Concurrent use of cisplatin or cetuximab with definitive radiotherapy for locally advanced head and neck squamous cell carcinomas. Strahlentherapie in Kombination mit platinbasierter Chemotherapie oder Cetuximab zur Behandlung von lokal fortgeschrittenen Plattenepithelkarzinomen im Kopf-Hals-Bereich.

AIM: The goal of the present work was to compare outcomes of definitive concurrent cisplatin-based chemoradiotherapy (CRT) with cetuximab-based bioradiotherapy (BRT) in locally advanced head-and-neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Between 2006 and 2012, 265 patients with locally advanced HNSCC were treated at our institution with CRT (n = 194; 73 %) with three cycles of cisplatin (100 mg/m(2), every 3 weeks) or BRT (n = 71; 27 %) with weekly cetuximab. Patients receiving BRT had more pre-existing conditions (Charlson index ≥ 2) than the CRT group (p = 0.005). RESULTS: Median follow-up was 29 months. In all, 56 % of patients treated with CRT received the planned three cycles (92 % at least two cycles) and 79 % patients treated with BRT received six cycles or more. The 2-year actuarial overall survival (OS) and progression-free survival (PFS) were 72 % and 61 %, respectively. In the multivariate analysis (MVA), T4 stage, N2-3 stage, smoking status (current smoker as compared with never smoker), and non-oropharyngeal locations predicted for OS, whereas BRT association with OS was of borderline significance (p = 0.054). The 2-year actuarial locoregional control (LRC) and distant control (DC) rates were 73 and 79 %, respectively. CRT was independently associated with an improved LRC (2-year LRC: 76 % for CRT vs. 61 % for BRT) and DC (2-year LRC: 81 % for CRT vs. 68 % for BRT) in comparison with BRT (p < 0.001 and p = 0.01 in the MVA). Subgroup analyses showed that T4 patients benefited significantly from CRT (vs. BRT) in LRC, while T1-3 did not. BRT patients had more G3-4 skin complications (p < 0.001) and CRT patients had higher rates of feeding tube placement (p = 0.006) and G3-4 gastrointestinal toxicities (p < 0.001). CONCLUSION: This retrospective analysis showed a better LRC in locally advanced HNSCC treated by cisplatin-based CRT than cetuximab-based BRT, and a nonsignificant trend towards an improved OS.

Cerebral perfusion CT in the evaluation of children with severe head trauma : 12.06

Purpose: To assess the value of cerebral perfusion CT (PCT) in children with traumatic brain injury in prediciting their consecutive clinical outcome. Materials and methods: Twelve paediatric patients with acute traumatic brain injury underwent cerebral CT coupled with PCT during their admission at the emergency room (ER). PCT maps were reviewed for mean transit time (MTT), regional cerebral blood flow (rCBF) and regional cerebral blood volume (rCBV) abnormalities. PCT results were compared to short- and mid-term clinical outcome. Results: 3 patients with low Glasgow Coma Scale (GCS) (98) and bad clinical outcome showed an increased MTT and decreased rCBV and rCBF. 5 patients with low GCS and good clinical outcome showed an increased MTT without abnormalities of rCBV and rCBF. In patients with GCS 08 and good outcome, PCT maps were normal in 2 cases; transient PCT abnormalities were identified in one case with an embedded fracture of the skull and in one case with an epileptic seizure. Conclusion: Cerebral PCT can identify diffuse abnormalities of cerebral perfusion in children with traumatic brain injury showing a low initial GCS and a bad outcome. PCT can be a valuable tool to predict the severity of the prognosis of these patients as soon as they are evaluated by CT-scan during their admission at the ER.

Diffusion tensor echo planar imaging using surface coil transceiver with a semiadiabatic RF pulse sequence at 14.1T.

Diffusion magnetic resonance studies of the brain are typically performed using volume coils. Although in human brain this leads to a near optimal filling factor, studies of rodent brain must contend with the fact that only a fraction of the head volume can be ascribed to the brain. The use of surface coil as transceiver increases Signal-to-Noise Ratio (SNR), reduces radiofrequency power requirements and opens the possibility of parallel transmit schemes, likely to allow efficient acquisition schemes, of critical importance for reducing the long scan times implicated in diffusion tensor imaging. This study demonstrates the implementation of a semiadiabatic echo planar imaging sequence (echo time=40 ms, four interleaves) at 14.1T using a quadrature surface coil as transceiver. It resulted in artifact free images with excellent SNR throughout the brain. Diffusion tensor derived parameters obtained within the rat brain were in excellent agreement with reported values.

Feasibility and efficacy of accelerated weekly concomitant boost postoperative radiation therapy combined with concomitant chemotherapy in patients with locally advanced head and neck cancer.

BACKGROUND: The aim of this study was to assess feasibility and efficacy of weekly concomitant boost accelerated postoperative radiation therapy (PORT) with concomitant chemotherapy (CT) in patients with locally advanced head and neck cancer (LAHNC). METHODS AND MATERIALS: Conformal or intensity-modulated 66-Gy RT was performed in 5.5 weeks in 40 patients. Cisplatin was given at days 1, 22, and 43. Median follow-up was 36 months. RESULTS AND DISCUSSION: Grade 3 mucositis, dysphagia, and erythema was observed in ten (25%), nine (23%), and six (13%) patients, respectively. Grade 3 or more anemia was observed in two (6%) patients, and leukopenia in five (13%) patients. No grade 3 or 4 thrombocytopenia was observed. Grade 3 nephrotoxicity was observed in one patient (3%). No treatment-related mortality was observed. Grade 2 or more xerostomia and edema were observed in ten (25%) and one (3%) patient, respectively. Locoregional relapse occurred in eight patients, and seven patients developed distant metastases. Median time to locoregional relapse was 6 months. Three-year overall, disease-free survival, and locoregional control rates were 63%, 62%, and 81%, respectively. Multivariate analysis revealed that the only prognostic factor was nodal status. CONCLUSION: Reducing overall treatment time using accelerated PORT/CT by weekly concomitant boost (six fractions per week) combined with concomitant cisplatin CT is easily feasible with acceptable morbidity.

The temporoparietal fascia flap: a versatile tool in head and neck reconstruction.

PURPOSE OF REVIEW: The article reviews recent significant advances and current applications of the temporoparietal fascia flap (TPFF) in head and neck surgery. RECENT FINDINGS: The recent literature describes a wide span of new applications of the TPFF in many areas. Significant developments and refinements in the reconstruction of orbitomaxillary composite defects and orbital exenteration cavities are reported. The TPFF combined with alloplastic framework is gaining in importance in external ear reconstruction. Innovative prefabricated skin or soft-tissue grafts based on the TPFF are used to restore facial contour or in the reconstruction of complex facial defects. The free TPFF finds a role in laryngotracheal reconstruction as a vascular carrier to support cartilage grafts. SUMMARY: Owing to its reliability and unequalled structural properties, the TPFF still plays a central role in facial reconstruction. Future investigation will likely incorporate the free TPFF as a vascular carrier of bioengineered tissues, such as cartilage and mucosa, for various head and neck indications.

The reasons for discrepancies in target volume delineation: a SASRO study on head-and-neck and prostate cancer

But : comprendre les raisons des divergences observées dans le tracé des volumes cibles entre radio-oncologues. Matériel et méthodes : 18 centres suisses de radio-oncologie ont été invités à tracer les volumes pour un cas de cancer de la prostate et pour un cas de cancer de la sphère ORL. Nous avons également envoyé un questionnaire pour évaluer d'une part les différences dans la définition- des volumes (GTV [ gross tumor volume= volume tumoral macroscopique ], CTV [clinical tumor volume= volume de la tumeur clinique, macroscopique et microscopique], PTV [planning target volume= volume cible pour la planification], et d'autre part des variations dans les marges appliquées et les ganglions considérés à risque. Pour chaque centre, on a calculé la corrélation entre les marges qui ont été dessinées et celles qui ont été annoncées. Nous avons inclus dans le questionnaire une série de questions non spécifiques pour évaluer les méthodes de planification utilisées dans les différents centres. Résultats : Dans les 2 situations cliniques, on a mis en évidence de relativement grandes différences tant au niveau des volumes dessinés par les différents centres que dans leur définition des volumes. La corrélation entre les marges dessinées et définies était assez correcte dans le cas de la prostate mais médiocre dans le cas ORL. Le questionnaire a révélé d'importantes différences dans les méthodes de planification utilisées par les centres. Conclusion : Ces grandes différences peuvent être expliquées par, (1) une connaissance/interprétation variable des définitions ICRU, (2) des appréciations différentes de l'extension tumorale microscopique potentielle, (3) des difficultés dans l'identification du GTV, (4) des différences de concept, et (5) des différences entre la théorie (par ex. la description des marges) et la pratiqué (par ex. les marges dessinées).

Different likelihood ratio approaches to evaluate the strength of evidence of MDMA tablet comparisons

Two likelihood ratio (LR) approaches are presented to evaluate the strength of evidence of MDMA tablet comparisons. The first one is based on a more 'traditional' comparison of MDMA tablets by using distance measures (e.g., Pearson correlation distance or a Euclidean distance). In this approach, LRs are calculated using the distribution of distances between tablets of the same-batch and that of different-batches. The second approach is based on methods used in some other fields of forensic comparison. Here LRs are calculated based on the distribution of values of MDMA tablet characteristics within a specific batch and from all batches. The data used in this paper must be seen as examples to illustrate both methods. In future research the methods can be applied to other and more complex data. In this paper, the methods and their results are discussed, considering their performance in evidence evaluation and several practical aspects. With respect to evidence in favor of the correct hypothesis, the second method proved to be better than the first one. It is shown that the LRs in same-batch comparisons are generally higher compared to the first method and the LRs in different-batch comparisons are generally lower. On the other hand, for operational purposes (where quick information is needed), the first method may be preferred, because it is less time consuming. With this method a model has to be estimated only once in a while, which means that only a few measurements have to be done, while with the second method more measurements are needed because each time a new model has to be estimated.

Prevalence and determinants of obesity in children in public schools of Sintra, Portugal

OBJECTIVE: To assess the prevalence of and the factors related to overweight and obesity in a sample of children from the region of Sintra, Portugal. METHODS AND PROCEDURES: Cross-sectional study, stratified for freguesia with random selection of schools. Height, weight, triceps skinfold, upper arm and waist circumferences were measured, and overweight/obesity defined according to international criteria. Breast-feeding, number of daily meals and parents' height and weight data were also collected. RESULTS: One thousand two hundred and twenty-five children aged 6-10 years were assessed. Overall prevalence of overweight and obesity was 35.6% (23% overweight and 12.6% obesity). Overweight or obese children had higher triceps skinfold, upper arm circumference, arm muscle area, and waist circumference than their normal weight counterparts (P < 0.001). On multivariate analysis, relatively to a child without obese progenitors, a child with one obese progenitor had an obesity risk multiplied by 2.78 (95% confidence interval (CI): 1.76-4.38), while a child with two obese progenitors had a risk multiplied by 6.47 (95% CI: 5.59-16.19). Conversely, being picky was significantly related with a smaller risk of obesity: for boys, odds ratio (OR) = 0.15 (95% CI: 0.04-0.63); for girls, OR = 0.19 (95% CI: 0.06-0.64). Finally, no relationships were found between obesity, birth weight, birth height or breast-feeding. DISCUSSION: Prevalence of overweight and obesity are elevated among children of the Sintra region in Portugal compared to most other regions of Europe. The relationship with the parents' nutritional state stresses the need to target families for preventing obesity.

Adipocytokines, Hepatic and Inflammatory Biomarkers and Incidence of Type 2 Diabetes. The CoLaus Study.

CONTEXT: There is contradictory information regarding the prognostic importance of adipocytokines, hepatic and inflammatory biomarkers on the incidence of type 2 diabetes. The objective was to assess the prognostic relevance of adipocytokine and inflammatory markers (C-reactive protein - CRP; interleukin-1beta - IL-1β; interleukin-6- IL-6; tumour necrosis factor-α - TNF-α; leptin and adiponectin) and gamma-glutamyl transpeptidase (γGT) on the incidence of type 2 diabetes. METHODS: Prospective, population-based study including 3,842 non-diabetic participants (43.3% men, age range 35 to 75 years), followed for an average of 5.5 years (2003-2008). The endpoint was the occurrence of type 2 diabetes. RESULTS: 208 participants (5.4%, 66 women) developed type 2 diabetes during follow-up. On univariate analysis, participants who developed type 2 diabetes had significantly higher baseline levels of IL-6, CRP, leptin and γGT, and lower levels of adiponectin than participants who remained free of type 2 diabetes. After adjusting for a validated type 2 diabetes risk score, only the associations with adiponectin: Odds Ratio and (95% confidence interval): 0.97 (0.64-1.47), 0.84 (0.55-1.30) and 0.64 (0.40-1.03) for the second, third and forth gender-specific quartiles respectively, remained significant (P-value for trend = 0.05). Adding each marker to a validated type 2 diabetes risk score (including age, family history of type 2 diabetes, height, waist circumference, resting heart rate, presence of hypertension, HDL cholesterol, triglycerides, fasting glucose and serum uric acid) did not improve the area under the ROC or the net reclassification index; similar findings were obtained when the markers were combined, when the markers were used as continuous (log-transformed) variables or when gender-specific quartiles were used. CONCLUSION: Decreased adiponectin levels are associated with an increased risk for incident type 2 diabetes, but they seem to add little information regarding the risk of developing type 2 diabetes to a validated risk score.

The release of antidiuretic hormone is appropriate in response to hypovolemia and/or sodium administration in children with severe head injury: a trial of lactated Ringer's solution versus hypertonic saline.

We conducted an open, randomized, and prospective study to determine the effect of hypertonic saline on the secretion of antidiuretic hormone (ADH) and aldosterone in children with severe head injury (Glasgow coma scale <8). Thirty-one consecutive patients at a level III pediatric intensive care unit at a children's hospital received either lactated Ringer's solution (Ringer's group, n = 16) or hypertonic saline (Hypertonic Saline group, n = 15) over a 3-day period. Serum ADH levels were significantly larger in the Hypertonic Saline group as compared with the Ringer's group (P = 0.001; analysis of variance) and were correlated to sodium intake (Ringer's group: r = 0.39, R(2) = 0.15, P = 0.02; Hypertonic Saline group: r = 0.42, R(2) = 0.18, P = 0.02) and volume of fluids given IV (Ringer's group: r = 0.38, R(2) = 0.15, P = 0.02; Hypertonic Saline group: r = 0.32, R(2) = 0.1, P = not significant). Correlation of ADH to plasma osmolality was significant if plasma osmolality was >280 mOsm/kg (r = 0.5, R(2) = 0.25, P = 0.06), indicating an osmotic threshold for ADH release. Serum aldosterone levels were larger on the first day than during Days 2 and 3 in both groups and inversely correlated to serum sodium levels only in the Ringer's group (r = -0.55, R(2) = 0.3, P < 0.001). This group received a significantly larger fluid volume on Day 1 (P = 0.05, Mann-Whitney U-test) than did patients in the Hypertonic Saline group, indicating hypovolemia during the first day. Head-injured children have appropriate levels of ADH. They may be hypovolemic during the first day of treatment, especially if they receive lactated Ringer's solution. IMPLICATIONS: In head-injured patients, we recommend fluid restriction to avoid inappropriate secretion of antidiuretic hormone. In a prospective, randomized, and controlled study in 31 children, we were able to show that the antidiuretic hormone levels are appropriate in response to hypovolemia, sodium load, or both.

p53 Mutation in histologically normal mucosa of the aero-digestive tract is not a marker of increased risk for second primary carcinoma in head and neck cancer patients.

Head and neck cancer patients are at high risk for developing second primary tumors. This is known as field cancerization of the aero-digestive tract. In a previous study, we showed that patients with multiple primary tumors were more likely to have p53 mutations in histologically normal mucosae than patients presenting with an isolated tumor. Based on this observation, we postulated that p53 mutations in normal tissue samples of patients bearing a single primary tumor could have a clinical value as a biomarker for the risk of developing second primary tumors. Thirty-five patients presenting with a single primary tumor were followed-up for a median of 51 months (range 1 month to 10.9 years) after biopsies of histologically normal squamous cell mucosa had been analyzed for p53 mutations with a yeast functional assay at the time of the primary tumor. During this follow-up, recurrences and non-sterilization of the primary tumor, occurrence of lymph node metastases, and of second primary tumors were evaluated. Sixteen (45.7%) patients were found to have p53 mutations in their normal squamous cell mucosa, and 19 (54.3%) patients showed no mutation. No relationship was found between p53 mutations and the occurrence of evaluated events during follow-up. Notably, the rate of second primary tumors was not associated with p53 mutations in the normal squamous mucosa. The correlation between p53 mutations in histologically normal mucosae and the incidence of second primary tumors is generally low. The benefit of analyzing p53 mutations in samples of normal squamous cell mucosa in every patient with a primary tumor of the head and neck is doubtful.

Is tumour size an underestimated feature in the current TNM system for malignancies of the pancreatic head?

BACKGROUND: As the long-term survival of pancreatic head malignancies remains dismal, efforts have been made for a better patient selection and a tailored treatment. Tumour size could also be used for patient stratification. METHODS: One hundred and fourteen patients underwent a pancreaticoduodenectomy for pancreatic adenocarcinoma, peri-ampullary and biliary cancer stratified according to: ≤20 mm, 21-34 mm, 35-45 mm and >45 mm tumour size. RESULTS: Patients with tumour sizes of ≤20 mm had a N1 rate of 41% and a R1/2 rate of 7%. The median survival was 3.4 years. N1 and R1/2 rates increased to 84% and 31% for tumour sizes of 21-34 mm (P = 0.0002 for N, P = 0.02 for R). The median survival decreased to 1.6 years (P = 0.0003). A further increase in tumour size of 35-45 mm revealed a further increase of N1 and R1/2 rates of 93% (P < 0.0001) and 33%, respectively. The median survival was 1.2 years (P = 0.004). Tumour sizes >45 mm were related to a further decreased median survival of 1.1 years (P = 0.2), whereas N1 and R1/2 rates were 87% and 20%, respectively. DISCUSSION: Tumour size is an important feature of pancreatic head malignancies. A tumour diameter of 20 mm seems to be the cut-off above which an increased rate of incomplete resections and metastatic lymph nodes must be encountered and the median survival is reduced.