Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib.

Familial gastrointestinal stromal tumors (GIST) are rare. We present a kindred with multiple family members affected with multifocal GIST who underwent whole genome sequencing of the germline and tumor. Affected individuals with GIST harbored a germline variant found within exon 13 of the KIT gene (c.1965T>G; p.Asn655Lys, p.N655K) and a variant in the MSR1 gene (c.877 C > T; p.Arg293*, pR293X). Multifocal GISTs in the proband and her mother were treated with preoperative imatinib, which resulted in severe intolerance. The clinical features of multifocal GIST, cutaneous mastocytosis, allergies, and gut motility disorders seen in the affected individuals may represent manifestations of the multifunctional roles of KIT in interstitial cells of Cajal or mast cells and/or may be suggestive of additional molecular pathways which can contribute to tumorigenesis.

Clinical Evaluation of Scout Accelerated Motion Estimation and Reduction Technique for 3D MR Imaging in the Inpatient and Emergency Department Settings.

BACKGROUND AND PURPOSE: A scout accelerated motion estimation and reduction (SAMER) framework has been developed for efficient retrospective motion correction. The goal of this study was to perform an initial evaluation of SAMER in a series of clinical brain MR imaging examinations. MATERIALS AND METHODS: Ninety-seven patients who underwent MR imaging in the inpatient and emergency department settings were included in the study. SAMER motion correction was retrospectively applied to an accelerated T1-weighted MPRAGE sequence that was included in brain MR imaging examinations performed with and without contrast. Two blinded neuroradiologists graded images with and without SAMER motion correction on a 5-tier motion severity scale (none = 1, minimal = 2, mild = 3, moderate = 4, severe = 5). RESULTS: The median SAMER reconstruction time was 1 minute 47 seconds. SAMER motion correction significantly improved overall motion grades across all examinations (P < .005). Motion artifacts were reduced in 28% of cases, unchanged in 64% of cases, and increased in 8% of cases. SAMER improved motion grades in 100% of moderate motion cases and 75% of severe motion cases. Sixty-nine percent of nondiagnostic motion cases (grades 4 and 5) were considered diagnostic after SAMER motion correction. For cases with minimal or no motion, SAMER had negligible impact on the overall motion grade. For cases with mild, moderate, and severe motion, SAMER improved the motion grade by an average of 0.3 (SD, 0.5), 1.1 (SD, 0.3), and 1.1 (SD, 0.8) grades, respectively. CONCLUSIONS: SAMER improved the diagnostic image quality of clinical brain MR imaging examinations with motion artifacts. The improvement was most pronounced for cases with moderate or severe motion.

A scintillator attenuation spectrometer for intense gamma-rays.

A new type of compact high-resolution high-sensitivity gamma-ray spectrometer for short-pulse intense gamma-rays (250 keV to 50 MeV) has been developed by combining the principles of scintillators and attenuation spectrometers. The first prototype of this scintillator attenuation spectrometer (SAS) was tested successfully in Trident laser experiments at LANL. Later versions have been used extensively in the Texas Petawatt laser experiments in Austin, TX, and more recently in OMEGA-EP laser experiments at LLE, Rochester, NY. The SAS is particularly useful for high-repetition-rate laser applications. Here, we give a concise description of the design principles, capabilities, and sample preliminary results of the SAS.

Evaluation of Ultrafast Wave-Controlled Aliasing in Parallel Imaging 3D-FLAIR in the Visualization and Volumetric Estimation of Cerebral White Matter Lesions.

BACKGROUND AND PURPOSE: Our aim was to evaluate an ultrafast 3D-FLAIR sequence using Wave-controlled aliasing in parallel imaging encoding (Wave-FLAIR) compared with standard 3D-FLAIR in the visualization and volumetric estimation of cerebral white matter lesions in a clinical setting. MATERIALS AND METHODS: Forty-two consecutive patients underwent 3T brain MR imaging, including standard 3D-FLAIR (acceleration factor = 2, scan time = 7 minutes 50 seconds) and resolution-matched ultrafast Wave-FLAIR sequences (acceleration factor = 6, scan time = 2 minutes 45 seconds for the 20-channel coil; acceleration factor = 9, scan time = 1 minute 50 seconds for the 32-channel coil) as part of clinical evaluation for demyelinating disease. Automated segmentation of cerebral white matter lesions was performed using the Lesion Segmentation Tool in SPM. Student t tests, intraclass correlation coefficients, relative lesion volume difference, and Dice similarity coefficients were used to compare volumetric measurements among sequences. Two blinded neuroradiologists evaluated the visualization of white matter lesions, artifacts, and overall diagnostic quality using a predefined 5-point scale. RESULTS: Standard and Wave-FLAIR sequences showed excellent agreement of lesion volumes with an intraclass correlation coefficient of 0.99 and mean Dice similarity coefficient of 0.97 (SD, 0.05) (range, 0.84-0.99). Wave-FLAIR was noninferior to standard FLAIR for visualization of lesions and motion. The diagnostic quality for Wave-FLAIR was slightly greater than for standard FLAIR for infratentorial lesions (P < .001), and there were fewer pulsation artifacts on Wave-FLAIR compared with standard FLAIR (P < .001). CONCLUSIONS: Ultrafast Wave-FLAIR provides superior visualization of infratentorial lesions while preserving overall diagnostic quality and yields white matter lesion volumes comparable with those estimated using standard FLAIR. The availability of ultrafast Wave-FLAIR may facilitate the greater use of 3D-FLAIR sequences in the evaluation of patients with suspected demyelinating disease.

Prognostic impact of pre-treatment neutrophil-to-lymphocyte ratio (NLR) in nasopharyngeal carcinoma: A retrospective study of 180 Taiwanese patients.

OBJECTIVES: Nasopharyngeal cancer (NPC) is an endemic disease in Taiwan. Prognostic factors the anatomical TNM stage are important for its prognostic stratification. An elevated neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with poor prognosis in various solid tumours. In this study, we analysed the prognostic impact of the NLR in NPC in Taiwan. DESIGN: Single-institution retrospective study. SETTING: Medical centre. PARTICIPANTS: One hundred and eighty patients with NPC treated at the Far Eastern Memorial Hospital, Taiwan, from January 2007 to December 2013. MAIN OUTCOME MEASURES: The association between the clinical or haematological presentations and the prognosis. RESULTS: The majority of the 180 patients included in this study were men (80%) and were <65 years old (91.7%). A neck mass (55.6%) was the most common clinical presentation, followed by nasal (39.4%) and aural (30.6%) symptoms. In addition, the majority (75.4%) of patients had advanced stage (III and IV) disease. Patients with a high NLR (≧3.6) had significantly lower progression-free survival, overall survival and disease-specific survival rates. The association between high NLR and poor prognosis was more pronounced in patients with advanced disease than in those with early-stage NPC. The results of a multivariate analysis revealed that advanced age, clinical symptoms including headache, diplopia and facial numbness, advanced disease stage, and high NLR were independent prognostic factors. CONCLUSION: A high NLR is an independent poor prognostic factor of NPC in Taiwan.

A real-time prediction model for post-irradiation malignant cervical lymph nodes.

OBJECTIVE: To establish a real-time predictive scoring model based on sonographic characteristics for identifying malignant cervical lymph nodes (LNs) in cancer patients after neck irradiation. METHODS: One-hundred forty-four irradiation-treated patients underwent ultrasonography and ultrasound-guided fine-needle aspirations (USgFNAs), and the resultant data were used to construct a real-time and computerised predictive scoring model. This scoring system was further compared with our previously proposed prediction model. RESULTS: A predictive scoring model, 1.35 × (L axis) + 2.03 × (S axis) + 2.27 × (margin) + 1.48 × (echogenic hilum) + 3.7, was generated by stepwise multivariate logistic regression analysis. Neck LNs were considered to be malignant when the score was ≥ 7, corresponding to a sensitivity of 85.5%, specificity of 79.4%, positive predictive value (PPV) of 82.3%, negative predictive value (NPV) of 83.1%, and overall accuracy of 82.6%. When this new model and the original model were compared, the areas under the receiver operating characteristic curve (c-statistic) were 0.89 and 0.81, respectively (P < .05). CONCLUSIONS: A real-time sonographic predictive scoring model was constructed to provide prompt and reliable guidance for USgFNA biopsies to manage cervical LNs after neck irradiation.

Effects of comorbidity and medication use on the haemodynamic status during office-based laryngeal procedures: A prospective cohort study.

OBJECTIVE: Office-based laryngeal procedures (OBLPs) are emerging as effective alternative modalities for vocal disorders. This study systematically investigates the haemodynamic status of patients, specifically focusing on the potential effects of underlying comorbidity and medication use. DESIGN: Prospective cohort study. SETTING: Tertiary referral centre. PARTICIPANTS: We prospectively recruited 214 consecutive patients who received OBLPs during January-December 2015. All procedures were performed under local anaesthesia without sedation, in an upright (sitting) position. MAIN OUTCOME MEASURES: We measured heart rate (HR), systolic and diastolic blood pressure, and oxygen saturations at baseline (before procedure), immediately after local anaesthesia to the pharynx and larynx, immediately after completing of procedure, and 20 minutes after the procedure. RESULTS: Systolic, diastolic blood pressures and HR all significantly increased after local anaesthesia, and gradually decreased after the procedure (P<.01). Oxygen concentration remained unchanged. Patients with comorbidity and those receiving vasoactive medications showed significantly higher perioperative blood pressures than the other patients (P<.05), but the trend remained similar. Prominent hypertension (systolic ≥160 mm Hg or diastolic ≥100 mm Hg) was noted in 17 patients, more commonly in patients with older age, higher baseline blood pressures and receiving vasoactive medications. Only 2% of patients with normal baseline measurements developed prominent hypertension perioperatively. Tachycardia (HR≥100 bpm) developed in 22 patients, more frequently in patients with higher baseline HRs, and perceiving greater discomforts. CONCLUSION: This study revealed that routine haemodynamic monitoring may not be necessary for all the OBLPs, but should be considered for older patients, those with higher baseline blood pressure or HR, sensitive patients who might be more susceptible to perioperative discomfort, and those receiving vasoactive medications.