Interventions for the treatment of oral cavity and oropharyngeal cancer:chemotherapy

<b>Background:</b> Oral cavity and oropharyngeal cancers are frequently described as part of a group of oral cancers or head and neck cancer. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects, notably impaired ability to eat, drink and talk. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients.<p></p> <b>Objectives:</b> To determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal cancer results in improved survival, disease free survival, progression free survival, locoregional control and reduced recurrence of disease. To determine which regimen and time of administration (induction, concomitant or adjuvant) is associated with better outcomes.<p></p> <b>Search strategy:</b> Electronic searches of the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE, AMED were undertaken on 28th July 2010. Reference lists of recent reviews and included studies were also searched to identify further trials.<p></p> <b>Selection criteria:</b> Randomised controlled trials where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and which compared the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration, were included.<p></p> <b>Data collection and analysis:</b> Trials which met the inclusion criteria were assessed for risk of bias using six domains: sequence generation, allocation concealment, blinding, completeness of outcome data, selective reporting and other possible sources of bias. Data were extracted using a specially designed form and entered into the characteristics of included studies table and the analysis sections of the review. The proportion of participants in each trial with oral cavity and oropharyngeal cancers are recorded in Additional Table 1.<p></p> <b>Main results:</b> There was no statistically significant improvement in overall survival associated with induction chemotherapy compared to locoregional treatment alone in 25 trials (hazard ratio (HR) of mortality 0.92, 95% confidence interval (CI) 0.84 to 1.00). Post-surgery adjuvant chemotherapy was associated with improved overall survival compared to surgery +/- radiotherapy alone in 10 trials (HR of mortality 0.88, 95% CI 0.79 to 0.99), and there was an additional benefit of adjuvant concomitant chemoradiotherapy compared to radiotherapy in 4 of these trials (HR of mortality 0.84, 95% CI 0.72 to 0.98). Concomitant chemoradiotherapy resulted in improved survival compared to radiotherapy alone in patients whose tumours were considered unresectable in 25 trials (HR of mortality 0.79, 95% CI 0.74 to 0.84). However, the additional toxicity attributable to chemotherapy in the combined regimens remains unquantified.<p></p> <b>Authors' conclusions:</b> Chemotherapy, in addition to radiotherapy and surgery, is associated with improved overall survival in patients with oral cavity and oropharyngeal cancers. Induction chemotherapy is associated with a 9% increase in survival and adjuvant concomitant chemoradiotherapy is associated with a 16% increase in overall survival following surgery. In patients with unresectable tumours, concomitant chemoradiotherapy showed a 22% benefit in overall survival compared with radiotherapy alone.<p></p&gt

A walk in the PARC:developing and implementing 21st century chemical risk assessment in Europe

Current approaches for the assessment of environmental and human health risks due to exposure to chemical substances have served their purpose reasonably well. Nevertheless, the systems in place for different uses of chemicals are faced with various challenges, ranging from a growing number of chemicals to changes in the types of chemicals and materials produced. This has triggered global awareness of the need for a paradigm shift, which in turn has led to the publication of new concepts for chemical risk assessment and explorations of how to translate these concepts into pragmatic approaches. As a result, next-generation risk assessment (NGRA) is generally seen as the way forward. However, incorporating new scientific insights and innovative approaches into hazard and exposure assessments in such a way that regulatory needs are adequately met has appeared to be challenging. The European Partnership for the Assessment of Risks from Chemicals (PARC) has been designed to address various challenges associated with innovating chemical risk assessment. Its overall goal is to consolidate and strengthen the European research and innovation capacity for chemical risk assessment to protect human health and the environment. With around 200 participating organisations from all over Europe, including three European agencies, and a total budget of over 400 million euro, PARC is one of the largest projects of its kind. It has a duration of seven years and is coordinated by ANSES, the French Agency for Food, Environmental and Occupational Health & Safety

Social Movements and International Relations: A Relational Framework

Social movements are increasingly recognized as significant features of contemporary world politics, yet to date their treatment in international relations theory has tended to obfuscate the considerable diversity of these social formations, and the variegated interactions they may establish with state actors and different structures of world order. Highlighting the difficulties conventional liberal and critical approaches have in transcending conceptions of movements as moral entities, the article draws from two under-exploited literatures in the study of social movements in international relations, the English School and Social Systems Theory, to specify a wider range of analytical interactions between different categories of social movements and of world political structures. Moreover, by casting social movement phenomena as communications, the article opens international relations to consideration of the increasingly diverse trajectories and second-order effects produced by social movements as they interact with states, intergovernmental institutions, and transnational actors

Ecological effects of pesticides in freshwater model ecosystems

In this thesis I have investigated the effects of pesticide exposure on the ecosystem level using various types of experimental ecosystems, i.e. microcosms. The direct effect of exposure to cyperemthrin, a pyretroid insecticide, was a rapid decrease of crustancean zooplankton in enclosures in a lake. In the exposed enclosures the biomass of algae, heterotrophic nanoflagellates, ciliates and bacteria increased, likely due to indirect effects of the exposure to cypermethrin. The effects of a sulfonylurea herbicide, metsulfuron-methyl, were investigated in two studies. The experiments showed that the macrophytes were negatively affected following exposure to concentrations of metsulfuron-methyl at which no negative effects were observed on the algal communities. Instead the algae proliferated in the exposed microcosms. The alterations of the primary producing community propagated to the zooplankton, and the species composition of the zooplankton community was altered, which thus was an indirect effect of exposure to metsulfuron-methyl. Hence, these studies show that both insecticides (i.e. cypermethrin) and herbicides (i.e. metsulfuron-methyl), through different mechanisms, can induce a competitive advantage for the algal communities in relation to the macrophytes. This suggests that exposure to pesticides may shift an aquatic ecosystem over to an algal dominated turbid state, i.e. cause alterations similar to changes induced by eutrophication. Furthermore, a study of the effects of a pesticide mixture on aquatic model ecosystems of different trophic status, indicated that the structure and trophic status of aquatic ecosystems is important for the final outcome of pesticide exposure. The effects of the pesticide treatment on the macrophytes and their associated algal community was different in the mesotrophic compared to the eutrophic model ecosystems and the effects were observed at lower concentrations in the mesothrophic microcosms

Effects of metsulfuron methyl and cypermethrin exposure on freshwater model ecosystems

The aim of this study was to investigate the short-term (2 weeks) effects of the herbicide metsulfuron methyl alone and in combination with the insecticide cypermethrin in freshwater enclosures (80 1). We used a factorial design with four levels of herbicide (0, 1, 5, 20 mug/1) and two levels of insecticide (0 and 0.05 mug/1). The root growth of the macrophyte species Elodea canadensis and Myriophyllum spicatum decreased following exposure to the lowest concentration of metsulfuron methyl tested. Metsulfuron methyl exposure resulted in a decreased pH in the aquatic enclosure at the lowest concentration tested, which is most likely a further indication of decreased macrophyte primary production. The biomass of periphytic algae growing on the leaves of M. spicatum increased in the enclosures exposed to metsulfuron methyl. The species composition of the periphytic algae differed significantly from the controls in the enclosures exposed to 20 mug/1 of the herbicide. The increased biomass of periphytic algae on the leaves of the macrophytes is probably an indirect effect of the herbicide exposure. The exposure to metsulfuron methyl possibly induced a leakage of nutrients from the macrophyte leaves, which promoted an increased algal growth. The exposure to metsulfuron methyl did not alter the biomass or the species composition of the phytoplankton community. The zooplankton communities in the enclosures were dominated by rotifers, which were not affected by the exposure to cypermethrin. However, a cypermethrin exposure of 0.05 mug/1 initially decreased the abundance of copepod nauplii. Ten days after exposure, the abundance of nauplii was significantly higher in the insecticide-exposed enclosures compared with the non-exposed enclosures. This might be an indication of a sub-lethal stress response, which either increased the number of offspring produced or induced an increased hatching of copepod resting stages. No combined effects of the herbicide and insecticide exposure, either direct or indirect, were observed in the enclosure study. Significant effects on the macrophytes were observed following exposure to 1 mug metsulfuron methyl per litre in the enclosure study. Furthermore, a single species laboratory assay indicated that the shoot elongation of E canadensis decreased following exposure to greater than or equal to 0. 1 mug metsulfuron methyl per litre. These concentrations are well within the range of expected environmental concentrations, thus this study shows that aquatic ecosystems, in particular those which are macrophyte-dominated, may be affected by metsulfuron methyl at concentrations that may well occur in water bodies adjacent to agricultural land. (C) 2002 Elsevier Science B.V. All rights reserved

Effects of the pyrethroid insecticide, cypermethrin, on a freshwater community studied under field conditions. I. Direct and indirect effects on abundance measures of organisms at different trophic levels

The effects of the pyrethroid insecticide cypermethrin on a natural freshwater community were studied in small in situ enclosures over an 11-day period. The experiment was conducted in a eutrophic lake using a regression design that included three untreated controls and a gradient of six unreplicated cypermethrin concentrations, ranging from 0.01 to 6.1 mug/l. This paper is the first in a series of two, and describes the fate of cypermethrin and its effects on the abundance of crustaceans, rotifers, protozoans (cilliates and heterotrophic nanoflagellates (HNF)) and bacteria and the biomass of periphytic and planktonic algae. The concentration of cypermethrin decreased quickly during the experiment, with a half-life of 48 h for the total and 25 h for the dissolved fractions of cypermethrin, respectively. Cypermethrin proved to be acutely toxic to crustaceans in enclosures receiving nominal cypermethrin concentrations of greater than or equal to0.13 mug/l. No Effect Concentration (NEC) and median Effect Concentration (EC50) for the total crustacean community and cladoceran and copepod subgroups ranged between 0.02-0.07 and 0.04-0.17 mug/l, respectively, with copepods being less sensitive than cladocerans. The abundance of rotifers, protozoans and bacteria and the chlorophyll-a concentration of planktonic and periphytic algae was significantly related to the concentration of cypermethrin. All groups proliferated within 2-7 days after the cypermethrin application in those enclosures where the abundance of crustaceans was seriously affected by cypermethrin (i.e. greater than or equal to0.13 mug/l). We hypothesise that the proliferation of rotifers, protozoans, bacteria and algae was due to a reduced grazer control from crustaceans and thereby mediated indirectly by cypermethrin. The results of this experiment provide knowledge on how an entire microplankton community may respond to pyrethroids in nature, and the indirect effects observed on the community clearly demonstrates the necessity of multispecies field experiments in ecotoxicological risk assessment. (C) 2003 Elsevier Science B.V. All rights reserved

The effects of a pesticide mixture on aquatic ecosystems differing in trophic status: responses of the macrophyte Myriophyllum spicatum and the periphytic algal community

The effects of a pesticide mixture (asulam, fluazinam, lambda-cyhalothrin, and metamitron) on aquatic ecosystems were investigated in 20 outdoor aquatic microcosms. Ten of the microcosms simulated mesotrophic aquatic ecosystems dominated by submerged macrophytes (Elodea). The others simulated eutrophic ecosystems with a high Lemna surface coverage (Lemna). This paper describes the fate of the chemicals as well as their effects on the growth of Myriophyllum spicatum and the periphytic algal community. In the Elodea-dominated microcosms significant increase in the biomass and alterations of species composition of the periphytic algae were observed, but no effect on M. spicatum growth could be recorded in response to the treatment. The opposite was found in the Lemna-dominated microcosms, in which decreased growth of M. spicatum was observed but no alterations could be found in the periphytic community. In the Elodea-dominated microcosms the species composition of the periphytic algae diverged from that of the control following treatment with 0.5% spray drift emission of the label-recommended rate (5% for lambda-cyhalothrin), while reduced growth of M. spicatum in the Lemna-dominated microcosms was recorded at 2% drift (20% for lambda-cyhalothrin). This study shows that the structure of the ecosystem influences the final effect of pesticide exposure. (C) 2003 Elsevier Inc. All rights reserved

The effects of a pesticide mixture on aquatic ecosystems differing in trophic status: responses of the macrophyte Myriophyllum spicatum and the periphytic algal community

The effects of a pesticide mixture (asulam, fluazinam, lambda-cyhalothrin, and metamitron) on aquatic ecosystems were investigated in 20 outdoor aquatic microcosms. Ten of the microcosms simulated mesotrophic aquatic ecosystems dominated by submerged macrophytes (Elodea). The others simulated eutrophic ecosystems with a high Lemna surface coverage (Lemna). This paper describes the fate of the chemicals as well as their effects on the growth of Myriophyllum spicatum and the periphytic algal community. In the Elodea-dominated microcosms significant increase in the biomass and alterations of species composition of the periphytic algae were observed, but no effect on M. spicatum growth could be recorded in response to the treatment. The opposite was found in the Lemna-dominated microcosms, in which decreased growth of M. spicatum was observed but no alterations could be found in the periphytic community. In the Elodea-dominated microcosms the species composition of the periphytic algae diverged from that of the control following treatment with 0.5% spray drift emission of the label-recommended rate (5% for lambda-cyhalothrin), while reduced growth of M. spicatum in the Lemna-dominated microcosms was recorded at 2% drift (20% for lambda-cyhalothrin). This study shows that the structure of the ecosystem influences the final effect of pesticide exposure