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Re-irradiation is becoming an established treatment option for recurrent or second primary head and neck cancer(HNC). However, acute and long-term RT-related toxicities could dramatically impact patients' quality of life. Due to the sparse literature regarding HNC re-irradiation, data on tolerance doses for various organs at risk (OARs) are scarce. Our aim was to systematically review the clinical literature regarding HNC re-irradiation, focusing on treatment toxicity, OARs tolerance, and dose limit recommendations. Thirty-nine studies (three randomized, five prospective, 31 retrospective) including 3766 patients were selected. The median interval time between the first course and re-irradiation was 28 months (range, 6–90). In 1043 (27.6%) patients, postoperative re-irradiation was performed. Re-irradiation doses ranged from 30 Gy in 3 fractions using stereotactic technique to 72 Gy in conventional fractionation using intensity-modulated radiotherapy. Pooled acute and late toxicityrates ≥G3 were 32% and 29.3%, respectively. The most common grade 3–4 toxic effects were radionecrosis, dysphagia requiring feeding tube placement and trismus. In 156 (4.1%) patients, carotid blowout was reported. Recommendations for limiting toxicity included the time interval between radiation treatments, the fractionation schedules, and the re-irradiation treatment volumes. Cumulative dose limit suggestions were found and discussed for the carotid arteries, temporal lobes, and mandible.

Additional file 3: figure 3.: fused FDG-PET/CT images of a 67-year old male with a T4aN3 oropharyngeal cancer: Tref assessment negative for residual tumor according to all scales

Additional file 4: figure 4. fused FDG-PET/CT images of a 69-year old male with a T4aN2b laryngeal cancer: Nref assessment negative for residual tumor according to all scales

Additional file 2: figure 2. overall survival (Kaplan Meyer method)

Purpose Response assessment to definitive non-surgical treatment for head and neck squamous cell carcinoma (HNSCC) is centered on the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET-CT) 12 weeks after treatment. The 5-point Hopkins score is the only qualitative system available for standardized reporting, albeit limited by suboptimal positive predictive value (PPV). The aim of our study was to explore the feasibility and assess the diagnostic accuracy of an experimental 6-point scale (“Cuneo score”). Methods We performed a retrospective, multicenter study on HNSCC patients who received a curatively-intended, radiation-based treatment. A centralized, independent qualitative evaluation of post-treatment FDG-PET/CT scans was undertaken by 3 experienced nuclear medicine physicians who were blinded to patients’ information, clinical data, and all other imaging examinations. Response to treatment was evaluated according to Hopkins, Cuneo, and Deauville criteria. The primary endpoint of the study was to evaluate the PPV of Cuneo score in assessing locoregional control (LRC). We also correlated semi-quantitative metabolic factors as included in PERCIST and EORTC criteria with disease outcome. Results Out of a total sample of 350 patients from 11 centers, 119 subjects (oropharynx, 57.1%; HPV negative, 73.1%) had baseline and post-treatment FDG-PET/CT scans fully compliant with EANM 1.0 guidelines and were therefore included in our analysis. At a median follow-up of 42 months (range 5-98), the median locoregional control was 35 months (95% CI, 32-43), with a 74.5% 3-year rate. Cuneo score had the highest diagnostic accuracy (76.5%), with a positive predictive value for primary tumor (Tref), nodal disease (Nref), and composite TNref of 42.9%, 100%, and 50%, respectively. A Cuneo score of 5-6 (indicative of residual disease) was associated with poor overall survival at multivariate analysis (HR 6.0; 95% CI, 1.88-19.18; p = 0.002). In addition, nodal progressive disease according to PERCIST criteria was associated with worse LRC (OR for LR failure, 5.65; 95% CI, 1.26-25.46; p = 0.024) and overall survival (OR for death, 4.81; 1.07-21.53; p = 0.04). Conclusions In the frame of a strictly blinded methodology for response assessment, the feasibility of Cuneo score was preliminarily validated. Prospective investigations are warranted to further evaluate its reproducibility and diagnostic accuracy.

Additional file 6: material. FDG-PET/CT analysis

Additional file 1: figure 1. progression-free survival (Kaplan Meyer method)

Additional file 5: table 1. positive predictive value and corresponding 95% CI of composite TNref for specific scores. PPV: positive predictive value

Aims and background The coexistence of tuberculous lymphadenitis of the neck region and head and neck cancer is extremely rare. In this clinical situation, the use of positron emission and computed tomography using fluorine-18 fluorodeoxyglucose (18F-FDG PET/CT) may facilitate the differentiation between malignancy and tuberculosis. Case Report We present a case of an Eastern European man with nasopharyngeal cancer and concurrent tuberculous lymphadenitis. Results and conclusion The adequate and critical interpretation of pretreatment 18F-FDG PET/CT scan addressed the multidisciplinary team to the proper staging of disease and to the correct therapeutic approach.

Aim: To evaluate the effect of oral caffeine supplementation and strenuous intermittent exercise on muscle damage markers in soccer players. Materials and Methods: 15 male professional soccer players completed a placebo controlled double blind test protocol. At 45 min before exercise, participants ingested 5.5 mg·kg -1 body mass of caffeine (CAF, n=8) or cellulose (CEL, n=7). The exercise was 2 trials of 6 sets of 10 sprints (20 m each) with 10 s recovery time between sprints, 2 min between sets and 15 min between trials. Blood samples were collected before (PRE), 24, 48 and 72 h after exercise. Serum activity of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransaminase (AST), and alanine aminotrasaminase (ALT) were quantified. Results: Serum enzyme activity was enhanced by exercise in both groups, without a synergistic effect of caffeine. Conclusion: Our results suggest muscle damage markers increases after physical activities, but caffeine supplementation (5.5 mg·kg -1 body mass) has no influence upon serum enzymes reflective of muscle

Objectives The purpose of this study was to assess the role of oral rapamycin in decreased restenosis after bare metal stent implantation. Background Small observational studies suggest that the administration of oral rapamycin reduces angiographic restenosis after bare metal stent implantation. Methods Between September 2003 and September 2004, 100 patients were randomized to either oral rapamycin (6-mg loading dose given 2.7 h before intervention followed by 3 mg/day for 14 days) plus diltiazem 180 mg/day or no therapy after the implantation of a coronary bare metal stent design. The primary study end point was incidence of angiographic binary restenosis and late loss at nine months. The secondary end points were target lesion revascularization, target vessel revascularization, and incidence of major adverse cardiovascular events at 1 year. Results Angiographic follow-up was completed in 87% of patients. In the rapamycin group, the drug was well tolerated (26% minor side effects) and was maintained in 96% of patients. At 9 months, the in-segment binary restenosis was reduced by 72% (11.6% rapamycin vs. 42.8% no-therapy group, p = 0.001) and the in-stent binary restenosis was reduced by 65% (12% rapamycin vs. 34.6% no-therapy group, p = 0.009). The in-segment late loss was also significantly reduced with oral therapy (0.66 vs. 1.13 mm, respectively; 43% reduction, p Conclusions This randomized, controlled, and unblinded study showed that the administration of oral rapamycin during 14 days after stent implantation significantly reduces angiographic and clinical parameters of restenosis.

Objective: To assess the role of oral rapamycin in the prevention of coronary restenosis in patients undergoing coronary stenting. Methods: From December 2001 through February 2003, 76 patients with 103 de novo lesions treated percutaneously with bare stents received a loading dose of oral rapamycin 6 mg followed by a daily dose of 2 mg during 28 days in phase I (49 arteries in 34 patients) and 2 mg/day plus 180 mg/day of diltiazem in phase II (54 arteries in 42 patients). Rapamycin blood concentrations were measured in all patients. A six month follow up angiogram was performed in 82.5% (85 of 103 arteries). Follow up angiographic binary restenosis (> 50%), target vessel revascularisation, late loss, treatment compliance, and major adverse cardiovascular events were analysed and correlated with rapamycin concentrations. Results: Rapamycin was well tolerated and only three patients discontinued the treatment for mild side effects. Angiographic restenosis was found in 15% of the arteries with angiographic restudy (13 of 85). The target vessel had been revascularised at follow up in 13.6% of the 103 vessels initially treated (14 of 103) and in 18.4% of the 76 patients (14 of 76). In-stent restenosis in phase I was 19% compared with 6.2% in phase II (p = 0.06). Angiographic in-stent restenosis in lesions of patients with rapamycin blood concentrations ⩾ 8 ng/ml was 6.2% and with rapamycin concentrations v 1.1 mm, p = 0.031). A Pearson test showed a linear correlation between follow up late loss and rapamycin blood concentration ( r = −0.826, p = 0.008). Conclusion: Oral rapamycin administered for one month after percutaneous coronary intervention was safe and with few minor side effects. High rapamycin blood concentrations were associated with significantly lower late loss and angiographic in-stent restenosis.

Basolateral Na + /Ca 2+ exchanger (NCX) and plasma membrane Ca 2+ ATPase (PMCA) are the primary transmembrane proteins that export calcium (Ca 2+ ) from cells. In our lab we use a nonmammalian animal model, the freshwater crayfish, to study cellular Ca 2+ regulation. Two experimental conditions are employed to effect Ca 2+ dyshomeostasis: (a) in the postmolt stage of the crustacean molting cycle increased unidirectional Ca 2+ influx associated with cuticular mineralization is accompanied by elevated basolateral Ca 2+ export (compared with intermolt Ca balance); and (h) exposure of the poikilothermic crayfish to cold acclimation (4°C) causes influx of Ca 2+ into cells, which is compensated by increased basolateral Ca 2+ export (compared with exposure to 23°C). This study compares expression of both NCX and PMCA mRNA (real-time PCR) and protein (Western) in both epithelial (kidney) and nonepithelial tissue (tail muscle) during elevated basolateral Ca 2+ export. Both experimental treatments produced increases in NCX and PMCA expression (mRNA and protein) in both tissues. Mineralization produced greater upregulation of mRNA in kidney than in tail, whereas cold acclimation yielded comparable increases in both tissues. Protein expression patterns were generally confirmatory of real-time PCR data although expression changes were less pronounced. Both experimental treatments appear to increase basolateral Ca 2+ export.

Background and purpose: Irradiation of the Pharyngeal Superior Constrictor Muscle (PSCM) seems to play a crucial role in radiation-related swallowing dysfunctions. Purpose of our study was to quantify operator-related variability in the contouring of PSCM on Computed Tomography (CT) scans and adherence with contours derived from MR images. Materials and methods: Three sets of treatment planning CT and their corresponding MR images were selected. Contouring of the PSCM was performed using both a literature-based method, derived from literature review, and an optimized method, derived from Magnetic Resonance (MR) images thus obtaining ‘‘literature-based’’ and ‘‘optimized’’ contours. Each operator contoured the PSCM on CT scans according to both methods for three times in three different days. Inter- and intra-operator variability and adherence to a contour obtained from MR images (named ‘‘MR-derived’’ contour) were analyzed. Results: Thirty-four operators participated and 612 contours were obtained. Both intra- and inter-operator variability and adherence to the ‘‘MR-derived’’ contour were significantly different between the two methods (p 6 0.05). The ‘‘optimized’’ method showed a lower intra- and inter-operator variability and a higher adherence to the ‘‘MR-derived’’ contour. Conclusions: The ‘‘optimized’’ method ameliorates both operator-related variability and adherence with MR images.

Poly(1-trimethylsilyl-1-propyne) (PTMSP)—styrene (St) grafted films were obtained by a radiochemical method. St monomer vapors were absorbed by the PTMSP, and the grafting reaction was thereafter accomplished by Co60 gamma irradiation in a nitrogen atmosphere. The films so grafted were tested for nitrogen—oxygen separation. The performances of the membranes were studied as functions of time and percent of grafting. The PTMSP—St grafted membranes showed an increased selectivity factor and better stability in comparison with pure PTMSP. The experimental data and some SEM observations confirmed that the grafting procedure changes the PTMSP matrix structure, filling the voids responsible for the PTMSP permeability change with time.

A radiochemical method was employed to obtain poly(1-trimethylsilyl-1-propyne)(PTMSP)-divinylbenzene (DVB) grafted films. DVB monomer vapors were absorbed by the PTMSP, and the grafting reaction was thereafter accomplished by {sup 60}Co {gamma}-irradiation in a nitrogen atmosphere. The films so obtained were tested for nitrogen-oxygen separation. The performances of the membranes were studied as functions of time and percent of grafting. The DVB-grafted membranes show an increased selectivity factor and stability with time. The experimental data and some SEM observations confirm the presence of large voids in the PTMSP matrix. These voids are responsible for permeability changes during operation and disappear after the grafting procedure. 8 refs., 5 figs.

Objectives: The aim of this study was the comparison of a new double-coated paclitaxeleluting coronary stent with bare-metal stent (BMS) in patients undergoing percutaneous coronary intervention. Background: Stent coating with biodegradable polymers as a platform for elution of drugs has the potential for complete elution of drugs and for decreasing the risk of late complications. Methods: Multicenter randomized trial comparing a paclitaxel-eluting stent (PES) coated with a biodegradable polymer and glycocalyx with the equivalent BMS. We randomly assigned 422 patients with de novo coronary lesions to PES (211 patients) or to BMS (211 patients). Primary end point was target vessel failure (TVF) defined as cardiac death, myocardial infarction, and target vessel revascularization. Clinical secondary end points were target vessel revascularization, target lesion revascularization, stent thrombosis (ST), and major adverse cardiovascular events (MACE). Angiographic secondary end points were late loss and binary restenosis. Results: At 1 year of follow-up, TVF rate was 9.5% in the PES group and 17.1% in the BMS group (P 5 0.02), and MACE rate was 10% in PES and 19% in BMS arm (P 5 0.009). All other secondary end points were reached but ST. ST rate was low and similar in both study arms. Conclusions: The study shows that patients treated with PES with dual coating technology had significantly lower incidence of TVF and MACE than those treated with BMS design; however, longer follow-up should be necessary to assess true advantages of this technology compared with the previous one. V C 2010 Wiley-Liss, Inc.

To compare the incidence of major adverse cardiac and cerebrovascular events (MACCE) in patients with multiple vessel coronary artery disease treated with drug eluted stents (DES), bare metal stents, percutaneous coronary interventions (PCI) or bypass surgery (CABG).In the Argentine Randomized Study Coronary Angioplasty versus Coronary Bypass Surgery in Multiple Vessel Disease (ERACI) III trial, 225 patients with multivessel disease who received DES met clinical and angiographic inclusion criteria for the ERACI II trial. This cohort (ERACI III-DES) was compared to both ERACI II treatment arms (ERACII-PCI and ERACI II-CABG). The primary end point was freedom from MACCE at one year.Comparison of baseline demographic and angiographic data, revealed that ERACI III-DES patients were older, smoked more, had more diabetes, hyperlipidaemia, hypertension, type C lesions and received more stents. At one year freedom from MACCE was significantly greater in ERACI III-DES cohort (88%) than ERACI II CABG (80.5% p=0.038) and ERACI II PCI (78% p=0.006) patients. The ERACI III-DES cohort had similar freedom from death and acute myocardial infarction (AMI) to ERACI II PCI patients but greater than ERACI II-CABG arm. Freedom from repeat revascularization was similar between ERACI III-DES to ERACI II-CABG (95.1% p=ns) patients, but both were significantly better than those in the ERACI II-PCI arm ( 91.2% and 83%p=0.002 and 0.02 respectively).Patients with multiple vessel disease treated with DES in ERACI III had better one year outcomes than those treated with PCI or CABG in ERACI II.

The radicals and the “soft” radiations produced by low pressure electrical discharges have been widely applied for modifying the surface properties of many polymers. In this study, we tried to change the transport properties of ultrafiltration membranes. Asymmetric membranes made of poly(vinyl chloride) were submitted to glow discharge in the presence of Ar, then reacted with acrylic acid vapours in order to achieve grafting on the surface. This two-step method allowed us to gain better control of the process and to obtain membranes with enhanced performance. The structure of the membranes so obtained was studied by SEM.

The purpose of this study was to assess the role of oral rapamycin in decreased restenosis after bare metal stent implantation.Small observational studies suggest that the administration of oral rapamycin reduces angiographic restenosis after bare metal stent implantation.Between September 2003 and September 2004, 100 patients were randomized to either oral rapamycin (6-mg loading dose given 2.7 h before intervention followed by 3 mg/day for 14 days) plus diltiazem 180 mg/day or no therapy after the implantation of a coronary bare metal stent design. The primary study end point was incidence of angiographic binary restenosis and late loss at nine months. The secondary end points were target lesion revascularization, target vessel revascularization, and incidence of major adverse cardiovascular events at 1 year.Angiographic follow-up was completed in 87% of patients. In the rapamycin group, the drug was well tolerated (26% minor side effects) and was maintained in 96% of patients. At 9 months, the in-segment binary restenosis was reduced by 72% (11.6% rapamycin vs. 42.8% no-therapy group, p = 0.001) and the in-stent binary restenosis was reduced by 65% (12% rapamycin vs. 34.6% no-therapy group, p = 0.009). The in-segment late loss was also significantly reduced with oral therapy (0.66 vs. 1.13 mm, respectively; 43% reduction, p0.001). At 1 year, patients in the oral rapamycin group also showed a significantly lower incidence of target vessel revascularization (8.3% vs. 38%, respectively, p0.001), target lesion revascularization (7.6% vs. 37.2%, respectively, p0.001), and major adverse cardiovascular events (20% vs. 44%, respectively, p = 0.018).This randomized, controlled, and unblinded study showed that the administration of oral rapamycin during 14 days after stent implantation significantly reduces angiographic and clinical parameters of restenosis.

Rapamycin-coated stents are associated with low restenosis rates, but the ability of oral rapamycin to prevent restenosis is unknown. From December 2001 through February 2002, thirty-four patients with 49 lesions were treated with oral rapamycin for 1 month following percutaneous coronary intervention (PCI) with bare stents. Patients received a loading dose of 6 mg rapamycin followed by a daily dose of 2 mg. Rapamycin blood levels were measured in all patients during the third week of treatment. Cholesterol and triglycerides were evaluated before and 1 month after treatment. A 6-month follow-up angiogram was performed in all patients. Angiographic binary restenosis (50%), target lesion revascularization (TLR), late loss, treatment compliance and major adverse cardiac events were analyzed independent of rapamycin levels. Baseline characteristics included a history of diabetes in 35% of patients and the presence of in-stent restenosis in 24.5% of lesions (12/49). The rapamycin was well tolerated and only 1 patient discontinued the therapy due to mild side effects. Angiographic restenosis and TLR at 6 months was present in 26.5% of lesions (13/49). Restenosis in de novo lesions was 18.9% (7/37) compared to 50% of in-stent restenotic lesions (6/12; p = 0.08). Restenosis in de novo lesions in patients with rapamycin levels8 ng/ml was 0% (0/12), whereas it was 24% (6/25) when the rapamycin levels were8 ng/ml (p = 0.07). Late loss was significantly lower when rapamycin levels were8 ng/ml (0.3 mm versus 0.9 mm, respectively; p = 0.04). Thus, in this observational study, oral rapamycin administered for 1 month after PCI with bare stenting was safe and well tolerated. Higher therapeutic rapamycin blood levels were associated with a lower late loss and a trend toward a lower restenosis rate in de novo lesions.

Percutaneous coronary interventions (PCIs) in diabetic patients with small reference diameter vessels remain an important challenge in interventional cardiology because it is associated with increased complications and restenosis rates. Plain old balloon angioplasty (POBA) has limited efficacy in patients with lesions in small vessels. Although coronary stenting (stent) has been demonstrated to improve both immediate and long-term results after coronary intervention, small reference diameter is a strong predictor of restenosis after stent implantation. Thus, the question of how to best treat diabetic patients with lesions in small reference diameter remains unanswered. The purpose of this international and multicenter study was to compare the incidence of angiographic restenosis between percutaneous transluminal coronary angioplasty (PTCA) and stent in diabetic patients undergoing PCI of small reference diameter vessels using a specially designed phosphoryl choline (PC)-coated stent for small vessels. The patient population comprised of 220 diabetic patients with lesions in small reference diameter (2.9 mm but2.0 mm) that were randomized into two different PCI strategies: PTCA with provisional stenting (n = 109) versus stent (n = 111). In the PTCA arm, 26 patients (24%) crossed over to stent during the initial procedure; glycoproteins IIb to IIIa was used in 40.5% of patients in both groups. During initial procedure and at 30 days, both strategies of revascularitation had similar clinical success and acute complications. During long-term follow-up, even though requirements of target vessel revascularization and incidence of major adverse cardiovascular event were similar with both techniques, angiographic binary restenosis (45% with PTCA and 28% with stents, P = .047), net gain (0.74 mm with POBA and 0.94 mm with stents, P = .008), and freedom from target vessel failure (66% with POBA and 81.2% with stents, P = .013) were significantly improved when diabetic patients were initially treated with stent therapy. In summary, in diabetic patients with small coronary arteries, the use of a coronary PC coated stent as a primary device during percutaneous interventions was associated with better angiographic and long-term outcome.

The electro-oxidation of dilute aqueous solutions of sodium lauryl sulfate (LS) was studied in the presence of metal ions and sulfuric acid, in order to achieve the complete destruction of the detergent. An undivided cell and rhodiated titanium electrodes were used. The LS concentration was studied as a function of time, added metal ion, pH, temperature, initial current density and detergent concentration. The results obtained showed that 99% LS destruction can be easily achieved and that complete oxidation occurs. LS depletion rate was found to increase with temperature, current density (up to 2 A dm−2) and detergent concentration but to decrease with pH. The best results were obtained with iron ions dissolved in the electrolyte, but the process rate was nearly independent of Fe concentration above 0.5 mM.

The preparation and properties of membranes obtained by radiation induced grafting are described, using vinylpyridine (VPy) on a polytetrafluoroethylene (PTFE) matrix. Subsequent quaternarization of the pyridine groups improves greatly the hyperfiltration properties of these membranes, considering both flux and rejection, and they may be developed for desalination purposes. The dependence of grafting yields on irradiation times was studied as well as the thermal and chemical properties of the membranes obtained. Flux and rejection to NaCl of quaternarized VPy/PTFE membranes was measured as a function of various chemical and physical properties.

Permselective cationic membranes were prepared by a radioinduced grafting method of styrene onto PTFE, and a preirradiation technique was used. Some attempts were made to characterize the membranes. They show mechanical properties similar to the PTFE matrix, and good electrochemical behavior, i.e., good permselectivity, which, nevertheless, decreased with decreasing solutions concentration. Such behavior has been related to a larger swelling in diluted solutions. Swelling properties in aqueous solutions of KCl and some organic solvents are also reported.

Grafting on polypropylene by pre-irradiation and exposure to some monomer-solvent mixtures has been investigated. The experimental results show that the mutual interactions between the polymeric matrix and the monomer-solvent mixtures are of the greatest importance.

To the Editor: In recent years, the introduction ([1][1]) of drug-eluting stents (DES) during percutaneous coronary interventions (PCI) has been one of the major breakthroughs in interventional procedures. Several observational and randomized studies have shown a significantly lower restenosis rate