Ambulant health care utilisation among children of childhood cancer survivors in Germany.

PURPOSE: Within the framework of a questionnaire-based health survey in Germany, we examined ambulant health care utilisation among childhood cancer survivors' offspring compared to utilisation among children of the general population. METHODS: In total, 1299 former patients received a questionnaire for every known biological child in two cross-sectional surveys, 2013/14 (n = 393) and 2015/16 (n = 906). For investigation of health care utilisation, questions on frequencies and kind of ambulant medical services were chosen for bivariate and multivariate analyses. Correlations between utilisation and anxiety, diagnosis of the parent, pain or preterm birth of the child and social indicators were conducted. For comparison with the general population, data of 17,640 children and adolescents aged 0 to 17 years were used for matched-pair analysis. These data were available from the KIGGS baseline study on the health of children and adolescents in Germany, conducted by the Robert Koch Institute. RESULTS: Overall, 852 (65.6%) of the contacted 1299 survivors completed 1340 questionnaires on their children's health. Childhood cancer survivors' offspring showed a similar attendance of ambulant primary health care compared to the general population (paediatricians 83.1% vs. 82.1%). However, the majority of specialist physicians was visited significantly more often (e.g. dermatologist 10.5% vs. 6.2%) by childhood cancer survivors' offspring compared to children from the general population. Logistic regression showed that parental diagnosis and anxiety on children's health significantly influenced health care utilisation. CONCLUSIONS: Further improvement of after-care for childhood cancer survivors by including topics on offspring seems necessary. Offspring's paediatricians should implement counselling and providing of information considering the special family anamnesis.

[True thymic hyperplasia : Differential diagnosis of thymic mass lesions in neonates and children]. / "Echte Thymushyperplasie" : Differenzialdiagnose der Thymusvergrößerung bei Säuglingen und Kindern.

Reactive and neoplastic thymic pathologies are the main considerations in the case of masses in the anterior and middle part of the mediastinum, while neurogenic tumors are predominant in the posterior mediastinum (which are not dealt with here). In neonates and infants, the commonest pathologies in the anterior mediastinum comprise germ cell tumors (mainly teratomas), congenital thymic cysts and true thymic hyperplasia (TTH). In toddlers, teratomas, yolk sac tumors and cysts predominate. In children over 5 years of age, lymphomas are the commonest mass lesions whereas thymomas and thymic carcinomas are rare. In addition, inflammation-linked hyperplasia in myasthenia gravis and rebound thymic hyperplasia after chemotherapy must be considered. Although rare at all ages, sarcomas must be considered in the differential diagnosis from birth onwards and throughout adolescence. Based on the report of a rare case of recurrent TTH, the differential diagnosis of this benign but potentially life-threatening condition is discussed.

Health-Related Behaviour Among Children of Childhood Cancer Survivors in Germany.

Purpose: Childhood cancer survivors fear that previous therapy could not only impair their own but also their children's health. We examined whether health-related behaviour in children of childhood cancer survivors differs from the general population. Methods: Our first nationwide survey wave (2013-2014) surveyed offspring health in 396 German childhood cancer survivors known to have a child of their own. Answers about health behaviour were analysed using descriptive statistics. Data were collected for 418 offspring and 394 could be integrated for matched-pair analyses with data from the German general population (KIGGS, n=17 641). Results: Teeth-cleaning routine, body-mass-index or subjective body image evaluation by parents were no different from children in the general population. Parents who included a cancer survivor smoked less in the presence of their children (p=0.01). During pregnancy, mothers in cancer survivor parent pairs abstained from drinking alcohol more often (p=0.01) and smoked less (p=0.05). While the calculated effect sizes (Phi) were generally low (0.135-0.247), children from cancer survivors played less outdoors than peers did (p=0.01). Boys participated in sports outside a club more often (p=0.05) and watched less TV on weekdays (p=0.01) and girls spent more time on the computer during weekdays than peers did (p=0.01). Conclusions: This study provides the first data for health-related behaviour in cancer survivors' offspring and sheds light on differences to parenting in the general population. Multivariate analyses in a larger study population are needed to relate these differences to fear issues in cancer survivors.

[Prevalence of the metabolic syndrome and its risk factors: results of a large work-site health assessment]. / Prävalenz des Metabolischen Syndroms und seiner Risikofaktoren: Ergebnisse einer großen betrieblichen Gesundheitsuntersuchung.

BACKGROUND: Facing the demographic change, cardiovascular risk factors have been assessed within an occupational checkup to establish health programs. PATIENTS AND METHODS: From 2006 to 2007, anthropometric and blood parameters of 27 359 employees of a large company of the German automobile industry were collected aiming to determine the prevalence of metabolic syndrome (by NCEP ATP III) and its risk factors. Data from 3048 employees (fasting state) were analyzed (age: ∅ 39,4 ± 10,3 years, 81.4% males). RESULTS: The most common risk factors were hypertension ≥ 130/85 mmHg (men [m]: 74,4%, 95%-confidence interval [CI] 73-76%, women [w]: 47,1%, 95%-CI 43-51%), elevated triglycerides (≥ 150 mg/dl; m: 32,8%, 95%-CI 31-35%, w: 13,8%, 95%-CI 11-17%) and waist-circumferences (> 102 cm for men: 15,1%, 95%-CI 14-17%; > 88 cm for women: 16,9%, 95%-CI 14-20%). The prevalence of metabolic syndrome (≥ 3 risk factors) was 11,7% (95%-CI 12-15%; m: 12,7%, 95%-CI 11-14%, w: 7,4%, 95%-CI 6-10%) increasing with physical inactivity and rising age up to 20%. The prevalence of hypertension in young (< 20 years) and elder men (≥ 50 years) was similarly high (79,1%, 95%-CI 70-86% vs. 79,9%, 95%-CI 75-82%). CONCLUSION: The prevalence of metabolic syndrome in this sample is rather low, but 75% of the men and nearly 50% of the women had hypertension. Health programs should focus on this risk factor in particular.

Combined SPECT/CT improves detection of initial bone invasion and determination of resection margins in squamous cell carcinoma of the head and neck compared to conventional imaging modalities.

PURPOSE: Knowledge of the presence and extent of bone infiltration is crucial for planning the resection of potential bone-infiltrating squamous cell carcinomas of the head and neck (HNSCC). Routinely, plain-film radiography, multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) are used for preoperative staging, but they show relatively high rates of false-positive and false-negative findings. Scintigraphy with (99m)Tc-bisphosphonate has the ability to show increased metabolic bone activity. If combined with anatomical imaging (e.g. (SPECT)/CT), it facilitates the precise localization of malignant bone lesions. The aim of this study was to analyse the indications and advantages of SPECT/CT compared with standard imaging modalities and histology with regard to specificity and sensitivity METHODS: A longitudinally evaluated group of 30 patients with biopsy-proven HNSCC adjacent to the mandible underwent (99m)Tc-bisphosphonate SPECT/CT, MRI, MSCT and conventional radiography before partial or rim resection of the mandible was performed. Bone infiltration was first evaluated with plain films, MSCT and MRI. In a second reading, SPECT/CT data were taken into account. The results (region and certainty of bone invasion) were evaluated among the different imaging modalities and finally compared with histological specimens from surgical resection as the standard of reference. For a better evaluation of the hybrid property of SPECT/CT, a retrospectively evaluated group of 20 additional patients with tumour locations similar to those of the longitudinally examined SPECT/CT group underwent SPECT, MSCT and MRI. To assess the influence of dental foci on the specificity of the imaging modalities, all patients were separated into two subgroups depending on the presence or absence of teeth in the area of potential tumour-bone contact. RESULTS: Histologically proven bone infiltration was found in 17 patients (57 %) when analysed by conventional imaging modalities. SPECT/CT data revealed bone infiltration in two additional patients (7 %), who both showed discrete cortical bone erosion not visible by MSCT or MRI. There were no false-positive or false-negative findings on SPECT/CT. The quality criteria for detecting bone involvement in HNSCC by SPECT/CT were as follows: sensitivity 100 % (lower 95 % confidence interval limit 80 %), specificity 100 % (75 %), positive predictive value 100 % (80 %) and negative predictive value 100 % (75 %). Corresponding data for MRI were 95 % (76 %), 94 % (73 %), 95 % (76 %) and 94 % (73 %), and for MSCT were 89 % (71 %), 100 % (85 %), 100 % (86 %) and 88 % (69 %). In the retrospective evaluation SPECT showed results similar to SPECT/CT. CONCLUSION: Hybrid SPECT/CT has a high specificity as it can provide additional information about the existence and local extent of malignant bone infiltration of the mandible. Although the sensitivity of conventional SPECT is similar to that of SPECT/CT, the latter provides a much better delineation of the local tumour-bone contact area. Based on this information, surgical intervention of the rim versus partial resection can be planned and performed more precisely. Patient outcome can be improved by avoiding undertreatment and unnecessary or overextended bone resections.

Transferring innovative freehand SPECT to the operating room: first experiences with sentinel lymph node biopsy in malignant melanoma.

PURPOSE: The purpose of this study was to report on the first experiences with freehand single-photon emission-computed tomography (freehand SPECT) in sentinel lymph node biopsy (SLNB) in patients with malignant melanoma. Freehand SPECT is a novel imaging modality combining gamma probes, surgical navigation systems, and emission tomography algorithms, designed to overcome some of the limitations of conventional gamma probes. METHODS: In this study 20 patients with malignant melanoma underwent conventional planar scintigraphy prior to surgery. In the operating room, the number and location of separable SLNs were detected first by a pre-incisional scan with freehand SPECT to render a 3D-image of the target site and afterwards by a scan with a conventional gamma probe. After SLNB another scan was performed to document the removal of all targeted SLNs. RESULTS: Planar scintigraphy identified 40 SLNs in 26 nodal basins. Pre-incisional freehand SPECT mapped 38 of these nodes as well as one additional node in one patient (95.0% node based sensitivity). The results of freehand SPECT were identical to those of planar scintigraphy in 25 basins, while it missed one basin (96.2% basin based sensitivity). In comparison, the gamma probe failed to detect 7 nodes in 4 basins (82.5% node based sensitivity and 84.6% basin based sensitivity). After resection freehand SPECT detected 9 remaining radioactive spots, two of whichwere resected as they matched the position of SLNs detected on preoperative planar scintigraphy. CONCLUSIONS: Freehand SPECT provides a real-time, intraoperative 3D-image of the radioactive labelled SLNs, facilitating their detection and resection.

Localization and quantification of the delivered dose to the spinal cord. Predicting actual delivered dose during daily MVCT image-guided tomotherapy.

PURPOSE: The goal of the present work was to localize and quantify the actual delivered dose to the cervical spinal cord (SC) during head and neck cancer (H&N) treatment. MATERIALS AND METHODS: A total of 20 H&N patients treated with bilateral nodal irradiation with helical tomotherapy (HT) were analyzed. Daily MVCTs were performed for image guidance. On every second MVCT, the SC was recontoured and the delivered dose for the given treatment fraction (12 fractions per patient) was recalculated. The magnitude and localization (CT slice, spinal cord quadrant) of the Dmax to the SC on the planning CT (PLAN-Dmax) and of the actual delivered Dmax (a-Dmax) were analyzed. RESULTS: A systematic deviation from the PLAN-Dmax was observed in 15 out of 20 patients. Large interpatient variability of the a-Dmax in the spinal cord was noted (4.5±4%). Intrapatient variability in a-Dmax was, generally, minimal (1.8±2.7%). Throughout the treatment course, the higher dose was located in the same CT slices and in the same quadrants (anterior right and anterior left) for the same patient. CONCLUSION: Exact localization and quantification of the change of the a-Dmax can be made for most patients by recalculating the dose on the daily IGRT-MVCTs. This could be helpful in assessing whether replanning is necessary in patients with doses close to the known tolerance doses of the spinal cord.

Somatic copy number changes in DPYD are associated with lower risk of recurrence in triple-negative breast cancers.

BACKGROUND: Genomic rearrangements at the fragile site FRA1E may disrupt the dihydropyrimidine dehydrogenase gene (DPYD) which is involved in 5-fluorouracil (5-FU) catabolism. In triple-negative breast cancer (TNBC), a subtype of breast cancer frequently deficient in DNA repair, we have investigated the susceptibility to acquire copy number variations (CNVs) in DPYD and evaluated their impact on standard adjuvant treatment. METHODS: DPYD CNVs were analysed in 106 TNBC tumour specimens using multiplex ligation-dependent probe amplification (MLPA) analysis. Dihydropyrimidine dehydrogenase (DPD) expression was determined by immunohistochemistry in 146 tumour tissues. RESULTS: In TNBC, we detected 43 (41%) tumour specimens with genomic deletions and/or duplications within DPYD which were associated with higher histological grade (P=0.006) and with rearrangements in the DNA repair gene BRCA1 (P=0.007). Immunohistochemical analysis revealed low, moderate and high DPD expression in 64%, 29% and 7% of all TNBCs, and in 40%, 53% and 7% of TNBCs with DPYD CNVs, respectively. Irrespective of DPD protein levels, the presence of CNVs was significantly related to longer time to progression in patients who had received 5-FU- and/or anthracycline-based polychemotherapy (hazard ratio=0.26 (95% CI: 0.07-0.91), log-rank P=0.023; adjusted for tumour stage: P=0.037). CONCLUSION: Genomic rearrangements in DPYD, rather than aberrant DPD protein levels, reflect a distinct tumour profile associated with prolonged time to progression upon first-line chemotherapy in TNBC.

Motional coherence of fermions immersed in a Bose gas.

We prepare a superposition of two motional states by addressing lithium atoms immersed in a Bose-Einstein condensate of sodium with a species-selective potential. The evolution of the superposition state is characterized by the populations of the constituent states as well as their coherence. The latter we extract employing a novel scheme analogous to the spin-echo technique. Comparing the results directly to measurements on freely evolving fermions allows us to isolate the decoherence effects induced by the bath. In our system, the decoherence time is close to the maximal possible value since the decoherence is dominated by population relaxation processes. The measured data are in good agreement with a theoretical model based on Fermi's golden rule.

Chronic adverse events and quality of life after radiochemotherapy in anal cancer patients. A single institution experience and review of the literature.

PURPOSE: To report on chronic adverse events (CAE) and quality of life (QOL) after radiochemotherapy (RCT) in patients with anal cancer (AC). PATIENTS AND METHODS: Of 83 patients who had received RCT at our department between 1988 and 2011, 51 accepted the invitation to participate in this QOL study. CAE were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0 and QOL was assessed with the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) questionnaire. RESULTS: CAE could be evaluated in 49 patients. There was a tendency toward a higher rate of grade 3 CAE in female patients, i.e. 18 out of 37 (49 %) vs. 2 out of 12 (17 %) male patients (p = 0.089). The most common grade 3 CAE were dyspareunia and vaginal symptoms (itching, burning and dryness) in 35 and 22 % of female patients, respectively, followed by stool incontinence in 13 % of all patients (6 out of 49). Both FACT-C and CAE information were available for 42 patients, allowing evaluation of the impact of CAE on QOL. The median total FACT-C score was 110 (40-132) out of a possible maximum of 136. The absence of grade 3 CAE (115 vs. 94, p = 0.001); an interval of ≥ 67 months after the end of the treatment (111 vs. 107, p = 0.010), no stool incontinence vs. grade 3 stool incontinence (111 vs. 74, p = 0.009), higher education (114 vs. 107, p = 0.013) and no dyspareunia vs. grade 3 dyspareunia (116 vs. 93, p = 0.012) were significantly associated with a higher median FACT-C score. CONCLUSION: The majority of AC patients treated with RCT have acceptable overall QOL scores, which are comparable to those of the normal population. Patients with grade 3 CAE-particularly dyspareunia and fecal incontinence-have a poorer QOL compared to patients without CAE. In order to improve long-term QOL, future strategies might aim at a reduction in dose to the genitalia and more intensive patient support measures.

Impact of pathologic complete response on disease-free survival in patients with esophagogastric adenocarcinoma receiving preoperative docetaxel-based chemotherapy.

BACKGROUND: The aim of this study was to evaluate the impact of pathologic complete response (pCR) on outcome in patients with gastric or esophagogastric junction (EGJ) adenocarcinoma after neoadjuvant docetaxel/platin/fluoropyrimidine-based chemotherapy. PATIENTS AND METHODS: Patients received at least one cycle of chemotherapy for potentially operable disease. Pretreatment clinicopathologic factors and pCR were investigated. Disease-free survival (DFS), overall survival (OS) and tumor-related death were correlated with pCR. RESULTS: One hundred twenty patients were included in this analysis. Eighteen patients (15%) achieved a pCR. Tumor localization in the EGJ was identified as the only significant predictor of pCR (P = 0.019). Median follow-up was 41.1 months. Median DFS and OS for all patients were 24.1 and 48.6 months, respectively. Median DFS for patients with a pCR was not reached versus 22.1 months non-pCR patients (hazard ratio, HR 0.38; 3-year DFS: 71.8% and 37.7%, respectively, P = 0.018). While OS was not significantly different, the risk for tumor-related death was significantly lower for pCR patients compared with non-pCR patients (3-year cumulative incidences of 6.4% and 45.4%, respectively, P = 0.009). CONCLUSION: A pCR following preoperative docetaxel/platin/fluoropyrimidine indicates favorable outcome in patients with gastric or EGJ adenocarcinoma. Tumor location in the EGJ is associated with a higher pCR rate.

[[¹¹C]choline as a pharmacodynamic marker for docetaxel therapy. Response assessment in a LNCaP prostate cancer xenograft mouse model]. / Ansprechen auf eine Docetaxeltherapie im LNCaP-Prostatakarzinom-Xenograft-Mausmodell. Untersuchung mit der [¹¹C]Cholin-Kleintier-PET/CT.

UNLABELLED: The AIM of this study was to determine whether [¹¹C]choline can be used for docetaxel therapy response assessment in a LNCaP-prostate cancer xenograft mouse model using [¹¹C]choline small-animal PET/CT. ANIMALS, METHODS: The androgen-dependent human prostate cancer cell line LNCaP was implanted subcutaneously into the left flanks of 17 SCID-mice, 12.5 mg testosterone platelets were implanted in the neck wrinkle. All mice were injected 4-6 weeks after xenograft implantation with 37 MBq [¹¹C]choline via the tail vein. Dynamic imaging was performed for 60 minutes with a small-animal PET/CT scanner. After the first [¹¹C]choline PET/CT imaging 8 mice were subsequently injected intravenously with docetaxel twice (days 1 and 5) at a dose of 3 mg/kg body weight. 8 mice were treated with PBS as a control. [¹¹C]choline PET/CT imaging was performed on day 7, 14 and 21 after treatment. Image analysis was performed using tumor/muscle (T/M) ratios (ROI(T)/ROI(M) = T/M ratio). RESULTS: All LNCaP tumours could be visualized by [¹¹C]choline PET/CT. Before treatment the mean T/M ratio was 2.0 ± 0.2 in the docetaxel-treated group and 1.9 ± 0.2 in the control group (p = 0.837). There was a reduction in the mean [¹¹C]choline uptake after docetaxel treatment of the tumours of the LNCaP cell line as early as 1 week after initiation of therapy (T/M(mean) ratio 1.5 ± 0.2 after one week, 1.3 ± 0.2 after 2 weeks and 1.4 ± 0.2 after 3 weeks). There was no decrease in [¹¹C]choline uptake in the control group. CONCLUSION: Our results show that [¹¹C]choline has the potential for use in the early monitoring of the therapeutic effect of docetaxel in a LNCaP prostate cancer xenograft animal model.

Advanced techniques in neoadjuvant radiotherapy allow dose escalation without increased dose to the organs at risk : Planning study in esophageal carcinoma.

PURPOSE: The goal of this work was to investigate the potential of advanced radiation techniques in dose escalation in the radiotherapy (RT) for the treatment of esophageal carcinoma. METHODS: A total of 15 locally advanced esophageal cancer (LAEC) patients were selected for the present study. For all 15 patients, we created a 3D conformal RT plan (3D-45) with 45 Gy in fractions of 1.8 Gy to the planning target volume (PTV1), which we usually use to employ in the neoadjuvant treatment of LAEC. Additionally, a 3D boost (as in the primary RT of LAEC) was calculated with 9 Gy in fractions of 1.8 Gy to the boost volume (PTV2) (Dmean) to a total dose of 54 Gy (3D-54 Gy), which we routinely use for the definitive treatment of LAEC. Three plans with a simultaneous integrated boost (SIB) were then calculated for each patient: sliding window intensity-modulated radiotherapy (IMRT-SIB), volumetric modulated arc therapy (VMAT-SIB), and helical tomotherapy (HT-SIB). For the SIB plans, the requirement was that 95 % of the PTV1 receive ≥ 100 % of the prescription dose (45 Gy in fractions of 1.8 Gy, D95) and the PTV2 was dose escalated to 52.5 Gy in fractions of 2.1 Gy (D95). RESULTS: The median PTV2 dose for 3D-45, 3D-54, HT-SIB, VMAT-SIB, and IMRT-SIB was 45, 55, 54, 56, and 55 Gy, respectively. Therefore, the dose to PTV2 in the SIB plans was comparable to the 3D-54 plan. The lung dose in the SIB plans was in the range of the standard 3D-45, which is applied for neoadjuvant radiotherapy. The mean lung dose for the same plans was 13, 15, 12, 12, and 13 Gy, respectively. The V5 lung volumes were 71, 74, 79, 75, and 73 %, respectively. The V20 lung volumes were 20, 25, 16, 18, and 19 %, respectively. CONCLUSION: New treatment planning techniques enable higher doses to be delivered for neoadjuvant radiotherapy of LAEC without a significant increase in the delivered dose to the organs at risk. Clinical investigations are warranted to study the clinical safety and feasibility of applying higher doses through advanced techniques in the neoadjuvant treatment of LAEC.

Children and adolescents with ureteropelvic junction obstruction: is an additional voiding cystourethrogram necessary? Results of a multicenter study.

PURPOSE: The incidence of ureteropelvic junction obstruction (UPJO) and concomitant vesicoureteral reflux (VUR) ranges from 14 to 18 %. Therefore, different guidelines recommend a voiding cystourethrogram (VCUG) to identify cases of VUR early in the diagnostic process. Aim of this multicenter study was to reassess the incidence of concomitant VUR and the need for additional VCUG in a large cohort of patients with UPJO. Furthermore, we asked for clinical objectives that defined the need for VCUG with the intention of minimizing radiation exposure and the need for invasive diagnostic procedures. METHODS: Medical records for 266 patients (69 girls, 197 boys) with UPJO were analyzed retrospectively. Data were obtained on gender, clinical symptoms, results of pre- and postnatal ultrasound, VCUG and 99(m)Technetium-MAG3 (MAG3) scan. They were correlated with the incidence of concomitant VUR. RESULTS: One hundred and seventy-eight patients (67 %) underwent VCUG. Concomitant VUR was detected in 13 patients. Dilating VUR (dVUR) was observed in 11 patients. In our study, the overall incidence of a concomitant VUR was 7.3 %. In cases of proven VUR, we observed a positive predictive value for female gender, ureteral dilatation, renal insufficiency, and recurrent urinary tract infections (UTI). But there was no correlation between concomitant VUR and the severity of hydronephrosis. CONCLUSIONS: Our data suggest that the low incidence of concomitant VUR in cases of UPJO does not justify the routine use of VCUG as a routine diagnostic tool. Especially, ureteral dilatation and recurrent UTI have a positive predictive value for concomitant VUR.

Analysis of patients with a cleft of the soft palate with special consideration to the problem of velopharyngeal insufficiency.

The evaluation of therapy concepts for children suffering from cleft palate is an enormous challenge in modern oral and maxillofacial surgery and related disciplines. In the present retrospective survey 1300 patients having clefts, including the soft palate, were studied with special regard to speech improvement operations. Nine hundred fifty four patients had a cleft lip, alveolus and palate and 346 patients only isolated cleft palate. In 25.6% of the patients it was necessary to perform a secondary velopharyngoplasty for speech improvement after soft palate closure. Age of the subjects at the time of operation, primary or secondary soft palate closure, and the type of clefting were not significant factors for performing subsequent velopharyngoplasty. However, significant differences with respect to the need for a secondary velopharyngoplasty after soft palate closure were found when comparing the surgical experience of the surgeons.

Erythropoietin in the prevention of experimental burn progression.

BACKGROUND: Damage control is essential in first aid of burn lesions. The aim of the present study was to investigate whether systemic erythropoietin (EPO) administration could prevent secondary burn progression in an experimental model. METHODS: The burn comb model creates four rectangular burn surfaces intercalated by three unburned zones prone to progression. Twenty-one Wistar rats were randomized to a control group or to receive intraperitoneal EPO (500 units per kg) once a day for 5 days starting 45 min (EPO45min) or 6 h (EPO6h) after burn injury. Histological analyses assessing burn depth, inflammation and neoangiogenesis, planimetric evaluation of burn progression, and laser Doppler flowmetry to assess perfusion were performed after 1, 4 and 7 days. Final scarring time and contracture rate were assessed once a week. RESULTS: Burn progression was decreased significantly with EPO45min but not EPO6h; progression of burn depth stopped in the intermediate dermis (mean(s.e.m.) burn depth score 3·3(0·6) for EPO45min versus 4·7(0·3) and 5·0(0·0) for EPO6h and control respectively on day 7; P = 0·026) and the surface extension was significantly reduced (45(8), 65(4) and 78(4) respectively on day 7; P = 0·017). This was paralleled by faster re-establishment of perfusion with EPO45min (114(5) per cent on day 4 versus 85(6) and 91(3) per cent for EPO6h and control respectively; P = 0·096). The reduction in progression resulted in a decreased healing time (7·3(0·7) weeks for EPO45min versus 11·5(1·0) and 10·8(0·5) weeks for EPO6h and control; P = 0·020) and contracture rate (P = 0·024). CONCLUSION: Early EPO prevented burn progression, mainly by improved vascular perfusion.

Adaptive radiotherapy for soft tissue changes during helical tomotherapy for head and neck cancer.

PURPOSE: The goal of the present study was to assess the frequency and impact of replanning triggered solely by soft tissue changes observed on the daily setup mega-voltage CT (MVCT) in head and neck cancer (H&N) helical tomotherapy (HT). MATERIAL AND METHODS: A total of 11 patients underwent adaptive radiotherapy (ART) using MVCT. Preconditions were a soft tissue change > 0.5 cm and a tight mask. The dose­volume histograms (DVHs) derived from the initial planning kVCT (inPlan), the recalculated DVHs of the fraction (fx) when replanning was decided (actSit) and the DVHs of the new plan (adaptPlan) were compared. Assessed were the following: maximum dose (Dmax), minimum dose (Dmin), and mean dose (Dmean) to the planning target volume (PTV) normalized to the prescribed dose; the Dmean/fx to the parotid glands (PG), oral cavity (OC), and larynx (Lx); and the Dmax/fx to the spinal cord (SC) in Gy/fx. RESULTS: No patient had palpable soft tissue changes. The median weight loss at the moment of replanning was 2.3 kg. The median PTV Dmean was 100% for inPlan, 103% for actSit, and 100% for adaptPlan. The PTV was always covered by the prescribed dose. A statistically significant increase was noted for all organs at risk (OAR) in the actSit. The Dmean to the Lx, the Dmean to the OC and the Dmax to the SC were statistically better in the adaptPlan. No statistically significant improvement was achieved by ART for the PGs. No significant correlations between weight and volume loss or between the volume changes of the organs to each other were observed, except a strong positive correlation of the shrinkage of the PGs (ρ = + 0.77, p = 0.005). CONCLUSION: Soft tissue shrinkage without clinical palpable changes will not affect the coverage of the PTV, but translates into a higher delivered dose to the PTV itself and the normal tissue outside the PTV. The gain by ART in individual patients­especially in patients who receive doses close to the tolerance doses of the OAR­could be substantial.

Acupuncture compared with oral antihistamine for type I hypersensitivity itch and skin response in adults with atopic dermatitis: a patient- and examiner-blinded, randomized, placebo-controlled, crossover trial.

BACKGROUND: Itch is the major symptom of atopic dermatitis (AD). Acupuncture has been shown to exhibit a significant effect on experimental itch in AD. Our study evaluated acupuncture and antihistamine itch therapy (cetirizine) on type I hypersensitivity itch and skin reaction in AD using a patient and examiner-blinded, randomized, placebo-controlled, crossover trial. METHODS: Allergen-induced itch was evaluated in 20 patients with AD after several interventions in separate sessions: preventive (preceding) and abortive (concurrent) verum acupuncture (VAp and VAa), cetirizine (10 mg, VC), corresponding placebo interventions (preventive, PAp, and abortive, PAa, placebo acupuncture; placebo cetirizine pill, PC) and a no-intervention control (NI). Itch was induced on the forearm and temperature modulated over 20 min, using our validated model. Outcome parameters included itch intensity, wheal and flare size and the D2 attention test. RESULTS: Mean itch intensity (SE: 0.31 each) was significantly lower following VAa (31.9) compared with all other groups (PAa: 36.5; VC: 36.8; VAp: 37.6; PC: 39.8; PAp: 39.9; NI: 45.7; P < 0.05). There was no significant difference between VAp and VC (P > 0.1), although both therapies were significantly superior to their respective placebo interventions (P < 0.05). Flare size following VAp was significantly smaller (P = 0.034) than that following PAp. D2 attention test score was significantly lower following VC compared with all other groups (P < 0.001). CONCLUSIONS: Both VA and cetirizine significantly reduced type I hypersensitivity itch in patients with AD, compared with both placebo and NI. Timing of acupuncture application was important, as VAa had the most significant effect on itch, potentially because of counter-irritation and/or distraction. Itch reduction following cetirizine coincided with reduced attention.

Hemodynamics after endoscopic submucosal injection of epinephrine in a porcine model.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal injection of epinephrine may cause systemic effects on the cardiovascular system. The aim of this experimental study was to assess systemic hemodynamic changes after submucosal injection of epinephrine during upper gastrointestinal endoscopy in a porcine model. METHODS: Measurements were taken from 12 pigs under general anesthesia. During gastroscopy 5 mL of normal saline, and 2.5 mL and 5 mL of epinephrine (1:10,000) were injected into the submucosal layers of the gastric antrum, corpus, and distal esophagus. After each injection, the cardiac index and global end diastolic volume index (GEDVI, reflecting preload) were measured every 3 minutes by transpulmonary thermodilution for a minimum of 12 minutes. The following parameters were also recorded: heart rate, mean arterial pressure (MAP), and systemic vascular resistance index (SVRI, reflecting afterload). RESULTS: Significant hemodynamic changes were observed after submucosal injection of epinephrine into the esophagus, including heart rate (maximum + 4 %) and MAP (maximum - 4%) after injection of 2.5 mL epinephrine, and stronger changes in heart rate (maximum +13%), cardiac index (maximum +21%), MAP (maximum -4%), and SVRI (maximum -12%) after the injection of 5 mL epinephrine. After submucosal injection of epinephrine into the gastric antrum and corpus, hemodynamic effects were less evident. Here significant changes were observed in heart rate (maximum +3%), MAP (maximum -2%), cardiac index (maximum +7%), and SVRI (maximum -8%) only after the injection of 5 mL epinephrine into the antrum. CONCLUSION: Endoscopic submucosal injection of epinephrine is associated with changes in systemic hemodynamic parameters, especially when performed in the esophagus, and the procedure might therefore induce harmful side effects.