Citations

PURPOSE: We postulated that the pathologic evaluation of the lymph nodes of surgical specimens from patients with rectal cancer can have a substantial impact on time to relapse and survival. PATIENTS AND METHODS: We analyzed data from 1,664 patients with T3, T4, or node-positive rectal cancer treated in a national intergroup trial of adjuvant therapy with chemotherapy and radiation therapy. Associations between the number of lymph nodes found by the pathologist in the surgical specimen and the time to relapse and survival outcomes were investigated. RESULTS: Patients were divided into groups by nodal status and the corresponding quartiles of numbers of nodes examined. The number of nodes examined was significantly associated with time to relapse and survival among patients who were node-negative. For the first through fourth quartiles, the 5-year relapse rates were 0.37, 0.34, 0.26, and 0.19 (P = .003), and the 5-year survival rates were 0.68, 0.73, 0.72, and 0.82 (P = .02). No significant differences were found by quartiles among patients determined to be node-positive. We propose that observed differences are primarily related to the incorrect determination of nodal status in node-negative patients. Approximately 14 nodes need to be studied to define nodal status accurately. CONCLUSION: These results suggest that the pathologic assessment of lymph nodes in surgical specimens is often inaccurate and that examining greater number of nodes increases the likelihood of proper staging. Some patients who might benefit from adjuvant therapy are misclassified as node-negative due to incomplete sampling of lymph nodes.

ObjectiveTo determine the sensitivity and specificity of ocular and cervical vestibular evoked myogenic potentials (VEMPs) in the diagnosis of superior semicircular canal dehiscence (SCD) and to describe the VEMP response characteristics that are most sensitive to SCD and compare the findings to previous reports.Study DesignCase series with chart review.SettingTwo tertiary neurotologic referral centers.Subjects and MethodsCervical and ocular VEMP peak‐to‐peak amplitudes and thresholds from 39 adult patients older than 18 years with surgically confirmed SCD were compared with 84 age‐matched controls.ResultsUsing receiver operating characteristic (ROC) curves, cervical VEMP (cVEMP) amplitudes, cVEMP thresholds, and ocular VEMP (oVEMP) amplitudes had areas under the curve of 0.731, 0.912, and 0.856, respectively, all of which were statistically significant (P <. 0001). For cVEMP thresholds, at the clinical equivalent ≤85‐dB normalized hearing level (nHL) threshold, the sensitivity and specificity were 97.3% and 31.3%, respectively. At the ≤70‐dB nHL threshold, the sensitivity and specificity were 73.0% and 94.0%, respectively. For oVEMP amplitudes >12.0 µV, the sensitivity and specificity were 78.6% and 81.7%, respectively.ConclusionData from this multicenter study suggest that both cVEMP thresholds and oVEMP amplitudes remain good diagnostic tests for identifying SCD, with each test dependent on a number of factors. The sensitivity and specificity of these individual tests may vary slightly between centers depending on testing parameters used.

Objectives: This study characterizes primary petroclival meningioma growth rates, before intervention, using volumetric analysis. In addition, predictors of growth are analyzed. Methods: Patients with previously untreated petroclival meningiomas were retrospectively reviewed (1999–2015). Image analysis software was used to perform volumetric analyses of tumor size and growth. Three-dimensional segmentation volumetric analyses were compared with volumes estimated utilizing three orthogonal dimensions. Tumor growth was defined as a 15% increase in volume. Results: Thirty-four patients who underwent at least two magnetic resonance imaging (MRI) studies before intervention were included. The mean age was 55.2 years, and 65.7% were women. The mean tumor volume at presentation was 5.6 cm 3 (range, 0.1–25.8 cm 3 ) as determined from segmentation volumetric analysis. At a mean follow-up of 44.5 months (range, 3.7–125.1 mo), 88.2% of tumors grew. The mean annual volumetric growth rate was 2.38 cm 3 /yr (−0.63 to 25.9 cm 3 /yr). Tumor volume, T2 hyperintensity within the tumor, peritumoral edema, and ataxia and/or cerebellar symptoms at presentation were all significantly associated with greater rates of tumor growth. Ultimately, 10 (29.4%) patients underwent treatment during the follow-up period. Conclusion: Our experience demonstrates that the vast majority (88%) of untreated petroclival meningiomas grow; the mean volumetric growth rate was noted to be 2.38 cm 3 /yr. We found a significant association between increased growth rate and larger tumor size at diagnosis, T2 hyperintensity within the tumor, peritumoral edema, and the presence of ataxia and/or cerebellar symptoms.

ObjectivePatients with incidental or minimally symptomatic superior semicircular canal dehiscence (SSCD) are usually observed, without surgical repair. However, it remains unknown whether a labyrinthine fistula of the superior semicircular canal is associated with progressive conductive or sensorineural hearing loss over time.Study DesignRetrospective review at two tertiary care academic referral centers.MethodsAdults analyzed were diagnosed with SSCD by high‐resolution temporal bone computed tomography and vestibular evoked myogenic potential testing and observed with a minimum of two sequential audiograms. Patients with other potential causes of hearing impairment were excluded.ResultsA total of 40 ears in 30 adult patients (median age: 59 years; 63% female) were analyzed. Median audiometric follow‐up was 23 months (range 1–136 months). None experienced a sudden hearing loss over the follow‐up period. In patients with audiometric follow‐up of at least 20 months (median 34 months), the median change in air‐conduction pure tone average and air–bone gap was 0.9 decibels (dB) per year (interquartile range [IQR] 0–2.1) and 0.7 dB per year (IQR 0–2.0), respectively. Speech discrimination scores did not differ when comparing median initial (100%) and median final (98%) scores (P = 0.77). There was no statistically significant change in bone‐conduction thresholds at 0.5, 1, 2, and 4 kHz over the period of observation.ConclusionThe risk of progressive hearing loss with observed SSCD is low during short‐ and intermediate‐term follow‐up. Further studies are necessary to determine whether late hearing loss occurs. Such information may be critical toward patient counseling regarding the need for and timing of surgery.Level of Evidence4. Laryngoscope, 127:1181–1186, 2017

Background and purposeAlthough the genetic contribution to stroke risk is well known, it remains unclear if young‐onset stroke has a stronger genetic contribution than old‐onset stroke. This study aims to compare the heritability of ischaemic stroke risk between young and old, using common genetic variants from whole‐genome array data in population‐based samples.MethodsThis analysis included 4050 ischaemic stroke cases and 5765 controls from six study populations of European ancestry; 47% of cases were young‐onset stroke (age < 55 years). To quantify the heritability for stroke risk in these unrelated individuals, the pairwise genetic relatedness was estimated between individuals based on their whole‐genome array data using a mixed linear model. Heritability was estimated separately for young‐onset stroke and old‐onset stroke (age ≥ 55 years).ResultsHeritabilities for young‐onset stroke and old‐onset stroke were estimated at 42% (±8%, P < 0.001) and 34% (±10%, P < 0.001), respectively.ConclusionsOur data suggest that the genetic contribution to the risk of stroke may be higher in young‐onset ischaemic stroke, although the difference was not statistically significant.

The microtubule-associated protein, tau, is the principal component of paired helical filaments (PHFs) in Alzheimer's disease. PHF-tau is highly phosphorylated and a total of 25 sites of phosphorylation have so far been identified. Many of these sites are serine or threonine residues that are immediately followed in the sequence by proline residues, and hence are candidate phosphorylation sites for proline-directed kinases. In vitro, glycogen synthase kinase-3 (GSK-3), extracellular signal-related kinase-1 and -2, and mitogen-activated protein kinases, p38 kinase and c-jun N-terminal kinase, all phosphorylate many of these sites, although with different efficiencies for particular sites. Phosphorylation studies in transfected cells and neurons show that GSK-3 phosphorylates tau more extensively than do these other proline-directed kinases. Mutations in tau have been shown to affect in vitro phosphorylation of tau by GSK-3. The Arg406--&gt;Trp (R406W) tau mutation also affects tau phosphorylation in cells.