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Petah Tikva, Israel

Chua Y.J.,Royal Marsden Hospital | Chua Y.J.,Medical Oncology Unit | Barbachano Y.,Royal Marsden Hospital | Cunningham D.,Royal Marsden Hospital | And 8 more authors.
The Lancet Oncology | Year: 2010

Background: Patients with poor-risk rectal cancer defined by MRI can be at high risk of disease recurrence despite standard chemoradiotherapy and optimum surgery. We aimed to assess the safety and long-term efficacy of neoadjuvant chemotherapy with capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision, a treatment strategy developed to enhance the outcome of this population. Methods: Between November, 2001, and August, 2005, we enrolled eligible patients with poor-risk rectal cancer defined by high-resolution MRI and without metastatic disease. The protocol was amended in January, 2004, following clinically significant cardiotoxic events (nine events in eight of 77 patients), to exclude patients with a recent history of clinically significant cardiac problems. Patients received 12 weeks of neoadjuvant capecitabine and oxaliplatin (oxaliplatin 130 mg/m2 on day 1 with capecitabine 1000 mg/m2 twice daily for 14 days every 3 weeks) followed by chemoradiotherapy (54 Gy over 6 weeks) with capecitabine (825 mg/m2 twice daily), total mesorectal excision, and 12 weeks of postoperative adjuvant capecitabine (1250 mg/m2 twice daily for 14 days every 3 weeks). The primary endpoint was pathological complete response rate. We followed up patients for a median of 55 months (IQR 47-67). Efficacy analyses were undertaken for the intention-to-treat population, unless otherwise specified. This study is registered with ClinicalTrials.gov, number NCT00220051. Findings: 105 eligible patients were enrolled. Radiological response rates after neoadjuvant chemotherapy and chemoradiotherapy were 74% (78/105) and 89% (93/105), respectively. 97 patients underwent surgery, of whom 95 underwent total mesorectal excision, of whom 93 had microscopically clear resection margins and 21 had pathological complete response (21/105 [20%]). 3-year progression-free and overall survival were 68% (95% CI 59-77) and 83% (76-91), respectively. 3-year relapse-free survival for patients who had complete resection was 74% (65-83). Following the protocol amendment for cardiovascular safety, only one further thromboembolic event was reported (fatal pulmonary embolism). Interpretation: Intensification of systemic therapy with neoadjuvant combination chemotherapy before standard treatment is feasible in poor-risk potentially operable rectal cancer, with acceptable safety and promising long-term outcomes. Future development of this multidisciplinary treatment strategy in randomised trials is warranted. Funding: UK National Health Service, Sanofi-Aventis. © 2010 Elsevier Ltd. All rights reserved.


Schmokel H.,Evidensia Spine Center | Rapp M.,Diagnostic Imaging
Veterinary and Comparative Orthopaedics and Traumatology | Year: 2016

Three German Shepherd Dogs that were presented for investigation of chronic unilateral hindlimb lameness and pain in the lumbosacral region were diagnosed with an intraspinal, extradural synovial cyst and reactive fibrosis protruding into the foramen of the lumbosacral articulation using magnetic resonance imaging and histology. This extra-dural mass compressed the nerve root in the foramen and the cauda equina. During a dorsal laminectomy and unilateral partial for-aminotomy, the cyst and the fibrotic tissue were removed with the aid of a 2.4 mm 30° arthroscope for visualization of the foramen. The fibrotic tissue surrounding the cysts was in all cases confluent with the annulus of the intervertebral disc. The histological examination confirmed the diagnosis of a synovial cyst in all three cases by finding inflamed synovial membrane in the samples from the wall of the cyst as well as reactive fibrosis and cartilaginous metaplasia in the surrounding tissue. The three patients improved after the surgery and were pain free during the follow-up evaluations. © Schattauer 2016.


Di Primio G.,Diagnostic Imaging
CMAJ | Year: 2011

The discovery of bone spots on a radiograph is often disturbing, and benign conditions need to be differentiated from indicators of serious disease. Osteopoikilosis is one of several uncommon benign variants of bone formation that must be distinguished from more worrisome disorders, most notably osteoblastic metastases. This differentiation can be done on the basis of the lack of internal architecture, irregular margins, the periarticular distribution and relative sparing of the skull. © 2011 Canadian Medical Association or its licensors.


Widjaja E.,Diagnostic Imaging | Go C.,The Hospital for Sick Children | McCoy B.,The Hospital for Sick Children | Snead O.C.,The Hospital for Sick Children
Epilepsy Research | Year: 2015

Background: The aims of this systematic review and meta-analysis were to assess (i) estimates of good neurodevelopmental outcome in infantile spasms (IS), (ii) if neurodevelopmental outcome has changed since the publication of the first guideline on medical treatment of IS in 2004 and (iii) effect of lead time to treatment (LTTT) Methods: The Medline, Embase, Cochrane, PsycINFO, Web of Science and Scopus databases, and reference lists of retrieved articles were searchedStudies inclusion criteria were: (i) >5 patients with IS, (ii) mean/median follow-up of >6 months, (iii) neurodevelopmental outcome, and (iv) randomized and observational studiesThe data extracted included proportion of good neurodevelopmental outcome, year of publication, cryptogenic or symptomatic IS and LTTT Results: Of the 1436 citations screened, 55 articles were included in final analysis, with a total of 2967 patientsThe pooled estimate for good neurodevelopmental outcome was 0.236 (95% CI: 0.193-0.286)There was no difference between the proportions of good neurodevelopmental outcome for the 21 studies published after 2004 [0.264 (95% CI: 0.197-0.344)] compared to the 34 studies published before 2004 [0.220 (95% CI: 0.168-0.283)] (Q value=0.862, p=0.353)The pooled estimate of good neurodevelopmental outcome for cryptogenic IS [0.543 (95% CI: 0.458-0.625)] was higher than symptomatic IS [0.125 (95% CI: 0.09-0.171)] (Q value=69.724, p<0.001)Risk ratio of LTTT <4weeks relative to >4weeks for good neurodevelopmental outcome of 8 studies was 1.519 (95% CI: 1.064-2.169) Conclusion: Neurodevelopmental outcome was overall poor in patients with IS and has not changed since the publication of first guideline on ISAlthough cryptogenic IS has better prognosis than symptomatic IS, the outcome for cryptogenic IS remained poorThere was heterogeneity in neurodevelopmental outcome ascertainment methods, highlighting the need for a more standardized and comprehensive assessment of cognitive, behavioural, emotional and functional outcomes. © 2014 Elsevier B.V.


Widjaja E.,Diagnostic Imaging | Skocic J.,Hospital for Sick Children | Go C.,Hospital for Sick Children | Snead O.C.,Hospital for Sick Children | And 2 more authors.
Epilepsia | Year: 2013

Summary Purpose The white matter (WM) is considered critical for linking cortical processing networks necessary for cognition. The aim of this study was to assess diffusion tensor imaging (DTI) measures of regional WM in children with nonlesional localization-related epilepsy in comparison to controls, and to determine the relation between lobar WM and neuropsychological performance. Methods Forty children with nonlesional localization-related epilepsy and 25 healthy controls with no neurological or psychiatric disorders and normal magnetic resonance imaging (MRI) were recruited. All patients and controls underwent neuropsychological testing that evaluated intelligence, language, memory, executive function, and motor function, as well as DTI to assess regional WM measures of fractional anisotropy (FA) and mean diffusivity (MD). The regional FA and MD were compared between patients and controls, and correlated with neuropsychological function. The relations between regional FA and MD with age at seizure onset and duration of epilepsy were assessed. Key Findings Twenty-one patients had left-sided and 19 patients had right-sided epilepsy. There were no significant differences in seizure-related variables including age at seizure onset, duration of epilepsy, seizure frequency, and number of antiepileptic medications, as well as no significant differences in neuropsychological function and DTI measures of white matter in left-sided compared to right-sided epilepsy. Therefore, all the patients with epilepsy were treated as one group. Patients with epilepsy performed significantly worse on intelligence (p < 0.001), language (p < 0.001), and executive function (p = 0.001) evaluation than controls. Patients had significantly reduced FA in left frontal (p = 0.015), right frontal (p = 0.004), left temporal (p = 0.039), right temporal (p = 0.003), right parietal (p = 0.014), and right occipital (p = 0.025) WM relative to controls. There were no significant regional WM differences (all p > 0.05) in MD between patients and controls. There was a significant positive correlation between right temporal FA with language (r = 0.535, p < 0.001) and executive function (r = 0.617, p < 0.001), as well as between body of corpus callosum FA with intelligence (r = 0.536, p < 0.001) and language (r = 0.529, p < 0.001) in patients. Left parietal MD was significantly correlated with language (r = -0.545, p < 0.001) in patients. FA of right temporal WM was significantly associated with age at seizure onset (t = 4.97, p < 0.001). Significance There was widespread regional WM abnormality in children with nonlesional localization-related epilepsy, which was associated with impaired neuropsychological function. The impairment in WM may reflect disruption in the connectivity for cortical processing networks, which is necessary for the development of cognition. © Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

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