High-frequency ultrasound quantification of acute radiation dermatitis: pilot study of patients undergoing radiotherapy for breast cancer.

BACKGROUND: Acute radiation dermatitis (ARD) is a frequent complication after breast cancer radiotherapy and is usually assessed by semi-quantitative clinical scores, which may be subject to inter-observer variability. High-frequency ultrasound imaging of the skin can reliably quantify thickness and edema in diseased skin. We aimed to compare the relative increase in dermal thickness of the irradiated zone in breast-cancer patients undergoing radiotherapy, with clinical severity. METHODS: A consecutive series of patients undergoing treatment for breast cancer by lumpectomy and radiotherapy in a 6-month period also underwent clinical and ultrasound evaluation of ARD. RESULTS: We included 34 female patients 17 had grade 1 (group 1), 17 had grade 2 or grade 3 ARD (group 2). The mean relative increase in dermal thickness in irradiated skin (RIDTIS) was greater for group 2 than 1: 0.53 vs 0.29 mm (P=.023). On univariate analysis, ARD was associated with skin phototype, breast volume and RIDTIS, and on multivariable analysis, breast volume and age remained predictive of the disease. CONCLUSION: Patients with more severe dermatitis showed significantly increased dermal thickness. Dermal thickness is a quantitative variable that could help quantify the efficacy of drugs and improve the treatment of this disease in patients undergoing radiotherapy.

[The morbidity and mortality review meetings in radiotherapy departments: Procedure, implementation and prospects of the "Proust" French national project]. / Revue de morbidité et mortalité en radiothérapie : procédure, implémentation et perspectives du projet national français « Proust ¼.

Radiation-induced acute and late toxicity depends on several parameters. The type, severity and duration of morbidity are mainly related to irradiated volume, total dose and its fractionation and the intrinsic radiosensitivity of the patients. The follow-up of these toxicities is essential. However, unlike many specialties, morbidity and mortality reviews procedures are not developed as part of quality governance programs in radiation therapy departments for the monitoring of toxicity which sometimes hinder the patients' quality of life. One French survey published within the framework of the project entitled Prospective Registration of Morbidity and Mortality, Individual Radiosensitivity and Radiation Technique (Proust), conclude that there was a lack of knowledge of morbidity and mortality reviews and considerable confusion between these reviews and other quality processes without perspective for the local morbidity and mortality reviews development in a large number of the participated centers. In this article, we will discuss the procedure of the "ideal morbidity and mortality reviews" and its implementation through a monocentric experience started in 2015. Thus, the Proust project is a unique opportunity to implement and standardize a national morbidity and mortality reviews implementation in radiation therapy departments by involving the French regions.

Effective thalamic deep brain stimulation for neuropathic tremor in a patient with severe demyelinating neuropathy.

Postural and action tremor in peripheral neuropathy is characteristic of Roussy-Levy syndrome. A patient with a severe demyelinating neuropathy and disabling neuropathic tremor successfully treated by deep brain stimulation (DBS) is reported. Disease onset was at age 63 years with sensory symptoms and slight action tremor. Within the following 9 years a severe, drug resistant, postural and action tremor developed rendering the patient unable to feed himself. At age 72 years the patient was treated by bilateral DBS of the ventral intermediate thalamic nucleus, with a useful 30% reduction in tremor. The clinical benefit of the stimulation remained stable over a 1 year postoperative observation period.

[Epithelioid hemangioendothelioma of the spine: A case report]. / Hémangioendothéliome épithélioïde rachidien : à propos d'un cas.

Epithelioid hemangioendothelioma is a rare vascular tumour, with features between hemangiomas and angiosarcomas. Evolution remains mainly local but may also metastasize. Here, we report a case of a patient with a spinal epithelioid hemangioendothelioma. After a first resection, local recurrence required a new excision and external radiotherapy. It was achieved by helical TomoTherapy® with intensity modulation. During the follow-up, a second inoperable spinal location necessitated a new sequence of radiotherapy in modulation of intensity with integrated boost. The patient was alive at 24 months of follow-up without evidence of local relapse or distance. This observation is followed by a discussion with review of the literature on other epithelioid hemangioendothelioma cases treated with radiation.

Impaired implicit learning and feedback processing after stroke.

The ability to learn is assumed to support successful recovery and rehabilitation therapy after stroke. Hence, learning impairments may reduce the recovery potential. Here, the hypothesis is tested that stroke survivors have deficits in feedback-driven implicit learning. Stroke survivors (n=30) and healthy age-matched control subjects (n=21) learned a probabilistic classification task with brain activation measured using functional magnetic resonance imaging in a subset of these individuals (17 stroke and 10 controls). Stroke subjects learned slower than controls to classify cues. After being rewarded with a smiley face, they were less likely to give the same response when the cue was repeated. Stroke subjects showed reduced brain activation in putamen, pallidum, thalamus, frontal and prefrontal cortices and cerebellum when compared with controls. Lesion analysis identified those stroke survivors as learning-impaired who had lesions in frontal areas, putamen, thalamus, caudate and insula. Lesion laterality had no effect on learning efficacy or brain activation. These findings suggest that stroke survivors have deficits in reinforcement learning that may be related to dysfunctional processing of feedback-based decision-making, reward signals and working memory.

Use of the alkaline comet assay to detect DNA repair deficiencies in human fibroblasts exposed to UVC, UVB, UVA and gamma-rays.

The alkaline single cell gel electrophoresis (comet) assay applied to human fibroblasts allowed us to analyze the response to components of the solar spectrum (UVB and UVA) in comparison with the well-established response to UVC and gamma-rays. DNA strand breaks related to nucleotide excision repair of DNA photoproducts were produced 1 h after exposure to UVB or UVC in the normal cell line but not in the repair deficient XPD and TTD-2 cell lines. In contrast, the immediate production of DNA strand breaks observed in all cell lines after exposure to UVA or gamma-rays was followed by restitution of high molecular weight DNA upon post-exposure incubation. These results imply that (1) fibroblasts as well as lymphocytes can be analysed by the comet assay and (2) the comet assay clearly distinguishes cellular nucleotide excision repair capacity without the use of inhibitors of DNA synthesis.

[Computed tomography option on simulator: a 14-month use at the Orléans hospital radiotherapy department]. / L'option scanneur sur simulateur: 14 mois d'utilisation dans le service de radiothérapie du CHR d'Orléans.

The purpose was to evaluate the use of the CT option for simulator during a 14-month period in the radiotherapy department. The CT option has been adapted on the Philips simulator SL23. The virtual tunnel diameter is 92 cm which allows slice acquisition regardless of the contention device used. This system is connected to the treatment planning system through an Ethernet link. Three fields of view are available which cover the standard radiotherapy use. Four hundred and twenty-seven patients benefited from this system over a 14-month period of use. The number of slices acquired per patient regularly increased. The use of the system was rapidly extended to all the standard treatments. Those slices were also used as additional information for these high technology treatments. The good quality of the images and the reliability of this system involved a rapid integration in the treatment preparation procedure. It will not replace the use of the scanner but will significantly improve the treatment quality.

[Use of fast neutrons in the treatment of tumors of the salivary glands: rationale, review of the literature and experience in Orleans]. / Utilisation des neutrons rapides dans le traitement des tumeurs des glandes salivaires: rationnel, revue de la littérature et expérience d'Orléans.

If low LET radiation therapy (photons, electrons), following radical microscopically and complete surgery can improve results in term of local control from 34 to 74% for salivary gland tumors, local control is more difficult to achieve in advanced tumors and only palliative treatment is usually attempted. In this survey, all the patient series treated worldwide were reviewed. They show an overall control rate of 31% with photon vs 64% with neutron therapy. A prospective randomised trial sponsored by the RTOG and the MRC published in 1988 and reviewed in 1993 showed an overall locoregional complete tumor clearance of 67% for neutrons and 17% for photons (P < 0.005), with 68% and 25% survival at two years for neutrons and photons respectively. This study was closed for ethical reasons. In Orleans, since 1987, 59 patients have been treated. At five years the persistent local control probability was 69.5%, the five-year crude survival probability 66% and the five-year tumor free survival probability was 64.5%. This review provides evidence that surgical treatment for salivary gland tumors should be limited to patients presenting a high likelihood of negative surgical margin and a small risk of facial nerve damage. Others patients should receive neutron radiation therapy alone as definitive treatment.

[Parkinson disease. Directed use of modern therapy]. / Parkinson-Krankheit. Moderne Therapie gezielt einsetzen.

The approval of new antiparkinsonian drugs such as novel dopamine agonists or COMT-inhibitors during the last years has improved the therapeutic possibilities in Parkinson's disease. The choice of the different drugs depends on their particular efficiency, their adverse effect profile, the stage of the disease, the cardinal symptoms, age, and comorbidity. Therefore the physician is challenged to adjust the therapeutic management of each patient to the particular medical and social needs. This article discusses the present therapeutic strategies for the different stages of the disease detailing the profile, the main applications and the most important side effects of each drug.

Differences between patients and medical professionals in the evaluation of aesthetic outcome following breast reconstruction with implants.

BACKGROUND AND AIM: Most studies on breast reconstruction evaluate different surgical techniques, types of implant or time of reconstruction. Moreover, evaluations are usually performed either by surgeons or by patients, but are rarely compared. We conducted a study on aesthetic outcome following breast reconstruction with implants comparing the evaluation by patients versus medical professionals. METHODS: Forty-seven patients, who had a breast reconstruction with implants between 2001 and 2010 (median follow-up 71 months), underwent a clinical examination, standardized photo documentation and filled out a questionnaire to evaluate their aesthetic result (rate 1 very good to 5 very poor). Photo documentation was independently evaluated by 18 medical professionals using the same evaluation instrument and the results were compared. Gender and patient aspects were taken into account. RESULTS: We found statistically significant differences between patients and medical professional ratings. The patient evaluation was better through all categories as compared to the evaluation by medical personnel. The degree of medical education or gender aspects did not significantly affect the professional ratings. Age at reconstruction, length of follow-up or primary versus secondary reconstruction did not seem to make a difference in the evaluations of the patients versus the medical professionals.. CONCLUSION: The differences between patient and expert opinion in rating of aesthetic results indicate that patient satisfaction is influenced by multiple factors and not only by good aesthetic outcome. Patient evaluation should therefore be carefully considered in treatment and outcome studies of breast reconstruction..

[Stereotactic radiotherapy for stage I and II lung cancer: a study of 33 patients]. / Radiothérapie en conditions stéréotaxiques dans les cancers bronchiques de stades I et II : résultats d'une série de 33 patients.

PURPOSE: Surgery is the main treatment of early stage non small cell lung cancer. However, in inoperable patients, the treatment is usually conventional radiotherapy. Results are poor and acute toxicity is severe. Stereotactic body radiation therapy provides better results in terms of local control and toxicity. Our purpose was to evaluate the clinical outcomes of patients with primary lung tumours treated by stereotactic body radiation therapy using a stereotactic body frame at the Orléans Regional Hospital. PATIENTS AND METHODS: Between June 2000 and December 2007, 33 patients with stage I and II non small cell lung cancer were treated by stereotactic body radiation therapy. Breathing control was obtained by passive diaphragm control. Two CT-scans were performed 1 week apart to determine the accuracy of patient repositioning and define target volumes. Five or six fields were set up to achieve a conformal dose distribution. According to tumour size, a total of 50 or 40 Gy was delivered in 10 fractions. RESULTS: Mean patient age was 70 years. Median follow-up was 25 months. Ten patients with a complete response are still alive. Eight patients have died from local progression, eight from metastasis, and six from comorbidity. Median disease-free survival was 22.6 months. No acute toxicity up to grade II (CTC AE 3.0) was observed. None of the patients still alive has developed any complications. CONCLUSION: In patients who cannot undergo radical surgery, stereotactic body radiation therapy using a sterotactic body frame is well-tolerated and seems to be an efficient treatment method.

Effective long-term subthalamic stimulation in PARK8 positive Parkinson's disease.

Whether patients with genetically defined Parkinson's disease (PD) may be particularly eligible to benefit from deep brain stimulation of the nucleus subthalamicus (STN-DBS) is currently the subject of debate. We report on a patient with advanced PD due to R793M missense mutation in the LRRK2 gene successfully treated by STN-DBS. Disease onset was at age 42 with bradykinesia, rigidity and rest tremor. During the course of the disease he developed severe motor fluctuations, dyskinesias, postural instability with falls, but preserved levodopa responsiveness. At age 60 the patient was treated by bilateral DBS of the STN. At one year after surgery a 66% improvement of the UPDRS motor score in the off-medication state was determined. During the long-term follow-up there was sustained benefit with 56% improvement of motor score after 8 years. Our report adds evidence that patients with LRRK2 monogenetic Parkinsonism are well suited candidates for DBS treatment and may indicate a potential genetic predictor for positive long-term effect of STN-DBS treatment.

The effect of subthalamic nucleus stimulation on kinaesthesia in Parkinson's disease.

BACKGROUND: Parkinson's disease is accompanied by deficits in passive motion and limb position sense. OBJECTIVE: To investigate whether deep brain stimulation of the subthalamic nucleus (STN-DBS) reverses these proprioceptive deficits. METHODS AND RESULTS: A passive movement task was applied to nine patients with Parkinson's disease and bilateral chronic STN-DBS and to seven controls. Thresholds for 75% correct responses were 0.9 degrees for controls, 2.5 degrees for Parkinson's disease patients when stimulation was OFF, and 2.0 degrees when stimulation was ON. CONCLUSIONS: STN-DBS improves kinaesthesic deficits in Parkinson's disease, but does not lead to a full recovery of proprioceptive function.

Striatal [123I]beta-CIT SPECT and prefrontal cognitive functions in Parkinson's disease.

Twenty non-demented patients with idiopathic Parkinson's disease (PD) underwent single photon emission computed tomography (SPECT) with [123I]beta-CIT to further investigate the contribution of nigrostriatal dysfunction to cognitive and motor deficits. Compared to matched controls PD patients showed normal verbal intelligence, short-term memory and phasic alertness. There were significant (p < 0.05) deficits in tests of verbal working memory (digit ordering, reading span), strategic memory (story recall) and executive functions (card sorting), indicating a "prefrontal" cognitive deficit. Significant (p < 0.05) correlations were observed between dopamine transporter (DAT) density in the putamen and motor deficits as well as between DAT density in both striatal compartments (head of the caudate nucleus and putamen) and prefrontal functioning. Age was a major contributing factor to both cognitive status and nigrostriatal integrity as measured by [123I]beta-CIT SPECT. These results support the view that the striatum is part of a neuronal network that is mediating prefrontal cognitive functions.

Probability detection mechanisms and motor learning.

The automatic detection of patterns or regularities in the environment is central to certain forms of motor learning, which are largely procedural and implicit. The rules underlying the detection and use of probabilistic information in the perceptual-motor domain are largely unknown. We conducted two experiments involving a motor learning task with direct and crossed mapping of motor responses in which probabilities were present at the stimulus set level, the response set level, and at the level of stimulus-response (S-R) mapping. We manipulated only one level at a time, while controlling for the other two. The results show that probabilities were detected only when present at the S-R mapping and motor levels, but not at the perceptual one (experiment 1), unless the perceptual features have a dimensional overlap with the S-R mapping rule (experiment 2). The effects of probability detection were mostly facilitatory at the S-R mapping, both facilitatory and inhibitory at the perceptual level, and predominantly inhibitory at the response-set level. The facilitatory effects were based on learning the absolute frequencies first and transitional probabilities later (for the S-R mapping rule) or both types of information at the same time (for perceptual level), whereas the inhibitory effects were based on learning first the transitional probabilities. Our data suggest that both absolute frequencies and transitional probabilities are used in motor learning, but in different temporal orders, according to the probabilistic properties of the environment. The results support the idea that separate neural circuits may be involved in detecting absolute frequencies as compared to transitional probabilities.

[Multimodal SPECT and MRT imaging data analysis for an improvement in the diagnosis of idiopathic Parkinson's syndrome]. / Multimodale SPECT- und MRT-Bilddatenanalyse zur Verbesserung der Diagnostik des idiopathischen Parkinson-Syndroms.

Parkinson's disease (PD) is characterized by a degeneration of nigrostriatal dopaminergic neurons, which can be imaged with 123I-labeled 2 beta-carbomethoxy-3 beta-(4-iodophenyl) tropane ([123I]beta-CIT) and single-photon emission computed tomography (SPECT). However, the quality of the region of interest (ROI) technique used for quantitative analysis of SPECT data is compromised by limited anatomical information in the images. We investigated whether the diagnosis of PD can be improved by combining the use of SPECT images with morphological image data from magnetic resonance imaging (MRI)/computed tomography (CT). We examined 27 patients (8 men, 19 women; aged 55 +/- 13 years) with PD (Hoehn and Yahr stage 2.1 +/- 0.8) by high-resolution [123I]beta-CIT SPECT (185-200 MBq, Ceraspect camera). SPECT images were analyzed both by a unimodal technique (ROIs defined directly within the SPECT studies) and a multimodal technique (ROIs defined within individual MRI/CT studies and transferred to the corresponding interactively coregistered SPECT studies). [123I]beta-CIT binding ratios (cerebellum as reference), which were obtained for heads of caudate nuclei (CA), putamina (PU), and global striatal structures were compared with clinical parameters. Differences between contra- and ipsilateral (related to symptom dominance) striatal [123I]beta-CIT binding ratios proved to be larger in the multimodal ROI technique than in the unimodal approach (e.g., for PU: 1.2 vs. 0.7). Binding ratios obtained by the unimodal ROI technique were significantly correlated with those of the multimodal technique (e.g., for CA: y = 0.97x + 2.8; r = 0.70; P < 0.001). Concerning the correlations between SPECT data and clinical parameters, the significance levels in the multimodal ROI technique, for example, for the correlation between CA and the UPDRScom subscore (r = -0.49 vs. -0.32). These results show that the impact of [123I]beta-CIT SPECT for diagnosing PD is affected by the method used to analyze the SPECT images. The described multimodal approach, which is based on coregistration of SPECT and morphological imaging data, leads to improved determination of the degree of this dopaminergic disorder.

Steele-Richardson-Olszewski-syndrome: the relation of dopamine D2 receptor binding and subcortical lesions in MRI.

We compared (123)I-iodobenzamide single photon emission computed tomography (IBZM-SPECT) for imaging of striatal dopamine D(2) receptors in vivo, and MRI in 32 patients with the clinical diagnosis of progressive supranuclear palsy (PSP). We found a significant inter-dependence of reduction of specific striatal IBZM binding indicative of striatal degeneration and of the absence of multiple signal hyperintensities in MRI; age had no influence neither on IBZM binding nor on signal hyperintensities. We conclude that the presence of multiple signal hyperintensities should raise doubt on the correct clinical diagnosis.