second analysis in which only ITA, ABCSG 8, and ARNO 95 trials were included and ATAC (upfront trial) was excluded, combined hazard rate for EFS was 0.64 (95%CI: 0.52–0.79) (P < 0.0001). In the third analysis including hazard rate for recurrence-free survival (excluding non-disease related deaths) of estrogen receptor-positive patients for ATAC trial and hazard rate for EFS of all patients for the rest of the trials, combined hazard rate was 0.73 (95%CI: 0.65–0.81) (P < 0.0001). Conclusion Anastrozole appears to have superior efficacy than tamoxifen in the adjuvant hormonal treatment of early breast cancer. Until further clinical evidence comes up, aromatase inhibitors should be the initial hormonal therapy in postmenopausal early breast cancer patients and switching should only be considered for patients who are currently receiving tamoxifen. PMID:18664277

  2. Bioactivity of Polyphenols: Preventive and Adjuvant Strategies toward Reducing Inflammatory Bowel Diseases—Promises, Perspectives, and Pitfalls

    PubMed Central

    Kaulmann, Anouk

    2016-01-01

    Inflammatory bowel diseases (IBDs) are characterized by autoimmune and inflammation-related complications of the large intestine (ulcerative colitis) and additional parts of the digestive tract (Crohn's disease). Complications include pain, diarrhoea, chronic inflammation, and cancer. IBD prevalence has increased during the past decades, especially in Westernized countries, being as high as 1%. As prognosis is poor and medication often ineffective or causing side effects, additional preventive/adjuvant strategies are sought. A possible approach is via diets rich in protective constituents. Polyphenols, the most abundant phytochemicals, have been associated with anti-inflammatory, antioxidant, immunomodulatory, and apoptotic properties. Locally reducing oxidative stress, they can further act on cellular targets, altering gene expression related to inflammation, including NF-κB, Nrf-2, Jak/STAT, and MAPKs, suppressing downstream cytokine formation (e.g., IL-8, IL-1β, and TNF-α), and boosting the bodies' own antioxidant status (HO-1, SOD, and GPx). Moreover, they may promote, as prebiotics, healthy microbiota (e.g., Bifidobacteria, Akkermansia), short-chain fatty acid formation, and reduced gut permeability/improved tight junction stability. However, potential adverse effects such as acting as prooxidants, or perturbations of efflux transporters and phase I/II metabolizing enzymes, with increased uptake of undesired xenobiotics, should also be considered. In this review, we summarize current knowledge around preventive and arbitrary actions of polyphenols targeting IBD. PMID:27478535

  3. Bioactivity of Polyphenols: Preventive and Adjuvant Strategies toward Reducing Inflammatory Bowel Diseases-Promises, Perspectives, and Pitfalls.

    PubMed

    Kaulmann, Anouk; Bohn, Torsten

    2016-01-01

    Inflammatory bowel diseases (IBDs) are characterized by autoimmune and inflammation-related complications of the large intestine (ulcerative colitis) and additional parts of the digestive tract (Crohn's disease). Complications include pain, diarrhoea, chronic inflammation, and cancer. IBD prevalence has increased during the past decades, especially in Westernized countries, being as high as 1%. As prognosis is poor and medication often ineffective or causing side effects, additional preventive/adjuvant strategies are sought. A possible approach is via diets rich in protective constituents. Polyphenols, the most abundant phytochemicals, have been associated with anti-inflammatory, antioxidant, immunomodulatory, and apoptotic properties. Locally reducing oxidative stress, they can further act on cellular targets, altering gene expression related to inflammation, including NF-κB, Nrf-2, Jak/STAT, and MAPKs, suppressing downstream cytokine formation (e.g., IL-8, IL-1β, and TNF-α), and boosting the bodies' own antioxidant status (HO-1, SOD, and GPx). Moreover, they may promote, as prebiotics, healthy microbiota (e.g., Bifidobacteria, Akkermansia), short-chain fatty acid formation, and reduced gut permeability/improved tight junction stability. However, potential adverse effects such as acting as prooxidants, or perturbations of efflux transporters and phase I/II metabolizing enzymes, with increased uptake of undesired xenobiotics, should also be considered. In this review, we summarize current knowledge around preventive and arbitrary actions of polyphenols targeting IBD. PMID:27478535

  4. Effects of postoperative adjuvant chemotherapy and radiotherapy on testicular function in men undergoing treatment for soft tissue sarcoma

    SciTech Connect

    Shamberger, R.C.; Sherins, R.J.; Rosenberg, S.A.

    1981-05-15

    Testicular function was studied in 26 men with sarcoma who received adjuvant treatment with doxorubicin, cyclophosphamide, and high-dose methotrexate (with or without radiotherapy). Testicular size, sperm output, and serum FSH, LH and testosterone levels were assessed after treatment. Five of 17 men who received chemotherapy or chemotherapy with radiotherapy to the neck, arm, chest or leg, had normal testicular function. Eight of the remaining 12 men who provided ejaculates were oligospermic or azoospermic and serum FSH was increased threefold and LH twofold; testosterone levels were normal. In men less than 40 years old, the mean FSH level was less than that of men over 40 years of age (P = 0.05), suggesting that recovery from the injury was age-related. By contrast, all nine men who received chemotherapy plus radiotherapy to the abdomen or thigh had decreased testicular size, azoospermia, fourfold increase in FSH, and twofold increase in LH levels; but testosterone concentration was normal. These data indicate that reversible testicular injury occurs after treatment with doxorubicin, cyclophosphamide, and high-dose methotrexate; recovery is age-related. However, these agents in combination with use of adjuvant radiotherapy to the thigh or abdomen may produce permanent testicular injury even in young patients.

  5. Evidence-based Management Strategies for Treatment of Chronic Wounds

    PubMed Central

    Werdin, Frank; Tennenhaus, Mayer; Schaller, Hans-Eberhardt; Rennekampff, Hans-Oliver

    2009-01-01

    The care and management of patients with chronic wounds and their far-reaching effects challenge both the patient and the practitioner. Further complicating this situation is the paucity of evidence-based treatment strategies for chronic wound care. After searching both MEDLINE and Cochrane databases, we reviewed currently available articles concerning chronic wound care. Utilizing this information, we have outlined a review of current, evidence-based concepts as they pertain to the treatment of chronic wounds, focusing on fundamental treatment principles for the management of venous, arterial, diabetic, and pressure ulcers. Individualized treatment options as well as general wound management principles applicable to all varieties of chronic wounds are described. Classification and treatment guidelines as well as the adoption of the TIME acronym facilitate an organized conceptional approach to wound care. In so doing, individual aspects of generalized wound care such as debridement, infection, and moisture control as well as attention to the qualities of the wound edge are comprehensively evaluated, communicated, and addressed. Effective adjuvant agents for the therapy of chronic wounds including nutritional and social support measures are listed, as is a brief review of strategies helpful for preventing recurrence. An appreciation of evidence-based treatment pathways and an understanding of the pathophysiology of chronic wounds are important elements in the management of patients with chronic wounds. To achieve effective and long-lasting results, a multidisciplinary approach to patient care, focused on the education and coordination of patient, family as well as medical and support staff can prove invaluable. PMID:19578487

  6. Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

    SciTech Connect

    Twu, Chih-Wen; Wang, Wen-Yi; Chen, Chien-Chih; Liang, Kai-Li; Jiang, Rong-San; Wu, Ching-Te; Shih, Yi-Ting; Lin, Po-Ju; Liu, Yi-Chun; Lin, Jin-Ching

    2014-05-01

    Purpose: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. Methods and Materials: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Results: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Conclusions: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.

  7. Intravitreal Ranibizumab Injection as an Adjuvant in the Treatment of Neovascular Glaucoma Accompanied by Vitreous Hemorrhage after Diabetic Vitrectomy

    PubMed Central

    Shen, Xi; Chen, Yanwei; Wang, Yanuo; Yang, Lu; Zhong, Yisheng

    2016-01-01

    Purpose. To determine the efficacy of intravitreal ranibizumab injection as adjuvant therapy in the treatment of neovascular glaucoma (NVG) accompanied by postvitrectomy diabetic vitreous hemorrhage (PDVH). Methods. Eighteen NVG patients (18 eyes) accompanied by PDVH were enrolled in this prospective, monocenter, 12-month, interventional case series. The consecutive 18 patients with an IOP ≥ 25 mmHg despite being treated with the maximum medical therapy were treated with intravitreal ranibizumab injections. Vitreous surgery or/with Ahmed valve implantation were indicated if no clinical improvement in vitreous haemorrhage and uncontrolled IOP was shown. Results. Ten patients got clear vitreous and controlled IOP only with 2.7 ± 1.8 injections of ranibizumab without additional surgery. Vitrectomy or/with Ahmed valve implantation was administered in the other 8 eyes due to uncontrolled VH and IOP. At follow-up month 12, all the 18 eyes gained clear vitreous. At month 12 BCVA improved significantly compared to baseline. The baseline and follow-up at month 12 IOP/medication usage were 36.7 ± 8.1 mmHg on 3.4 ± 0.7 medications and 16.2 ± 4.9 mmHg on 0.67 ± 0.77 medications, respectively. Conclusions. The findings suggest that intravitreal ranibizumab injection as adjuvant therapy for treatment of NVG accompanied by PDVH may be safe and potentially effective. This clinical trial is registered with NCT02647515. PMID:27293875

  8. GSTP1 and MTHFR polymorphisms are related with toxicity in breast cancer adjuvant anthracycline-based treatment.

    PubMed

    Zárate, R; González-Santigo, S; de la Haba, J; Bandres, E; Morales, R; Salgado, J; Gómez, A; Aranda, E; García-Foncillas, J

    2007-06-01

    We have analyzed several members of drug-metabolizing enzymes (DMEs) and other polymorphisms in genes implicated in tumor aggressivity regarding possible links between specific genetic variability in systemic drug bioavailability and toxicity in breast cancer patients treated with adjuvant anthracycline-based treatment. PCR-RFLP and sequencing analyses technique were used for evaluating fourteen previously identified polymorphisms in 94 patients. GSTP1A>G and MTHFR 1298A>C genotypes remained as significant predictors in a multivariate logistic regression analysis. GSTP1 polymorphism was linked to haematological GIII-IV toxicity (P = 0.044, HR= 6.4, 95% CI = 1.05 to 39. Increased and significant HR was obtained for MTHFR-1298 AC+CC group when non-haematological toxicities GIII-IV toxicities were evaluated (HR = 24; 95% CI = 2.3 to 254), P = 0.008. Our results suggest that GSTP1 and MTHFR genotypes may be consider relevant and independent factors of toxicity in adjuvant anthracycline-based treatment of breast cancer. PMID:17584018

  9. Treatment Strategies for Mucocutaneous Leishmaniasis

    PubMed Central

    Palumbo, Emilio

    2010-01-01

    Mucocutaneous is an infection caused by a single celled parasite transmitted by sand fly bites. There are about 20 species of Leishmania that may cause mucocutaneous leishmaniasis. Some Leishmania species are closely linked to humans and are therefore found in cities (L. tropica) whereas some others are more traditionally associated with animal species and therefore considered zoonoses (L. major). The evidence for optimal treatment of mucocutaneous leishmaniasis is patchy. Although the cutaneous form of the disease is often self-limiting, it does result in significant scarring and can spread to more invasive, mucocutaneous disease. Therefore, treatment may be considered to prevent these complications. Drugs for systemic and topical treatment are presented and discussed with regard to their application, use and adverse effects. PMID:20606970

  10. Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma

    PubMed Central

    Benekli, Mustafa; Unal, Olcun Umit; Unek, İlkay Tugba; Tastekin, Didem; Dane, Faysal; Algın, Efnan; Ulger, Sukran; Eren, Tulay; Topcu, Turkan Ozturk; Turkmen, Esma; Babacan, Nalan Akgül; Tufan, Gulnihal; Urakci, Zuhat; Ustaalioglu, Basak Oven; Uysal, Ozlem Sonmez; Ercelep, Ozlem Balvan; Taskoylu, Burcu Yapar; Aksoy, Asude; Canhoroz, Mustafa; Demirci, Umut; Dogan, Erkan; Berk, Veli; Balakan, Ozan; Ekinci, Ahmet Şiyar; Uysal, Mukremin; Petekkaya, İbrahim; Ozturk, Selçuk Cemil; Tonyalı, Önder; Çetin, Bülent; Aldemir, Mehmet Naci; Helvacı, Kaan; Ozdemir, Nuriye; Oztop, İlhan; Coskun, Ugur; Uner, Aytug; Ozet, Ahmet; Buyukberber, Suleyman

    2015-01-01

    Background We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC). Methods A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013. Results Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered. Conclusions Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection. PMID:26361410

  11. Conformal radiotherapy in the adjuvant treatment of gastric cancer: Review of 82 cases

    SciTech Connect

    Kassam, Zahra |; Lockwood, Gina |; O'Brien, Catherine; Brierley, James |; Swallow, Carol ||; Oza, Amit |; Siu, Lillian |; Knox, Jennifer J. |; Wong, Rebecca |; Cummings, Bernard; Kim, John |; Moore, Malcolm |; Ringash, Jolie |. E-mail: jolie.ringash@rmp.uhn.on.cag

    2006-07-01

    Background: The Intergroup 0116 study showed a survival benefit with adjuvant chemoradiotherapy (CRT) for resected gastric cancer. We report our experience using conformal radiotherapy (RT). Methods and Materials: Eighty-two patients with resected gastric or gastroesophageal junction (GEJ) adenocarcinoma, Stage IB to IV (M0), were treated with 45 Gy in 25 fractions using a 5-field conformal technique. Chemotherapy was in accordance with the Intergroup 0116 study, or infusional 5-fluorouracil and cisplatin in a phase I/II trial. Results: Mean age was 56.4 years. Median follow-up was 22.8 months. Grade 3 or greater acute toxicity (National Cancer Institute Common Terminology Criteria of Adverse Events, version 3.0) was noted in 57% of patients (upper gastrointestinal tract 34%, hematologic 33%). One patient died of neutropenic sepsis. Radiation Therapy Oncology Group Grade 3 late toxicity included esophageal strictures (3 patients) and small bowel obstruction (1 patient). Full course CRT was completed by 67% of patients. Of 26 patients who relapsed, 20 died. Site of first relapse was available on 23 patients: 8 locoregional and distant, 4 locoregional alone, 11 distant alone. Overall and relapse-free survival were 69% and 54% at 3 years. Conclusion: Adjuvant CRT for gastric cancer, even with conformal RT, is associated with significant toxicity. Survival was comparable to that reported in the Intergroup 0116 study.

  12. Impact of CYP2D6 polymorphisms in tamoxifen adjuvant breast cancer treatment.

    PubMed

    Ramón y Cajal, T; Altés, A; Paré, L; del Rio, E; Alonso, C; Barnadas, A; Baiget, M

    2010-01-01

    The aim of this study is to evaluate the impact of CYP2D6 genotyping in predicting disease-free survival and toxicity in breast cancer patients treated with adjuvant tamoxifen. DNA from 91 patients was genotyped using the AmpliChip CYP450 GeneChip, Roche that facilitates the classification of individuals by testing 27 alleles. When patients were grouped into group 1 (*4/*4, *4/*41, *1/*5 and *2/*5) and group 2 (the remaining genotypes), a significant difference in disease-free survival (DFS) was observed between groups (P = 0.016). The mean DFS in group 1 was 95 months in contrast with 119 months in group 2. No significant relationship was found between the CYP2D6 genotype classification and severe, mild or no toxicity (P = 0.2). Nevertheless, severe, and mild toxicity was more frequent among poor metabolizer patients than in patients with a normal metabolizer pattern (18.8 and 43.8% vs. 10.7 and 36%, respectively). In breast cancer, patients treated with adjuvant tamoxifen, non-functional and severely impaired CYP2D6 variants are associated with a worse DFS and with a higher frequency of severe and mild toxicities. Larger studies of the CYP2D6 genotype-clinical outcomes association are needed to complement initial results. PMID:19189210

  13. Vaginal brachytherapy alone is sufficient adjuvant treatment of surgical stage I endometrial cancer

    SciTech Connect

    Solhjem, Matthew C. . E-mail: petersen.ivy@mayo.edu; Petersen, Ivy A.; Haddock, Michael G.

    2005-08-01

    Purpose To determine the efficacy and complications of adjuvant vaginal high-dose-rate brachytherapy alone for patients with Stage I endometrial cancer in whom complete surgical staging had been performed. Methods and Materials Between April 1998 and March 2004, 100 patients with Stage I endometrial cancer underwent surgical staging (total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic {+-} paraaortic nodal sampling) and postoperative vaginal high-dose-rate brachytherapy at our institution. The total dose was 2100 cGy in three fractions. Results With a median follow-up of 23 months (range 2-62), no pelvic or vaginal recurrences developed. All patients underwent pelvic dissection, and 42% underwent paraaortic nodal dissection. A median of 29.5 pelvic nodes (range 1-67) was removed (84% had >10 pelvic nodes removed). Most patients (73%) had endometrioid (or unspecified) adenocarcinoma, 16% had papillary serous carcinoma, and 11% had other histologic types. The International Federation of Gynecology and Obstetrics stage and grade was Stage IA, grade III in 5; Stage IB, grade I, II, or III in 6, 27, or 20, respectively; and Stage IC, grade I, II, or III in 13, 17, or 10, respectively. The Common Toxicity Criteria (version 2.0) complications were mild (Grade 1-2) and consisted primarily of vaginal mucosal changes, temporary urinary irritation, and temporary diarrhea. Conclusion Adjuvant vaginal high-dose-rate brachytherapy alone may be a safe and effective alternative to pelvic external beam radiotherapy for surgical Stage I endometrial cancer.

  14. Imiquimod 5% cream as an adjuvant pre-operative treatment for basal cell carcinoma of the periocular area.

    PubMed

    Bonilla, Rosa; Solebo, Ameenat L; Khandwala, Mona A; Jones, Carole A

    2014-12-01

    Despite national guidelines in the UK, patients with low-grade periocular malignancies frequently wait a period of months for their surgery. We have devised a protocol of pre-treatment with an immune modulator in an attempt to reduce the tumour size whilst patients await surgery. We present a case series of 5 patients who used Imiquimod 5% cream (Aldara) for 4 weeks as an adjuvant treatment prior to the excision of periocular nodular basal cell carcinomas. We also assessed tolerability of the cream using a visual analogue scale and recorded adverse events. Our patients had an average 22% reduction in tumour area (range 3.31%-39.64%) whilst awaiting surgery. The medication had a good tolerability profile and there were no ocular adverse events. Due to the promising results, this pilot study demonstrates the feasibility and value of a planned multicentre, prospective research project to further explore these initial findings. PMID:25255050

  15. NKT cell adjuvant-based tumor vaccine for treatment of myc oncogene-driven mouse B-cell lymphoma

    PubMed Central

    West, Alison C.; Steegh, Kim; Duret, Helene; Paget, Christophe; Martin, Ben; Matthews, Geoffrey M.; Shortt, Jake; Chesi, Marta; Bergsagel, P. Leif; Bots, Michael; Zuber, Johannes; Lowe, Scott W.; Johnstone, Ricky W.

    2012-01-01

    Immunomodulators are effective in controlling hematologic malignancy by initiating or reactivating host antitumor immunity to otherwise poorly immunogenic and immune suppressive cancers. We aimed to boost antitumor immunity in B-cell lymphoma by developing a tumor cell vaccine incorporating α-galactosylceramide (α-GalCer) that targets the immune adjuvant properties of NKT cells. In the Eμ-myc transgenic mouse model, single therapeutic vaccination of irradiated, α-GalCer–loaded autologous tumor cells was sufficient to significantly inhibit growth of established tumors and prolong survival. Vaccine-induced antilymphoma immunity required NKT cells, NK cells, and CD8 T cells, and early IL-12–dependent production of IFN-γ. CD4 T cells, gamma/delta T cells, and IL-18 were not critical. Vaccine treatment induced a large systemic spike of IFN-γ and transient peripheral expansion of both NKT cells and NK cells, the major sources of IFN-γ. Furthermore, this vaccine approach was assessed in several other hematopoietic tumor models and was also therapeutically effective against AML-ETO9a acute myeloid leukemia. Replacing α-GalCer with β-mannosylceramide resulted in prolonged protection against Eμ-myc lymphoma. Overall, our results demonstrate a potent immune adjuvant effect of NKT cell ligands in therapeutic anticancer vaccination against oncogene-driven lymphomas, and this work supports clinical investigation of NKT cell–based immunotherapy in patients with hematologic malignancies. PMID:22932803

  16. Neoadjuvant vs. adjuvant treatment of Siewert type II gastroesophageal junction cancer: an analysis of data from the surveillance, epidemiology, and end results (SEER) registry

    PubMed Central

    Miccio, Joseph A.; Oladeru, Oluwadamilola T.; Yang, Jie; Xue, Yaqi; Choi, Minsig; Zhang, Yue; Yoon, Hannah; Ryu, Samuel

    2016-01-01

    Background Cancer of the gastroesophageal junction (GEJ) has been rising in incidence in recent years. The role of radiation therapy (RT) in the treatment of GEJ cancer remains unclear, as the largest prospective trials advocating for either adjuvant or neoadjuvant chemoradiotherapy (CRT) combine GEJ cancer with either gastric or esophageal cancer. The aim of the present study is to examine the association of neoadjuvant versus adjuvant treatment with overall and disease-specific survival (DSS) for patients with surgically resected cancer of the true GEJ (Siewert type II). Methods The surveillance, epidemiology, and end results (SEER) registry database (2001–2011) was queried for cases of surgically resected Siewert type II GEJ cancer. A total of 1,497 patients with resectable GEJ cancer were identified, with 746 receiving adjuvant RT and 751 receiving neoadjuvant RT. Retrospective analysis was performed with the endpoints of overall and DSS. Results Using cox regression and controlling for independent covariates (age, sex, race, stage, grade, histology, and year of diagnosis), we showed that adjuvant RT was associated with a significantly lower death risk [hazard ratio (HR), 0.84; 95% confidence interval 0.73–0.97; P value=0.0168] and significantly lower disease-specific death risk (HR, 0.84; 95% confidence interval, 0.72–0.97; P value=0.0211) as compared to neoadjuvant RT. Conclusions This analysis of SEER data showed that adjuvant RT was associated with a survival benefit as compared to neoadjuvant RT for the treatment of Siewert type II GEJ cancer. We suggest future prospective studies to compare outcomes of adjuvant versus neoadjuvant treatment for true GEJ cancer. PMID:27284473

  17. Pegylated interferon alpha-2b as adjuvant treatment of Stage III malignant melanoma: an evidence-based review

    PubMed Central

    Okuyama, Sonia; Gonzalez, Rene; Lewis, Karl D

    2010-01-01

    Introduction: Stage III melanoma, also referred to as regional metastatic melanoma, has five-year survival rates ranging between 40% and 78%. In order to reduce the likelihood of recurrence in this high-risk population, patients undergo resection of primary tumors and all involved nodal basins. Systemic therapy is being pursued in an effort to improve outcome data, but the best strategy has yet to be defined. Interferon alpha-2b remains to date the most promising approach available. Toxicities and intensive intravenous administration, unfortunately, are major concerns. An alternative is the use of interferon in its pegylated subcutaneous form. The aim of this research was to review the evidence for the use of pegylated interferon alpha-2b in Stage III malignant melanoma. Evidence review: ECOG 1684 was the pivotal trial that first demonstrated a statistically significant benefit in relapse-free and overall survival for adjuvant interferon alpha-2b in high-risk melanoma. Other larger studies, such as ECOG 1690, confirmed a relapse-free survival benefit but did not achieve statistical significance for overall survival. The first study of the pegylated form of interferon alpha-2b in Stage III melanoma, EORTC 18991, is reviewed here. This trial showed a statistically significant improvement in relapse-free survival but not overall survival. Encouraging data of potential equivalent efficacy, easier administration, and fewer Grade 3 and 4 adverse reactions compared with high-dose intravenous interferon raises the question of its potential role in Stage III melanoma in the adjuvant setting. PMID:21042541

  18. Drug delivery strategies for the treatment of Helicobacter pylori infections.

    PubMed

    Conway, B R

    2005-01-01

    Helicobacter pylori is one of the most common pathogenic bacterial infections, colonising an estimated half of all humans. It is associated with the development of serious gastroduodenal disease - including peptic ulcers, gastric lymphoma and acute chronic gastritis. Current recommended regimes are not wholly effective and patient compliance, side-effects and bacterial resistance can be problematic. Drug delivery to the site of residence in the gastric mucosa may improve efficacy of the current and emerging treatments. Gastric retentive delivery systems potentially allow increased penetration of the mucus layer and therefore increased drug concentration at the site of action. Proposed gastric retentive systems for the enhancement of local drug delivery include floating systems, expandable or swellable systems and bioadhesive systems. Generally, problems with these formulations are lack of specificity, limited to mucus turnover or failure to persist in the stomach. Gastric mucoadhesive systems are hailed as a promising technology to address this issue, penetrating the mucus layer and prolonging activity at the mucus-epithelial interface. This review appraises gastroretentive delivery strategies specifically with regard to their application as a delivery system to target Helicobacter. As drug-resistant strains emerge, the development of a vaccine to eradicate and prevent reinfection is an attractive proposition. Proposed prophylactic and therapeutic vaccines have been delivered using a number of mucosal routes using viral and non-viral vectors. The delivery form, inclusion of adjuvants, and delivery regime will influence the immune response generated. PMID:15777232

  19. A Meta-Analysis on the Impact of Platinum-Based Adjuvant Treatment on the Outcome of Borderline Ovarian Tumors With Invasive Implants

    PubMed Central

    Olschewski, Jessica; Braicu, Ioana; Sehouli, Jalid

    2015-01-01

    Background. Treatment of borderline ovarian tumors (BOTs) remains contentious, and there is no consensus regarding therapy for BOTs with invasive implants (BOTi). The benefits of platinum-based adjuvant treatment were evaluated in patients with BOTi at primary diagnosis. Methods. The PubMed database was systematically searched for articles using the following terms: ((borderline) OR (low malignant potential) AND (ovarian)) AND ((tumor) OR (cancer)) AND (invasive implants) AND ((follow-up) OR (survival) OR (treatment) OR (chemotherapy) OR (adjuvant treatment) OR (surgery) OR (surgical treatment)). Results. We identified 27 articles including 3,124 patients, 181 with invasive implants. All studies provided information regarding mortality or recurrence rates. Central pathological examination was performed in 19 studies. Eight studies included more than 75% stage I patients; 7 included only advanced-stage patients, and 14 included only serous BOT. The pooled recurrence estimates for both treatment groups (adjuvant treatment: 44.0%, upfront surgery: 21.3%) did not differ significantly (p = .114). A meta-analysis of the 6 studies providing separate mortality data for both treatment groups favored surgical treatment only, but this difference did not reach statistical significance (.05 < p < .1; odds ratio: 0.33; 95% confidence interval: 0.09–1.71; p = .086). We were unable to pool the results of the included studies because not all studies registered events in both treatment groups. Egger’s regression indicated low asymmetry of the studies (p = .39), and no heterogeneity was found (I2 = 0%). Conclusion. We did not find evidence supporting platinum-based adjuvant therapy for BOT with invasive implants. PMID:25601963

  20. Treatment strategies for colorectal carcinoma with synchronous liver metastases: Which way to go?

    PubMed Central

    Ihnát, Peter; Vávra, Petr; Zonča, Pavel

    2015-01-01

    AIM: To offer an up-to-date review of all available treatment strategies for patients with synchronous colorectal liver metastases (CLM). METHODS: A comprehensive literature search was performed to identify articles related to the management of patients with synchronous CLM. A search of the electronic databases PubMed, MEDLINE, and Google Scholar was conducted in September 2014. The following search terms were used: synchronous colorectal liver metastases, surgery, stage IV colorectal cancer, liver-first approach, and up-front hepatectomy. These terms were employed in various combinations to maximize the search. Only articles written in English were included. Particular attention was devoted to studies and review articles that were published within the last six years (2009-2014). Additional searches of the cited references from primary articles were performed to further improve the review. The full texts of all relevant articles were accessed by two independent reviewers. RESULTS: Poor long-term outcomes of patients with synchronous CLM managed by a traditional treatment strategy have led to questions about the timing and sequence of possible therapeutic interventions. Thus, alternative paradigms called reverse strategies have been proposed. Presently, there are four treatment strategies available: (1) primary first approach (or traditional approach) comprises resection of the primary colorectal tumor followed by chemotherapy; subsequent liver resection is performed 3-6 mo after colorectal resection (provided that CLM are still resectable); (2) simultaneous resection of the primary colorectal tumor and CLM during a single operation presents intriguing options for a highly select group of patients, which can be associated with significant postoperative morbidity; (3) liver-first (or chemotherapy-first) approach comprises preoperative chemotherapy (3-6 cycles) followed by liver resection, adjuvant chemotherapy, and resection of the primary colorectal tumor (it is

  1. New pharmacological treatment strategies for relapse prevention.

    PubMed

    Spanagel, Rainer; Vengeliene, Valentina

    2013-01-01

    Here we discuss treatment strategies that are based on pharmacological interventions to reduce craving and relapse in alcohol-dependent patients. We will first provide a historical overview about relapse prevention strategies. We will then review the development of disulfiram, naltrexone, acamprosate, and nalmefene and discuss their neurobiological modes of action. Then the concept of convergent genomic analysis will be introduced for the discovery of new molecular treatment targets. Finally, we will provide convincing evidence for the use of N-methyl-D-aspartate (NMDA) receptor channel blockers as substitution drugs. Important conclusions of this review are: (i) learning from other addictive substances is very helpful-e.g., substitution therapies as applied to opiate addiction for decades could also be translated to alcoholics, (ii) the glutamate theory of alcohol addiction provides a convincing framework for the use of NMDA receptor antagonists as substitution drugs for alcohol-dependent patients, (iii) a combination of behavioral and pharmacological therapies may be the optimal approach for future treatment strategies-one promising example concerns the pharmacological disruption of reconsolidation processes of alcohol cue memories, (iv) given that many neurotransmitter systems are affected by chronic alcohol consumption, numerous druggable targets have been identified; consequently, a "cocktail" of different compounds will further improve the treatment situation, (v) in silico psychopharmacology, such as drug repurposing will yield new medications, and finally, (vi) the whole organism has to be taken into consideration to provide the best therapy for our patients. In summary, there is no other field in psychiatric research that has, in recent years, yielded so many novel, druggable targets and innovative treatment strategies than for alcohol addiction. However, it will still be several years before the majority of the "treatment-seeking population" will benefit

  2. Amblyopia treatment strategies and new drug therapies.

    PubMed

    Pescosolido, Nicola; Stefanucci, Alessio; Buomprisco, Giuseppe; Fazio, Stefano

    2014-01-01

    Amblyopia is a unilateral or bilateral reduction of visual acuity secondary to abnormal visual experience during early childhood. It is one of the most common causes of vision loss and monocular blindness and is commonly associated with strabismus, anisometropia, and visual deprivation (in particular congenital cataract and ptosis). It is clinically defined as a two-line difference of best-corrected visual acuity between the eyes. The purpose of this study was to understand the neural mechanisms of amblyopia and summarize the current therapeutic strategies. In particular, the authors focused on the concept of brain plasticity and its implication for new treatment strategies for children and adults with amblyopia. PMID:24410693

  3. Effects of postoperative adjuvant chemotherapy and radiotherapy on ovarian function in women undergoing treatment for soft tissue sarcoma

    SciTech Connect

    Shamberger, R.C.; Sherins, R.J.; Ziegler, J.L.; Glatstein, E.; Rosenberg, S.A.

    1981-12-01

    Ovarian function was evaluated in 11 women 16 to 43 years of age at treatment who received doxorubicin, cyclophosphamide, and high doses of methotrexate with or without radiotherapy in adjuvant therapy of soft tissue sarcoma. Five women (16-33 yr old) who received chemotherapy alone or combined with radiotherapy only at sites distant from the ovaries (chest wall, thigh, and leg) had minimal menstrual irregularities or temporary cessation of menses during therapy; cyclic menses returned promptly after therapy. Gonadotropin levels (expressed as means +/- SD (follicle-stimulating hormone (FSH), 10 +/- 5 mlU/ml; luteinizing hormone (LH), 10 +/- 4 mlU/ml) and 17 beta-estradiol (E2) levels (means +/- SD, 208 +/- 147 pg/ml) were normal. By contrast, 4 older women (ages 36-43 yr) who received similar treatment developed persistent amenorrhea with postmenopausal levels of gonadotropin (FSH, 108 +/- 29 mlU/ml; LH, 72 +/- 19 mlU/ml) and E2 (19 +/- 8 pg/ml). Two additional women (ages 21 and 39 yr) who received radiation (7,000 rad) to the pelvis plus chemotherapy developed prompt cessation of menses and became functional castrates (FSH, 77 and 80 mlU/ml; LH, 40 and 58 mlU/ml; E2, 10 and 19 pg/ml). However, this result would be expected from the radiation dose alone. The data demonstrated that ovarian dysfunction may follow the use of doxorubicin, cyclophosphamide, and high doses of methotrexate and that the injury is age related.

  4. Impact of UGT2B7 His268Tyr polymorphism on the outcome of adjuvant epirubicin treatment in breast cancer

    PubMed Central

    2011-01-01

    Introduction Epirubicin is a common adjuvant treatment for breast cancer. It is mainly eliminated after glucuronidation through uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7). The present study aimed to describe the impact of the UGT2B7His268Tyr polymorphism on invasive disease-free survival in breast cancer patients after epirubicin treatment. Methods This is a pharmacogenetic study based on samples collected from 745 breast cancer patients of the Austrian Tumor of breast tissue: Incidence, Genetics, and Environmental Risk factors (TIGER) cohort who did not present metastases at baseline. This cohort included 205 women with epirubicin-based combination chemotherapy, 113 patients having received chemotherapy without epirubicin and 427 patients having received no chemotherapy at all. Of the epirubicin-treated subgroup, 120 were subsequently treated with tamoxifen. For all women UGT2B7His268Tyr was genotyped. Invasive disease-free survival was assessed using Kaplan-Meier and Cox's proportional hazard regression analysis. Results Among the 205 epirubicin-treated patients, carriers of two UGT2B7268Tyr alleles had a mean invasive disease-free survival of 8.6 (95% confidence interval (CI) 7.9 to 9.3) years as compared to 7.5 (95% CI 6.9 to 8.0) years in carriers of at least one UGT2B7268His allele (adjusted hazard ratio (HR) = 2.64 (95% CI 1.22 to 5.71); P = 0.014). In addition, the impact of the UGT2B7His268Tyr polymorphism became even more pronounced in patients subsequently treated with tamoxifen (adjusted HR = 5.22 (95% CI 1.67 to 26.04); P = 0.015) whereas no such difference in invasive disease-free survival was observed in patients not receiving epirubicin. Conclusions Breast cancer patients carrying the UGT2B7268Tyr/Tyr genotype may benefit most from adjuvant epirubicin-based chemotherapy. These results warrant confirmation in further studies. PMID:21658222

  5. A treatment strategy for psychogenic vomiting.

    PubMed

    Willard, S G; Swain, B S; Winstead, D K

    1989-01-01

    Although the literature supports the existence of psychogenic vomiting as a distinct psychiatric disorder, the DSM III-R does not include it as a diagnostic category. Of the numerous articles in the literature which describe this disorder, few discuss treatment. The purposes of this paper are to review the existing literature, to describe the family dynamics which are thought to precipitate the evolution of psychogenic vomiting in the identified patient, and to describe a treatment protocol which has been successfully employed in an outpatient setting. The illness is characterized as an eating disorder in terms of etiology, symptomatology, and treatment. A treatment strategy is described which includes insight-oriented psychotherapy with cognitive/behavioral interventions and family therapy. Two case studies are included which illustrate that a combined therapy approach is efficacious in treating psychogenic vomiting. PMID:2813832

  6. Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer.

    PubMed

    Gollins, S; Sebag-Montefiore, D

    2016-02-01

    Improved surgical technique plus selective preoperative radiotherapy have decreased rectal cancer pelvic local recurrence from, historically, 25% down to about 5-10%. However, this improvement has not reduced distant metastatic relapse, which is the main cause of death and a key issue in rectal cancer management. The current standard is local pelvic treatment (surgery ± preoperative radiotherapy) followed by adjuvant chemotherapy, depending on resection histology. For circumferential resection margin (CRM)-threatened cancer on baseline magnetic resonance imaging, downstaging long-course preoperative chemoradiation (LCPCRT) is generally used. However, for non-CRM-threatened disease, varying approaches are currently adopted in the UK, including straight to surgery, short-course preoperative radiotherapy and LCPCRT. Clinical trials are investigating intensification of concurrent chemoradiation. There is also increasing interest in investigating preoperative neoadjuvant chemotherapy (NAC) as a way of exposing micro-metastatic disease to full-dose systemic chemotherapy as early as possible and potentially reducing metastatic relapse. Phase II trials suggest that this strategy is feasible, with promising histological response and low rates of tumour progression during NAC. Phase III trials are needed to determine the benefit of NAC when added to standard therapy and also to determine if it can be used instead of neoadjuvant radiotherapy-based schedules. Although several measures of neoadjuvant treatment response assessment based on imaging or pathology are promising predictive biomarkers for long-term survival, none has been validated in prospective phase III studies. The phase III setting will enable this, also providing translational opportunities to examine molecular predictors of response and survival. PMID:26645661

  7. Oral 2.01: Proton beam radiation therapy for adjuvant and definitive treatment of thymoma and thymic carcinoma

    PubMed Central

    Vogel, Jennifer H.; Berman, Abigail T.; Pechet, Taine T.; William, Levin P.; Gabriel, Peter E.; Khella, Sami; Singhal, Sunil; Kucharczuk, John C.; Simone, Charles B.

    2015-01-01

    Background Radiation therapy is a critical component of treatment for thymic tumors. However, radiation-induced toxicity may reduce benefit, particularly in the adjuvant setting. Proton beam therapy (PBT), due to its characteristic Bragg peak, is ideally suited to treat the anterior mediastinum while sparing organs at risk. To date, PBT to treat thymic tumors has only been reported in three single-patient case studies. In this study, we evaluated patterns of failure and toxicity in patients treated for thymoma and thymic carcinoma using PBT and hypothesized that PBT can achieve excellent local control with limited high grade toxicity. Methods All patients with thymoma or thymic carcinoma treated with PBT between 2011–2015 were analyzed. Either double scattered proton therapy (DS-PT) or pencil beam scanning (PBS) were used. Toxicity was assessed using CTCAE v 4.2. Local control, distant control, and overall survival were analyzed by the Kaplan-Meier method from the time of PBT completion. Results Twenty-seven patients were included. Patients were a median age of 56 years, predominantly female (56%), and had thymoma (85%) or thymic carcinoma (15%). They were treated with definitive (22%) or salvage (15%) PBT or adjuvant (63%) PBT following resection with predominantly close (23%) or positive (50%) margins. Forty-one percent also received chemotherapy. Patients were treated to a median of 61.2 Gy (range 50.4–70.2 Gy) using DS-PT (85%) or PBS (15%). Median mean lung dose, volume of lung receiving ≥20 Gy (V20), and V5 were 98 cGy (1–2,050 cGy), 18% (0–38%), and 26.2% (0–55%). Median mean heart and esophagus doses were 1,065 cGy (105–3,356cGy) and 1,072cGy (0–4,655 cGy). No patient experienced grade ≥3 acute or chronic toxicity. Acute grade ≥2 toxicities included fatigue (11%), esophagitis (7%), dermatitis (37%), and pneumonitis in one patient (4%) who received 2 prior thoracic radiotherapy courses. Late grade ≥2 toxicity was limited to a single

  8. A systematic review of quality of life in head and neck cancer treated with surgery with or without adjuvant treatment.

    PubMed

    Rathod, Shrinivas; Livergant, Jonathan; Klein, Jonathan; Witterick, Ian; Ringash, Jolie

    2015-10-01

    Quality of life (QoL) is an important consideration in the management of head and neck cancers (HNC). We systematically reviewed the literature to assess the impact of curative surgical resection (+/- adjuvant therapy) of HNC on QoL. Eligible studies (participants>age 18 years, reported fully in English, and prospectively assessed QoL) were filtered using quality criteria, and classified according to the added value, using a published taxonomy. MEDLINE and EMBASE searching yielded 302 distinct reports, 49 met eligibility, and 26 met quality criteria. Among the eligible studies, achievement of certain quality criteria was poor: a priori hypothesis (8%), statistical accounting of missing data (8%), reporting of assessment interval (35%) and rationale for chosen measure (53%). The most frequent ways QoL added value were: understanding of treatment benefit and risk (100%), comparing treatments for QoL effect (92%) and advancing QoL research methodology (50%). QoL (physical/social functioning and various symptom domains) deteriorated with treatment, gradually recovering to baseline (cancer diagnosis) level. Swallowing, chewing, saliva, taste, eating disruption, and aesthetic deficits may persist. Advanced tumors, extensive surgical resection, need for flap reconstruction, neck dissection, and postoperative radiation are associated with worse QoL outcomes. Knowledge of these trends can be applied in shared decision making, identification of commonly faced QoL issues, and to develop and provide survivorship resources. Future research should focus on routinely incorporating QoL in randomized studies, reporting the result according to guidelines, and following knowledge translation principles to maximize the clinician's and patient's ability to use QoL data. PMID:26209066

  9. Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant Temozolomide Chemotherapy: A Review.

    PubMed

    Moisi, Marc; Cruz, Aurora S; Benkers, Tara; Rostad, Steven; Broyles, Frances Broyles; Yuen, Kevin; Mayberg, Marc

    2016-01-01

    Most prolactin-secreting pituitary adenomas demonstrate slow growth and are effectively managed with medical/surgical therapy. Rarely, these tumors can behave aggressively with rapid growth and invasion of local tissues, and are refractory to medical, surgical, or radio-surgical therapies. We report a case of a prolactin-secreting adenoma in a young woman, which became progressively aggressive and refractory to usual treatment modalities, but responded to treatment with the chemotherapeutic agent temozolomide. In addition, we review the literature for treatment of refractory adenomas with temozolomide. The clinical and pathologic characteristics of aggressive prolactin-secreting adenomas are reviewed, as well as their response to dopamine agonists, surgery, radiotherapy, and chemotherapy. PMID:27489751

  10. Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant Temozolomide Chemotherapy: A Review

    PubMed Central

    Cruz, Aurora S; Benkers, Tara; Rostad, Steven; Broyles, Frances Broyles; Yuen, Kevin; Mayberg, Marc

    2016-01-01

    Most prolactin-secreting pituitary adenomas demonstrate slow growth and are effectively managed with medical/surgical therapy. Rarely, these tumors can behave aggressively with rapid growth and invasion of local tissues, and are refractory to medical, surgical, or radio-surgical therapies. We report a case of a prolactin-secreting adenoma in a young woman, which became progressively aggressive and refractory to usual treatment modalities, but responded to treatment with the chemotherapeutic agent temozolomide. In addition, we review the literature for treatment of refractory adenomas with temozolomide. The clinical and pathologic characteristics of aggressive prolactin-secreting adenomas are reviewed, as well as their response to dopamine agonists, surgery, radiotherapy, and chemotherapy. PMID:27489751

  11. Slightly focused high-energy shockwave therapy: a potential adjuvant treatment for osteoporotic fracture

    PubMed Central

    Chen, Xiao-Feng; Huang, Hai-Ming; Li, Xiao-Lin; Liu, Ge-Jun; Zhang, Hui

    2015-01-01

    Slightly focused high-energy shockwave (HESW) therapy is characterized by a wide focal area, a large therapy zone, easy positioning and less pain during treatment. The objective of this study was to perform for the first time an in vivo test of the slightly focused HESWs for osteoporotic fractures. Bilateral proximal tibial osteotomies were made in 30 ovariectomized (OVX) Sprague-Dawley rats and secured with internal fixation. The osteotomy site in the left tibia was subsequently treated with slightly focused HESWs with the energy flux density of 0.26 mj/mm2, shock repetition frequency of 1 Hz and 2000 shocks (OVX + HESW group). The contralateral right tibia was not treated and served as the control (OVX group). Roentgenographic examination 2, 4, 6, and 8 weeks after osteotomy showed that HESW treatment accelerated tibia fracture healing in osteoporotic rats. Histological examination 2, 4, and 8 weeks after HESW treatment showed a greater inflammatory reaction in the OVX + HESW group, with more mature collagen and trabeculae than in the OVX group. Micro computer tomography (Micro-CT) scanning after 4 and 8 weeks showed that bone volume (BV), bone volume/tissue volume (BV/TV), mean trabecular thickness (Tb.Th), and mean trabecular number (Tb.N) were about 45.0% and 33.1%, 18.4% and 20.1%, 38.2% and 20.9%, 26.7% and 28.4%, respectively, higher in the treatment group than in the control group (P < 0.05); and the mean trabecular separation (Tb.Sp) was about 16.7% and 27.3% lower in the treatment group (P < 0.05). Four and eight weeks after HESW treatment, the maximum compressive callus endurance was about 72.3% and 25.5%, respectively, higher in the treatment group than in the control group (P < 0.05). These results show that slightly focused HESW therapy has a beneficial effect on osteoporotic tibial fracture healing. Slightly focused HESWs could increase callus endurance, induce bone formation, and improve trabecular bone microarchitecture and biomechanical

  12. Adjuvant therapy for gastric cancer: What have we learned since INT0116?

    PubMed Central

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

    2015-01-01

    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. PMID:25852269

  13. Successful Treatment of Advanced Ovarian Cancer with Thermochemotherapy and Adjuvant Immune Therapy

    PubMed Central

    Kleef, R.; Kekic, S.; Ludwig, N.

    2012-01-01

    We report on a 4-year progression-free survival of a 54-year-old female first diagnosed in December 2007 with advanced bilateral ovarian cancer FIGO IIIc, disseminated peritoneal carcinosis and malignant diaphragm invasion. Treatment started in January 2008 with 6 cycles of Taxol 175 mg/m2/carboplatin AUC 5 in 3-week intervals. Twenty-four hours following each chemotherapy session, fever-range long-duration whole-body hyperthermia (WBH) was performed at the temperature plateau of 40°C body core temperature for 6 h. Three months after completion of chemotherapy, 4 more long-duration WBH procedures were performed in monthly intervals. Importantly, long-duration WBH was paralleled with intradermal vaccination of autologous dendritic cells. No other treatment was given to the patient. Four years following the first diagnosis, the patient is still in complete remission with no evidence of disease. PMID:22679425

  14. Multimodal MRI and cognitive function in patients with breast cancer prior to adjuvant treatment--the role of fatigue.

    PubMed

    Menning, Sanne; de Ruiter, Michiel B; Veltman, Dick J; Koppelmans, V; Kirschbaum, Clemens; Boogerd, Willem; Reneman, Liesbeth; Schagen, Sanne B

    2015-01-01

    An increasing body of literature indicates that chemotherapy (ChT) for breast cancer (BC) is associated with adverse effects on the brain. Recent research suggests that cognitive and brain function in patients with BC may already be compromised before the start of chemotherapy. This is the first study combining neuropsychological testing, patient-reported outcomes, and multimodal magnetic resonance imaging (MRI) to examine pretreatment cognition and various aspects of brain function and structure in a large sample. Thirty-two patients with BC scheduled to receive ChT (pre-ChT+), 33 patients with BC not indicated to undergo ChT (pre-ChT-), and 38 no-cancer controls (NCs) were included. The examination consisted of a neuropsychological test battery, self-reported aspects of psychosocial functioning, and multimodal MRI. Patients with BC reported worse scores on several aspects of quality of life, such as higher levels of fatigue and stress. However, cortisol levels were not elevated in the patient groups compared to the control group. Overall cognitive performance was lower in the pre-ChT+ and the pre-ChT- groups compared to NC. Further, patients demonstrated prefrontal hyperactivation with increasing task difficulty on a planning task compared to NC, but not during a memory task. White matter integrity was lower in both patient groups. No differences in regional brain volume and brain metabolites were found. The cognitive and imaging data converged to show that symptoms of fatigue were associated with the observed abnormalities; the observed differences were no longer significant when fatigue was accounted for. This study suggests that cancer-related psychological or biological processes may adversely impact cognitive functioning and associated aspects of brain structure and function before the start of adjuvant treatment. Our findings stress the importance to further explore the processes underlying the expression of fatigue and to study whether it has a

  15. Effects of postoperative adjuvant chemotherapy and radiotherapy on ovarian function in women undergoing treatment for soft tissue sarcoma

    SciTech Connect

    Shamberger, R.C.; Sherins, R.J.; Ziegler, J.L.; Glatstein, E.; Rosenberg, S.A.

    1981-12-01

    Ovarian function was evaluated in 11 women 16 to 43 years of age at treatment who received doxorubicin, cyclophosphamide, and high doses of methotrexate with or without radiotherapy in adjuvant therapy of soft tissue sarcoma. Five women (16-33 yr old) who received chemotherapy alone or combined with radiotherapy only at sites distant from the ovaries (chest wall, thigh, and leg) had minimal menstrual irregularities or temporary cessation of menses during therapy; cyclic menses returned promptly after therapy. Gonadotropin levels (expressed as means +/- SD) (follicle-stimulating hormone (FSH), 10 +/- 15 mlU/ml; luteinizing hormone (LH), 10 +/- 4 mlU/ml) and 17 ..beta..-estradiol (E/sub 2/) levels (means +/- SD, 208 +/- 147 pg/ml) were normal. By contrast, 4 older women (ages 36-43 yr) who received similar treatment developd persistent amenorrhea with postmenopausal levels of gonadotropin (FSH, 109 +/- 29 mlU/ml; LH, 72 +/- 19 mlU/ml) and E/sub 2/ (19 +/- 8 pg/ml). Two additional women (ages 21 and 39 yr) who received radiation (7000 rad) to the pelvis plus chemotherapy developed prompt cessation of menses and became functional castrates (FSH, 77 and 80mlU/ml; LH, 40 and 58 mlU/ml; E/sub 2/, 10 and 19 pg/ml). However, this result would be expected from the radiation dose alone. The data demonstrated that ovarian dysfunction may follow the use of doxorubicin, cyclophosphamide, and high doses of methotrexate and that the injury is age related.

  16. Multimodal MRI and cognitive function in patients with breast cancer prior to adjuvant treatment — The role of fatigue

    PubMed Central

    Menning, Sanne; de Ruiter, Michiel B.; Veltman, Dick J.; Koppelmans, V.; Kirschbaum, Clemens; Boogerd, Willem; Reneman, Liesbeth; Schagen, Sanne B.

    2015-01-01

    An increasing body of literature indicates that chemotherapy (ChT) for breast cancer (BC) is associated with adverse effects on the brain. Recent research suggests that cognitive and brain function in patients with BC may already be compromised before the start of chemotherapy. This is the first study combining neuropsychological testing, patient-reported outcomes, and multimodal magnetic resonance imaging (MRI) to examine pretreatment cognition and various aspects of brain function and structure in a large sample. Thirty-two patients with BC scheduled to receive ChT (pre-ChT+), 33 patients with BC not indicated to undergo ChT (pre-ChT−), and 38 no-cancer controls (NCs) were included. The examination consisted of a neuropsychological test battery, self-reported aspects of psychosocial functioning, and multimodal MRI. Patients with BC reported worse scores on several aspects of quality of life, such as higher levels of fatigue and stress. However, cortisol levels were not elevated in the patient groups compared to the control group. Overall cognitive performance was lower in the pre-ChT+ and the pre-ChT− groups compared to NC. Further, patients demonstrated prefrontal hyperactivation with increasing task difficulty on a planning task compared to NC, but not during a memory task. White matter integrity was lower in both patient groups. No differences in regional brain volume and brain metabolites were found. The cognitive and imaging data converged to show that symptoms of fatigue were associated with the observed abnormalities; the observed differences were no longer significant when fatigue was accounted for. This study suggests that cancer-related psychological or biological processes may adversely impact cognitive functioning and associated aspects of brain structure and function before the start of adjuvant treatment. Our findings stress the importance to further explore the processes underlying the expression of fatigue and to study whether it has a

  17. New treatment strategies for hepatitis C infection

    PubMed Central

    Ermis, Fatih; Senocak Tasci, Elif

    2015-01-01

    Hepatitis C infection can lead to cirrhosis and hepatocellular carcinoma and it is an important cause of mortality and morbidity. Achieving a sustained virological response has been the major aim for decades. Interferon treatment was the primarily developed therapy against the infection. Addition of the guanosine analog ribavirin to stop viral RNA synthesis increased the response rates as well as the adverse effects of the treatment. The increasing demands for alternative regimens led to the development of direct-acting antivirals (DAAs). The approval of sofosbuvir and simeprevir signaled a new era of antiviral treatment for hepatitis C infection. Although the majority of studies have been performed with DAAs in combination with interferon and resulted in a decrease in treatment duration and increase in response rates, the response rates achieved with interferon-free regimens provided hope for patients ineligible for therapy with interferon. Most DAA studies are in phase II leading to phase III. In the near future more DAAs are expected to be approved. The main disadvantage of the therapy remains the cost of the drugs. Here, we focus on new treatment strategies for hepatitis C infection as well as agents targeting hepatitis C virus replication that are in clinical development. PMID:26301052

  18. Clinical Outcome of Adjuvant Treatment of Endometrial Cancer Using Aperture-Based Intensity-Modulated Radiotherapy

    SciTech Connect

    Bouchard, Myriam; Nadeau, Sylvain M.Sc.; Gingras, Luc; Raymond, Paul-Emile; Beaulieu, Frederic; Beaulieu, Luc; Fortin, Andre; Germain, Isabelle

    2008-08-01

    Purpose: To assess disease control and acute and chronic toxicity with aperture-based intensity-modulated radiotherapy (AB-IMRT) for postoperative pelvic irradiation of endometrial cancer. Methods and Materials: Between January and July 2005, after hysterectomy for endometrial cancer, 15 patients received 45 Gy to the pelvis using AB-IMRT. The AB-IMRT plans were generated by an in-house treatment planning system (Ballista). The AB-IMRT plans were used for treatment and were dosimetrically compared with three other approaches: conventional four-field, enlarged four-field, and beamlet-based IMRT (BB-IMRT). Disease control and toxicity were prospectively recorded and compared with retrospective data from 30 patients treated with a conventional four-field technique. Results: At a median follow-up of 27 months (range, 23-30), no relapse was noted among the AB-IMRT group compared with five relapses in the control group (p = 0.1). The characteristics of each group were similar, except for the mean body mass index, timing of brachytherapy, and applicator type used. Patients treated with AB-IMRT experienced more frequent Grade 2 or greater gastrointestinal acute toxicity (87% vs. 53%, p 0.02). No statistically significant difference was noted between the two groups regarding the incidence or severity of chronic toxicities. AB-IMRT plans significantly improved target coverage (93% vs. 76% of planning target volume receiving 45 Gy for AB-IMRT vs. conventional four-field technique, respectively). The sparing of organs at risk was similar to that of BB-IMRT. Conclusion: The results of our study have shown that AB-IMRT provides excellent disease control with equivalent late toxicity compared with the conventional four-field technique. AB-IMRT provided treatment delivery and quality assurance advantages compared with BB-IMRT and could reduce the risk of second malignancy compared with BB-IMRT.

  19. New pre-pandemic influenza vaccines: an egg- and adjuvant-independent human adenoviral vector strategy induces long-lasting protective immune responses in mice.

    PubMed

    Hoelscher, M A; Jayashankar, L; Garg, S; Veguilla, V; Lu, X; Singh, N; Katz, J M; Mittal, S K; Sambhara, S

    2007-12-01

    Highly pathogenic avian H5N1 influenza viruses that are currently circulating in southeast Asia may acquire the potential to cause the next influenza pandemic. A number of alternate approaches are being pursued to generate cross-protective, dose-sparing, safe, and effective vaccines, as traditional vaccine approaches, i.e., embryonated egg-grown, are not immunogenic. We developed a replication-incompetent adenoviral vector-based, adjuvant- and egg-independent pandemic influenza vaccine strategy as a potential alternative to conventional egg-derived vaccines. In this paper, we address suboptimal dose and longevity of vaccine-induced protective immunity and demonstrate that a vaccine dose as little as 1 x 10(6) plaque-forming unit (PFU) is sufficient to induce protective immune responses against a highly pathogenic H5N1 virus. Furthermore, the vaccine-induced humoral and cellular immune responses and protective immunity persisted at least for a year. PMID:17957181

  20. Micro and Macro Element Composition of Kalanchoe integra Leaves: An Adjuvant Treatment for Hypertension in Ghana

    PubMed Central

    Frimpong-Manso, S.; Asiedu-Gyekye, I. J.; Naadu, J. P.; Magnus-Aryitey, G. T.; Nyarko, A. K.; Boamah, D.; Awan, M.

    2015-01-01

    Two samples, water extract and blended whole leaves, of fresh Kalanchoe integra leaves (Crassulaceae), a traditional antihypertensive medicine used in Ghana, were analyzed with Energy Dispersive X-Ray Fluorescence spectroscopy (EDXRF). Analysis revealed 12 macro and 26 micro elements in both extracts. Further quantitative assessment of the results for amounts of elements that are pharmacologically significant revealed that the amounts of calcium, potassium, and magnesium present in the extracts could be correlated to its traditional usage in managing hypertension and arrhythmias. However, heavy metals (lead and inorganic arsenic) detected in the extracts may pose a threat at doses normally used traditionally for the treatment of hypertension. PMID:26495138

  1. Adjuvant Therapy for Melanoma

    PubMed Central

    Davar, Diwakar; Tarhini, Ahmad A.

    2012-01-01

    Estimates from the U.S. Surveillance, Epidemiology, and End Results (SEER) registry suggest that melanoma incidence will reach 70,230 in 2011, of which 8,790 will die. The rising incidence and predilection for young individuals makes this tumor a leading source of lost productive years in the society. High-dose interferon-α2b is the only agent approved for adjuvant therapy of melanoma; the improvement in relapse-free survival has been observed across nearly all published studies and meta-analyses. However toxicity affects compliance and current research is focusing upon biomarkers that may allow selection of patients with greater likelihood of response, and exploring new agents either singly or in combination that may improve upon the benefit of IFN. In this article, we review the data for the adjuvant therapy of malignant melanoma - focusing on the results obtained with various regimens testing the several formulations of interferon-α2, and the adjuvant studies of vaccines and radiotherapy. Recent advances in the treatment of metastatic disease have established a role for CTLA-4 blockade and BRAF-inhibition, and raising hopes that these agents may have a role in the adjuvant setting. At present, several trials investigating combinations of novel agents with existing immunomodulators are underway. PMID:22453021

  2. Treatment of stage D bladder cancer with adjuvant doxorubicin hydrochloride and radiation

    SciTech Connect

    Schaeffer, A.J.; Grayhack, J.T.; Merrill, J.M.; Bulkley, G.J.; Shetty, R.M.

    1982-10-01

    pathologic Stage D bladder cancer was recognized in 16 patients by evaluation tissue obtained by radical cystectomy and pelvic lymphadenectomy (7), pelvic lymph node dissection (3) or biopsies (3), ileal conduit and pelvic lymph node biopsy (1), or transurethral biopsy of the bladder and prostate (2). Treatment of these patients with radiation preceded and followed by doxorubicin hydrochloride (Adriamycin) was initiated three to four weeks postoperatively. The treatment regimen consisted of the following: (1) doxorubicin 60 mg/M2 intravenously every three weeks for three cycles; (2) 5,000 rad external radiation to the whole pelvis in five to six weeks; and (3) doxorubicin for five cycles. The mean survival was twenty-three months. The survival rate was as follows: one year, 10 of 15 patients at risk; two years, 6 of 11; three years, 5 of 9; four years, 1 of 4; and five years, 0 of 2. Ten patients died six to thirty-six months (mean 13.6) postoperatively. In 6 of the patients significant obstruction of small bowel developed. These preliminary observations indicate encouraging therapeutic results with an acceptable morbidity for this regimen.

  3. Tamoxifen with ovarian function suppression versus tamoxifen alone as an adjuvant treatment for premenopausal breast cancer: a meta-analysis of published randomized controlled trials

    PubMed Central

    Yan, Shunchao; Li, Kai; Jiao, Xin; Zou, Huawei

    2015-01-01

    Background Ovarian function suppression (OFS) significantly downregulates the concentration of plasma estrogens. However, it is unclear whether it offers any survival benefits if combined with adjuvant tamoxifen treatment in premenopausal women. This meta-analysis was designed to assess data from previous studies involving adjuvant tamoxifen treatment plus OFS in premenopausal breast cancer. Methods Electronic literature databases (PubMed, Embase, the Web of Science, and the Cochrane Library) were searched for relevant randomized controlled trials published prior to February 1, 2015. Only randomized controlled trials that compared tamoxifen alone with tamoxifen plus OFS for premenopausal women with breast cancer were selected. The evaluated endpoints were disease-free survival and overall survival. Results Four randomized controlled trials comprising 6,279 patients (OFS combination, n=3,133; tamoxifen alone, n=3,146) were included in the meta-analysis. There was no significant improvement in disease-free survival or overall survival with addition of OFS in either the whole population or the hormone receptor-positive subgroup. The risk of distant recurrence was not reduced with the addition of OFS in the whole population. A subgroup analysis showed that addition of OFS significantly improved overall survival in patients who were administered chemotherapy. Conclusion Based on the available studies, concurrent administration of OFS and adjuvant tamoxifen treatment for premenopausal women with breast cancer has no effect on prolonging disease-free survival and overall survival, excluding patients who were administered chemotherapy. It should not be widely recommended, except perhaps for women who were hormone-receptor positive and who were also administered adjuvant chemotherapy. PMID:26109867

  4. Emerging treatment strategies for glioblastoma multiforme

    PubMed Central

    Carlsson, Steven K; Brothers, Shaun P; Wahlestedt, Claes

    2014-01-01

    Glioblastoma multiforme (GBM) is the deadliest form of brain tumor with a more than 90% 5-year mortality. GBM has a paltry median survival of 12.6 months attributed to the unique treatment limitations such as the high average age of onset, tumor location, and poor current understandings of the tumor pathophysiology. The resection techniques, chemotherapic strategies, and radiation therapy currently used to treat GBM have slowly evolved, but the improvements have not translated to marked increases in patient survival. Here, we will discuss the recent progress in our understanding of GBM pathophysiology, and the diagnostic techniques and treatment options. The discussion will include biomarkers, tumor imaging, novel therapies such as monoclonal antibodies and small-molecule inhibitors, and the heterogeneity resulting from the GBM cancer stem cell population. PMID:25312641

  5. Adjuvant percutaneous radiofrequency ablation of feeding artery of hepatocellular carcinoma before treatment

    PubMed Central

    Hou, Yi-Bin; Chen, Min-Hua; Yan, Kun; Wu, Jin-Yu; Yang, Wei

    2009-01-01

    AIM: To evaluate the feasibility and efficacy of percutaneous radiofrequency ablation (RFA) of the feeding artery of hepatocellular carcinoma (HCC) in reducing the blood-flow-induced heat-sink effect of RFA. METHODS: A total of 154 HCC patients with 177 pathologically confirmed hypervascular lesions participated in the study and were randomly assigned into two groups. Seventy-one patients with 75 HCCs (average tumor size, 4.3 ± 1.1 cm) were included in group A, in which the feeding artery of HCC was identified by color Doppler flow imaging, and were ablated with multiple small overlapping RFA foci [percutaneous ablation of feeding artery (PAA)] before routine RFA treatment of the tumor. Eighty-three patients with 102 HCC (average tumor size, 4.1 ± 1.0 cm) were included in group B, in which the tumors were treated routinely with RFA. Contrast-enhanced computed tomography was used as post-RFA imaging, when patients were followed-up for 1, 3 and 6 mo. RESULTS: In group A, feeding arteries were blocked in 66 (88%) HCC lesions, and the size of arteries decreased in nine (12%). The average number of punctures per HCC was 2.76 ± 1.12 in group A, and 3.36 ± 1.60 in group B (P = 0.01). The tumor necrosis rate at 1 mo post-RFA was 90.67% (68/75 lesions) in group A and 90.20% (92/102 lesions) in group B. HCC recurrence rate at 6 mo post-RFA was 17.33% (13/75) in group A and 31.37% (32/102) in group B (P = 0.04). CONCLUSION: PAA blocked effectively the feeding artery of HCC. Combination of PAA and RFA significantly decreased post-RFA recurrence and provided an alternative treatment for hypervascular HCC. PMID:19496195

  6. Evaluating dynamic treatment strategies: does it have to be more costly?

    PubMed

    Buyze, Jozefien; Goetghebeur, Els

    2013-01-01

    Dynamic treatment strategies are designed to change treatments over time in response to intermediate outcomes. They can be deployed for primary treatment as well as for the introduction of adjuvant treatment or other treatment-enhancing interventions. When treatment interventions are delayed until needed, more cost-efficient strategies will result. Sequential multiple assignment randomized (SMAR) trials allow for unbiased estimation of the marginal effects of different sequences of history-dependent treatment decisions. Because a single SMAR trial enables evaluation of many different dynamic regimes at once, it is naturally thought to require larger sample sizes than the parallel randomized trial. In this paper, we compare power between SMAR trials studying a regime, where treatment boosting enters when triggered by an observed event, versus the parallel design, where a treatment boost is consistently prescribed over the entire study period. In some settings, we found that the dynamic design yields the more efficient trial for the detection of treatment activity. We develop one particular trial to compare a dynamic nursing intervention with telemonitoring for the enhancement of medication adherence in epilepsy patients. To this end, we derive from the SMAR trial data either an average of conditional treatment effects ('conditional estimator') or the population-averaged ('marginal') estimator of the dynamic regimes. Analytical sample size calculations for the parallel design and the conditional estimator are compared with simulated results for the population-averaged estimator. We conclude that in specific settings, well-chosen SMAR designs may require fewer data for the development of more cost-efficient treatment strategies than parallel designs. PMID:23208788

  7. Self-adjuvanted hyaluronate--antigenic peptide conjugate for transdermal treatment of muscular dystrophy.

    PubMed

    Kong, Won Ho; Sung, Dong Kyung; Kim, Hyemin; Yang, Jeong-A; Ieronimakis, Nicholas; Kim, Ki Su; Lee, Jeehun; Kim, Deok-Ho; Yun, Seok Hyun; Hahn, Sei Kwang

    2016-03-01

    Duchenne's muscular dystrophy (DMD) is a neuromuscular disorder accompanied with muscle weakness and wasting. Since myostatin was reported to be a key regulator of muscle wasting, myostatin inhibitors have been investigated as therapeutic candidates for the treatment of muscular diseases. Here, we report an antigenic peptide of myostatin fragment (MstnF) conjugated to hyaluronate (HA) with a low molecular weight (MW, 17 kDa) for transdermal immunotherapy of DMD. Facilitating the transdermal delivery, the low MW HA showed a boosting effect on the immunization of MstnF possibly by engaging both toll-like receptors and cluster of differentiation 44 (CD44). In vivo two-photon microscopy clearly visualized the effective transdermal penetration of HA-MstnF conjugates into deep intact skin layers. The transdermal immunization of mdx mice significantly increased antibody titers against myostatin. Furthermore, the mdx mice immunized with HA-MstnF conjugates resulted in statistically significant improvement in the biochemical and pathological status of skeletal musculature as well as functional behaviors. PMID:26724457

  8. What is the optimal neo-adjuvant treatment for liver metastasis?

    PubMed Central

    Haraldsdottir, Sigurdis; Wu, Christina; Bloomston, Mark

    2013-01-01

    Colorectal cancer is the third most common cancer in the Western population and has a 5-year overall survival of 5–10% when metastatic. Approximately 30% of the patients with metastatic colorectal cancer have limited disease apparently isolated to the liver and, if this can be resected, the 5-year overall survival is improved to 30–60%. Therefore, it is important to identify patients who have both resectable disease and those with initially unresectable tumors who can potentially be downsized with chemotherapy to allow resection. First-line doublet chemotherapy regimens lead to response rates of 50–60%, triplet chemotherapy regimens may result in a response rate of up to 70%, and biological agents may add to responses or induce morphologic changes that facilitate disease resection. Surgical advances in recent years have also increased resectability rates and have challenged prior rules of resectability. Local therapies including ablation and radiation, often performed in conjunction with resection, may further aid in control of disease. The aim of this article is to focus on the role of neoadjuvant therapy in the treatment of colorectal liver metastases. PMID:23858331

  9. Telomerase expression and telomere length in breast cancer and their associations with adjuvant treatment and disease outcome

    PubMed Central

    2011-01-01

    Introduction Telomere length plays important roles in maintaining genome stability and regulating cell replication and death. Telomerase has functions not only to extend telomere length but also to repair DNA damage. Studies have shown that telomerase may increase cancer cell resistance to DNA-damaging anticancer agents; tamoxifen may suppress telomerase expression in breast cancer cells. This study aimed to investigate the role of telomere length and telomerase activity in breast cancer prognosis. Methods qPCR and qRT-PCR were used to analyze telomere length and telomerase expression, respectively, in tumor samples of 348 breast cancer patients. Cox regression analysis was performed to examine telomere length and telomerase expression in association with disease-free survival and cause-specific mortality. Results Telomere length had no relation to tumor features or disease outcomes. Telomerase expression was detected in 53% of tumors. Larger tumors or aggressive disease were more likely to have telomerase expression. Among patients treated with chemotherapy, high telomerase was found to be associated with increased risk of death (hazard ratio (HR) = 3.15; 95% CI: 1.34 to 7.40) and disease recurrence (HR = 2.04; 95% CI: 0.96 to 4.30) regardless of patient age, disease stage, tumor grade, histological type or hormone receptor status. Patients treated with endocrine therapy had different results regarding telomerase: high telomerase appeared to be associated with better survival outcomes. Telomerase expression made no survival difference in patients who received both chemotherapy and endocrine therapy. Conclusions Overall, telomerase expression was not associated with disease outcome, but this finding may be masked by adjuvant treatment. Patients with high telomerase expression responded poorly to chemotherapy in terms of disease-free and overall survival, but fared better if treated with endocrine therapy. PMID:21645396

  10. The Efficacy of Adjuvant Intratympanic Steroid Treatment for Otitis Media with Effusion in Children

    PubMed Central

    Amer, Hazem Saeed; El-Anwar, Mohammad Waheed; Elfeky, Alaa Eldin

    2015-01-01

    Introduction  Otitis media with effusion (OME) is a leading cause of hearing impairment in children. Therefore, early and proper management is essential. Objectives  The objective of this research is to assess the efficacy of intratympanic (IT) steroids injection for management of otitis media with effusion (OME). Methods  This study involved 42 children (84 ears) with bilateral OME. We used tympanometry to confirm the childreńs middle ear effusion and pure tone audiometry to determine hearing threshold. We performed myringotomy and inserted ventilation tubes (VTs) bilaterally, followed by a steroid injection of 0.4–0.6 mL methylprednisolone (40 mg/mL) into one randomly selected middle ear. This procedure was followed by once-weekly administration of steroids (0.5 mL methylprednisolone at a concentration of 40 mg/mL) into the middle ear for three consecutive weeks. Results  We found recurrent OME after VT alone in nine (21.4%) ears; whereas, after VT combined with steroid administration, we found two (4.76%), with statistically significant difference. We noted tympanosclerosis postoperatively in six (12.9%) ears and in one of the injected ears (2.3%) (p = 0.0484). Otorrhea occurred in eight (19%) ears with VT alone and in three (7.1%) injected ears, with non-significant difference. The duration between VT insertion and its extrusion was 6.6 = 1.1 months for ears with VT alone and 6.95 =1.12 months in injected ears (p = 0.1541 NS). Conclusion  IT Steroids injection for treatment of OME is a safe and simple intervention with lower incidence of symptoms recurrence and postoperative complications. Thus, its use in management of OME is recommended.

  11. The impact of the 21-gene assay on adjuvant treatment decisions in oestrogen receptor-positive early breast cancer: a prospective study

    PubMed Central

    Kuchel, Anna; Robinson, Tim; Comins, Charles; Shere, Mike; Varughese, Mohini; Sparrow, Geoff; Sahu, Ajay; Saunders, Louise; Bahl, Amit; Cawthorn, Simon J; Braybrooke, Jeremy P

    2016-01-01

    Background: International guidelines, including NICE, recommend using the 21-gene Recurrence Score assay for guiding adjuvant treatment decisions in ER+, HER2-negative early breast cancer (BC). We investigated the impact of adding this assay to standard pathological tests on clinicians'/patients' treatment decisions and on patients' decisional conflict in the United Kingdom. Methods: In this prospective multicentre study, eligibility criteria included: ER+ HER2-negative BC (N0/Nmic for patients ⩽50 years; ⩽3 positive lymph nodes for patients >50 years) and being fit for chemotherapy. Physicians'/patients' treatment choices and patients' decisional conflict were recorded pre- and post testing. Results: The analysis included 137 patients. Overall, adjuvant treatment recommendations changed in 40.7% of patients, with the direction of the change consistent with the Recurrence Score results (net decrease in chemotherapy recommendation rate in low Recurrence Score patients and net increase in high Recurrence Score patients). Patients' choices were generally consistent with physicians' recommendations. Post-testing, patients' decisional conflict decreased significantly (P<0.0001). In the 67 patients meeting the NICE criteria for testing, the recommendation change rate was 49.3%. Conclusions: Recurrence Score testing significantly influenced treatment recommendations overall and in the subgroup of patients meeting the NICE criteria, suggesting that this test could substantially alter treatment patterns in the United Kingdom. PMID:26954715

  12. Prior Adjuvant Tamoxifen Treatment in Breast Cancer Is Linked to Increased AIB1 and HER2 Expression in Metachronous Contralateral Breast Cancer

    PubMed Central

    Alkner, Sara; Bendahl, Pär-Ola; Ehinger, Anna; Lövgren, Kristina; Rydén, Lisa; Fernö, Mårten

    2016-01-01

    Aim The estrogen receptor coactivator Amplified in Breast Cancer 1 (AIB1) has been associated with an improved response to adjuvant tamoxifen in breast cancer, but also with endocrine treatment resistance. We hereby use metachronous contralateral breast cancer (CBC) developed despite prior adjuvant tamoxifen for the first tumor as an “in vivo”-model for tamoxifen resistance. AIB1-expression in the presumable resistant (CBC after prior tamoxifen) and naïve setting (CBC without prior tamoxifen) is compared and correlated to prognosis after CBC. Methods From a well-defined population-based cohort of CBC-patients we have constructed a unique tissue-microarray including >700 patients. Results CBC developed after adjuvant tamoxifen more often had a HER2-positive/triple negative-subtype and a high AIB1-expression (37% vs. 23%, p = 0.009), than if no prior endocrine treatment had been administered. In patients with an estrogen receptor (ER) positive CBC, a high AIB1-expression correlated to an inferior prognosis. However, these patients seemed to respond to tamoxifen, but only if endocrine therapy had not been administered for BC1. Conclusions Metachronous CBC developed after prior endocrine treatment has a decreased ER-expression and an increased HER2-expression. This is consistent with endocrine treatment escape mechanisms previously suggested, and indicates metachronous CBC to be a putative model for studies of treatment resistance “in vivo”. The increased AIB1-expression in CBC developed after prior tamoxifen suggests a role of AIB1 in endocrine treatment resistance. In addition, we found indications that the response to tamoxifen in CBC with a high AIB1-expression seem to differ depending on previous exposure to this drug. A different function for AIB1 in the tamoxifen treatment naïve vs. resistant setting is suggested, and may explain previously conflicting results where a high AIB1-expression has been correlated to both a good response to adjuvant

  13. Inhalation injury: epidemiology, pathology, treatment strategies

    PubMed Central

    2013-01-01

    Lung injury resulting from inhalation of smoke or chemical products of combustion continues to be associated with significant morbidity and mortality. Combined with cutaneous burns, inhalation injury increases fluid resuscitation requirements, incidence of pulmonary complications and overall mortality of thermal injury. While many products and techniques have been developed to manage cutaneous thermal trauma, relatively few diagnosis-specific therapeutic options have been identified for patients with inhalation injury. Several factors explain slower progress for improvement in management of patients with inhalation injury. Inhalation injury is a more complex clinical problem. Burned cutaneous tissue may be excised and replaced with skin grafts. Injured pulmonary tissue must be protected from secondary injury due to resuscitation, mechanical ventilation and infection while host repair mechanisms receive appropriate support. Many of the consequences of smoke inhalation result from an inflammatory response involving mediators whose number and role remain incompletely understood despite improved tools for processing of clinical material. Improvements in mortality from inhalation injury are mostly due to widespread improvements in critical care rather than focused interventions for smoke inhalation. Morbidity associated with inhalation injury is produced by heat exposure and inhaled toxins. Management of toxin exposure in smoke inhalation remains controversial, particularly as related to carbon monoxide and cyanide. Hyperbaric oxygen treatment has been evaluated in multiple trials to manage neurologic sequelae of carbon monoxide exposure. Unfortunately, data to date do not support application of hyperbaric oxygen in this population outside the context of clinical trials. Cyanide is another toxin produced by combustion of natural or synthetic materials. A number of antidote strategies have been evaluated to address tissue hypoxia associated with cyanide exposure. Data

  14. Contribution of ABCB1 and CYP2D6 genotypes to the outcome of tamoxifen adjuvant treatment in premenopausal women with breast cancer.

    PubMed

    Argalácsová, S; Slanař, O; Vítek, P; Tesařová, P; Bakhouche, H; DraŽďáková, M; Bartošová, O; Zima, T; PertuŽelka, L

    2015-01-01

    Recent pre-clinical evidence suggests that the active metabolite of tamoxifen, endoxifen, is a substrate for efflux pump P-glycoprotein. The aim of our study was to evaluate, if the polymoprhisms within ABCB1 gene alter tamoxifen adjuvant treatment efficacy in premenopausal women. Totally 71 premenopausal women with estrogen receptor positive breast cancer indicated for tamoxifen adjuvant treatment were followed retrospectively for median period of 56 months. The gentic polymorphisms of CYP2D6 and ABCB1 were analyzed and potential covariates as tumor grading, staging, age at the diagnosis, comedication, quantitative positivity of ER or PR were also evaluated. Cox proportional-hazards regression model indicated that patients carrying at least one variant allele in ABCB1 rs1045642 had significantly longer time to event survival compared to wild type subjects. Non-significant trend was noted for better treatment outcome of patients carrying at least one variant allele in the SNP rs2032582, while for the CYP2D6 polymorphism poor metabolizer phenotype resulted in worse outcome in comparison to extensive metabolizers subjects with HR of 4.04 (95 % CI 0.31-52.19). Similarly, patients using CYP2D6 inhibitors had non-significantly shorter time-to-event as compared to never users resulting in hazard ratio of 2.06 (95 % CI 0.40-10.63). ABCB1 polymorphisms may affect outcome of tamoxifen adjuvant treatment in premenopausal breast cancer patiens. This factor should be taken into account in addition to the CYP2D6 polymorphism or phenotypic inhibition of CYP2D6 activity. PMID:26681084

  15. Selecting the best strategy of treatment in newly diagnosed advanced-stage ovarian cancer patients

    PubMed Central

    Minig, Lucas; Zorrero, Cristina; Iserte, Pablo Padilla; Poveda, Andres

    2015-01-01

    Although it is assumed that the combination of chemotherapy and radical surgery should be indicated in all newly diagnosed advanced-stage ovarian cancer patients, one of the main raised questions is how to select the best strategy of initial treatment in this group of patients, neoadjuvant chemotherapy followed by interval debulking surgery or primary debulking surgery followed by adjuvant chemotherapy. The selection criteria to offer one strategy over the other as well as a stepwise patient selection for initial treatment are described. Selecting the best strategy of treatment in newly diagnosed advanced stage ovarian cancer patients is a multifactorial and multidisciplinary decision. Several factors should be taken into consideration: (1) the disease factor, related to the extension and localization of the disease as well as tumor biology; (2) the patient factor, associated with patient age, poor performance status, and co-morbidities; and (3) institutional infrastructure factor, related to the lack of prolonged operative time, an appropriate surgical armamentarium, as well as well-equipped intensive care units with well-trained personnel. PMID:26713279

  16. Adjuvant Therapy Trials.

    PubMed

    Ursem, Carling; Van Loon, Katherine; Venook, Alan

    2016-01-01

    In 2015, ramucirumab and TAS-102 became the 10th and 11th drugs approved by the Food and Drug administration for the treatment of patients with colorectal cancer, not counting leucovorin, and yet only 3 agents, 5-fluorouracil, capecitabine, and oxaliplatin, have proven benefit in adjuvant treatment. In fact, there have been no additions (and 1 subtraction levamisole) to our arsenal of therapies for patients with stages II and III colon cancer for more than a decade. How did we get here? Are we stuck? And how do we move forward? PMID:27341598

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

    PubMed Central

    Zhang, Ying; Le, Trong Kim; Shaw, James W; Kotapati, Srividya

    2015-01-01

    Background 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 demonstrated the largest difference between IFN-treated and observation patients. Outpatient service costs for IFN-treated patients were $32,414±$2,498, over three times greater than those for observation patients ($10,556±$1,128; P<0.0001). Conclusion The majority of adjuvant melanoma patients in this study was treated with observation versus IFN treatment. Among those who attempted IFN treatment, most could not complete the recommended course of therapy. Health care costs were

  18. A retrospective study on IVF/ICSI outcome in patients with anti-nuclear antibodies: the effects of prednisone plus low-dose aspirin adjuvant treatment

    PubMed Central

    2013-01-01

    Background Anti-nuclear antibodies (ANA) are suspected of having relevance to adverse reproductive events. Methods This study aims to investigate the potential effect of ANA on IVF/ICSI outcome and the therapeutic role of prednisone plus low-dose aspirin (P + A) adjuvant treatment in ANA + patients. The first IVF/ICSI cycles without P + A of sixty-six ANA + women were enrolled as the ANA + group, and the 233 first IVF/ICSI cycles of matched ANA- women served as the ANA- group. The ANA + group was divided into the Titre < =1:320 subgroup and the Titre > 1:320 subgroup. Twenty-one ANA + women with adverse outcomes in their first cycles (ANA + cycles without P + A) received P + A adjuvant treatment for three months before the second IVF/ICSI cycle (ANA + cycles with P + A). The clinical characteristics and the IVF/ICSI outcomes were compared, respectively, between 1) the ANA + group and the ANA- group, 2) the Titre < =1:320 subgroup and the Titre > 1:320 subgroup, and 3) the ANA + cycles without P + A and the ANA + cycles with P + A. Results No significant differences were observed between each of the two-group pairs in the clinical characteristics. The ANA + group exhibited significantly lower MII oocytes rate, normal fertilisation, pregnancy and implantation rates, as well as remarkably higher abnormal fertilisation and early miscarriage rates. The Titre < =1:320 subgroup’s IVF/ICSI outcomes were as poor as those of the Titre > 1:320 subgroup. After the P + A adjuvant treatment, the number of two pro-nuclei, perfect embryos and available embryos, and the implantation rate increased significantly. Conclusions These observations suggest that ANA could exert a detrimental effect on IVF/ICSI outcome that might not be titre-dependent, and P + A adjuvant treatment could be useful for ANA + patients. This hypothesis should be verified in further prospective randomised studies. PMID:24093222

  19. The Promher Study: An Observational Italian Study on Adjuvant Therapy for HER2-Positive, pT1a-b pN0 Breast Cancer

    PubMed Central

    Gori, Stefania; Inno, Alessandro; Fiorio, Elena; Foglietta, Jennifer; Ferro, Antonella; Gulisano, Marcella; Pinotti, Graziella; Gubiotti, Marta; Cavazzini, Maria Giovanna; Turazza, Monica; Duranti, Simona; De Simone, Valeria; Iezzi, Laura; Bisagni, Giancarlo; Spazzapan, Simon; Cavanna, Luigi; Saggia, Chiara; Bria, Emilio; Cretella, Elisabetta; Vici, Patrizia; Santini, Daniele; Fabi, Alessandra; Garrone, Ornella; Frassoldati, Antonio; Amaducci, Laura; Saracchini, Silvana; Evangelisti, Lucia; Barni, Sandro; Gamucci, Teresa; Mentuccia, Lucia; Laudadio, Lucio; Zoboli, Alessandra; Marchetti, Fabiana; Bogina, Giuseppe; Lunardi, Gianluigi; Boni, Luca

    2015-01-01

    Background The management of pT1a-b pN0 HER2-positive breast cancer is controversial and no data about the efficacy of trastuzumab in this setting are available from randomized clinical trials. The aims of this retrospective study were to assess how patients are managed in clinical practice in Italy, which clinical or biological characteristics influenced the choice of adjuvant systemic therapy and the outcome of patients. Methods Data of consecutive patients who underwent surgery from January 2007 to December 2012 for HER2-positive, pT1a-b pN0 M0 breast cancer were retrospectively collected from 28 Italian centres. Analysis of contingency tables and multivariate generalized logit models were used to investigate the association between the baseline clinical and biological features and the treatment strategy adopted. Results Among 303 enrolled patients, 204 received adjuvant systemic therapy with trastuzumab, 65 adjuvant systemic therapy without trastuzumab and 34 did not receive adjuvant systemic therapy. At the multivariate analysis age, tumor size, proliferation index and hormone receptor status were significantly associated with the treatment choice. Five-year disease-free survival (DFS) probability was 95%, 94.3% and 69.6% for patients treated with adjuvant systemic therapy and trastuzumab, with adjuvant systemic therapy without trastuzumab and for patients who did not receive adjuvant systemic therapy, respectively (p<0.001). Conclusions The majority of patients (66%) with pT1a-b pN0 HER2-positive breast cancer enrolled in this retrospective study received adjuvant systemic therapy with trastuzumab, whereas only 11% patients did not receive any adjuvant systemic therapy. The choice of treatment type seems to be mainly influenced by tumor size, proliferation index, hormone receptor status and age. The 5-year DFS probability was significantly higher for patients receiving adjuvant systemic therapy with trastuzumab compared with patients not receiving adjuvant

  20. Multimodal treatment strategies for advanced hilar cholangiocarcinoma.

    PubMed

    Weiss, Matthew J; Cosgrove, David; Herman, Joseph M; Rastegar, Neda; Kamel, Ihab; Pawlik, Timothy M

    2014-08-01

    Cholangiocarcinoma (CCA) is the second most common primary malignancy of the liver arising from malignant transformation and growth of biliary ductal epithelium. Approximately 50-70 % of CCAs arise at the hilar plate of the biliary tree, which are termed hilar cholangiocarcinoma (HC). Various staging systems are currently employed to classify HCs and determine resectability. Depending on the pre-operative staging, the mainstays of treatment include surgery, chemotherapy, radiation therapy, and photodynamic therapy. Surgical resection offers the only chance for cure of HC and achieving an R0 resection has demonstrated improved overall survival. However, obtaining longitudinal and radial surgical margins that are free of tumor can be difficult and frequently requires extensive resections, particularly for advanced HCs. Pre-operative interventions may be necessary to prepare patients for major hepatic resections, including endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography, and portal vein embolization. Multimodal therapy that combines chemotherapy with external beam radiation, stereotactic body radiation therapy, bile duct brachytherapy, and/or photodynamic therapy are all possible strategies for advanced HC prior to resection. Orthotopic liver transplantation is another therapeutic option that can achieve complete extirpation of locally advanced HC in judiciously selected patients following standardized neoadjuvant protocols. PMID:24962146

  1. Adjuvant treatment in patients at high risk of recurrence of thymoma: efficacy and safety of a three-dimensional conformal radiation therapy regimen

    PubMed Central

    Perri, Francesco; Pisconti, Salvatore; Conson, Manuel; Pacelli, Roberto; Della Vittoria Scarpati, Giuseppina; Gnoni, Antonio; D’Aniello, Carmine; Cavaliere, Carla; Licchetta, Antonella; Cella, Laura; Giuliano, Mario; Schiavone, Concetta; Falivene, Sara; Di Lorenzo, Giuseppe; Buonerba, Carlo; Ravo, Vincenzo; Muto, Paolo

    2015-01-01

    Background The clinical benefits of postoperative radiation therapy (PORT) for patients with thymoma are still controversial. In the absence of defined guidelines, prognostic factors such as stage, status of surgical margins, and histology are often considered to guide the choice of adjuvant treatment (radiotherapy and/or chemotherapy). In this study, we describe our single-institution experience of three-dimensional conformal PORT administered as adjuvant treatment to patients with thymoma. Methods Twenty-two consecutive thymoma patients (eleven male and eleven female) with a median age of 52 years and treated at our institution by PORT were analyzed. The patients were considered at high risk of recurrence, having at least one of the following features: stage IIB or III, involved resection margins, or thymic carcinoma histology. Three-dimensional conformal PORT with a median total dose on clinical target volume of 50 (range 44–60) Gy was delivered to the tumor bed by 6–20 MV X-ray of the linear accelerator. Follow-up after radiotherapy was done by computed tomography scan every 6 months for 2 years and yearly thereafter. Results Two of the 22 patients developed local recurrence and four developed distant metastases. Median overall survival was 100 months, and the 3-year and 5-year survival rates were 83% and 74%, respectively. Median disease-free survival was 90 months, and the 5-year recurrence rate was 32%. On univariate analysis, pathologic stage III and presence of positive surgical margins had a significant impact on patient prognosis. Radiation toxicity was mild in most patients and no severe toxicity was registered. Conclusion Adjuvant radiotherapy achieved good local control and showed an acceptable toxicity profile in patients with high-risk thymoma. PMID:26089683

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

    PubMed

    Kim, Ji-Yeon; Shin, Eun; Kim, Jin Won; Lee, Hye Seung; Lee, Dae-Won; Kim, Se-Hyun; Lee, Jeong-Ok; Kim, Yu Jung; Kim, Jee Hyun; Bang, Soo-Mee; Ahn, Sang-Hoon; Park, Do Joong; Lee, Jong Seok; Lee, Ju-Seog; Kim, Hyung-Ho; Lee, Keun-Wook

    2015-01-01

    We analyzed the expression levels of fluoropyrimidine-metabolizing enzymes (thymidylate synthase [TS], dihydropyrimidine dehydrogenase [DPD], thymidine phosphorylase [TP] and orotate phosphoribosyltransferase [OPRT]) to identify potential biomarkers related to treatment outcomes in gastric cancer (GC) patients receiving adjuvant S-1 chemotherapy. In this study, 184 patients who received curative gastrectomy (D2 lymph node dissection) and adjuvant S-1 were included. Immunohistochemistry and quantitative reverse transcription polymerase chain reaction were performed to measure the protein and mRNA levels of TS, DPD, TP, and OPRT in tumor tissue. In univariate analysis, low intratumoral DPD protein expression was related to poorer 5-year disease-free survival (DFS; 78% vs. 88%; P = 0.068). Low intratumoral DPD mRNA expression (1st [lowest] quartile) was also related to poorer DFS (69% vs. 90%; P < 0.001) compared to high intratumoral DPD expression (2nd to 4th quartiles). In multivariate analyses, low intratumoral DPD protein or mRNA expression was related to worse DFS (P < 0.05), irrespective of other clinical variables. TS, TP, and OPRT expression levels were not related to treatment outcomes. Severe non-hematologic toxicities (grade ≥ 3) had a trend towards more frequent development in patients with low intratumoral DPD mRNA expression (29% vs. 16%; P = 0.068). In conclusion, GC patients with high intratumoral DPD expression did not have inferior outcome following adjuvant S-1 therapy compared with those with low DPD expression. Instead, low intratumoral DPD expression was related to poor DFS. PMID:25793299

  3. Optimizing Hypoxia Detection and Treatment Strategies

    PubMed Central

    Koch, Cameron J.; Evans, Sydney M.

    2015-01-01

    Clinical studies using Eppendorf® needle sensors have invariably documented the resistance of hypoxic human tumors to therapy. These studies first documented the need for individual patient measurement of hypoxia, since hypoxia varied from tumor-to-tumor. Furthermore, hypoxia in sarcomas & cervical cancer leads to distant metastasis or local/regional spread, respectively. For various reasons, the field has moved away from direct needle-sensor oxygen measurements to indirect assays (HIF-related changes; bioreductive metabolism) and the latter can be imaged non-invasively. Many of hypoxia’s detrimental therapeutic effects are reversible in mice but little treatment-improvement in hypoxic human tumors has been seen. The question is why? What factors cause human tumors to be refractory to anti-hypoxia strategies? We suggest the primary cause to be the complexity of hypoxia formation and its characteristics. Three basic types of hypoxia exist, encompassing various diffusional (distance from perfused vessel), temporal (on/off cycling) and perfusional (blood-flow efficiency) limitations. Surprisingly, there is no current information on their relative prevalence in human tumors and even animal models. This is important because different hypoxia sub-types are predicted to require different diagnostic and therapeutic approaches, but the implications of this remain unknown. Even more challenging, no agreement exists for the best way to measure hypoxia. Some results even suggest that hypoxia is unlikely to be targetable therapeutically. In this review, the authors will revisit various critical aspects of this field that are sometimes forgotten or misrepresented in the recent literature. Since most current non-invasive imaging studies involve PET-isotope-labelled 2-nitroimidazoles, we will emphasize key findings made in our studies using EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide] and F18-labelled EF5. These will show the importance of

  4. Cancer Treatment Strategies Targeting Sphingolipid Metabolism

    PubMed Central

    Oskouian, Babak; Saba, Julie D.

    2011-01-01

    Ceramide and sphingosine-1-phosphate are related sphingolipid metabolites that can be generated through a de novo biosynthetic route or derived from the recycling of membrane sphingomyelin. Both these lipids regulate cellular responses to stress, with generally opposing effects. Sphingosine-1-phosphate functions as a growth and survival factor, acting as a ligand for a family of G protein-coupled receptors, whereas ceramide activates intrinsic and extrinsic apoptotic pathways through receptor-independent mechanisms. A growing body of evidence has implicated ceramide, sphingosine-1-phosphate and the genes involved in their synthesis, catabolism and signaling in various aspects of oncogenesis, cancer progression and drug- and radiation resistance. This may be explained in part by the finding that both lipids impinge upon the PI3K/AKT pathway, which represses apoptosis and autophagy. In addition, sphingolipids influence cell cycle progression, telomerase function, cell migration and stem cell biology. Considering the central role of ceramide in mediating physiological as well as pharmacologically stimulated apoptosis, ceramide can be considered a tumor-suppressor lipid. In contrast, sphingosine-1-phosphate can be considered a tumor-promoting lipid, and the enzyme responsible for its synthesis functions as an oncogene. Not surprisingly, genetic mutations that result in reduced ceramide generation, increased sphingosine-1-phosphate synthesis or which reduce steady state ceramide levels and increase sphingosine-1-phosphate levels have been identified as mechanisms of tumor progression and drug resistance in cancer cells. Pharmacological tools for modulating sphingolipid pathways are being developed and represent novel therapeutic strategies for the treatment of cancer. PMID:20919655

  5. Differences in Supratentorial Damage of White Matter in Pediatric Survivors of Posterior Fossa Tumors With and Without Adjuvant Treatment as Detected by Magnetic Resonance Diffusion Tensor Imaging

    SciTech Connect

    Rueckriegel, Stefan Mark; Driever, Pablo Hernaiz; Blankenburg, Friederike; Luedemann, Lutz; Henze, Guenter; Bruhn, Harald

    2010-03-01

    Purpose: To elucidate morphologic correlates of brain dysfunction in pediatric survivors of posterior fossa tumors by using magnetic resonance diffusion tensor imaging (DTI) to examine neuroaxonal integrity in white matter. Patients and Methods: Seventeen medulloblastoma (MB) patients who had received surgery and adjuvant treatment, 13 pilocytic astrocytoma (PA) patients who had been treated only with surgery, and age-matched healthy control subjects underwent magnetic resonance imaging on a 3-Tesla system. High-resolution conventional T1- and T2-weighted magnetic resonance imaging and DTI data sets were obtained. Fractional anisotropy (FA) maps were analyzed using tract-based spatial statistics, a part of the Functional MRI of the Brain Software Library. Results: Compared with control subjects, FA values of MB patients were significantly decreased in the cerebellar midline structures, in the frontal lobes, and in the callosal body. Fractional anisotropy values of the PA patients were not only decreased in cerebellar hemispheric structures as expected, but also in supratentorial parts of the brain, with a distribution similar to that in MB patients. However, the amount of significantly decreased FA was greater in MB than in PA patients, underscoring the aggravating neurotoxic effect of the adjuvant treatment. Conclusions: Neurotoxic mechanisms that are present in PA patients (e.g., internal hydrocephalus and damaged cerebellar structures affecting neuronal circuits) contribute significantly to the alteration of supratentorial white matter in pediatric posterior fossa tumor patients.

  6. Utility of PET/CT Imaging Performed Early After Surgical Resection in the Adjuvant Treatment Planning for Head and Neck Cancer

    SciTech Connect

    Shintani, Stephanie A.; Foote, Robert L. Lowe, Val J.; Brown, Paul D.; Garces, Yolanda I.; Kasperbauer, Jan L.

    2008-02-01

    Purpose: To evaluate the utility of positron emission tomography (PET)/computed tomography (CT) early after surgical resection and before postoperative adjuvant radiation therapy. Methods and Materials: We studied a prospective cohort of 91 consecutive patients referred for postoperative adjuvant radiation therapy after complete surgical resection. Tumor histologies included 62 squamous cell and 29 non-squamous cell cancers. Median time between surgery and postoperative PET/CT was 28 days (range, 13-75 days). Findings suspicious for persistent/recurrent cancer or distant metastasis were biopsied. Correlation was made with changes in patient care. Results: Based on PET/CT findings, 24 patients (26.4%) underwent biopsy of suspicious sites. Three patients with suspicious findings did not undergo biopsy because the abnormalities were not easily accessible. Eleven (45.8%) biopsies were positive for cancer. Treatment was changed for 14 (15.4%) patients (11 positive biopsy and 3 nonbiopsied patients) as a result. Treatment changes included abandonment of radiation therapy and switching to palliative chemotherapy or hospice care (4), increasing the radiation therapy dose (6), extending the radiation therapy treatment volume and increasing the dose (1), additional surgery (2), and adding palliative chemotherapy to palliative radiation therapy (1). Treatment for recurrent cancer and primary skin cancer were significant predictors of having a biopsy-proven, treatment-changing positive PET/CT (p < 0.03). Conclusions: Even with an expectedly high rate of false positive PET/CT scans in this early postoperative period, PET/CT changed patient management in a relatively large proportion of patients. PET/CT can be recommended in the postoperative, preradiation therapy setting with the understanding that treatment-altering PET/CT findings should be biopsied for confirmation.

  7. Long-term quality of life after intensified multi-modality treatment of oral cancer including intra-arterial induction chemotherapy and adjuvant chemoradiation

    PubMed Central

    Kovács, Adorján F.; Stefenelli, Ulrich; Thorn, Gerrit

    2015-01-01

    Background: Quality of life (QoL) studies are well established when accompanying trials in head and neck cancer, but studies on long-term survivors are rare. Aims: The aim was to evaluate long-term follow-up patients treated with an intensified multi-modality therapy. Setting and Design: Cross-sectional study, tertiary care center. Patients and Methods: A total of 135 oral/oropharyngeal cancer survivors having been treated with an effective four modality treatment (intra-arterial induction chemotherapy, radical surgery, adjuvant radiation, concurrent systemic chemotherapy) filled European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and HN35 questionnaires. Mean distance to treatment was 6.1 (1.3–16.6) years. Results were compared with a reference patient population (EORTC reference manual). In-study group comparison was also carried out. Statistical Analysis: One-sample t-test, Mann–Whitney-test, Kruskal–Wallis analysis. Results: QoL scores of both populations were well comparable. Global health status, cognitive and social functioning, fatigue, social eating, status of teeth, mouth opening and dryness, and sticky saliva were significantly worse in the study population; pain and need for pain killers, cough, need for nutritional support, problems with weight loss and gain were judged to be significantly less. Patients 1-year posttreatment had generally worse scores as compared to patients with two or more years distance to treatment. Complex reconstructive measures and adjuvant (chemo) radiation were main reasons for significant impairment of QoL. Conclusion Subjective disease status of patients following a maximized multi-modality treatment showed an expectable high degree of limitations, but was generally comparable to a reference group treated less intensively, suggesting that the administration of an intensified multi-modality treatment is feasible in terms of QoL/effectivity ratio. PMID:26389030

  8. The neurovascular unit and combination treatment strategies for stroke

    PubMed Central

    Zhang, Li; Zhang, Zhang Gang; Chopp, Michael

    2012-01-01

    Tissue plasminogen activator (tPA) administered within 4.5 hours of symptom onset restores cerebral blood flow and promotes neurological recovery of stroke patients. However, the narrow therapeutic time window and the risk of intracerebral hemorrhage after tPA treatment pose major hurdles to its clinical usage. In light of the failures of neuroprotective therapies in clinical trials, emerging concepts suggest that neuroprotection alone without restoration of tissue perfusion and vascular integrity may not be adequate for treatment of acute stroke. Here we review evidence of the use of adjuvant pharmacological agents to extend the therapeutic window for tPA via targeting the neurovascular unit and the underlying mechanisms of the combination therapy in experimental stroke. PMID:22595494

  9. Standard of Care and Controversies in the Adjuvant Endocrine Treatment of Hormone-Responsive Early Breast Cancer

    PubMed Central

    Bauerschlag, Dirk O.; Maass, Nicolai; Schem, Christian

    2014-01-01

    Summary Hormone-responsive early breast cancer is a highly curable disease. In premenopausal women, tamoxifen (TAM) is still the standard treatment. Nowadays, up to 10 years of TAM can be safely administered, especially in women who remain premenopausal. Patients who are considered to be perimenopausal should be initially treated like premenopausal patients. Depending on their serum hormone levels, these patients can be safely switched to an aromatase inhibitor (AI) therapy once the estradiol (E2) and follicle-stimulating hormone (FSH) levels prove the established postmenopausal status. In postmenopausal women, several sequences of endocrine treatment are available. The AI therapy can be induced upfront or sequentially by switching from Tam to AI and vice versa. Extended endocrine therapy, by adding up to 5 years of letrozole after 5 years of TAM, has also been proven to be beneficial in certain patient subgroups. Genotyping of cytochromes such as CYP2D6 did not have any added value in identifying patients who are at higher risk of recurrence. Nevertheless, in all patients the side effects need to be given high consideration. New strategies developed to overcome endocrine resistance are tested in clinical studies. New co-administered drugs such as specific inhibitors of mammalian target of rapamycin (mTOR), Src, or phosphatidylinositol 3-kinase (PI3K) do improve endocrine responsiveness in metastatic disease and will eventually be introduced in the treatment of early breast cancer. PMID:25404889

  10. Mastectomy With Immediate Expander-Implant Reconstruction, Adjuvant Chemotherapy, and Radiation for Stage II-III Breast Cancer: Treatment Intervals and Clinical Outcomes

    SciTech Connect

    Wright, Jean L.; Cordeiro, Peter G.; Ben-Porat, Leah; Van Zee, Kimberly J.; Hudis, Clifford; Beal, Kathryn; McCormick, Beryl

    2008-01-01

    Purpose: To determine intervals between surgery and adjuvant chemotherapy and radiation in patients treated with mastectomy with immediate expander-implant reconstruction, and to evaluate locoregional and distant control and overall survival in these patients. Methods and Materials: Between May 1996 and March 2004, 104 patients with Stage II-III breast cancer were routinely treated at our institution under the following algorithm: (1) definitive mastectomy with axillary lymph node dissection and immediate tissue expander placement, (2) tissue expansion during chemotherapy, (3) exchange of tissue expander for permanent implant, (4) radiation. Patient, disease, and treatment characteristics and clinical outcomes were retrospectively evaluated. Results: Median age was 45 years. Twenty-six percent of patients were Stage II and 74% Stage III. All received adjuvant chemotherapy. Estrogen receptor staining was positive in 77%, and 78% received hormone therapy. Radiation was delivered to the chest wall with daily 0.5-cm bolus and to the supraclavicular fossa. Median dose was 5040 cGy. Median interval from surgery to chemotherapy was 5 weeks, from completion of chemotherapy to exchange 4 weeks, and from exchange to radiation 4 weeks. Median interval from completion of chemotherapy to start of radiation was 8 weeks. Median follow-up was 64 months from date of mastectomy. The 5-year rate for locoregional disease control was 100%, for distant metastasis-free survival 90%, and for overall survival 96%. Conclusions: Mastectomy with immediate expander-implant reconstruction, adjuvant chemotherapy, and radiation results in a median interval of 8 weeks from completion of chemotherapy to initiation of radiation and seems to be associated with acceptable 5-year locoregional control, distant metastasis-free survival, and overall survival.

  11. Current Strategies for the Treatment of Aneurysmal Bone Cysts.

    PubMed

    Tsagozis, Panagiotis; Brosjö, Otte

    2015-12-28

    Aneurysmal bone cysts are benign bone tumors that usually present in childhood and early adulthood. They usually manifest as expansile osteolytic lesions with a varying potential to be locally aggressive. Since their first description in 1942, a variety of treatment methods has been proposed. Traditionally, these tumors were treated with open surgery. Either intralesional surgical procedures or en bloc excisions have been described. Furthermore, a variety of chemical or physical adjuvants has been utilized in order to reduce the risk for local recurrence after excision. Currently, there is a shift to more minimally invasive procedures in order to avoid the complications of open surgical excision. Good results have been reported during percutaneous surgery, or the use of embolization. Recently, sclerotherapy has emerged as a promising treatment, showing effective consolidation of the lesions and functional results that appear to be superior to the ones of open surgery. Lastly, non-invasive treatment, such as pharmaceutical intervention with denosumab or bisphosphonates has been reported to be effective in the management of the disease. Radiotherapy has also been shown to confer good local control, either alone or in conjunction to other treatment modalities, but is associated with serious adverse effects. Here, we review the current literature on the methods of treatment of aneurysmal bone cysts. The indication for each type of treatment along reported outcome of the intervention, as well as potential complications are systematically presented. Our review aims to increase awareness of the different treatment modalities and facilitate decision-making regarding each individual patient. PMID:26793296

  12. Current Strategies for the Treatment of Aneurysmal Bone Cysts

    PubMed Central

    Brosjö, Otte

    2015-01-01

    Aneurysmal bone cysts are benign bone tumors that usually present in childhood and early adulthood. They usually manifest as expansile osteolytic lesions with a varying potential to be locally aggressive. Since their first description in 1942, a variety of treatment methods has been proposed. Traditionally, these tumors were treated with open surgery. Either intralesional surgical procedures or en bloc excisions have been described. Furthermore, a variety of chemical or physical adjuvants has been utilized in order to reduce the risk for local recurrence after excision. Currently, there is a shift to more minimally invasive procedures in order to avoid the complications of open surgical excision. Good results have been reported during percutaneous surgery, or the use of embolization. Recently, sclerotherapy has emerged as a promising treatment, showing effective consolidation of the lesions and functional results that appear to be superior to the ones of open surgery. Lastly, non-invasive treatment, such as pharmaceutical intervention with denosumab or bisphosphonates has been reported to be effective in the management of the disease. Radiotherapy has also been shown to confer good local control, either alone or in conjunction to other treatment modalities, but is associated with serious adverse effects. Here, we review the current literature on the methods of treatment of aneurysmal bone cysts. The indication for each type of treatment along reported outcome of the intervention, as well as potential complications are systematically presented. Our review aims to increase awareness of the different treatment modalities and facilitate decision-making regarding each individual patient. PMID:26793296

  13. A2A Adenosine Receptors Are Differentially Modulated by Pharmacological Treatments in Rheumatoid Arthritis Patients and Their Stimulation Ameliorates Adjuvant-Induced Arthritis in Rats

    PubMed Central

    Vincenzi, Fabrizio; Padovan, Melissa; Targa, Martina; Corciulo, Carmen; Giacuzzo, Sarah; Merighi, Stefania; Gessi, Stefania; Govoni, Marcello; Borea, Pier Andrea; Varani, Katia

    2013-01-01

    A2A adenosine receptors (ARs) play a key role in the inhibition of the inflammatory process. The purpose of this study was to evaluate the modulation of A2AARs in rheumatoid arthritis (RA) patients after different pharmacological treatments and to investigate the effect of A2AAR stimulation in a rat model of arthritis. We investigated A2AAR density and functionality in RA progression by using a longitudinal study in RA patients before and after methotrexate (MTX), anti-TNFα agents or rituximab treatments. A2AARs were analyzed by saturation binding assays in lymphocytes from RA patients throughout the 24-month study timeframe. In an adjuvant-induced arthritis model in rats we showed the efficacy of the A2AAR agonist, CGS 21680 in comparison with standard therapies by means of paw volume assessment, radiographic and ultrasonographic imaging. Arthritic-associated pain was investigated in mechanical allodynia and thermal hyperalgesia tests. IL-10 release following A2AAR stimulation in lymphocytes from RA patients and in serum from arthritic rats was measured. In lymphocytes obtained from RA patients, the A2AAR up-regulation was gradually reduced in function of the treatment time and the stimulation of these receptors mediated a significant increase of IL-10 production. In the same cells, CGS 21680 did not affected cell viability and did not produced cytotoxic effects. The A2AAR agonist CGS 21680 was highly effective, as suggested by the marked reduction of clinical signs, in rat adjuvant-induced arthritis and associated pain. This study highlighted that A2AAR agonists represent a physiological-like therapeutic alternative for RA treatment as suggested by the anti-inflammatory role of A2AARs in lymphocytes from RA patients. The effectiveness of A2AAR stimulation in a rat model of arthritis supported the role of A2AAR agonists as potential pharmacological treatment for RA. PMID:23326596

  14. Closed Fuel Cycle Waste Treatment Strategy

    SciTech Connect

    Vienna, J. D.; Collins, E. D.; Crum, J. V.; Ebert, W. L.; Frank, S. M.; Garn, T. G.; Gombert, D.; Jones, R.; Jubin, R. T.; Maio, V. C.; Marra, J. C.; Matyas, J.; Nenoff, T. M.; Riley, B. J.; Sevigny, G. J.; Soelberg, N. R.; Strachan, D. M.; Thallapally, P. K.; Westsik, J. H.

    2015-02-01

    This study is aimed at evaluating the existing waste management approaches for nuclear fuel cycle facilities in comparison to the objectives of implementing an advanced fuel cycle in the U.S. under current legal, regulatory, and logistical constructs. The study begins with the Global Nuclear Energy Partnership (GNEP) Integrated Waste Management Strategy (IWMS) (Gombert et al. 2008) as a general strategy and associated Waste Treatment Baseline Study (WTBS) (Gombert et al. 2007). The tenets of the IWMS are equally valid to the current waste management study. However, the flowsheet details have changed significantly from those considered under GNEP. In addition, significant additional waste management technology development has occurred since the GNEP waste management studies were performed. This study updates the information found in the WTBS, summarizes the results of more recent technology development efforts, and describes waste management approaches as they apply to a representative full recycle reprocessing flowsheet. Many of the waste management technologies discussed also apply to other potential flowsheets that involve reprocessing. These applications are occasionally discussed where the data are more readily available. The report summarizes the waste arising from aqueous reprocessing of a typical light-water reactor (LWR) fuel to separate actinides for use in fabricating metal sodium fast reactor (SFR) fuel and from electrochemical reprocessing of the metal SFR fuel to separate actinides for recycle back into the SFR in the form of metal fuel. The primary streams considered and the recommended waste forms include; Tritium in low-water cement in high integrity containers (HICs); Iodine-129: As a reference case, a glass composite material (GCM) formed by the encapsulation of the silver Mordenite (AgZ) getter material in a low-temperature glass is assumed. A number of alternatives with distinct advantages are also considered including a fused silica waste form

  15. Adjuvants: Classification, Modus Operandi, and Licensing

    PubMed Central

    Apostólico, Juliana de Souza

    2016-01-01

    Vaccination is one of the most efficient strategies for the prevention of infectious diseases. Although safer, subunit vaccines are poorly immunogenic and for this reason the use of adjuvants is strongly recommended. Since their discovery in the beginning of the 20th century, adjuvants have been used to improve immune responses that ultimately lead to protection against disease. The choice of the adjuvant is of utmost importance as it can stimulate protective immunity. Their mechanisms of action have now been revealed. Our increasing understanding of the immune system, and of correlates of protection, is helping in the development of new vaccine formulations for global infections. Nevertheless, few adjuvants are licensed for human vaccines and several formulations are now being evaluated in clinical trials. In this review, we briefly describe the most well known adjuvants used in experimental and clinical settings based on their main mechanisms of action and also highlight the requirements for licensing new vaccine formulations. PMID:27274998

  16. The relationship between nuclear factor (NF)-κB family gene expression and prognosis in triple-negative breast cancer (TNBC) patients receiving adjuvant doxorubicin treatment

    PubMed Central

    Kim, Ji-Yeon; Jung, Hae Hyun; Ahn, Soomin; Bae, SooYoun; Lee, Se Kyung; Kim, Seok Won; Lee, Jeong Eon; Nam, Seok Jin; Ahn, Jin Seok; Im, Young-Hyuck; Park, Yeon Hee

    2016-01-01

    We investigated gene expression profiles of the NF-κB pathway in patients with triple-negative breast cancer (TNBC) receiving adjuvant chemotherapy to determine the prognostic value of NF-κB pathway genes according to chemotherapeutic regimen. We used the nCounter expression assay to measure expression of 11 genes (NFKB1, NFKB2, RELA, RELB, REL, TP53, FOXC1, TBP, SP1, STAT3 and IRF1 genes) belonging to the NF-κB pathway using mRNA extracted from paraffin-embedded tumor tissues from 203 patients diagnosed with TNBC. Of the 203 patients, 116 were treated with a chemotherapeutic regimen containing doxorubicin. As revealed by the expression profiles of the 11 genes, increased expression of SP1 was associated with poor prognosis in TNBC patients treated with adjuvant doxorubicin chemotherapy (5-year distant recurrence-free survival [5Y DRFS], low vs. high expression [cut-off: median]: 92.3% vs. 71.6%, P = 0.001). In a multivariate Cox regression model, SP1 expression was a useful marker for predicting long-term prognosis in TNBC patients receiving doxorubicin treatment, and we thus suggest that SP1 expression could serve as a prognostic marker in these patients. PMID:27545642

  17. First report of a permanent breast {sup 103}Pd seed implant as adjuvant radiation treatment for early-stage breast cancer

    SciTech Connect

    Pignol, Jean-Philippe . E-mail: Jean-Philippe.Pignol@sw.ca; Keller, Brian; Rakovitch, Eileen; Sankreacha, Raxa; Easton, Harry; Que, William

    2006-01-01

    Purpose: A new technique of adjuvant partial breast irradiation using {sup 103}Pd permanent breast seed implants (PBSI) is presented. The procedure is performed in a single 1-hour session under local anesthesia. Methods and Materials: Patients referred to a single institution for adjuvant radiotherapy after lumpectomy for an infiltrating ductal carcinoma {<=}3 cm in diameter, surgical margin {>=}2 mm, no extensive in situ carcinoma, no lymphovascular invasion, and minimal or negative lymph node involvement were offered a PBSI. Results: Between May and December 2004, 31 eligible patients underwent CT scan and ultrasound simulations assessing PBSI feasibility. Fifteen were excluded because of feasibility issues, and 16 received PBSI. A minimal peripheral dose of 90 Gy was prescribed to the planning target volume corresponding to the clinical target volume identified on the CT scan plus a margin of 1 cm. The procedure was well tolerated; 56% of the patients reported no pain during the procedure, and 46% of the patients developed National Cancer Institute Common Toxicity Criteria Grade 1 acute reaction. None experienced toxicity Grade 2 or 3. Conclusions: Permanent breast seed implantation seems feasible and well tolerated on these preliminary clinical data and represents an ultimate step in the reduction of treatment fraction for partial breast irradiation.

  18. The relationship between nuclear factor (NF)-κB family gene expression and prognosis in triple-negative breast cancer (TNBC) patients receiving adjuvant doxorubicin treatment.

    PubMed

    Kim, Ji-Yeon; Jung, Hae Hyun; Ahn, Soomin; Bae, SooYoun; Lee, Se Kyung; Kim, Seok Won; Lee, Jeong Eon; Nam, Seok Jin; Ahn, Jin Seok; Im, Young-Hyuck; Park, Yeon Hee

    2016-01-01

    We investigated gene expression profiles of the NF-κB pathway in patients with triple-negative breast cancer (TNBC) receiving adjuvant chemotherapy to determine the prognostic value of NF-κB pathway genes according to chemotherapeutic regimen. We used the nCounter expression assay to measure expression of 11 genes (NFKB1, NFKB2, RELA, RELB, REL, TP53, FOXC1, TBP, SP1, STAT3 and IRF1 genes) belonging to the NF-κB pathway using mRNA extracted from paraffin-embedded tumor tissues from 203 patients diagnosed with TNBC. Of the 203 patients, 116 were treated with a chemotherapeutic regimen containing doxorubicin. As revealed by the expression profiles of the 11 genes, increased expression of SP1 was associated with poor prognosis in TNBC patients treated with adjuvant doxorubicin chemotherapy (5-year distant recurrence-free survival [5Y DRFS], low vs. high expression [cut-off: median]: 92.3% vs. 71.6%, P = 0.001). In a multivariate Cox regression model, SP1 expression was a useful marker for predicting long-term prognosis in TNBC patients receiving doxorubicin treatment, and we thus suggest that SP1 expression could serve as a prognostic marker in these patients. PMID:27545642

  19. Adjuvant-induced Human Monocyte Secretome Profiles Reveal Adjuvant- and Age-specific Protein Signatures.

    PubMed

    Oh, Djin-Ye; Dowling, David J; Ahmed, Saima; Choi, Hyungwon; Brightman, Spencer; Bergelson, Ilana; Berger, Sebastian T; Sauld, John F; Pettengill, Matthew; Kho, Alvin T; Pollack, Henry J; Steen, Hanno; Levy, Ofer

    2016-06-01

    Adjuvants boost vaccine responses, enhancing protective immunity against infections that are most common among the very young. Many adjuvants activate innate immunity, some via Toll-Like Receptors (TLRs), whose activities varies with age. Accordingly, characterization of age-specific adjuvant-induced immune responses may inform rational adjuvant design targeting vulnerable populations. In this study, we employed proteomics to characterize the adjuvant-induced changes of secretomes from human newborn and adult monocytes in response to Alum, the most commonly used adjuvant in licensed vaccines; Monophosphoryl Lipid A (MPLA), a TLR4-activating adjuvant component of a licensed Human Papilloma Virus vaccine; and R848 an imidazoquinoline TLR7/8 agonist that is a candidate adjuvant for early life vaccines. Monocytes were incubated in vitro for 24 h with vehicle, Alum, MPLA, or R848 and supernatants collected for proteomic analysis employing liquid chromatography-mass spectrometry (LC-MS) (data available via ProteomeXchange, ID PXD003534). 1894 non-redundant proteins were identified, of which ∼30 - 40% were common to all treatment conditions and ∼5% were treatment-specific. Adjuvant-stimulated secretome profiles, as identified by cluster analyses of over-represented proteins, varied with age and adjuvant type. Adjuvants, especially Alum, activated multiple innate immune pathways as assessed by functional enrichment analyses. Release of lactoferrin, pentraxin 3, and matrix metalloproteinase-9 was confirmed in newborn and adult whole blood and blood monocytes stimulated with adjuvants alone or adjuvanted licensed vaccines with distinct clinical reactogenicity profiles. MPLA-induced adult monocyte secretome profiles correlated in silico with transcriptome profiles induced in adults immunized with the MPLA-adjuvanted RTS,S malaria vaccine (Mosquirix™). Overall, adjuvants such as Alum, MPLA and R848 give rise to distinct and age-specific monocyte secretome profiles

  20. Prognostic Value of Log Odds of Positive Lymph Nodes after Radical Surgery Followed by Adjuvant Treatment in High-Risk Cervical Cancer

    PubMed Central

    Kwon, Jeanny; Eom, Keun-Yong; Kim, In Ah; Kim, Jae-Sung; Kim, Young-Beom; No, Jae Hong; Kim, Kidong

    2016-01-01

    Purpose The purpose of this study is to compare the prognostic efficacy of the number and location of positive lymph nodes (LN), LN ratio (LNR), and log odds of positive LNs (LODDs) in high-risk cervical cancer treated with radical surgery and adjuvant treatment. Materials and Methods Fifty high-risk patients who underwent radical hysterectomy and pelvic node dissection followed by adjuvant treatment were analyzed retrospectively. The patients had International Federation of Gynecology and Obstetrics (FIGO) stage IA2-IIB. Upper LN is defined as common iliac or higher LN, and LNR is the ratio of positive LNs to harvested LNs. LODDs is log odds between positive LNs and negative LNs. Radiotherapy was delivered to the whole pelvis with median 50.4 Gy/28 Fx± to the para-aortic regions. Platinum-based chemotherapy was used in most patients (93%). The median follow-up duration was 80 months. Results The 5-year disease-free survival (DFS) rate was 76.1%, and the overall survival (OS) rate was 86.4%. Treatment failure occurred in 11 patients, and distant failure (DF) was the dominant pattern (90.9%). In univariate analysis, significantly lower DFSwas observed in patients with perineural invasion, ≥ 2 LN metastases, LNR ≥ 10%, upper LN metastasis, and ≥ –1.05 LODDs. In multivariate analysis, ≥ –1.05 LODDs was the only significant factor for DFS (p=0.011). Of patients with LODDs ≥ –1.05, 40.9% experienced DF. LODDs was the only significant prognostic factor for OS as well (p=0.006). Conclusion LODDs ≥ –1.05 was the only significant prognostic factor for both DFS and OS. In patients with LODDs ≥ –1.05, intensified chemotherapy might be required, considering the high rate of DF. PMID:26194370

  1. Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized, phase III trial†

    PubMed Central

    Skorupski, K. A.; Uhl, J. M.; Szivek, A; Allstadt Frazier, S. D.; Rebhun, R. B.; Rodriguez, C. O.

    2016-01-01

    Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease-free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin. PMID:24118677

  2. Breast-Conserving Treatment in the Elderly: Long-Term Results of Adjuvant Hypofractionated and Normofractionated Radiotherapy

    SciTech Connect

    Kirova, Youlia M. Campana, Francois; Savignoni, Alexia; Laki, Fatima; Muresan, Marius; Dendale, Remi; Bollet, Marc A.; Salmon, Remy J.; Fourquet, Alain

    2009-09-01

    Purpose: To evaluate the long-term cause-specific survival (CSS), locoregional recurrence-free survival (LRFS), and metastases-free survival (MFS) in elderly breast cancer patients receiving adjuvant normofractionated (NF) or hypofractionated (HF) radiotherapy (RT). Methods and Materials: Between 1995 and 1999, 367 women aged {>=}70 years with nonmetastatic Stage T1 or T2 tumors were treated by breast-conserving surgery and adjuvant RT at the Institut Curie. They underwent wide tumor excision with or without lymph node dissection followed by RT. They received either a NF-RT schedule, which delivered a total dose of 50 Gy (25 fractions, 5 fractions weekly) to the whole breast, followed by a boost to the tumor bed when indicated, or a HF-RT schedule, which delivered a total dose of 32.5 Gy (five fractions of 6.5 Gy, once weekly) with no subsequent boost. The HF-RT schedule was indicated for the more elderly patients. Results: A total of 317 patients were in the NF-RT group, with 50 in the HF-RT group. The median follow-up was 93 months (range, 9-140). The 5- and 7-year CSS, LRFS, and MFS rates were similar in both groups. The 5-year NF-RT and HF-RT rate was 96% and 95% for CSS, 95% and 94% for LRFS, and 94% and 95% for MFS, respectively. The 7-year NF-RT and HF-RT rate was 93% and 87% for CSS, 93% and 91% for LRFS, and 92% and 93% for MFS, respectively. Conclusion: According to the findings from this retrospective study, the HF-RT schedule is an acceptable alternative to NF-RT for elderly patients. However, large-scale prospective randomized trials are needed to confirm these results.

  3. Current Treatment Strategies in Pediatric Alopecia Areata

    PubMed Central

    Wang, Etienne; Lee, Joyce SS; Tang, Mark

    2012-01-01

    Alopecia areata (AA) is a non-scarring autoimmune disease of the hair follicle that can present at any age. Pediatric cases are commonly seen in a dermatology clinic, and management can potentially be challenging, with a small proportion of cases experiencing a chronic relapsing course marked by distressing hair loss that can bring about significant psychosocial morbidity. We review the established treatments for pediatric alopecia areata, alongside second and third line therapies that have shown to be efficacious. We also offer a treatment algorithm as a guide to the treatment of pediatric AA. PMID:23248364

  4. Current treatment strategies in autoimmune hemolytic disorders.

    PubMed

    Barcellini, Wilma

    2015-10-01

    Autoimmune hemolytic anemia (AIHA) is a heterogeneous disease usually classified according to the thermal range of the autoantibody in warm, cold and mixed forms. The treatment of AIHA is still not evidence-based. Corticosteroids are the first-line therapy for warm AIHA. For refractory/relapsed cases, the choice is between splenectomy (effective in ∼70% cases but with a presumed cure rate of 20%) and rituximab (effective in ∼70-80% of cases), which is becoming the preferred second-line treatment, and thereafter any of the immunosuppressive drugs (azathioprine, cyclophosphamide, cyclosporin, mycophenolate mofetil). Additional therapies are intravenous immunoglobulins and danazol. For severe or refractory cases, last option treatments are plasma-exchange, high-dose cyclophosphamide and alemtuzumab. As regards cold agglutinin disease, rituximab is now recommended as first-line treatment. PMID:26343892

  5. Gynecologic cancer: Diagnosis and treatment strategies

    SciTech Connect

    Rutledge, F.N.; Freedman, R.S.; Gershenson, D.M.

    1987-01-01

    This book contains 36 chapters divided into seven sections. The section headings are: Heath Memorial Award Lecture; Ovarian Cancer; Cervical and Vulvar Cancer; Endometrial Cancer; Trophoblastic Disease; Diagnostic Procedures; and New Treatment Modalities.

  6. The treatment strategy for tracheoesophageal fistula

    PubMed Central

    Wu, Xuemei; Zeng, Junli

    2015-01-01

    With the development of endoscopic techniques, the treatment of tracheoesophageal fistula (TEF) has made marked progress. As surgical intervention is often not an advisable option due to advanced malignancy and poor performance status of the patients, bronchoscopic intervention provides a good choice to palliate symptoms and reconstruct the airway and esophagus. In this review, we focus on the application of interventional therapy of TEF, especially the application of airway stenting, and highlight some representative cases referred to our department for treatment. PMID:26807286

  7. Phosphorylated p-70S6K predicts tamoxifen resistance in postmenopausal breast cancer patients randomized between adjuvant tamoxifen versus no systemic treatment

    PubMed Central

    2014-01-01

    Introduction Activation of the phosphatidylinositol-3-kinase (PI3K) and/or mitogen-activated protein kinase (MAPK) pathways results in anti-estrogen resistance in vitro, but a biomarker with clinical validity to predict intrinsic resistance has not been identified. In metastatic breast cancer patients with previous exposure to endocrine therapy, the addition of a mammalian target of rapamycine (mTOR) inhibitor has been shown to be beneficial. Whether or not patients on adjuvant endocrine treatment might benefit from these drugs is currently unclear. A biomarker that predicts intrinsic resistance could potentially be used as companion diagnostic in this setting. We tested the clinical validity of different downstream-activated proteins in the PI3K and/or MAPK pathways to predict intrinsic tamoxifen resistance in postmenopausal primary breast cancer patients. Methods We recollected primary tumor tissue from patients who participated in a randomized trial of adjuvant tamoxifen (1–3 years) versus observation. After constructing a tissue micro-array, cores from 563 estrogen receptor α positive were immunostained for p-AKT(Thr308), p-AKT(Ser473), p-mTOR, p-p706SK and p-ERK1/2. Cox proportional hazard models for recurrence free interval were used to assess hazard ratios and interactions between these markers and tamoxifen treatment efficacy. Results Interactions were identified between tamoxifen and p-AKT(Thr308), p-mTOR, p-p70S6K and p-ERK1/2. Applying a conservative level of significance, p-p70S6K remained significantly associated with tamoxifen resistance. Patients with p-p70S6K negative tumors derived significant benefit from tamoxifen (HR 0.24, P < 0.0001), while patients whose tumor did express p-p70S6K did not (HR = 1.02, P =0.95), P for interaction 0.004. In systemically untreated breast cancer patients, p-p70S6K was associated with a decreased risk for recurrence. Conclusions Patients whose tumor expresses p-p70S6K, as a marker of downstream PI3K and

  8. Monitoring the effects of wastewater treatment strategies.

    PubMed

    de-la-Ossa-Carretero, J A; Del-Pilar-Ruso, Y; Giménez-Casalduero, F; Sánchez-Lizaso, J L

    2016-02-01

    Wastewater disposal in coastal waters causes widespread environmental problems. Secondary treatment is expected to reduce the adverse effects of insufficiently treated wastewater. The environmental impact of sewage disposal via 18 wastewater treatment plants was analysed using the benthic opportunistic polychaetes and amphipods (BOPA) index. In previous studies this index proved to be an effective tool for monitoring sewage pollution. The impact of these discharges was highly related to treatment level, which ranged from pre-treatment to biological, as well as to flow rates and outfall position. Locations affected by pre-treated wastewater showed environmental degradation, especially marked near outfalls with higher flow rates. At most locations, biologically treated wastewater did not cause a significant impact and an improvement in ecological integrity was detected after this secondary treatment had been implemented. The impact of discharge was highly related to chemical oxygen demand (COD), suspended solids and nutrient concentrations, which are all lower in biologically treated wastewater. A 'moderate' ecological status was observed not only near sewage outfalls with high wastewater flow rates (>1,500,000 m(3)/month) with a COD over 200 mg/l but also near those with lower flow rates but with a COD over 400 mg/l. To reduce the impact of sewage disposal, it is necessary to carry out adequate treatment, have site outfalls deep enough, and implement water recycling. PMID:26801153

  9. [Treatment strategies for advanced prostate cancer].

    PubMed

    Küronya, Zsófia; Bíró, Krisztina; Géczi, Lajos; Németh, Hajnalka

    2015-09-01

    There has been dramatic improvement in the diagnosis and treatment of prostate cancer recently. The treatment of localized disease became more successful with the application of new, sophisticated techniques available for urologic surgeons and radiotherapists. Nevertheless a significant proportion of patients relapses after the initial local treatment or is diagnosed with metastatic disease at the beginning. In the past five years, six new drugs became registered for the treatment of metastatic, castration-resistant prostate cancer, such as sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, the α-emitting radionuclide alpharadin and the receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor denosumab. The availability of these new treatment options raises numerous questions. In this review we present the standard of care of metastatic prostate cancer by disease stage (hormone naive/ hormone sensitive metastatic prostate cancer, non-metastatic castration-resistant prostate cancer, oligometastatic/multimetastatic castration-resistant prostate cancer) and the emerging treatment modalities presently assessed in clinical trials. We would also like to give advice on debatable aspects of the management of metastatic prostate cancer. PMID:26339912

  10. Adjuvant Therapy: Melanoma

    PubMed Central

    Davar, Diwakar; Tarhini, Ahmad; Kirkwood, John M.

    2011-01-01

    With an incidence that is increasing at 2–5% per year, cutaneous melanoma is an international scourge that disproportionately targets young individuals. Despite much research, the treatment of advanced disease is still quite challenging. Immunotherapy with high-dose interferon-α2b or interleukin-2 benefits a select group of patients in the adjuvant and metastatic settings, respectively, with significant attendant toxicity. Advances in the biology of malignant melanoma and the role of immunomodulatory therapy have produced advances that have stunned the field. In this paper, we review the data for the use of interferon-α2b in various dosing ranges, vaccine therapy, and the role of radiotherapy in the adjuvant setting for malignant melanoma. Recent trials in the metastatic setting using anticytoxic T-lymphocyte antigen-4 (anti-CTLA-4) monoclonal antibody therapy and BRAF inhibitor therapy have demonstrated clear benefit with prolongation of survival. Trials investigating combinations of these novel agents with existing immunomodulators are at present underway. PMID:22220281

  11. The Influence of Metastatic Lymph Node Ratio on the Treatment Outcomes in the Adjuvant Chemoradiotherapy in Stomach Tumors (ARTIST) Trial: A Phase III Trial

    PubMed Central

    Kim, Youjin; Kim, Kyoung-Mee; Choi, Min Gew; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung; Lee, Su Jin; Kim, Seung Tae; Lee, Jeeyun; Park, Joon Oh; Park, Young Suk; Lim, Ho Yeong; Kang, Won Ki

    2016-01-01

    Purpose In the Adjuvant Chemoradiotherapy in Stomach Tumors (ARTIST) trial, we investigated whether chemoradiotherapy after D2 gastrectomy reduces the rate of recurrence. Recently, the ratio of metastatic lymph nodes to examined lymph nodes (N ratio) has been proposed as an independent prognostic factor in gastric cancer (GC). The aim of this study was to investigate the relationship between the metastatic N ratio and prognosis of GC after curative D2 surgery. Materials and Methods We retrospectively reviewed the data of 458 ARTIST patients who underwent D2 gastrectomy followed by adjuvant chemotherapy (XP, n=228) or chemoradiotherapy (XPRT, n=230). The disease-free survival (DFS) rates of patients were used to evaluate the influence of N ratio on the treatment outcome. To achieve this, 4 different N ratio categories (0%, 1%~9%, 10%~25%, and >25%) were compared on the basis of their influence on the treatment outcome. Results On multivariate analysis, the N ratio remained an independent prognostic factor for DFS. The hazard ratios (HRs) for the N ratio categories of 0%, 1%~9%, 10%~25%, and >25% were 1, 1.061, 1.202, and 3.571, respectively. In patients having N ratio >25%, the 5-year DFS rates were 55% and 28% for the XPRT and XP arms, respectively (HR, 0.527; 95% confidence interval, 0.307~0.904; P=0.020). Conclusions In patients with curatively resected GC, the N ratio was independently associated with DFS. Although this finding warrants further investigation in future prospective studies, the benefit of chemoradiotherapy for D2 resected GC appears to be more beneficial in cancers having N ratios >25%. PMID:27433396

  12. Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma: 9 years of follow-up.

    PubMed

    Finocchiaro, L M E; Glikin, G C

    2012-12-01

    We present here the updated results after 9 years of the beginning of a trial on canine patients with malignant melanoma. This surgery adjuvant approach combined local suicide gene therapy with a subcutaneous vaccine composed by tumor cells extracts and xenogeneic cells producing human interleukin-2 and granulocyte-macrophage colony-stimulating factor. Toxicity was absent or minimal in all patients (0≤VCOG-CTCAE grade≤1). With respect to surgery-treated controls (ST), the complete surgery (CS) arm of this combined treatment (CT) significantly increased the fraction of local disease-free patients from 13 to 81% and distant metastases free from 32 to 84%. Even though less effective than the CS arm, the partial surgery (PS) arm of this CT was significantly better controlling the disease than only surgery (14% while PS-ST: 0%, P<0.01 and CS-ST: 5%, P<0.05). In addition, CT produced a significant sevenfold (CS) and threefold (PS) increase in overall survival. The CS-CT arm significantly improved both CS-ST metastasis-free- and melanoma overall survival from 99 days (respective ranges: 11-563 and 10-568) to >2848 days (81-2848 and 35-2848). Thus, more of 50% of our CT patients died of melanoma unrelated causes, transforming a lethal disease into a chronic one. Finally, surgery adjuvant CT delayed or prevented post-surgical recurrence and distant metastasis, significantly improved disease-free and overall survival maintaining the quality of life. Long-term safety and efficacy of this treatment are supported by the high number of CT patients (283) and extensive follow-up (>9 years). The successful clinical outcome encourages the further translation of similar approaches to human gene therapy trials. PMID:23059870

  13. SECONDARY WASTE MANAGEMENT STRATEGY FOR EARLY LOW ACTIVITY WASTE TREATMENT

    SciTech Connect

    TW, CRAWFORD

    2008-07-17

    This study evaluates parameters relevant to River Protection Project secondary waste streams generated during Early Low Activity Waste operations and recommends a strategy for secondary waste management that considers groundwater impact, cost, and programmatic risk. The recommended strategy for managing River Protection Project secondary waste is focused on improvements in the Effiuent Treatment Facility. Baseline plans to build a Solidification Treatment Unit adjacent to Effluent Treatment Facility should be enhanced to improve solid waste performance and mitigate corrosion of tanks and piping supporting the Effiuent Treatment Facility evaporator. This approach provides a life-cycle benefit to solid waste performance and reduction of groundwater contaminants.

  14. Acute behavioral interventions and outpatient treatment strategies with suicidal adolescents

    PubMed Central

    O’Brien, Kimberly H. McManama; Singer, Jonathan B.; LeCloux, Mary; Duarté-Vélez, Yovanska; Spirito, Anthony

    2015-01-01

    Despite the prevalence of suicidal thoughts and behaviors among adolescents, there is limited knowledge of effective interventions to use with this population. This paper reviews the findings of studies on behavioral interventions for adolescents who are at acute suicide risk, as well as outpatient treatment and risk management strategies with suicidal adolescents. The importance of addressing comorbid behaviors and enhancing protective factors are discussed. Cultural considerations in working with suicidal adolescents and strategies for conducting culturally competent treatment are explored. PMID:26279646

  15. Nonsurgical Treatment Strategies after Osteoporotic Hip Fractures

    PubMed Central

    Song, Kwang-Soon; Bae, Ki-Cheor; Cho, Chul-Hyun; Son, Eun-Suck; Lee, Kyung-Jae

    2015-01-01

    Osteoporosis is a metabolic disease that is increasing in prevalence as people live longer. Because the orthopedic surgeon is frequently the first and often the only physician to manage patients with osteoporotic hip fractures, every effort should be made to prevent future fractures. A multidisciplinary approach is essential in treatment of osteoporotic fractures. Basic treatment includes calcium and vitamin D supplementation, fall prevention, hip protection, and balance and exercise programs. Currently available pharmacologic agents are divided into antiresorptive and anabolic groups. Antiresorptive agents such as bisphosphonates limit bone resorption through inhibition of osteoclastic activity. Anabolic agents such as parathyroid hormone promote bone formation.

  16. Treatment strategies for tics in Tourette syndrome

    PubMed Central

    Eddy, Clare M.; Rickards, Hugh E.; Cavanna, Andrea E.

    2011-01-01

    Tourette syndrome (TS) is a chronic neurodevelopmental disorder characterized by tics: repetitive, involuntary movements and vocalizations. These symptoms can have a significant impact on patients’ daily functioning across many domains. Tics tend to be most severe in child and adolescent sufferers, so their presence has the potential to impact a period of life that is both critical for learning and is often associated with the experience of greater social tension and self-consciousness than adulthood. Furthermore, control over tics that lead to physical impairment or self-injurious behaviour is of vital importance in maintaining health and quality of life. There are numerous complicating factors in the prescription of treatment for tics, due to both the side effects associated with alleviating agents and patient characteristics, such as age and comorbid conditions. This review summarizes literature pertaining to the efficacy and safety of both traditionally prescribed and more modern medications. We also discuss the merits of behavioural and surgical techniques and highlight newer emerging treatments. Although treatment response is to some extent variable, there are a number of agents that are clearly useful as first-line treatments for TS. Other interventions may be of most benefit to patients exhibiting refractory tics or more specific symptom profiles. PMID:21339906

  17. Personalized treatment strategies in glioblastoma: MGMT promoter methylation status

    PubMed Central

    Thon, Niklas; Kreth, Simone; Kreth, Friedrich-Wilhelm

    2013-01-01

    The identification of molecular genetic biomarkers considerably increased our current understanding of glioma genesis, prognostic evaluation, and treatment planning. In glioblastoma, the most malignant intrinsic brain tumor entity in adults, the promoter methylation status of the gene encoding for the repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) indicates increased efficacy of current standard of care, which is concomitant and adjuvant chemoradiotherapy with the alkylating agent temozolomide. In the elderly, MGMT promoter methylation status has recently been introduced to be a predictive biomarker that can be used for stratification of treatment regimes. This review gives a short summery of epidemiological, clinical, diagnostic, and treatment aspects of patients who are currently diagnosed with glioblastoma. The most important molecular genetic markers and epigenetic alterations in glioblastoma are summarized. Special focus is given to the physiological function of DNA methylation–in particular, of the MGMT gene promoter, its clinical relevance, technical aspects of status assessment, its correlation with MGMT mRNA and protein expressions, and its place within the management cascade of glioblastoma patients. PMID:24109190

  18. Developing adaptive treatment strategies in substance abuse research.

    PubMed

    Murphy, Susan A; Lynch, Kevin G; Oslin, David; McKay, James R; TenHave, Tom

    2007-05-01

    For many individuals, substance abuse possesses characteristics of chronic disorders in that individuals experience repeated cycles of cessation and relapse; hence viewing drug dependence as a chronic, relapsing disorder is increasingly accepted. The development of a treatment for a chronic disorder requires consideration of the ordering of treatments, the timing of changes in treatment, and the use of measures of response, burden and adherence collected during treatment to make further treatment decisions. Adaptive treatment strategies provide a vehicle through which these issues can be addressed and thus provide a means toward improving and informing the clinical management of chronic substance abuse disorders. The sequential multiple assignment randomized trial (SMART) is particularly useful in developing adaptive treatment strategies. Simple analyses that can be used with the SMART design are described. Furthermore, the SMART design is compared with standard experimental designs. PMID:17056207

  19. Treatment resistant depression: strategies for primary care.

    PubMed

    Preston, Taylor C; Shelton, Richard C

    2013-07-01

    Depression is commonly diagnosed and treated in primary care. Recent evidence indicates that the majority of depressed patients will not fully recover with an initial antidepressant treatment. This paper reviews commonly used options for treatment after an inadequate initial antidepressant response. The alternatives range widely, and include escalating the dose of the initial antidepressant, switching to an alternative medication, combining two antidepressants with different mechanisms of action (e.g., bupropion + SSRI or mirtazapine + venlafaxine), adding other medications such as lithium or certain atypical antipsychotics (olanzapine, aripiprazole, or quetiapine) to the antidepressant, adding a natural product such as l-methylfolate or s-adenosylmethionine (SAMe), or adding cognitive behavioral psychotherapy. What agent to be used will depend on the comfort level of the primary care practitioner and the availability of Psychiatry referral. However, it is reasonable to take one or more additional steps to attempt to achieve remission. PMID:23712721

  20. Female urinary incontinence: effective treatment strategies.

    PubMed

    Castro, R A; Arruda, R M; Bortolini, M A T

    2015-04-01

    Urinary incontinence is a dysfunction that tremendously affects women's quality of life, involving social, emotional and economic aspects. Although various treatments for urinary incontinence have been described, it is important to know which of them are truly effective. This review seeks to determine the current available therapies for women with stress urinary incontinence and overactive bladder syndrome, based on the best scientific evidence. PMID:25307986

  1. Three-Dimensional Non-Coplanar Conformal Radiotherapy Yields Better Results Than Traditional Beam Arrangements for Adjuvant Treatment of Gastric Cancer

    SciTech Connect

    Soyfer, Viacheslav Corn, Benjamin W.; Melamud, Alex B.S.; Alani, Shlomi; Tempelhof, Haim; Agai, Reuben; Shmueli, Anat; Figer, Arie; Kovner, Felix

    2007-10-01

    Purpose: The current standard of adjuvant treatment for gastric cancer after curative resection is concurrent administration of radiotherapy and 5-fluorouracil-based chemotherapy. The radiation fields are often arranged as anterioposterior-posteroanterior opposed parallel fields with general recommendations for sparing at least two-thirds of one kidney. We investigated whether a better radiation distribution would be achievable with three-dimensional conformal approaches compared with the classic anterioposterior-posteroanterior fields. Methods and Materials: A total of 19 patients with adenocarcinoma of the stomach were treated with adjuvant chemoradiotherapy using a non-coplanar four-field arrangement. In each case, parallel planning using an anterioposterior-posteroanterior arrangement and a four-field 'box' was performed, and the generated plans were subsequently compared for coverage of target volumes and doses to irradiated organs next to the tumor bed. A separate analysis was performed for kidneys exposed to greater and lower doses in each patient. The mean radiation dose and percentage of kidney volume receiving a dose >20 Gy were registered. Statistical analysis was performed using the two-tailed t test. Results: The clinical target volume was adequately covered in all three plans. In the greater-dose kidney group, all the differences were statistically significant with a benefit for the three-dimensional plan. In the lower-dose kidney group, the differences in the mean radiation dose did not reach the level of statistical significance, and the differences in the kidney volume receiving a dose >20 Gy showed a statistically significant benefit for the three-dimensional plan. Conclusion: Non-coplanar three-dimensional-based conformal planning for postoperative radiotherapy for gastric cancer provided the best results regarding kidney and spinal cord exposure with adequate clinical target volume coverage. This technique was readily implemented in clinical

  2. Burnout: Treatment and Prevention Strategies for College Student Affairs Professionals.

    ERIC Educational Resources Information Center

    Keener, Roger

    1990-01-01

    Presents possible prevention and treatment strategies for combating burnout among college student affairs professionals. Includes definition of burnout, review of symptoms of burnout, discussion of causes of burnout, and suggestions for treatment and prevention of burnout. Interventions discussed include personal counseling, using stress…

  3. [Phantom limb pain. Psychological treatment strategies].

    PubMed

    Diers, M; Flor, H

    2013-04-01

    Similar to other pain syndromes phantom limb pain is characterized by learning and memory processes that maintain the pain and increase maladaptive plastic changes of the brain: therefore, psychological interventions that change maladaptive memory processes are useful. In addition to traditional psychological interventions, such as pain management training and biofeedback, more recent developments that involve sensory discrimination training, mirror treatment, graded motor imagery, prosthesis training and training in virtual reality are interesting. These interventions not only reduce phantom limb pain but also reverse the associated maladaptive brain changes. PMID:23588803

  4. Research strategies for the treatment of biothreats.

    PubMed

    Cherwonogrodzky, John W

    2005-10-01

    Whether it is a layperson in the street or a politician in the Senate, there is widespread fear over the consequences of biothreats. In response to these fears, a wide range of treatments has been developed. These include antibiotics (conventional and unconventional uses), nucleic acids (analogues, antisense, ribozymes and DNAzymes), immunomodulators, antibodies, bacteriophage therapy and micro-encapsulation. Furthermore, there are often additional benefits when these therapeutics are used in combination, rather than alone. Although there has been much investment in therapeutics against a terrorist threat for reasons of national security, there are likely to be far greater benefits and applications on domestic and world health. PMID:16084772

  5. HDT mixtures treatment strategies by gas chromatography

    SciTech Connect

    Laquerbe, C.; Contreras, S.; Demoment, J.

    2008-07-15

    Gas phase chromatographic processes are of interest for the separation of hydrogen isotopes from an HDT mixture. For a certain quantity, they are very competitive and present several benefits. Nevertheless no active packing material allows to have simultaneously good enrichment performances for tritium production and high decontamination capabilities for HD gases. The influence of the packing material is first described in this article. Then two specific processes (TCAP and Reverse Chromatography), each well adapted to perform one target, are presented. Finally, the problematic to propose an optimized treatment scheme associating these two processes is formulated. (authors)

  6. Pharmacologic Strategies for Treatment of Poisonings.

    PubMed

    Roberts, Eric; Gooch, Michael D

    2016-03-01

    Poisoning is the leading cause of injury-related mortality in the United States. Data suggest that nonmedical use of pharmaceuticals is increasing, along with a proportional increase in subsequent adverse events. The widespread use of illegal drugs contributes to the challenge, because these drugs may produce a wide array of clinical presentations that warrant time-critical recognition and treatment. Common legal and illegal poisonings highlighting clinical presentations in terms of toxidromes as a means of categorically recognizing these emergencies is the focus of this article. To optimize outcomes for situations such as these, pharmacologic considerations are discussed and explored. PMID:26897424

  7. Present and New Treatment Strategies in the Management of Glaucoma

    PubMed Central

    Kolko, M

    2015-01-01

    Glaucoma is a neurodegenerative disease characterized by retinal ganglion cell (RGC) death and axonal loss. It remains a major cause of blindness worldwide. All current modalities of treatment are focused on lowering intraocular pressure (IOP), and it is evident that increased IOP is an important risk factor for progression of the disease. However, it is clear that a significant number of glaucoma patients show disease progression despite of pressure lowering treatments. Much attention has been given to the development of neuroprotective treatment strategies, but the identification of such has been hampered by lack of understanding of the etiology of glaucoma. Hence, in spite of many attempts no neuroprotective drug has yet been clinically approved. Even though neuroprotection is without doubt an important treatment strategy, many glaucoma subjects are diagnosed after substantial loss of RGCs. In this matter, recent approaches aim to rescue RGCs and regenerate axons in order to restore visual function in glaucoma. The present review seeks to provide an overview of the present and new treatment strategies in the management of glaucoma. The treatment strategies are divided into current available glaucoma medications, new pressure lowering targets, prospective neuroprotective interventions, and finally possible neuroregenrative strategies. PMID:26069521

  8. Nanotechnology-based water treatment strategies.

    PubMed

    Kumar, Sandeep; Ahlawat, Wandit; Bhanjana, Gaurav; Heydarifard, Solmaz; Nazhad, Mousa M; Dilbaghi, Neeraj

    2014-02-01

    The most important component for living beings on the earth is access to clean and safe drinking water. Globally, water scarcity is pervasive even in water-rich areas as immense pressure has been created by the burgeoning human population, industrialization, civilization, environmental changes and agricultural activities. The problem of access to safe water is inevitable and requires tremendous research to devise new, cheaper technologies for purification of water, while taking into account energy requirements and environmental impact. This review highlights nanotechnology-based water treatment technologies being developed and used to improve desalination of sea and brackish water, safe reuse of wastewater, disinfection and decontamination of water, i.e., biosorption and nanoadsorption for contaminant removal, nanophotocatalysis for chemical degradation of contaminants, nanosensors for contaminant detection, different membrane technologies including reverse osmosis, nanofiltration, ultrafiltration, electro-dialysis etc. This review also deals with the fate and transport of engineered nanomaterials in water and wastewater treatment systems along with the risks associated with nanomaterials. PMID:24749460

  9. Heart Failure in Adult Congenital Heart Disease: Nonpharmacologic Treatment Strategies.

    PubMed

    LeMond, Lisa; Mai, Tuan; Broberg, Craig S; Muralidaran, Ashok; Burchill, Luke J

    2015-11-01

    In early stages, heart failure (HF) in adult congenital heart disease (ACHD) remains an elusive diagnosis. Many ACHD patients seem well-compensated owing to chronic physical and psychological adaptations. HF biomarkers and cardiopulmonary exercise tests are often markedly abnormal, although patients report stable health and good quality of life. Treatment differs from acquired HF. Evidence for effective drug therapy in ACHD-related HF is lacking. Residual ventricular, valvular, and vascular abnormalities contribute to HF pathophysiology, leading to an emphasis on nonpharmacologic treatment strategies. This article reviews emerging perspectives on nonpharmacologic treatment strategies, including catheter-based interventions, surgical correction, and palliative care. PMID:26471822

  10. Oral Curcumin (Meriva) Is Effective as an Adjuvant Treatment and Is Able to Reduce IL-22 Serum Levels in Patients with Psoriasis Vulgaris

    PubMed Central

    Bonciolini, Veronica; Volpi, Walter; Del Bianco, Elena; Caproni, Marzia

    2015-01-01

    Curcumin is a complementary therapy that may be helpful for the treatment of psoriasis due to its anti-inflammatory, antiangiogenic, antioxidant, and antiproliferative effects. In the present study we performed a randomized, double-blind, placebo-controlled clinical trial to assess the effectiveness of a bioavailable oral curcumin in the treatment of psoriasis. Sixty-three patients with mild-to-moderate psoriasis vulgaris (PASI < 10) were randomly divided into two groups treated with topical steroids and Meriva, a commercially available lecithin based delivery system of curcumin, at 2 g per day (arm 1), or with topical steroids alone (arm 2), both for 12 weeks. At the beginning (T0) and at the end of the therapy (T12), clinical assessment and immunoenzymatic analysis of the serum levels of IL-17 and IL-22 were performed. At T12, both groups achieved a significant reduction of PASI values that, however, was higher in patients treated with both topical steroids and oral curcumin than in patients treated only with topical steroids. Moreover, IL-22 serum levels were significantly reduced in patients treated with oral curcumin. In conclusion, curcumin was demonstrated to be effective as an adjuvant therapy for the treatment of psoriasis vulgaris and to significantly reduce serum levels of IL-22. PMID:26090395

  11. Current surgical treatment strategies for hepatocellular carcinoma in North America.

    PubMed

    Khan, Adeel S; Fowler, Kathryn J; Chapman, William C

    2014-11-01

    Hepatocellular carcinoma (HCC) is an aggressive tumor that often occurs in the setting of chronic liver disease. Many patients do not initially manifest any symptoms of HCC and present late when cure with surgical resection or transplantation is no longer possible. For this reason, patients at high risk for developing HCC are subjected to frequent screening processes. The surgical management of HCC is complex and requires an inter-disciplinary approach. Hepatic resection is the treatment of choice for HCC in patients without cirrhosis and is indicated in some patients with early cirrhosis (Child-Pugh A). Liver transplantation has emerged in the past decade as the standard of care for patients with cirrhosis and HCC meeting Milan criteria and in select patients with HCC beyond Milan criteria. Loco-regional therapy with transarterial chemoembolization, transarterial embolization, radiofrequency ablation and other similar local treatments can be used as neo-adjuvant therapy to downstage HCC to within Milan criteria or as a bridge to transplantation in patients on transplant wait list. PMID:25386049

  12. Regulation of the CCN genes by vitamin D: A possible adjuvant therapy in the treatment of cancer and fibrosis.

    PubMed

    Piszczatowski, Richard T; Lents, Nathan H

    2016-10-01

    The CCN family is composed of six cysteine-rich, modular, and conserved proteins whose functions span a variety of tissues and include cell proliferation, adhesion, angiogenesis, and wound healing. Roles for the CCN proteins throughout the entire body including the skin, kidney, brain, blood vessels, hematopoietic compartment and others, are continuously being elucidated. Likewise, an understanding of the regulation of this important gene family is constantly becoming clearer, through identification of transcription factors that directly activate, repress, or respond to upstream cell signaling pathways, as well as other forms of gene expression control. Vitamin D (1,25-dihydroxyvitamin D3 or calcitriol), a vitamin essential for numerous biological processes, acts as a potent gene expression modulator. The regulation of the CCN gene family members by calcitriol has been described in many contexts. Here, we provide a concise and thorough overview of what is known about calcitriol and its regulation of the CCN genes, and argue that its regulation is of physiological importance in a wide breadth of tissues in which CCN genes function. In addition, we highlight the effects of vitamin D on CCN gene expression in the setting of two common pathologic conditions, fibrosis and cancer, and propose that the therapeutic effects of vitamin D3 described in these disease states may in part be attributable to CCN gene modulation. As vitamin D is perfectly safe in a wide range of doses and already showing promise as an adjuvant therapeutic agent, a deeper understanding of its control of CCN gene expression may have profound implications in clinical management of disease. PMID:27460560

  13. Treatment strategies for aggressive lymphomas: what works?

    PubMed

    Wilson, Wyndham H

    2013-01-01

    Over the past 30 years, many treatment platforms have been developed for diffuse large B-cell lymphoma, but none proved better than CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone/prednisolone). In the immunochemotherapy era, however, there is convincing evidence for superior chemotherapy platforms. A randomized study from the Groupe d'Etude des Lymphomes de l'Adulte showed that R-ACVBP (rituximab plus doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) was superior to rituximab plus CHOP (R-CHOP) in patients under 60 years of age, but toxicity limits its use to younger patients. Studies also suggest that DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab) is more effective in some subtypes of diffuse large B-cell lymphoma and a randomized comparison with R-CHOP is now nearing completion. The simplicity and safety of R-CHOP and the long history of failed contenders, however, has set a high bar for new approaches. PMID:24319235

  14. Unilateral condylar hyperplasia: a treatment strategy.

    PubMed

    Ferreira, Sabrina; da Silva Fabris, André Luis; Ferreira, Gabriel Ramalho; Faverani, Leonardo Perez; Francisconi, Giovanna Barbosa; Souza, Francisley Avila; Garcia, Idelmo Rangel

    2014-05-01

    Condylar hyperplasia (CH) is a pathologic condition that causes overdevelopment of the condylar head and neck as well as the mandible. Slowly progressive unilateral enlargement of the head and the neck of the condyle causes crossbite malocclusion, facial asymmetry, and shifting of the midpoint of the chin to the unaffected side. The etiology and the pathogenesis of CH remain uncertain. The diagnosis is made by clinical and radiologic examinations and bone scintigraph. A difference in uptake of 10% or more between condyles is regarded as indicative of CH, and the affected condyles had a relative uptake of 55% or more. When the diagnosis of active CH is established, the treatment consists of removal of the growth center by a partial condylectomy. The authors present the case of a 46-year-old male patient with right active type II CH or hemimandibular hyperplasia who underwent a high condylectomy. PMID:24820728

  15. Endovascular Treatment Strategies in Aortoiliac Occlusion

    SciTech Connect

    Ozkan, Ugur Oguzkurt, Levent Tercan, Fahri Gumus, Burcak

    2009-05-15

    The aim of this study was to report our experience in endovascular treatment of total aortoiliac occlusion. Five patients who underwent endovascular recanalization procedures including manual aspiration thrombectomy, balloon angioplasty, and stent placement for total aortoiliac occlusion in a 4-year period were reviewed retrospectively. The mean age of patients was 51 years (range, 43 to 58 years). All patients had abdominal aorta and bilateral common iliac artery occlusion with or without external iliac artery occlusion. All patients either had a contraindication to surgery or refused it. Initial technical success was obtained in four of five (80%) patients. Endovascular techniques were successful in four patients who had good distal runoff and short-segment aortoiliac occlusion, but failed in a patient who had the worst distal runoff and long-segment aortoiliac occlusion. We observed two major complications, one of which was bilateral rupture of the common iliac arteries treated with covered stent placement. Another patient had extension of intra-aortic thrombus into the iliac stent after primary stenting. This was successfully treated with manual aspiration thrombectomy. Aortic and iliac stents remained patent during the follow-up period (median, 18 months; range, 3 to 26 months) in four patients. Primary patency rates at 6, 12, and 24 months were all 80%. In conclusion, endovascular treatment can be an alternative for aortoiliac occlusion in selected patients. Short- to midterm follow-up so far is satisfactory. Removal of intra-aortic thrombus with manual aspiration thrombectomy before balloon angioplasty and/or stenting is possible and a good alternative to thrombolysis.

  16. Novel strategies for treatment of resistant hypertension.

    PubMed

    Judd, Eric K; Oparil, Suzanne

    2013-12-01

    Resistant hypertension, defined as blood pressure (BP) remaining above goal despite the use of 3 or more antihypertensive medications at maximally tolerated doses (one ideally being a diuretic) or BP that requires 4 or more agents to achieve control, occurs in a substantial proportion (>10%) of treated hypertensive patients. Refractory hypertension is a recently described subset of resistant hypertension that cannot be controlled with maximal medical therapy (⩾5 antihypertensive medications of different classes at maximal tolerated doses). Patients with resistant or refractory hypertension are at increased cardiovascular risk and comprise the target population for novel antihypertensive treatments. Device-based interventions, including carotid baroreceptor activation and renal denervation, reduce sympathetic nervous system activity and have effectively reduced BP in early clinical trials of resistant hypertension. Renal denervation interrupts afferent and efferent renal nerve signaling by delivering radiofrequency energy, other forms of energy, or norepinephrine-depleting pharmaceuticals through catheters in the renal arteries. Renal denervation has the advantage of not requiring general anesthesia, surgical intervention, or device implantation and has been evaluated extensively in observational proof-of-principle studies and larger randomized controlled trials. It has been shown to be safe and effective in reducing clinic BP, indices of sympathetic nervous system activity, and a variety of hypertension-related comorbidities. These include impaired glucose metabolism/insulin resistance, end-stage renal disease, obstructive sleep apnea, cardiac hypertrophy, heart failure, and cardiac arrhythmias. This article reviews the strengths, limitations, and future applications of novel device-based treatment, particularly renal denervation, for resistant hypertension and its comorbidities. PMID:25028641

  17. Trends in the Utilization of Adjuvant Vaginal Cuff Brachytherapy and/or External Beam Radiation Treatment in Stage I and II Endometrial Cancer: A Surveillance, Epidemiology, and End-Results Study

    SciTech Connect

    Patel, Mehul K.; Cote, Michele L.; Ali-Fehmi, Rouba; Buekers, Thomas; Munkarah, Adnan R.; Elshaikh, Mohamed A.

    2012-05-01

    Purpose: The optimal adjuvant radiation treatment for endometrial carcinoma (EC) remains controversial. Adjuvant vaginal cuff brachytherapy (VB) has emerged as an increasingly common treatment modality. However, the time trends for using VB, external beam radiation therapy (EBRT), or combined therapy (VB+EBRT) have not been well characterized. We therefore examined the utilization trends of VB, EBRT, and VB+EBRT for adjuvant RT in International Federation of Gynecologic Oncology (FIGO) stage I and II EC over time. Methods and Materials: We evaluated treatment patterns for 48,122 patients with EC diagnosed between January 1995 and December 2005, using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) public use database. Chi-squared tests were used to assess differences by radiation type (VB, EBRT, and VB+EBRT) and various demographic and clinical variables. Results: Analyses were limited to 9,815 patients (20.4%) with EC who met the inclusion criteria. Among women who received adjuvant RT, the proportion receiving VB increased yearly (12.9% in 1995 compared to 32.8% in 2005 (p < 0.0001). The increasing use of VB was proportional to the decreasing use of EBRT (56.1% in 1995 to 45.8% in 2005; p < 0.0001) and VB+EBRT (31.0% in 1995 to 21.4% in 2005; p < 0.001). Conclusions: This population-based report demonstrates an increasing trend in the use of VB in the adjuvant setting after hysterectomy for treatment of women with FIGO stage I-II EC. VB alone appears to be replacing pelvic EBRT and VB+EBRT therapy in the management of stage I-II EC.

  18. Perimenstrual asthma: from pathophysiology to treatment strategies.

    PubMed

    Graziottin, Alessandra; Serafini, Audrey

    2016-01-01

    The prevalence of asthma is about 9,7 % in women and 5,5 % in men. Asthma can deteriorate during the perimenstrual period, a phenomenon known as perimenstrual asthma (PMA), which represents a unique, highly symptomatic asthma phenotype. It is distinguished from traditional allergic asthma by aspirin sensitivity, less atopy, and lower lung capacity. PMA incidence is reported to vary between 19 and 40 % of asthmatic women. The presence of PMA has been related to increases in asthma-related emergency department visits, hospitalizations and emergency treatment including intubations. It is hypothesized that hormonal status may influence asthma in women, focusing on the role of sex hormones, and specifically on the impact of estrogens' fluctuations at ovulation and before periods. This paper will focus on the pathophysiology of hormone triggered cycle related inflammatory/allergic events and their relation with asthma. We reviewed the scientific literature on Pubmed database for studies on PMA. Key word were PMA, mastcells, estrogens, inflammation, oral contraception, hormonal replacement therapy (HRT), and hormone free interval (HFI). Special attention will be devoted to the possibility of reducing the perimenstrual worsening of asthma and associated symptoms by reducing estrogens fluctuations, with appropriate hormonal contraception and reduced HFI. This novel therapeutical approach will be finally discussed. PMID:27482380

  19. Diagnostic and treatment strategies in mucopolysaccharidosis VI

    PubMed Central

    Vairo, Filippo; Federhen, Andressa; Baldo, Guilherme; Riegel, Mariluce; Burin, Maira; Leistner-Segal, Sandra; Giugliani, Roberto

    2015-01-01

    Mucopolysaccharidosis VI (MPS VI) is a very rare autosomal recessive disorder caused by mutations in the ARSB gene, which lead to deficient activity of the lysosomal enzyme ASB. This enzyme is important for the breakdown of the glycosaminoglycans (GAGs) dermatan sulfate and chondroitin sulfate, which accumulate in body tissues and organs of MPS VI patients. The storage of GAGs (especially dermatan sulfate) causes bone dysplasia, joint restriction, organomegaly, heart disease, and corneal clouding, among several other problems, and reduced life span. Despite the fact that most cases are severe, there is a spectrum of severity and some cases are so attenuated that diagnosis is made late in life. Although the analysis of urinary GAGs and/or the measurement of enzyme activity in dried blood spots are useful screening methods, the diagnosis is based in the demonstration of the enzyme deficiency in leucocytes or fibroblasts, and/or in the identification of pathogenic mutations in the ARSB gene. Specific treatment with enzyme replacement has been available since 2005. It is safe and effective, bringing measurable benefits and increased survival to patients. As several evidences indicate that early initiation of therapy may lead to a better outcome, newborn screening is being considered for this condition, and it is already in place in selected areas where the incidence of MPS VI is increased. However, as enzyme replacement therapy is not curative, associated therapies should be considered, and research on innovative therapies continues. The management of affected patients by a multidisciplinary team with experience in MPS diseases is highly recommended. PMID:26586959

  20. Treatment Strategy Profiles in Substance Use Disorder Treatment Programs: A Latent Class Analysis

    PubMed Central

    Aletraris, Lydia; Paino, Maria; Roman, Paul M.

    2015-01-01

    Background Modern treatment options for substance use disorder are diverse. While studies have analyzed the adoption of individual evidence-based practices in treatment centers, little is known about the specific make-up of treatment strategy profiles in treatment centers throughout the United States. The current study used latent class analysis to profile underlying treatment strategies and to evaluate philosophical and structural supports associated with each profile. Methods Utilizing three aggregated and secondary datasets of nationally representative samples of substance use disorder treatment centers (N=775), we employed latent class analysis to determine treatment strategy profiles. Using multinomial logistic regression, we then examined organizational characteristics associated with each profile. Results We found three distinct treatment strategy profiles: Centers that primarily relied on Motivational Interviewing and Motivational Enhancement Therapy, centers that utilized psychosocial and alternative therapies, and centers that employed comprehensive treatments including pharmacotherapy. The multinomial logistic regression revealed that philosophical and structural center characteristics were associated with membership in the comprehensive class. Centers with philosophical orientations conducive to holistic care and pharmacotherapy-acceptance, resource-rich infrastructures, and an entrepreneurial reliance on insured clients were more likely to offer diverse interventions. All associations were significant at the .05 level. Principle Conclusion The findings from this study help us understand the general strategies of treatment centers. From a practical perspective, practitioners and clients should be aware of the variation in treatment center practices where they may offer or receive treatment. PMID:26105707

  1. Adjuvant Surgical Oophorectomy Plus Tamoxifen in Premenopausal Women With Operable Hormone Receptor-Positive Breast Cancer: A Global Treatment Option.

    PubMed

    Love, Richard R

    2016-08-01

    One third of annual new cases of breast cancer globally are now hormone receptor-positive tumors in premenopausal women from low- and middle-income countries. For this subgroup of women with breast cancer, high-income country guidelines suggest impractical and unaffordable adjuvant treatments. The balance of clinical trial evidence now suggests that surgical oophorectomy plus tamoxifen is a safe and practical treatment for these women in low- and middle-income countries. Additionally, new randomized trial data suggest that women in the second half of an anovulatory cycle benefit minimally from surgical oophorectomy done at this time, which implies that regularly cycling women will benefit more than has been shown from this procedure. Allred scoring of levels of hormone receptors is a practical and inexpensive approach to the assessment of magnitudes of response to oophorectomy plus tamoxifen. These circumstances suggest that more detailed consideration of this option should characterize clinical practice guidelines in high-income countries because of their global impact. PMID:27117241

  2. Developments in the rat adjuvant arthritis model and its use in therapeutic evaluation of novel non-invasive treatment by SOD in Transfersomes.

    PubMed

    Simões, S I; Delgado, T C; Lopes, R M; Jesus, S; Ferreira, A A; Morais, J A; Cruz, M E M; Corvo, M L; Martins, M B F

    2005-03-21

    The aim of this study was firstly to refine a rat model of arthritis, the adjuvant arthritis (AA) model, by studying the time course of the disease, introducing new evaluation methods such as haematological and biochemical parameters in order to identify the main stages of the disease. An optimisation of treatment schedule and evaluation criteria was developed. This refinement provided novel non-invasive anti-inflammatory treatment of the AA with SOD by using mixed lipid vesicles specially developed for transdermal delivery, Transfersomes (Tfs), this being the second major aim. The time course of AA includes a first stage: 1 day after the disease induction, the induced paw volume more than doubled and the paw circumference increased by approx. 50%. Two weeks later, another stage occurred where the disease shifted from the local arthritis form towards polyarthritis: an additional increase of volume and circumference of the induced and non-induced paws, occurred. The animals also started to loose weight around day 14 after the disease induction. Radiographic observable lesions increased correspondingly. Treatment of animals, started at day 1 after induction, by epicutaneous application of SOD-Tfs showed that 1 mg SOD/kg body weight is more efficient than 0.66 mg SOD /kg body weight. As a positive control, SOD liposomes intravenously injected were used for comparison and confirmed the biological efficiency of epicutaneously applied SOD in Tfs. SOD solution and empty Tfs epicutaneously applied exerted no effect. In addition, epicutaneous application of SOD-Tfs used prophylactically was able to suppress the induced rat paw oedema. Radiographic images showed less joint lesions in SOD-Tfs treated animals in comparison with control and placebo treated rats. It was shown for the first time that SOD incorporated into Tfs and applied onto a skin area not necessarily close to the inflamed tissue is able to promote non-invasive treatment of induced arthritis. PMID:15763624

  3. Novel therapeutic strategies for treatment of visceral leishmaniasis.

    PubMed

    Jain, Keerti; Jain, Narendra K

    2013-12-01

    Leishmaniasis reveals itself in two forms, cutaneous and visceral, but the later exerts serious complications and may lead to death, if untreated. The availability of limited number of antileishmanial chemotherapeutic agents, the high cost of treatment, growing incidences of resistance to first line drugs as well as severe toxicities associated with the drugs complicate the treatment of visceral leishmaniasis. To overcome these problems, critical investigation of new therapeutic strategies with potential antileishmanial activity and good tolerability are essential. In this review we explore the different facets of novel therapeutic strategies for treatment of visceral leishmaniasis with a purpose to summarize all the possible treatment tactics, which will help scientists working in this arena to implement their research in a systematic manner. PMID:23973338

  4. Beyond antigens and adjuvants: formulating future vaccines.

    PubMed

    Moyer, Tyson J; Zmolek, Andrew C; Irvine, Darrell J

    2016-03-01

    The need to optimize vaccine potency while minimizing toxicity in healthy recipients has motivated studies of the formulation of vaccines to control how, when, and where antigens and adjuvants encounter immune cells and other cells/tissues following administration. An effective subunit vaccine must traffic to lymph nodes (LNs), activate both the innate and adaptive arms of the immune system, and persist for a sufficient time to promote a mature immune response. Here, we review approaches to tailor these three aspects of vaccine function through optimized formulations. Traditional vaccine adjuvants activate innate immune cells, promote cell-mediated transport of antigen to lymphoid tissues, and promote antigen retention in LNs. Recent studies using nanoparticles and other lymphatic-targeting strategies suggest that direct targeting of antigens and adjuvant compounds to LNs can also enhance vaccine potency without sacrificing safety. The use of formulations to regulate biodistribution and promote antigen and inflammatory cue co-uptake in immune cells may be important for next-generation molecular adjuvants. Finally, strategies to program vaccine kinetics through novel formulation and delivery strategies provide another means to enhance immune responses independent of the choice of adjuvant. These technologies offer the prospect of enhanced efficacy while maintaining high safety profiles necessary for successful vaccines. PMID:26928033

  5. [Influenza vaccine and adjuvant].

    PubMed

    Nakayama, Tetsuo

    2011-01-01

    Adjuvant is originated from the Latin word "adjuvare" which means "help" in English to enhance the immunological responses when given together with antigens. The beginning of adjuvant was mineral oil which enhanced the immune response when it was given with inactivated Salmonella typhimurium. Aluminium salt was used to precipitate diphtheria toxoid and increased level of antibody response was demonstrated when administered with alum-precipitated antigens. Since 1930, aluminium salt has been used as DTaP (diphtheria-tetanus-acellular pertussis vaccine) adjuvant. Many candidates were tested for adjuvant activity but only aluminum salt is allowed to use for human vaccines. New adjuvant MF59, oil-in-water emulsion type, was developed for influenza vaccine for elderly (Fluad) and series of AS adjuvant are used for hepatitis B, pandemic flue, and human papiloma virus vaccines. Oil-adjuvanted influenza pandemic vaccines induced higher antibody response than alum-adjuvanted vaccine with higher incidence of adverse events, especially for local reactions. Alum-adjuvanted whole virion inactivated H5N1 vaccine was developed in Japan, and it induced relatively well immune responses in adults. When it applied for children, febrile reaction was noted in approximately 60% of the subjects, with higher antibodies. Recent investigation on innate immunity demonstrates that adjuvant activity is initiated from the stimulation on innate immunity and/or inflammasome, resulting in cytokine induction and antigen uptake by monocytes and macrophages. The probable reason for high incidence of febrile reaction should be investigated to develop a safe and effective influenza vaccine. PMID:22129866

  6. [Drug delivery strategies for targeted treatment of inflammatory bowel disease].

    PubMed

    Lautenschläger, C; Schmidt, C; Lange, K; Stallmach, A

    2015-03-01

    Inflammatory bowel disease (IBD) is a frequently occurring disease in young people, which is characterized by chronic inflammation of the gastrointestinal tract. The therapy of IBD is dominated by the administration of anti-inflammatory and immunosuppressive agents, which suppress the intestinal inflammatory burden and improve the disease-related symptoms. Present treatment strategies are characterized by a limited therapeutical efficacy and the occurrence of adverse drug reactions. The development of novel disease-targeted drug delivery strategies is preferable for a more effective therapy and thus demonstrates the potential to address unmet medical needs. This review gives an overview about drug delivery strategies for the treatment of IBD. Therefore, established intestine-targeting strategies for a selective drug release into the diseased part of the gastrointestinal tract will be presented, including prodrugs, and dosage forms with pH-/time-dependent drug release. Furthermore future-oriented disease-targeting strategies for a selective drug release into the intestinal inflammation will be described, including micro-/nanosized synthetic and biologic drug carriers. This novel therapeutic approach may enable a more effective anti-inflammatory treatment of IBD with reduced risks of adverse reactions. PMID:25723326

  7. [Rectal cancer and adjuvant chemotherapy: which conclusions?].

    PubMed

    Bachet, J-B; Rougier, P; de Gramont, A; André, T

    2010-01-01

    Adenocarcinoma of the rectum represents about a third of cases of colorectal cancer, with an annual incidence of 12,000 cases in France. On the contrary of colon cancer, the benefice of adjuvant chemotherapy in rectal cancer has not been definitively proved, more because this question was assessed in few recent studies than because negative results. Preoperative radiochemotherapy is now the reference treatment for mid and lower rectal cancers, and allow to increase the local control without improvement of progression free survival and overall survival. The data of the "historical studies" of adjuvant treatment in rectal cancer published before 1990, of the meta-analysis of adjuvant trials in rectal cancer and of the QUASAR study suggest that adjuvant chemotherapy with fluoropyrimidines (intravenous or oral), in absence of pre-operative treatment, decrease the risk of metastatic relapse after curative surgery for a rectal cancer of stage II or III. This benefice seems similar to the one observed in colon cancer. In the EORTC radiotherapy group trial 22921, an adjuvant chemotherapy with 5-fluorouracil and low dose of leucovorin was not associated with a significantly improvement of overall survival but, despite the fact that only 42.9% of patients received all planed cycles, the progression free survival was increased (not significantly) in groups receiving adjuvant chemotherapy. The French recommendations are to discuss the indication of adjuvant chemotherapy by fluoropyrimidines in cases of stage III rectal cancer on histopathologic reports and no chemotherapy in case of stade II. Despite the fact that none study have assessed a combination of fluoropyrimidines and oxaliplatin in adjuvant setting in rectal cancer, like in colon cancer, the Folfox4, modified Folfox6 or Xelox regimens are valid options in stage III (experts opinion). In cases of pathologic complete remission or in absence of involved nodes, the benefice of adjuvant chemotherapy is not assessed. In

  8. MRI evaluation of BBB disruption after adjuvant AcSDKP treatment of stroke with tPA in rat.

    PubMed

    Ding, G; Zhang, Z; Chopp, M; Li, L; Zhang, L; Li, Q; Wei, M; Jiang, Q

    2014-06-20

    The primary limitation of thrombolytic treatment of ischemic stroke with tissue plasminogen activator (tPA) is the hemorrhagic risk. We tested AcSDKP (N-acetyl-seryl-aspartyl-lysyl-proline), as an auxiliary therapeutic agent, to reduce blood-brain barrier (BBB) disruption in a combination tPA thrombolytic treatment of stroke. Wistar rats subjected to embolic stroke were randomly assigned to either the tPA monotherapy group (n=9) or combination of tPA and AcSDKP treatment group (n=9) initiated at 4 h after ischemia. Magnetic resonance imaging (MRI) measurements were performed before and after the treatments. Immunohistochemical staining and measurements were performed to confirm MRI findings. Longitudinal MRI permeability measurements with gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) demonstrated that combination treatment of acute embolic stroke with AcSDKP and tPA significantly reduced BBB leakage, compared to tPA monotherapy, at 3 and 6 days (18.3±9.8 mm3 vs. 65.0±21.0 mm3, p<0.001) after the onset of stroke, although BBB leakage was comparable between the two groups prior to the treatments (6.8±4.4 mm3 vs. 4.3±3.3 mm3, p>0.18). The substantial reduction of BBB leakage observed in the combination treatment group was closely associated with reduced ischemic lesions measured by T2 maps (113.6±24.9 mm3 vs. 188.1±60.8 mm3, p<0.04 at 6 days). Histopathological analysis of the same population of rats showed that the combination treatment significantly reduced parenchymal fibrin deposition (0.063±0.059 mm2 vs. 0.172±0.103 mm2, p<0.03) and infarct volume (146.7±35.9 mm3 vs. 199.3±60.4 mm3, p<0.05) compared to the tPA monotherapy at 6days after stroke. MRI provides biological insight into the therapeutic benefit of combination treatment of stroke with tPA and AcSDKP 4h after onset, and demonstrates significantly improved cerebrovascular integrity with neuroprotective effects compared with tPA monotherapy. PMID:24769225

  9. Semi-individualised Chinese medicine treatment as an adjuvant management for diabetic nephropathy: a pilot add-on, randomised, controlled, multicentre, open-label pragmatic clinical trial

    PubMed Central

    Chan, Kam Wa; Ip, Tai Pang; Kwong, Alfred Siu Kei; Lui, Sing Leung; Chan, Gary Chi Wang; Cowling, Benjamin John; Yiu, Wai Han; Wong, Dickson Wai Leong; Liu, Yang; Feng, Yibin; Tan, Kathryn Choon Beng; Chan, Loretta Yuk Yee; Leung, Joseph Chi Kam; Lai, Kar Neng; Tang, Sydney Chi Wai

    2016-01-01

    Introduction Diabetes mellitus and diabetic nephropathy (DN) are prevalent and costly to manage. DN is the leading cause of end-stage kidney disease. Conventional therapy blocking the renin–angiotensin system has only achieved limited effect in preserving renal function. Recent observational data show that the use of Chinese medicine (CM), a major form of traditional medicine used extensively in Asia, could reduce the risk of end-stage kidney disease. However, existing clinical practice guidelines are weakly evidence-based and the effect of CM remains unclear. This trial explores the effect of an existing integrative Chinese–Western medicine protocol for the management of DN. Objective To optimise parameters and assess the feasibility for a subsequent phase III randomised controlled trial through preliminary evaluation on the effect of an adjuvant semi-individualised CM treatment protocol on patients with type 2 diabetes with stages 2–3 chronic kidney disease and macroalbuminuria. Methods and analysis This is an assessor-blind, add-on, randomised, controlled, parallel, multicentre, open-label pilot pragmatic clinical trial. 148 patients diagnosed with DN will be recruited and randomised 1:1 to a 48-week additional semi-individualised CM treatment programme or standard medical care. Primary end points are the changes in estimated glomerular filtration rate and spot urine albumin-to-creatinine ratio between baseline and treatment end point. Secondary end points include fasting blood glucose, glycated haemoglobin, brain natriuretic peptide, fasting insulin, C peptide, fibroblast growth factor 23, urinary monocyte chemotactic protein-1, cystatin C, nephrin, transforming growth factor-β1 and vascular endothelial growth factor. Adverse events are monitored through self-completed questionnaire and clinical visits. Outcomes will be analysed by regression models. Enrolment started in July 2015. Ethics and registration This protocol is approved by the Institutional

  10. Recent Advances of Vaccine Adjuvants for Infectious Diseases

    PubMed Central

    Nguyen, Minh Trang

    2015-01-01

    Vaccines are the most effective and cost-efficient method for preventing diseases caused by infectious pathogens. Despite the great success of vaccines, development of safe and strong vaccines is still required for emerging new pathogens, re-emerging old pathogens, and in order to improve the inadequate protection conferred by existing vaccines. One of the most important strategies for the development of effective new vaccines is the selection and usage of a suitable adjuvant. Immunologic adjuvants are essential for enhancing vaccine potency by improvement of the humoral and/or cell-mediated immune response to vaccine antigens. Thus, formulation of vaccines with appropriate adjuvants is an attractive approach towards eliciting protective and long-lasting immunity in humans. However, only a limited number of adjuvants is licensed for human vaccines due to concerns about safety and toxicity. We summarize current knowledge about the potential benefits of adjuvants, the characteristics of adjuvants and the mechanisms of adjuvants in human vaccines. Adjuvants have diverse modes of action and should be selected for use on the basis of the type of immune response that is desired for a particular vaccine. Better understanding of current adjuvants will help exploring new adjuvant formulations and facilitate rational design of vaccines against infectious diseases. PMID:25922593

  11. Treatment strategies for acute metabolic disorders in neonates

    PubMed Central

    Mohamed, Sarar

    2011-01-01

    Acute metabolic emergencies in neonates represent a challenge to the medical and nursing staff. If not treated optimally, these disorders are associated with poor outcome. Early diagnosis, supportive therapy and specific measures addressing the derranged metabolic process are the gold standards for favorable results. This review highlights treatment strategies for Inborn Errors of Metabolism (IEM) presenting in the neonatal period.

  12. Novel Interventional Strategies for the Treatment of Atrial Fibrillation

    PubMed Central

    Siontis, Konstantinos C; Oral, Hakan

    2016-01-01

    The landscape of the invasive management of atrial fibrillation, the most common sustained arrhythmia in humans, has changed dramatically in the last decade owing to numerous advances in arrhythmia mapping and ablation technologies. The current review critically appraises novel interventional strategies for the treatment of atrial fibrillation with a focus on clinical effectiveness and safety. PMID:27403294

  13. Optimal management of familial hypercholesterolemia: treatment and management strategies

    PubMed Central

    Nemati, Mohammad Hassan; Astaneh, Behrooz

    2010-01-01

    Familial hypercholesterolemia is an autosomally dominant disorder caused by various mutations in low-density lipoprotein receptor genes. This will lead to elevated levels of total and low-density lipoprotein cholesterol, which may in turn lead to premature coronary atherosclerosis and cardiac-related death. The symptoms are more severe in the homozygous type of the disease. Different options for the treatment of affected patients are now available. Diet therapy, pharmacologic therapy, lipid apheresis, and liver transplantation are among the various treatments. We clinically review the treatment and management strategies for the disease in order to shed light on the optimal management of familial hypercholesterolemia. PMID:21191428

  14. Noninfectious uveitis: strategies to optimize treatment compliance and adherence

    PubMed Central

    Dolz-Marco, Rosa; Gallego-Pinazo, Roberto; Díaz-Llopis, Manuel; Cunningham, Emmett T; Arévalo, J Fernando

    2015-01-01

    Noninfectious uveitis includes a heterogenous group of sight-threatening ocular and systemic disorders. Significant progress has been made in the treatment of noninfectious uveitis in recent years, particularly with regard to the effective use of corticosteroids and non-corticosteroid immunosuppressive drugs, including biologic agents. All of these therapeutic approaches are limited, however, by any given patient’s ability to comply with and adhere to their prescribed treatment. In fact, compliance and adherence are among the most important patient-related determinants of treatment success. We discuss strategies to optimize compliance and adherence. PMID:26316689

  15. Adjuvant progestagens for endometrial cancer

    PubMed Central

    Martin-Hirsch, Pierre PL; Bryant, Andrew; Keep, Sarah L; Kitchener, Henry C; Lilford, Richard

    2014-01-01

    Background Endometrial cancer is the most common genital tract carcinoma among women in developed countries, with most women presenting with stage 1 disease. Adjuvant progestagen therapy has been advocated following primary surgery to reduce the risk of recurrence of disease. Objectives To evaluate the effectiveness and safety of adjuvant progestagen therapy for the treatment of endometrial cancer. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Specilaised Register, Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2009. MEDLINE and EMBASE up to April 2009. Selection criteria Randomised controlled trials (RCTs) of progestagen therapy in women who have had surgery for endometrial cancer. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Risk ratios (RRs) comparing survival in women who did and did not receive progestagen were pooled in random effects meta-analyses.. Main results Seven trials assessing 4556 women were identified. Three trials included women with stage one disease only, whereas four included women with more advanced disease. Meta-analysis of four trials showed that there was no significant difference in the risk of death at five years between adjuvant progestagen therapy and no further treatment (RR = 1.00, 95% CI 0.85 to 1.18). This conclusion is also robust to single trial analyses at 4 and 7 years and in one trial across all points in time using a hazard ratio (HR). There was also no significant difference between progestagen therapy and control in terms of the risk of death from endometrial cancer, cardiovascular disease and intercurrent disease. Relapse of disease appeared to be reduced by progestagen therapy in one trial (HR = 0.71, 95% CI 0.52 to 0.97 and 5 year RR = 0.74, 95% CI 0.58 to 0.96), but there was no evidence of a difference in disease recurrence in another trial at 7 years (RR = 1.34, 95% CI 0.79 to 2.27). Authors’ conclusions There

  16. Treatment-resistant Schizophrenia: Evidence-based Strategies

    PubMed Central

    Englisch, Susanne; Zink, Mathias

    2012-01-01

    Treatment-resistant symptoms complicate the clinical course of schizophrenia, and a large proportion of patients do not reach functional recovery. In consequence, polypharmacy is frequently used in treatment-refractory cases, addressing psychotic positive, negative and cognitive symptoms, treatment-emergent side effects caused by antipsychotics and comorbid depressive or obsessive-compulsive symptoms. To a large extent, such strategies are not covered by pharmacological guidelines which strongly suggest antipsychotic monotherapy. Add-on strategies comprise combinations of several antipsychotic agents and augmentations with mood stabilizers; moreover, antidepressants and experimental substances are applied. Based on the accumulated evidence of clinical trials and meta-analyses, combinations of clozapine with certain second-generation antipsychotic agents and the augmentation of antipsychotics with antidepressants seem recommendable, while the augmentation with mood stabilizers cannot be considered superior to placebo. Forthcoming investigations will have to focus on innovative pharmacological agents, the clinical spectrum of cognitive deficits and the implementation of cognitive behavioral therapy. PMID:22654380

  17. Rehabilitating antisocial personalities: treatment through self-governance strategies.

    PubMed

    McRae, Leon

    2013-02-01

    Offenders with antisocial personality disorder (ASPD) are widely assumed to reject psychotherapeutic intervention. Some commentators, therefore, argue that those with the disorder are better managed in the criminal justice system, where, following the introduction of indeterminate sentences, engagement with psychological treatment is coercively linked to the achievement of parole. By comparison, National Institute of Clinical Excellence guidelines on the management and treatment of ASPD recommend that those who are treatment seeking should be considered for admission to specialist psychiatric hospitals. The rationale is that prison-based interventions are underresourced, and the treatment of ASPD is underprioritised. The justification is that offenders with ASPD can be rehabilitated, if they are motivated. One problem, however, is that little is known about why offenders with ASPD seek treatment or what effect subsequent treatment has on their self-understanding. The aim of this paper is to address these unresolved issues. It draws on the findings of Economic and Social Research Council (ESRC) funded qualitative study examining the experiences of sentenced male offenders admitted to a specialist personality disorder ward within the medium secure estate and the medical practitioners who treat them. The data are analysed with reference to Michel Foucault's work on governmentality and strategy in power relations. Two arguments are advanced: first, offenders with ASPD are motivated by legal coercive pressures to implement a variety of Foucauldian-type strategies to give the false impression of treatment progress. Second, and related, treatment does not result in changes in self-understanding in the resistive client with ASPD. This presupposes that, in respect of this group at least, Foucault was mistaken in his claim that resistive behaviours merely mask the effectiveness of treatment norms over time. Nevertheless, the paper concludes that specialist treatment in the

  18. Rehabilitating antisocial personalities: treatment through self-governance strategies

    PubMed Central

    McRae, Leon

    2012-01-01

    Offenders with antisocial personality disorder (ASPD) are widely assumed to reject psychotherapeutic intervention. Some commentators, therefore, argue that those with the disorder are better managed in the criminal justice system, where, following the introduction of indeterminate sentences, engagement with psychological treatment is coercively linked to the achievement of parole. By comparison, National Institute of Clinical Excellence guidelines on the management and treatment of ASPD recommend that those who are treatment seeking should be considered for admission to specialist psychiatric hospitals. The rationale is that prison-based interventions are underresourced, and the treatment of ASPD is underprioritised. The justification is that offenders with ASPD can be rehabilitated, if they are motivated. One problem, however, is that little is known about why offenders with ASPD seek treatment or what effect subsequent treatment has on their self-understanding. The aim of this paper is to address these unresolved issues. It draws on the findings of Economic and Social Research Council (ESRC) funded qualitative study examining the experiences of sentenced male offenders admitted to a specialist personality disorder ward within the medium secure estate and the medical practitioners who treat them. The data are analysed with reference to Michel Foucault's work on governmentality and strategy in power relations. Two arguments are advanced: first, offenders with ASPD are motivated by legal coercive pressures to implement a variety of Foucauldian-type strategies to give the false impression of treatment progress. Second, and related, treatment does not result in changes in self-understanding in the resistive client with ASPD. This presupposes that, in respect of this group at least, Foucault was mistaken in his claim that resistive behaviours merely mask the effectiveness of treatment norms over time. Nevertheless, the paper concludes that specialist treatment in the

  19. Application of combined rigid choledochoscope and accurate positioning method in the adjuvant treatment of bile duct stones

    PubMed Central

    Wang, Ping; Chen, Xiaowu; Sun, Beiwang; Liu, Yanmin

    2015-01-01

    To explore the clinical effect of percutaneous transhepatic cholangioscopic lithotomy (PTCSL) combined with rigid choledochoscope and accurate positioning in the treatment of calculus of bile duct. This study retrospectively reviewed 162 patients with hepatolithiasis at the First Affiliated Hospital of Guangzhou Medical University between 2001 and 2013 were assigned to hard lens group or traditional PTCSL group. Compared with the traditional PTCSL, PTCSL with rigid choledochoscope can shorten the interval time which limit the PTCSL application. The operation time (45 vs 78, P=0.003), the number of operation (1.62 vs 1.97, P=0.031), and blood loss (37.8 vs 55.1, P=0.022) were better in hard lens group while the stone residual and complication had no significant differences. Rigid choledochoscope is a safe, minimally invasive and effective method in the treatment of bile duct stones. Accurate positioning method can effectively shorten operation process time. PMID:26629183

  20. Effective rheumatoid arthritis treatment requires comprehensive management strategies.

    PubMed

    Boomershine, Chad S

    2009-01-01

    Work by Lee and colleagues has shown that decreased sleep quality and increased psychiatric distress increase pain sensitivity at both articular and nonarticular sites in rheumatoid arthritis (RA) patients. This work is consistent with prior studies showing that factors independent of RA disease activity can influence RA outcome measures. Owing to increasing pressure on rheumatologists to use outcome measures to inform treatment decisions, the work by Lee and colleagues highlights the need for comprehensive RA management strategies to understand and address the human factors that influence outcomes measures. Such strategies will ensure appropriate use of increasingly expensive therapies while maximizing patient satisfaction and reimbursement. PMID:20067592

  1. Effective rheumatoid arthritis treatment requires comprehensive management strategies

    PubMed Central

    2009-01-01

    Work by Lee and colleagues has shown that decreased sleep quality and increased psychiatric distress increase pain sensitivity at both articular and nonarticular sites in rheumatoid arthritis (RA) patients. This work is consistent with prior studies showing that factors independent of RA disease activity can influence RA outcome measures. Owing to increasing pressure on rheumatologists to use outcome measures to inform treatment decisions, the work by Lee and colleagues highlights the need for comprehensive RA management strategies to understand and address the human factors that influence outcomes measures. Such strategies will ensure appropriate use of increasingly expensive therapies while maximizing patient satisfaction and reimbursement. PMID:20067592

  2. Characterization and treatment monitoring of inflammatory arthritis by photoacoustic imaging: a study on adjuvant-induced arthritis rat model

    NASA Astrophysics Data System (ADS)

    Wang, Xueding; Rajian, Justin; Shao, Xia; Chamberland, David L.; Girish, Gandikota

    2014-03-01

    Neovascularity also known as angiogenesis is an early feature of inflammatory arthritis disease. Therefore, identifying the development of neovascularity is one way to potentially detect and characterize arthritis. Laser-based photoacoustic imaging (PAI) is an emerging biomedical imaging modality which may aid in detection of both early and continued development of neovascularity. In this work, we investigated the feasibility of PAI to measure angiogenesis, for the purpose of evaluating and monitoring inflammatory arthritis after treatment. The imaging results on an arthritis rat model demonstrate that 1) there is noticeable enhancement in image intensity in the arthritic ankle joints when compared to the normal joints, and 2) there is noticeable decrease in image intensity in the arthritic ankle joints after treatment when compared to the untreated arthritic joints. In order to validate the findings from PAI, we performed positron emission tomography (PET) and histology on the same joints. The diameters of the ankle joints, as a clinical score of the arthritis, were also measured at each time point.

  3. Strategies for maximizing clinical effectiveness in the treatment of schizophrenia.

    PubMed

    Tandon, Rajiv; Targum, Steven D; Nasrallah, Henry A; Ross, Ruth

    2006-11-01

    The ultimate clinical objective in the treatment of schizophrenia is to enable affected individuals to lead maximally productive and personally meaningful lives. As with other chronic diseases that lack a definitive cure, the individual's service/recovery plan must include treatment interventions directed towards decreasing manifestations of the illness, rehabilitative services directed towards enhancing adaptive skills, and social support mobilization aimed at optimizing function and quality of life. In this review, we provide a conceptual framework for considering approaches for maximizing the effectiveness of the array of treatments and other services towards promoting recovery of persons with schizophrenia. We discuss pharmacological, psychological, and social strategies that decrease the burden of the disease of schizophrenia on affected individuals and their families while adding the least possible burden of treatment. In view of the multitude of treatments necessary to optimize outcomes for individuals with schizophrenia, effective coordination of these services is essential. In addition to providing best possible clinical assessment and pharmacological treatment, the psychiatrist must function as an effective leader of the treatment team. To do so, however, the psychiatrist must be knowledgeable about the range of available services, must have skills in clinical-administrative leadership, and must accept the responsibility of coordinating the planning and delivery of this multidimensional array of treatments and services. Finally, the effectiveness of providing optimal individualized treatment/rehabilitation is best gauged by measuring progress on multiple effectiveness domains. Approaches for efficient and reliable assessment are discussed. PMID:17122696

  4. Multimodality treatment strategies have changed prognosis of peritoneal metastases.

    PubMed

    Lungoci, Corneliu; Mironiuc, Aurel Ion; Muntean, Valentin; Oniu, Traian; Leebmann, Hubert; Mayr, Max; Piso, Pompiliu

    2016-01-15

    For a long time, treatment of peritoneal metastases (PM) was mostly palliative and thus, this status was link with "terminal status/despair". The current multimodal treatment strategy, consisting of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), has been strenuously achieved over time, but seems to be the best treatment option for PM patients. As we reviewed the literature data, we could emphasize some milestones and also, controversies in the history of proposed multimodal treatment and thus, outline the philosophy of this approach, which seems to be an unusual one indeed. Initially marked by nihilism and fear, but benefiting from a remarkable joint effort of human and material resources (multi-center and -institutional research), over a period of 30 years, CRS and HIPEC found their place in the treatment of PM. The next 4 years were dedicated to the refinement of the multimodal treatment, by launching research pathways. In selected patients, with requires training, it demonstrated a significant survival results (similar to the Hepatic Metastases treatment), with acceptable risks and costs. The main debates regarding CRS and HIPEC treatment were based on the oncologists' perspective and the small number of randomized clinical trials. It is important to statement the PM patient has the right to be informed of the existence of CRS and HIPEC, as a real treatment resource, the decision being made by multidisciplinary teams. PMID:26798438

  5. Multimodality treatment strategies have changed prognosis of peritoneal metastases

    PubMed Central

    Lungoci, Corneliu; Mironiuc, Aurel Ion; Muntean, Valentin; Oniu, Traian; Leebmann, Hubert; Mayr, Max; Piso, Pompiliu

    2016-01-01

    For a long time, treatment of peritoneal metastases (PM) was mostly palliative and thus, this status was link with “terminal status/despair”. The current multimodal treatment strategy, consisting of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), has been strenuously achieved over time, but seems to be the best treatment option for PM patients. As we reviewed the literature data, we could emphasize some milestones and also, controversies in the history of proposed multimodal treatment and thus, outline the philosophy of this approach, which seems to be an unusual one indeed. Initially marked by nihilism and fear, but benefiting from a remarkable joint effort of human and material resources (multi-center and -institutional research), over a period of 30 years, CRS and HIPEC found their place in the treatment of PM. The next 4 years were dedicated to the refinement of the multimodal treatment, by launching research pathways. In selected patients, with requires training, it demonstrated a significant survival results (similar to the Hepatic Metastases treatment), with acceptable risks and costs. The main debates regarding CRS and HIPEC treatment were based on the oncologists’ perspective and the small number of randomized clinical trials. It is important to statement the PM patient has the right to be informed of the existence of CRS and HIPEC, as a real treatment resource, the decision being made by multidisciplinary teams. PMID:26798438

  6. [Current Conservative Treatment and Management Strategies of Skeletal Muscle Injuries].

    PubMed

    Hotfiel, T; Carl, H-D; Swoboda, B; Heinrich, M; Heiß, R; Grim, C; Engelhardt, M

    2016-06-01

    Muscle injuries frequently occur during sport and are one of the commonest injuries. The diagnosis and treatment of muscle injuries impose high demands on medical treatment, in order to ensure successful regeneration and a rapid return to sport. Most of the injuries can be treated conservatively, as skeletal muscles have a high endogenous capacity for repair and regeneration. Conservative treatment includes initial on-field therapy. This is known as the "RICE" principle and is common and recommended for initial treatment for most sports injuries. The primary therapy target is to reduce pain, swelling and bleeding and thus to limit the initial inflammatory process and prevent further damage. During the first days after injury, brief immobilization helps to reduce the re-injury rate and accelerates the formation of granulation tissue. There are many possible additional treatments, including intramuscular injections, manipulation of the sacroiliac joint or rehabilitation programs, including stretching and strengthening. If the acute treatment phase is complete after 3 to 5 days, more active treatment, including trunk stabilisation, stretching and strengthening, can be started gradually. Despite their high prevalence, there have only been a few studies on the treatment and management of these injuries. The aim of this manuscript is to review the literature on the classification, pathobiology and treatment strategies for muscle injuries. PMID:27351158

  7. Sprouty2 protein in prediction of post-treatment ascites in epithelial ovarian cancer treated with adjuvant carbotaxol chemotherapy

    PubMed Central

    Masoumi-Moghaddam, Samar; Amini, Afshin; Wei, Ai-Qun; Robertson, Gregory; Morris, David L

    2015-01-01

    Ascites development and resistance to chemotherapy with carbotaxol are common clinical problems in epithelial ovarian cancer, partly due to the activation of MAPK/ERK signaling. Sprouty proteins are negative modulators of MAPK/ERK pathway, but their role in predicting resistance to carbotaxol chemotherapy and ascites development is unknown. In this study, we evaluated the expression of Sprouty protein isoforms by immunohistochemistry. The associations between the Sprouty expression and the clinicopathological features, including chemoresistance and the presence of ascites, were then explored. We found that the decreased expression of Spry2 was correlated with the post-treatment development of ascites and represented an independent predictor of this condition in carbotaxol-treated patients. However, no association was observed between the Sprouty expression and chemoresistance. In conclusion, our results suggest that Spry2 may be useful for patient follow-up and monitoring as it predicts the development of ascites in epithelial ovarian cancer cases treated with carbotaxol. PMID:26396926

  8. Innate immunity and adjuvants.

    PubMed

    Akira, Shizuo

    2011-10-12

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection. PMID:21893536

  9. Innate immunity and adjuvants

    PubMed Central

    Akira, Shizuo

    2011-01-01

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection. PMID:21893536

  10. Cerebrolysin adjuvant treatment in Broca's aphasics following first acute ischemic stroke of the left middle cerebral artery

    PubMed Central

    Muresanu, DF; Bajenaru, O; Popescu, BO; Deme, SM; Moessler, H; Meinzingen, SZ; Petrica, L; Serpe, M; Ursoniu, S

    2010-01-01

    Background: The aim of our study was to assess the efficacy of Cerebrolysin administration in Broca's aphasics with acute ischemic stroke. Methods: We registered 2,212 consecutive Broca's aphasics following an acute ischemic stroke admitted in four departments of neurology in Romania, between September 2005 and September 2009. Language was evaluated with the Romanian version of the Western Aphasia Battery (WAB). The following inclusion criteria were used for this study: age 20%75 years, admission in the hospital within 12 hours from the onset of the symptoms, diagnosis of first acute left middle cerebral artery (MCA) ischemic stroke, presence of large artery disease (LAD) stroke, a NIHSS score of 5%22 points, and a therapeutic time window within 72 h. Fifty two patients were treated with Cerebrolysin (Cerebrolysin group) as an adjunctive treatment. A placebo group, which received saline infusions (n=104 patients) were matched to the NIHSS and WAB scores, gender and age of the Cerebrolysin group at baseline. We assessed spontaneous speech (SS), comprehension (C), repetition (R), naming (N), and Aphasia Quotient (AQ) scores of the two groups in an open label design, over 90 days, the mRS scores and mortality. Results: The Cerebrolysin and the placebo groups had similar age (66+/%8 versus 65+/%8 years) and sex ratio (14/38 versus 30/74). The mean AQ scores and the mean subscores for 3 subtests of WAB (SS, R, N) were similar at baseline and improved in the Cerebrolysin group significantly (p<0.05) over placebo group at all study time points. The mRS score at 90 days was also lower in the Cerebrolysin group than in the placebo group. Cerebrolysin and placebo were both tolerated and safe, and no difference in the mortality rate was seen (3.8% in each group). Conclusion: Cerebrolysin is effective for the treatment of Broca's aphasics with a first acute ischemic stroke of the left MCA territory. PMID:20945821

  11. Tissue and Serum miRNA Profile in Locally Advanced Breast Cancer (LABC) in Response to Neo-Adjuvant Chemotherapy (NAC) Treatment

    PubMed Central

    Al-Khanbashi, Manal; Caramuta, Stefano; Alajmi, Adil M.; Al-Haddabi, Ibrahim; Al-Riyami, Marwa; Lui, Weng-Onn; Al-Moundhri, Mansour S.

    2016-01-01

    Introduction MicroRNAs (miRNAs) are small non-coding RNA that plays a vital role in cancer progression. Neo-adjuvant chemotherapy (NAC) has become the standard of care for locally advanced breast cancer. The aim of this study was to evaluate miRNA alterations during NAC using multiple samples of tissue and serum to correlate miRNA expression with clinico-pathological features and patient outcomes. Methods Tissue and serum samples were collected from patients with locally advanced breast cancer undergoing NAC at four time points: time of diagnosis, after the first and fourth cycle of doxorubicin/cyclophosphamide treatment, and after the fourth cycle of docetaxel administration. First, we evaluated the miRNA expression profiles in tissue and correlated expression with clinico-pathological features. Then, a panel of four miRNAs (miR-451, miR-3200, miR-21, and miR-205) in serum samples was further validated using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). The alterations in serum levels of miRNA, associations with clinical and pathological responses, correlation with clinico-pathological features, and survival outcomes were studied using Friedman, Mann-Whitney U, and Spearman, Wilcoxon signed-ranks tests. P≤0.05 was considered statistically significant. Results We analyzed 72 tissue samples and 108 serum samples from 9 patients and 27 patients, respectively. MicroRNA expression profiling of tumor versus normal tissue revealed more than 100 differentially expressed miRNAs. Serum miR-451 levels were significantly decreased during treatment, and higher serum levels were associated with improved clinical and pathological responses and disease-free survival. This is one of the early reports on miR-3200 in response to treatment in breast cancer, as serum levels of miR-3200 found to decline during NAC, and higher serum levels were associated with lower residual breast cancer burden and relapse rates at time of diagnosis. Conclusion Variations in

  12. Novel treatment strategies for patients with relapsed classical Hodgkin lymphoma

    PubMed Central

    Jona, Adam; Younes, Anas

    2011-01-01

    The treatment of patients with relapsed and refractory Hodgkin lymphoma (HL), especially those who relapse after autologous stem cell transplantation, remains challenging. Patients with HL whose disease relapses after stem cell transplantation are rarely cured with current treatment modalities, and have a median survival is less than 3 years. With no new drugs have been approved by the FDA for HL in more than three decades, there is a clear unmet medical need for drug development for this patients population. New treatment strategies that are based on targeting oncogenic signaling pathways are currently explored. This review will focus on emerging new treatment modalities that are currently under investigation for patients with relapsed classical HL. PMID:20828898

  13. New Strategies for the Treatment of Phenylketonuria (PKU)

    PubMed Central

    Strisciuglio, Pietro; Concolino, Daniela

    2014-01-01

    Phenylketonuria (PKU) was the first inherited metabolic disease in which dietary treatment was found to prevent the disease’s clinical features. Treatment of phenylketonuria remains difficult due to progressive decrease in adherence to diet and the presence of neurocognitive defects despite therapy. This review aims to summarize the current literature on new treatment strategies. Additions to treatment include new, more palatable foods based on glycomacropeptide that contains very limited amount of aromatic amino acids, the administration of large neutral amino acids to prevent phenylalanine entry into the brain or tetrahydropterina cofactor capable of increasing residual activity of phenylalanine hydroxylase. Moreover, human trials have recently been performed with subcutaneous administration of phenylalanine ammonia-lyase, and further efforts are underway to develop an oral therapy containing phenylanine ammonia-lyase. Gene therapy also seems to be a promising approach in the near future. PMID:25375236

  14. Reducing Fatal Opioid Overdose: Prevention, Treatment and Harm Reduction Strategies

    PubMed Central

    Hawk, Kathryn F.; Vaca, Federico E.; D’Onofrio, Gail

    2015-01-01

    The opioid overdose epidemic is a major threat to the public’s health, resulting in the development and implementation of a variety of strategies to reduce fatal overdose [1-3]. Many strategies are focused on primary prevention and increased access to effective treatment, although the past decade has seen an exponential increase in harm reduction initiatives. To maximize identification of opportunities for intervention, initiatives focusing on prevention, access to effective treatment, and harm reduction are examined independently, although considerable overlap exists. Particular attention is given to harm reduction approaches, as increased public and political will have facilitated widespread implementation of several initiatives, including increased distribution of naloxone and policy changes designed to increase bystander assistance during a witnessed overdose [4-7]. PMID:26339206

  15. Adjuvant chemotherapy for rectal cancer: Is it needed?

    PubMed Central

    Milinis, Kristijonas; Thornton, Michael; Montazeri, Amir; Rooney, Paul S

    2015-01-01

    Adjuvant chemotherapy has become a standard treatment of advanced rectal cancer in the West. The benefits of adjuvant chemotherapy after surgery alone have been well established. However, controversy surrounds the use adjuvant chemotherapy in patients who received preoperative chemoradiotherapy, despite it being recommended by a number of international guidelines. Results of recent multicentre randomised control trials showed no benefit of adjuvant chemotherapy in terms of survival and rates of distant metastases. However, concerns exist regarding the quality of the studies including inadequate staging modalities, out-dated chemotherapeutic regimens and surgical approaches and small sample sizes. It has become evident that not all the patients respond to adjuvant chemotherapy and more personalised approach should be employed when considering the benefits of adjuvant chemotherapy. The present review discusses the strengths and weaknesses of the current evidence-base and suggests improvements for future studies. PMID:26677436

  16. Treatment strategies in early and advanced Parkinson disease.

    PubMed

    Ossig, Christiana; Reichmann, Heinz

    2015-02-01

    The initiation of therapy in Parkinson disease (PD), altering the medication, adding new substances, and switching to alternative therapies throughout the disease is always a matter of debate. In the past, experts in PD have propagated different medication strategies. Even though there is no new medical treatment on the horizon, much has changed in consideration of the known treatments in the early and advanced therapy for PD. Therapeutic regimens have to be adapted and adjusted on a regular basis to accomplish the best medical care for the predominant symptom of the individual patient with PD. PMID:25432721

  17. Assessment and treatment strategies for rotator cuff tears

    PubMed Central

    Al-Hakim, Wisam; Noorani, Ali

    2014-01-01

    Tears of the rotator cuff are common and becoming an increasingly frequent problem. There is a vast amount of literature on the merits and limitations of the various methods of clinical and radiological assessment of rotator cuff tears. This is also the case with regard to treatment strategies. Certain popular beliefs and principles practiced widely and the basis upon which they are derived may be prone to inaccuracy. We provide an overview of the historical management of rotator cuff tears, as well as an explanation for how and why rotator cuff tears should be managed, and propose a structured methodology for their assessment and treatment.

  18. [Pleural empyema - treatment strategies in light of etiology].

    PubMed

    Hecker, E; Hecker, H C; Hecker, K A

    2013-06-01

    The variety of strategies in the treatment of parapneumonic pleural empyema demonstrates the ambiguity for the method of choice. Parapneumonic pleural empyema has been classified into different stages and classes. While the American Thoracic Society (ATS) classification is based on the natural course of the disease, or according to the radiological, physical and biochemical characteristics respectively, the American College of Chest Physicians (ACCP) has categorized the patients with pleural empyema according to the risk of a poor outcome. The British Thoracic Society (BTS) developed a treatment algorithm based on a systematic review of peer-reviewed literature. With regard to this classification the management of parapneumonic and postoperative pleural empyema is based on the stage of the disease. Therapeutic strategies include chest tube alone, chest tube with fibrinolysis, thoracoscopic debridement and decortication in open or minimally invasive techniques, closed empyemectomy, or treatment with thoracomyoplasty, open window treatment or vacuum clothing with negative pressure. The different conservative and operative therapeutic possibilities determinate the central treatment function of thoracic surgery. PMID:23807591

  19. New strategies for local treatment of vaginal infections.

    PubMed

    Palmeira-de-Oliveira, Rita; Palmeira-de-Oliveira, Ana; Martinez-de-Oliveira, José

    2015-09-15

    Vaginal infections are extremely prevalent, particularly among women of reproductive age. Although they do not result in high mortality rates, these infections are associated with high levels of anxiety and reduction of quality of life. In most cases, topical treatment of vaginal infections has been shown to be at least as effective as oral treatment, resulting in higher local drug concentrations, with fewer drug interactions and adverse effects. Furthermore, the emergence of microbial resistance to chemotherapeutics and the difficulties in managing infection recurrences sustain the need for more effective local treatments. However, conventional dosage forms have been associated with low retention in the vagina and discomfort. Formulation strategies such as the development of bioadhesive, thermogelling systems and microtechnological or nanotechnological approaches have been proposed to improve delivery of traditional drugs, and other treatment modalities such as new drugs, plant extracts, and probiotics are being studied. This article reviews the recent strategies studied to improve the treatment and prevention of the commonest vaginal infections-namely, vaginal bacteriosis, aerobic vaginitis, vulvovaginal candidosis, and trichomoniasis-through the intravaginal route. PMID:26144995

  20. Health from the Hive: Propolis as an Adjuvant in the Treatment of Chronic Periodontitis - A Clinicomicrobiologic Study

    PubMed Central

    Sanghani, Nehal N; S, Savita

    2014-01-01

    Objectives: This study was aimed at the clinical and microbiological evaluation of the efficacy of subgingivally delivered Indian propolis extract as an adjunct to scaling and root planing (SRP) in the treatment of periodontitis. Materials and Methods: Twenty patients diagnosed with chronic periodontitis presenting a minimum of two pockets (probing depth ≥5 mm) were selected. Sites were assigned randomly into control sites (n=20) which received SRP alone or test sites (n=20) which received SRP and locally delivered propolis. At selected sites, the clinical parameters were assessed and subgingival plaque samples were collected at baseline, 15 days and one month. The samples were cultured anerobically for periodontal pathogens. Results: The results indicated that there was a significant improvement in both clinical and microbiological parameters (p<0.01) in the test sites compared to the control sites at the end of the study. Conclusion: Subgingival delivery of propolis showed promising results as an adjunct to SRP in patients with chronic periodontitis when assessed by clinical and microbiological parameters. PMID:25386520

  1. Treatment Strategies for Patients with an INTERMACS I Profile

    PubMed Central

    Abu Saleh, Walid K.; Jabbari, Odeaa Al; Guha, Ashrith; Loebe, Matthias; Bruckner, Brian A.

    2015-01-01

    Treatment of patients with INTERMACS class I heart failure can be very challenging, and temporary long-term device support may be needed. In this article, we review the currently available temporary support devices in order to support these severely ill patients with decompensated heart failure. Strategies of using a temporary assist as a bridge to long-term device support are also discussed. PMID:25793022

  2. Treatment strategies for patients with an INTERMACS I profile.

    PubMed

    Abu Saleh, Walid K; Jabbari, Odeaa Al; Guha, Ashrith; Loebe, Matthias; Bruckner, Brian A

    2015-01-01

    Treatment of patients with INTERMACS class I heart failure can be very challenging, and temporary long-term device support may be needed. In this article, we review the currently available temporary support devices in order to support these severely ill patients with decompensated heart failure. Strategies of using a temporary assist as a bridge to long-term device support are also discussed. PMID:25793022

  3. Analysis of Regional Timelines To Set Up a Global Phase III Clinical Trial in Breast Cancer: The Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Experience

    PubMed Central

    de Azambuja, Evandro; Bradbury, Ian; Saini, Kamal S.; Bines, José; Simon, Sergio D.; Dooren, Veerle Van; Aktan, Gursel; Pritchard, Kathleen I.; Wolff, Antonio C.; Smith, Ian; Jackisch, Christian; Lang, Istvan; Untch, Michael; Boyle, Frances; Xu, Binghe; Baselga, Jose; Perez, Edith A.; Piccart-Gebhart, Martine

    2013-01-01

    Purpose. This study measured the time taken for setting up the different facets of Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO), an international phase III study being conducted in 44 participating countries. Methods. Time to regulatory authority (RA) approval, time to ethics committee/institutional review board (EC/IRB) approval, time from study approval by EC/IRB to first randomized patient, and time from first to last randomized patient were prospectively collected in the ALTTO study. Analyses were conducted by grouping countries into either geographic regions or economic classes as per the World Bank's criteria. Results. South America had a significantly longer time to RA approval (median: 236 days, range: 21–257 days) than Europe (median: 52 days, range: 0–151 days), North America (median: 26 days, range: 22–30 days), and Asia-Pacific (median: 62 days, range: 37–75 days). Upper-middle economies had longer times to RA approval (median: 123 days, range: 21–257 days) than high-income (median: 47 days, range: 0–112 days) and lower-middle income economies (median: 57 days, range: 37–62 days). No significant difference was observed for time to EC/IRB approval across the studied regions (median: 59 days, range 0–174 days). Overall, the median time from EC/IRB approval to first recruited patient was 169 days (range: 26–412 days). Conclusion. This study highlights the long time intervals required to activate a global phase III trial. Collaborative research groups, pharmaceutical industry sponsors, and regulatory authorities should analyze the current system and enter into dialogue for optimizing local policies. This would enable faster access of patients to innovative therapies and enhance the efficiency of clinical research. PMID:23359433

  4. [Adjuvant chemotherapy of adults soft tissue sarcomas].

    PubMed

    Bui-Nguyen, B; Italiano, A; Delva, F; Toulmond, M

    2010-06-01

    The main progress in the management of soft tissue sarcomas have been obtained in the field of local control. Although the main evolutive, vital, risk of these diseases is metastatic dissemination, efficacy of adjuvant chemotherapy remains a controversial issue. Thus, adjuvant chemotherapy cannot be considered as a standard for any situation. The last results of clinical trials, meta-analysis and population studies are presented and discussed in this article. New therapeutic strategies are to be developed to prevent metastases in soft tissue sarcomas. This needs a better understanding of the biology of those tumors, of metastases risk factors and of the determinants of systemic therapies efficacy in these tumors. PMID:20547481

  5. Multimodal treatment for stage IVA thymoma: a proposable strategy.

    PubMed

    Rena, Ottavio; Mineo, Tommaso Claudio; Casadio, Caterina

    2012-04-01

    A retrospective review of a series of consecutive patients was carried out to evaluate the feasibility and the efficacy of a multimodal treatment in the management of stage IVA thymoma at first diagnosis. From 1998 to 2008, 18 patients affected by stage IVA thymoma underwent neoadjuvant chemotherapy, surgery and subsequent mediastinal radiation therapy. There were 10 males and 8 females, mean age 54.5 years (range 29-68). Not specific symptoms were present in 12 cases and thymus-related syndromes were reported in 4. Histological subtypes were 1 AB, 2 B1, 4 B2, 7 B3, 1 mixed B1-B2, 1 mixed B1-B3 and 2 mixed B2-B3 thymomas. Neoadjuvant chemotherapy (4 courses of cisplatin-based chemotherapy) was well tolerated in all cases. Those patients demonstrating clinical response at restaging (16/18) received surgical resection: "en-bloc" thymoma, residual thymic tissue and tumour involved organs resection was carried out together with the pleural implants removal. Complete macroscopic resection was achieved 10/16 patients (64%). Postoperative mortality and morbidity were null and 24%, respectively. Adjuvant radiation therapy consisted of 45-54 Gy administered by a 6 MV linear accelerator to the whole mediastinum and previous tumour bed. Mean follow-up was 82±33 months (range 31-143); overall survival was 85% and 53% at 5- and 10-years. Disease-related survival of the entire cohort was 100% and 58% at 5- and 10-years, whereas freedom from relapse survival for patients submitted to complete resection was 58% and 42% at 5- and 10-years. Disease-related survival when complete and not complete resection were considered were 100% and 52% and 72% and 0% at 5- and 10-years respectively (p=0.048). Multimodal management based on induction chemotherapy, subsequent surgery and postoperative mediastinal radiation allows a good complete resection rate and it is demonstrated to be a safe and effective treatment to warrant a good long-term survival in stage IVA thymoma patients. PMID

  6. Sequence variation in mature microRNA-608 and benefit from neo-adjuvant treatment in locally advanced rectal cancer patients.

    PubMed

    Sclafani, Francesco; Chau, Ian; Cunningham, David; Lampis, Andrea; Hahne, Jens Claus; Ghidini, Michele; Lote, Hazel; Zito, Domenico; Tabernero, Josep; Glimelius, Bengt; Cervantes, Andres; Begum, Ruwaida; De Castro, David Gonzalez; Wilson, Sanna Hulkki; Peckitt, Clare; Eltahir, Zakaria; Wotherspoon, Andrew; Tait, Diana; Brown, Gina; Oates, Jacqueline; Braconi, Chiara; Valeri, Nicola

    2016-09-01

    Single nucleotide polymorphisms (SNPs) in microRNA genes have been associated with colorectal cancer (CRC) risk, survival and response to treatment. Conflicting results are available on the association between rs4919510, a SNP in mature miR-608 and clinical outcome in CRC. Here, we analyzed the association between rs4919510 and benefit from perioperative treatment in a randomised phase II trial of neoadjuvant Capecitabine and Oxaliplatin (CAPOX) followed by chemo-radiotherapy, surgery and adjuvant CAPOX ± Cetuximab in high-risk locally advanced rectal cancer (LARC). A total of 155/164 (94.5%) patients were assessable. 95 (61.3%) were homozygous for CC, 55 (35.5%) heterozygous (CG) and 5 (3.2%) homozygous for GG. Median follow-up was 64.9 months. In the CAPOX arm the 5-year progression-free survival (PFS) and overall survival (OS) rates were 54.6% and 60.7% for CC and 82.0% and 82.1% for CG/GG, respectively (HR PFS 0.13, 95% CI: 0.12-0.83, P = 0.02; HR OS 0.38, 95% CI: 0.14-1.01, P = 0.05). In the CAPOX-C arm PFS and OS were 73.2 and 82.2%, respectively for CC carriers and 64.6 and 73.1% for CG/GG carriers (HR PFS 1.38, 95% CI: 0.61-3.13, P = 0.44; HR OS 1.34, 95% CI: 0.52-3.48, P = 0.55). An interaction was found between study treatment and rs4919510 genotype for both PFS (P = 0.02) and OS (P = 0.07). This is the first study investigating rs4919510 in LARC. The CC genotype appeared to be associated with worse prognosis compared to the CG/GG genotype in patients treated with chemotherapy and chemo-radiotherapy alone. Addition of Cetuximab to chemotherapy and chemo-radiotherapy in CC carriers appeared to improve clinical outcome. PMID:27381831

  7. Sequence variation in mature microRNA-608 and benefit from neo-adjuvant treatment in locally advanced rectal cancer patients

    PubMed Central

    Sclafani, Francesco; Chau, Ian; Cunningham, David; Lampis, Andrea; Hahne, Jens Claus; Ghidini, Michele; Lote, Hazel; Zito, Domenico; Tabernero, Josep; Glimelius, Bengt; Cervantes, Andres; Begum, Ruwaida; De Castro, David Gonzalez; Wilson, Sanna Hulkki; Peckitt, Clare; Eltahir, Zakaria; Wotherspoon, Andrew; Tait, Diana; Brown, Gina; Oates, Jacqueline; Braconi, Chiara; Valeri, Nicola

    2016-01-01

    Single nucleotide polymorphisms (SNPs) in microRNA genes have been associated with colorectal cancer (CRC) risk, survival and response to treatment. Conflicting results are available on the association between rs4919510, a SNP in mature miR-608 and clinical outcome in CRC. Here, we analyzed the association between rs4919510 and benefit from perioperative treatment in a randomised phase II trial of neoadjuvant Capecitabine and Oxaliplatin (CAPOX) followed by chemo-radiotherapy, surgery and adjuvant CAPOX ± Cetuximab in high-risk locally advanced rectal cancer (LARC). A total of 155/164 (94.5%) patients were assessable. 95 (61.3%) were homozygous for CC, 55 (35.5%) heterozygous (CG) and 5 (3.2%) homozygous for GG. Median follow-up was 64.9 months. In the CAPOX arm the 5-year progression-free survival (PFS) and overall survival (OS) rates were 54.6% and 60.7% for CC and 82.0% and 82.1% for CG/GG, respectively (HR PFS 0.13, 95% CI: 0.12–0.83, P = 0.02; HR OS 0.38, 95% CI: 0.14–1.01, P = 0.05). In the CAPOX-C arm PFS and OS were 73.2 and 82.2%, respectively for CC carriers and 64.6 and 73.1% for CG/GG carriers (HR PFS 1.38, 95% CI: 0.61–3.13, P = 0.44; HR OS 1.34, 95% CI: 0.52–3.48, P = 0.55). An interaction was found between study treatment and rs4919510 genotype for both PFS (P = 0.02) and OS (P = 0.07). This is the first study investigating rs4919510 in LARC. The CC genotype appeared to be associated with worse prognosis compared to the CG/GG genotype in patients treated with chemotherapy and chemo-radiotherapy alone. Addition of Cetuximab to chemotherapy and chemo-radiotherapy in CC carriers appeared to improve clinical outcome. PMID:27381831

  8. Strategies for microwave thermal treatment planning, navigation, and assessment

    NASA Astrophysics Data System (ADS)

    Ryan, Thomas P.

    2011-03-01

    Thermal treatment is commonly performed interstitially in either surgical or percutaneous procedures, using microwave antenna sources at 915 or 2540 MHz. There are a number of tools or aids as well as challenges for clinicians performing these procedures in the course of patient treatment. These challenges will be present whether the procedure is surgical, laparoscopic, or percutaneous, and include treatment planning, image guidance, navigation, coregistration in 3D, and treatment assessment. Treatment planning has been used historically in hyperthermia for microwave antenna arrays, but has yet to be properly applied in thermal ablation. Image assessment of thermal treatment is not typically performed in real time, although these tools will provide the clinician with further information to understand the extent of treatment and whether further treatment is needed. 3D imaging is available, but not coregistered to patient space. Navigation has been used in many medical specialties, but is also not in the clinician's toolbox in thermal treatment. Although treatment planning will lay out the skin entry and trajectory for each antenna placed, subsequently, each antenna needs to be tracked to accurately show placement in the patient and overlaid in patient space, along with the tumor target location. Some patient treatments may consist of multiple, but sequential single placements of an antenna, and guidance is even more critical to track positions and plan for the next insertion. Lastly, real-time image assessment will show the extent and shape of the coagulated lesion and which targets may have been undertreated. If used synchronously in arrays, MW power steering may also aid in filling in the ablation as the treatment progresses. This paper will analyze the present state-of-the art as well as a strategy to incorporate the various facets of planning, guidance, and assessment of treatment. The integration of thermal treatment planning, navigation and guidance, robotics

  9. [Treatment strategy for advanced prostate cancer with bone metastases].

    PubMed

    Sugimoto, Mikio; Kakehi, Yoshiyuki

    2006-08-01

    The introduction of PSA screening has led to confirming a shift towards an earlier pathological stage in the diagnosis of prostate cancer. Consequently, the proportion of detecting early stage prostate cancer has clearly been increasing. On the other hand, progressive cancers in the form of distant metastases and locally advanced ones that have been confirmed at the initial diagnosis exhibit a constant rate. In addition, there have been a lot of cases where hormonal resistance was acquired during hormonal therapy which resulted in advanced metastases of the prostate. Prostate cancer has a tendency to be metastatic to bones. Combining the fact that the survival period of patients undergoing treatment is prolonged after metastases, the length of suffering caused by complications, such as ostealgia, pathological fracture and myelopathy, becomes an issue in which QOL and ADL of the patient are sacrificed for a long time. As for treatment of prostate cancer with metastases, a palliative treatment is common in the clinical scene. However, we can extend a life prognosis with use of radiotherapy and surgical treatment in addition to the palliative treatment at an appropriate time. It appears that a combination of new chemotherapy and hormonal therapy will be promising. In the future, we believe that the appearance of new anticancer drugs, endocrine therapies, bisphosphonates and strontium treatment could be used as a part of the treatment strategy for prostate cancer with bone metastases. PMID:16912523

  10. Mechanisms of Action of Adjuvants

    PubMed Central

    Awate, Sunita; Babiuk, Lorne A.; Mutwiri, George

    2013-01-01

    Adjuvants are used in many vaccines, but their mechanisms of action are not fully understood. Studies from the past decade on adjuvant mechanisms are slowly revealing the secrets of adjuvant activity. In this review, we have summarized the recent progress in our understanding of the mechanisms of action of adjuvants. Adjuvants may act by a combination of various mechanisms including formation of depot, induction of cytokines and chemokines, recruitment of immune cells, enhancement of antigen uptake and presentation, and promoting antigen transport to draining lymph nodes. It appears that adjuvants activate innate immune responses to create a local immuno-competent environment at the injection site. Depending on the type of innate responses activated, adjuvants can alter the quality and quantity of adaptive immune responses. Understanding the mechanisms of action of adjuvants will provide critical information on how innate immunity influences the development of adaptive immunity, help in rational design of vaccines against various diseases, and can inform on adjuvant safety. PMID:23720661

  11. SMARTer Discontinuation Trial Designs for Developing an Adaptive Treatment Strategy

    PubMed Central

    Compton, Scott N.; Rynn, Moira A.; Walkup, John T.; Murphy, Susan A.

    2012-01-01

    Abstract Objective Developing evidenced-based practices for the management of childhood psychiatric disorders requires research studies that address how to treat children during both the acute phase of the disorder and beyond. Given the selection of a medication for acute treatment, discontinuation trials are used to evaluate the effects of treatment duration (e.g., time on medication) and/or maintenance strategies following successful acute-phase treatment. Recently, sequential multiple assignment randomized trials (SMART) have been proposed for use in informing sequences of critical clinical decisions such as those mentioned. The objective of this article is to illustrate how a SMART study is related to the standard discontinuation trial design, while addressing additional clinically important questions with similar trial resources. Method The recently completed Child/Adolescent Anxiety Multimodal Study (CAMS), a randomized trial that examined the relative efficacy of three acute-phase treatments for pediatric anxiety disorders, along with a next logical step, a standard discontinuation trial design, is used to clarify the ideas. This example is used to compare the discontinuation trial design relative to the SMART design. Results We find that the standard discontinuation trial can be modified slightly using a SMART design to yield high-quality data that can be used to address a wider variety of questions in addition to the impact of treatment duration. We discuss how this innovative trial design is ultimately more efficient and less costly than the standard discontinuation trial, and may result in more representative comparisons between treatments. Conclusions Mental health researchers who are interested in addressing questions concerning the effects of continued treatment (for different durations) following successful acute-phase treatment should consider SMART designs in place of discontinuation trial designs in their research. SMART designs can be used to

  12. Bioengineering Strategies for the Treatment of Type I Diabetes.

    PubMed

    Liu, Xiaoyan; Li, Xiaowei; Zhang, Ning; Zhao, Zhanzheng; Wen, Xuejun

    2016-04-01

    Diabetes mellitus, the third most common disease in the world, is a chronic metabolic disorder caused by a failure of insulin production and/or an inability to respond to insulin. Specifically, type 1 diabetes is a disease resulted by the autoimmune destruction of a patient's β-cell population within the pancreatic islets of Langerhans. The current primary treatment for type 1 diabetes is daily multiple insulin injections. However, this treatment cannot provide sustained physiological release, and the insulin amount is not finely tuned to glycemia. Pancreatic transplants or islet transplants would be the preferred treatment method but the lack of donor tissue and immunoincompatibility has been shown to be a roadblock to their widespread use. Bioengineering strategies are poised to combat these challenges. In this review, bioengineering approaches for the treatment of type 1 diabetes, including insulin controlled release systems, strategies for immunoisolation of transplanted islets, and cell-based therapies, such as β-cells and stem cells, are discussed. PMID:27301187

  13. Optimal Pharmacologic Treatment Strategies in Obesity and Type 2 Diabetes

    PubMed Central

    Goswami, Gayotri; Shinkazh, Nataliya; Davis, Nichola

    2014-01-01

    The prevalence of obesity has increased to pandemic levels worldwide and is related to increased risk of morbidity and mortality. Metabolic comorbidities are commonly associated with obesity and include metabolic syndrome, pre-diabetes, and type 2 diabetes. Even if the prevalence of obesity remains stable until 2030, the anticipated numbers of people with diabetes will more than double as a consequence of population aging and urbanization. Weight reduction is integral in the prevention of diabetes among obese adults with pre-diabetes. Lifestyle intervention and weight reduction are also key in the management of type 2 diabetes. Weight loss is challenging for most obese patients, but for those with diabetes, it can pose an even greater challenge due to the weight gain associated with many treatment regimens. This article will review optimal treatment strategies for patients with comorbid obesity and type 2 diabetes. The role of anti-obesity agents in diabetes will also be reviewed. This literature review will provide readers with current strategies for the pharmacologic treatment of obesity and diabetes with a focus on the weight outcomes related to diabetes treatments. PMID:26237392

  14. 4D Proton treatment planning strategy for mobile lung tumors

    SciTech Connect

    Kang Yixiu; Zhang Xiaodong; Chang, Joe Y.; Wang He; Wei Xiong; Liao Zhongxing; Komaki, Ritsuko; Cox, James D.; Balter, Peter A.; Liu, Helen; Zhu, X. Ronald; Mohan, Radhe; Dong Lei . E-mail: ldong@mdanderson.org

    2007-03-01

    Purpose: To investigate strategies for designing compensator-based 3D proton treatment plans for mobile lung tumors using four-dimensional computed tomography (4DCT) images. Methods and Materials: Four-dimensional CT sets for 10 lung cancer patients were used in this study. The internal gross tumor volume (IGTV) was obtained by combining the tumor volumes at different phases of the respiratory cycle. For each patient, we evaluated four planning strategies based on the following dose calculations: (1) the average (AVE) CT; (2) the free-breathing (FB) CT; (3) the maximum intensity projection (MIP) CT; and (4) the AVE CT in which the CT voxel values inside the IGTV were replaced by a constant density (AVE{sub R}IGTV). For each strategy, the resulting cumulative dose distribution in a respiratory cycle was determined using a deformable image registration method. Results: There were dosimetric differences between the apparent dose distribution, calculated on a single CT dataset, and the motion-corrected 4D dose distribution, calculated by combining dose distributions delivered to each phase of the 4DCT. The AVE{sub R}IGTV plan using a 1-cm smearing parameter had the best overall target coverage and critical structure sparing. The MIP plan approach resulted in an unnecessarily large treatment volume. The AVE and FB plans using 1-cm smearing did not provide adequate 4D target coverage in all patients. By using a larger smearing value, adequate 4D target coverage could be achieved; however, critical organ doses were increased. Conclusion: The AVE{sub R}IGTV approach is an effective strategy for designing proton treatment plans for mobile lung tumors.

  15. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment

    PubMed Central

    Lee, Youjin; Auh, Sogyong L.; Wang, Yugang; Burnette, Byron; Wang, Yang; Meng, Yuru; Beckett, Michael; Sharma, Rohit; Chin, Robert; Tu, Tony

    2009-01-01

    Patients with locally advanced cancer or distant metastasis frequently receive prolonged treatment with chemotherapy and/or fractionated radiotherapy (RT). Despite the initial clinical response, treatment resistance frequently develops and cure in these patients is uncommon. Developments in RT technology allow for the use of high-dose (or ablative) RT to target local tumors, with limited damage to the surrounding normal tissue. We report that reduction of tumor burden after ablative RT depends largely on T-cell responses. Ablative RT dramatically increases T-cell priming in draining lymphoid tissues, leading to reduction/eradication of the primary tumor or distant metastasis in a CD8+ T cell–dependent fashion. We further demonstrate that ablative RT-initiated immune responses and tumor reduction are abrogated by conventional fractionated RT or adjuvant chemotherapy but greatly amplified by local immunotherapy. Our study challenges the rationale for current RT/chemotherapy strategies and highlights the importance of immune activation in preventing tumor relapse. Our findings emphasize the need for new strategies that not only reduce tumor burden but also enhance the role of antitumor immunity. PMID:19349616

  16. CpG DNA as mucosal adjuvant.

    PubMed

    McCluskie, M J; Davis, H L

    1999-09-01

    We have previously found synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs to be a potent adjuvant to protein administered by intramuscular injection or intranasal inhalation to BALB/c mice. Herein we have further evaluated the potential of CpG ODN as a mucosal adjuvant to purified hepatitis B surface antigen (HBsAg) when administered alone or with cholera toxin (CT). CpG ODN and CT both augmented systemic (humoral and cellular) and mucosal immune responses against HBsAg, and these could be further enhanced with higher doses of adjuvant or boosting. Overall, antibody isotypes with CT alone were predominantly IgG1 (Th2-like) whereas they were predominantly IgG2a (Th1-like) with CpG ODN alone or in combination with CT. Results from this study indicate that stimulatory CpG ODN are promising new adjuvants for mucosal vaccination strategies, whether used alone or in combination with other mucosal adjuvants. PMID:10506647

  17. Recent Strategies in Treatment of Pulmonary Arterial Hypertension, A Review

    PubMed Central

    Fallah, Flora

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a disease characterized by an elevation in pulmonary artery pressure that can lead to right ventricular failure and death. The pulmonary circulation has to accommodate the entire cardiac output in each cardiac cycle and evolution has adapted to this by making it a low-pressure high-flow system. However, pathology can affect both the arterial and venous components of this system. Pulmonary venous hypertension mainly refers to diseases that result in elevated venous pressure and occurs mainly from mitral valve and left-sided heart disease. Standard treatment options include oral anticoagulation, diuretics, oxygen supplementation, and for a small percentage of patients, calcium channel blockers. Newer treatments include prostacyclin analogues, endothelin receptor antago¬nists, and phosphodiesterase type 5 inhibitors. This article reviews the current treatments strategies for PAH and provides guidelines for its management. PMID:25946920

  18. Adjuvant Embolization with N-butyl Cyanoacrylate in the Treatment of Cerebral Arteriovenous Malformations: Outcomes, Complications, and Predictors of Neurologic Deficits

    PubMed Central

    Starke, Robert M.; Komotar, Ricardo J.; Otten, Marc L.; Hahn, David K.; Fischer, Laura E.; Hwang, Brian Y.; Garrett, Matthew C.; Sciacca, Robert R.; Sisti, Michael B.; Solomon, Robert A.; Lavine, Sean D.; Connolly, E. Sander; Meyers, Philip M.

    2009-01-01

    Background and Purpose To assess the frequency, severity, and predictors of neurologic deficits following adjuvant embolization for cerebral arteriovenous malformations (AVMs). Methods From 1997-2006, 202 of 275 AVM patients received embolization prior to microsurgery (n=176) or radiosurgery (n=26). Patients were examined before and after endovascular embolization, and at clinical follow-up (mean 43.4±34.6 months). Outcome was classified according to the modified Rankin Scale (mRS). New neurological deficits after embolization were defined as minimal (no change in overall mRS), moderate (mRS≤2), or significant (mRS>2). Results 202 patients were treated in 377 embolization procedures. There were a total of 29 new clinical deficits after embolization (8% of procedures; 14% of patients), of which 19 were moderate or significant. Post-embolization deficits resolved in a significant number of patients over time (p<0.0001). Five patients suffered persistent neurological deficits due to embolization (1.3% of procedures; 2.5% of patients). In multivariate analysis, the following variables significantly predicted new neurological deficit following embolization: complex AVM with treatment plan specifying more than one embolization procedure (OR=2.7; 95% CI, 1.4-8.6), diameter <3cm (OR=3.2; 95%, CI 1.2-9.1), diameter >6cm (OR=6.2; 95% CI, 1.0-57.0), deep venous drainage (OR=2.7; 95% CI, 1.1-6.9) or eloquent location (OR=2.4; 95% CI, 1.0-5.7). These variables were weighted and used to compute an AVM Embolization Prognostic Risk Score for each patient. A score of 0 predicted no new deficits, a score of 1 predicted a new deficit rate of 6%, a score of 2 predicted a new deficit rate of 15%, a score of 3 predicted a new deficit rate of 21%, and a score of 4 predicted a new deficit rate of 50% (p<0.0001). Conclusions Small and large size, eloquent location, deep venous drainage, and complex vascular anatomy requiring multiple embolization procedures are risk factors for the

  19. Update on prolactinomas. Part 2: Treatment and management strategies.

    PubMed

    Wong, Anni; Eloy, Jean Anderson; Couldwell, William T; Liu, James K

    2015-10-01

    The authors present an update on the various treatment modalities and discuss management strategies for prolactinomas. Prolactinomas are the most common type of functional pituitary tumor. Effective hyperprolactinemia treatment is of great importance, due to its potential deleterious effects including infertility, gonadal dysfunction and osteoporosis. Dopamine agonist therapy is the first line of treatment for prolactinomas because of its effectiveness in normalizing serum prolactin levels and shrinking tumor size. Though withdrawal of dopamine agonist treatment is safe and may be implemented following certain recommendations, recurrence of disease after cessation of the drug occurs in a substantial proportion of patients. Concerns regarding the safety of dopamine agonists have been raised, but its safety profile remains high, allowing its use during pregnancy. Surgery is typically indicated for patients who are resistant to medical therapy or intolerant of its adverse side effects, or are experiencing progressive tumor growth. Surgical resection can also be considered as a primary treatment for those with smaller focal tumors where a biochemical cure can be expected as an alternative to lifelong dopamine agonist treatment. Stereotactic radiosurgery also serves as an option for those refractory to medical and surgical therapy. PMID:26243714

  20. [Pharmacological treatment strategy and mirror visual feedback treatment for neuropathic pain].

    PubMed

    Sumitani, Masahiko; Miyauchi, Satoru; Yamada, Yoshitsugu

    2012-11-01

    Neuropathic pain is a debilitating condition, and pharmacotherapy is the most established treatment strategy. A variety of pharmacotherapies is used for neuropathic pain management: however, pharmacotherapies with evidence for analgesic potency are less common. Several pharmacotherapeutic treatment guidelines for neuropathic pain treatment recommend the first- to third-line drugs on the basis of evidence-based medicine; however, neuropathic pain is often resistant to pharmacotherapies. We have treated pharmacotherapy-resistant neuropathic pain with neurorehabilitation techniques such as mirror visual feedback (MVF) treatment. Further to our clinical experience using MVF, we discuss the cerebral mechanism associated with neuropathic pain in this study. PMID:23131739

  1. Dietary Strategies for the Treatment of Cadmium and Lead Toxicity

    PubMed Central

    Zhai, Qixiao; Narbad, Arjan; Chen, Wei

    2014-01-01

    Cadmium (Cd) and lead (Pb) are toxic heavy metals that cause adverse health effects in humans and animals. Chelation therapy, the conventional treatment for heavy metal toxicity, is reported to have a number of safety and efficacy issues. Recent studies have shown that dietary supplements play important roles in protecting against Cd and Pb toxicity. This paper reviews the evidence for protective effects of essential metals, vitamins, edible plants, phytochemicals, probiotics and other dietary supplements against Cd and Pb toxicity and describes the proposed possible mechanisms. Based on these findings, dietary strategies are recommended for people at risk of Cd and Pb exposure. The application of these strategies is advantageous for both the prevention and alleviation of Cd and Pb toxicity, as such supplements can be added easily and affordably to the daily diet and are expected to have very few side effects compared to the chelation therapy. PMID:25594439

  2. Combined bacterial and viral treatment: a novel anticancer strategy

    PubMed Central

    2015-01-01

    An idea for a new combination therapy will be described herein. It is a proposition to combine viral and bacterial anticancer therapies and make them fight cancer in concert. We analyzed biological anticancer therapies and found overlapping advantages and disadvantages which led us to the conclusion that the combination therapy has the potential to create a new therapeutic quality. It is surprising how many weaknesses of viral anticancer therapy are the strengths of bacterial anticancer therapies and the other way round. We review the facts behind this concept and try to assess its value. We propose a few strategies how to combine these two therapies but as far as the review can go, final answers will have to come from the experiments. This review is the first attempt to describe a new strategy and understand the means for this idea but also to raise new questions and discuss new ways to look at anti-cancer treatment. PMID:26648783

  3. Dietary strategies for the treatment of cadmium and lead toxicity.

    PubMed

    Zhai, Qixiao; Narbad, Arjan; Chen, Wei

    2015-01-01

    Cadmium (Cd) and lead (Pb) are toxic heavy metals that cause adverse health effects in humans and animals. Chelation therapy, the conventional treatment for heavy metal toxicity, is reported to have a number of safety and efficacy issues. Recent studies have shown that dietary supplements play important roles in protecting against Cd and Pb toxicity. This paper reviews the evidence for protective effects of essential metals, vitamins, edible plants, phytochemicals, probiotics and other dietary supplements against Cd and Pb toxicity and describes the proposed possible mechanisms. Based on these findings, dietary strategies are recommended for people at risk of Cd and Pb exposure. The application of these strategies is advantageous for both the prevention and alleviation of Cd and Pb toxicity, as such supplements can be added easily and affordably to the daily diet and are expected to have very few side effects compared to the chelation therapy. PMID:25594439

  4. Novel treatment strategies for brain tumors and metastases

    PubMed Central

    El-Habashy, Salma E.; Nazief, Alaa M.; Adkins, Chris E.; Wen, Ming Ming; El-Kamel, Amal H.; Hamdan, Ahmed M.; Hanafy, Amira S.; Terrell, Tori O.; Mohammad, Afroz S.; Lockman, Paul R.; Nounou, Mohamed Ismail

    2015-01-01

    This review summarizes patent applications in the past 5 years for the management of brain tumors and metastases. Most of the recent patents discuss one of the following strategies: the development of new drug entities that specifically target the brain cells, the blood–brain barrier and the tumor cells, tailor-designing a novel carrier system that is able to perform multitasks and multifunction as a drug carrier, targeting vehicle and even as a diagnostic tool, direct conjugation of a US FDA approved drug with a targeting moiety, diagnostic moiety or PK modifying moiety, or the use of innovative nontraditional approaches such as genetic engineering, stem cells and vaccinations. Until now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are actively ongoing to take brain tumor targeting, and novel and targeted CNS delivery systems to potential clinical application. PMID:24998288

  5. Novel treatment strategies for brain tumors and metastases.

    PubMed

    El-Habashy, Salma E; Nazief, Alaa M; Adkins, Chris E; Wen, Ming Ming; El-Kamel, Amal H; Hamdan, Ahmed M; Hanafy, Amira S; Terrell, Tori O; Mohammad, Afroz S; Lockman, Paul R; Nounou, Mohamed Ismail

    2014-05-01

    This review summarizes patent applications in the past 5 years for the management of brain tumors and metastases. Most of the recent patents discuss one of the following strategies: the development of new drug entities that specifically target the brain cells, the blood-brain barrier and the tumor cells, tailor-designing a novel carrier system that is able to perform multitasks and multifunction as a drug carrier, targeting vehicle and even as a diagnostic tool, direct conjugation of a US FDA approved drug with a targeting moiety, diagnostic moiety or PK modifying moiety, or the use of innovative nontraditional approaches such as genetic engineering, stem cells and vaccinations. Until now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are actively ongoing to take brain tumor targeting, and novel and targeted CNS delivery systems to potential clinical application. PMID:24998288

  6. A new strategy for TiO2 whiskers mediated multi-mode cancer treatment

    NASA Astrophysics Data System (ADS)

    Xu, Peipei; Wang, Ruju; Ouyang, Jian; Chen, Bing

    2015-02-01

    Traditional Chinese medicine (TCM) which functions as chemotherapeutic or adjuvantly chemotherapeutic agents has been drawing a great many eyeballs for its easy obtain and significant antitumor effects accompanied with less toxic and side effects. PDT (photodynamic therapy) utilizes the fact that certain compounds coined as photosensitizers, when exposed to light of a specific wavelength, are capable of generating cytotoxic reactive oxygen species (ROS) such as hydroxyl radical, hydrogen peroxide, and superoxide to kill cancer cells. Combinations of cancer therapeutic modalities are studied to improve the efficacy of treatment. This study aimed to explore a new strategy of coupling of titanium dioxide whiskers (TiO2 Ws) with the anticancer drug gambogic acid (GA) in photodynamic therapy. The nanocomposites were coined as GA-TiO2. The combination of TiO2 Ws with GA induced a remarkable enhancement in antitumor activity estimated by MTT assay, nuclear DAPI staining, and flow cytometry. Furthermore, the possible signaling pathway was explored by reverse transcription polymerase chain reaction (RT-PCR) and Western blot assay. These results identify TiO2 Ws of good biocompatibility and photocatalytic activity. In human leukemia cells (K562 cells), TiO2 Ws could obviously increase the intracellular concentration of GA and enhance its potential antitumor efficiency, suggesting that TiO2 Ws could act as an efficient drug delivery carrier targeting GA to carcinoma cells. Moreover, photodynamic GA-TiO2 nanocomposites could induce an evident reinforcement in antitumor activity with UV illumination. These results reveal that such modality combinations put forward a promising proposal in cancer therapy.

  7. Novel adjuvant systems.

    PubMed

    McCluskie, M J; Weeratna, R D

    2001-11-01

    Vaccination remains the single most valuable tool in the prevention of infectious disease. Nevertheless, there exists a need to improve the performance of existing vaccines such that fewer boosts are needed or to develop novel vaccines. For the development of effective vaccines for humans, a great need exists for safe and effective adjuvants. A number of novel adjuvants have been reported in recent years including: i) bacterial toxins such as cholera toxin, CT, and the Escherichia coli heat-labile enterotoxin, LT; ii) less toxic derivatives of CT and LT; iii) endogenous human immunomodulators, such as IL-2, IL-12, GM-CSF; iv) hormones; v) lipopeptides; vi) saponins, such as QS-21; vii) synthetic oligonucleotides containing CpG motifs (CpG ODN); viii) lipid 'A derivatives, such as monophosphoryl lipid A, MPL, and ix) muramyl dipeptide (MDP) derivatives. Herein, we will review recent findings using these novel adjuvant systems. PMID:12455400

  8. Randomized phase III trial of treatment duration for oral uracil and tegafur plus leucovorin as adjuvant chemotherapy for patients with stage IIB/III colon cancer: final results of JFMC33-0502

    PubMed Central

    Sadahiro, S.; Tsuchiya, T.; Sasaki, K.; Kondo, K.; Katsumata, K.; Nishimura, G.; Kakeji, Y.; Baba, H.; Sato, S.; Koda, K.; Yamaguchi, Y.; Morita, T.; Matsuoka, J.; Usuki, H.; Hamada, C.; Kodaira, S.

    2015-01-01

    Background While adjuvant chemotherapy is preferable for high-risk colon cancer, treatment duration is controversial. Oral uracil and tegafur (UFT)/leucovorin (LV) is widely used as a standard adjuvant chemotherapy for colon cancer in Japan. We conducted a phase III trial to investigate the optimal duration of adjuvant chemotherapy for stage IIB/III colon cancer. Patients and methods Patients with curatively resected stage IIB/III colon cancer were eligible for enrollment in this trial. Patients were registered within 6 weeks after surgery and were randomly assigned to receive UFT/LV for 28 of 35 days for 6 months in the control group or for 5 consecutive days per week for 18 months in the study group. The primary end point was the disease-free survival (DFS), and the secondary end points were overall survival (OS) and safety. Result A total of 1071 patients were registered from 233 centers. A statistically significant difference in DFS was not observed between the study group and the control group; the 5-year DFS was 69% in the study group and 69% in the control group. The 5-year OS was 85% in the study group and 85% in the control group. Conclusion Eighteen-month treatment with UFT/LV did not improve DFS or OS compared with 6-month UFT/LV treatment in patients with stage IIB/III colon cancer. The important finding from this study is that not 18 months but 6 months of treatment is enough for postoperative UFT/LV for stage IIB/III colon cancer. Clinical trial number UMIN-CTR C000000245. PMID:26347106

  9. Update on Adjuvant Chemotherapy for Early Breast Cancer

    PubMed Central

    Rampurwala, Murtuza M; Rocque, Gabrielle B; Burkard, Mark E

    2014-01-01

    Breast cancer is the second most common cancer in women worldwide. Although most women are diagnosed with early breast cancer, a substantial number recur due to persistent micro-metastatic disease. Systemic adjuvant chemotherapy improves outcomes and has advanced from first-generation regimens to modern dose-dense combinations. Although chemotherapy is the cornerstone of adjuvant therapy, new biomarkers are identifying patients who can forego such treatment. Neo-adjuvant therapy is a promising platform for drug development, but investigators should recognize the limitations of surrogate endpoints and clinical trials. Previous decades have focused on discovering, developing, and intensifying adjuvant chemotherapy. Future efforts should focus on customizing therapy and reducing chemotherapy for patients unlikely to benefit. In some cases, it may be possible to replace chemotherapy with treatments directed at specific genetic or molecular breast cancer subtypes. Yet, we anticipate that chemotherapy will remain a critical component of adjuvant therapy for years to come. PMID:25336961

  10. Energy Efficiency Strategies for Municipal Wastewater Treatment Facilities

    SciTech Connect

    Daw, J.; Hallett, K.; DeWolfe, J.; Venner, I.

    2012-01-01

    Water and wastewater systems are significant energy consumers with an estimated 3%-4% of total U.S. electricity consumption used for the movement and treatment of water and wastewater. Water-energy issues are of growing importance in the context of water shortages, higher energy and material costs, and a changing climate. In this economic environment, it is in the best interest for utilities to find efficiencies, both in water and energy use. Performing energy audits at water and wastewater treatment facilities is one way community energy managers can identify opportunities to save money, energy, and water. In this paper the importance of energy use in wastewater facilities is illustrated by a case study of a process energy audit performed for Crested Butte, Colorado's wastewater treatment plant. The energy audit identified opportunities for significant energy savings by looking at power intensive unit processes such as influent pumping, aeration, ultraviolet disinfection, and solids handling. This case study presents best practices that can be readily adopted by facility managers in their pursuit of energy and financial savings in water and wastewater treatment. This paper is intended to improve community energy managers understanding of the role that the water and wastewater sector plays in a community's total energy consumption. The energy efficiency strategies described provide information on energy savings opportunities, which can be used as a basis for discussing energy management goals with water and wastewater treatment facility managers.

  11. Treatment strategies for Middle East respiratory syndrome coronavirus

    PubMed Central

    Modjarrad, Kayvon

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging infectious disease of growing global importance, has caused severe acute respiratory disease in more than 1600 people, resulting in almost 600 deaths. The high case fatality rate, growing geographic distribution and vaguely defined epidemiology of this novel pathogen have created an urgent need for effective public health countermeasures, including safe and effective treatment strategies. Despite the relatively few numbers of cases to date, research and development of MERS-CoV therapeutic candidates is advancing quickly. This review surveys the landscape of these efforts and assesses their potential for use in affected populations. PMID:26866060

  12. Effective treatment of bipolar depression: monotherapy and combination strategies.

    PubMed

    Manning, J Sloan

    2015-11-01

    Managing patients with bipolar disorder remains a challenge due to its chronic nature. In addition, bipolar depression remains understudied even though patients spend more time in depressive episodes than in manic ones. Effective treatment requires an accurate and timely diagnosis, psychoeducation, psychotherapy, pharmacotherapy, and implementation of elements of the chronic care model. Pharmacologic strategies for treating bipolar depression differ from those for bipolar mania as well as those for unipolar depression and require knowledge of the efficacy and safety of agents including mood stabilizers, atypical antipsychotics, and antidepressants both as monotherapy and in combination. PMID:26646048

  13. Chronic type B aortic dissection: indications and strategies for treatment.

    PubMed

    Rohlffs, F; Tsilimparis, N; Diener, H; Larena-Avellaneda, A; Von Kodolitsch, Y; Wipper, S; Debus, E S; Kölbel, T

    2015-04-01

    Chronic type B aortic dissection is a distinctive condition that needs individual treatment strategies and different considerations than in therapy of acute or subacute type B aortic dissection. The most common indication for treatment of this complex disease is aneurysmal dilatation of the dissected aortic segment. While open repair of the enlarged dissected aorta remains the best option for good-risk patients and patients with connective tissue disorders in high-volume centers with respective expertise, endovascular management of chronic type B aortic dissection with postdissection aneurysms has significantly gained ground in the past years. But the concept of TEVAR with implantation of a tubular stent-graft into the thoracic aorta to seal the proximal entry tear and reroute the blood flow into the true lumen alone, is not associated with satisfactory results. This is mainly due to the sparse remodeling capacity of the aortic tissue compared to earlier stages of the disease as the aortic wall and the dissection membrane are thickened and more rigid. On the other hand, it is restricted by the most limiting factor for endovascular success in chronic type B aortic dissection: persistent false lumen perfusion. This problem also affects patients with residual dissection after surgical repair of a DeBakey type I aortic dissection or dissection after ascending aortic repair for other pathologies. Hence, it is evident that strategies to achieve endovascular false lumen occlusion are of increasing importance and novel techniques have been introduced to solve the problem of persisting false lumen flow. Thus, the evolution of a large variety of techniques to address the false lumen perfusion issue indicates that complicated chronic type B dissection involves a high diversity in clinical presentation and morphology. A large armamentarium of catheter skills as well as critical individualized treatment strategies are required to address the heterogenous morphological disease

  14. Adjuvant High-Dose Interferon-α for Resected Melanoma in a Patient with HIV Infection

    PubMed Central

    Saba, Nakhle S.; George, Thomas J.

    2010-01-01

    Adjuvant interferon (IFN)-α remains the standard adjuvant therapy for intermediate and high-risk melanoma after definitive surgical resection. Data addressing the role and safety of adjuvant immunotherapy in HIV-infected patients with melanoma are lacking. We report on an HIV+ patient who received IFN-α as adjuvant treatment for high-risk melanoma. To our knowledge, this is the first reported case of such an approach. PMID:20555019

  15. Adjuvant and Definitive Radiotherapy for Adrenocortical Carcinoma

    SciTech Connect

    Sabolch, Aaron; Feng, Mary; Griffith, Kent; Hammer, Gary; Doherty, Gerard; Ben-Josef, Edgar

    2011-08-01

    Purpose: To evaluate the impact of both adjuvant and definitive radiotherapy on local control of adrenocortical carcinoma. Methods and Materials: Outcomes were analyzed from 58 patients with 64 instances of treatment for adrenocortical carcinoma at the University of Michigan's Multidisciplinary Adrenal Cancer Clinic. Thirty-seven of these instances were for primary disease, whereas the remaining 27 were for recurrent disease. Thirty-eight of the treatment regimens involved surgery alone, 10 surgery plus adjuvant radiotherapy, and 16 definitive radiotherapy for unresectable disease. The effects of patient, tumor, and treatment factors were modeled simultaneously using multiple variable Cox proportional hazards regression for associations with local recurrence, distant recurrence, and overall survival. Results: Local failure occurred in 16 of the 38 instances that involved surgery alone, in 2 of the 10 that consisted of surgery plus adjuvant radiotherapy, and in 1 instance of definitive radiotherapy. Lack of radiotherapy use was associated with 4.7 times the risk of local failure compared with treatment regimens that involved radiotherapy (95% confidence interval, 1.2-19.0; p = 0.030). Conclusions: Radiotherapy seems to significantly lower the risk of local recurrence/progression in patients with adrenocortical carcinoma. Adjuvant radiotherapy should be strongly considered after surgical resection.

  16. Gliadel wafer implantation combined with standard radiotherapy and concurrent followed by adjuvant temozolomide for treatment of newly diagnosed high-grade glioma: a systematic literature review.

    PubMed

    Ashby, Lynn S; Smith, Kris A; Stea, Baldassarre

    2016-01-01

    Since 2003, only two chemotherapeutic agents, evaluated in phase III trials, have been approved by the US Food and Drug Administration for treatment of newly diagnosed high-grade glioma (HGG): Gliadel wafers (intracranially implanted local chemotherapy) and temozolomide (TMZ) (systemic chemotherapy). Neither agent is curative, but each has been shown to improve median overall survival (OS) compared to radiotherapy (RT) alone. To date, no phase III trial has tested these agents when used in sequential combination; however, a number of smaller trials have reported favorable results. We performed a systematic literature review to evaluate the combination of Gliadel wafers with standard RT (60 Gy) plus concurrent and adjuvant TMZ (RT/TMZ) for newly diagnosed HGG. A literature search was conducted for the period of January 1995 to September 2015. Data were extracted and categorized, and means and ranges were determined. A total of 11 publications met criteria, three prospective trials and eight retrospective studies, representing 411 patients who received Gliadel plus standard RT/TMZ. Patients were similar in age, gender, and performance status. The weighted mean of median OS was 18.2 months (ten trials, n = 379, range 12.7 to 21.3 months), and the weighted mean of median progression-free survival was 9.7 months (seven trials, n = 287, range 7 to 12.9 months). The most commonly reported grade 3 and 4 adverse events were myelosuppression (10.22 %), neurologic deficit (7.8 %), and healing abnormalities (4.3 %). Adverse events reflected the distinct independent safety profiles of Gliadel wafers and RT/TMZ, with little evidence of enhanced toxicity from their use in sequential combination. In the 11 identified trials, an increased benefit from sequentially combining Gliadel wafers with RT/TMZ was strongly suggested. Median OS tended to be improved by 3 to 4 months beyond that observed for Gliadel wafers or TMZ when used alone in the respective phase III

  17. Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

    NASA Astrophysics Data System (ADS)

    Payne, Richard; McDonald, David; Byrne, Scott

    2015-10-01

    Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

  18. Treatment strategies for gastric cancer patients with peritoneal metastasis.

    PubMed

    Imano, Motohiro; Okuno, Kiyotaka

    2014-03-01

    Although the treatment of gastric cancer improves the clinical outcomes, the survival of gastric cancer patients with peritoneal metastasis is still very poor. Effective drugs against peritoneal metastasis, coupled with new therapeutic modalities, are needed to improve the prognoses of these patients. Paclitaxel and TS-1 are candidate drugs for peritoneal metastasis, and intraperitoneal chemotherapy and targeted therapy are potential new therapeutic modalities. Two phase II studies using TS-1 and intraperitoneal and systemic paclitaxel for gastric cancer patients with peritoneal metastasis showed respectable survival results. In addition, peritoneal metastatic lesions showed high levels of epithelial cellular adhesion molecule (ECAM) and very low levels of human epidermal growth factor receptor 2 (HER2), thus indicating that an anti-ECAM monoclonal antibody, catumaxomab, would be effective against gastric cancer-derived peritoneal metastasis. Although catumaxomab and intraperitoneally administered paclitaxel are not generally used in Japan at present, these treatment strategies might therefore be effectively used in Japan in the near future. PMID:23677598

  19. The efficacy and safety of postoperative adjuvant transarterial embolization and radiotherapy in hepatocellular carcinoma patients with portal vein tumor thrombus

    PubMed Central

    Bai, Tao; Chen, Jie; Xie, Zhi-Bo; Wu, Fei-Xiang; Wang, Si-Da; Liu, Jun-Jie; Li, Le-Qun

    2016-01-01

    Objective This study aims to find out the safety and efficiency of postoperative adjuvant transarterial chemoembolization (TACE) and radiotherapy (RT) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). Methods From 2009 to 2010, a total of 92 HCC patients with PVTT were enrolled in this retrospective study. Patients were divided into three groups according to their adjuvant therapies (conservative group, n=51; TACE group, n=31; RT group, n=10). Results In our analysis, median survival in patients with postoperative adjuvant TACE (21.91±3.60 months) or RT (14.53±1.61 months) was significantly longer than patients with hepatectomy alone (8.99±1.03 months). But the difference between adjuvant TACE and RT was of no significance (P=0.716). Also a similar result could be observed in median disease-free survival: conservative group (6.51±1.44 months), TACE group (13.98±3.38 months), and RT group (14.03±2.40 months). Treatment strategies (hazard ratio [HR] =0.411, P<0.001) and PVTT type (HR =4.636, P<0.001) were the independent prognostic factors for overall survival. Similarly, the risk factors were the same when multivariate analysis was conducted in disease-free survival (treatment strategies, HR =0.423, P<0.001; PVTT type, HR =4.351, P<0.001) and recurrence (treatment strategies, HR =0.459, P=0.030; PVTT type, HR =2.908, P=0.047). Patients with PVTT type I had longer overall survival than patients with PVTT type II (median survival: 18.43±2.88 months vs 11.59±1.45 months, P=0.035). Conclusion Postoperative adjuvant TACE and RT may be a choice for HCC patients with PVTT. PMID:27390524

  20. Clean option: Berkeley Pit water treatment and resource recovery strategy

    SciTech Connect

    Gerber, M.A.; Orth, R.J.; Elmore, M.R.; Monzyk, B.F.

    1995-09-01

    The US Department of Energy (DOE), Office of Technology Development, established the Resource Recovery Project (RRP) in 1992 as a five-year effort to evaluate and demonstrate multiple technologies for recovering water, metals, and other industrial resources from contaminated surface and groundwater. Natural water resources located throughout the DOE complex and the and western states have been rendered unusable because of contamination from heavy metals. The Berkeley Pit, a large, inactive, open pit copper mine located in Butte, Montana, along with its associated groundwater system, has been selected by the RRP for use as a feedstock for a test bed facility located there. The test bed facility provides the infrastructure needed to evaluate promising technologies at the pilot plant scale. Data obtained from testing these technologies was used to assess their applicability for similar mine drainage water applications throughout the western states and at DOE. The objective of the Clean Option project is to develop strategies that provides a comprehensive and integrated approach to resource recovery using the Berkeley Pit water as a feedstock. The strategies not only consider the immediate problem of resource recovery from the contaminated water, but also manage the subsequent treatment of all resulting process streams. The strategies also employ the philosophy of waste minimization to optimize reduction of the waste volume requiring disposal, and the recovery and reuse of processing materials.

  1. Advances in Risk Classification and Treatment Strategies for Neuroblastoma.

    PubMed

    Pinto, Navin R; Applebaum, Mark A; Volchenboum, Samuel L; Matthay, Katherine K; London, Wendy B; Ambros, Peter F; Nakagawara, Akira; Berthold, Frank; Schleiermacher, Gudrun; Park, Julie R; Valteau-Couanet, Dominique; Pearson, Andrew D J; Cohn, Susan L

    2015-09-20

    Risk-based treatment approaches for neuroblastoma have been ongoing for decades. However, the criteria used to define risk in various institutional and cooperative groups were disparate, limiting the ability to compare clinical trial results. To mitigate this problem and enhance collaborative research, homogenous pretreatment patient cohorts have been defined by the International Neuroblastoma Risk Group classification system. During the past 30 years, increasingly intensive, multimodality approaches have been developed to treat patients who are classified as high risk, whereas patients with low- or intermediate-risk neuroblastoma have received reduced therapy. This treatment approach has resulted in improved outcome, although survival for high-risk patients remains poor, emphasizing the need for more effective treatments. Increased knowledge regarding the biology and genetic basis of neuroblastoma has led to the discovery of druggable targets and promising, new therapeutic approaches. Collaborative efforts of institutions and international cooperative groups have led to advances in our understanding of neuroblastoma biology, refinements in risk classification, and stratified treatment strategies, resulting in improved outcome. International collaboration will be even more critical when evaluating therapies designed to treat small cohorts of patients with rare actionable mutations. PMID:26304901

  2. Biological treatment strategies for disc degeneration: potentials and shortcomings

    PubMed Central

    Nerlich, Andreas G.; Boos, Norbert

    2006-01-01

    Recent advances in molecular biology, cell biology and material sciences have opened a new emerging field of techniques for the treatment of musculoskeletal disorders. These new treatment modalities aim for biological repair of the affected tissues by introducing cell-based tissue replacements, genetic modifications of resident cells or a combination thereof. So far, these techniques have been successfully applied to various tissues such as bone and cartilage. However, application of these treatment modalities to cure intervertebral disc degeneration is in its very early stages and mostly limited to experimental studies in vitro or in animal studies. We will discuss the potential and possible shortcomings of current approaches to biologically cure disc degeneration by gene therapy or tissue engineering. Despite the increasing number of studies examining the therapeutic potential of biological treatment strategies, a practicable solution to routinely cure disc degeneration might not be available in the near future. However, knowledge gained from these attempts might be applied in a foreseeable future to cure the low back pain that often accompanies disc degeneration and therefore be beneficial for the patient. PMID:16983559

  3. European Perspective on Multiple Myeloma Treatment Strategies in 2014

    PubMed Central

    Sonneveld, Pieter; Davies, Faith; Bladé, Joan; Boccadoro, Mario; Cavo, Michele; Morgan, Gareth; de la Rubia, Javier; Delforge, Michel; Dimopoulos, Meletios; Einsele, Hermann; Facon, Thierry; Goldschmidt, Hartmut; Moreau, Philippe; Nahi, Hareth; Plesner, Torben; San-Miguel, Jesús; Hajek, Roman; Sondergeld, Pia; Palumbo, Antonio

    2014-01-01

    The treatment of multiple myeloma has undergone significant changes and has resulted in the achievement of molecular remissions, the prolongation of remission duration, and extended survival becoming realistic goals, with a cure being possible in a small but growing number of patients. In addition, nowadays it is possible to categorize patients more precisely into different risk groups, thus allowing the evaluation of therapies in different settings and enabling a better comparison of results across trials. Here, we review the evidence from clinical studies, which forms the basis for our recommendations for the management of patients with myeloma. Treatment approaches depend on “fitness,” with chronological age still being an important discriminator for selecting therapy. In younger, fit patients, a short three drug-based induction treatment followed by autologous stem cell transplantation (ASCT) remains the preferred option. Consolidation and maintenance therapy are attractive strategies not yet approved by the European Medicines Agency, and a decision regarding post-ASCT therapy should only be made after detailed discussion of the pros and cons with the individual patient. Two- and three-drug combinations are recommended for patients not eligible for transplantation. Treatment should be administered for at least nine cycles, although different durations of initial therapy have only rarely been compared so far. Comorbidity and frailty should be thoroughly assessed in elderly patients, and treatment must be adapted to individual needs, carefully selecting appropriate drugs and doses. A substantial number of new drugs and novel drug classes in early clinical development have shown promising activity. Their introduction into clinical practice will most likely further improve treatment results. PMID:25063227

  4. European perspective on multiple myeloma treatment strategies in 2014.

    PubMed

    Ludwig, Heinz; Sonneveld, Pieter; Davies, Faith; Bladé, Joan; Boccadoro, Mario; Cavo, Michele; Morgan, Gareth; de la Rubia, Javier; Delforge, Michel; Dimopoulos, Meletios; Einsele, Hermann; Facon, Thierry; Goldschmidt, Hartmut; Moreau, Philippe; Nahi, Hareth; Plesner, Torben; San-Miguel, Jesús; Hajek, Roman; Sondergeld, Pia; Palumbo, Antonio

    2014-08-01

    The treatment of multiple myeloma has undergone significant changes and has resulted in the achievement of molecular remissions, the prolongation of remission duration, and extended survival becoming realistic goals, with a cure being possible in a small but growing number of patients. In addition, nowadays it is possible to categorize patients more precisely into different risk groups, thus allowing the evaluation of therapies in different settings and enabling a better comparison of results across trials. Here, we review the evidence from clinical studies, which forms the basis for our recommendations for the management of patients with myeloma. Treatment approaches depend on "fitness," with chronological age still being an important discriminator for selecting therapy. In younger, fit patients, a short three drug-based induction treatment followed by autologous stem cell transplantation (ASCT) remains the preferred option. Consolidation and maintenance therapy are attractive strategies not yet approved by the European Medicines Agency, and a decision regarding post-ASCT therapy should only be made after detailed discussion of the pros and cons with the individual patient. Two- and three-drug combinations are recommended for patients not eligible for transplantation. Treatment should be administered for at least nine cycles, although different durations of initial therapy have only rarely been compared so far. Comorbidity and frailty should be thoroughly assessed in elderly patients, and treatment must be adapted to individual needs, carefully selecting appropriate drugs and doses. A substantial number of new drugs and novel drug classes in early clinical development have shown promising activity. Their introduction into clinical practice will most likely further improve treatment results. PMID:25063227

  5. Is epirubicin effective in first-line chemotherapy of metastatic breast cancer (MBC) after an epirubicin-containing adjuvant treatment? A single centre phase III trial

    PubMed Central

    Pacilio, C; Morabito, A; Nuzzo, F; Gravina, A; Labonia, V; Landi, G; Rossi, E; De Maio, E; Di Maio, M; D'aiuto, G; Botti, G; Normanno, N; Chiodini, P; Gallo, C; Perrone, F; de Matteis, A

    2006-01-01

    The aim of the study was to demonstrate the superiority of docetaxel and epirubicin vs docetaxel alone as first-line therapy in metastatic breast cancer patients pretreated with adjuvant or neoadjuvant epirubicin. We compared single agent docetaxel 100 mg m−2 (D) with the combination of docetaxel 80 mg m−2 and epirubicin 75 mg m−2 (ED). The response rate (72 vs 79%), the progression-free survival (median 9 vs 11 months) and the overall survival (median 18 vs 21 months) were not significantly different between the ED (n=26) and D arms (n=25), respectively. Leucopaenia, nausea and stomatitis were significantly worse with ED. In conclusion, epirubicin should not be administered in combination with taxanes in metastatic breast cancer patients relapsed after an anthracycline-based adjuvant or neoadjuvant therapy. PMID:16622454

  6. Adjuvant treatment of node-positive breast cancer with adriamycin-cyclophosphamide with or without radiation therapy: interim results of an ongoing clinical trial.

    PubMed

    Jones, S E; Salmon, S E; Allen, H; Giordano, G F; Davis, S; Chase, E; Moon, T E; Heusinkveld, R S

    1982-01-01

    During 1974-1980, 138 women with node-positive stage II breast cancer were treated with either eight courses of adriamycin-cyclophosphamide (AC) chemotherapy (82 patients) or AC chemotherapy plus comprehensive regional radiotherapy (56 patients). The overall relapse-free survival of the treated patients was significantly superior (P less than 0.001) to a comparable group of women who underwent surgery alone. This effect of adjuvant therapy was clearly manifest in all groups of patients irrespective of nodal involvement or menopausal status. To date, relapse-free survival for patients receiving AC compared to AC plus radiotherapy is not different (P = 0.7). In summary, wer have demonstrated that a brief 6-month course of adjuvant chemotherapy with AC can significantly reduce the recurrence rate in women with stage II breast cancer. PMID:7036279

  7. Laser vaccine adjuvants

    PubMed Central

    Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C

    2014-01-01

    Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines. PMID:25424797

  8. Adjuvants and Inactivated Polio Vaccine: A Systematic Review

    PubMed Central

    Hawken, Jennifer; Troy, Stephanie B.

    2012-01-01

    Poliomyelitis is nearing universal eradication; in 2011, there were 650 cases reported globally. When wild polio is eradicated, global oral polio vaccine (OPV) cessation followed by universal use of inactivated polio vaccine (IPV) is believed to be the safest vaccination strategy as IPV does not mutate or run the risk of vaccine derived outbreaks that OPV does. However, IPV is significantly more expensive than OPV. One strategy to make IPV more affordable is to reduce the dose by adding adjuvants, compounds that augment the immune response to the vaccine. No adjuvants are currently utilized in stand-alone IPV; however, several have been explored over the past six decades. From aluminum, used in many licensed vaccines, to newer and more experimental adjuvants such as synthetic DNA, a diverse group of compounds has been assessed with varying strengths and weaknesses. This review summarizes the studies to date evaluating the efficacy and safety of adjuvants used with IPV. PMID:23041122

  9. Coronary microvascular dysfunction, microvascular angina, and treatment strategies.

    PubMed

    Marinescu, Mark A; Löffler, Adrián I; Ouellette, Michelle; Smith, Lavone; Kramer, Christopher M; Bourque, Jamieson M

    2015-02-01

    Angina without coronary artery disease (CAD) has substantial morbidity and is present in 10% to 30% of patients undergoing angiography. Coronary microvascular dysfunction (CMD) is present in 50% to 65% of these patients. The optimal treatment of this cohort is undefined. We performed a systematic review to evaluate treatment strategies for objectively-defined CMD in the absence of CAD. We included studies assessing therapy in human subjects with angina and coronary flow reserve or myocardial perfusion reserve <2.5 by positron emission tomography, cardiac magnetic resonance imaging, dilution methods, or intracoronary Doppler in the absence of coronary artery stenosis ≥50% or structural heart disease. Only 8 papers met the strict inclusion criteria. The papers were heterogeneous, using different treatments, endpoints, and definitions of CMD. The small sample sizes severely limit the power of these studies, with an average of 11 patients per analysis. Studies evaluating sildenafil, quinapril, estrogen, and transcutaneous electrical nerve stimulation application demonstrated benefits in their respective endpoints. No benefit was found with L-arginine, doxazosin, pravastatin, and diltiazem. Our systematic review highlights that there is little data to support therapies for CMD. We assess the data meeting rigorous inclusion criteria and review the related but excluded published data. We additionally describe the next steps needed to address this research gap, including a standardized definition of CMD, routine assessment of CMD in studies of chest pain without obstructive CAD, and specific therapy assessment in the population with confirmed CMD. PMID:25677893

  10. Near-Infrared Laser Adjuvant for Influenza Vaccine

    PubMed Central

    Kashiwagi, Satoshi; Yuan, Jianping; Forbes, Benjamin; Hibert, Mathew L.; Lee, Eugene L. Q.; Whicher, Laura; Goudie, Calum; Yang, Yuan; Chen, Tao; Edelblute, Beth; Collette, Brian; Edington, Laurel; Trussler, James; Nezivar, Jean; Leblanc, Pierre; Bronson, Roderick; Tsukada, Kosuke; Suematsu, Makoto; Dover, Jeffrey; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C.

    2013-01-01

    Safe and effective immunologic adjuvants are often essential for vaccines. However, the choice of adjuvant for licensed vaccines is limited, especially for those that are administered intradermally. We show that non-tissue damaging, near-infrared (NIR) laser light given in short exposures to small areas of skin, without the use of additional chemical or biological agents, significantly increases immune responses to intradermal influenza vaccination without augmenting IgE. The NIR laser-adjuvanted vaccine confers increased protection in a murine influenza lethal challenge model as compared to unadjuvanted vaccine. We show that NIR laser treatment induces the expression of specific chemokines in the skin resulting in recruitment and activation of dendritic cells and is safe to use in both mice and humans. The NIR laser adjuvant technology provides a novel, safe, low-cost, simple-to-use, potentially broadly applicable and clinically feasible approach to enhancing vaccine efficacy as an alternative to chemical and biological adjuvants. PMID:24349390

  11. Opioids, adjuvants, and interventional options for pain management of symptomatic metastases.

    PubMed

    Ghosh, Amrita; Berger, Ann

    2014-07-01

    Cancer pain is a complex issue that unfortunately affects a majority of cancer patients, the assessment and treatment of which are equally essential in alleviating many facets of this pain. The objective of this section is to address the many facets of cancer pain: its assessment, management, and its varied treatment modalities. We will discuss characteristics of pain, essential aspects of the patient interview, and management using opioids, adjuvants, and interventional and invasive strategies as well as side effects of these techniques. Many of these modalities are used for palliation but may and should be used in cancer patients who experience side effects from both their cancer and their chemotherapeutics. PMID:25841694

  12. Current and emerging strategies for treatment of childhood dystonia.

    PubMed

    Bertucco, Matteo; Sanger, Terence D

    2015-01-01

    Childhood dystonia is a movement disorder characterized by involuntary sustained or intermittent muscle contractions causing twisting and repetitive movements, abnormal postures, or both (Sanger et al, 2003). Dystonia is a devastating neurological condition that prevents the acquisition of normal motor skills during critical periods of development in children. Moreover, it is particularly debilitating in children when dystonia affects the upper extremities such that learning and consolidation of common daily motor actions are impeded. Thus, the treatment and rehabilitation of dystonia is a challenge that continuously requires exploration of novel interventions. This review will initially describe the underlying neurophysiological mechanisms of the motor impairments found in childhood dystonia followed by the clinical measurement tools that are available to document the presence and severity of symptoms. Finally, we will discuss the state-of-the-art of therapeutic options for childhood dystonia, with particular emphasis on emergent and innovative strategies. PMID:25835254

  13. Novel Strategies for the Treatment of Pseudomonas aeruginosa Infections.

    PubMed

    Wagner, Stefanie; Sommer, Roman; Hinsberger, Stefan; Lu, Cenbin; Hartmann, Rolf W; Empting, Martin; Titz, Alexander

    2016-07-14

    Infections with Pseudomonas aeruginosa have become a concerning threat in hospital-acquired infections and for cystic fibrosis patients. The major problem leading to high mortality lies in the appearance of drug-resistant strains. Therefore, a vast number of approaches to develop novel anti-infectives is currently pursued. These diverse strategies span from killing (new antibiotics) to disarming (antivirulence) the pathogen. Particular emphasis lies on the development of compounds that inhibit biofilms formed in chronic infections to restore susceptibility toward antibiotics. Numerous promising results are summarized in this perspective. Antibiotics with a novel mode of action will be needed to avoid cross resistance against currently used therapeutic agents. Importantly, antivirulence drugs are expected to yield a significantly reduced rate of resistance development. Most developments are still far from the application. It can however be expected that combination therapies, also containing antivirulence agents, will pave the way toward novel treatment options against P. aeruginosa. PMID:26804741

  14. Comparison of treatment strategies for space motion sickness

    NASA Technical Reports Server (NTRS)

    Davis, J. R.; Jennings, R. T.; Beck, B. G.

    1991-01-01

    Treatment strategies for space motion sickness were compared using the results of postflight oral debriefings. Standardized questionnaires were administered to all crewmembers immediately following Space Shuttle flights by NASA flight surgeons. Cases of space motion sickness were graded as mild, moderate, or severe based on published criteria, and medication effectiveness was judged based on subjective reports of symptom relief. Since October 1989, medication effectiveness is reported inflight through private medical conferences with the crew. A symptom matrix was analyzed for nineteen crewmembers treated with an oral combination of scopolomine and dextroamphetamine (scopdex) and fifteen crewmembers treated with promethazine delivered by intramuscular or suppository routes. Scopdex has been given preflight as prophylaxis for space motion sickness but analysis showed delayed symptom presentation in nine crewmembers or failed to prevent symptoms in seven.

  15. Current and emerging strategies for treatment of childhood dystonia

    PubMed Central

    Bertucco, Matteo; Sanger, Terence D.

    2014-01-01

    Childhood dystonia is a movement disorder characterized by involuntary sustained or intermittent muscle contractions causing twisting and repetitive movements, abnormal postures, or both (Sanger et al. 2003). Dystonia is a devastating neurological condition that prevents the acquisition of normal motor skills during critical periods of development in children. Moreover, it is particularly debilitating in children when dystonia affects the upper extremities such that learning and consolidation of common daily motor actions are impeded. Thus, the treatment and rehabilitation of dystonia is a challenge that continuously requires exploration of novel interventions. This review will initially describe the underlying neurophysiological mechanisms of the motor impairments found in childhood dystonia followed by the clinical measurement tools that are available to document the presence and severity of symptoms. Finally, we will discuss the state-of-the-art of therapeutic options for childhood dystonia, with particular emphasis on emergent and innovative strategies. PMID:25835254

  16. Treatment strategies in obstructed defecation and fecal incontinence

    PubMed Central

    Khaikin, Marat; Wexner, Steven D

    2006-01-01

    Obstructed defecation (OD) and fecal incontinence (FI) are challenging clinical problems, which are commonly encountered in the practice of colorectal surgeons and gastroenterologists. These disorders socially and psychologically distress patients and greatly impair their quality of life. The underlying anatomical and pathophysiological changes are complex, often incompletely understood and cannot always be determined. As a consequence, many medical, surgical, and behavioral approaches have been described, with no panacea. Over the past decade, advances in an understanding of these disorders together with rational and similar methods of evaluation in anorectal physiology laboratories (ARP), radiology studies, and new surgical techniques have led to promising results. In this brief review, we discuss treatment strategies and recent updates on clinical and therapeutic aspects of obstructed defecation and fecal incontinence. PMID:16718835

  17. Biomaterial Design Strategies for the Treatment of Spinal Cord Injuries

    PubMed Central

    Straley, Karin S.; Po Foo, Cheryl Wong

    2010-01-01

    Abstract The highly debilitating nature of spinal cord injuries has provided much inspiration for the design of novel biomaterials that can stimulate cellular regeneration and functional recovery. Many experts agree that the greatest hope for treatment of spinal cord injuries will involve a combinatorial approach that integrates biomaterial scaffolds, cell transplantation, and molecule delivery. This manuscript presents a comprehensive review of biomaterial-scaffold design strategies currently being applied to the development of nerve guidance channels and hydrogels that more effectively stimulate spinal cord tissue regeneration. To enhance the regenerative capacity of these two scaffold types, researchers are focusing on optimizing the mechanical properties, cell-adhesivity, biodegradability, electrical activity, and topography of synthetic and natural materials, and are developing mechanisms to use these scaffolds to deliver cells and biomolecules. Developing scaffolds that address several of these key design parameters will lead to more successful therapies for the regeneration of spinal cord tissue. PMID:19698073

  18. Knowledge of, and treatment strategies for, endometriosis among general practitioners.

    PubMed

    van der Zanden, Moniek; Nap, Annemiek W

    2016-05-01

    Endometriosis is the most common benign gynaecological disorder. The general practitioner (GP) plays an important role in identifying women at early stages of the disease. This study was conducted to acquire information about awareness and knowledge of endometriosis among Dutch GPs, and clinical strategies taken. A total of 101 GPs completed a questionnaire either by email or at a local education meeting. The GPs annually encounter 2.8 women they suspect of having endometriosis. The estimated time to diagnosis was 65.7 months (39.1 months patient delay and 26.6 months doctors delay); 56.7% of GPs primarily refer to a gynaecologist for consultation or diagnostic tests. The GPs answered on average 16.6 out of 28 knowledge questions correctly. Seventy-six out of 87 GPs stated that they needed further education. The results of this study indicate that if a GP considers endometriosis as a diagnosis, adequate action is undertaken. As only limited numbers of women with endometriosis are encountered in their practice, GPs do not recognize immediately the symptoms that may be caused by endometriosis, leading to diagnostic delay. Our findings may help to set up teaching programmes and awareness strategies for first-line medical professionals to enhance timely diagnosis and treatment of endometriosis. PMID:26947452

  19. Impaired movement timing in neurological disorders: rehabilitation and treatment strategies

    PubMed Central

    Hove, Michael J.; Keller, Peter E.

    2014-01-01

    Timing abnormalities have been reported in many neurological disorders, including Parkinson’s disease (PD). In PD, motor-timing impairments are especially debilitating in gait. Despite impaired audiomotor synchronization, PD patients’ gait improves when they walk with an auditory metronome or with music. Building on that research, we make recommendations for optimizing sensory cues to improve the efficacy of rhythmic cuing in gait rehabilitation. Adaptive rhythmic metronomes (that synchronize with the patient’s walking) might be especially effective. In a recent study we showed that adaptive metronomes synchronized consistently with Parkinson patients’ footsteps without requiring attention; this improved stability and reinstated healthy gait dynamics. Other strategies could help optimize sensory cues for gait rehabilitation. Groove music strongly engages the motor system and induces movement; bass-frequency tones are associated with movement and provide strong timing cues. Thus, groove and bass-frequency pulses could deliver potent rhythmic cues. These strategies capitalize on the close neural connections between auditory and motor networks; and auditory cues are typically preferred. However, moving visual cues greatly improve visuomotor synchronization and could warrant examination in gait rehabilitation. Together, a treatment approach that employs groove, auditory, bass-frequency, and adaptive (GABA) cues could help optimize rhythmic sensory cues for treating motor and timing deficits. PMID:25773624

  20. Impaired movement timing in neurological disorders: rehabilitation and treatment strategies.

    PubMed

    Hove, Michael J; Keller, Peter E

    2015-03-01

    Timing abnormalities have been reported in many neurological disorders, including Parkinson's disease (PD). In PD, motor-timing impairments are especially debilitating in gait. Despite impaired audiomotor synchronization, PD patients' gait improves when they walk with an auditory metronome or with music. Building on that research, we make recommendations for optimizing sensory cues to improve the efficacy of rhythmic cuing in gait rehabilitation. Adaptive rhythmic metronomes (that synchronize with the patient's walking) might be especially effective. In a recent study we showed that adaptive metronomes synchronized consistently with PD patients' footsteps without requiring attention; this improved stability and reinstated healthy gait dynamics. Other strategies could help optimize sensory cues for gait rehabilitation. Groove music strongly engages the motor system and induces movement; bass-frequency tones are associated with movement and provide strong timing cues. Thus, groove and bass-frequency pulses could deliver potent rhythmic cues. These strategies capitalize on the close neural connections between auditory and motor networks; and auditory cues are typically preferred. However, moving visual cues greatly improve visuomotor synchronization and could warrant examination in gait rehabilitation. Together, a treatment approach that employs groove, auditory, bass-frequency, and adaptive (GABA) cues could help optimize rhythmic sensory cues for treating motor and timing deficits. PMID:25773624

  1. [Peritoneal carcinomatosis: new strategies for more efficacious treatment].

    PubMed

    Zanon, Claudio

    2002-09-01

    The peritoneal carcinomatosis is considered an unlikely treatable disease using standard procedures as surgery or systemic chemotherapy. New improvements in the knowledge of the peritoneum are inducing to consider the mesothelium of the abdominal cavity as an organ similar to the other body organs. This new consideration, unified with the understanding of conditions permitting the implant of the tumor cell into the peritoneal space previous or during the surgical manipulation of the abdominal cancers, leads to the application of news strategies as the advanced cytoreduction with every nodes reduced less than 2.5 mm followed by the chemohyperthermic peritoneal perfusion (CHPP). Last papers indicate improvements in overall survival and quality of the life in ovarian, colonic and gastric cancer treated with an extensive surgical debulking plus CHPP. These results induce surgeons and oncologists to avoid incorrect strategies in the treatment of peritoneal carcinomatosis originating from ovarian and gastrointestinal tumors. In case of malignant untreatable ascites a peritoneo-venous shunt allows a control of the ascites avoiding several hospital admissions for continuous fastidious and sometime dangerous paracentesis. A palliative surgical operation in selected patients effected by trained surgical group permits an improvement of the patient's conditions in more than 80% with a positive feed back on his or her psychological behavior. PMID:12355981

  2. Potential regenerative treatment strategies for intervertebral disc degeneration in dogs

    PubMed Central

    2014-01-01

    Pain due to spontaneous intervertebral disc (IVD) disease is common in dogs. In chondrodystrophic (CD) dogs, IVD disease typically develops in the cervical or thoracolumbar spine at about 3–7 years of age, whereas in non-chondrodystrophic (NCD) dogs, it usually develops in the caudal cervical or lumbosacral spine at about 6–8 years of age. IVD degeneration is characterized by changes in the biochemical composition and mechanical integrity of the IVD. In the degenerated IVD, the content of glycosaminoglycan (GAG, a proteoglycan side chain) decreases and that of denatured collagen increases. Dehydration leads to tearing of the annulus fibrosus (AF) and/or disc herniation, which is clinically characterized by pain and/or neurological signs. Current treatments (physiotherapy, anti-inflammatory/analgesic medication, surgery) for IVD disease may resolve neurological deficits and reduce pain (although in many cases insufficient), but do not lead to repair of the degenerated disc. For this reason, there is interest in new regenerative therapies that can repair the degenerated disc matrix, resulting in restoration of the biomechanical function of the IVD. CD dogs are considered a suitable animal model for human IVD degeneration because of their spontaneous IVD degeneration, and therefore studies investigating cell-, growth factor-, and/or gene therapy-based regenerative therapies with this model provide information relevant to both human and canine patients. The aim of this article is to review potential regenerative treatment strategies for canine IVD degeneration, with specific emphasis on cell-based strategies. PMID:24387033

  3. Activity of glycated chitosan and other adjuvants to PDT vaccines

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Banáth, Judit; Čiplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

    2015-03-01

    Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

  4. [Strategies for the treatment of postoperative sternal infections].

    PubMed

    Akil, A; Schnorr, P; Wiebe, K

    2016-02-01

    Postoperative sternal infections are associated with significant morbidity and mortality. An incidence of up to 8 % has to be expected. Typically, a highly inflammatory acute infection with a marked soft tissue component is observed. However, the infection may also be present as a less symptomatic reaction and localised chronic osteomyelitis with fistula formation. The treatment strategy for a deep sternal wound infection consists of several steps. A radical debridement of the wound requires the opening of all abscesses, the resection of non-vital bone and the removal of all infected allomaterial. This is followed by a period of VAC therapy (Vacuum-Assisted Closure Therapy) for infection treatment and conditioning of the wound. Secondary closure of the wound may be planned only after the infection is completely controlled. The sternum is stabilised by osteosynthesis. Sternal defects are covered. In most cases adequate soft tissue coverage is achieved by mobilisation of both pectoral muscles together with the precostal soft tissues. Following resection of the sternum, the reconstruction of the thoracic wall requires the implantation of material for stabilisation as well as soft tissue coverage. For complicated or large defects various muscle flaps and the omentum majus have been advocated. The latissimus dorsi muscle with skin is the muscle flap most frequently used. PMID:26492536

  5. Comparison of treatment strategies for Space Motion Sickness

    NASA Astrophysics Data System (ADS)

    Davis, J. R.; Jennings, R. T.; Beck, B. G.

    Treatment strategies for Space Motion Sickness (SMS) were compared using the results of postflight oral debriefings. Standardized questionnaires were administered to all crewmembers immediately following Space Shuttle flights by NASA flight surgeons. Cases of SMS were graded as mild, moderate, or severe based on published criteria, and medication effectiveness was judged based on subjective reports of symptom relief. Since October 1989, medication effectiveness is reported inflight through Private Medical Conferences with the crew. A symptom matrix was analyzed for 19 crewmembers treated with oral combination of scopolamine and dextroamphetamine (scopdex) and 15 crewmembers treated with promethazine delivered by intramuscular i.m. or suppository routes. Scopdex has been given preflight as prophylaxis for SMS, but analysis showed delayed symptom presentation in 9 crewmembers or failed to prevent symptoms in 7. Only 3 crewmembers who took scopdex had no symptoms inflight. Fourteen out of 15 crewmembers treated with i.m. promethazine and 6 of 8 treated with promethazine suppositories after symptom development had immediate (within 1-2h) symptom relief and required no additional medication. There were no cases of delayed symptom presentation in the crewmembers treated with promethazine. This response is in contrast to untreated crewmembers who typically have slow symptom resolution over 72-96h. We conclude that promethazine is an effective treatment of SMS symptoms inflight. NASA policy currently recommends treating crewmembers with SMS after symptom development, and no longer recommends prophylaxis with scopdex due to delayed symptom development and apparent variable absorption of oral medications during early flight days.

  6. Tissue Engineering Strategies as Tools for Personalized Meningioma Treatment.

    PubMed

    Ferroni, Letizia; Della Puppa, Alessandro; D'Avella, Domenico; Isola, Maurizio; Scienza, Renato; Gardin, Chiara; Zavan, Barbara

    2015-07-01

    Pharmacogenomics, the science of how genetic makeup influences an individual's reaction to drugs, is an innovative tool for providing critical insights into how a patient will respond to a particular treatment. In the present work, we constructed cancer-like tissues to be used as tools for determining the most effective drug for an individual patient. Using tissue engineering strategies, we generated two different solid tumor-like tissues in vitro, a neuronal tumor (meningioma) and a nonmelanoma skin cancer. Samples were tested by both histological and genetic approaches (using a comparative genomic hybridization array, and the relative World Health Organization classification of the samples was compared with the results obtained by the molecular analyses. Our data confirmed the ability of the cells to maintain their phenotype in three-dimensional scaffolds as well as the strong relationship between chromosomal alterations and histological malignancy grades. We then validated the in vitro construction of tumor-like tissues as a potential tool for developing personalized drug treatments. PMID:25894852

  7. A review of current treatment strategies for gestational diabetes mellitus

    PubMed Central

    Kelley, Kristi W; Carroll, Dana G; Meyer, Allison

    2015-01-01

    Approximately 90% of diabetes cases in pregnant women are considered gestational diabetes mellitus (GDM). It is well known that uncontrolled glucose results in poor pregnancy outcomes in both the mother and fetus. Worldwide there are many guidelines with recommendations for appropriate management strategies for GDM once lifestyle modifications have been instituted and failed to achieve control. The efficacy and particularly the safety of other treatment modalities for GDM has been the source of much debate in recent years. Studies that have demonstrated the safety and efficacy of both glyburide and metformin in the management of patients with GDM will be reviewed. There is a lack of evidence with other oral and injectable non-insulin agents to control blood glucose in GDM. The role of insulin will be discussed, with emphasis on insulin analogs. Ideal patient characteristics for each treatment modality will be reviewed. In addition, recommendations for postpartum screening of patients will be described as well as recommendations for use of agents to manage subsequent type 2 diabetes in patients who are breastfeeding. PMID:26213555

  8. Various Strategies for Pain-Free Root Canal Treatment

    PubMed Central

    Parirokh, Masoud; V. Abbott, Paul

    2014-01-01

    Introduction: Achieving successful anesthesia and performing pain-free root canal treatment are important aims in dentistry. This is not always achievable and therefore, practitioners are constantly seeking newer techniques, equipments, and anesthetic solutions for this very purpose. The aim of this review is to introduce strategies to achieve profound anesthesia particularly in difficult cases. Materials and Methods: A review of the literature was performed by electronic and hand searching methods for anesthetic agents, techniques, and equipment. The highest level of evidence based investigations with rigorous methods and materials were selected for discussion. Results: Numerous studies investigated to pain management during root canal treatment; however, there is still no single technique that will predictably provide profound pulp anesthesia. One of the most challenging issues in endodontic practice is achieving a profound anesthesia for teeth with irreversible pulpitis especially in mandibular posterior region. Conclusion: According to most investigations, achieving a successful anesthesia is not always possible with a single technique and practitioners should be aware of all possible alternatives for profound anesthesia. PMID:24396370

  9. Strategies for implementation of harm reduction in treatment settings.

    PubMed

    Denning, P

    2001-01-01

    Harm reduction is a set of strategies that we all use everyday to protect us from the harms of living in a complex world. Central to the principles of harm reduction is the need to respect the client's autonomy and develop a relationship of mutual collaboration with the goal of reducing drug- and alcohol-related harm. Additional principles stress the need to develop a hierarchy of client needs, a list that includes all other services, with the importance for each set by the client. Harm reduction implementation includes a range of interventions including abstinence. Some interventions are controversial, including needle exchange, but most are traditional health promotion activities such as videos, health fairs, and drug education. Essential to implementing harm reduction is a recognition that, even for those who wish to become abstinent, this goal is difficult to achieve and maintain. We must acknowledge this and stop the practice of imposing punitive sanctions on clients who use drugs while in treatment. Exclusion or expulsion from treatment settings does nothing to reduce drug use and greatly increases the harm to the client. In conclusion, just as we need to respect diversity among our clients, staff must find a way to respect each others' ideas and concerns as we develop new ways to implement harm reduction in our work. PMID:11332997

  10. Current Research Therapeutic Strategies for Alzheimer's Disease Treatment

    PubMed Central

    Folch, Jaume; Petrov, Dmitry; Ettcheto, Miren; Abad, Sonia; Sánchez-López, Elena; García, M. Luisa; Olloquequi, Jordi; Beas-Zarate, Carlos; Auladell, Carme; Camins, Antoni

    2016-01-01

    Alzheimer's disease (AD) currently presents one of the biggest healthcare issues in the developed countries. There is no effective treatment capable of slowing down disease progression. In recent years the main focus of research on novel pharmacotherapies was based on the amyloidogenic hypothesis of AD, which posits that the beta amyloid (Aβ) peptide is chiefly responsible for cognitive impairment and neuronal death. The goal of such treatments is (a) to reduce Aβ production through the inhibition of β and γ secretase enzymes and (b) to promote dissolution of existing cerebral Aβ plaques. However, this approach has proven to be only modestly effective. Recent studies suggest an alternative strategy centred on the inhibition of the downstream Aβ signalling, particularly at the synapse. Aβ oligomers may cause aberrant N-methyl-D-aspartate receptor (NMDAR) activation postsynaptically by forming complexes with the cell-surface prion protein (PrPC). PrPC is enriched at the neuronal postsynaptic density, where it interacts with Fyn tyrosine kinase. Fyn activation occurs when Aβ is bound to PrPC-Fyn complex. Fyn causes tyrosine phosphorylation of the NR2B subunit of metabotropic glutamate receptor 5 (mGluR5). Fyn kinase blockers masitinib and saracatinib have proven to be efficacious in treating AD symptoms in experimental mouse models of the disease. PMID:26881137

  11. Dendritic cell-targeting DNA-based mucosal adjuvants for the development of mucosal vaccines

    PubMed Central

    Kataoka, Kosuke; Fujihashi, Kohtaro

    2009-01-01

    In order to establish effective mucosal immunity against various mucosal pathogens, vaccines must be delivered via the mucosal route and contain effective adjuvant(s). Since mucosal adjuvants can simply mix with the antigen, it is relatively easy to adapt them for different types of vaccine development. Even in simple admixture vaccines, the adjuvant itself must be prepared without any complications. Thus, CpG oligodeoxynucleotides or plasmids encoding certain cDNA(s) would be potent mucosal adjuvant candidates when compared with other substances that can be used as mucosal adjuvants. The strategy of a DNA-based mucosal adjuvant facilitates the targeting of mucosal dendritic cells, and thus is an effective and safe approach. It would also provide great flexibility for the development of effective vaccines for various mucosal pathogens. PMID:19722892

  12. Intramedullary spinal cord tumors: a review of current and future treatment strategies.

    PubMed

    Tobin, Matthew K; Geraghty, Joseph R; Engelhard, Herbert H; Linninger, Andreas A; Mehta, Ankit I

    2015-08-01

    Intramedullary spinal cord tumors have low incidence rates but are associated with difficult treatment options. The majority of patients with these tumors can be initially treated with an attempted resection. Unfortunately, those patients who cannot undergo gross-total resection or have subtotal resection are left with few treatment options, such as radiotherapy and chemotherapy. These adjuvant treatments, however, are associated with the potential for significant adverse side effects and still leave patients with a poor prognosis. To successfully manage these patients and improve both their quality of life and prognosis, novel treatment options must be developed to supplement subtotal resection. New research is underway investigating alternative therapeutic approaches for these patients, including directed, localized drug delivery and nanomedicine techniques. These and other future investigations will hopefully lead to promising new therapies for these devastating diseases. PMID:26235012

  13. Current and emerging treatment strategies for Duchenne muscular dystrophy.

    PubMed

    Mah, Jean K

    2016-01-01

    Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, leading to progressive muscle weakness, loss of independent ambulation by early teens, and premature death due to cardiorespiratory complications. The diagnosis can usually be made after careful review of the history and examination of affected boys presenting with developmental delay, proximal weakness, and elevated serum creatine kinase, plus confirmation by muscle biopsy or genetic testing. Precise characterization of the DMD mutation is important for genetic counseling and individualized treatment. Current standard of care includes the use of corticosteroids to prolong ambulation and to delay the onset of secondary complications. Early use of cardioprotective agents, noninvasive positive pressure ventilation, and other supportive strategies has improved the life expectancy and health-related quality of life for many young adults with DMD. New emerging treatment includes viral-mediated microdystrophin gene replacement, exon skipping to restore the reading frame, and nonsense suppression therapy to allow translation and production of a modified dystrophin protein. Other potential therapeutic targets involve upregulation of compensatory proteins, reduction of the inflammatory cascade, and enhancement of muscle regeneration. So far, data from DMD clinical trials have shown limited success in delaying disease progression; unforeseen obstacles included immune response against the generated mini-dystrophin, inconsistent evidence of dystrophin production in muscle biopsies, and failure to demonstrate a significant improvement in the primary outcome measure, as defined by the 6-minute walk test in some studies. The long-term safety and efficacy of emerging treatments will depend on the selection of appropriate clinical end points and sensitive biomarkers to detect meaningful changes in disease progression. Correction of the underlying

  14. Current and emerging treatment strategies for Duchenne muscular dystrophy

    PubMed Central

    Mah, Jean K

    2016-01-01

    Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, leading to progressive muscle weakness, loss of independent ambulation by early teens, and premature death due to cardiorespiratory complications. The diagnosis can usually be made after careful review of the history and examination of affected boys presenting with developmental delay, proximal weakness, and elevated serum creatine kinase, plus confirmation by muscle biopsy or genetic testing. Precise characterization of the DMD mutation is important for genetic counseling and individualized treatment. Current standard of care includes the use of corticosteroids to prolong ambulation and to delay the onset of secondary complications. Early use of cardioprotective agents, noninvasive positive pressure ventilation, and other supportive strategies has improved the life expectancy and health-related quality of life for many young adults with DMD. New emerging treatment includes viral-mediated microdystrophin gene replacement, exon skipping to restore the reading frame, and nonsense suppression therapy to allow translation and production of a modified dystrophin protein. Other potential therapeutic targets involve upregulation of compensatory proteins, reduction of the inflammatory cascade, and enhancement of muscle regeneration. So far, data from DMD clinical trials have shown limited success in delaying disease progression; unforeseen obstacles included immune response against the generated mini-dystrophin, inconsistent evidence of dystrophin production in muscle biopsies, and failure to demonstrate a significant improvement in the primary outcome measure, as defined by the 6-minute walk test in some studies. The long-term safety and efficacy of emerging treatments will depend on the selection of appropriate clinical end points and sensitive biomarkers to detect meaningful changes in disease progression. Correction of the underlying

  15. Potential Role of Adjuvant Radiation Therapy in Cervical Thymic Neoplasm Involving Thyroid Gland or Neck

    PubMed Central

    Noh, Jae Myoung; Ha, Sang Yun; Ahn, Yong Chan; Oh, Dongryul; Seol, Seung Won; Oh, Young Lyun; Han, Joungho

    2015-01-01

    Purpose The purpose of this study is to assess the clinicopathologic features, treatment outcomes, and role of adjuvant radiation therapy (RT) in cervical thymic neoplasm involving the thyroid gland or neck. Materials and Methods The medical and pathologic records of eight patients with cervical thymic neoplasm were reviewed retrospectively. All patients underwent surgical resection, including thyroidectomy or mass excision. Adjuvant RT was added in five patients with adverse clinicopathologic features. The radiation doses ranged from 54 Gy/27 fractions to 66 Gy/30 fractions delivered to the primary tumor bed and pathologically involved regional lymphatics using a 3-dimensional conformal technique. Results Eight cases of cervical thymic neoplasm included three patients with carcinoma showing thymus-like differentiation (CASTLE) and five with ectopic cervical thymoma. The histologic subtypes of ectopic cervical thymoma patients were World Health Organization (WHO) type B3 thymoma in one, WHO type B1 thymoma in two, WHO type AB thymoma in one, and metaplastic thymoma in one, respectively. The median age was 57 years (range, 40 to 76 years). Five patients received adjuvant RT: three with CASTLE; one with WHO type B3; and one with WHO type AB with local invasiveness. After a median follow-up period of 49 months (range, 11 to 203 months), no recurrence had been observed, regardless of adjuvant RT. Conclusion Adjuvant RT after surgical resection might be worthwhile in patients with CASTLE and ectopic cervical thymoma with WHO type B2-C and/or extraparenchymal extension, as similarly indicated for primary thymic epithelial tumors. A longer follow-up period may be needed in order to validate this strategy. PMID:25648096

  16. Micro/nanoparticle adjuvants for antileishmanial vaccines: present and future trends.

    PubMed

    Badiee, Ali; Heravi Shargh, Vahid; Khamesipour, Ali; Jaafari, Mahmoud Reza

    2013-01-21

    Leishmania infection continues to have a major impact on public health inducing significant morbidity and mortality mostly in the poorest populations. Drug resistance, toxicity and side effects associated with expensive chemotherapeutic treatments and difficult reservoir control emphasize the need for a safe and effective vaccine which is not available yet. Although, Leishmanization (LZ) was shown to be effective against cutaneous leishmaniasis, standardization and safety are the main problems of LZ. First generation killed parasites demonstrated limited efficacy in phase 3 trials and moreover well defined molecules have not reached to phase 3 yet. Limited efficacy in vaccines against leishmaniasis is partly due to lack of an appropriate adjuvant. Hence, the use of particulate delivery systems as carriers for antigen and/or immunostimulatory adjuvants for effective delivery to the antigen-presenting cells (APCs) is a valuable strategy to enhance vaccine efficacies. Particle-based delivery systems such as emulsions, liposomes, virosomes, and polymeric microspheres have the potential for successfully delivering antigens, which can then be further improved via incorporation of additional antigenic or immustimulatory adjuvant components in or onto the particle carrier system. In this review, we have attempted to provide a list of particulate vaccine delivery systems involved in the production of candidate leishmaniasis vaccines and introduced some potentially useful vaccine delivery systems for leishmaniasis in future experiments. In conclusion, combination vaccines (adjuvant systems) composed of candidate antigens and more importantly well-developed particulate delivery systems, such as lipid-based particles containing immunostimulatory adjuvants, have a chance to succeed as antileishmanial vaccines. PMID:23219436

  17. Vaccine Adjuvants in Fish Vaccines Make a Difference: Comparing Three Adjuvants (Montanide ISA763A Oil, CpG/Poly I:C Combo and VHSV Glycoprotein) Alone or in Combination Formulated with an Inactivated Whole Salmonid Alphavirus Antigen.

    PubMed

    Thim, Hanna L; Villoing, Stéphane; McLoughlin, Marian; Christie, Karen Elina; Grove, Søren; Frost, Petter; Jørgensen, Jorunn B

    2014-01-01

    Most commercial vaccines offered to the aquaculture industry include inactivated antigens (Ag) formulated in oil adjuvants. Safety concerns are related to the use of oil adjuvants in multivalent vaccines for fish, since adverse side effects (e.g., adhesions) can appear. Therefore, there is a request for vaccine formulations for which protection will be maintained or improved, while the risk of side effects is reduced. Here, by using an inactivated salmonid alphavirus (SAV) as the test Ag, the combined use of two Toll-like receptor (TLR) ligand adjuvants, CpG oligonucleotides (ODNs) and poly I:C, as well as a genetic adjuvant consisting of a DNA plasmid vector expressing the viral haemorrhagic septicaemia virus (VHSV) glycoprotein (G) was explored. VHSV-G DNA vaccine was intramuscularly injected in combination with intraperitoneal injection of either SAV Ag alone or combined with the oil adjuvant, Montanide ISA763, or the CpG/polyI:C combo. Adjuvant formulations were evaluated for their ability to boost immune responses and induce protection against SAV in Atlantic salmon, following cohabitation challenge. It was observed that CpG/polyI:C-based formulations generated the highest neutralizing antibody titres (nAbs) before challenge, which endured post challenge. nAb responses for VHSV G-DNA- and oil-adjuvanted formulations were marginal compared to the CpG/poly I:C treatment. Interestingly, heat-inactivated sera showed reduced nAb titres compared to their non-heated counterparts, which suggests a role of complement-mediated neutralization against SAV. Consistently elevated levels of innate antiviral immune genes in the CpG/polyI:C injected groups suggested a role of IFN-mediated responses. Co-delivery of the VHSV-G DNA construct with either CpG/polyI:C or oil-adjuvanted SAV vaccine generated higher CD4 responses in head kidney at 48 h compared to injection of this vector or SAV Ag alone. The results demonstrate that a combination of pattern recognizing receptor (PRR

  18. The role of surgical margins in treatment of Ewing's sarcoma family tumors: Experience of a single institution with 512 patients treated with adjuvant and neoadjuvant chemotherapy

    SciTech Connect

    Bacci, Gaetano . E-mail: gaetano.bacci@ior.it; Longhi, Alessandra; Briccoli, Antonio; Bertoni, Franco; Versari, Michela; Picci, Piero

    2006-07-01

    Purpose: To evaluate the importance of surgical margins for local and systemic control of Ewing's sarcoma family tumors (ESFT). Methods and Materials: Between 1979 and 1999, 512 patients with ESFTs entered 4 different adjuvant and neoadjuvant studies performed at a single institution. Of these patients, 335 were treated with surgery alone (196) or surgery followed by radiotherapy at doses of 44.8 Gy (139). We compared their outcome with that of the 177 patients who were locally treated by radiotherapy at 60 Gy. Results: Local control (88.8% vs. 80.2%, p < 0.009) and 5-year disease-free survival (63.8% vs. 47.6%, p < 0.0007) were significantly better in patients treated with surgery and, among them, in those with adequate surgical margins (96.6% vs. 71,7%, p < 0.0008, and 69.6% vs. 46.3%, p < 0.0002). Nonetheless, better results were observed only in extremity tumors. Conclusions: Surgery is better than radiotherapy in cases of extremity ESFT with achievable adequate surgical margins, and in cases of inadequate surgical margins, adjuvant reduced-dose radiotherapy is ineffective. Therefore, when inadequate margins are expected, patients are better treated with full-dose radiotherapy from the start.

  19. Combotherapy and current concepts as well as future strategies for the treatment of Alzheimer’s disease

    PubMed Central

    Fan, Ling-Yun; Chiu, Ming-Jang

    2014-01-01

    It has been estimated that 35.6 million people globally had dementia in 2010 and the prevalence of dementia has been predicted to double every 20 years. Thus, 115.4 million people may be living with dementia in 2050. Alzheimer’s disease (AD) is the leading cause of dementia and is present in 60%–70% of people with dementia. Unfortunately, there are few approved drugs that can alleviate the cognitive or behavioral symptoms of AD dementia. Recent studies have revealed that pathophysiological changes related to AD occur decades before the appearance of clinical symptoms of dementia. This extended preclinical phase of AD provides a critical chance for disease-modifying agents to halt or delay the relentless process of AD. Although several trials targeting various pathological processes are ongoing, the examination of the combined use of different approaches to combat AD seems warranted. In this article, we will review current therapies, future strategies, and ongoing clinical trials for the treatment of AD with a special focus on combination therapies. Furthermore, preventive strategies for cognitively normal subjects in the presymptomatic stages of AD will also be addressed. In this review, we discuss current hypotheses of the disease process. In the decades since the approval of cholinesterase inhibitors, no new drug has ultimately demonstrated clear success in clinical trials. Given the difficulties that have been encountered in attempts to identify a single drug that can treat AD, we must pursue effective multi-target strategies, ie, combination therapies. The combination of cholinesterase inhibitors and memantine is considered well tolerated and safe, and this combination benefits patients with moderate-to-severe AD. In contrast, with the exception of adjuvant therapies of conventional drugs, combinations of different disease-modifying agents with different mechanisms may have promising synergic effects and benefit cognition, behavior, and daily living

  20. Holospinal epidural abscess of the spinal axis: two illustrative cases with review of treatment strategies and surgical techniques.

    PubMed

    Smith, Gabriel A; Kochar, Arshneel S; Manjila, Sunil; Onwuzulike, Kaine; Geertman, Robert T; Anderson, James S; Steinmetz, Michael P

    2014-08-01

    Despite the increasing prevalence of spinal infections, the subcategory of holospinal epidural abscesses (HEAs) is extremely infrequent and requires unique management. Panspinal imaging (preferably MRI), modern aggressive antibiotic therapy, and prompt surgical intervention remain the standard of care for all spinal axis infections including HEAs; however, the surgical decision making on timing and extent of the procedure still remain ill defined for HEAs. Decompression including skip laminectomies or laminoplasties is described, with varied clinical outcomes. In this review the authors present the illustrative cases of 2 patients with HEAs who were treated using skip laminectomies and epidural catheter irrigation techniques. The discussion highlights different management strategies including the role of conservative (nonsurgical) management in these lesions, especially with an already identified pathogen and the absence of mass effect on MRI or significant neurological defects. Among fewer than 25 case reports of HEA published in the past 25 years, the most important aspect in deciding a role for surgery is the neurological examination. Nearly 20% were treated successfully with medical therapy alone if neurologically intact. None of the reported cases had an associated cranial infection with HEA, because the dural adhesion around the foramen magnum prevented rostral spread of infection. Traditionally a posterior approach to the epidural space with irrigation is performed, unless an extensive focal ventral collection is causing cord compression. Surgical intervention for HEA should be an adjuvant treatment strategy for all acutely deteriorating patients, whereas aspiration of other infected sites like a psoas abscess can determine an infective pathogen, and appropriate antibiotic treatment may avoid surgical intervention in the neurologically intact patient. PMID:25081960

  1. Treatment patterns of adjuvant interferon-α2b for high-risk melanoma: a retrospective study of the Grupo Español Multidisciplinar de Melanoma – Prima study

    PubMed Central

    Soriano, Virtudes; Malvehy, Josep; Berrocal, Alfonso; Martínez de Prado, Purificación; Quindós, María; Soria, Ainara; Márquez-Rodas, Iván; Palacio, Isabel; Cerezuela, Pablo; López-Vivanco, Guillermo; Alonso, Lorenzo; Samaniego, Elia; Ballesteros, Ana; Puértolas, Teresa; Díaz-Beveridge, Rodrigo; de la Cruz-Merino, Luis; López Castro, Rafael; López López, Rafael; Stevinson, Kendall; del Barrio, Patricia; Tornamira, Maria V.; Guillém, Vicente; Martín-Algarra, Salvador

    2016-01-01

    Adjuvant interferon-α2b (IFN-α2b) has been studied extensively in clinical trials, but there have been few studies of real-world use. The aim of this study is to describe the IFN-α2b real-world patterns in patients with high-risk melanoma in Spain. This was a retrospective and multicentre chart review study of an unselected cohort of patients with melanoma at high risk for relapse (stage IIB/IIC/III) treated with IFN-α2b. Patterns were assessed in terms of dose and compliance to planned treatment. A survival analysis was carried out for the full population and according to Kirkwood scheme compliance and the presence of ulceration. Of 327 patients treated with IFN-α2b, 318 received a high-dose regimen following the standard Kirkwood scheme; thus, patterns are described for this regimen. A total of 121 (38%) and 88 (28%) patients had at least one dose reduction during the induction and maintenance phases, respectively. Dose delay was required in fewer than 10% of patients. A total of 78, 40 and 38% of the patients completed the induction phase, maintenance phase and completed treatment, respectively. The median progression-free and overall survival for the full population were 3.2 and 10.5 years, respectively. There were no differences in progression-free survival and overall survival according to Kirkwood scheme compliance and the presence of ulceration. The most frequent adverse events were neutropenia (31%) and fatigue (30%). High-dose IFN-α2b is the most frequently used regimen in Spain as an adjuvant systemic treatment for high-risk melanoma. Despite poor compliance, in this retrospective study, IFN-α2b treatment provided a benefit consistent with that described previously. PMID:26958991

  2. Treatment patterns of adjuvant interferon-α2b for high-risk melanoma: a retrospective study of the Grupo Español Multidisciplinar de Melanoma - Prima study.

    PubMed

    Espinosa, Enrique; Soriano, Virtudes; Malvehy, Josep; Berrocal, Alfonso; Martínez de Prado, Purificación; Quindós, María; Soria, Ainara; Márquez-Rodas, Iván; Palacio, Isabel; Cerezuela, Pablo; López-Vivanco, Guillermo; Alonso, Lorenzo; Samaniego, Elia; Ballesteros, Ana; Puértolas, Teresa; Díaz-Beveridge, Rodrigo; de la Cruz-Merino, Luis; López Castro, Rafael; López López, Rafael; Stevinson, Kendall; Del Barrio, Patricia; Tornamira, Maria V; Guillém, Vicente; Martín-Algarra, Salvador

    2016-06-01

    Adjuvant interferon-α2b (IFN-α2b) has been studied extensively in clinical trials, but there have been few studies of real-world use. The aim of this study is to describe the IFN-α2b real-world patterns in patients with high-risk melanoma in Spain. This was a retrospective and multicentre chart review study of an unselected cohort of patients with melanoma at high risk for relapse (stage IIB/IIC/III) treated with IFN-α2b. Patterns were assessed in terms of dose and compliance to planned treatment. A survival analysis was carried out for the full population and according to Kirkwood scheme compliance and the presence of ulceration. Of 327 patients treated with IFN-α2b, 318 received a high-dose regimen following the standard Kirkwood scheme; thus, patterns are described for this regimen. A total of 121 (38%) and 88 (28%) patients had at least one dose reduction during the induction and maintenance phases, respectively. Dose delay was required in fewer than 10% of patients. A total of 78, 40 and 38% of the patients completed the induction phase, maintenance phase and completed treatment, respectively. The median progression-free and overall survival for the full population were 3.2 and 10.5 years, respectively. There were no differences in progression-free survival and overall survival according to Kirkwood scheme compliance and the presence of ulceration. The most frequent adverse events were neutropenia (31%) and fatigue (30%). High-dose IFN-α2b is the most frequently used regimen in Spain as an adjuvant systemic treatment for high-risk melanoma. Despite poor compliance, in this retrospective study, IFN-α2b treatment provided a benefit consistent with that described previously. PMID:26958991

  3. Dual drug loaded nanoliposomal chemotherapy: A promising strategy for treatment of head and neck squamous cell carcinoma.

    PubMed

    Mohan, Aarti; Narayanan, Shridhar; Balasubramanian, Gopalan; Sethuraman, Swaminathan; Krishnan, Uma Maheswari

    2016-02-01

    The rising incidence of head and neck cancer and the drawbacks of currently used therapeutic strategies such as salvage surgery followed by adjuvant chemo- or radiotherapy have encouraged pursuits for better therapeutic approaches. This work describes the development and characterization of a PEGylated liposomal nanocarrier encapsulated with trans-resveratrol (Res), a plant stilbenoid, and doxorubicin hydrochloride (Dox), a standard chemotherapeutic agent for treatment of oral squamous cell carcinoma. The two drugs were loaded in liposomes prepared from egg phosphatidylcholine and DSPE-PEG with maximum encapsulation efficiencies of about 80% for each drug achieved at Res to Dox ratio of 2:1. The liposomal suspension was found to be stable with a zeta potential of -30.53 mV and size of approximately 250 nm. Thermal properties and release kinetics of the dual drug loaded liposomes were determined. The nanoformulation was evaluated for its in vitro anticancer efficacy on an oral squamous cell carcinoma cell line (NT8e). The cell uptake mechanism of the liposomal formulation was determined using pharmacological inhibitors for different endocytosis pathways. The combination effect of the two drugs was evaluated in free form and was found to have synergistic effects. The formulation was found to have a higher IC50 value than that of free doxorubicin hydrochloride but was found to have a superior effect on the signaling proteins involved in apoptosis and cell cycle. PMID:26690333

  4. Conservation Strategies in the Genus Hypericum via Cryogenic Treatment

    PubMed Central

    Bruňáková, Katarína; Čellárová, Eva

    2016-01-01

    In the genus Hypericum, cryoconservation offers a strategy for maintenance of remarkable biodiversity, emerging from large inter- and intra-specific variability in morphological and phytochemical characteristics. Long-term cryostorage thus represents a proper tool for preservation of genetic resources of endangered and threatened Hypericum species or new somaclonal variants with unique properties. Many representatives of the genus are known as producers of pharmacologically important polyketides, namely naphthodianthrones and phloroglucinols. As a part of numerous in vitro collections, the nearly cosmopolitan Hypericum perforatum – Saint John’s wort – has become a suitable model system for application of biotechnological approaches providing an attractive alternative to the traditional methods for secondary metabolite production. The necessary requirements for efficient cryopreservation include a high survival rate along with an unchanged biochemical profile of plants regenerated from cryopreserved cells. Understanding of the processes which are critical for recovery of H. perforatum cells after the cryogenic treatment enables establishment of cryopreservation protocols applicable to a broad number of Hypericum species. Among them, several endemic taxa attract a particular attention due to their unique characteristics or yet unrevealed spectrum of bioactive compounds. In this review, recent advances in the conventional two-step and vitrification-based cryopreservation techniques are presented in relation to the recovery rate and biosynthetic capacity of Hypericum spp. The pre-cryogenic treatments which were identified to be crucial for successful post-cryogenic recovery are discussed. Being a part of genetic predisposition, the freezing tolerance as a necessary precondition for successful post-cryogenic recovery is pointed out. Additionally, a beneficial influence of cold stress on modulating naphthodianthrone biosynthesis is outlined. PMID:27200032

  5. Radiation treatment of brain tumors: Concepts and strategies

    SciTech Connect

    Marks, J.E. )

    1989-01-01

    Ionizing radiation has demonstrated clinical value for a multitude of CNS tumors. Application of the different physical modalities available has made it possible for the radiotherapist to concentrate the radiation in the region of the tumor with relative sparing of the surrounding normal tissues. Correlation of radiation dose with effect on cranial soft tissues, normal brain, and tumor has shown increasing effect with increasing dose. By using different physical modalities to alter the distribution of radiation dose, it is possible to increase the dose to the tumor and reduce the dose to the normal tissues. Alteration of the volume irradiated and the dose delivered to cranial soft tissues, normal brain, and tumor are strategies that have been effective in improving survival and decreasing complications. The quest for therapeutic gain using hyperbaric oxygen, neutrons, radiation sensitizers, chemotherapeutic agents, and BNCT has met with limited success. Both neoplastic and normal cells are affected simultaneously by all modalities of treatment, including ionizing radiation. Consequently, one is unable to totally depopulate a tumor without irreversibly damaging the normal tissues. In the case of radiation, it is the brain that limits delivery of curative doses, and in the case of chemical additives, it is other organ systems, such as bone marrow, liver, lung, kidneys, and peripheral nerves. Thus, the major obstacle in the treatment of malignant gliomas is our inability to preferentially affect the tumor with the modalities available. Until it is possible to directly target the neoplastic cell without affecting so many of the adjacent normal cells, the quest for therapeutic gain will go unrealized.72 references.

  6. Comparison of treatment strategies for Space Motion Sickness

    NASA Technical Reports Server (NTRS)

    Davis, J. R.; Jennings, R. T.; Beck, B. G.

    1992-01-01

    Treatment strategies for Space Motion Sickness were compared using the results of postflight oral debriefings. Standardized questionnaires were administered to all crewmembers immediately following Space Shuttle flights by NASA flight surgeons. Cases of Space Motion Sickness were graded as mild, moderate or severe based on published criteria, and medication effectiveness was judged based on subjective reports of symptom relief. Since October 1989, medication effectiveness is reported inflight through Private Medical Conferences with the crew. A symptom matrix was analyzed for 19 crewmembers treated with an oral combination of scopolamine and dextroamphetamine (scopdex) and 15 crewmembers treated with promethazine delivered by intramuscular (IM) or suppository routes. Scopdex has been given preflight as prophaxis for Space Motion Sickness but analysis showed delayed symptom presentation in 9 crewmembers or failed to prevent symptoms in 7. Only three crewmembers who took scopdex had no symptoms inflight. Fourteen out of 15 crewmembers treated with IM promethazine and 6 of 8 treated with promethazine suppositories after symptom development had immediate (within 12 h) symptom relief and required no additional medication. There were no cases of delayed symptom presentation in the crewmembers treated with promethazine. This response is in contrast to untreated crewmembers who typically have slow symptom resolution over 72-96 h. We conclude that promethazine is an effective treatment of Space Motion Sickness symptoms inflight. NASA policy currently recommends treating crewmembers with Space Motion Sickness after symptom development, and no longer recommends prophylaxis with scopdex due to delayed symptom development and apparent variable absorption of oral medications during early flight days.

  7. Solitary Large Hepatocellular Carcinoma: Staging and Treatment Strategy

    PubMed Central

    Liu, Po-Hong; Su, Chien-Wei; Hsu, Chia-Yang; Hsia, Cheng-Yuan; Lee, Yun-Hsuan; Huang, Yi-Hsiang; Lee, Rheun-Chuan; Lin, Han-Chieh; Huo, Teh-Ia

    2016-01-01

    Background & Aims Controversies exist on staging and management of solitary large (>5 cm) hepatocellular carcinoma (HCC). This study aims to evaluate the impact of tumor size on Barcelona Clinic Liver Cancer (BCLC) staging and treatment strategy. Methods BCLC stage A and B patients were included and re-classified as single tumor 2–5 cm or up to 3 tumors ≤3 cm (group A; n = 657), single tumor >5 cm (group SL; n = 224), and multiple tumors >3 cm (group B; n = 351). Alternatively, 240 and 229 patients with solitary large HCC regardless of tumor stage received surgical resection (SR) and transarterial chemoembolization (TACE), respectively. The propensity score analysis identified 156 pairs of patients from each treatment arm for survival comparison. Results The survival was significantly higher for group A but was comparable between group SL and group B patients. Of patients with solitary large HCC, the 1-, 3- and 5-year survival rates were 88% versus 74%, 76% versus 44%, and 63% versus 35% between SR and TACE group, respectively (p<0.001). When baseline demographics were adjusted in the propensity model, the respective 1-, 3- and 5-year survival rates were 87% versus 79%, 76% versus 46%, and 61% versus 36% (p<0.001). The Cox proportional hazards model identified TACE with a 2.765-fold increased risk of mortality compared with SR (95% confidence interval: 1.853–4.127, p<0.001). Conclusions Patients with solitary large HCC should be classified at least as intermediate stage HCC. SR provides significantly better survival than TACE for solitary large HCC regardless of tumor stage. Further amendment to the BCLC classification is mandatory. PMID:27176037

  8. Conservation Strategies in the Genus Hypericum via Cryogenic Treatment.

    PubMed

    Bruňáková, Katarína; Čellárová, Eva

    2016-01-01

    In the genus Hypericum, cryoconservation offers a strategy for maintenance of remarkable biodiversity, emerging from large inter- and intra-specific variability in morphological and phytochemical characteristics. Long-term cryostorage thus represents a proper tool for preservation of genetic resources of endangered and threatened Hypericum species or new somaclonal variants with unique properties. Many representatives of the genus are known as producers of pharmacologically important polyketides, namely naphthodianthrones and phloroglucinols. As a part of numerous in vitro collections, the nearly cosmopolitan Hypericum perforatum - Saint John's wort - has become a suitable model system for application of biotechnological approaches providing an attractive alternative to the traditional methods for secondary metabolite production. The necessary requirements for efficient cryopreservation include a high survival rate along with an unchanged biochemical profile of plants regenerated from cryopreserved cells. Understanding of the processes which are critical for recovery of H. perforatum cells after the cryogenic treatment enables establishment of cryopreservation protocols applicable to a broad number of Hypericum species. Among them, several endemic taxa attract a particular attention due to their unique characteristics or yet unrevealed spectrum of bioactive compounds. In this review, recent advances in the conventional two-step and vitrification-based cryopreservation techniques are presented in relation to the recovery rate and biosynthetic capacity of Hypericum spp. The pre-cryogenic treatments which were identified to be crucial for successful post-cryogenic recovery are discussed. Being a part of genetic predisposition, the freezing tolerance as a necessary precondition for successful post-cryogenic recovery is pointed out. Additionally, a beneficial influence of cold stress on modulating naphthodianthrone biosynthesis is outlined. PMID:27200032

  9. [Pathology and strategies for the treatment of ischemic brain injury].

    PubMed

    Takagi, Norio

    2009-10-01

    Cerebral ischemia, a pathological condition in which brain tissue experiences a shortage or lack of glucose and oxygen, provokes an irreversible neurodegenerative disorder that may lead clinically to a progressive dementia and global cognitive deterioration. Accumulating evidence indicates many biochemical cascades that lead ultimately to ischemia-induced cell death. However, the cellular and molecular aspects of cerebral ischemia are not yet fully understood. Since the pattern of pathophysiological alterations is not the same for all cells in the ischemic brain, a good understanding of the cellular and molecular alterations induced by cerebral ischemia is needed to develop strategies for the treatment of stroke. This review summarizes recent advances concerning the pathophysiological alterations caused by cerebral ischemia, focusing on the modification of properties of glutamate receptors, which modification may be linked to the development of cerebral infarction. Furthermore, the effects of hepatocyte growth factor on learning dysfunction and cerebral vessel injury after cerebral ischemia are also summarized. Finally, this review describes a possible ameliorative effect of the injection of exogenous neural progenitor cells on cerebral ischemia-induced learning and memory dysfunction. PMID:19797876

  10. [Pilon fractures. Part 1: Diagnostics, treatment strategies and approaches].

    PubMed

    Krettek, C; Bachmann, S

    2015-01-01

    Intraarticular fractures of the distal tibia (pilon fractures) are caused by axial forces, usually in combination with torsional moments. Routine diagnostics include plain films and three dimensional (3D) imaging with computed tomography (CT). Treatment is often impaired by complex fracture configurations and thin soft tissue layers. The management of complex pilon fractures with soft tissue injuries has seen many trends, with changes toward staged protocols of temporary external fixation followed by delayed open reduction and internal fixation (ORIF), minimally invasive percutaneous plate osteosynthesis (MIPPO) techniques and special implants, the benefits of negative pressure wound sealing and early "fix and flap" efforts to reconstruct soft tissue defects. Reduction and fixation must involve respectful management and careful handling of soft tissues in order to minimize the well-known complications of this difficult fracture. The proper approach is one of the keys to success. Approach planning is based on the careful and thorough analysis of the fracture pattern in the 3D data set, which is the basis for a successful strategy for articular reconstruction. PMID:25591416

  11. Treatment strategies for infertile women with polycystic ovary syndrome.

    PubMed

    Vitek, Wendy; Hoeger, Kathleen; Legro, Richard S

    2016-08-01

    Polycystic ovary syndrome (PCOS) is a common reproductive disorder that can be diagnosed when two of the following three criteria are present: menstrual irregularity, hyperandrogenism and polycystic ovaries. Factors such as the individual's body weight influence the severity of the phenotype and risk of metabolic comorbidities. While anovulatory infertility is a common issue among lean and obese reproductive-aged women with PCOS, obesity is associated with resistance to oral ovulation induction agents, lower pregnancy rates and a higher risk of pregnancy complications. Lifestyle modification is recommended as first line therapy among obese women with PCOS in order to optimize their outcomes. Among lean and obese women with PCOS, ovulation induction can be achieved with aromatase inhibitors, selective estrogen receptor modulators, insulin sensitizing agents, gonadotropins and ovarian drilling with varying rates of ovulation, live birth and multiple gestations. Assisted reproductive technologies are reserved for women who do not conceive despite restoration of ovulation or couples with additional factors contributing to their infertility. This review will outline treatment strategies for achieving a healthy pregnancy among lean and obese women with PCOS and infertility. PMID:26765152

  12. From Hippocrates to tissue engineering: surgical strategies in wound treatment.

    PubMed

    Nicoli Aldini, Nicolò; Fini, Milena; Giardino, Roberto

    2008-09-01

    The history of wound treatment has been virtually the history of surgery for many centuries and also is a history of alliance and conflicts between the physician and nature. The Hippocratic statement about natura medicatrix has been well known since antiquity, but often was neglected. Suppuration was considered a necessary event in the healing process and was elicited by the surgeons with traumatic and painful procedures. The concept of simplicity in treating the wounds was suggested by Teodorico Borgognone and Henry de Mondeville in 13th century and was confirmed only three centuries later by the works of Ambroise Paré and Cesare Magati. The history of wound management has been characterized by empiricism since the 18th century, but it took a physiopathological direction during the 19th century when Virchow investigated tissue reaction to injuries, and Lister introduced antiseptic procedures in surgery. By establishing the basis for a biological method to treat wounds, the seeds were sown to enhance the pathways involved in tissue repair, also with the support of new strategies and technology. PMID:18581166

  13. Pharmacologic Treatment Strategies in Children with Type 2 Diabetes Mellitus

    PubMed Central

    Urakami, Tatsuhiko; Kuwabara, Remi; Habu, Masako; Yoshida, Ayako; Okuno, Misako; Suzuki, Junichi; Takahashi, Shori; Mugishima, Hideo

    2013-01-01

    We treated 80 obese and 28 nonobese children diagnosed as having type 2 diabetes mellitus (T2DM). Among these patients, 26 obese and 23 nonobese children were assigned to pharmacologic therapies during the course of diabetes. Pharmacologic therapies were started if the HbA1c (NGSP) value exceeded 7.0% despite dietary and exercise management. For the 26 obese patients, metformin alone or in combination with an additional medication was frequently used. Only 2 patients independently received sulfonylureas (SUs) in the form of glimepiride. In addition, 9 patients were treated with basal insulin supported with oral hypoglycemic drugs (OHDs) or biphasic premix insulin. On the other hand, the 23 nonobese patients were frequently treated with insulin alone or in combination with an additional medication followed by SUs. The nonobese patients tended to require pharmacologic therapies, in particular insulin, at an earlier stage of diabetes as compared with the obese patients. New antidiabetic drugs, DPP-4 inhibitors and GLP-1 receptor agonists, seemed to exert positive effects on glycemic control without occurrence of hypoglycemic episodes in some patients regardless of the type of diabetes. These results suggest that pharmacologic treatment strategies in childhood T2DM should be tailored to individual patient characteristics. PMID:23966754

  14. Imaging of coronary atherosclerosis - evolution towards new treatment strategies.

    PubMed

    Dweck, Marc R; Doris, Mhairi K; Motwani, Manish; Adamson, Philip D; Slomka, Piotr; Dey, Damini; Fayad, Zahi A; Newby, David E; Berman, Daniel

    2016-09-01

    Coronary atherosclerosis and the precipitation of acute myocardial infarction are highly complex processes, which makes accurate risk prediction challenging. Rapid developments in invasive and noninvasive imaging technologies now provide us with detailed, exquisite images of the coronary vasculature that allow direct investigation of a wide range of these processes. These modalities include sophisticated assessments of luminal stenoses and myocardial perfusion, complemented by novel measures of the atherosclerotic plaque burden, adverse plaque characteristics, and disease activity. Together, they can provide comprehensive, individualized assessments of coronary atherosclerosis as it occurs in patients. Not only can this information provide important pathological insights, but it can also potentially be used to guide personalized treatment decisions. In this Review, we describe the latest advances in both established and emerging imaging techniques, focusing on the strengths and weakness of each approach. Moreover, we discuss how these technological advances might be translated from attractive images into novel imaging strategies and definite improvements in clinical risk prediction and patient outcomes. This process will not be easy, and the many potential barriers and difficulties are also reviewed. PMID:27226154

  15. Liver transplantation for malignancy: Current treatment strategies and future perspectives

    PubMed Central

    Hackl, Christina; Schlitt, Hans J; Kirchner, Gabriele I; Knoppke, Birgit; Loss, Martin

    2014-01-01

    In 1967, Starzl et al performed the first successful liver transplantation for a patient diagnosed with hepatoblastoma. In the following, liver transplantation was considered ideal for complete tumor resection and potential cure from primary hepatic malignancies. Several reports of liver transplantation for primary and metastatic liver cancer however showed disappointing results and the strategy was soon dismissed. In 1996, Mazzaferro et al introduced the Milan criteria, offering liver transplantation to patients diagnosed with limited hepatocellular carcinoma. Since then, liver transplantation for malignant disease is an ongoing subject of preclinical and clinical research. In this context, several aspects must be considered: (1) Given the shortage of deceased-donor organs, long-term overall and disease free survival should be comparable with results obtained in patients transplanted for non-malignant disease; (2) In this regard, living-donor liver transplantation may in selected patients help to solve the ethical dilemma of optimal individual patient treatment vs organ allocation justice; and (3) Ongoing research focusing on perioperative therapy and anti-proliferative immunosuppressive regimens may further reduce tumor recurrence in patients transplanted for malignant disease and thus improve overall survival. The present review gives an overview of current indications and future perspectives of liver transplantation for malignant disease. PMID:24833863

  16. WEEE recovery strategies and the WEEE treatment status in China.

    PubMed

    He, Wenzhi; Li, Guangming; Ma, Xingfa; Wang, Hua; Huang, Juwen; Xu, Min; Huang, Chunjie

    2006-08-25

    The electric and electronic equipment has been developed, applied, and consumed world wide at a very high speed. Subsequently, the ever-increasing amount of waste electric and electronic equipment (WEEE) has become a common problem facing the world. In view of the deleterious effects of WEEE on the environment and the valuable materials that can be reused in them, legislations in many countries have focused their attention on the management of WEEE, and new techniques have been developed for the recovery of WEEE. In China, rapid economic growth, coupled with urbanization and growing demand for consumer goods, has increased the consumption of EEE in large quantity, thus made the WEEE manifold rapidly, posing a severe threat to the environment and the sustainable economic growth as well. This article reviewed the implementation of strategies of WEEE treatment and the recovery technologies of WEEE. It presented the current status of WEEE and corresponding responses adopted so far in China. The concept and implementation of scientific development is critical to the sector of electronics, one of the important industrial sectors in China's economy. To achieve this objective, it is significant to recycle WEEE sufficiently to comply with regulations regarding WEEE management, and to implement green design and cleaner production concepts within the electronics industry to comply with the upcoming EU and China legislation in a proactive manner. PMID:16820262

  17. Risk factor adapted treatment of Hodgkin's lymphoma: strategies and perspectives.

    PubMed

    Loeffler, M; Pfreundschuh, M; Rühl, U; Hiller, E; Gerhartz, H; Roloff, R; Adler, M; Schoppe, W; Hagen-Aukamp, U; Schmitt, G

    1989-01-01

    prognostic impact. In contrast, a pretreatment erythrocyte sedimentation rate (ESR) above 80 mm/h and a serum alkaline phosphatase (AP) above 230 IU/ml each appeared as significant prognostic factors (P less than 0.01; relative risk, 2.3). The two parameters can be combined to separate two groups (A: ESR and AP both low; B: ESR and/or AP high) which differ significantly for FFTF (P less than 0.001) and survival (P less than 0.04). The decision for risk-adapted treatment requires identification of groups of patients in the frame of specified diagnostic and therapeutic strategies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2690225

  18. Adjuvant treatment with interleukin-2- and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumour nephrectomy: Results of a prospectively randomised Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN)

    PubMed Central

    Atzpodien, J; Schmitt, E; Gertenbach, U; Fornara, P; Heynemann, H; Maskow, A; Ecke, M; Wöltjen, H H; Jentsch, H; Wieland, W; Wandert, T; Reitz, M

    2005-01-01

    We conducted a prospectively randomised clinical trial to investigate the role of adjuvant outpatient immunochemotherapy administered postoperatively in high-risk patients with renal cell carcinoma. In total, 203 renal carcinoma patients' status post radical tumour nephrectomy were stratified into three risk groups: patients with tumour extending into renal vein/vena cava or invading beyond Gerota's fascia (pT3b/c pN0 or pT4pN0), patients with locoregional lymph node infiltration (pN+), and patients after complete resection of tumour relapse or solitary metastasis (R0). Patients were randomised to undergo either (A) 8 weeks of outpatient subcutaneous interleukin-2 (sc-rIL-2), subcutaneous interferon-alpha2a (sc-rIFN-α2a), and intravenous 5-fluorouracil (iv-5-FU) according to the standard Atzpodien regimen (Atzpodien et al, 2004) or (B) observation. Two-, 5-, and 8-year survival rates were 81, 58, and 58% in the treatment arm, and 91, 76, and 66% in the observation arm (log rank P=0.0278), with a median follow-up of 4.3 years. Two, 5-, and 8-year relapse-free survival rates were calculated at 54, 42, and 39% in the treatment arm, and at 62, 49, and 49% in the observation arm (log rank P=0.2398). Stage-adapted subanalyses revealed no survival advantages of treatment over observation, as well. Our results established that there was no relapse-free survival benefit and the overall survival was inferior with an adjuvant 8-week-outpatient sc-rIL-2/sc-rIFN-α2a/iv-5-FU-based immunochemotherapy compared to observation in high-risk renal cell carcinoma patients following radical tumour nephrectomy. PMID:15756254

  19. High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation as Adjuvant Treatment in High-Risk Breast Cancer: Data from the European Group for Blood and Marrow Transplantation Registry.

    PubMed

    Martino, Massimo; Lanza, Francesco; Pavesi, Lorenzo; Öztürk, Mustafa; Blaise, Didier; Leno Núñez, Rubén; Schouten, Harry C; Bosi, Alberto; De Giorgi, Ugo; Generali, Daniele; Rosti, Giovanni; Necchi, Andrea; Ravelli, Andrea; Bengala, Carmelo; Badoglio, Manuela; Pedrazzoli, Paolo; Bregni, Marco

    2016-03-01

    The aim of this retrospective study was to assess toxicity and efficacy of adjuvant high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (AHSCT) in 583 high-risk breast cancer (BC) patients (>3 positive nodes) who were transplanted between 1995 and 2005 in Europe. All patients received surgery before transplant, and 55 patients (9.5%) received neoadjuvant treatment before surgery. Median age was 47.1 years, 57.3% of patients were premenopausal at treatment, 56.5% had endocrine-responsive tumors, 19.5% had a human epidermal growth factor receptor 2 (HER2)-negative tumor, and 72.4% had ≥10 positive lymph nodes at surgery. Seventy-nine percent received a single HDC procedure. Overall transplant-related mortality was 1.9%, at .9% between 2001 and 2005, whereas secondary tumor-related mortality was .9%. With a median follow-up of 120 months, overall survival and disease-free survival rates at 5 and 10 years in the whole population were 75% and 64% and 58% and 44%, respectively. Subgroup analysis demonstrated that rates of overall survival were significantly better in patients with endocrine-responsive tumors, <10 positive lymph nodes, and smaller tumor size. HER2 status did not affect survival probability. Adjuvant HDC with AHSCT has a low mortality rate and provides impressive long-term survival rates in patients with high-risk BC. Our results suggest that this treatment modality should be considered in selected high-risk BC patients and further investigated in clinical trials. PMID:26723932

  20. Radical prostatectomy and adjuvant radioactive gold seed placement: Results of treatment at 5 and 10 years for clinical stages A2, B1 and B2 cancer of the prostate

    SciTech Connect

    Kwon, E.D.; Loening, S.A.; Hawtrey, C.E. )

    1991-03-01

    Between 1977 and 1988, 131 patients with adenocarcinoma of the prostate underwent combined radical prostatectomy and intraoperative radioactive gold seed placement. Of these 131 patients 80 were clinically assessed as having stage A2 (12), B1 (43) or B2 (25) cancer and they are the subject of this review. The average dose of radioactivity administered to each patient was 96.6 mCi, and mean followup was 65 months (median 64 months). No patient in this series received any other form of adjuvant therapy until disease recurrence was demonstrated. Local recurrences were observed in 2 patients (2.5%) in this series while distant recurrences were observed in 10 (12.5%). Cancer specific survival free of disease at 5 years was 100% for clinical stage A2, 91% for B1 and 75% for B2 cancers. The 10-year survival free of disease was 100% for clinical stage A2, 82% for B1 and 68% for B2 cancers. Covariants of clinical stage and seminal vesicle involvement influenced survival free of disease in a statistically significant manner (p less than 0.05) while pathological stage and degree of tumor differentiation did not. Mild to severe complications were observed in 12 patients (15%). Intraoperative placement of radioactive gold seeds into unresected pelvic tissues surrounding the site of prostatectomy offers a theoretical advantage in treatment by delivering tumoricidal levels of irradiation to residual foci of cancer not appreciated at the time of surgery. Our results suggest that increases in cancer specific survival free of disease over that previously reported for prostatectomy alone may be achieved through this combined treatment regimen. Furthermore, it is our opinion that therapeutic gains can be achieved without the attendant increases in morbidity and treatment delay often associated with adjuvant external beam radiotherapy.

  1. Adjuvant radiotherapy for early head and neck squamous cell carcinoma with perineural invasion: A systematic review.

    PubMed

    Bur, Andrés M; Lin, Alexander; Weinstein, Gregory S

    2016-04-01

    Perineural invasion (PNI) is widely regarded as a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). Treatment guidelines recommend adjuvant radiotherapy (RT) for patients with adverse pathologic features, including PNI. The purpose of this study was to systematically review the literature to determine if patients with PNI as their only indication for adjuvant therapy benefit from adjuvant RT. In total, 339 abstracts were reviewed for relevance leaving 85 articles, which were evaluated in detail. Thirteen retrospective studies addressed the role of adjuvant RT for patients with PNI. Evidence is lacking to recommend adjuvant RT for all patients with HNSCC with PNI. However, the literature suggests that large nerve or multifocal PNI may predict worse outcome and may be a more appropriate indication for adjuvant therapy. We advocate that patients decide whether to undergo adjuvant therapy after a discussion of the limitations of current evidence. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2350-E2357, 2016. PMID:26613965

  2. Carbohydrate-based immune adjuvants

    PubMed Central

    Petrovsky, Nikolai; Cooper, Peter D

    2011-01-01

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

  3. Evaluation of different heterologous prime-boost immunization strategies against Babesia bovis using viral vectored and protein-adjuvant vaccines based on a chimeric multi-antigen.

    PubMed

    Jaramillo Ortiz, José Manuel; Molinari, María Paula; Gravisaco, María José; Paoletta, Martina Soledad; Montenegro, Valeria Noely; Wilkowsky, Silvina Elizabeth

    2016-07-19

    Protection against the intraerythrocytic bovine parasite Babesia bovis requires both humoral and cellular immune responses. Therefore, tailored combinations of immunogens targeted at both arms of the immune system are strategies of choice to pursue sterilizing immunity. In this study, different heterologous prime-boost vaccination schemes were evaluated in mice to compare the immunogenicity induced by a recombinant adenovirus, a modified vaccinia Ankara vector or a subunit vaccine all expressing a chimeric multi-antigen. This multi-antigen includes the immunodominant B and T cell epitopes of three B. bovis proteins: Merozoite Surface Antigen - 2c (MSA-2c), Rhoptry Associated Protein - 1 (RAP-1) and Heat Shock Protein 20 (HSP20). Both priming with the adenovirus or recombinant multi-antigen and boosting with the modified vaccinia Ankara vector achieved a high degree of activation of TNFα and IFNγ-secreting CD4(+) and CD8(+) specific T cells 60days after the first immunization. High titers of specific IgG antibodies were also detected at the same time point and lasted up to day 120 of the first immunization. Only the adenovirus - MVA combination triggered a marked isotype skew for the IgG2a antibody subclass meanwhile for the other immune traits analyzed here, both vaccination schemes showed similar performances. The immunological characterization in the murine model of these rationally designed immunogens led us to propose that adenoviruses as well as the bacterially expressed multi-antigen are highly reliable primer candidates to be considered in future experiments in cattle to test protection against bovine babesiosis. PMID:27269058

  4. Feasibility of subcutaneous gentamicin and pressurized irrigation as adjuvant strategies to reduce surgical site infection in colorectal surgery: results of a pilot study.

    PubMed

    Dineen, Sean P; Pham, Thai H; Murray, Bryce W; Parker, Betty J; Hartless, Kathleen; Anthony, Thomas; Huerta, Sergio

    2015-06-01

    Surgical site infections (SSIs) remain a common and costly morbidity after colorectal surgery. This rate remains high even in the setting of strict adherence to Surgical Care Improvement Project Protocols. The aim of our pilot study was to determine the feasibility and safety of subcutaneous gentamicin injection or pressurized irrigation as adjuncts to reduce SSI. A total of 132 patients who underwent colorectal surgery at the VA North Texas Health Care System were prospectively assigned to a pressurized irrigation group (n = 44), a preincision gentamicin injection group (n = 48), or control (n = 40). The primary objective was to assess safety and feasibility of these strategies. Patient demographics were matched among groups. Univariate and multivariate analyses were performed to identify possible predictions of SSI in this cohort. The rate of SSI in the control group was 25 per cent, 13.5 per cent in the pressurized irrigation group, and 12.5 per cent in the gentamicin group (P = 0.26). Combined, the intervention groups had a 13 per cent SSI versus 25 per cent control (P = 0.09). Operative time was not increased by the interventions and no intraoperative complications specifically related to the interventions were noted. Postoperative complications were not different between groups. Both albumin and body mass index were associated with SSI. Body mass index was and independent predictor of SSI (P = 0.006). In conclusion, this pilot study demonstrates the feasibility of the interventions described. There was no detrimental effect of either intervention. There was trend toward a reduction in SSI in the intervention group, which warrants further investigation. PMID:26031269

  5. Strategies for automatic online treatment plan reoptimization using clinical treatment planning system: A planning parameters study

    SciTech Connect

    Li, Taoran; Wu, Qiuwen; Zhang, You; Vergalasova, Irina; Lee, W. Robert; Yin, Fang-Fang; Wu, Q. Jackie

    2013-11-15

    Purpose: Adaptive radiation therapy for prostate cancer using online reoptimization provides an improved control of interfractional anatomy variations. However, the clinical implementation of online reoptimization is currently limited by the low efficiency of current strategies and the difficulties associated with integration into the current treatment planning system. This study investigates the strategies for performing fast (∼2 min) automatic online reoptimization with a clinical fluence-map-based treatment planning system; and explores the performance with different input parameters settings: dose-volume histogram (DVH) objective settings, starting stage, and iteration number (in the context of real time planning).Methods: Simulated treatments of 10 patients were reoptimized daily for the first week of treatment (5 fractions) using 12 different combinations of optimization strategies. Options for objective settings included guideline-based RTOG objectives, patient-specific objectives based on anatomy on the planning CT, and daily-CBCT anatomy-based objectives adapted from planning CT objectives. Options for starting stages involved starting reoptimization with and without the original plan's fluence map. Options for iteration numbers were 50 and 100. The adapted plans were then analyzed by statistical modeling, and compared both in terms of dosimetry and delivery efficiency.Results: All online reoptimized plans were finished within ∼2 min with excellent coverage and conformity to the daily target. The three input parameters, i.e., DVH objectives, starting stage, and iteration number, contributed to the outcome of optimization nearly independently. Patient-specific objectives generally provided better OAR sparing compared to guideline-based objectives. The benefit in high-dose sparing from incorporating daily anatomy into objective settings was positively correlated with the relative change in OAR volumes from planning CT to daily CBCT. The use of the

  6. Treatment strategies for inherited optic neuropathies: past, present and future

    PubMed Central

    Yu-Wai-Man, P; Votruba, M; Moore, A T; Chinnery, P F

    2014-01-01

    Bilateral visual loss secondary to inherited optic neuropathies is an important cause of registrable blindness among children and young adults. The two prototypal disorders seen in clinical practice are Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA). About 90% of LHON cases are due to one of three mitochondrial DNA (mtDNA) point mutations: m.3460G>A, m.11778G>A, and m.14484T>C, which affect critical complex I subunits of the mitochondrial respiratory chain. The majority of patients with DOA harbour pathogenic mutations within OPA1, a nuclear gene that codes for a multifunctional inner mitochondrial membrane protein. Despite their contrasting genetic basis, LHON and DOA share overlapping pathological and clinical features that serve to highlight the striking tissue-specific vulnerability of the retinal ganglion cell (RGC) layer to disturbed mitochondrial function. In addition to severe visual loss secondary to progressive optic nerve degeneration, a subgroup of patients will also develop a more aggressive syndromic phenotype marked by significant neurological deficits. The management of LHON and DOA remains largely supportive, but major advances in our understanding of the mechanisms underpinning RGC loss in these two disorders are paving the way for novel forms of treatment aimed at halting or reversing visual deterioration at different stages of the disease process. In addition to neuroprotective strategies for rescuing RGCs from irreversible cell death, innovative in vitro fertilisation techniques are providing the tantalising prospect of preventing the germline transmission of pathogenic mtDNA mutations, eradicating in so doing the risk of disease in future generations. PMID:24603424

  7. Management strategies in the treatment of neonatal and pediatric gastroenteritis

    PubMed Central

    Ciccarelli, Simona; Stolfi, Ilaria; Caramia, Giuseppe

    2013-01-01

    Acute gastroenteritis, characterized by the onset of diarrhea with or without vomiting, continues to be a major cause of morbidity and mortality in children in mostly resource-constrained nations. Although generally a mild and self-limiting disease, gastroenteritis is one of the most common causes of hospitalization and is associated with a substantial disease burden. Worldwide, up to 40% of children aged less than 5 years with diarrhea are hospitalized with rotavirus. Also, some microorganisms have been found predominantly in resource-constrained nations, including Shigella spp, Vibrio cholerae, and the protozoan infections. Prevention remains essential, and the rotavirus vaccines have demonstrated good safety and efficacy profiles in large clinical trials. Because dehydration is the major complication associated with gastroenteritis, appropriate fluid management (oral or intravenous) is an effective and safe strategy for rehydration. Continuation of breastfeeding is strongly recommended. New treatments such as antiemetics (ondansetron), some antidiarrheal agents (racecadotril), and chemotherapeutic agents are often proposed, but not yet universally recommended. Probiotics, also known as “food supplement,” seem to improve intestinal microbial balance, reducing the duration and the severity of acute infectious diarrhea. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the European Society of Paediatric Infectious Diseases guidelines make a stronger recommendation for the use of probiotics for the management of acute gastroenteritis, particularly those with documented efficacy such as Lactobacillus rhamnosus GG, Lactobacillus reuteri, and Saccharomyces boulardii. To date, the management of acute gastroenteritis has been based on the option of “doing the least”: oral rehydration-solution administration, early refeeding, no testing, no unnecessary drugs. PMID:24194646

  8. Single-arc volumetric-modulated arc therapy (sVMAT) as adjuvant treatment for gastric cancer: Dosimetric comparisons with three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT)

    SciTech Connect

    Wang, Xin; Li, Guangjun; Zhang, Yingjie; Bai, Sen; Xu, Feng; Wei, Yuquan; Gong, Youling

    2013-01-01

    To compare the dosimetric differences between the single-arc volumetric-modulated arc therapy (sVMAT), 3-dimensional conformal radiotherapy (3D-CRT), and intensity-modulated radiotherapy (IMRT) techniques in treatment planning for gastric cancer as adjuvant radiotherapy. Twelve patients were retrospectively analyzed. In each patient's case, the parameters were compared based on the dose-volume histogram (DVH) of the sVMAT, 3D-CRT, and IMRT plans, respectively. Three techniques showed similar target dose coverage. The maximum and mean doses of the target were significantly higher in the sVMAT plans than that in 3D-CRT plans and in the 3D-CRT/IMRT plans, respectively, but these differences were clinically acceptable. The IMRT and sVMAT plans successfully achieved better target dose conformity, reduced the V{sub 20/30}, and mean dose of the left kidney, as well as the V{sub 20/30} of the liver, compared with the 3D-CRT plans. And the sVMAT technique reduced the V{sub 20} of the liver much significantly. Although the maximum dose of the spinal cord were much higher in the IMRT and sVMAT plans, respectively (mean 36.4 vs 39.5 and 40.6 Gy), these data were still under the constraints. Not much difference was found in the analysis of the parameters of the right kidney, intestine, and heart. The IMRT and sVMAT plans achieved similar dose distribution to the target, but superior to the 3D-CRT plans, in adjuvant radiotherapy for gastric cancer. The sVMAT technique improved the dose sparings of the left kidney and liver, compared with the 3D-CRT technique, but showed few dosimetric advantages over the IMRT technique. Studies are warranted to evaluate the clinical benefits of the VMAT treatment for patients with gastric cancer after surgery in the future.

  9. Optimising treatment strategies in spinal ependymoma based on 20years of experience at a single centre.

    PubMed

    Keil, Vera C; Schmitt, Anne J; Martin, Sean C; Cadoux-Hudson, Tom A D; Pereira, Erlick A C

    2016-07-01

    Spinal ependymomas are rare tumours, with total resection favoured where possible. Several case series assessing the outcome following neurosurgical treatment for spinal ependymoma advocate the usage of adjuvant radiotherapy in cases of subtotal resection, or in unencapsulated tumours. We assessed the outcome of 61 consecutive cases of spinal ependymoma in a single centre over a 20year period using a variety of outcome measures. Sex distribution was equal, with a mean age at surgery of 43.6years (range 5-76years). Overall, most tumours occurred in the lumbosacral region (70.5%), with fewer in the thoracic (27.9%) and cervical regions (18.0%). Myxopapillary features were seen in 41.0% of tumours, and were more common when occurring in the lumbar region (51.2%). Gross total resection was achieved in 52.5%, subtotal resection in 37.7% and biopsy alone in 9.8% of patients and 31.1% received adjuvant radiotherapy. Two-thirds of patients achieved an excellent post-operative neurological outcome (Frankel grade E). Tumour recurrence was rare. Gross total resection and good preoperative neurological condition were most strongly predictive of good outcome. Post-operative radiotherapy did not seem to confer survival benefit in this case series, even in cases of incomplete resection, leading us to question its utility for all cases of spinal cord ependymoma. PMID:26944215

  10. Postoperative adjuvant radiotherapy for patients with gastric adenocarcinoma.

    PubMed

    Lim, Do Hoon

    2012-12-01

    In gastric adenocarcinoma, high rates of loco-regional recurrences have been reported even after complete resection, and various studies have been tried to find the role of postoperative adjuvant therapy. Among them, Intergroup 0116 trial was a landmark trial, and demonstrated the definite survival benefit in adjuvant chemoradiotherapy, compared with surgery alone. However, the INT 0116 trial had major limitation for global acceptance of the INT 0116 regimen as an adjuvant treatment modality because of the limited lymph node dissection. Lately, several randomized studies that were performed to patients with D2-dissected gastric cancer were published. This review summarizes the data about patterns of failure after surgical resection and the earlier prospective studies, including INT 0116 study. Author will introduce the latest studies, including ARTIST trial and discuss whether external beam radiotherapy should be applied to patients receiving extended lymph node dissection and adjuvant chemotherapy. PMID:23346491

  11. Evaluation of monophosphoryl lipid A as an immune adjuvant for photodynamic therapy in a rat sarcoma model: preliminary results

    NASA Astrophysics Data System (ADS)

    Lucroy, Michael D.; Edwards, Benjamin F.; Griffey, Stephen M.; Madewell, Bruce R.

    1999-06-01

    Photodynamic therapy (PDT) is a treatment option for several forms of human cancer, and like traditional chemotherapy and ionizing radiation therapy, PDT alone is not curative for some cases. Recent efforts have aimed at developing strategies for adjuvant therapy for PDT. Given the nature of PDT-mediated cell damage, immunotherapy is a promising adjuvant for long-term control of solid tumors. A candidate immune stimulant for use with PDT is monophosphoryl lipid A (MLA), a non-toxic fraction of the endotoxin molecule. The hypothesis is that adjuvant MLA immunotherapy with PDT will improve local tumor control and prevent growth of subsequently implanted tumor cells when compared to PDT alone. To date, no significant differences in circulating leukocyte populations or tumor infiltrating lymphocyte populations have been identified in 9L tumor-bearing F344 rats after systemic administrations of MLA. Likewise, no significant difference has been identified in local tumor control following PDT of 9L tumors with or without adjuvant MLA. Further results are pending.

  12. The adjuvanted influenza vaccines with novel adjuvants: experience with the MF59-adjuvanted vaccine.

    PubMed

    Podda, A

    2001-03-21

    Elderly people and subjects with underlying chronic diseases are at increased risk for influenza and related complications. Conventional influenza vaccines provide only limited protection in the elderly population. In order to enhance the immune response to influenza vaccines, several adjuvants have been evaluated. Among these, an oil in water adjuvant emulsion containing squalene, MF59, has been combined with subunit influenza antigens and tested in clinical trials in comparison with non-adjuvanted conventional vaccines. Data from a clinical database of over 10000 elderly subjects immunised with this adjuvanted vaccine (Fluad, Chiron Vaccines, Siena, Italy) demonstrate that, although common postimmunisation reactions are more frequent in recipients of the adjuvanted vaccine, this vaccine is well tolerated, also after re-immunisation in subsequent influenza seasons. Immunogenicity analyses demonstrate a consistently higher immune response with statistically significant increases of postimmunisation geometric mean titres, and of seroconversion and seroprotection rates compared to non-adjuvanted subunit and split influenza vaccines, particularly for the A/H3N2 and the B strains. The higher immunogenicity profile of the MF59-adjuvanted vaccine is maintained also after subsequent immunisations. An even higher adjuvant effect was shown in subjects with low pre-immunisation titre and in those affected by chronic underlying diseases. In conclusion, the addition of MF59 to subunit influenza vaccines enhances significantly the immune response in elderly subjects without causing clinically important changes in the safety profile of the influenza vaccine. PMID:11257408

  13. Melanoma and IFN alpha: potential adjuvant therapy.

    PubMed

    Bottoni, U; Clerico, R; Paolino, G; Corsetti, P; Ambrifi, M; Brachini, A; Richetta, A; Nisticò, S; Pranteda, G; Calvieri, S

    2014-01-01

    Interferon alpha (IFNalpha) is the most used adjuvant treatment in clinical practice for melanoma (MEL) high-medium risk patients; however, the use of IFNalpha has yielded conflicting data on Overall Survival (OS) and disease free survival (DFS) rates. Starting from these considerations, we carried out an analysis on our MEL patients who received adjuvant IFNalpha therapy, in order to identify possible predictors for their outcome. A total of 140 patients were included in our analysis. Patients with Breslow thickness ≤2.00 mm presented a significantly longer mean DFS than patients with Breslow ≥2.01 mm (p = 0.01). Using non- parametric Spearman’s Coefficient test we found association between DFS and Breslow thickness (p < 0.001) and between DFS and ulceration (p = 0.03). Performing Multiple Regression test, Breslow thickness (p < 0.001) remained the only statistically significant predictor. From the OS analysis we found that patients with lower Breslow values ≤ 2.00 mm (p < 0.0001), and absence of ulceration (p <0.004) showed a significantly better long-term survival. From the current analysis we found that the use of low dose IFNalpha is justified only for cutaneous melanoma ≤ 4.01 mm that was not ulcerated; patients with Breslow ≥ 4.01 mm, in our opinion, should not carry out adjuvant treatment with low dose IFNalpha, because its side effects could be higher than the its benefits. PMID:25001659

  14. [Therapeutic strategies for obsessive-compulsive disorder refractory to treatment].

    PubMed

    Mussa, Alexis

    2008-01-01

    Obsessive-compulsive disorder (OCD) is a chronic disabling disease with profound implications for social functioning. OCD affects all spheres of functioning of patients who suffer the disorder. Treatment with serotonin reuptake inhibitors is effective in 40% to 60% of patients with OCD, but a large percentage of patients are non responsive to treatment. Those patients who do respond often do not fully remit, which should be the standard goal of treatment in OCD. Treatment refractory patients with OCD are those who undergo adequate trials of first-line therapies without a satisfactory response. Conventional treatment and alternative treatment options for this population are reviewed. PMID:18997908

  15. Non-viral in vivo immune gene therapy of cancer: combined strategies for treatment of systemic disease.

    PubMed

    Tangney, M; Casey, G; Larkin, J O; Collins, C G; Soden, D; Cashman, J; Whelan, M C; O'Sullivan, G C

    2006-11-01

    Many patients with various types of cancers have already by the time of presentation, micrometastases in their tissues and are left after treatment in a minimal residual disease state [Am J Gastroenterol 95(12), 2000]. To prevent tumour recurrence these patients require a systemic based therapy, but current modalities are limited by toxicity or lack of efficacy. We have previously reported that immune reactivity to the primary tumour is an important regulator of micrometastases and determinant of prognosis. This suggests that recruitment of specific anti-tumour mechanisms within the primary tumour could be used advantageously for tumour control as either primary or neo-adjuvant treatments. Recently, we have focused on methods of stimulating immune eradication of solid tumours and minimal residual disease using gene therapy approaches. Gene therapy is now a realistic prospect and a number of delivery approaches have been explored, including the use of viral and non-viral vectors. Non-viral vectors have received significant attention since, in spite of their relative delivery inefficiency, they may be safer and have greater potential for delivery of larger genetic units. By in vivo electroporation of the primary tumour with plasmid expressing GM-CSF and B7-1, we aim to stimulate immune eradication of the treated tumour and associated metastases. In this symposium report, we describe an effective gene based approach for cancer immunotherapy by inducing cytokine and immune co-stimulatory molecule expression by the growing cells of the primary tumour using a plasmid electroporation gene delivery strategy. We discuss the potential for enhancement of this therapy by its application as a neoadjuvant to surgical excision and by its use in combination with suppressor T cell depletion. PMID:16612593

  16. Human prophylactic vaccine adjuvants and their determinant role in new vaccine formulations

    PubMed Central

    Pérez, O.; Batista-Duharte, A.; González, E.; Zayas, C.; Balboa, J.; Cuello, M.; Cabrera, O.; Lastre, M.; Schijns, V.E.J.C.

    2012-01-01

    Adjuvants have been considered for a long time to be an accessory and empirical component of vaccine formulations. However, accumulating evidence of their crucial role in initiating and directing the immune response has increased our awareness of the importance of adjuvant research in the past decade. Nevertheless, the importance of adjuvants still is not fully realized by many researchers working in the vaccine field, who are involved mostly in the search for better target antigens. The choice of a proper adjuvant can be determinant for obtaining the best results for a given vaccine candidate, but it is restricted due to intellectual property and know-how issues. Consequently, in most cases the selected adjuvant continues to be the aluminum salt, which has a record of safety, but predominantly constitutes a delivery system (DS). Ideally, new strategies should combine immune potentiators (IP) and DS by mixing both compounds or by obtaining structures that contain both IP and DS. In addition, the term immune polarizer has been introduced as an essential concept in the vaccine design strategies. Here, we review the theme, with emphasis on the discussion of the few licensed new adjuvants, the need for safe mucosal adjuvants and the adjuvant/immunopotentiating activity of conjugation. A summary of toxicology and regulatory issues will also be discussed, and the Finlay Adjuvant Platform is briefly summarized. PMID:22527130

  17. Human prophylactic vaccine adjuvants and their determinant role in new vaccine formulations.

    PubMed

    Pérez, O; Batista-Duharte, A; González, E; Zayas, C; Balboa, J; Cuello, M; Cabrera, O; Lastre, M; Schijns, V E J C

    2012-08-01

    Adjuvants have been considered for a long time to be an accessory and empirical component of vaccine formulations. However, accumulating evidence of their crucial role in initiating and directing the immune response has increased our awareness of the importance of adjuvant research in the past decade. Nevertheless, the importance of adjuvants still is not fully realized by many researchers working in the vaccine field, who are involved mostly in the search for better target antigens. The choice of a proper adjuvant can be determinant for obtaining the best results for a given vaccine candidate, but it is restricted due to intellectual property and know-how issues. Consequently, in most cases the selected adjuvant continues to be the aluminum salt, which has a record of safety, but predominantly constitutes a delivery system (DS). Ideally, new strategies should combine immune potentiators (IP) and DS by mixing both compounds or by obtaining structures that contain both IP and DS. In addition, the term immune polarizer has been introduced as an essential concept in the vaccine design strategies. Here, we review the theme, with emphasis on the discussion of the few licensed new adjuvants, the need for safe mucosal adjuvants and the adjuvant/immunopotentiating activity of conjugation. A summary of toxicology and regulatory issues will also be discussed, and the Finlay Adjuvant Platform is briefly summarized. PMID:22527130

  18. Radium and Other Radiological Chemicals: Drinking Water Treatment Strategies

    EPA Science Inventory

    Radium and Other Radiological Chemicals: Drinking Water Treatment Technologies Topics include: Introduction to Rad Chemistry, Summary of the Rad, Regulations Treatment Technology, and Disposal. The introductions cover atoms, ions, radium and uranium and the removal of radioac...

  19. Randomized Trial of Drug Abuse Treatment-Linkage Strategies

    ERIC Educational Resources Information Center

    Sorenson, James L.; Masson, Carmen L.; Delucchi, Kevin; Sporer, Karl; Barnett, Paul G.; Mitsuishi, Fumi; Lin, Christine; Song, Yong; Chen, TeChieh; Hall, Sharon M.

    2005-01-01

    A clinical trial contrasted 2 interventions designed to link opioid-dependent hospital patients to drug abuse treatment. The 126 out-of-treatment participants were randomly assigned to (a) case management, (b) voucher for free methadone maintenance treatment (MMT), (c) case management plus voucher, or (d) usual care. Services were provided for 6…

  20. The economic effects of whole-herd versus selective anthelmintic treatment strategies in dairy cows.

    PubMed

    Charlier, J; Levecke, B; Devleesschauwer, B; Vercruysse, J; Hogeveen, H

    2012-06-01

    Current control practices against gastrointestinal nematodes in dairy cows rely strongly on anthelmintic use. To reduce the development of anthelmintic resistance or disposition of drug residues in the environment, novel control approaches are currently proposed that target anthelmintic treatment to individual animals instead of the whole herd. However, such selective treatment strategies come with additional costs for labor and diagnostics and, so far, no studies have addressed whether they could be economically sustainable. The objectives of this study were to (1) investigate the economic effects at farm level of whole-herd versus more selective anthelmintic treatment strategies in adult dairy cows, and (2) determine how these economic effects depend on level of infection and herd size. A Monte Carlo simulation, fed by current epidemiological and economical knowledge, was used to estimate the expected economic effects and possible variation of different control strategies under Belgian conditions. Four treatment strategies were compared with a baseline situation in which no treatments were applied: whole herd at calving (S1), selective at calving with (S2) or without (S3) treatment of the first-calf cows, and whole-herd when animals are moved from grazing to the barn in the fall (housing treatment, S4). The benefit per lactation for an average dairy herd varied between -$2 and $131 (average $64) for S1, between -$2 and $127 (average $62) for S2, between -$17 and $104 (average $43) for S3, and between -$41 and $72 (average $15) for S4. The farmer's risk associated with any treatment strategy, as indicated by the width of the 95% credible intervals of economic benefit of anthelmintic treatment, decreased with increasing level of exposure, as assessed by bulk tank milk ELISA. The order of the different strategies when sorted by expected benefit was robust to changes in economic input parameters. We conclude that, on average, strategies applying anthelmintic

  1. Endorectal MRI assessment of local relapse after surgery for prostate cancer: A model to define treatment field guidelines for adjuvant radiotherapy in patients at high risk for local failure

    SciTech Connect

    Miralbell, Raymond . E-mail: Raymond.Miralbell@hcuge.ch; Vees, Hansjoerg; Lozano, Joan; Khan, Haleem; Molla, Meritxell; Hidalgo, Alberto; Linero, Dolors; Rouzaud, Michel

    2007-02-01

    Purpose: To assess the role of endorectal magnetic resonance imaging (MRI) in defining local relapse after radical prostatectomy for prostate cancer to help to reassess the clinical target volume (CTV) for adjuvant postprostatectomy radiotherapy. Methods and Materials: Sixty patients undergoing an endorectal MRI before salvage radiotherapy were selected. Spatial coordinates of the relapses were assessed using two reference points: the inferior border of the pubic symphysis (point 1) and the urethro-vesical anastomosis (point 2). Every lesion on MRI was delineated on the planning computed tomography and center of mass coordinates were plotted in two separate diagrams (along the x, y, and z axes) with the urethro-vesical anastomosis as the coordinate origin. An 'ideal' CTV was constructed, centered at a point defined by the mathematical means of each of the three coordinates with dimensions defined as twice 2 standard deviations in each of the three axes. The dosimetric impact of the new CTV definition was evaluated in six adjuvantly treated patients. Results: The ideal CTV center of mass was located at coordinates 0 (x), -5 (y), and -3 (z) mm with SDs of 6 (x), 6 (y), and 9 (z) mm, respectively. The CTV size was 24 (x) x 24 (y) x 36 (z) mm. Significant rectal sparing was observed with the new CTV. Conclusions: A CTV with an approximately cylindrical shape ({approx}4 x 3 cm) centered 5 mm posterior and 3 mm inferior to the urethro-vesical anastomosis was defined. Such CTV may reduce the irradiation of normal nontarget tissue in the pelvis potentially improving treatment tolerance.

  2. Chitin, Chitosan, and Glycated Chitosan Regulate Immune Responses: The Novel Adjuvants for Cancer Vaccine

    PubMed Central

    Li, Xiaosong; Min, Min; Du, Nan; Gu, Ying; Hode, Tomas; Naylor, Mark; Chen, Dianjun; Nordquist, Robert E.; Chen, Wei R.

    2013-01-01

    With the development of cancer immunotherapy, cancer vaccine has become a novel modality for cancer treatment, and the important role of adjuvant has been realized recently. Chitin, chitosan, and their derivatives have shown their advantages as adjuvants for cancer vaccine. In this paper, the adjuvant properties of chitin and chitosan were discussed, and some detailed information about glycated chitosan and chitosan nanoparticles was also presented to illustrate the trend for future development. PMID:23533454

  3. [Adjuvant drug therapies for breast cancer].

    PubMed

    Huovinen, Riikka; Auvinen, Päivi; Mattson, Johanna; Joensuu, Heikki

    2015-01-01

    Most breast cancers are hormone receptor positive and exhibit a slow growth pattern. Based on biological properties, breast cancers are divided into four different biological subtypes. Furthermore, these subtypes are indicative of the risk of recurrence, which is also influenced by the size of the tumor and extension to lymph nodes. Postoperative adjuvant drug therapy is chosen on the basis of the biological type. Chemotherapy can be used in all subtypes. Hormonal therapies are used exclusively for the treatment of hormone receptor positive breast cancer. Trastuzumab antibody belongs to the treatment of the HER2 positive subtype. PMID:26245052

  4. Optimizing Adherence to Adjuvant Imatinib in Gastrointestinal Stromal Tumor

    PubMed Central

    Tetzlaff, Eric D.; Davey, Monica P.

    2013-01-01

    The increasing use of patient-administered oral anticancer drugs is paralleled by new challenges in maintaining treatment adherence. These challenges are particularly significant with adjuvant therapies for prevention of disease recurrence, where the benefits of ongoing treatment are not readily apparent to patients. Nurse practitioners and physician assistants (collectively referred to as advanced practitioners) play integral roles in providing education on disease and treatment to patients that can increase adherence to oral therapies and ideally improve outcomes. For patients with gastrointestinal stromal tumor (GIST), the oral targeted therapy imatinib has become the mainstay of treatment for advanced and recurrent disease and as adjuvant therapy following surgical resection. Recent data indicate significantly improved overall survival with 3 years vs. 1 year of adjuvant imatinib therapy. Continuous dosing with imatinib is needed for optimal efficacy and to limit additional health-care costs associated with management of disease progression in GIST. However, longer duration of therapy increases the risk of nonadherence. Imatinib adherence rates, as well as factors contributing to nonadherence to adjuvant therapy in routine clinical practice, are discussed in this review. Also explored are practical approaches for improving adherence to adjuvant imatinib therapy through greater patient education, in light of the increased duration of therapy in select patients. PMID:25032004

  5. Phase I-II study of hypofractionated simultaneous integrated boost using volumetric modulated arc therapy for adjuvant radiation therapy in breast cancer patients: a report of feasibility and early toxicity results in the first 50 treatments

    PubMed Central

    2012-01-01

    Background To report results in terms of feasibility and early toxicity of hypofractionated simultaneous integrated boost (SIB) approach with Volumetric Modulated Arc Therapy (VMAT) as adjuvant treatment after breast-conserving surgery. Methods Between September 2010 and May 2011, 50 consecutive patients presenting early-stage breast cancer were submitted to adjuvant radiotherapy with SIB-VMAT approach using RapidArc in our Institution (Istituto Clinico Humanitas ICH). Three out of 50 patients were irradiated bilaterally (53 tumours in 50 patients). All patients were enrolled in a phase I-II trial approved by the ICH ethical committee. All 50 patients enrolled in the study underwent VMAT-SIB technique to irradiate the whole breast with concomitant boost irradiation of the tumor bed. Doses to whole breast and surgical bed were 40.5 Gy and 48 Gy respectively, delivered in 15 fractions over 3 weeks. Skin toxicities were recorded during and after treatment according to RTOG acute radiation morbidity scoring criteria with a median follow-up of 12 months (range 8–16). Cosmetic outcomes were assessed as excellent/good or fair/poor. Results The median age of the population was 68 years (range 36–88). According to AJCC staging system, 38 breast lesions were classified as pT1, and 15 as pT2; 49 cases were assessed as N0 and 4 as N1. The maximum acute skin toxicity by the end of treatment was Grade 0 in 20/50 patients, Grade 1 in 32/50, Grade 2 in 0 and Grade 3 in 1/50 (one of the 3 cases of bilateral breast irradiation). No Grade 4 toxicities were observed. All Grade 1 toxicities had resolved within 3 weeks. No significant differences in cosmetic scores on baseline assessment vs. 3 months and 6 months after the treatment were observed: all patients were scored as excellent/good (50/50) compared with baseline; no fair/poor judgment was recorded. No other toxicities or local failures were recorded during follow-up. Conclusions The 3-week course of

  6. Targeted photodynamic therapy--a promising strategy of tumor treatment.

    PubMed

    Bugaj, Andrzej M

    2011-07-01

    Targeted therapy is a new promising therapeutic strategy, created to overcome growing problems of contemporary medicine, such as drug toxicity and drug resistance. An emerging modality of this approach is targeted photodynamic therapy (TPDT) with the main aim of improving delivery of photosensitizer to cancer tissue and at the same time enhancing specificity and efficiency of PDT. Depending on the mechanism of targeting, we can divide the strategies of TPDT into "passive", "active" and "activatable", where in the latter case the photosensitizer is activated only in the target tissue. In this review, contemporary strategies of TPDT are described, including new innovative concepts, such as targeting assisted by peptides and aptamers, multifunctional nanoplatforms with navigation by magnetic field or "photodynamic molecular beacons" activatable by enzymes and nucleic acid. The imperative of introducing a new paradigm of PDT, focused on the concepts of heterogeneity and dynamic state of tumor, is also called for. PMID:21547329

  7. Otitis media with effusion: benefits and harms of strategies in use for treatment and prevention.

    PubMed

    Principi, Nicola; Marchisio, Paola; Esposito, Susanna

    2016-04-01

    Otitis media with effusion (OME) is a common clinical condition that is associated with hearing loss. It can be diagnosed at least once in approximately 80% of preschool children: 30-40% of them have recurrent episodes, and 5-10% have chronic disease. OME, in recurrent and persistent cases, might significantly delay or impair communication skills, resulting in behavioral and educational difficulties. Several therapeutic approaches have been used to avoid these problems. Most, however, have not been adequately studied, and no definitive conclusions can be drawn. Official guidelines do not recommend the use of decongestants, antihistamines, steroids, or antibiotics. The data are too scanty to assess other interventions, although autoinflation, because it incurs neither cost nor adverse events, deserves attention. Surgical procedures (i.e., tympanostomy tube insertion and adenoidectomy as an adjuvant) can be useful in some cases. This review evaluates all the current OME treatments and preventive measures, including their possible adverse events. PMID:26853095

  8. Capecitabine and Oxaliplatin in the Preoperative Multimodality Treatment of Rectal Cancer: Surgical End Points From National Surgical Adjuvant Breast and Bowel Project Trial R-04

    PubMed Central

    O'Connell, Michael J.; Colangelo, Linda H.; Beart, Robert W.; Petrelli, Nicholas J.; Allegra, Carmen J.; Sharif, Saima; Pitot, Henry C.; Shields, Anthony F.; Landry, Jerome C.; Ryan, David P.; Parda, David S.; Mohiuddin, Mohammed; Arora, Amit; Evans, Lisa S.; Bahary, Nathan; Soori, Gamini S.; Eakle, Janice; Robertson, John M.; Moore, Dennis F.; Mullane, Michael R.; Marchello, Benjamin T.; Ward, Patrick J.; Wozniak, Timothy F.; Roh, Mark S.; Yothers, Greg; Wolmark, Norman

    2014-01-01

    Purpose The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy (RT) for patients with rectal cancer is unknown. National Surgical Adjuvant Breast and Bowel Project trial R-04 compared four chemotherapy regimens administered concomitantly with RT. Patients and Methods Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in 25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous intravenous infusional fluorouracil (CVI FU; 225 mg/m2, 5 days per week), with or without intravenous oxaliplatin (50 mg/m2 once per week for 5 weeks) or oral capecitabine (825 mg/m2 twice per day, 5 days per week), with or without oxaliplatin (50 mg/m2 once per week for 5 weeks). Before random assignment, the surgeon indicated whether the patient was eligible for sphincter-sparing surgery based on clinical staging. The surgical end points were complete pathologic response (pCR), sphincter-sparing surgery, and surgical downstaging (conversion to sphincter-sparing surgery). Results From September 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, sphincter-sparing surgery, or surgical downstaging were identified between the CVI FU and capecitabine regimens or between the two regimens with or without oxaliplatin. Patients treated with oxaliplatin experienced significantly more grade 3 or 4 diarrhea (P < .001). Conclusion Administering capecitabine with preoperative RT achieved similar rates of pCR, sphincter-sparing surgery, and surgical downstaging compared with CVI FU. Adding oxaliplatin did not improve surgical outcomes but added significant toxicity. The definitive analysis of local tumor control, disease-free survival, and overall survival will be performed when the protocol-specified number of events has occurred. PMID:24799484

  9. Comparison of different treatment strategies for industrial landfill leachate.

    PubMed

    Gotvajn, A Zgajnar; Tisler, T; Zagorc-Koncan, J

    2009-03-15

    The aim of our research was to determine appropriate treatment technique for effective treatment of heavily polluted tannery landfill leachate. We have accomplished several treatment experiments: (i) aerobic biological treatment, (ii) air stripping at various pH, (iii) adsorption to activated carbon, (iv) coagulation-flocculation and (v) advanced oxidation process with Fe(2+)/H(2)O(2). Efficiency of each procedure was monitored by chemical analysis and changes in biodegradability and acute toxicity were also evaluated (Vibrio fischeri and Daphnia magna). Biological treatment of raw leachate was effective only for very diluted leachate (up to 6Vol.%). It has been confirmed that air stripping at pH 11.0 effectively removed volatile organics and ammonia for 33% and 84%, respectively and contributed to lower toxicity of the leachate. Fenton's oxidation was the most effective among all used treatment procedures. COD removal reached 86%, biodegradability has been increased and toxicity reduced. Adsorption to activated carbon increased BOD(5)/COD ratio from 0.18 to 0.56 and it removed 40% of organics. Coagulation and flocculation procedures with FeCl(3) were also very effective. At lowered pH and added flocculant treatment efficiency reached 50%. But no method alone was effective enough to meet effluent limits for release into local surface waters. Future work was focused on the study of different promising treatment schemes, especially combination of Fenton's oxidation and biological treatment. PMID:18650010

  10. Roles of adjuvant and salvage radiotherapy for desmoplastic melanoma.

    PubMed

    Oliver, Daniel E; Patel, Kirtesh R; Switchenko, Jeffrey; Parker, Douglas; Lawson, David H; Delman, Keith A; Kudchadkar, Ragini R; Khan, Mohammad K

    2016-02-01

    Current guidelines are unclear as to the precise role of radiotherapy (RT) in patients with desmoplastic melanoma (DM). The purpose of this study was to evaluate our institutional outcomes in patients with DM, and to explore the roles of both adjuvant and salvage RT in these patients. We identified 100 patients with a histopathologic diagnosis of DM who received treatment at our institution from 2000 to 2014. Local control, distant metastasis-free survival, and overall survival (OS) were evaluated in the 95 patients managed surgically with or without adjuvant and/or salvage RT. The overall rate of local recurrence (LR) was 10%. There was no LR in either adjuvant or salvage RT cohort. Adjuvant RT did not significantly improve LR-free survival at 5 years (100 vs. 81%, P=0.59), despite the RT patients having worse pathological features. Four of seven (57%) salvage patients developed distant metastases, despite 100% local control. Adjuvant RT did not significantly impact 5-year overall survival (86 vs. 82%, P=0.43). RT shows a trend towards improved local control in both the adjuvant and salvage settings for patients with DM, and likely overcomes adverse risk factors after surgery in appropriately selected patients. Future prospective studies are needed to better address the optimal management for these patients. PMID:26397051

  11. Roles of adjuvant and salvage radiotherapy for desmoplastic melanoma

    PubMed Central

    Oliver, Daniel E.; Patel, Kirtesh R.; Switchenko, Jeffrey; Parker, Douglas; Lawson, David H.; Delman, Keith A.; Kudchadkar, Ragini R.; Khan, Mohammad K.

    2016-01-01

    Current guidelines are unclear as to the precise role of radiotherapy (RT) in patients with desmoplastic melanoma (DM). The purpose of this study was to evaluate our institutional outcomes in patients with DM, and to explore the roles of both adjuvant and salvage RT in these patients. We identified 100 patients with a histopathologic diagnosis of DM who received treatment at our institution from 2000 to 2014. Local control, distant metastasis-free survival, and overall survival (OS) were evaluated in the 95 patients managed surgically with or without adjuvant and/or salvage RT. The overall rate of local recurrence (LR) was 10%. There was no LR in either adjuvant or salvage RT cohort. Adjuvant RT did not significantly improve LR-free survival at 5 years (100 vs. 81%, P = 0.59), despite the RTpatients having worse pathological features. Four of seven (57%) salvage patients developed distant metastases, despite 100% local control. Adjuvant RT did not significantly impact 5-year overall survival (86 vs. 82%, P = 0.43). RT shows a trend towards improved local control in both the adjuvant and salvage settings for patients with DM, and likely overcomes adverse risk factors after surgery in appropriately selected patients. Future prospective studies are needed to better address the optimal management for these patients. PMID:26397051

  12. Utility of adjuvant systemic therapy in melanoma

    PubMed Central

    Eggermont, A. M. M.; Testori, A.; Marsden, J.; Hersey, P.; Quirt, I.; Petrella, T.; Gogas, H.; MacKie, R. M.; Hauschild, A.

    2009-01-01

    The lack of effective drugs in stage IV melanoma has impacted the effectiveness of adjuvant therapies in stage II/III disease. To date, chemotherapy, immunostimulants and vaccines have been used with minimal success. Interferon (IFN) has shown an effect on relapse-free survival (RFS) in several clinical trials; however, without a clinically significant effect on overall survival (OS). A recently conducted meta-analysis demonstrated prolongation of disease-free survival (DFS) in 7% and OS benefit in 3% of IFN-treated patients when compared with observation-only patients. There were no clear differences for the dose and duration of treatment observed. Observation is still an appropriate control arm in adjuvant clinical trials. Regional differences exist in Europe in the adjuvant use of IFN. In Northwest Europe, IFN is infrequently prescribed. In Central and Mediterranean Europe, dermatologists commonly prescribe low-dose IFN therapy for AJCC stage II and III disease. High-dose IFN regimens are not commonly used. The population of patients that may benefit from IFN needs to be further characterised, potentially by finding biomarkers that can predict response. Such studies are ongoing. PMID:19617295

  13. Tau-targeted treatment strategies in Alzheimer's disease.

    PubMed

    Götz, Jürgen; Ittner, Arne; Ittner, Lars M

    2012-03-01

    With populations ageing worldwide, the need for treating and preventing diseases associated with high age is pertinent. Alzheimer's disease (AD) is reaching epidemic proportions, yet the currently available therapies are limited to a symptomatic relief, without halting the degenerative process that characterizes the AD brain. As in AD cholinergic neurons are lost at high numbers, the initial strategies were limited to the development of acetylcholinesterase inhibitors, and more recently the NMDA receptor antagonist memantine, in counteracting excitotoxicity. With the identification of the protein tau in intracellular neurofibrillary tangles and of the peptide amyloid-β (Aβ) in extracellular amyloid plaques in the AD brain, and a better understanding of their role in disease, newer strategies are emerging, which aim at either preventing their formation and deposition or at accelerating their clearance. Interestingly, what is well established to combat viral diseases in peripheral organs - vaccination - seems to work for the brain as well. Accordingly, immunization strategies targeting Aβ show efficacy in mice and to some degree also in humans. Even more surprising is the finding in mice that immunization strategies targeting tau, a protein that forms aggregates in nerve cells, ameliorates the tau-associated pathology. We are reviewing the literature and discuss what can be expected regarding the translation into clinical practice and how the findings can be extended to other neurodegenerative diseases with protein aggregation in brain. PMID:22044248

  14. Tank waste remediation system optimized processing strategy with an altered treatment scheme

    SciTech Connect

    Slaathaug, E.J.

    1996-03-01

    This report provides an alternative strategy evolved from the current Hanford Site Tank Waste Remediation System (TWRS) programmatic baseline for accomplishing the treatment and disposal of the Hanford Site tank wastes. This optimized processing strategy with an altered treatment scheme performs the major elements of the TWRS Program, but modifies the deployment of selected treatment technologies to reduce the program cost. The present program for development of waste retrieval, pretreatment, and vitrification technologies continues, but the optimized processing strategy reuses a single facility to accomplish the separations/low-activity waste (LAW) vitrification and the high-level waste (HLW) vitrification processes sequentially, thereby eliminating the need for a separate HLW vitrification facility.

  15. Live birth rates after combined adjuvant therapy in IVF-ICSI cycles: a matched case-control study.

    PubMed

    Motteram, C; Vollenhoven, B; Hope, N; Osianlis, T; Rombauts, L J

    2015-04-01

    The effectiveness of combined co-treatment with aspirin, doxycycline, prednisolone, with or without oestradiol patches, was investigated on live birth (LBR) rates after fresh and frozen embryo transfers (FET) in IVF and intracytoplasmic sperm injection cycles. Cases (n = 485) and controls (n = 485) were extensively matched in a one-to-one ratio on nine physical and clinical parameters: maternal age, body mass index, smoking status, stimulation cycle number, cumulative dose of FSH, stimulation protocol, insemination method, day of embryo transfer and number of embryos transferred. No significant differences were found in fresh cycles between cases and controls for the pregnancy outcomes analysed, but fewer surplus embryos were available for freezing in the combined adjuvant group. In FET cycles, LBR was lower in the treatment group (OR: 0.49, 95% CI 0.25 to 0.95). The lower LBR in FET cycles seemed to be clustered in patients receiving combined adjuvant treatment without luteal oestradiol (OR 0.37, 95% CI 0.17 to 0.80). No difference was found in LBR between cases and controls when stratified according to the number of previous cycles (<3 or ≥3). There is no benefit of this combined adjuvant strategy in fresh IVF cycles, and possible harm when used in frozen cycles. PMID:25676168

  16. [Treatment of non-small cell lung carcinoma in early stages].

    PubMed

    Meneses, José Carlos; Avila Martínez, Régulo J; Ponce, Santiago; Zuluaga, Mauricio; Bartolomé, Adela; Gámez, Pablo

    2013-12-01

    Treatment of lung carcinoma is multidisciplinary. There are different therapeutic strategies available, although surgery shows the best results in those patients with lung carcinoma in early stages. Other options such as stereotactic radiation therapy are relegated to patients with small tumors and poor cardiopulmonary reserve or to those who reject surgery. Adjuvant chemotherapy is not justified in patients with stage i of the disease and so double adjuvant chemotherapy should be considered. This adjuvant chemotherapy should be based on cisplatin after surgery in those patients with stages ii and IIIA. PMID:23829961

  17. Adjuvant chemotherapy for gastric cancer: Current evidence and future challenges

    PubMed Central

    Miceli, Rosalba; Tomasello, Gianluca; Bregni, Giacomo; Di Bartolomeo, Maria; Pietrantonio, Filippo

    2014-01-01

    Gastric cancer still represents one of the major causes of cancer mortality worldwide. Patients survival is mainly related to stage, with a high proportion of patients with metastatic disease at presentation. Thus, the cure rate largely depend upon surgical resection. Despite the additional, albeit small, benefit of adjuvant chemotherapy has been clearly demonstrated, no general consensus has been reached on the best treatment option. Moreover, the narrow therapeutic index of adjuvant chemotherapy (i.e., limited survival benefit with considerable toxicity) requires a careful assessment of expected risks and benefits for individual patients. Treatment choices vary widely based on the different geographic areas, with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States. In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses. The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery; the same Authors also showed that disease-free survival may be used as a surrogate end-point for overall survival. We finally discuss future research issues such as the need of economic evaluations, development of prognostic or predictive biomarkers, and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment. PMID:24782604

  18. Arthrogryposis: an update on clinical aspects, etiology, and treatment strategies

    PubMed Central

    Feluś, Jarosław

    2016-01-01

    Arthrogryposes – multiple joint contractures – are a clinically and etiologically heterogeneous class of diseases, where accurate diagnosis, recognition of the underlying pathology and classification are of key importance for the prognosis as well as for selection of appropriate management. This treatment remains challenging and optimally in arthrogrypotic patients should be carried out by a team of specialists familiar with all aspects of arthrogryposis pathology and treatment modalities: rehabilitation, orthotics and surgery. In this comprehensive review article, based on literature and clinical experience, the authors present an update on current knowledge on etiology, classifications and treatment options for skeletal deformations possible in arthrogryposis. PMID:26925114

  19. New treatment strategies against hepatitis C viral infection

    PubMed Central

    Bilodeau, Marc; Lamarre, Daniel

    2006-01-01

    Treatment of hepatitis C virus infection is currently based on a combination of pegylated interferon and ribavirin. Because efficacy of this therapy remains suboptimal and side effects sometimes problematic, major efforts have been put forward by scientists and the pharmaceutical industry to develop alternative treatments for this chronic infection. Over the past few years, clinical studies performed with some of these new agents have been presented at major international meetings. The present paper aims to review the rationale underlying the development of these new forms of treatment as well as the current available data concerning their clinical efficacy. PMID:17111056

  20. [Integrative management of operation, perioperative rehabilitation and postoperative adjuvant chemotherapy in elderly patients with colorectal carcinoma].

    PubMed

    Xu, Dong; Jiao, Yurong; Ding, Kefeng

    2016-05-25

    With the aging of the Chinese population, it seems obvious that the number of elderly patients with the disease of colorectal carcinoma grows significantly. Meanwhile, no evidence-based practical guideline for the treatment of colorectal carcinoma are available in this particular age group. Therefore, the concept of integrative management has been brought up by the Colorectal Cancer Center of the Second Affiliated Hospital of Zhejiang University, which combines the processes of surgery, perioperative rehabilitation and adjuvant chemotherapy together. In this way, the cooperation and complementarity between different clinical departments could cooperate and complete tasks together to integrate the treatment processes into a cohesive one. To achieve the goal of integrative management, the project is divided into horizontal and vertical aspects. The horizontal integration means the cooperation between different clinical departments, which is also known as multi-discipline treatment (MDT). The vertical integration reflects the completeness of the entire treatment under the goal of consistency, strictness and job separation, which could also be explained as the clinical pathway. Furthermore, this review stresses on the integrative strategy of both clinical and biochemical indexes rehabilitation, as well as the operation and postoperative adjuvant chemotherapy which has been put in execution several years by the Colorectal Cancer Center of the Second Affiliated Hospital of Zhejiang University. PMID:27215515

  1. Fetal Alcohol Spectrum Disorders: Experimental Treatments and Strategies for Intervention

    PubMed Central

    Idrus, Nirelia M.; Thomas, Jennifer D.

    2011-01-01

    Despite the known damaging effects of prenatal alcohol exposure, women continue to drink during pregnancy, creating a need for effective interventions and treatments for fetal alcohol spectrum disorders (FASD). Experimental models can be useful in identifying potential treatments, and this article describes the spectrum of experimental therapeutics that currently are being investigated, including pharmacological, nutritional, and environmental/behavioral interventions. Some treatments target the underlying mechanisms that contribute to alcohol-induced damage, protecting against alcohol’s teratogenic effects, whereas other treatments may enhance central nervous system plasticity either during alcohol exposure or long after alcohol exposure has ceased. The insights gained to date from experimental models offer several candidates for attenuating the deficits associated with FASD. PMID:23580044

  2. Toxicity Assessment of a Phase III Study Evaluating FEC-Doc and FEC-Doc Combined with Gemcitabine as an Adjuvant Treatment for High-Risk Early Breast Cancer: the SUCCESS-A Trial

    PubMed Central

    Schröder, L.; Rack, B.; Sommer, H.; Koch, J. G.; Weissenbacher, T.; Janni, W.; Schneeweiss, A.; Rezai, M.; Lorenz, R.; Jäger, B.; Schramm, A.; Häberle, L.; Fasching, P. A.; Friedl, T. W. P.; Beckmann, M. W.; Scholz, C.

    2016-01-01

    Introduction: This paper aims to evaluate the toxicity profile of additive gemcitabine to adjuvant taxane-based chemotherapy in breast cancer patients. Methods: Patients enrolled in this open-label randomized controlled Phase III study were treated with 3 cycles of epirubicin-fluorouracil-cyclophosphamide (FEC) chemotherapy followed by 3 cycles of docetaxel with those receiving 3 cycles of FEC followed by 3 cycles of gemcitabine-docetaxel (FEC-DG). 3690 patients were evaluated according to National Cancer Institute (NCI) toxicity criteria (CTCAE). The study medications were assessed by the occurrence of grade 3–4 adverse events, dose reductions, postponements of treatment cycles and granulocyte colony-stimulating factor (G-CSF) support. Results: No differences in neutropenia or febrile neutropenia were demonstrated. However, thrombocytopenia was significantly increased with FEC-DG treatment (2.0 vs. 0.5 %, p < 0.001), as was leukopenia (64.1 vs. 58.5 %, p < 0.001). With FEC-DG significantly more G-CSF support in cycles 4 to 6 (FEC-DG: 57.8 %, FEC-D: 36.3 %, p < 0.001) was provided. Transaminase elevation was significantly more common with FEC-DG (SGPT: 6.3 %, SGOT: 2 %), whereas neuropathy (1.2 %), arthralgia (1.6 %) and bone pain (2.6 %) were more common using FEC-D. Dose reductions > 20 % (4 vs. 2.4 %) and postponement of treatment cycles (0.9 vs. 0.4 %) were significantly more frequent in the FEC-DG arm. Eight deaths occurred during treatment in the FEC-DG arm and four in the FEC-D arm. Conclusion: The addition of gemcitabine increased hematological toxicity and was associated with more dose reductions and postponements of treatment cycles. PMID:27239063

  3. Treatment strategies for radioactive iodine-refractory differentiated thyroid cancer

    PubMed Central

    2014-01-01

    Until recently, no truly effective treatment options have existed for patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), a serious disease with poor prognosis. In November 2013, the targeted multikinase inhibitor, sorafenib, was approved for use in these patients based on substantially improved progression-free survival compared with placebo. A number of other targeted agents, including lenvatinib, are being investigated in phase II and phase III trials. With the advent of these new treatment options, practitioners are faced with making important decisions in determining which patients are candidates for systemic treatment and the optimal timing for treatment initiation. Since patients may remain asymptomatic for a protracted period of time, tumor size and growth rate are the primary considerations for making these choices. Proactive management of side effects is also critical in optimizing the effectiveness of treatment. Here we review targeted systemic agents that are either in use or are under investigation for RAI-refractory DTC and provide recommendations on the rationale for initiating systemic treatment and on managing adverse events. Four illustrative case studies are provided. PMID:25364392

  4. Effect of galantamine on adjuvant-induced arthritis in rats.

    PubMed

    Gowayed, Mennatallah A; Refaat, Rowaida; Ahmed, Walid M; El-Abhar, Hanan S

    2015-10-01

    Stimulation of the vagus nerve suppresses cytokine production and macrophage activation, via the interaction of its neurotransmitter acetylcholine (ACh) with the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR), present on neurons and inflammatory cells. The present study aimed to verify the potential anti-inflammatory effect of galantamine against experimental arthritis induced in rats. Fourteen days post adjuvant injection, Sprague-Dawley rats were treated orally with three doses of galantamine (1.25, 2.5 and 5 mg/kg) or leflunomide (10 mg/kg) for 2 weeks and arthritis progression was assessed by hind paw swelling. Additionally, serum biomarkers, viz., anti-cyclic citrullinated peptide antibodies (Anti-CCP), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) were measured. Radiological examination of the hind paws was also carried out to evaluate the degree of joint damage. Adjuvant arthritis led to a significant weight loss, marked swelling of the hind paw and alteration in the serum levels of anti-CCP, TNF-α, IL-10 and MCP-1. These alterations were associated with significant radiological changes of the joints. Galantamine, in a dose-dependent manner, reduced significantly all biomarkers of inflammation, with the highest dose showing the best beneficial anti-inflammatory effect that was superior in magnitude to the reference drug leflunomide in most of the studied parameters. In conclusion, these results suggest that galantamine may represent a novel, inexpensive and effective therapeutic strategy in the treatment of rheumatoid arthritis. PMID:26189022

  5. Insights Into Severe Form of Dwarfism Could Lead to New Treatment Strategies

    MedlinePlus

    ... Could Lead to New Treatment Strategies Observations of mice engineered to carry a mutation that causes a ... to 1 month of age are shown for mice engineered to have PSACH (on right) compared to ...

  6. Therapeutic Strategies for Treatment of Pulmonary Lymphangioleiomyomatosis (LAM)

    PubMed Central

    Krymskaya, Vera P.

    2015-01-01

    Introduction Pulmonary lymphangioleiomyomatosis (LAM) is a rare progressive lung disease affecting almost exclusively women. Neoplastic growth of atypical smooth muscle-like cells in the lung induces destruction of lung parenchyma leading to the formation of lung cysts, rupture of which results in spontaneous pneumothorax. LAM occurs sporadically or in association with inherited hamartoma syndrome tuberous sclerosis complex (TSC). Progression of LAM often results in loss of pulmonary function and death. Increasing understanding of neoplastic LAM cell growth is driving the development of therapeutic approaches targeting the disease progression. Areas covered This review provides background to understand the rationale for current treatments used in patients with LAM, to critically appraise the evidence for these treatments, and to discuss future treatment approaches. The literature review includes publications from PubMed and clinicaltrials.gov/. Expert Opinion Targeting mTOR activation with rapamycin analogs sirolimus and everolimus are awaiting approval by the FDA for treatment of LAM. A number of other treatment options have been investigated and are currently tested in clinical trials to target LAM cell survival and metastasis. Key remaining and poorly understood areas for development and validation of therapeutic targeting in LAM are destruction of lungs, pathological lymphangiogenesis, and hormonal regulation. Future will reveal whether they could be targeted therapeutically. PMID:26779398

  7. Synergistic effects of laser and adjuvant therapies for cancer: progress in the development of novel cancer treatment methods using combinations of photothermal, photochemical, immunotherapy, and chemotherapy

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Bartels, Kenneth E.; Korbelik, Mladen; Liu, Hong; Nordquist, Robert E.

    2005-04-01

    Combination therapy has been commonly used in chemotherapy, taking advantage of different effects of different chemotherapeutic agents. The treatment effects are often synergistic. The same approach has been investigated in laser phototherapy. Specifically, different combinations of laser photothermal interaction, laser photochemical interaction, immunotherapy and chemotherapy have been used in the treatment of tumors. These novel approaches showed promise in cancer treatment, particularly against metastatic tumors. The recent development in this area is discussed in this paper. Furthermore, a specific combination of photodynamic therapy (PDT) with a novel immunoadjuvant, glycated chitosan (GC), has shown to be effective in the treatment mammary tumors and lung tumors in mice. In the treatment of EMT6 tumor-bearing mice, the Photofrin-based PDT and GC has significantly increased the survival rates from 37.5% with PDT alone to 62.5% when a 0.1-ml 0.5% GC was peritumoral injected immediately after PDT treatment. The survival rate was further increased to 75.0% when GC of higher concentration was used. In comparison, the individual components of the PDT-GC treatment showed either no effect or very limited effects. In the treatment of a poorly immunogenic tumor model, Line 1 lung tumors in mice, the combination of PDT and GC resulted in a 37.5% survival rate, while no survival mice were observed with PDT alone.

  8. Strategies for the cost effective treatment of Oak Ridge legacy wastes

    SciTech Connect

    Compere, A.L.; Griffith, W.L.; Huxtable, W.P.; Wilson, D.F.

    1998-03-01

    Research and development treatment strategies for treatment or elimination of several Oak Ridge plant liquid, solid, and legacy wastes are detailed in this report. Treatment strategies for volumetrically contaminated nickel; enriched uranium-contaminated alkali metal fluorides; uranium-contaminated aluminum compressor blades; large, mercury-contaminated lithium isotope separations equipment; lithium process chlorine gas streams; high-concentration aluminum nitrate wastes, and high-volume, low-level nitrate wastes are discussed. Research needed to support engineering development of treatment processes is detailed.

  9. Coping Strategies in Bulimia Nervosa Treatment: Impact on Outcome in Group Cognitive-Behavioral Therapy

    ERIC Educational Resources Information Center

    Binford, Roslyn B.; Mussell, Melissa Pederson; Crosby, Ross D.; Peterson, Carol B.; Crow, Scott J.; Mitchell, James E.

    2005-01-01

    This study's purpose was to examine the extent to which participants (N = 143) receiving cognitive-behavioral therapy for bulimia nervosa (BN) reported implementing therapeutic strategies to abstain from BN behaviors, and to assess whether use of specific strategies predicts outcome at treatment end and 1-and 6-month follow-up. Frequency of…

  10. Strategies for managing aortoiliac occlusions: access, treatment and outcomes

    PubMed Central

    Clair, Daniel G; Beach, Jocelyn M

    2015-01-01

    Treatment of severe aortoiliac disease has dramatically evolved from a dependence on open aortobifemoral grafting to hybrid and endovascular only approaches. Open surgery has been the gold standard treatment of severe aortoiliac disease with excellent patency rates, but with increased length of stay and major complications. In contrast, endovascular interventions can successfully treat almost any lesion with decreased risk, compared to open surgery. Although primary patency rates remain inferior, secondary endovascular interventions are often minor procedures resulting in comparable long-term outcomes. The risks of renal insufficiency, embolization and access complications are not insignificant; however, most can be prevented or managed without significant clinical consequence. Endovascular therapies should be considered a first-line treatment option for all patients with aortoiliac disease, especially those with high-risk cardiovascular comorbidities. PMID:25907618

  11. Mechanical valve obstruction: Review of diagnostic and treatment strategies

    PubMed Central

    Salamon, Jason; Munoz-Mendoza, Jerson; Liebelt, Jared J; Taub, Cynthia C

    2015-01-01

    Prosthetic valve obstruction (PVO) is a rare but feared complication of mechanical valve replacement. Diagnostic evaluation should focus on differentiating prosthetic valve thrombosis (PVT) from pannus formation, as their treatment options differ. History of sub-optimal anti-coagulation and post-op time course to development of PVO are useful clinical characteristics in differentiating thrombus from pannus formation. Treatment of PVT is influenced by the patient’s symptoms, valve location, degree of obstruction and thrombus size and may include thrombolysis or surgical intervention. Alternatively, pannus formation requires surgical intervention. The purpose of this article is to review the pathophysiology, epidemiology, diagnostic approach and treatment options for aortic and mitral valve PVO. PMID:26730292

  12. Behavioral activation: a strategy to enhance treatment response.

    PubMed

    Sudak, Donna M; Majeed, Muhammad H; Youngman, Branden

    2014-07-01

    Behavioral activation is an empirically validated treatment for depression pioneered in 1973 by Ferster, based on B.F. Skinner's behavioral principles. After publication of Beck's work on cognitive therapy, the boundaries of behavioral and cognitive therapies were blurred and the two now overlap substantially. Behavioral activation is also used as a stand-alone treatment and can also be effective in conjunction with antidepressant medication. Case conceptualization in behavioral activation entails an assessment of the behaviors that the patient has stopped that produce pleasure or are of importance, as well as behaviors essential to self-care. Activity monitoring, which provides treatment targets and leads to the case conceptualization in behavioral activation, consists of using charts, forms, or other prompts to track the relationship between activities and other variables (e.g., mood, enjoyment). That technique is also used to target rumination, procrastination, and avoidance and may also be helpful for patients with psychosis. PMID:25036582

  13. [Adherence to psychopharmacological treatment: Psychotherapeutic strategies to enhance adherence].

    PubMed

    Lencer, R; Korn, D

    2015-05-01

    Effective psychopharmacological medication with good tolerability represents the cornerstone of treatment for severe mental illness; however, the 1-year adherence rates are only approximately 50%. The term adherence emphasizes the collaborative responsibility of the clinician and the patient for a positive treatment outcome. Reasons for non-adherence are manifold and include patient-specific factors, such as self-stigmatization, lack of social and familial support, cognitive impairment and substance use besides insufficient effectiveness and the occurrence of side effects of the psychotropic drugs. To enhance adherence, both clinician and patient have to fully understand all the reasons for and against adherence to medication before a collaborative decision is made on future long-term treatment. A positive attitude towards medication critically depends on whether patients feel that the medication supports the attainment of the individual goals. PMID:25903501

  14. Minimising time to treatment: targeted strategies to minimise time to thrombolysis for acute ischaemic stroke.

    PubMed

    Tai, Y J; Yan, B

    2013-11-01

    Time to thrombolysis is a critical determinant of favourable outcomes in acute ischaemic stroke. It is not infrequent that patient outcomes are compromised due to out-of-hospital and in-hospital time delays. On the other hand, time delays could be minimised through the identification of barriers and the implementation of targeted solutions. This review outlines the different strategies in minimising treatment delays and offers recommendations. Literature search in PubMed, Medline and EBSCO Host was conducted to identify studies that are relevant to reduction of time to treatment from January 1995 to December 2012. Strategies to reduce time to thrombolysis are categorised into pre-hospital strategies, in-hospital strategies and post-treatment decision strategies. Proposed pre-hospital strategies include public education on stroke symptoms awareness, prioritising stroke by emergency medical services, increasing ease of access to medical records, pre-hospital notification, and mobile computed tomography scanning. In-hospital strategies include a streamlined code stroke system, computed tomography scanner co-location with emergency department, 24/7 availability of stroke physicians, point-of-care laboratory testing and access to expert neuroimaging interpretation. Post-decision strategies include increasing availability of intravenous thrombolysis and simplification of informed consent procurement. Time to thrombolysis delays is multifactorial. Effective reduction of time delays for acute ischaemic stroke requires the correct identification of and targeted strategies to overcome time barriers. PMID:23734983

  15. Antidepressant Use During Pregnancy: Current Controversies and Treatment Strategies

    PubMed Central

    Payne, Jennifer L.; Meltzer-Brody, Samantha

    2009-01-01

    The treatment of depression during pregnancy is both a common and complex clinical challenge. The decision to expose the fetus to antidepressant medication during pregnancy must be weighed against the risks of untreated maternal depression to both mother and fetus. Maternal depression during pregnancy has been associated with increased rates of preterm birth and maternal substance use. The safety of antidepressant use during pregnancy appears to be largely reassuring but there remain two areas of controversy including neonatal withdrawal syndrome and primary pulmonary hypertension of the newborn (PPHN). Individualized treatment recommendations based on the patient's history are essential in order to optimize outcomes. PMID:19661762

  16. Strategies for Training Counselors in Evidence-Based Treatments

    PubMed Central

    Martino, Steve

    2010-01-01

    Evidence-based treatments (EBTs) for substance abuse and dependence have demonstrated superiority over treatment as usual when applied with strict fidelity in controlled clinical trials. Effective counselor training is critical if substance abuse programs are to realize these interventions’ full potential to enhance client outcomes in community practice. Although few empirical evaluations of training in EBTs have been conducted to date, the existing data warrant tentative conclusions concerning the appropriate roles and effectiveness of workshops, clinical supervision, distance learning, and blended learning. Among several outstanding research issues are questions of benchmarks for counselors’ performance in training and the relationships between such performance and clients’ substance abuse outcomes. PMID:22002451

  17. Glutamatergic treatment strategies for age-related memory disorders.

    PubMed

    Müller, W E; Scheuer, K; Stoll, S

    1994-01-01

    Age-related changes of N-methyl-D-aspartate (NMDA) receptors have been found in cortical areas and in the hippocampus of many species. On the basis of a variety of experimental observations it has been suggested that the decrease of NMDA receptor density might be one of the causative factors of the cognitive decline with aging. Based on these findings several strategies have been developed to improve cognition by compensating the NMDA receptor deficits in aging. The most promising approaches are the indirect activation of glutamatergic neurotransmission by agonists of the glycine site or the restoration of the age-related deficit of receptor density by several nootropics. PMID:7997073

  18. Strategies for the reduction of Legionella in biological treatment systems.

    PubMed

    Nogueira, R; Utecht, K-U; Exner, M; Verstraete, W; Rosenwinkel, K-H

    2016-01-01

    A community-wide outbreak of Legionnaire's disease occurred in Warstein, Germany, in August 2013. The epidemic strain, Legionella pneumophila Serogruppe 1, was isolated from an industrial wastewater stream entering the municipal wastewater treatment plant (WWTP) in Wartein, the WWTP itself, the river Wäster and air/water samples from an industrial cooling system 3 km downstream of the WWTP. The present study investigated the effect of physical-chemical disinfection methods on the reduction of the concentration of Legionella in the biological treatment and in the treated effluent entering the river Wäster. Additionally, to gain insight into the factors that promote the growth of Legionella in biological systems, growth experiments were made with different substrates and temperatures. The dosage rates of silver micro-particles, hydrogen peroxide, chlorine dioxide and ozone and pH stress to the activated sludge were not able to decrease the number of culturable Legionella spp. in the effluent. Nevertheless, the UV treatment of secondary treated effluent reduced Legionella spp. on average by 1.6-3.4 log units. Laboratory-scale experiments and full-scale measurements suggested that the aerobic treatment of warm wastewater (30-35 °C) rich in organic nitrogen (protein) is a possible source of Legionella infection. PMID:27533856

  19. Four treatment strategies for complex regional pain syndrome type 1.

    PubMed

    Lee, Sang Ki; Yang, Dae Suk; Lee, Jae Won; Choy, Won Sik

    2012-06-01

    Complex regional pain syndrome (CRPS) poses a dilemma for many clinicians due to its unknown etiology and largely unsuccessful treatment modalities. The purpose of this study was to compare the clinical results of 4 treatment modalities for CRPS type 1. A total of 59 patients were divided into 4 groups based on treatment modality: group A, an oral nonsteroidal anti-inflammatory drug (NSAID) (n=10); group B, oral gabapentin (n=12); group C, intravenous (IV) 10% mannitol and steroid (n=11); group D, a combination of IV 20% mannitol and steroid with oral gabapentin (n=26). The patients remained under medical supervision after discharge and were evaluated either once a month or once every 2 months until final follow-up at a mean of 8 months. Patients in group A showed improvement in pain level, finger range of motion, swelling, and grip strength, without statistical significance (P=.076, P=.062, P=.312, and P=.804, respectively). Patients in group B showed significant improvement in pain level (P<.001), and patients in group C showed improvement in pain, finger range of motion, and swelling (P=.127), which rendered functional impairment unchanged. In comparison, patients in group D showed recovery of grip strength and improvement in pain level, finger range of motion, and (P<.001, P=.016, P=.031, and P=.047, respectively). Based on these results, a protocol including a combination of IV 20% mannitol and steroid with oral gabapentin is an acceptable and effective treatment for CRPS type 1. PMID:22691654

  20. Anti-inflammatory strategies in the treatment of schizophrenia.

    PubMed

    Andrade, Chittaranjan

    2016-01-01

    Schizophrenia is a major mental illness with a lifetime prevalence of about 1%. Antipsychotic drugs, with a primary mechanism of action that involves dopamine receptor blockade, are the mainstay in the treatment of the disorder. However, despite optimum antipsychotic treatment, few patients return to pre-morbid levels; the treatment deficit includes refractory positive symptoms, negative symptoms, mood impairments, cognitive impairments, social impairments, and/or a variety of medication-related adverse effects, including extrapyramidal symptoms, metabolic disturbances, hyperprolactinemia, and others. To address these, antipsychotic treatment has been augmented with psychosocial interventions, cognitive rehabilitation, different kinds of electrical and magnetic brain stimulation, and a large range of drugs from the neuropsychiatric as well as, surprise, the general medical pharmacopeia. The pleomorphic pathophysiology of schizophrenia includes abnormalities in immunological and inflammatory pathways, and so it is not surprising that anti-inflammatory drugs have also been trialed as augmentation agents in schizophrenia. This article critically examines the outcomes after augmentation with conventional anti-inflammatory interventions; results from randomized controlled trials do not encourage the use of either aspirin (1000 mg/day) or celecoxib (400 mg/day), both of which have been studied for this indication during the past decade and a half. PMID:26427750

  1. VETERINARY PHARMACEUTICALS: POTENTIAL ENVIRONMENTAL IMPACT AND TREATMENT STRATEGIES

    EPA Science Inventory

    In the late 1970s it was recognized that there were increasing occurrences of antibiotic-resistant organisms in Europe and the US. Even in the early stages, concerns were raised that large-scale treatment of farm animals for infectious disease as well as growth enhancement may be...

  2. Current Treatment Strategies for Castration-Resistant Prostate Cancer

    PubMed Central

    Kim, Sun Il

    2011-01-01

    Prostate cancer is the most common cancer in men in United States and the fifth most common cancer in men in Korea. Although the majority of patients with metastatic prostate cancer initially respond to androgen deprivation therapy, almost all patients will eventually progress to develop castration-resistant prostate cancer (CRPC). Treatment options for CRPC remain limited. Prostate cancer was considered unresponsive to chemotherapy until the mid-1990s, when mitoxantrone combined with prednisone was shown to play a role in the palliative treatment of patients with CRPC. In 2004, two large randomized clinical trials demonstrated for the first time a small but significant survival advantage of docetaxel-based chemotherapy compared with mitoxantrone in patients with metastatic CRPC. Recently, cabazitaxel was shown to improve survival in patients with metastatic CRPC who progressed after docetaxel-based chemotherapy. Sipuleucel-T was also demonstrated to improve overall survival in patients with asymptomatic or minimally symptomatic metastatic CRPC. Along with mitoxantrone and docetaxel, cabazitaxel and sipuleucel-T are now approved for use in metastatic CRPC by the US Food and Drug Administration. There have been multiple early-phase clinical trials of various agents for the treatment of CRPC, and some are in phase III development. This review focuses on the key clinical trials of various treatment options of CRPC currently in use and under investigation. PMID:21461278

  3. Self-Injurious Behavior: Characteristics and Innovative Treatment Strategies

    ERIC Educational Resources Information Center

    Dykes, Michelle; Specian, Victoria; Nelson, Meredith; Gray, Neal

    2006-01-01

    Self-injurious behavior is the intentional harming of one's own body. Little attention has been given to SIB in the past, particularly in terms of innovative treatment approaches. Adolescents are at a particularly high-risk for developing this ineffectual coping mechanism. School counselors are in a unique position to aid in the identification of…

  4. Rational-Emotive Therapy with Children and Adolescents: Treatment Strategies.

    ERIC Educational Resources Information Center

    Bernard, Michael E.

    1990-01-01

    Presents rational-emotive therapy (RET) conceptualization of childhood disorders, discussing interaction of child temperament and parenting styles. Discusses RET child treatment goals, which involve modification of negative and inappropriate childhood emotions. Illustrates particular RET cognitive change methods (philosophical disputation;…

  5. Orgasm During Intercourse: A Treatment Strategy for Women

    ERIC Educational Resources Information Center

    Zeiss, Antonette M.; And Others

    1977-01-01

    A six-step treatment program for women who are inorgasmic during intercourse is described. Teaches women to associate orgasms brought on by manual clitoral stimulation with arousing thoughts about intercourse and vaginal containment of a dildo. Learning is generalized to vaginal containment of the partner's penis and thrusting movements. (Author)

  6. A Medication Combination for the Treatment of Central Poststroke Pain via the Adjuvant Use of Prednisone With Gabapentin: A Case Report.

    PubMed

    Batlle, Luis; Mattie, Ryan; Irwin, Robert

    2016-03-01

    Central poststroke pain is a neuropathic pain syndrome that can occur from pathology of the brain. The case presented is of a woman with multiple comorbidities who was found to have an acute infarct in the left middle and anterior cerebral artery territories. She began to complain of worsening diffuse right upper and lower extremity pain, and central poststroke pain was diagnosed. First-line agents were contraindicated as the result of medical comorbidities, and chronic kidney disease only permitted the use of low-dose gabapentin. The patient's morbid obesity inspired the use of an adjunct medication protocol of a prednisone taper for proper treatment. After starting this treatment regimen, the patient experienced significant pain relief with eventual resolution. A steroid-based treatment protocol was used successfully in the early stages of central poststroke pain with proper side effect management and may have prevented difficult treatment management in the outpatient setting. PMID:26409194

  7. Impact of three empirical tuberculosis treatment strategies for people initiating antiretroviral therapy

    PubMed Central

    Van Rie, Annelies; Westreich, Daniel; Sanne, Ian

    2016-01-01

    Background Early mortality in people initiating antiretroviral treatment (ART) in Africa remains high. Empiric TB treatment strategies aim to reduce early mortality by initiating TB treatment in individuals without clinical suspicion of TB who are at high-risk of death from undiagnosed TB. Methods Using data from 16,913 individuals starting ART under programmatic conditions, we simulated the impact of three empiric treatment strategies on mortality and incident TB: two randomized clinical trials (REMEMBER and PrOMPT) and a pragmatic approach. The main analysis assumed that 50% of early deaths and 100% of incident TB is averted in those eligible and ignored outcomes in those lost to follow up. Results The increase in individuals eligible for TB treatment under empirical TB treatment strategies ranged from 4.4% to 31.4% as compared to those started on clinical or mycobacteriological grounds. The proportion of deaths averted by empiric treatment strategies ranged from 5.5% to 25.4%. The proportion of incident TB cases averted ranged from 10.9% to 57.3%. The proportion receiving any TB treatment during the first six months of ART increased from the observed 24.0% to an estimated 27.5%, 40.4% and 51.3% under the PrOMPT, REMEMBER and pragmatic approach, respectively. Conclusion The impact of empiric TB treatment strategies depends greatly on the eligibility criteria chosen. The additional strain placed on TB treatment facilities and the relatively limited impact of some empirical TB strategies raise the question whether the benefits will outweigh the risks at population level. PMID:25299868

  8. Treatment Strategy after Incomplete Endoscopic Resection of Early Gastric Cancer

    PubMed Central

    Kim, Sang Gyun

    2016-01-01

    Endoscopic resection of early gastric cancer is defined as incomplete when tumor cells are found at the resection margin upon histopathological examination. However, a tumor-positive resection margin does not always indicate residual tumor; it can also be caused by tissue contraction during fixation, by the cautery effect during endoscopic resection, or by incorrect histopathological mapping. Cases of highly suspicious residual tumor require additional endoscopic or surgical resection. For inoperable patients, argon plasma coagulation can be used as an alternative endoscopic treatment. Immediately after the incomplete resection or residual tumor has been confirmed by the pathologist, clinicians should also decide upon any additional treatment to be carried out during the follow-up period. PMID:27435699

  9. Treatment Strategy after Incomplete Endoscopic Resection of Early Gastric Cancer.

    PubMed

    Kim, Sang Gyun

    2016-07-01

    Endoscopic resection of early gastric cancer is defined as incomplete when tumor cells are found at the resection margin upon histopathological examination. However, a tumor-positive resection margin does not always indicate residual tumor; it can also be caused by tissue contraction during fixation, by the cautery effect during endoscopic resection, or by incorrect histopathological mapping. Cases of highly suspicious residual tumor require additional endoscopic or surgical resection. For inoperable patients, argon plasma coagulation can be used as an alternative endoscopic treatment. Immediately after the incomplete resection or residual tumor has been confirmed by the pathologist, clinicians should also decide upon any additional treatment to be carried out during the follow-up period. PMID:27435699

  10. Nanomedicine strategies for treatment of secondary spinal cord injury

    PubMed Central

    White-Schenk, Désirée; Shi, Riyi; Leary, James F

    2015-01-01

    Neurological injury, such as spinal cord injury, has a secondary injury associated with it. The secondary injury results from the biological cascade after the primary injury and affects previous uninjured, healthy tissue. Therefore, the mitigation of such a cascade would benefit patients suffering a primary injury and allow the body to recover more quickly. Unfortunately, the delivery of effective therapeutics is quite limited. Due to the inefficient delivery of therapeutic drugs, nanoparticles have become a major field of exploration for medical applications. Based on their material properties, they can help treat disease by delivering drugs to specific tissues, enhancing detection methods, or a mixture of both. Incorporating nanomedicine into the treatment of neuronal injury and disease would likely push nanomedicine into a new light. This review highlights the various pathological issues involved in secondary spinal cord injury, current treatment options, and the improvements that could be made using a nanomedical approach. PMID:25673988

  11. Alcoholic liver disease. Treatment strategies for the potentially reversible stages.

    PubMed

    Hill, D B; Kugelmas, M

    1998-04-01

    Even modest alcohol ingestion can increase the risk of steatosis, and long-term, excessive consumption can lead to alcoholic hepatitis and eventually cirrhosis. Most patients with clinically significant alcoholic liver disease have histologic findings typical of all three conditions. The only clearly beneficial treatment is abstinence from alcohol. Abstinence in combination with proper nutrition and general supportive care is state of the art. Steatosis is reversible upon withdrawal of alcohol, but alcoholic hepatitis can persist even with abstinence and may progress to cirrhosis. Corticosteroid therapy may reduce short-term mortality rates in patients with moderate or severe alcoholic hepatitis who have hepatic encephalopathy but no evidence of infection or gastrointestinal bleeding. Treatment with colchicine may decrease the risk of cirrhosis; however, once cirrhosis has developed, the liver damage is irreversible. The prognosis is improved with abstinence, but complications (e.g., ascites, gastrointestinal bleeding) often occur. Liver transplantation may be considered in patients with severe complications. PMID:9553600

  12. Leachate pre-treatment strategies before recirculation in landfill bioreactors.

    PubMed

    Vigneron, V; Bouchez, T; Bureau, C; Mailly, N; Mazeas, L; Duquennoi, C; Audic, J M; Hébé, L; Bernet, N

    2005-01-01

    Nitrified leachate recirculation represents a promising strategy for a more sustainable landfill management. Our objective was to determine the reactions involved in nitrate reduction in municipal solid waste batch biodegradation tests. Anaerobic digestion of waste in the three control reactors showed a good reproducibility. In two test reactors, nitrate was added at various moments of the waste degradation process. We observed that: (1) H2S concentration controlled the nitrate reduction pathway: above a certain threshold of H2S, dissimilatory nitrate reduction to ammonium (DNRA) replaced denitrification. (2) N2O/N2 ratio varied with the organic carbon concentration: the lower the easily biodegradable carbon concentration, the higher the N2O/N2 ratio. (3) N2 was consumed after denitrification. The possibility of a nitrogen fixation reaction in the presence of NH4 is discussed. Nitrified leachate recirculation during acidogenesis should be avoided because of higher H2S production which could induce DNRA. PMID:16180441

  13. Classification of Laser Vaccine Adjuvants

    PubMed Central

    Kashiwagi, Satoshi; Brauns, Timothy; Poznansky, Mark C

    2016-01-01

    An immunologic adjuvant, which enhances the magnitude and quality of immune responses to vaccine antigens, has become an essential part of modern vaccine practice. Chemicals and biologicals have been typically used for this purpose, but there are an increasing number of studies that are being conducted on the vaccine adjuvant effect of laser light on the skin. Currently, four different types or classes of laser devices have been shown to systemically enhance immune responses to intradermal vaccination: ultra-short pulsed lasers, non-pulsed lasers, non-ablative fractional lasers and ablative fractional lasers. Aside from involving the application of laser light to the skin in a manner that minimizes discomfort and damage, each type of laser vaccine adjuvant involves emission parameters, modes of action and immunologic adjuvant effects that are quite distinct from each other. This review provides a summary of the four major classes of “laser vaccine adjuvant” and clarifies and resolves their characteristics as immunologic adjuvants. These aspects of each adjuvant’s properties will ultimately help define which laser would be most efficacious in delivering a specific clinical benefit with a specific vaccine. PMID:27104047

  14. Overactive bladder: strategies to ensure treatment compliance and adherence

    PubMed Central

    Dhaliwal, Prabhpreet; Wagg, Adrian

    2016-01-01

    Overactive bladder is a common, debilitating condition for many patients who may benefit from pharmacological management of their condition. However, adherence to medication in this condition is markedly worse than other chronic medical conditions. This review explores what is known about persistence and the factors which influence medication adherence for overactive bladder, those factors that might be modifiable to improve adherence, and the measures the health care provider can take to optimize adherence to therapy and thereby improve treatment outcomes. PMID:27350744

  15. [Prevention and treatment strategy for burn wound sepsis in children].

    PubMed

    Niu, Xihua; Li, Xiaoling

    2016-02-01

    Wound sepsis is one of the main causes of death in patients with severe burn and trauma. The high incidence of burn wound sepsis in children is attributed to their imperfect immune system function, poor resistance against infection, and the weakened skin barrier function after burn. The key to reduce the mortality of pediatric patients with burn wound sepsis is to enhance the understanding of its etiology, epidemiology, pathogenesis, and diagnostic criteria, in order to improve its early diagnosis and treatment. PMID:26902271

  16. New and improved strategies for the treatment of gout

    PubMed Central

    Dubchak, Natalie; Falasca, Gerald F

    2010-01-01

    The Western world appears to be in the midst of the third great gout epidemic of all time. In this century, gout is increasing in prevalence despite an increased understanding of its risk factors and pathophysiology, and the availability of reasonably effective treatment. The main cultural factors responsible for this appear to be diet, obesity, ethanol use and medications. Excess fructose consumption is a newly recognized modifiable risk factor. The debate has been renewed concerning hyperuricemia as an independent risk factor for renal insufficiency and cardiovascular disease. Prevention is still rooted in lifestyle choices. Existing treatments have proven to be unsatisfactory in many patients with comorbidities. New treatments are available today and on the horizon for tomorrow, which offer a better quality of life for gout sufferers. These include febuxostat, a nonpurine inhibitor of xanthine oxidase with a potentially better combination of efficacy and safety than allopurinol, and investigational inhibitors of URAT-1, an anion exchanger in the proximal tubule that is critical for uric acid homeostasis. New abortive treatments include interleukin-1 antagonists that can cut short the acute attack in 1 to 2 days in persons who cannot take nonsteroidal anti-inflammatory drugs, colchicine or corticosteroids. Lastly, newer formulations of uricase have the ability to dissolve destructive tophi over weeks or months in patients who cannot use currently available hypouricemic agents. Diagnostically, ultrasound and magnetic resonance imaging offer advanced ways to diagnose gout noninvasively, and just as importantly, a way to follow the progress of tophus dissolution. The close association of hyperuricemia with metabolic syndrome, hypertension and renal insufficiency ensures that nephrologists will see increasing numbers of gout-afflicted patients. PMID:21694941

  17. [The modern strategies for the treatment of allergic rhinitis].

    PubMed

    Nosulya, E V; Kim, I A

    2016-01-01

    The present literature review had the objective to analyze the published data concerning the effectiveness of intranasal administration of antihistamine preparations and intranasal glucocorticoids for the treatment of allergic rhinitis. Special emphasis is placed on the clinical significance and the further prospects for the application of a fixed combination of these medications including azelastineplusmometasonefuroateas the first choice therapy of moderately severe and severe manifestations of allergic rhinitis. PMID:27213663

  18. Adjuvant chemotherapy for soft tissue sarcoma.

    PubMed

    Casali, Paolo G

    2015-01-01

    Adjuvant chemotherapy is not standard treatment in soft tissue sarcoma (STS). However, when the risk of relapse is high, it is an option for shared decision making with the patient in conditions of uncertainty. This is because available evidence is conflicting, even if several randomized clinical trials have been performed for 4 decades and also have been pooled into meta-analyses. Indeed, available meta-analyses point to a benefit in the 5% to 10% range in terms of survival and distant relapse rate. Some local benefit also was suggested by some trials. Placing chemotherapy in the preoperative setting may help gain a local advantage in terms of the quality of surgical margins or decreased sequelae. This may be done within a personalized approach according to the clinical presentation. Attempts to personalize treatment on the basis of the variegated pathology and molecular biology of STS subgroups are ongoing as well, according to what is done in the medical treatment of advanced STS. Thus, decision making for adjuvant and neoadjuvant indications deserves personalization in clinical research and in clinical practice, taking profit from all multidisciplinary clinical skills available at a sarcoma reference center, though with a degree of subjectivity because of the limitations of available evidence. PMID:25993233

  19. The role of adjuvant chemotherapy in nasopharyngeal carcinoma with bulky neck lymph nodes in the era of IMRT

    PubMed Central

    Xu, Tingting; Shen, Chunying; Ou, Xiaomin; He, Xiayun; Ying, Hongmei; Hu, Chaosu

    2016-01-01

    Nasopharyngeal carcinoma (NPC) patients with N2–3 diseases are prone to develop distant metastasis even treated with standard concurrent chemoradiotherapy (CCRT). Our study is aim to determine the optimal treatment strategy of these patients. Patients with histologically proven NPC were retrospectively analyzed according to the AJCC 2002 stage classification system. A total of 547 patients who had N2–3 diseases were enrolled. They were all treated with Intensity-modulated radiation therapy (IMRT) combined with systemic treatments, including radiotherapy alone (RT alone), neoadjuvant chemotherapy followed by radiotherapy (NACT+RT), CCRT, NACT+CCRT, NACT followed by radiotherapy and adjuvant chemotherapy (NACT+RT+AC), CCRT+AC and NACT+CCRT+AC. A subgroup analysis was also conducted. With a median follow-up time of 53.8 months, adjuvant chemotherapy significantly decreased the risk of distant metastasis (HR 0.413, 95% CI 0.194–0.881, p = 0.022) as well as significantly increased the OS (HR 0.398, 95% CI 0.187–0.848, p = 0.017) in patients with N3 disease. The addition of adjuvant chemotherapy seemed to provide benefits to patients with N3 stage NPC and the current study may indicate the need for further randomized investigation. PMID:26942700

  20. The role of adjuvant chemotherapy in nasopharyngeal carcinoma with bulky neck lymph nodes in the era of IMRT.

    PubMed

    Xu, Tingting; Shen, Chunying; Ou, Xiaomin; He, Xiayun; Ying, Hongmei; Hu, Chaosu

    2016-04-12

    Nasopharyngeal carcinoma (NPC) patients with N2-3 diseases are prone to develop distant metastasis even treated with standard concurrent chemoradiotherapy (CCRT). Our study is aim to determine the optimal treatment strategy of these patients. Patients with histologically proven NPC were retrospectively analyzed according to the AJCC 2002 stage classification system. A total of 547 patients who had N2-3 diseases were enrolled. They were all treated with Intensity-modulated radiation therapy (IMRT) combined with systemic treatments, including radiotherapy alone (RT alone), neoadjuvant chemotherapy followed by radiotherapy (NACT+RT), CCRT, NACT+CCRT, NACT followed by radiotherapy and adjuvant chemotherapy (NACT+RT+AC), CCRT+AC and NACT+CCRT+AC. A subgroup analysis was also conducted. With a median follow-up time of 53.8 months, adjuvant chemotherapy significantly decreased the risk of distant metastasis (HR 0.413, 95% CI 0.194-0.881, p = 0.022) as well as significantly increased the OS (HR 0.398, 95% CI 0.187-0.848, p = 0.017) in patients with N3 disease. The addition of adjuvant chemotherapy seemed to provide benefits to patients with N3 stage NPC and the current study may indicate the need for further randomized investigation. PMID:26942700

  1. Spontaneous fractures of the mandible concept & treatment strategy

    PubMed Central

    Marcussen, Mette

    2016-01-01

    Background Spontaneous fractures of the mandible dispose a surgical challenge in comparisons to fractures caused by trauma due to several complicating factors. Additionally: controversies exist concerning the terminology of the field. Material and Methods We conducted a retrospective study of all patients with mandibular fractures, with exclusion of fractures of the coronoid process and the alveolar process, treated at the Department of Oral and Maxillofacial Surgery, Aalborg University Hospital, Denmark between February 2003 and February 2013. Data collected from the medical records included sex, age, cause of fracture, site of fracture, and treatment. Results We identified 517 patients with 684 mandible fractures. Twenty-five of these were spontaneous fractures and 659 fractures were of traumatic origin. Condylar fractures rarely occur spontaneously, but constitute the majority of the traumatic fractures. Excluding these fractures from the analysis, we found a non-surgical approach in 14 of 24 (58%) of the spontaneous fractures and 110 of 376 (29%) of the traumatic fractures. This was statistically significant. Conclusions We found a statistical significant difference in favor of non-surgical approach in spontaneous fractures and we discussed the treatment challenges of these fractures. We addressed the terminological controversies regarding pathological fractures, and suggested the term spontaneous fractures denoting a fracture occurring during normal jaw function being either pathological or non-pathological. Key words:Mandibular fractures, spontaneous fractures, pathological fractures, traumatic fractures, treatment. PMID:26636905

  2. Treatment strategy in schizophrenia combined with eating disorder.

    PubMed

    Dadić-Hero, Elizabeta; Ružić, Klementina; Grahovac, Tanja; Valković, Toni; Petranović, Duška

    2011-03-01

    Like any other patient, a schizophrenic patient can get a physical illness, too. As such patients tend to ignore reality and neglect themselves and are stigmatized by society, due to which their physical symptomatology is often ignored, physical illness can remain undetected. If the schizophrenic patient is observed and adequate care is provided by the family, family doctor and a psychiatrist, it is possible to recognize the physical illness and intervene promptly. We are presenting a case of a female patient who has been treated for schizophrenia for a number of years. The treatment was mostly ambulatory (i.e. the patient was hospitalized twice) and consisted of first-generation antipsychotics. During the past two years, for reasons unknown, the patient stopped taking regular meals and as a result lost significant body weight, became apathetic and withdrawn, started avoiding social contacts and neglected personal hygiene. She reportedly took the psychopharmaca regularly, but rarely attended psychiatric follow-up consultations. Due to substantial weight loss and hypotonia, correction of antipsychotic was made and internist treatment administered. The choice of olanzapine was not an accidental one. We decided to take advantage of its side effect for the treatment of an anorectic syndrome. Interdisciplinary cooperation proved to be a justified decision. PMID:21448107

  3. Antifungal agents for onychomycosis: new treatment strategies to improve safety.

    PubMed

    Zane, Lee T; Chanda, Sanjay; Coronado, Dina; Del Rosso, James

    2016-01-01

    Onychomycosis is a common and difficult-to-treat fungal infection of the nail unit that gradually leads to dystrophic changes of the nail plate and nail bed. If untreated, infection progresses and may lead to discomfort, reduced quality of life, and risk of complications in patients with comorbid conditions (eg, diabetes, human immunodeficiency virus, peripheral vascular disease). Onychomycosis treatments are designed to eradicate causative pathogens (most commonly Trichophyton rubrum and Trichophyton mentagrophytes), restore healthy nails, and prevent recurrence or spread of infection. Given the deep-seated nature of most cases of onychomycosis, an effective antifungal agent needs to achieve and maintain sufficient drug concentrations throughout the nail unit for the duration of healthy nail in-growth. Oral antifungal drugs are the most effective available therapy and are generally well tolerated, but may be limited by safety concerns and the potential for drug-drug interactions (DDIs). Thus, treating physicians and pharmacists must be cognizant of a patient's current medications; indeed, it may not be feasible to treat onychomycosis in patients with diabetes, heart disease, or depression because of the risk for DDIs. Current topical therapy is not associated with risk of DDIs. Tavaborole and efinaconazole, two recently approved topical agents, have demonstrated good nail penetration and high negative culture rates in clinical trials of patients with onychomycosis. This article provides the treating physician and pharmacist with information on the safety and effectiveness of current oral (allylamine, azole) and topical (ciclopirox, efinaconazole, tavaborole) treatment to aid in making informed treatment decisions based on the unique characteristics (medication history, comorbidities, nature of onychomycosis) of each patient. PMID:27136621

  4. Semantic Feature Analysis: Incorporating Typicality Treatment and Mediating Strategy Training to Promote Generalization

    ERIC Educational Resources Information Center

    Wambaugh, Julie L.; Mauszycki, Shannon; Cameron, Rosalea; Wright, Sandra; Nessler, Christina

    2013-01-01

    Purpose: This investigation was designed to examine the generalization effects of semantic treatment for word retrieval deficits in people with aphasia. Semantic feature analysis (SFA; Boyle & Coelho, 1995), typicality treatment (Kiran & Thompson, 2003), and mediating strategy training were combined to maximize potential generalization effects.…

  5. Recommended treatment strategies for patients with excessive daytime sleepiness.

    PubMed

    Rosenberg, Russell P

    2015-10-01

    Excessive daytime sleepiness (EDS) is a common and bothersome phenomenon. It can be associated with insufficient sleep syndrome, narcolepsy, idiopathic hypersomnia, obstructive sleep apnea, shift work disorder, Kleine-Levin syndrome, or Parkinson's disease. Once the underlying cause of the excessive sleepiness is determined, clinicians must select the most appropriate behavioral and pharmacologic interventions to reduce daytime sleepiness, alleviate other symptoms, improve functioning, and ensure the safety of patients and those around them. Patient history, adverse effects, and efficacy in specific conditions should be considered in pharmacologic treatment options for patients with EDS. PMID:26528660

  6. Impetigo and scabies - Disease burden and modern treatment strategies.

    PubMed

    Yeoh, Daniel K; Bowen, Asha C; Carapetis, Jonathan R

    2016-07-01

    Impetigo and scabies both present different challenges in resource-limited compared with industrialised settings. Severe complications of these skin infections are common in resource-limited settings, where the burden of disease is highest. The microbiology, risk factors for disease, diagnostic approaches and availability and suitability of therapies also vary according to setting. Taking this into account we aim to summarise recent data on the epidemiology of impetigo and scabies and describe the current evidence around approaches to individual and community based treatment. PMID:27180311

  7. Therapeutic Strategies for the Treatment of Severe Cushing's Syndrome.

    PubMed

    Alexandraki, Krystallenia I; Grossman, Ashley B

    2016-03-01

    Severe Cushing's syndrome presents an acute emergency and is defined by massively elevated random serum cortisol [more than 36 μg/dL (1000 nmol/L)] at any time or a 24-h urinary free cortisol more than fourfold the upper limit of normal and/or severe hypokalaemia (<3.0 mmol/L), along with the recent onset of one or more of the following: sepsis, opportunistic infection, intractable hypokalaemia, uncontrolled hypertension, heart failure, gastrointestinal haemorrhage, glucocorticoid-induced acute psychosis, progressive debilitating myopathy, thromboembolism or uncontrolled hyperglycaemia and ketocacidosis. Treatment focuses on the management of the severe metabolic disturbances followed by rapid resolution of the hypercortisolaemia, and subsequent confirmation of the cause. Emergency lowering of the elevated serum cortisol is most rapidly achieved with oral metyrapone and/or ketoconazole; if parenteral therapy is required then intravenous etomidate is rapidly effective in almost all cases, but all measures require careful supervision. The optimal order and combination of drugs to treat severe hypercortisolaemia-mostly in the context of ectopic ACTH-secreting syndrome, adrenocortical carcinoma or an ACTH-secreting pituitary adenoma (mainly macroadenomas)-is not yet established. Combination therapy may be useful not only to rapidly control cortisol excess but also to lower individual drug dosages and consequently the possibility of adverse effects. If medical treatments fail, bilateral adrenalectomy should be performed in the shortest possible time span to prevent the debilitating complications of uncontrolled hypercortisolaemia. PMID:26833215

  8. Strategy for the treatment of Helicobacter pylori infection.

    PubMed

    Shiota, Seiji; Yamaoka, Yoshio

    2014-01-01

    The eradication of Helicobacter pylori not only heals peptic ulcers but also prevents their recurrence and reduces the risk of development of gastric cancer and other H. pylori-associated disorders. H. pylori eradication heals gastritis and may prevent the spread of infection, reducing the future costs required for the treatment of subsequent H. pylori-associated diseases. There are various guidelines for the management of H. pylori infection worldwide, such as the guidelines of the American College of Gastroenterology, Maastricht IV, the Second Asia-Pacific Consensus Conference, and Japan. The Japanese health insurance system approved H. pylori eradication therapy for H. pylori-related chronic gastritis in 2013. Triple therapy regimens comprising 1 proton pump inhibitor and 2 antimicrobial agents such as amoxicillin, clarithromycin, metronidazole, levofloxacin, or tetracycline have been widely used to eradicate this bacterium. The rate of successful eradication has declined owing to the increased rate of drug resistance stemming from the wide usage of antibiotics. This issue is of particular relevance with regard to clarithromycin. In worldwide, clarithromycin-based triple therapy should be abandoned, as it is no longer effective. Quadruple therapy and sequential therapy are reasonable alternatives for initial therapy. First-line treatment should be recommended on the basis of an understanding of the local prevalence of H. pylori antimicrobial resistance. PMID:24180402

  9. Current management strategies and emerging treatments for functional dyspepsia.

    PubMed

    Camilleri, Michael; Stanghellini, Vincenzo

    2013-03-01

    Functional dyspepsia refers to painful and nonpainful symptoms that are perceived to arise in the upper digestive tract but are not secondary to organic, systemic or metabolic diseases. The symptoms of this syndrome often overlap with those of GERD and IBS, making its management far from simple. If Helicobacter pylori infection is diagnosed in patients with functional dyspepsia, it should be treated. In patients with mild or intermittent symptoms, reassurance and lifestyle advice might be sufficient; in patients not responding to these measures, or in those with more severe symptoms, drug therapy should be considered. Both PPIs and prokinetics can be used in initial empirical pharmacotherapy based on symptom patterns--a PPI is more likely to be effective in the presence of retrosternal or epigastric burning or epigastric pain, whereas a prokinetic is more effective in dyspepsia with early satiation or postprandial fullness. Although combinations of PPIs and prokinetics might have additive symptomatic effects, single-drug therapy is initially preferable. Antidepressants or referral to a psychiatrist or psychotherapist can be considered in nonresponders and in those whose symptoms have a marked effect on daily functioning. Despite extensive research, functional dyspepsia treatment often remains unsatisfactory. Better characterization of dyspeptic subgroups and understanding of underlying mechanisms will enable treatment advances to be made in the future. PMID:23381190

  10. New Strategies in the Treatment of Multiple Myeloma

    PubMed Central

    Munshi, Nikhil C.; Anderson, Kenneth C.

    2014-01-01

    Multiple myeloma (MM) is the second most common hematologic malignancy affecting terminally differentiated plasma cells. Although high-dose chemotherapy and autologous stem cell transplantation improved survival in younger patients, the natural history of MM has been changed with the availability of five new agents approved in last 10 years (thalidomide, bortezomib, lenalidomide, liposomal doxorubicin and carfilzomib). Despite this significant improvement in overall outcome, MM remains incurable in majority of patients prompting continued search for additional therapeutic options. Extensive molecular and genomic characterization of MM cells in its bone marrow milieu, which affects myeloma cell growth and survival, has provided number of novel drugable targets and pathways. Perturbation of protein catabolism at multiple levels has become an important target in MM. Similarly with improvements in monoclonal antibody generation and vaccine development along with identification of number of cell surface and cellular targets have led to development of various strategies including antibodies and antibody-drug conjugates which are under investigation both preclinically as well as in early clinical studies. We propose that eventually, molecularly-informed multi-agent combination therapies will be required to eliminate the MM cell clone for a long-term disease control. PMID:23515406

  11. Pharmacological treatments and strategies for reducing oral and intestinal acetaldehyde.

    PubMed

    Salaspuro, Ville

    2007-01-01

    Strong epidemiological, genetic and biochemical evidence indicates that local acetaldehyde exposure is a major factor behind gastrointestinal cancers especially associated with alcohol drinking and smoking. Thus, reducing the exposure to carcinogenic acetaldehyde either by decreasing the production or by eliminating acetaldehyde locally might offer a preventive strategy against acetaldehyde-induced gastrointestinal cancers. Thiol products, such as the amino acid cysteine, are known to be able to protect against acetaldehyde toxicity. Cysteine is able to bind acetaldehyde efficiently by forming a stable thiazolidine-carboxylic acid compound. Special cysteine preparations (such as lozenge and chewing gum) have already been developed to bind smoking and alcohol drinking derived acetaldehyde from the oral cavity. Most importantly, these type of drug formulations offer a novel method for intervention studies aimed to resolve the eventual role of acetaldehyde in the pathogenesis of upper digestive tract cancers. Acetaldehyde exposure could also be influenced by modifying the acetaldehyde producing microbiota. With regard to the upper digestive tract, acetaldehyde production from ingested ethanol could be significantly reduced by using an antiseptic mouthwash, chlorhexidine. In the large intestine acetaldehyde production could be markedly decreased either by reducing the Gram-negative microbes by ciprofloxacin antibiotic or by lowering the intraluminal pH by lactulose. PMID:17590993

  12. Use of gentamicin sulfate-impregnated sponges as adjuvant therapy for the treatment of chronic foreign body associated sternal osteomyelitis in a dog

    PubMed Central

    Wainberg, Shannon H.; Brisson, Brigitte A.; Hayes, Galina M.; Mackenzie, Shawn

    2015-01-01

    A 2-year-old Labrador retriever dog was referred for evaluation of parasternal chronic draining sinus tracts associated with sternal osteomyelitis secondary to the presence of a residual wooden foreign body. The use of gentamicin-impregnated collagen sponges as adjunctive therapy to osteomyelitis treatment is reported herein. PMID:26538672

  13. Effectiveness of a back care pillow as an adjuvant physical therapy for chronic non-specific low back pain treatment: a randomized controlled trial

    PubMed Central

    Prommanon, Bundit; Puntumetakul, Rungthip; Puengsuwan, Punnee; Chatchawan, Uraiwan; Kamolrat, Torkamol; Rittitod, Theera; Yamauchi, Junichiro

    2015-01-01

    [Purpose] The aim of this study was to investigate the effect of a back care pillow (BCP) on pain, lumbar range of motion (LROM) and functional disability of patients with chronic non-specific low back pain (LBP). [Subjects and Methods] Fifty-two subjects who were aged between 20–69 years old, who presented with LBP of more than 3 months duration with a numerical rating scale (NRS) value of at least 4 were randomly assigned to treatment (BCP) and control (CON) groups. Participants in each group received six sessions of the 30 minutes treatment for two weeks. The BCP group was asked to wear the BCP during the daytime during the study period. Pain, lumbar ROM and functional disability were assessed before and after the 2-week treatment, and at the end of a 12-week follow up. [Results] After the 2-week treatment and 12-week follow up, all outcomes had improved in both groups; the BCP group had maintained the decrease in pain intensity and improved lumbar ROM in the extension position after the 12-week follow up, and showed better improvements in all outcomes at 2 weeks and after the 12-week follow up. [Conclusion] BCP combined with physical therapy had better pain, lumbar ROM and functional disability outcomes than physical therapy alone. PMID:26311921

  14. Effect of particulate adjuvant on the anthrax protective antigen dose required for effective nasal vaccination.

    PubMed

    Bento, Dulce; Staats, Herman F; Borges, Olga

    2015-07-17

    Successful vaccine development is dependent on the development of effective adjuvants since the poor immunogenicity of modern subunit vaccines typically requires the use of potent adjuvants and high antigen doses. In recent years, adjuvant formulations combining both immunopotentiators and delivery systems have emerged as a promising strategy to develop effective and improved vaccines. In this study we investigate if the association of the mast cell activating adjuvant compound 48/80 (C48/80) with chitosan nanoparticles would promote an antigen dose sparing effect when administered intranasally. Even though the induction of strong mucosal immunity required higher antigen doses, incorporation of C48/80 into nanoparticles provided significant dose sparing when compared to antigen and C48/80 in solution with no significant effect on serum neutralizing antibodies titers. These results suggest the potential of this novel adjuvant combination to improve the immunogenicity of a vaccine and decrease the antigen dose required for vaccination. PMID:26087299

  15. Chemokines as Cancer Vaccine Adjuvants

    PubMed Central

    Bobanga, Iuliana D.; Petrosiute, Agne; Huang, Alex Y.

    2013-01-01

    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. PMID:24967094

  16. Transoral treatment strategies for head and neck tumors

    PubMed Central

    Arens, Christoph

    2012-01-01

    The introduction of transoral endoscopic surgery has initiated a fundamental change in the treatment of head and neck cancer. The endoscopic approach minimizes the intraoperative trauma. Due to the lower burden for the patient and the savings potential these methods have gained wide acceptance. These transoral accesses routes allow experienced surgeons to reduce the morbidity of surgical resection with no deterioration of oncologic results. This suggests a further extension of the indication spectrum and a high growth potential for these techniques and equipment in the coming years. For selected patients with selected tumors the minimally invasive transoral surgery offers improved oncological and functional results. In the present paper, different surgical access routes are presented and their indications discussed. PMID:23320057

  17. Alternative pharmacological strategies for adult ADHD treatment: a systematic review.

    PubMed

    Buoli, Massimiliano; Serati, Marta; Cahn, Wiepke

    2016-01-01

    Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard pharmacotherapy (methylphenidate and atomoxetine) improves ADHD symptoms in the short-term, but poor data were published about long-term treatment. In addition a number of patients present partial or no response to methylphenidate and atomoxetine. Research into the main database sources has been conducted to obtain an overview of alternative pharmacological approaches in adult ADHD patients. Among alternative compounds, amphetamines (mixed amphetamine salts and lisdexamfetamine) have the most robust evidence of efficacy, but they may be associated with serious side effects (e.g. psychotic symptoms or hypertension). Antidepressants, particularly those acting as noradrenaline or dopamine enhancers, have evidence of efficacy, but they should be avoided in patients with comorbid bipolar disorder. Finally metadoxine and lithium may be particularly suitable in case of comorbid alcohol misuse or bipolar disorder. PMID:26693882

  18. Current strategies for treatment of relapsed/refractory multiple myeloma.

    PubMed

    Laubach, Jacob P; Voorhees, Peter M; Hassoun, Hani; Jakubowiak, Andrzej; Lonial, Sagar; Richardson, Paul G

    2014-02-01

    In spite of significant advances in the management of multiple myeloma (MM), the disease remains incurable and nearly all patients ultimately relapse and require salvage chemotherapy. As such, relapsed and relapsed-refractory MM remains a critical area of research pertaining to biological mechanisms of progression and chemotherapy resistance, as well as to the development of new pharmacologic agents and immunologic approaches for the disease. The immunomodulatory agents and proteasome inhibitors represent the cornerstone of treatment in this setting, with combination regimens incorporating these drugs demonstrating encouraging rates and duration of response, including the newer agents, pomalidomide and carfilzomib. In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat. PMID:24471924

  19. [Child and adolescent obesity, psychosocial consequences and treatment strategies].

    PubMed

    Hartmann, A S; Hilbert, A

    2013-04-01

    Being overweight and obese in childhood and adolescence is associated with various somatic and psychosocial sequelae. Psychosocial problems can negatively influence the future weight trajectory. Therefore, weight reduction or stabilization should be complemented by the treatment of significant psychosocial problems. This review provides an overview of the psychosocial problems associated with being overweight and obese in childhood and adolescence. Evidence on weight-related stigmatization and discrimination, eating disorder symptoms, general psychopathology, impaired quality of life, lowered self-esteem, social skill deficits, as well as academic problems is summarized. Furthermore, state-of-the-art diagnostic and therapeutic procedures for the psychosocial problems are summarized. Future research should focus on the development of interventions targeting the destigmatization of obesity, as experiences of stigmatization and discrimination likely aggravate the psychosocial sequelae of overweight and obesity. PMID:23529599

  20. Mechanism and Treatment Strategy of Osteoporosis after Transplantation.

    PubMed

    Song, Lei; Xie, Xu-Biao; Peng, Long-Kai; Yu, Shao-Jie; Peng, Ya-Ting

    2015-01-01

    Osteoporosis (OP) has emerged as a frequent and devastating complication of organ solid transplantation process. Bone loss after organ transplant is related to adverse effects of immunosuppressants on bone remodeling and bone quality. Many factors contribute to the pathogenesis of OP in transplanted patients. Many mechanisms of OP have been deeply approached. Drugs for OP can be generally divided into "bone resorption inhibitors" and "bone formation accelerators," the former hindering bone resorption by osteoclasts and the latter increasing bone formation by osteoblasts. Currently, bisphosphonates, which are bone resorption inhibitors drugs, are more commonly used clinically than others. Using the signaling pathway or implantation bone marrow stem cell provides a novel direction for the treatment of OP, especially OP after transplantation. This review addresses the mechanism of OP and its correlation with organ transplantation, lists prevention and management of bone loss in the transplant recipient, and discusses the recipients of different age and gender. PMID:26273295

  1. [The lazy eye - contemporary strategies of amblyopia treatment].

    PubMed

    Sturm, V

    2011-02-16

    Amblyopia is a condition of decreased monocular or binocular visual acuity caused by form deprivation or abnormal binocular interaction. Amblyopia is the most common cause of monocular vision loss in children with a prevalence of 2 to 5%. During the last decade, several prospective randomized studies have influenced our clinical management. Based on these studies, optimum refractive correction should be prescribed first. However, most patients will need additional occlusion therapy which is still considered the «gold standard» of amblyopia management. Now much lower doses have been shown to be effective. In moderate amblyopia, penalization with atropine is as effective as patching. New treatment modalities including perceptual learning, pharmacotherapy with levodopa and citicholine or transcranial magnetic stimulation have not yet been widely accepted. PMID:21328237

  2. Understanding the neuroinflammatory response following concussion to develop treatment strategies

    PubMed Central

    Patterson, Zachary R.; Holahan, Matthew R.

    2012-01-01

    Mild traumatic brain injuries (mTBI) have been associated with long-term cognitive deficits relating to trauma-induced neurodegeneration. These long-term deficits include impaired memory and attention, changes in executive function, emotional instability, and sensorimotor deficits. Furthermore, individuals with concussions show a high co-morbidity with a host of psychiatric illnesses (e.g., depression, anxiety, addiction) and dementia. The neurological damage seen in mTBI patients is the result of the impact forces and mechanical injury, followed by a delayed neuroimmune response that can last hours, days, and even months after the injury. As part of the neuroimmune response, a cascade of pro- and anti-inflammatory cytokines are released and can be detected at the site of injury as well as subcortical, and often contralateral, regions. It has been suggested that the delayed neuroinflammatory response to concussions is more damaging then the initial impact itself. However, evidence exists for favorable consequences of cytokine production following traumatic brain injuries as well. In some cases, treatments that reduce the inflammatory response will also hinder the brain's intrinsic repair mechanisms. At present, there is no evidence-based pharmacological treatment for concussions in humans. The ability to treat concussions with drug therapy requires an in-depth understanding of the pathophysiological and neuroinflammatory changes that accompany concussive injuries. The use of neurotrophic factors [e.g., nerve growth factor (NGF)] and anti-inflammatory agents as an adjunct for the management of post-concussion symptomology will be explored in this review. PMID:23248582

  3. Treatment strategies for osteoarthritis patients with pain and hypertension.

    PubMed

    Verdecchia, Paolo; Angeli, Fabio; Mazzotta, Giovanni; Martire, Paola; Garofoli, Marta; Gentile, Giorgio; Reboldi, Gianpaolo

    2010-08-01

    Out of 100 patients with osteoarthritis (OA), almost 40 have a concomitant diagnosis of hypertension. Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors may trigger a rise in blood pressure (BP), which is more marked in patients with established hypertension. NSAIDs and COX-2 inhibitors attenuate the antihypertensive effect of several antihypertensive agents. Frequent BP controls are needed in treated hypertensive patients who are concomitantly receiving NSAIDs or COX-2 inhibitors because even a small increase in BP may be associated with an important rise in the risk of major cardiovascular complications. In meta-analyses, an increase in systolic BP of 5mmHg was associated with a 25% higher risk of cardiovascular events. These data have been confirmed in randomized studies with rofecoxib and celecoxib, where a modest increase in BP was associated with a significantly higher risk of cardiovascular disease. There is emerging evidence that the COX-inhibiting nitric oxide donator (CINOD) class is promising in the treatment of patients with OA. Naproxcinod, the first CINOD investigated in clinical trials, is composed of the traditional NSAID naproxen covalently bound to the nitric oxide (NO)-donating moiety butanediol mono-nitrate (BDMN). The molecule has the potential to provide a sustained release of NO. In clinical studies, naproxcinod prevented the BP rise in normotensive and hypertensive patients observed with naproxen. The BP benefit of naproxcinod over naproxen was greater in patients concomitantly receiving angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. These investigational data suggest that naproxcinod is a valuable alternative to NSAIDs and COX-2 inhibitors for treatment of OA patients. PMID:22870450

  4. Treatment Strategies for Osteoarthritis Patients with Pain and Hypertension

    PubMed Central

    Verdecchia, Paolo; Angeli, Fabio; Mazzotta, Giovanni; Martire, Paola; Garofoli, Marta; Gentile, Giorgio; Reboldi, Gianpaolo

    2010-01-01

    Out of 100 patients with osteoarthritis (OA), almost 40 have a concomitant diagnosis of hypertension. Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors may trigger a rise in blood pressure (BP), which is more marked in patients with established hypertension. NSAIDs and COX-2 inhibitors attenuate the antihypertensive effect of several antihypertensive agents. Frequent BP controls are needed in treated hypertensive patients who are concomitantly receiving NSAIDs or COX-2 inhibitors because even a small increase in BP may be associated with an important rise in the risk of major cardiovascular complications. In meta-analyses, an increase in systolic BP of 5mmHg was associated with a 25% higher risk of cardiovascular events. These data have been confirmed in randomized studies with rofecoxib and celecoxib, where a modest increase in BP was associated with a significantly higher risk of cardiovascular disease. There is emerging evidence that the COX-inhibiting nitric oxide donator (CINOD) class is promising in the treatment of patients with OA. Naproxcinod, the first CINOD investigated in clinical trials, is composed of the traditional NSAID naproxen covalently bound to the nitric oxide (NO)-donating moiety butanediol mono-nitrate (BDMN). The molecule has the potential to provide a sustained release of NO. In clinical studies, naproxcinod prevented the BP rise in normotensive and hypertensive patients observed with naproxen. The BP benefit of naproxcinod over naproxen was greater in patients concomitantly receiving angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. These investigational data suggest that naproxcinod is a valuable alternative to NSAIDs and COX-2 inhibitors for treatment of OA patients. PMID:22870450

  5. AN EFFICIENT TREATMENT STRATEGY FOR HISTOTRIPSY BY REMOVING CAVITATION MEMORY

    PubMed Central

    Wang, Tzu-Yin; Xu, Zhen; Hall, Timothy L.; Fowlkes, J. Brian; Cain, Charles A.

    2012-01-01

    Cavitation memory effects occur when remnants of cavitation bubbles (nuclei) persist in the host medium and act as seeds for subsequent events. In pulsed cavitational ultrasound therapy, or histotripsy, this effect may cause cavitation to repeatedly occur at these seeded locations within a target volume, producing inhomogeneous tissue fractionation or requiring an excess number of pulses to completely homogenize the target volume. We hypothesized that by removing the cavitation memory, i.e., the persistent nuclei, the cavitation bubbles could be induced at random locations in response to each pulse; therefore, complete disruption of a tissue volume may be achieved with fewer pulses. To test the hypothesis, the cavitation memory was passively removed by increasing the intervals between successive pulses, Δt, from 2, 10, 20, 50 and 100, to 200 ms. Histotripsy treatments were performed in red blood cell tissue phantoms and ex vivo livers using 1-MHz ultrasound pulses of 10 cycles at P−/P+ pressure of 21/59 MPa. The phantom study allowed for direct visualization of the cavitation patterns and the lesion development process in real time using high-speed photography; the ex vivo tissue study provided validation of the memory effect in real tissues. Results of the phantom study showed an exponential decrease in the correlation coefficient between cavitation patterns in successive pulses from 0.5 ± 0.1 to 0.1 ± 0.1 as Δt increased from 2–200 ms; correspondingly, the lesion was completely fractionated with significantly fewer pulses for longer Δts. In the tissue study, given the same number of therapy pulses, complete and homogeneous tissue fractionation with well-defined lesion boundaries was achieved only for Δt ≥ 100 ms. These results indicated that the removal of the cavitation memory resulted in more efficient treatments and homogeneous lesions. PMID:22402025

  6. [Acute necrotizing pancreatitis--diagnostic and treatment strategy].

    PubMed

    Madzhov, R; Georgiev, K; Arnaudov, P; Radev, R; Bankov, P

    2003-01-01

    Despite of the current achievements of medicine, the mortality of necrotizing pancreatitis (NP) is still too high--up to 35-40% and stands as a serious diagnostic and treatment problem. The results of treatment of 148 patients, admitted in the clinic with diagnosis NP, 95 males and 53 females, are discussed. The ratio between patients with acute oedematic and acute NP is 81.1% to 18.9%. According to the hystopatology findings, the results are as follows: pancreatic necrosis--128 patients, peripancreatic necrosis--42 patients, retropancreatic necrosis--29 patients, phlegmonous cholecystitis--31 patients. For the exact diagnostic estimation of the development and prognosis of NP, we are based on: Clinic symptomatology, biochemical constellations (the prognostic scale of Ranson), ultrasonography, CT, ERCP, ES, laparoscopy (48 pts), and laparoscopic drainage (34 pts) of the abdominal cavity with one or two drains, in order to decrease the intoxication and manage intraperitoneal irrigation with antibiotics and enzymes. The operative intervations consists of a thorough exploration, broad necrectomy combined with lavage and large drainage. COLD (controlled open lesser sac drainage) has been performed at 34 cases. In 31 pts cholecystectomy and choledochotomy with T-tube drainage of d. choledochus (Kehr drainage) was performed. Reoperations have been made at 34 pts (22.9%); in 11 of them--2 operative revisions have been carried out, in 3 cases--three, and in 3 cases--4 operative revisions were performed. The total postoperative death rate was 21.6% (32 patients). The most common postoperative complications were as follows: pulmonary complications at 11 cases, pleural effusions--9 pts, intraabdominal abscesses--6 patients, postnecrotic pseudocysts--9 cases, pancreatic fistulas--6 cases, fistulas of the colon--2 pts, bleeding--4 patients. PMID:15584453

  7. Probiotic as a Novel Treatment Strategy Against Liver Disease

    PubMed Central

    Imani Fooladi, Abbas Ali; Mahmoodzadeh Hosseini, Hamideh; Nourani, Mohammad Reza; Khani, Soghra; Alavian, Seyed Moayed

    2013-01-01

    Context A symbiotic relationship between the liver and intestinal tract enables the healthy status of both organs. Microflora resident in intestinal lumen plays a significant role in hepatocytes function. Alterations to the type and amount of microorganisms that live in the intestinal tract can result in serious and harmful liver dysfunctions such as cirrhosis, nonalcoholic fatty liver disease, alcoholic liver disease, and hepatic encephalopathy. An increased number of pathogens, especially enterobacteriaceae, enterococci, and streptococci species causes the elevation of intestinal permeability and bacterial translocation. The presence of high levels of lipopolysaccharide (LPS) and bacterial substances in the blood result in a portal hypertension and ensuing hepatocytes damage. Several methods including the usage of antibiotics, prebiotics, and probiotics can be used to prevent the overgrowth of pathogens. Compared to prebiotic and antibiotic therapy, probiotics strains are a safer and less expensive therapy. Probiotics are "live microorganisms (according to the FAO/WHO) which when administered in adequate amounts confer a health benefit on the host”. Evidence Acquisitions Data from numerous preclinical and clinical trials allows for control of the flora bacteria quantity, decreases in compounds derived from bacteria, and lowers proinflammatory production such as TNF-α, IL-6 and IFN-γ via down-regulation of the nuclear factor kappa B (NF-κ B). Results On the other hand, probiotic can reduce the urease activity of bacterial microflora. Furthermore, probiotic decreases fecal pH value and reduces ammonia adsorption. In addition, the serum level of liver enzymes and other substances synthesized by the liver are modulated subsequent to probiotic consumption. Conclusions According to our knowledge, Probiotic therapy as a safe, inexpensive and a noninvasive strategy can reduce pathophysiological symptoms and improve different types of liver diseases without side

  8. [Novel treatment strategies for refractory patients with obsessive-compulsive disorder].

    PubMed

    Nakamae, Takashi

    2013-01-01

    Although selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD), response rates to these therapies are 40-60%. There may be many treatment-refractory patients who do not respond to several SSRIs and intensive CBT treatment. The current treatment guidelines suggest various strategies for treatment-refractory cases, but there is no established evidence for most of them. Augmentation therapies with antipsychotics and glutamate modulator drugs have yielded some supporting evidence. When all drugs and CBT are ineffective, non-pharmacological treatment including deep brain stimulation (DBS) should be applied. However, it is necessary to establish criteria for treatment-refractory patients and standardize conventional treatment before neuromodulation treatment is applied in Japan. PMID:24228478

  9. A Canadian Critical Care Trials Group project in collaboration with the international forum for acute care trialists - Collaborative H1N1 Adjuvant Treatment pilot trial (CHAT): study protocol and design of a randomized controlled trial

    PubMed Central

    2011-01-01

    Background Swine origin influenza A/H1N1 infection (H1N1) emerged in early 2009 and rapidly spread to humans. For most infected individuals, symptoms were mild and self-limited; however, a small number developed a more severe clinical syndrome characterized by profound respiratory failure with hospital mortality ranging from 10 to 30%. While supportive care and neuraminidase inhibitors are the main treatment for influenza, data from observational and interventional studies suggest that the course of influenza can be favorably influenced by agents not classically considered as influenza treatments. Multiple observational studies have suggested that HMGCoA reductase inhibitors (statins) can exert a class effect in attenuating inflammation. The Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial sought to investigate the feasibility of conducting a trial during a global pandemic in critically ill patients with H1N1 with the goal of informing the design of a larger trial powered to determine impact of statins on important outcomes. Methods/Design A multi-national, pilot randomized controlled trial (RCT) of once daily enteral rosuvastatin versus matched placebo administered for 14 days for the treatment of critically ill patients with suspected, probable or confirmed H1N1 infection. We propose to randomize 80 critically ill adults with a moderate to high index of suspicion for H1N1 infection who require mechanical ventilation and have received antiviral therapy for ≤ 72 hours. Site investigators, research coordinators and clinical pharmacists will be blinded to treatment assignment. Only research pharmacy staff will be aware of treatment assignment. We propose several approaches to informed consent including a priori consent from the substitute decision maker (SDM), waived and deferred consent. The primary outcome of the CHAT trial is the proportion of eligible patients enrolled in the study. Secondary outcomes will evaluate adherence to medication administration

  10. Xuan Bai Cheng Qi formula as an adjuvant treatment of acute exacerbation of chronic obstructive pulmonary disease of the syndrome type phlegm-heat obstructing the lungs: a multicenter, randomized, double-blind, placebo-controlled clinical trial

    PubMed Central

    2014-01-01

    Background Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common cause of morbidity and mortality. Traditional Chinese medicine (TCM) is used to treat AECOPD as adjunctive therapy. This study aimed to evaluate the efficacy and safety of the TCM formula Xuan Bai Cheng Qi as an adjuvant therapy for AECOPD patients with the syndrome type of phlegm-heat obstructing the lungs. Methods A multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 244 patients were divided into the intervention group (n = 122, treated with conventional medicine and Xuan Bai Cheng Qi) and the control group (n = 122, treated with conventional medicine and placebo). Total symptom scores (cough, phlegm, wheezing, chest congestion) before treatment and at 3, 5, 7, 10 days post-treatment were recorded. Lung function, arterial blood gas, serum inflammatory cytokines, oxidation/anti-oxidation index were observed before treatment and at the end of the 10-day treatment. Results A total of 242 patients completed the study. The full analysis set (FAS) population was 244 and the per-protocol analysis set (PPS) population was 229. After the 10-day treatment, symptom scores of the Xuan Bai Cheng Qi group were significantly lower over time compared with the control group (FAS: mean difference -1.84, 95% CI -2.66 to -1.03, P < .001; PPS: mean difference -1.87, 95% CI -2.71 to -1.03, P < .001). FEV1, FVC, and FEV1%pred were significantly higher over time in the Xuan Bai Cheng Qi group compared with those in the control group (day 10, FAS and PPS: P < .05). PaO2 and PaCO2 were significantly improved in the Xuan Bai Cheng Qi group (day 10, FAS and PPS: P < .05). Xuan Bai Cheng Qi was also found to ameliorate cytokine levels and oxidation/antioxidant index compared with placebo. There were no differences in safety variables and adverse events between the two groups. Conclusions Xuan Bai Cheng Qi formula appears to be a

  11. A global logrank test for adaptive treatment strategies based on observational studies.

    PubMed

    Li, Zhiguo; Valenstein, Marcia; Pfeiffer, Paul; Ganoczy, Dara

    2014-02-28

    In studying adaptive treatment strategies, a natural question that is of paramount interest is whether there is any significant difference among all possible treatment strategies. When the outcome variable of interest is time-to-event, we propose an inverse probability weighted logrank test for testing the equivalence of a fixed set of pre-specified adaptive treatment strategies based on data from an observational study. The weights take into account both the possible selection bias in an observational study and the fact that the same subject may be consistent with more than one treatment strategy. The asymptotic distribution of the weighted logrank statistic under the null hypothesis is obtained. We show that, in an observational study where the treatment selection probabilities need to be estimated, the estimation of these probabilities does not have an effect on the asymptotic distribution of the weighted logrank statistic, as long as the estimation of the parameters in the models for these probabilities is n-consistent. Finite sample performance of the test is assessed via a simulation study. We also show in the simulation that the test can be pretty robust to misspecification of the models for the probabilities of treatment selection. The method is applied to analyze data on antidepressant adherence time from an observational database maintained at the Department of Veterans Affairs' Serious Mental Illness Treatment Research and Evaluation Center. PMID:24108518

  12. Super-oxidized solution (Dermacyn Wound Care) as adjuvant treatment in the postoperative management of complicated diabetic foot osteomyelitis: preliminary experience in a specialized department.

    PubMed

    Aragón-Sánchez, Javier; Lázaro-Martínez, Jose Luis; Quintana-Marrero, Yurena; Sanz-Corbalán, Irene; Hernández-Herrero, Maria J; Cabrera-Galván, Juan J

    2013-06-01

    Surgery is usually used to treat diabetic foot osteomyelitis (DFO), whether primarily or in cases in which antibiotics are not able to control infection. In many cases, the bone is only partially removed, which means that residual infection remains in the bone margins, and the wound is left open to heal by secondary intent. The use of culture-guided postoperative antibiotic treatment and adequate management of the wound must be addressed. No trials exist dealing with local treatment in the postoperative management of these cases of complicated DFO. We decided to test a super-oxidized solution, Dermacyn Wound Care (DWC; Oculus Innovative Sciences Netherlands BV, Sittard, Netherlands) to obtain preliminary experience in patients in whom infected bone remained in the surgical wounds. Our hypothesis was that DWC could be useful to control infection in the residual infected bone and surrounding soft tissues and would thus facilitate healing. Fourteen consecutive patients who underwent conservative surgery for DFO, in whom clean bone margins could not be assured, were treated in the postoperative period with DWC. Eleven cases were located in the forefoot, 6 on the first ray and the rest in lesser toes, 1 in the Lisfranc joint, and 2 on the calcaneus. No side effects appeared during treatment. Neither allergies nor skin dermatitis were found. Limb salvage was successfully achieved in 100% of the cases. Healing was achieved in a median period of 6.8 weeks. PMID:23446366

  13. Opioid and adjuvant analgesics: compared and contrasted.

    PubMed

    Khan, Mohammed Ilyas Ahmed; Walsh, Declan; Brito-Dellan, Norman

    2011-08-01

    AAs (1-2 days). Rotation among opioids is a useful therapeutic strategy to improve analgesic response or minimize toxicity. Most AAs are unsuitable for rescue dosing because of their pharmacological characteristics. The mu agonist side effect profile is similar among the different opioid agents, regardless of the route of administration. The appropriate use of AAs will reduce opioid-related side effects. No apparent tolerance to analgesia develops with AAs. Abrupt discontinuation of an opioid after chronic repeated use for more than a few days will cause a withdrawal syndrome of variable severity. Adjuvant analgesics are an essential tool in cancer pain. PMID:21622486

  14. Safety assessment of adjuvanted vaccines: Methodological considerations

    PubMed Central

    Da Silva, Fernanda Tavares; Di Pasquale, Alberta; Yarzabal, Juan P; Garçon, Nathalie

    2015-01-01

    Adjuvants mainly interact with the innate immune response and are used to enhance the quantity and quality of the downstream adaptive immune response to vaccine antigens. Establishing the safety of a new adjuvant-antigen combination is achieved through rigorous evaluation that begins in the laboratory, and that continues throughout the vaccine life-cycle. The strategy for the evaluation of safety pre-licensure is guided by the disease profile, vaccine indication, and target population, and it is also influenced by available regulatory guidelines. In order to allow meaningful interpretation of clinical data, clinical program methodology should be optimized and standardized, making best use of all available data sources. Post-licensure safety activities are directed by field experience accumulated pre- and post-licensure clinical trial data and spontaneous adverse event reports. Continued evolution of safety evaluation processes that keep pace with advances in vaccine technology and updated communication of the benefit-risk profile is necessary to m