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Purpose: Radiation therapy with chemotherapy (CCR) is currently the gold standard treatment for nasopharyngeal carcinoma (NPC). Anatomical changes are mainly due to weight loss. Our prospective study aimed to evaluate the nutritional status and the quality of weight loss in our patients to adapt the subsequent nutritional management of patients during treatment for NPC., Patients and Methods: A prospective, single-center study of 27 patients with non-metastatic NPC treated in our oncology radiotherapy department between August 2020 and March 2021. Data from interrogation, physical examination, and bioelectrical impedancemetry (weight [W], body mass index [BMI], fat index [GI], fat mass [FM], and fat-free mass (FFM]) were collected at the beginning, the mid, and the end of treatment., Results: Weight loss from mid to end of treatment (median=-4kg [-9.4; -0.9]) was greater than that from baseline to mid-treatment (median=-2.9kg [-8.8; 1.8]) (P=0.016). Weight loss during the entire treatment was -6.2kg [-15.6; -2.5] (8.4%). The losses of FM were identical between the beginning-mid treatment and the mid-end treatment; they were respectively -1.4kg [-8.5; 4.2] and -1.4kg [-8.2; 7.8] (P=0.4). FFM losses between the mid- and the end of treatment (-2.5kg [-27.8; 0.5]) were greater than those between baseline and mid-treatment (-1.1kg [-7.1; 4.7]) (P=0.014). Median FFM loss during treatment was -3.6kg [-28.1; 2.6])., Conclusion: The results of our study show that weight loss during CCR for NPC is complex and is not just about loss but about a disruption of body composition. Regular follow-ups by nutritionists are required to prevent denutrition during treatment., (Copyright © 2023 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Nasopharyngeal carcinoma diagnosis is often made at a locally advanced stage (75 to 90% of cases) due to its deep localization. Concomitant radio-chemotherapy is the cornerstone of the treatment of locally advanced forms. The advent of intensity-modulated radiotherapy has improved oncological outcomes and reduced toxicity and is currently the gold standard for irradiation technique. For the locally advanced stage, the addition of induction chemotherapy has become the new standard care according to the latest international recommendations to reduce tumor volumes and act early on micro-metastases. Despite these therapeutic advances, the local and especially distant failure rate remains high. This article reviews current treatment strategies and discuss new approaches and perspectives of locoregional and systemic treatment to reduce treatment failures., (Copyright © 2022 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: The pre- and post-induction chemotherapy tumor volumes of nasopharyngeal carcinomas may be prognostic indicators for adapting the therapeutic strategy. The objective of our study is to assess the prognostic impact of pre- and post-induction chemotherapy volumes in patients treated for locally advanced nasopharyngeal carcinomas., Patients and Methods: This is a retrospective study including 52 patients with locally advanced nasopharyngeal carcinoma treated with 3 courses of induction chemotherapy (TPF) followed by intensity modulated radiotherapy associated with concomitant chemotherapy., Results: The median initial and post induction chemotherapy total volumes were 92.3 and 41.5mL, respectively. At 3 years, the LRFS, DMFS, DFS and OS were respectively 85.9%, 63.5%, 56.8% and 67.8%. In multivariate study, the combination of a high initial volume (>100mL) and post-chemotherapy volume (>35mL) was an independent factor for LRFS, DMFS, DFS and OS. The total baseline volume had a better predictive prognostic value for DFS and OS than the TNM classification (8th edition 2017)., Conclusion: The prognostic weight of tumor and nodal volumes was greater than the TNM classification (8th edition). The pre- and post-chemotherapy tumor volumes allow selecting a high-risk patients' subgroup "high initial and post chemotherapy volumes" in which it would be advisable to offer more intensive treatment regimens., (Copyright © 2022 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Staphylococcus aureus biofilms are poorly responsive to antibiotics. Underlying reasons include a matrix effect preventing drug access to embedded bacteria, or the presence of dormant bacteria with reduced growth rate. Using 18 clinical isolates previously characterized for their moxifloxacin-resistant and moxifloxacin-persister character in stationary-phase culture, we studied their biofilm production and matrix composition and the anti-biofilm activity of moxifloxacin. Biofilms were grown in microtiter plates and their abundance quantified by crystal violet staining and colony counting; their content in polysaccharides, extracellular DNA and proteins was measured. Moxifloxacin activity was assessed after 24 h of incubation with a broad range of concentrations to establish full concentration-response curves. All clinical isolates produced more biofilm biomass than the reference strain ATCC 25923, the difference being more important for those with high relative persister fractions to moxifloxacin, most of which being also resistant. High biofilm producers expressed icaA to higher levels, enriching the matrix in polysaccharides. Moxifloxacin was less potent against biofilms from clinical isolates than from ATCC 25923, especially against moxifloxacin-resistant isolates with high persister fractions, which was ascribed to a lower concentration of moxifloxacin in these biofilms. Time-kill curves in biofilms revealed the presence of a moxifloxacin-tolerant subpopulation, with low multiplication capacity, whatever the persister character of the isolate. Thus, moxifloxacin activity depends on its local concentration in biofilm, which is reduced in most isolates with high-relative persister fractions due to matrix effects, and insufficient to kill resistant isolates due to their high MIC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nguyen, Peyrusson, Siala, Pham, Nguyen, Tulkens and Van Bambeke.)

Modern high-precision radiotherapy techniques have recently incorporated the notion of anatomical variations of the patient during treatment and have tried to adapt the treatment planning to them. Adaptive radiotherapy for nasopharyngeal tumors is starting to prove its benefit nowadays. His interest is constantly being evaluated. The variations encountered during the treatment are both geometric and dosimetric. They are represented by a reduction in the macroscopic tumors volume, a change in its position and a consequent dosimetric impact. The changes also concern organs at risk with a reduction of glandular structure volumes, and a different position which increases their doses. Delivered doses to noble structures (brainstem and spinal cord) may also increase. However, difficulties are encountered in its realization. There is a problem to perfectly reproduce the patient position during the second acquisition, which impacts the fusion quality between the two CT scans. This generates an imprecision in the definition of the same treatment isocentre on the second scanner. Also, there is a difficulty in accumulated doses calculation. The indication of adaptive radiotherapy remains a subject of controversy. It should be proposed for a subgroup of patients who could benefit from this new strategy. We present here an update on the state of the art of adaptive radiotherapy for nasopharyngeal cancer., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: The aim of this work is to evaluate the anatomical changes of the glandular structures during the NPC IMRT and to study their dosimetric impacts., Patients and Methods: Twenty patients receiving IMRT for NPC were included. For each patient, a second dosimetric CT was performed at a dose of 38Gy, which was fused with the initial planning dosimetric CT. We calculated the volume percent change, the positional and dosimetric variation between the 2 scanners for the glandular structures (parotid, submaxillary, thyroid and pituitary)., Results: We observed a decrease in the volume of right and left parotids (-27.9% and -27.54%). It was correlated with the initial dose planned at its level. For the sub maxillary glands, the decrease was -36.1% on the right and -27.28% on the left. The value of reduction of the thyroid gland was -18.01%. A medial supra-millimeter migration of 2 and 1.15mm was found for right and left parotid glands respectively, correlated with GTV N reduction volume. We found a significant increase in mean doses for the parotid glands. It was 1.8±2.3Gy for the right and 1.5±2.7Gy for the left. For the right sub maxillary gland, the increase was about 0.35±2Gy and 3.79±5.2Gy for the thyroid., Conclusion: The modifications observed for glandular structures during NPC IMRT can explain the different toxicities caused by radiation. It seems also that a careful adaptation of the treatment plan should be considered during therapy., (Copyright © 2020 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background and Purpose: To assess anatomic changes during intensity modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) and to determine its dosimetric impact., Patients and Methods: Twenty patients treated with IMRT for NPC were enrolled in this study. A second CT was performed at 38 Gy. Manual contouring of the macroscopic tumor volumes (GTV) and the planning target volumes (PTV) were done on the second CT. We recorded the volumes of the different structures, D98 %, the conformity, and the homogeneity indexes for each PTV. Volume percent changes were calculated., Results: We observed a significant reduction in tumor volumes (58.56 % for the GTV N and 29.52 % for the GTV T). It was accompanied by a significant decrease in the D98 % for the 3 PTV (1.4 Gy for PTV H, p = 0.007; 0.3 Gy for PTV I, p = 0.03 and 1.15 Gy for PTV L, p = 0 0.0066). In addition, we observed a significant reduction in the conformity index in the order of 0.02 (p = 0.001) and 0.01 (p = 0.007) for PTV H and PTV I, respectively. The conformity variation was not significant for PTV L. Moreover, results showed a significant increase of the homogeneity index for PTV H (+ 0.03, p = 0.04) and PTV L (+ 0.04, p = 0.01)., Conclusion: Tumor volume reduction during the IMRT of NPC was accompanied by deterioration of the dosimetric coverage for the different target volumes. It is essential that a careful adaptation of the treatment plan be considered during therapy for selected patients., (© 2019 Greater Poland Cancer Centre. Published by Elsevier B.V. All rights reserved.)

Background: To evaluate the patterns of failure in patients treated for head and neck carcinoma of unknown primary and to discuss treatment practices concerning radiotherapy target volumes definition and dose prescription., Methods: Eleven patients presenting a locoregional recurrence after head and neck carcinoma of unknown primary treatment with curative-intent radiochemotherapy performed between 2007 and 2017 in the departments of radiation oncology of 2 French cancer institutes. Images of the computed tomography scan or the magnetic resonance imaging performed at the time of the recurrence were fused with those of the simulation computed tomography scan to delimit a volume corresponding to the recurrence and to define the area of relapse compared to the volumes treated., Results: Irradiation was unilateral in 6 cases and bilateral in 5 cases. The median time to onset of recurrence was 7.24 months (extreme 3-67.7 months). Six patients had only a neck node recurrence, 3 had a neck node and subsequent primary recurrence, and 1 had only a median subsequent primary recurrence. Only 1 patient had synchronous distance progression to local recurrence. All neck node recurrences were solitary and ipsilateral. The subsequent primary recurrences were in the oropharynx in 3 cases and in the contralateral oral cavity in one case. All neck node recurrences were into the irradiated volume. The subsequent primary recurrences were either within or in border of the irradiated volumes. The median of the mean dose, received by neck node recurrences, was 69.9 Gy and that of the mean dose, minimum dose, maximum dose, and dose received by 95% of the volume of recurrence was 66.7 Gy. For the primary relapses, the median of the mean dose was 52.1 Gy and that of the mean dose, minimum dose, maximum dose, and dose received by 95% of the volume of recurrence was 39.9 Gy., Conclusions: All local nodal recurrences occurred at sites that received high radiotherapy doses and doses received by sites of eventual failure did not vary significantly from sites that remain in control.

Purpose: We report in this study, the dosimetric and carcinologic results of intensity-modulated technique for the reirradiation of nasopharyngeal carcinomas., Patients and Methods: Eight patients reirradiated with intensity-modulation technique between January 2015 and December 2017 were included. We noted for each patient: the minimum, maximum and average doses, the dose received by 95% (D95%), 98% (D98%) and 2% (D2%) of the volume to be irradiated, the homogeneity and conformity indices and doses to the organs at risk., Results: Target volume coverage was satisfactory with a median of D95% greater than 57Gy (95% of the prescribed dose). The median maximum dose received by the spinal cord and brainstem were 8.2Gy and 18.25Gy, respectively. After a median follow-up of 14.5 months [1-29 months], five patients were in complete remission of their disease. Overall survival at 2 years was 66.7%. An increase in preexisting late toxicity after the first irradiation (now grade 2 or above) was found in four patients (50% of cases)., Conclusion: Intensity-modulation is an attractive technique for reirradiation of the nasopharynx. It allows a better conformity of the dose to the target and a reduction of the doses on the already irradiated critical organs. This offers good control of the disease with fewer severe late toxicities., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Objectives: We aimed to establish a novel murine intra-abdominal foreign body infection model to study the activity of anidulafungin and tigecycline against dual species Candida albicans/Staphylococcus aureus biofilms., Methods: In vitro and in vivo single and dual species biofilms were developed inside serum-coated triple-lumen catheters placed in 24-well plates or implanted intraperitoneally in BALB/c mice. The effect of tigecycline and anidulafungin alone and in combination was tested using clinically relevant concentrations. Scanning electron microscopy was used to visualize the mature biofilm structure developed intraperitoneally. Flow cytometry was used to determine the immunological response upon infection. Immunoblot analysis allowed us to determine the effect of anidulafungin on poly-β-(1,6)-N-acetylglucosamine in in vitro-grown S. aureus biofilms., Results: We determined the MIC, MBC and in vitro susceptibility profile for anidulafungin and tigecycline against C. albicans and S. aureus in mixed and single species biofilms. We demonstrated that anidulafungin acts synergistically when combined with tigecycline against in vivo intra-abdominal biofilms. Moreover, we reveal that anidulafungin reduces the abundance of S. aureus poly-β-(1,6)-N-acetylglucosamine. The influx of neutrophils is much increased when infected with mixed biofilms compared with single species biofilms., Conclusions: Currently, treatment of intra-abdominal infections, in particular polymicrobial catheter-associated peritonitis, is ineffective. To the best of our knowledge, this is the first study that provides insight into new possible options for treatment of C. albicans/S. aureus biofilms present in the abdominal cavity.

Staphylococcal biofilms are a major cause of therapeutic failure, especially when caused by multiresistant strains. Oral fusidic acid is currently being redeveloped in the United States for skin, skin structure, and orthopedic infections, in which biofilms play a major role. The aim of this study was to examine the activity of fusidic acid alone or combined with other antistaphylococcal drugs against biofilms made by a reference strain and five clinical isolates of Staphylococcus aureus or Staphylococcus epidermidis in in vitro static and dynamic models (microtiter plates and a CDC reactor) exposed to clinically relevant concentrations. In microtiter plates, antibiotics alone were poorly active, with marked differences among strains. At concentrations mimicking the free-drug human maximum concentration of drug in serum ( C max ), the combination of fusidic acid with linezolid, daptomycin, or vancomycin resulted in increased activity against 4 to 5 strains, while the combination with doxycycline, rifampin, or moxifloxacin increased activity against 1 to 3 strains only. In the CDC reactor, biofilms were grown under constant flow and antibiotic concentrations decreased over time according to human elimination rates. A bactericidal effect was obtained when fusidic acid was combined with daptomycin or linezolid, but not with vancomycin. The higher tolerance of biofilms to antibiotics in the CDC reactor is probably attributable to the more complex architecture they adopt when growing under constant flow. Because biofilms grown in the CDC reactor are considered more similar to those developing in vivo , the data support further testing of combinations of fusidic acid with daptomycin or linezolid in models pertinent to chronic skin, skin structure, or orthopedic infections., (Copyright © 2018 American Society for Microbiology.)

Purpose: A retrospective study to evaluate the efficacy and safety of the addition of neoadjuvant chemotherapy to concurrent chemoradiotherapy in the treatment of nasopharyngeal carcinoma., Patients and Methods: Data from 62 patients treated for non-metastatic nasopharyngeal carcinoma were analyzed by comparing two groups of patients: a first group of 32 patients treated with 3 cycles of neoadjuvant chemotherapy based on docetaxel, cisplatin and 5-fluoro-uracil every 21 days followed by concurrent chemoradiotherapy (weekly cisplatin 40mg/m 2 with radiotherapy 70Gy, 2Gy per session, 5 sessions per week) and a second group of 30 patients treated with the same concurrent chemoradiotherapy., Results: After a median follow-up of 53.5 months, neoadjuvant chemotherapy showed a significant reduction in the rate of a distant metastatic relapses (3.3% vs. 10%, P=0.03). No significant difference in disease-free survival at 5 years (65.6% vs. 68.8%, P=0.46) or overall survival at 5 years (68.8% vs. 73.3%, P=0.46) was noted between the two groups. Induction chemotherapy was associated with febrile neutropenia of 15.6%. During concurrent chemoradiotherapy, hematological complications were greater in the first chemotherapy group (53% vs. 33%)., Conclusion: Induction chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil is a safe and effective option in the treatment of nasopharyngeal carcinoma. A better definition of high risk of relapse group would optimize the indications of this chemotherapy in the therapeutic arsenal., (Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: Retrospective analysis of clinical aspects and therapeutic results of nasopharynx cancer local failures., Patients and Methods: Forty patients with local failure with or without nodal involvement of nasopharyngeal carcinoma were treated between 1993 and 2013. Reirradiation of nasopharynx was delivered at the dose of 60Gy. Platinum-based chemotherapy was indicated in case of locally advanced disease and/or associated nodal failure., Results: The mean age at diagnosis of primitive tumour was 41.9 years (26-67 years). The mean time of relapse occurrence was 31.7 months (6-104 months). Sixty five percent of failures were confined to the nasopharynx. Nodal failure was seen in 14 cases. Twenty-eight patients had chemotherapy. Twenty-five patients had reirradiation of nasopharynx. Mean follow-up was 98 months (12-191 months). Fourteen patients were still alive and in complete remission. Five-year survival was 40.7%. Xerostomia was the most frequent late toxicity. No haemorrhage was seen., Conclusion: Reirradiation is the mainstay treatment of nasopharyngeal local failure. Late toxicity seems to decrease with novel techniques of reirradiation., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Biofilms play a major role in Staphylococcus aureus pathogenicity but respond poorly to antibiotics. Here, we show that the antifungal caspofungin improves the activity of fluoroquinolones (moxifloxacin, delafloxacin) against S. aureus biofilms grown in vitro (96-well plates or catheters) and in vivo (murine model of implanted catheters). The degree of synergy among different clinical isolates is inversely proportional to the expression level of ica operon, the products of which synthesize poly-N-acetyl-glucosamine polymers, a major constituent of biofilm matrix. In vitro, caspofungin inhibits the activity of IcaA, which shares homology with β-1-3-glucan synthase (caspofungin's pharmacological target in fungi). This inhibition destructures the matrix, reduces the concentration and polymerization of exopolysaccharides in biofilms, and increases fluoroquinolone penetration inside biofilms. Our study identifies a bacterial target for caspofungin and indicates that IcaA inhibitors could potentially be useful in the treatment of biofilm-related infections., Competing Interests: F.V.B. and P.M.T. have received research grants from Melinta Therapeutics for projects unrelated to the present work. The remaining authors declare no competing financial interests.

Antibiotic resistance of bacteria growing in biofilms compared to their planktonic counterparts enhances the difficulty to eradicate biofilm-associated infections. In the last decade, combination antibiotic therapy has emerged as an attractive strategy for treating biofilm infections, even if in most of tolerant biofilms the optimal combinations are still unknown. In this study, an antimicrobial cationic polyacrylamide was used in combination with daptomycin or moxifloxacin against mature biofilms of Staphylococcus aureus clinical isolates to examine a possible improvement of the antibiofilm activity of the two antibiotics. The polymer did not have an effect on moxifloxacin but significantly increased the antibiofilm efficacy of daptomycin. These findings are presumably related to the different mechanism of action of the two drugs. In summary, our data highlighted the ability of polycations to increase daptomycin antibiofilm activity providing a potential strategy to eradicate biofilms in industrial or medical settings., (© FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Biofilm-related infections remain a scourge. In an in vitro model of biofilms using Staphylococcus aureus reference strains, delafloxacin and daptomycin were found to be the most active among the antibiotics from 8 different pharmacological classes (J. Bauer, W. Siala, P. M. Tulkens, and F. Van Bambeke, Antimicrob. Agents Chemother. 57:2726-2737, 2013, doi:10.1128/AAC.00181-13). In this study, we compared delafloxacin to daptomycin and vancomycin using biofilms produced by 7 clinical strains (S. aureus epidemic clones CC5 and CC8) in order to rationalize the differences observed between the antibiotics and strains. The effects of the antibiotics on bacterial viability (resazurin reduction assay) and biomass (crystal violet staining) were measured and correlated with the proportion of polysaccharides in the matrix, the local microenvironmental pH (micro-pH), and the antibiotic penetration in the biofilm. At clinically meaningful concentrations, delafloxacin, daptomycin, and vancomycin caused a ≥25% reduction in viability against the biofilms formed by 5, 4, and 3 strains, respectively. The antibiotic penetration within the biofilms ranged from 0.6 to 52% for delafloxacin, 0.2 to 10% for daptomycin, and 0.2 to 1% for vancomycin; for delafloxacin, this was inversely related to the polysaccharide proportion in the matrix. Six biofilms were acidic, explaining the high potency of delafloxacin (lower MICs at acidic pH). Norspermidine and norspermine (disassembling the biofilm matrix) drastically increased delafloxacin potency and efficacy (50% reduction in viability for 6 biofilms at clinically meaningful concentrations) in direct correlation with its increased penetration within the biofilm, while they only modestly improved daptomycin efficacy (50% reduction in viability for 2 biofilms) and penetration, and they showed marginal effects with vancomycin. Delafloxacin potency and efficacy against biofilms are benefited by its penetration into the matrix and the local acidic micro-pH., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Neuroendocrine carcinoma of the head and neck is a rare entity. The parotid gland is the most commonly affected site. A nasopharyngeal site has not been previously described. We report a 35-year-old patient who consulted for tinnitus and nasal obstruction. The assessment found a nasopharyngeal tumour T4N0M0. The patient underwent 6 cycles of chemotherapy based on VP16 and cisplatin, followed by radiotherapy at a dose of 70 Gy to the nasopharynx and 50 Gy to the neck. The evolution was marked by clinical improvement and radiological stability. Six months after the end of treatment, the patient had a local and meningeal relapse. He received palliative care. He died 19 months after the end of treatment., (Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Thioredoxins (TRX) are key components of cellular redox balance, regulating many target proteins through thiol/disulfide exchange reactions. In higher plants, TRX constitute a complex multigenic family whose members have been found in almost all cellular compartments. Although chloroplastic and cytosolic TRX systems have been largely studied, the presence of a nuclear TRX system has been elusive for a long time. Nucleoredoxins (NRX) are potential nuclear TRX found in most eukaryotic organisms. In contrast to mammals, which harbor a unique NRX, angiosperms generally possess multiple NRX organized in three subfamilies. Here, we show that Arabidopsis thaliana has two NRX genes (AtNRX1 and AtNRX2), respectively, belonging to subgroups I and III. While NRX1 harbors typical TRX active sites (WCG/PPC), NRX2 has atypical active sites (WCRPC and WCPPF). Nevertheless, both NRX1 and NRX2 have disulfide reduction capacities, although NRX1 alone can be reduced by the thioredoxin reductase NTRA. We also show that both NRX1 and NRX2 have a dual nuclear/cytosolic localization. Interestingly, we found that NTRA, previously identified as a cytosolic protein, is also partially localized in the nucleus, suggesting that a complete TRX system is functional in the nucleus. We show that NRX1 is mainly found as a dimer in vivo. nrx1 and nrx2 knockout mutant plants exhibit no phenotypic perturbations under standard growth conditions. However, the nrx1 mutant shows a reduced pollen fertility phenotype, suggesting a specific role of NRX1 at the haploid phase.

Purpose: To compare therapeutic results of nasopharyngeal carcinoma between adults and children., Patients and Methods: Three hundred and seventy seven patients with nasopharyngeal carcinoma received a radiotherapy between 1993 and 2007. Sixty-nine of them were 20years old or less. Two hundred and sixty eight patients received a chemotherapy (neoadjuvant or concomitant)., Results: Overall survival and disease-free survival at 5 years were 67 % and 59.4 % in all patients, respectively. Overall survival rates at 5 years in children and adults were 66 % and 64 %, respectively (P=0.17), disease-free survival rates at 5 years were 66 % and 57 %, respectively (P=0.17). Local failures occurred more frequently in adults than in children (1.4 % versus 14 %). However, metastatic events were frequently seen in children. Late toxicities were important in children, xerostomia was the most common one., Conclusion: Despite locally advanced disease in children, therapeutic results were better than in adults but not statistically significant. The use of treatment combination (chemotherapy and radiotherapy) in juvenile nasopharyngeal carcinoma may explain our findings., (Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Biofilms are associated with persistence of Staphylococcus aureus infections and therapeutic failures. Our aim was to set up a pharmacodynamic model comparing antibiotic activities against biofilms and examining in parallel their effects on viability and biofilm mass. Biofilms of S. aureus ATCC 25923 (methicillin-sensitive S. aureus [MSSA]) or ATCC 33591 (methicillin-resistant S. aureus [MRSA]) were obtained by culture in 96-well plates for 6 h/24 h. Antibiotic activities were assessed after 24/48 h of exposure to concentrations ranging from 0.5 to 512 times the MIC. Biofilm mass and bacterial viability were quantified using crystal violet and the redox indicator resazurin. Biofilms stained with Live/Dead probes were observed by using confocal microscopy. Concentration-effect curves fitted sigmoidal regressions, with a 50% reduction toward both matrix and viability obtained at sub-MIC or low multiples of MICs against young biofilms for all antibiotics tested. Against mature biofilms, maximal efficacies and potencies were reduced, with none of the antibiotics being able to completely destroy the matrix. Delafloxacin and daptomycin were the most potent, reducing viability by more than 50% at clinically achievable concentrations against both strains, as well as reducing biofilm depth, as observed in confocal microscopy. Rifampin, tigecycline, and moxifloxacin were effective against mature MRSA biofilms, while oxacillin demonstrated activity against MSSA. Fusidic acid, vancomycin, and linezolid were less potent overall. Antibiotic activity depends on biofilm maturity and bacterial strain. The pharmacodynamic model developed allows ranking of antibiotics with respect to efficacy and potency at clinically achievable concentrations and highlights the potential utility of daptomycin and delafloxacin for the treatment of biofilm-related infections.

Objectives: To analyze retrospectively the risk factors for occurrence of thyroid toxicity after radiotherapy for nasopharyngeal cancer and to demonstrate the necessity of a long-term post-therapeutic screening., Patients and Methods: Between 1993 and 2004, 239 patients with non-metastatic nasopharyngeal carcinoma were treated by conventional radiotherapy with or without chemotherapy. Radiotherapy was delivered by a standard fractionation (2 Gy/fraction, 5 fractions/week) for 157 patients and hyperfractionation (1.6 Gy/fraction, 2 fractions/day, 5 days/week) for 82 patients. An evaluation of thyroid late toxicity was performed according to tumor stage, age, gender, time after treatment, irradiation method and association or not with chemotherapy., Results: After a median follow up of 111 months, 72 patients (30%) had primitive and/or pituitary thyroid dysfunction. Fifty-seven patients (24%) experienced hypothyroidism, peripheral in 92% of cases (biological 73%, clinical 19%) and central in 8% of cases. Hypothyroidism was detected at a mean 37 months follow up. All patients received replacement treatment with l-thyroxin. The actuarial rate of hypothyroidism was 18.1%, 24.3% and 35% at respectively 3, 5 and 10 years. Only female gender was found as a risk factor for occurrence of hypothyroidism in univariate analysis. However, younger age and advanced tumor stage were associated with a higher risk but the difference was not significant (P = 0.08 for each). There was no difference for other factors: nodal stage, modality of radiation and chemotherapy treatment. The multivariate analysis did not show any risk factor., Conclusion: Thyroid dysfunction after radiotherapy for nasopharyngeal carcinoma is frequent and requires systematic screening to begin adequate treatment earlier. Only gender has been identified as risk factor in univariate analysis in this study., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Nasopharyngeal carcinoma (NPC) represents one of the most frequent epithelial tumours of the child in intermediate risk regions. In the Maghreb, it represents the first cancer of teenagers of 15-20 years old. The Epstein Barr virus (EBV) is the most important etiologic factor. Its role in the pathogeneses of NPC has been confirmed by several studies. Young NPCs are characterized by a low rate of EBV antibodies and a high level of LMP1 cell expression than in adult's NPC. The undifferentiated carcinoma nasopharyngeal type (UCNT) represents the most frequent histological type. Immunohistochemical analyses of North Africa early onset NPC is characterized by a weak expression of bcl-2 and p53 and a strong expression of LMP1 and c-kit what makes them different from the adult's NPC. Clinically, cervical node involvement is constantly present. Juvenile NPC is characterized by a very important locoregional extension as well as a high rate of distant metastases. More than 15% of patients had metastases at diagnosis. Radiotherapy is still the standard therapy of NPC. Only some retrospectives studies have been published to determine the benefit, the type and the timing of the chemotherapy in the treatment of juvenile NPC. Metastatic relapses constitute the main cause of death at these young patients. An improvement of the prognosis can be waited with concomitant chemotherapy and intensity modulated radiotherapy. However, randomized multi institutional studies are necessary to standardize the treatment of the NPC in childhood.

Nasopharyngeal carcinoma (NPC) is an unusual head and neck cancer because of its unequal geographical distribution and its consistent association with the Epstein-Barr virus (EBV). This malignant tumor poses a serious public health problem in many countries, especially in Southeast Asia and North Africa where the recorded incidence are highest. During the past decade, a growing number of studies were undertaken to define the molecular basis of NPC. However, the analysis of several clinical and biological parameters of North African and Southeast Asian NPCs has shown notable differences, suggesting that they could result from a distinct combination of etiological factors. One intriguing characteristic of North African NPC, concerns its bimodal age distribution with a secondary peak of incidence in the range of 15-25 years, not observed in Asian NPC. In this juvenile form of NPC, immuno-histochemistry assay has shown that the two key proteins controlling the apoptotic-survival balance p53 and Bcl-2 are less frequently expressed whereas the transmembrane tyrosine-kinase receptor c-kit and the main EBV oncoprotein LMP1 were more abundant. In addition, the EBV serological alterations are less informative for the diagnosis of the juvenile compared to the adult form. In addition, most North African NPCs contain EBV strains with genetic polymorphisms distinct from those described in the Southeast Asia series (predominance of F, D, H1-H2, XhoI+ and f, C, H, XhoI- respectively). In contrast, studies relating on tumor chromosomal alterations or aberrant promoter methylation result in data very similar to those obtained from the Southeast Asia series, supporting the concept of a common molecular basis for all NPC regardless of patient geographic origin.

Purpose: A retrospective analysis of risk factors for late neurological toxicity after nasopharyngeal carcinoma radiotherapy., Patients and Methods: Between 1993 and 2004, 239 patients with non metastatic nasopharyngeal carcinoma were treated by radiotherapy associated or not to chemotherapy. Radiotherapy was delivered with two modalities: hyperfractionated for 82 patients and conventional fractionation for 157 patients. We evaluated the impact of tumour stage, age, gender, radiotherapy schedule and chemotherapy on neurological toxicity., Results: After a mean follow-up of 107 months (35-176 months), 21 patients (8.8%) developed neurological complications, such as temporal necrosis in nine cases, brain stem necrosis in five cases, optics nerve atrophy in two cases and myelitis in one case. Five- and ten-year free of toxicity survival was 95 and 84% respectively. Young patients had greater risk of temporal necrosis, and hyperfractionated radiotherapy was associated with a significantly higher risk of neurological complications (14.6% vs 5.7%, p=0.02). On multivariate analysis, hyperfractionation and age were insignificant., Conclusion: Late neurological toxicity after radiotherapy for nasopharyngeal carcinoma was rare. Younger age and hyperfractionation were considered as risk factors of neurological toxicity in our study.

Tight control of cellular redox homeostasis is essential for protection against oxidative damage and for maintenance of normal metabolism as well as redox signaling events. Under oxidative stress conditions, the tripeptide glutathione can switch from its reduced form (GSH) to oxidized glutathione disulfide (GSSG), and thus, forms an important cellular redox buffer. GSSG is normally reduced to GSH by 2 glutathione reductase (GR) isoforms encoded in the Arabidopsis genome, cytosolic GR1 and GR2 dual-targeted to chloroplasts and mitochondria. Measurements of total GR activity in leaf extracts of wild-type and 2 gr1 deletion mutants revealed that approximately 65% of the total GR activity is attributed to GR1, whereas approximately 35% is contributed by GR2. Despite the lack of a large share in total GR activity, gr1 mutants do not show any informative phenotype, even under stress conditions, and thus, the physiological impact of GR1 remains obscure. To elucidate its role in plants, glutathione-specific redox-sensitive GFP was used to dynamically measure the glutathione redox potential (E(GSH)) in the cytosol. Using this tool, it is shown that E(GSH) in gr1 mutants is significantly shifted toward more oxidizing conditions. Surprisingly, dynamic reduction of GSSG formed during induced oxidative stress in gr1 mutants is still possible, although significantly delayed compared with wild-type plants. We infer that there is functional redundancy in this critical pathway. Integrated biochemical and genetic assays identify the NADPH-dependent thioredoxin system as a backup system for GR1. Deletion of both, NADPH-dependent thioredoxin reductase A and GR1, prevents survival due to a pollen lethal phenotype.

Introduction: Head and neck sarcomas comprise a heterogeneous and biologically diverse set of rare neoplasms. The difficulty treating the disease requires multidisciplinary consultation to improve outcome. In an effort to clarify the clinical behavior of head and neck sarcomas and evaluate treatment, we present our experience and review the relevant literature., Patients and Methods: This is a retrospective analysis of 15 patients with histologically proven head and neck sarcoma treated in the ENT department between 1998 and 2007. All cases were confirmed by histologic exam with immunohistochemical analysis., Results: Nine women and six men were included in the study. The mean age was 38.4 years (range: 6-73 years). Computed tomography and MRI were done in 66.7% and 60% of the patients, respectively, to evaluate tumor extension. Metastases were demonstrated in three cases. Curative treatment in eight cases was based on different combinations of chemotherapy, radiotherapy, and surgery. Complete remission was obtained in eight cases. Local recurrence was noted in two cases. Two patients died from tumor metastasis. Two patients were lost to follow-up., Conclusion: Head and neck sarcomas present diverse rare neoplasms. They make up 5%-20% of all soft tissue sarcomas. All age groups can be affected by this neoplasm, with no predominance in one sex or the other. The most common histologic type is rhabdomyosarcoma, especially in children. Because of the potential for systemic metastasis, extension must be assessed. Treatment is based essentially on the association of surgery, radiotherapy, and chemotherapy to optimize therapeutic results. Five-year survival varies between 44% and 80%.

During the 70s and 80s two plant thioredoxin systems were identified. The chloroplastic system is composed of a ferredoxin-dependent thioredoxin, with two thioredoxin types (m and f) regulating the activity of enzymes implicated in photosynthetic carbon assimilation. In the cytosol of heterotrophic tissues, an NADP dependent thioredoxin reductase and a thioredoxin (h) were identified. The first plant glutaredoxin was only identified later, in 1994. Our view of plant thioredoxins and glutaredoxins was profoundly modified by the sequencing programs which revealed an unexpected number of genes encoding not only the previously identified disulfide reductases, but also numerous new types. At the same time it became clear that plant genomes encode chloroplastic, cytosolic and mitochondrial peroxiredoxins, suggesting a major role for redoxins in anti-oxidant defense. Efficient proteomics approaches were developed allowing the characterization of numerous thioredoxin target proteins. They are implicated in different aspects of plant life including development and adaptation to environmental changes and stresses. The most important challenge for the next years will probably be to identify in planta which redoxin reduces which target, a question which remains unsolved due to the low specificities of redoxins in vitro and the numerous redundancies which in most cases mask the phenotype of redoxin mutants.

Background and Purpose: Nasopharyngeal carcinoma (NPC) is generally responsive to radiation therapy. However therapeutic results after conventional radiotherapy remain relatively poor especially for patients with locoregional advanced NPC. The aim of this study was to evaluate the impact of a split course bifractionated radiotherapy regimen in a phase III randomised trial., Patients and Methods: From January 1997 to September 2003, 154 patients with M0 histologically proven NPC were treated in our institution. They were staged according to the American Joint Committee on Cancer - International Union Against Cancer (AJCC-UICC) 1986 TNM classification. Patients with locally advanced nodal disease (N2-N3) received induction chemotherapy. All patients were randomised to receive either conventional radiotherapy at 2 Gy/fraction/day, 5 days/week to 70 Gy/7 weeks or split course bifractionated radiotherapy at 1.6 Gy/fraction, twice daily, 5 days/week to 70.4 Gy/6 weeks. Response and toxicity were evaluated according to the WHO and RTOG criteria., Results: Patients were well balanced between the two arms. The complete remission rate was 91% in conventional radiotherapy arm and 93% in bifractionated radiotherapy arm (p=0.3). There was more grade II-III skin fibrosis in experimental arm with a 5 year actuarial probability of 66% vs 52% (p=0.04). Locoregional and distant relapses occurred in 34% of cases in conventional arm and 38% in experimental arm (p=0.28). With a median follow-up of 56 months, the 5 year overall survival and the disease free survival rates were, respectively (71% and 61%), in conventional arm and (62% and 60%) in bifractionated arm, the difference being statistically non significant., Comments: The present trial comparing conventional radiotherapy to a split course bifractionated radiation therapy failed to demonstrate significant improvement in locoregional control and survival in experimental arm which was associated with more grade II-III skin fibrosis.

Purpose: 1/ To evaluate the incidence of hypothyroidism following radiotherapy in the management of breast and nasopharyngeal carcinomas, 2/ to define the role of a systematic post therapeutic screening., Patients and Methods: From January 1996 through March 2001 a systematic evaluation of the clinical and the biological thyroid function was performed on a cohort of 84 patients that received supraclavicular irradiation. Selected patients had either a mammary (37 cases) or a nasopharyngeal (47 cases) carcinoma. Initial work up included thyroid inspection and palpation, and biological tests: serum FT4 and TSH levels, radioimmunochemistry, completed by dynamic thyroid stimulation, using TRH, in case of border line low T4 or isolated high TSH levels. Tests were repeated every three months the first year, and then every six months. Replacement therapy with L Thyroxin was administered in case of hypothyroidism., Results: All selected patients had a normal function initially. With a mean two years follow up (1-5 years), 24 patients (29%) experienced hypothyroidism, half of whom (13 cases) being purely biological. Five patients (11%), with a nasopharyngeal carcinoma, presented also with associated pituitary failure. Clinical symptoms were minor or mild in all cases. Hypothyroidism was detected at a mean 21 months follow up. In 2 patients, hypothyroidism disappeared spontaneously within 6 months. Possible predictive factors were evaluated: age of the time of radiation, gender, percentage of irradiated thyroid, total dose, dose per fraction, tumour type and chemotherapy. Only age appeared significantly correlated with thyroid dysfunction (range: 10-30 years, P=0.002)., Conclusion: Hypothyroidism is a frequent and certainly underestimated complication following radiotherapy of the neck. In such patients, a systematic clinical and biological evaluation every three months the first year, and then every six months until five years is recommended.

Aims: The thyroid dysfunction after radiotherapy has led to evaluate the dose received by thyroid during nasopharynx and breast carcinoma irradiation. This evaluation was facilitated by in vivo dosimetry. The aims of this work were to evaluate the thyroid dose and to compare released dose at the reference point in the two localizations., Patients and Methods: A total of 30 patients were evaluated: 18 patients with nasopharynx carcinoma and 12 patients with breast carcinoma were included in the final analysis. In the first group, the total thyroid but the isthmus was irradiated. On the other hand, in the second group, only one thyroid lobe was included into the target volume. All patients have been treated by gamma rays of cobalt 60 and the thyroid absorbed dose was measured by semiconductor dosimeters (Scanditronix DPD6). These dosimeters were calibrated in the same geometric conditions of the irradiation., Results: The measured absorbed dose of the thyroid parenchyma was equal to the calculated absorbed dose at the target that has been specified at a depth of -3 cm. Under the block, the isthmus received 5.1 +/- 0.9 Gy (9.9 +/- 1.8%) in nasopharynx carcinoma irradiation. However, in breast carcinoma irradiation, the distal thyroid lobe and the isthmus received 2.9 +/- 0.7 Gy (6.55 +/- 1.56%) and 3.69 +/- 0.77 (8.39 +/- 1.76%), respectively., Conclusions: This study shows that the thyroid received a dose equal to the prescribed dose in both nasopharynx and breast cancer patients. It is recommended to follow the function of the thyroid gland in these patients.

Background: Study of the epidemiological, clinical and evolutive characteristics of the erysipelas of patients treated for breast cancer., Patients and Methods: Between February 93 and December 99, 20 patients among 700 (2.85%) treated for breast cancer in the radiotherapy department of sfax have presented an erysipelas. All of these patients had undergone a chirurgical treatment containing an axillary lymph node dissection with radiotherapy in 95% and adjuvent chemotherapy in 80% of cases., Results: The medium delay between the appearance of the eryslpelas and the end of treatment was 23 months. The preferential localisation was the homolateral upper limb to the treated breast (95%). The immediate evolution was favourable in 85% after antibiotherapy. Recurrence of erysipelas was seen in 20% in cases., Discussion: Erysipelas after treatment of breast cancer is known but rarely reported. The secondary lymphedema of the upper limb is the major favouring factor., Conclusion: Appearance of erysipelas among women treated for breast cancer is frequent, his recurrent character must always lead to antibiotic prophylaxis.