Citations

AbstractThe 2016 World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms (MPN) underscore the prognostically‐relevant distinction between essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (pre‐PMF). In addition, leukocytosis has been identified as an important prognostic marker in otherwise WHO‐defined ET. However, controversy remains regarding the objectivity of morphologic criteria in distinguishing ET from pre‐PMF and the precise prognostic cutoff values for leukocytosis. Serum lactate dehydrogenase (LDH) level might be a biologically more accurate measure of leukocyte turnover and a more sensitive marker of pre‐PMF, in otherwise WHO‐defined ET. In the current study of 183 consecutive patients with WHO‐defined ET, the presence of grade 1 bone marrow (BM) fibrosis did not affect presenting clinical or laboratory features; in contrast, increased serum LDH at diagnosis was associated with leukocytosis (p = .002), thrombocytosis (p < .001), palpable splenomegaly (p = .03) and higher international prognostic score (IPSET) (p = .002); serum LDH did not correlate with BM fibrosis, JAK2/CALR/MPL or TET2/ASXL1 mutations. In univariate analysis, risk factors for survival included age ≥60 years (p = .002; HR 10.2, 95% CI 2.3‐44.6), male sex (p = .02; HR 3.2, 95% CI 1.2‐8.2), leukocyte count ≥15 × 109/L (p = .007; HR 4.7, 95% CI 1.5‐14.6), and increased serum LDH (p = .002; HR 3.7, 95% CI 1.5‐9.1), but not BM fibrosis (p = .17). In multivariable analysis, age, sex and serum LDH remained significant; serum LDH also remained significant, in the context of IPSET (p = .003) and in patients with leukocytosis (p = .003). We conclude that serum LDH level carries an independent prognostic value for survival in ET and might represent a biologically more accurate surrogate for leukocytosis.

Abstract BACKGROUND Late adverse radiation effects (ARE) typically occur many years after stereotactic radiosurgery (SRS) of intracranial arteriovenous malformations (AVM). They are characterized by perilesional edema or cyst formation and are distinct from radiation-induced changes (RIC) noted in the first 1 to 2 years after AVM SRS and radiation necrosis. OBJECTIVE To determine the incidence of late ARE after AVM SRS. METHODS Retrospective review of 233 AVM patients having SRS from 1990 to 2009. Patients had sporadic AVM, no prior radiation, and a minimum of 5 years of magnetic resonance imaging (MRI) follow-up. The median MRI follow-up after SRS was 9.8 years (range, 5-24.2). RESULTS Late ARE were observed in 16 patients (6.9%) at a median of 8.7 years after SRS (range, 2.0-16.1). The 5-, 10-, and 15-year incidence of late ARE was 0.4%, 7.7%, and 12.5%, respectively. Eight patients (3.4%) were symptomatic at the time of ARE detection. Three of 8 patients who were initially asymptomatic had documented cyst progression (at 11, 40, and 42 months), for an overall symptomatic rate of 4.7%. Five patients with asymptomatic ARE have been observed for a median of 9.3 years (range, 2.0-14.1) without progression. Patients having early RIC (hazard ratio [HR] = 2.11, P < .001), patients having obliteration (HR = 1.24, P = .02), and patients having SRS before April 1997 (HR = 1.12, P = .02) were more likely to develop late ARE. CONCLUSION Late ARE are common in AVM patients who develop early RIC after SRS. Resection of the thrombosed AVM and the adjacent damaged tissue is effective at eliminating the mass effect and improving patients’ neurological condition.

Purpose: To report the outcomes of patients with favorable risk oropharyngeal cancer that underwent adjuvant radiation therapy with omission of the primary site from the clinical target volume (CTV). Material/Methods: A retrospective study of 40 patients treated with transoral surgery (TOS) followed by neck only radiation using intensity modulated radiation therapy (IMRT) with exclusion of the primary site. For all patients, a CTV of the primary surgical bed was contoured to obtain the estimated incidental dose to the primary site. Results: Median follow-up was 51 months (range, 13-155 months). The median radiation therapy (RT) dose to the neck was 6000 cGy (range, 5400-6400 cGy). The mean incidental dose to the primary tonsillar site was 4320 cGy (SD ± 480 cGy) and to the primary base of tongue site was 4060 cGy (SD ± 420 cGy). There were no local failures and only 1 regional failure, resulting in 97.5% locoregional control rate at 4 years. Two patients developed distant metastases, without evidence of locoregional recurrence, for a 4-year overall survival rate of 97%. Conclusions: Our analysis suggests that mucosal sparing RT after TOS in favorable risk oropharyngeal cancer patients may provide comparable oncologic and improved functional outcomes compared to conventional treatment in selected patients.

AbstractIntroductionWe hypothesized that common Alzheimer's disease (AD)‐associated variants within the triggering receptor expressed on myeloid (TREM) gene cluster influence disease through gene expression.MethodsExpression microarrays on temporal cortex and cerebellum from ∼400 neuropathologically diagnosed subjects and two independent RNAseq replication cohorts were used for expression quantitative trait locus analysis.ResultsA variant within a DNase hypersensitive site 5′ of TREM2, rs9357347‐C, associates with reduced AD risk and increased TREML1 and TREM2 levels (uncorrected P = 6.3 × 10−3 and 4.6 × 10−2, respectively). Meta‐analysis on expression quantitative trait locus results from three independent data sets (n = 1006) confirmed these associations (uncorrected P = 3.4 × 10−2 and 3.5 × 10−3, Bonferroni‐corrected P = 6.7 × 10−2 and 7.1 × 10−3, respectively).DiscussionOur findings point to rs9357347 as a functional regulatory variant that contributes to a protective effect observed at the TREM locus in the International Genomics of Alzheimer's Project genome‐wide association study meta‐analysis and suggest concomitant increase in TREML1 and TREM2 brain levels as a potential mechanism for protection from AD.

Key Points More than half of patients with PV or ET harbor DNA mutations/variants other than JAK2/CALR/MPL. The presence of some of these mutations adversely affects overall, leukemia-free, or myelofibrosis-free survival.

Key Points More than 80% of patients with PMF harbor DNA variants/mutations other than JAK2/CALR/MPL. Some of these variants/mutations adversely affect overall or leukemia-free survival independent of conventional risk stratification.

Abstract Neurological disorders are one of the most important public health concerns in developed countries. Established brain imaging techniques such as magnetic resonance imaging (MRI) and x-ray computerised tomography (CT) have been essential in the identification and diagnosis of a wide range of disorders, although usually are insufficient in sensitivity for detecting subtle pathological alterations to the brain prior to the onset of clinical symptoms—at a time when prognosis for treatment is more favourable. The mechanical properties of biological tissue provide information related to the strength and integrity of the cellular microstructure. In recent years, mechanical properties of the brain have been visualised and measured non-invasively with magnetic resonance elastography (MRE), a particularly sensitive medical imaging technique that may increase the potential for early diagnosis. This review begins with an introduction to the various methods used for the acquisition and analysis of MRE data. A systematic literature search is then conducted to identify studies that have specifically utilised MRE to investigate the human brain. Through the conversion of MRE-derived measurements to shear stiffness (kPa) and, where possible, the loss tangent (rad), a summary of results for global brain tissue and grey and white matter across studies is provided for healthy participants, as potential baseline values to be used in future clinical investigations. In addition, the extent to which MRE has revealed significant alterations to the brain in patients with neurological disorders is assessed and discussed in terms of known pathophysiology. The review concludes by predicting the trends for future MRE research and applications in neuroscience.

Objective To identify factors associated with regional recurrence after lymph node dissection ( LND ) for squamous cell carcinoma ( SCC ) to determine which patients might benefit from adjuvant therapy. Patients and Methods Men who underwent LND for penile SCC from 1977 to 2014 were identified from an institutional database. Kaplan–Meier curves estimated recurrence‐free survival ( RFS ) calculated from the date of LND . Cox regression models evaluated the association between RFS and patient and tumour characteristics. Results In all, 182 men who underwent LND for penile SCC were identified. The median patient age was 62 years and the median follow‐up was 4.2 years. After LND 34 men had regional recurrence, of which 24 developed isolated regional recurrences without distant metastasis. The median RFS was 5.7 months, and the 3‐year RFS rate was 70%. On univariate analysis, lymphovascular invasion, clinical and pathological nodal stage, pathological inguinal laterality, pelvic nodal involvement, lymph node density ≥5.2%, ≥3 pathologically involved lymph nodes, and extranodal extension ( ENE ) were associated with worse RFS (all P < 0.05). On multivariate analysis, clinical N3 disease [adjusted hazard ratio ( AHR )] 3.53, 95% confidence interval ( CI ) 1.68–7.45; P = 0.001), ≥3 pathologically involved lymph nodes ( AHR 3.78, 95% CI 2.12–6.65; P < 0.001), and ENE ( AHR 3.32, 95% CI 1.93–5.76; P < 0.001) were associated with worse RFS . The 3‐year RFS for patients with cN 0, cN 1, cN 2, and cN 3 disease was 91.7%, 64.5%, 54.7%, and 38.3%, respectively. For men with ≥3 involved nodes, the 3‐year RFS was 17% vs 82.4% in men with <3 involved nodes. The 3‐year RFS was 29.7% in men with ENE and 85.7% in men without ENE. Conclusion The presence of clinical N3 disease, ≥3 pathologically involved lymph nodes, and ENE was associated with worse RFS . As regional recurrence portends a dismal prognosis with few salvage options, adjuvant therapies should be developed for men with the aforementioned adverse factors.