OtoRhinoLaryngology News: 08/09/17

Τετάρτη 9 Αυγούστου 2017

Upper airway surgery for obstructive sleep apnea reduces blood pressure

Objectives/Hypothesis

To evaluate if upper airway surgery reduces blood pressure in patients with obstructive sleep apnea (OSA).

Study Design

Prospective series.

Methods

A prospective series of 112 consecutive OSA patients with hypertension (HTN). All patients were > 18 years old, respiratory disturbance index >5, all levels of apnea-hypopnea index (AHI), with a history of HTN treated with medication for at least 6 months. Surgical procedures included septoplasty, turbinate reduction, palate surgery, and tongue base reduction.

Results

There were 92 men and 20 women, with a mean age of 48.6 years, mean body mass index (BMI) was 27.5 (range, 19.7–34.7). Mean follow-up was 16.1 months. The mean preoperative AHI was 32.6 (range, 1.2–104), with the mean lowest oxygen saturation (LSAT) of 79.9% (range, 52%–93%). The mean adjusted preoperative and postoperative systolic blood pressure (SBP) was reduced from 146 ± 15.3 mm Hg to 122 ± 12.5 mm Hg (P < .001), and diastolic blood pressure (DBP) was reduced from 91 ± 10.2 mm Hg to 76 ± 7.8 mm Hg (P < .001). There was a decrease in overall BMI from 27.5 ± 3.6 to 25.5 ± 3.0 (P < .001); however, based on multivariate analysis, the reduction in SBP and DBP was not affected by this BMI reduction. Fifty-eight patients (51.8%) did not require their antihypertensive after surgery. There was poor correlation noted between HTN with AHI, LSAT, and oxygen duration <90%.

Conclusions

Upper airway surgery does reduce SBP and DBP in patients with OSA.

Level of Evidence

4. Laryngoscope, 2017

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Prognostic Stratification of Patients With Advanced Oral Cavity Squamous Cell Carcinoma

Abstract

Purpose of Review

Prognosis of advanced oral squamous cell carcinoma remains a challenge for clinicians despite progress in its diagnosis and treatment over the past decades. In this review, we assessed clinicopathological factors and potential biomarkers along with their prognostic relevance in an attempt to develop optimal treatment strategies for these patients.

Recent Findings

In addition to several pathologic factors that have been proposed to improve prognostic stratification and treatment planning in the eighth edition of the American Joint Committee staging manual on cancer, we reviewed some other imaging and clinicopathological parameters demonstrated to be closely associated with patient prognosis, along with the biomarkers related to novel target or immune therapy.

Summary

Evaluation of current literature regarding the prognostic stratification used in contemporary clinicopathological studies and progress in the development of targeted or immune therapy may help these patients benefit from tailored and personalized treatment and obtain better oncological results.

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Immunotherapy in Breast Cancer: the Emerging Role of PD-1 and PD-L1

Abstract

Purpose of Review

The purpose of the review is to summarize the data regarding PD-L1 expression in breast cancer and the results of first clinical trials with PD-1 or PD-L1 inhibitors in patients with metastatic breast cancer.

Recent Findings

PD-L1 expression is heterogeneous across primary breast cancers, and is generally associated with the presence of tumor-infiltrating lymphocytes and the presence of poor-prognosis features such as high grade, and aggressive molecular subtypes (triple-negative (TN), basal, HER2-enriched). Early phase clinical trials using PD-1 or PD-L1 inhibitors alone or in combination have shown objective tumor responses and durable long-term disease control, in heavily pre-treated patients, notably in the TN subtype.

Summary

Blockade of PD-1 or PD-L1 shows impressive antitumor activity in some subsets of breast cancer patients. Many clinical trials are ongoing in the metastatic and neoadjuvant setting, alone and in combination with chemotherapy, targeted therapy, radiotherapy, and/or other immune therapy. The identification of biomarkers predictive for a clinical benefit is warranted.

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A combination of anti-PD-L1 mAb plus Lm-LLO-E6 vaccine efficiently suppresses tumor growth and metastasis in HPV-infected cancers

Abstract

PD-1/PD-L1 immunotherapy is viewed as having clinical benefits in advanced cancers but is effective in only a few patients, suggesting that an efficient combination approach is needed to improve efficacy. Immunohistochemistry analysis indicated that PD-L1 expression was correlated with the E6 expression in tumors from 122 lung cancer patients. The poorest survival occurred in PD-L1-positive/E6-positive tumor. PD-L1 expression was increased by the expression of E6, but not the E7, oncoprotein in lung and cervical cancer cells. PD-L1 expression was responsible for E6-mediated colony formation and soft agar growth. Therefore, PD-L1 secreted from tumor cells may directly promote tumor progression, particularly in E6-positive tumors. Immune deficiency nude mice were used to test the possibility that combining anti-PD-L1 mAb with Lm-LLO-E6 vaccine could have a higher antitumor activity compared with anti-PD-L1 mAb or Lm-LLO-E6 vaccine alone. A greater antitumor activity was obtained with anti-PD-L1 mAb + Lm-LLO-E6 vaccine than with anti-PD-L1 mAb or Lm-LLO-E6 alone in subcutaneous and metastatic tumors induced by TL-1 and SiHa cells. The longest survival time for nude mice was observed in the anti-PD-L1 mAb + Lm-LLO-E6 vaccine group. In conclusion, an anti-PD-L1 mAb + Lm-LLO-E6 vaccine may be an efficient treatment for suppression of tumor growth and metastasis induced by HPV-infected cells.

We have provided evidence that an anti-PD-L1 mAb + Lm-LLO-E6 vaccine combination is an efficient therapeutic approach against HPV-infected NSCLC. In addition, the anti-PD-L1 mAb + Lm-LLO-E6 vaccine combination also efficiently suppresses SiHa cell-induced tumors in nude mice. Therefore, we suggest that anti-PD-L1 mAb + Lm-LLO-E6 vaccine combination therapy may have a greater clinical benefit than anti-PD-L1 or HPV DNA vaccine immunotherapy in cancer patients with HPV-infected tumors.

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Novel method of extracting motion from natural movies

Publication date: Available online 9 August 2017
Source:Journal of Neuroscience Methods
Author(s): Wataru Suzuki, Noritaka Ichinohe, Toshiki Tani, Taku Hayami, Naohisa Miyakawa, Satoshi Watanabe, Hiroshige Takeichi
BackgroundThe visual system in primates can be segregated into motion and shape pathways. Interaction occurs at multiple stages along these pathways. Processing of shape-from-motion and biological motion is considered to be a higher-order integration process involving motion and shape information. However, relatively limited types of stimuli have been used in previous studies on these integration processes.New methodWe propose a new algorithm to extract object motion information from natural movies and to move random dots in accordance with the information. The object motion information is extracted by estimating the dynamics of local normal vectors of the image intensity projected onto the x-y plane of the movie.ResultsAn electrophysiological experiment on two adult common marmoset monkeys (Callithrix jacchus) showed that the natural and random dot movies generated with this new algorithm yielded comparable neural responses in the middle temporal visual area.Comparison with existing methodsIn principle, this algorithm provided random dot motion stimuli containing shape information for arbitrary natural movies. This new method is expected to expand the neurophysiological and psychophysical experimental protocols to elucidate the integration processing of motion and shape information in biological systems.ConclusionsThe novel algorithm proposed here was effective in extracting object motion information from natural movies and provided new motion stimuli to investigate higher-order motion information processing.

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Reply to the Letter to the Editor of Zehao Jing et al. concerning “Scoliosis convexity and organ anatomy are related” by T. P. C. Schlösser et al. (Eur Spine J; 2017: doi:10.1007/s00586-017-4970-5)

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Intraparenchymal intracranial pressure monitoring for hydrocephalus and cerebrospinal fluid disorders

Abstract

Background

Elective intraparenchymal intracranial pressure (ICP) monitoring is useful for the diagnosis and treatment of hydrocephalus and cerebrospinal fluid (CSF) disorders. This retrospective study analyzes median ICP and pulse amplitude (PA) recordings in neurosurgically naïve patients undergoing elective ICP monitoring for suspected CSF disorders.

Methods

Retrospective review of prospectively collated database of neurosurgically naïve patients undergoing elective ICP monitoring for suspected hydrocephalus and CSF disorders. Following extraction of the median ICP and PA values (separated into all, day and night time recordings), principal component analysis (PCA) was performed to identify the principal factors determining the spread of the data. Exploratory comparisons and correlations of ICP and PA values were explored, including by post hoc diagnostic groupings and age.

Results

A total of 198 patients were identified in six distinct diagnostic groups (n = 21–47 in each).

The PCA suggested that there were two main factors accounting for the spread in the data, with 61.4% of the variance determined largely by the PA and 33.0% by the ICP recordings.

Exploratory comparisons of PA and ICP between the diagnostic groups showed significant differences between the groups. Specifically, significant differences were observed in PA between a group managed conservatively and the Chiari/syrinx, IIH, and NPH/LOVA groups and in the ICP between the conservatively managed group and high-pressure, IIH, and low-pressure groups. Correlations between ICP and PA revealed some interesting trends in the different diagnostic groups and correlations between ICP, PA, and age revealed a decreasing ICP and increasing PA with age.

Conclusions

This study provides insights into hydrodynamic disturbances in different diagnostic groups of patients with CSF hydrodynamic disorders. It highlights the utility of analyzing both median PA and ICP recordings, stratified into day and night time recordings.

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A novel method for sex estimation using 3D computed tomography models of tooth roots: A volumetric analysis

Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Seyedeh M. Kazzazi, Elena F. Kranioti
Advances in technologies such as computed tomography (CT) scanning have allowed for further examination of dental sexual dimorphism in modern and archaeological populations.

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Clinical outcomes of patients with epithelioid sarcomas: impact and management of nodal metastasis

Abstract

Purpose

An epithelioid sarcoma is a rare histological subtype of a soft tissue sarcoma with a high local recurrence rate, which frequently shows lymph node metastasis. However, because of the rarity of this tumor, the impact of nodal metastasis and its appropriate management remain unclear. The present study investigated the clinical outcomes of patients with epithelioid sarcomas, with a focus on lymph node metastasis.

Methods

We retrospectively evaluated the clinical outcomes of 27 patients with epithelioid sarcomas treated between 1985 and 2015. The log-rank test was used to assess the prognostic variables.

Results

The overall local recurrence rate was 33%, and the estimated overall 5-year survival rate was 62%. Hand and foot locations were associated with favorable overall survival. During the follow-up period, new nodal metastasis was noted in 14 patients (52%). The incidence of local recurrence was higher in patients with new nodal metastasis than in patients who did not develop nodal metastasis. The development of new nodal metastasis had a tendency to worsen survival; however, this association was not statistically significant. Lymphadenectomy did not affect overall survival.

Conclusions

Peripheral tumor location is associated with a better prognosis. The development of new nodal metastasis tends to be associated with poor prognosis; however, among patients with nodal metastasis, resection of the metastatic lesions has a low impact on survival.

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Issue Information - Contents

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Cover Image

The cover image, by Jacqui Allen et al., is based on the Original Article Assessment of videofluoroscopic swallow study findings before and after cricopharyngeal myotomy, DOI: 10.1002/hed.24846.

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Patient characteristics and overall survival in patients with post-docetaxel metastatic castration-resistant prostate cancer in the community setting

Abstract

It is unclear how treatment sequencing for metastatic castration-resistant prostate cancer (mCRPC) affects real-world patient outcomes. We assessed treatment sequences, patient characteristics and overall survival (OS) in post-docetaxel mCRPC patients. mCRPC patients receiving second-line cabazitaxel or androgen receptor-targeted therapy (ART; abiraterone/enzalutamide) post-docetaxel were identified using electronic medical records. OS was assessed from second-line therapy initiation using Cox regressions adjusting for: metastases; prostate-specific antigen (PSA); hemoglobin; alkaline phosphatase (ALP); albumin; second-line therapy initiation year. Following docetaxel (n = 629), 123 (19.6%) and 506 (80.4%) patients received cabazitaxel and ART, respectively. One hundred and ninety-five patients received additional treatments thereafter (54 following cabazitaxel; 141 following ART). Although patients receiving second-line cabazitaxel versus ART had similar disease characteristics at first-line therapy initiation, at second-line therapy initiation they had higher mean PSA (386.6 vs. 233.9 ng/mL) and ALP (182.0 vs. 167.3 u/L), lower mean hemoglobin (10.8 vs. 11.5 g/dL), and more frequently had intermediate/high-risk Halabi scores (61.8 vs. 48.4%); all p < 0.05. Overall, crude survival was not significantly different. Among Halabi high-risk patients, adjusted median OS was significantly longer in patients receiving cabazitaxel versus ART (HR 0.48; 95% CI 0.24–0.93; p = 0.030). Low albumin and hemoglobin led to similar findings (HR 0.43; 95% CI 0.23–0.80; p = 0.0077; HR 0.60; 95% CI 0.40–0.90; p = 0.014). Most post-docetaxel patients received second-line ART. Patients receiving second-line cabazitaxel had more high-risk features; however, second-line cabazitaxel administered after docetaxel may improve OS in patients with Halabi high-risk scores or low albumin/hemoglobin.

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Comparison of Visual Evoked Potential Monitoring During Spine Surgeries under Total Intravenous Anesthesia versus Balanced General Anesthesia

Visual Evoked Potential (VEP) is the illustration of electrical activity recorded from sensors placed on the subject's scalp overlying the visual cortex in response to visual stimuli. Changes in this electroencephalographic signal are characterized by a waveform, where changes in latency, amplitude, and morphology could be associated with specific pathologies (Holy et al., 2009; Ota et al., 2010; Andersson et al., 2012; Chung et al., 2012; Kamio et al., 2014; Luo et al., 2015). There exists a variety of stimuli that can be used in awake subjects, the most common being checkboard pattern-reversal VEP (Andersson et al., 2012).

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Parkinsonian rest tremor can be detected accurately based on neuronal oscillations recorded from the subthalamic nucleus

Deep brain stimulation (DBS) is a widely used treatment for patients with advanced Parkinson's disease (Perlmutter and Mink 2006). While its efficacy is well established, its efficiency can potentially be optimized. Conventional DBS is applied continuously although motor symptoms are usually fluctuating. Moreover, the benefit of DBS is often compromised by side-effects, which can usually be alleviated by reducing stimulation power, i.e. the energy applied per unit of time. Suggested approaches to reduce power include electric field steering (Contarino et al.

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Electroencephalogram dynamics in children during different levels of anaesthetic depth

Loss of consciousness induced by general anaesthetic agents has been proposed to be related to disruptions of connectivity between neuronal networks of the thalamus and the cerebral cortex (Alkire et al., 2000). Accordingly, the electroencephalogram (EEG), as a tool to measure synchronicity of network connectivity, has gained a position as the de-facto standard to monitor the depth of anaesthesia. However, EEG signatures used to identify different levels of anaesthesia are not well characterized in children, and still need to be properly described before implementation in clinical practice.

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Randomized sham-controlled trials in endoscopy: a systematic review and meta-analysis of adverse events

Sham procedures in endoscopy are used with the intention of controlling for placebo response, potentially allowing more precise evaluation of treatment effect. Nevertheless, this type of study may impose significant risk without potential benefit for those in the sham group. The aim of the current study is to systematically review and analyze the endoscopic literature to assess the safety of sham controls.

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The absence or temporal offset of visual feedback does not influence adaptation to novel movement dynamics

Delays in transmitting and processing sensory information require correctly associating delayed feedback to issued motor commands for accurate error compensation. The flexibility of this alignment between motor signals and feedback has been demonstrated for movement recalibration to visual manipulations, but the alignment dependence for adapting movement dynamics is largely unknown. Here we examined the effect of visual feedback manipulations on force-field adaptation. Three subject groups used a manipulandum while experiencing a lag in the corresponding cursor motion (0, 75 or 150 ms). When the offset was applied at the start of the session (continuous condition) adaptation was not significantly different between groups. However, these similarities may be due to acclimation to the offset prior to motor adaptation. We tested additional subjects that experienced the same delays concurrent with the introduction of the perturbation (abrupt condition). In this case adaptation was statistically indistinguishable from the continuous condition, indicating that acclimation to feedback delay was not a factor. In addition, endpoint errors were not significantly different across the delay or onset conditions, but endpoint correction (e.g., deceleration duration) was influenced by the temporal offset. As an additional control, we tested a group of subjects that performed without visual feedback and found comparable movement adaptation results. These results suggest that visual feedback manipulations (the absence or temporal misalignment) does not affect adaptation to novel dynamics, independent of both acclimation and perceptual awareness. These findings could have implications for modeling how the motor system adjusts to errors despite concurrent delays in sensory feedback information.

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Sequential hemifield gating of alpha and beta behavioral performance oscillations after microsaccades

Microsaccades are tiny saccades that occur during gaze fixation. Even though visual processing has been shown to be strongly modulated close to the time of microsaccades, both at central and peripheral eccentricities, it is not clear how these eye movements might influence longer-term fluctuations in brain activity and behavior. Here we found that visual processing is significantly affected, and in a rhythmic manner, even several hundreds of milliseconds after a microsaccade. Human visual detection efficiency, as measured by reaction time, exhibited coherent rhythmic oscillations in the α and β frequency bands for up to ~650-700 ms after a microsaccade. Surprisingly, the oscillations were sequentially pulsed across visual hemifields relative to microsaccade direction, first occurring in the same hemifield as the movement vector for ~400 ms and then the opposite. Such pulsing also affected perceptual detection performance. Our results suggest that visual processing is subject to long-lasting oscillations that are phase-locked to microsaccade generation, and that these oscillations are dependent on microsaccade direction.

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Neural correlates for task switching in the macaque superior colliculus

Successful task switching requires a network of brain areas to select, maintain, implement, and execute the appropriate task. Although frontoparietal brain areas are thought to play a critical role in task switching by selecting and encoding task rules and exerting top-down control, how brain areas closer to the execution of tasks participate in task switching is unclear. The superior colliculus (SC) integrates information from various brain areas to generate saccades and is likely influenced by task switching. Here, we investigated switch costs in non-human primates and their neural correlates in the activity of SC saccade-related neurons in monkeys performing cued, randomly interleaved pro- and anti-saccade trials. We predicted that behavioral switch costs would be associated with differential modulations of SC activity in trials on which the task was switched versus repeated, with activity on the current trial resembling that associated with the task-set of the previous trial when a switch occurred. We observed both error rate and reaction time switch costs and changes in the discharge rate and timing of activity in SC neurons between switch and repeat trials. These changes were present later in the task, only after fixation on the cue stimuli, but prior to saccade onset. These results further establish switch costs in macaque monkeys and suggest that SC activity is modulated by task switching processes in a manner inconsistent with the concept of task-set inertia.

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Object comparison in the lateral intraparietal area

We can search for and locate specific objects in our environment by looking for objects with similar features. Object recognition involves stimulus similarity responses in ventral visual areas and task related responses in prefrontal cortex. We tested whether neurons in the lateral intraparietal area (LIP) of posterior parietal cortex could form an intermediary representation, collating information from object specific similarity map representations to allow general decisions about whether a stimulus matches the object being looked for. We hypothesized that responses to stimuli would correlate with how similar they are to a sample stimulus. When animals compared two peripheral stimuli to a sample at their fovea, the response to the matching stimulus was similar, independent of the sample identity, but the response to the non-match depended on how similar it was to the sample: the more similar, the greater the response to the non-match stimulus. These results could not be explained by task difficulty or confidence. We propose that LIP uses its known mechanistic properties to integrate incoming visual information, including that from the ventral stream about object identity, to create a dynamic representation that is concise, low dimensional and task relevant, and which signifies the choice priorities in mental matching behavior.

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Hyperalgesia and sensitization of dorsal horn neurons following activation of NK-1 receptors in the rostral ventromedial medulla

Neurons in the rostral ventromedial medulla (RVM) project to the spinal cord and are involved in descending modulation of pain. Several studies have shown that activation of neurokinin-1 (NK-1) receptors in the RVM produces hyperalgesia, although underlying mechanisms are not clear. In parallel studies, we compared behavioral measures of hyperalgesia to electrophysiological responses of nociceptive dorsal horn neurons produced by activation of NK-1 receptors in the RVM. Injection of the selective NK-1 receptor agonist, Sar9,Met(O₂)¹¹-Substance P (SSP) into the RVM produced dose-dependent mechanical and heat hyperalgesia that was blocked by co-administration of the selective NK-1 receptor antagonist, L-733,060. In electrophysiological studies, responses evoked by mechanical and heat stimuli were obtained from identified high threshold (HT) and wide dynamic range (WDR) neurons. Injection of SSP into the RVM enhanced responses of WDR neurons, including identified neurons that project to the parabrachial area, to mechanical and heat stimuli. Since intraplantar injection of capsaicin produces robust hyperalgesia and sensitization of nociceptive spinal neurons, we examined whether this sensitization was dependent on NK-1 receptors in the RVM. Pretreatment with L-733,060 into the RVM blocked the sensitization of dorsal horn neurons produced by capsaicin. C-Fos labeling was used to determine the spatial distribution of dorsal horn neurons that were sensitized by NK-1 receptor activation in the RVM. Consistent with our electrophysiological results, administration of SSP into the RVM increased pinch-evoked c-Fos expression in the dorsal horn. It is suggested that targeting this descending pathway may be effective in reducing persistent pain.

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Induced oscillations in turtle cortex are coherent at the mesoscale of population activity, but not at the microscale of the membrane potential of neurons

Bursts of oscillatory neural activity have been hypothesized to be a core mechanism by which remote brain regions can communicate. Such hypothesis raises the question to what extent oscillations are coherent across spatially distant neural populations. To address this question, we obtained local field potential (LFP) and membrane potential recordings from the visual cortex of turtle in response to visual stimulation of the retina. The time-frequency analysis of these recordings revealed pronounced bursts of oscillatory neural activity and a large trial-to-trial variability in the spectral and temporal properties of the observed oscillations. First, local bursts of oscillations varied from trial-to-trial in both burst durations and peak frequencies. Second, oscillations of a given recording site were not autocoherent, i.e., the phase did not progress linearly in time. Third, local field potential oscillations at spatially separate locations within the visual cortex were more phase coherent in the presence of visual stimulation than during ongoing activity. In contrast, the membrane potential oscillations from pairs of simultaneously recorded pyramidal neurons showed smaller phase coherence, which did not change when switching from black screen to visual stimulation. In conclusion, neuronal oscillations at distant locations in visual cortex are coherent at the mesoscale of population activity, but coherence is largely absent at the microscale of the membrane potential of neurons.

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Limbic-motor integration by neural excitations and inhibitions in the nucleus accumbens

The nucleus accumbens (NAc) has often been described as a "limbic-motor interface," implying that the NAc integrates the value of expected rewards with the motor planning required to obtain them. However, there is little direct evidence that the signaling of individual NAc neurons combines information about predicted reward and behavioral response. Here, we report that cue-evoked neural responses in the NAc form a likely physiological substrate for its limbic-motor integration function. Across task contexts, individual NAc neurons in behaving rats robustly encode the reward-predictive qualities of a cue, as well as the probability of behavioral response to the cue, as coexisting components of the neural signal. In addition, cue-evoked activity encodes spatial and locomotor aspects of the behavioral response, including proximity to a reward-associated target and the latency and speed of approach to the target. Notably, there are important limits to the ability of NAc neurons to integrate motivational information into behavior: in particular, updating of predicted reward value appears to occur on a relatively long time scale, as NAc neurons fail to discriminate between cues with reward associations that change frequently. Overall, these findings suggest that NAc cue-evoked signals - including inhibition of firing (as noted here for the first time) - provide a mechanism for linking reward prediction and other motivationally relevant factors, such as spatial proximity, to the probability and vigor of a reward-seeking behavioral response.

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Firing Rate Estimation Using Infinite Mixture Models and Its Application to Neural Decoding

Neural decoding is a framework for reconstructing external stimuli from spike trains recorded in brains. Kloosterman et al. (2014) proposed a new decoding method using marked point processes. This method does not require spike sorting and thereby improves decoding accuracy dramatically. In this method, they used kernel density estimation to estimate intensity functions of marked point processes. However, using kernel density estimation causes problems. To overcome these problems, we propose a new decoding method using infinite mixture models to estimate intensity. The proposed method improves decoding performance in terms of accuracy and computation speed. We apply the proposed method to simulation and experimental data to verify its performance.

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Time of day influences on respiratory sequelae following maximal electroshock induced seizures in mice

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in refractory epilepsy patients. While specific mechanisms underlying SUDEP are not well understood, evidence suggests most SUDEP occurs due to seizure-induced respiratory arrest. SUDEP also tends to happen at night. While this may be due to circumstances humans find themselves in at night, such as being alone without supervision or sleeping prone, or due to independent influences of sleep state, there are a number of reasons why the night (i.e. circadian influences) could be an independent risk factor for SUDEP. We explored this possibility here. Adult male WT mice were instrumented for EEG, EMG and EKG recording and subjected to maximal electroshock (MES) seizures during wakefulness, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep during the nighttime/dark phase. These data were compared to data collected following seizures induced during the daytime/light phase. Seizures induced during the nighttime were similar in severity and duration compared to those induced during the daytime; however, seizures induced during the nighttime were associated with a lesser degree of respiratory dysregulation and post ictal EEG suppression. Seizures induced during REM sleep during the nighttime were universally fatal, as is seen when seizures are induced during REM during the daytime. Taken together these data implicate a role for time of day in influencing the physiological consequences of seizures that may contribute to seizure-induced death.

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Diagnostic and Therapeutic Strategies for Patients with Malignant Epidural Spinal Cord Compression

Opinion statement

Malignant epidural spinal cord compression (MESCC) is an oncologic emergency with the potential for devastating consequences for patients if not promptly diagnosed and treated. MESCC is diagnosed by imaging. MRI is by far the most sensitive test, preferably with gadolinium. Once the diagnosis of MESCC is suspected, patients with neurologic deficits should receive prompt administration of dexamethasone with a 10-mg IV loading dose followed by 4 mg every 6 h. Quick taper is recommended once the definitive treatment is established. Consultation with medical oncology, radiation oncology, and neurosurgery is imperative in order to facilitate a multidisciplinary approach. Although spine surgery is the most effective method for relief of cord compression and is necessary if there is spinal instability, surgery is only used in selected patients because most patients have a poor overall condition and short life expectancy. Radiation therapy, therefore, is the most commonly used therapy for patients with MESCC after surgical decompression or in patients who are not surgical candidates. Conventional fractionated radiation alone can achieve modest neurologic outcomes in selected radiosensitive tumors. Radiosurgery techniques which deliver intense focal irradiation to a delimited area with imaging guidance and contoured radiation delivery to the shape of the tumor have recently emerged as increasing effective treatments in MESCC, especially in radioresistant tumors. Stereotactic radiosurgery and different radiation technologies have been studied in recent clinical trials.

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Dermatofibrosarcoma Protuberans

Opinion statement

Dermatofibrosarcoma protuberans (DFSP) is a slow growing tumor with a very low metastatic potential but with significant subclinical extension and great capacity for local destruction. Thus, the first surgeon approached with such challenging tumor must attempt to cure the patient with a method that spares healthy tissue and ensures an optimal oncological, functional, and esthetic result. The treatment of DFSP often requires a multidisciplinary approach. Depending on location, dermatologic surgeons, surgical oncologists, head and neck surgeons, neurosurgeons, plastic surgeons, and occasionally medical oncologists may be involved with the management. Mohs micrographic surgery (MMS) is the preferred method when available. In our institution, most of the DFSP cases are often advanced cases; thus, dermatologic surgeons obtain clear margins peripherally and other surgical specialties assist with resection of the fascia and any critical deeper structures. When MMS is not available, wide local excision (at least 2- to 3-cm margins of resection) with exhaustive pathologic assessment of margin status is recommended, and it is best to confirm tumor extirpation prior to any reconstruction. Subclinical extension of the tumor could be related to the size; how long it has been growing or histological markers that are unknown right now. No clinical trials comparing MMS vs WLE are available, and further research should be focused on these subjects as well as the use of imatinib and other targeted therapies for recurrent and metastatic tumors and for neoadjuvant treatment.

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Letter to the Editor: Implications of BRAF Mutations in dMMR Colorectal Cancers

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Expression of Caspase Signaling Components in the Outer Membranes of Chronic Subdural Hematomas

Journal of Neurotrauma , Vol. 0, No. 0.

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Diagnostic and Therapeutic Strategies for Patients with Malignant Epidural Spinal Cord Compression

Opinion statement

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Dermatofibrosarcoma Protuberans

Opinion statement

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Letter to the Editor: Implications of BRAF Mutations in dMMR Colorectal Cancers

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Variations in the labyrinthine segment of facial nerve canal revealed by high-resolution computed tomography

To study variations in the labyrinthine segment of fallopian canal and the associated middle and inner ear malformations.

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Auditory-Perceptual Evaluation of Dysphonia: A Comparison Between Narrow and Broad Terminology Systems

In auditory-perceptual voice analysis, a multiparameter approach and a more reductionist approach may be compared with narrow and broad phonetic transcription and used interchangeably, depending on the purpose. The aim of this study was to investigate the perspectives of a translation of the terminology used in the multiparameter Danish Dysphonia Assessment (DDA) approach into the five-parameter GRBAS system.

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Effect of circulating glucagon and free fatty acids on hepatic FGF21 production in dairy cows

Modern dairy cows meet the energy demand of early lactation by calling on hormonally-driven mechanisms to increase the use of lipid reserves. In this context, we recently reported that fibroblast growth factor-21 (FGF21), a hormone required for efficient use of lipid reserves in rodents, is upregulated in periparturient dairy cows. Increased plasma FGF21 in early lactation coincides with elevated circulating concentrations of glucagon (GCG) and non-esterified fatty acids (NEFA). To assess the relative contribution of these factors in regulating FGF21, two experiments were performed in energy sufficient, non-pregnant, non-lactating dairy cows. In the first study, cows were injected with saline or GCG every 8 h over 72 h. GCG increased hepatic FGF21 mRNA by an average of 5-fold over matched controls but had no effect on plasma FGF21. In the second study, cows were infused and injected with saline, infused with intralipid and injected with saline or infused with intralipid and injected with GCG. Infusions and injections were respectively administered IV over 16 hours and SC every 8 h. Intralipid infusion increased plasma NEFA from 92 to 550 µM within 3 h and increased plasma FGF21 from 1.3 ng/ml to >11 ng/ml 6 h later; FGF21 mRNA increased by 34-fold in liver but remained invariant in adipose tissue. GCG injections during the intralipid infusion had no additional effects on plasma NEFA, liver FGF21 mRNA or plasma FGF21. These data implicate plasma NEFA as a key factor triggering hepatic production and increased circulating concentrations of FGF21 in early lactation.

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Left ventricular diastolic dysfunction in women with non-obstructive ischemic heart disease: Insights from magnetic resonance imaging and spectroscopy

Ischemic Heart Disease, in the absence of obstructive coronary artery disease, is prevalent in women, and constitutes a major risk factor for developing major adverse cardiovascular events, including myocardial infarction, stroke, and heart failure. For decades, diagnosis was considered benign and often minimized; however, it is now known that this etiology caries much risk and is a significant burden to the health care system. This review summarizes the current state-of-knowledge on non-obstructive ischemic heart disease (NOIHD), the association between NOIHD and left ventricular diastolic dysfunction, potential links between NOIHD and the development of heart failure with preserved ejection fraction (HFpEF), and therapeutic options and knowledge gaps for patients living with NOIHD.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2wvW1km

Modulation of Taste Processing by Temperature

Taste stimuli have a temperature that can stimulate thermosensitive neural machinery in the mouth during gustatory experience. Although taste and oral temperature are sometimes discussed as different oral sensory modalities, there is a body of literature that demonstrates temperature is an important component and modulator of the intensity of gustatory neural and perceptual responses. Available data indicate that the influence of temperature on taste, herein referred to as "thermogustation", can vary across taste qualities, can also vary among stimuli presumed to share a common taste quality, and is conditioned on taste stimulus concentration, with neuronal and psychophysical data revealing larger modulatory effects of temperature on gustatory responding to weakened taste solutions compared to concentrated. What is more, thermogustation is evidenced to involve interplay between mouth and stimulus temperature. Given these and other dependencies, identifying principles by which thermal input affects gustatory information flow in the nervous system may be important for ultimately unravelling the organization of neural circuits for taste and defining their involvement with multisensory processing related to flavor. Yet thermal effects are relatively understudied in gustatory neuroscience. Major gaps in our understanding of the mechanisms and consequences of thermogustation include delineating supporting receptors, the potential involvement of oral thermal and somatosensory trigeminal neurons in thermo-gustatory interactions, and the broader operational roles of temperature in gustatory processing. This review will discuss these and other issues in the context of the literature relevant to understanding thermogustation.

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Prenatal Hypoxia and Placental Oxidative Stress: Linkages to Developmental Origins of Cardiovascular Disease

Intrauterine growth restriction (IUGR, a pregnancy complication where the fetus does not reach its genetic growth potential) is a leading cause of fetal morbidity and mortality with a significant impact on population health. IUGR is associated with gestational hypoxia; which can lead to placental oxidative stress and fetal programming of cardiovascular disease. Mitochondria are a major source of placental oxidative stress and may provide a therapeutic target to mitigate the detrimental effects of placental oxidative stress on pregnancy outcomes. A nanoparticle-mediated delivery of a mitochondrial antioxidant to the placenta is a potential novel approach that may avoid unwanted off-target effects on the developing offspring.

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Optogenetics and Pharmacogenetics: Principles and Applications

Remote and selective spatiotemporal control of the activity of neurons to regulate behavior and physiological functions has been a long-sought goal in system neuroscience. Identification and subsequent bioengineering of light-sensitive ion channels (e.g., channelrhodopsins, halorhodopsin and archaerhodopsins) from the bacteria has made it possible to utilize light to artificially modulate neuronal activity, namely optogenetics. Recent advance in genetics has also allowed development of novel pharmacological tools to selectively and remotely control neuronal activity using engineered G-protein coupled receptors which can be activated by otherwise inert drug-like small molecules such as the Designer Receptors Exclusively Activated by Designer Drug (DREADD) - a form of chemogenetics. The cutting-edge optogenetics and pharmacogenetics are powerful tools in neuroscience which allow selective and bidirectional modulation of the activity of defined populations of neurons with unprecedented specificity. These novel toolboxes are enabling significant advances in deciphering how the nervous system works and its influence on various physiological processes in health and disease. Here, we discuss the fundamental elements of optogenetics and chemogenetics approaches and some of the applications that yielded significant advances in various areas of neuroscience and beyond.

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Recent Advances in the Classification and Treatment of Ependymomas

Opinion Statement

Ependymomas are a subgroup of ependymal glia-derived neoplasms that affect children as well as adults. Arising within any CNS compartment, symptoms at presentation can range from acute onset due to increased intracranial pressure to insidious myelopathy. The overall survival (OS) outcomes in adult patients across the subgroups is heterogeneous with subependymoma having an excellent prognosis often even in the absence of any treatment, whereas supratentorial ependymomas tend to be higher grade in nature and may have an OS of 5 years despite gross total resection and adjuvant radiation. The rarity of ependymal tumors, together still only representing 1.8% of all primary CNS tumors, has been a long-standing challenge in defining optimal treatment guidelines via prospective randomized trials. Retrospective studies have supported maximal safe resection, ideally gross total resection, as the optimal treatment with adjuvant radiation therapy proffering additional tumor control. The evidence for efficacy of chemotherapy and targeted agents in adult ependymomas is minimal. Recent investigations of the molecular, genetic, and DNA methylation profiles of ependymal tumors across all age groups and CNS compartments have identified distinct oncogenic gene products as well as nine molecular subgroups correlating with similar outcomes. The 2016 World Health Organization of Tumors of the Central Nervous System update addresses some of these findings, although their clinical significance has not yet been fully validated. There are inconsistent survival outcomes in retrospective studies for ependymomas graded as II versus III, bringing into question the validity of histologic grading which is subject to high interobserver variability in part due to inconsistent application of mitotic count parameters.

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Treatment of Lung Carcinosarcoma and Other Rare Histologic Subtypes of Non-small Cell Lung Cancer

Opinion statement

Lung carcinosarcoma (PCS) and other histological subtypes of non-small cell lung cancer, such as primary pulmonary lymphoma (PPL), pulmonary carcinoid (PC), and primary pulmonary lymphoepithelioma-like carcinoma (LELC), are rare. For their low incidence, the diagnosis and treatment are still controversial. Some patients only need surgery, while others may need chemotherapy, radiotherapy, or targeted therapy. In this paper, we retrospectively reviewed the literature of some rare histological subtype of NSCLC for the recent 20 years, and try to get some conclusions.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2uqZAXD

Novel Agents in the Treatment of Thymic Malignancies

Opinion statement

The management of thymic tumours is a paradigm of multidisciplinary collaboration. Chemotherapy may be administered part of curative-intent sequential strategy integrating subsequent surgery or radiotherapy, or as an exclusive treatment if local treatment is not achievable. Recurrences of thymic epithelial tumors should be managed according to the same strategy as newly diagnosed tumors. Given the limited activity of cytotoxic agents in the advanced, refractory setting, novel and innovative agents are needed. The better understanding of thymic carcinogenesis may provide a rationale in this setting.

Targeted agents approved for other solid tumors that have shown activity in thymic tumors include mTOR, KIT inhibitors, as well as somatostatin analogues. Anti-angiogenic agent sunitinib may be considered a standard in advanced lines of treatment. Ongoing studies are assessing the opportunity of targeting emerging targets, including PI3K, CDK, and immune checkpoint PD-1/PD-L1.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vQ1ZhP

Lung cancer as a cardiotoxic state: a review

Abstract

As the overall survival of patients with lung cancer continues to increase, more cancer survivors are faced with the risk of developing treatment-related cardiovascular toxicities. The increased knowledge of the molecular biology of non-small cell lung cancer has led to new and more personalized treatments. Nevertheless, the usual chemotherapy schemes and radiation therapy induce cardiac toxicities that are frequently underappreciated or go unnoticed. Up to date, the majority of cardiotoxicity studies have been focused in breast cancer, but new treatments in lung cancer patients, such as immune checkpoint-blocking antibodies or tyrosine kinase inhibitors, may also exert these cardiac toxic effects and therefore demand of the close collaboration of oncologists and cardiologists, in order to be addressed. The aim of this review is to provide more detailed information in regard to drug-induced cardiac toxicity focused in non-small cell lung cancer patients.

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Recent Advances in the Classification and Treatment of Ependymomas

Opinion Statement

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2urFv36

Treatment of Lung Carcinosarcoma and Other Rare Histologic Subtypes of Non-small Cell Lung Cancer

Opinion statement

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2uqZAXD

Novel Agents in the Treatment of Thymic Malignancies

Opinion statement

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vQ1ZhP

Radiation-induced gliomas: a report of four cases and analysis of molecular biomarkers

Abstract

Radiation-induced glioma (RIG) is a rare secondary glioma. The tumors morphologically resemble their sporadically arising counterparts. Recently, the WHO classification of tumors of the central nervous system was revised to incorporate molecular biomarkers together with classic histological features. The status of molecular biomarkers in RIG, however, remains unclear. The objective of this study was to investigate if commonly accepted glioma-specific biomarkers are relevant in RIGs. Among 269 gliomas diagnosed as WHO grade 2, 3 and 4 in our institution, four were diagnosed as RIGs. Immunohistochemical (IHC) staining for isocitrate dehydrogenase 1 (IDH1), p53, alpha thalassemia/mental retardation syndrome X-linked (ATRX), and H3K27M, and direct DNA sequencing of IDH1/2, telomerase reverse transcriptase (TERT) promoter, Histone H3.3 (H3F3A) and B-Raf (BRAF) genes was performed. All tumor specimens were IDH1-, p53- and H3K27M-negative. The nuclei of tumor cells in all cases exhibited positive staining for ATRX. In direct DNA sequencing analysis, no IDH1, IDH2, TERT promoter, H3F3A or BRAF mutations were found in any of the cases. Our findings suggest that these characteristic glioma-associated molecular mutations may be rare events in RIGs. More RIGs need to be tested for analysis of molecular biomarkers to clarify the clinical and histopathological spectra of this tumor.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vP4eSD

Ultrasound versus magnetic resonance imaging of the temporomandibular joint in juvenile idiopathic arthritis: a systematic review

A systematic review of published articles on ultrasound (US) and magnetic resonance imaging (MRI) of the temporomandibular joint (TMJ) in juvenile idiopathic arthritis (JIA) was performed to answer the question "What is the sensitivity and specificity of US as compared to MRI in diagnosing acute and chronic joint changes in patients with JIA?" The most recent evidence was sought in published articles via a search of the PubMed, Ovid, and Embase databases. Article appraisal was performed by two reviewers.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2wJJhWr

Clinical application of autogenous partially demineralized dentin matrix prepared immediately after extraction for alveolar bone regeneration in implant dentistry: a pilot study

The aim of this study was to examine the efficacy and safety of autogenous partially demineralized dentin matrix (APDDM) prepared onsite, for clinical application in bone regeneration procedures related to implant dentistry, including socket preservation, alveolar ridge augmentation, and maxillary sinus floor augmentation. In this study, 16 patients underwent dental implant placement using APDDM transplantation. There were no systemic or local complications (including surgical site infection) in any of the cases, and oral rehabilitation using dental implants was successful in all cases for at least 2 years after attachment of the suprastructure.

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Hsa_circ_0045714 regulates chondrocyte proliferation, apoptosis and extracellular matrix synthesis by promoting the expression of miR-193b target gene IGF1R

Abstract

In recent years, some studies have been made on the effects of circular RNA (circRNA) in osteoarthritis (OA) and so on; however, its mechanisms remain to be further explored. Studies have shown that tumor necrosis factor-alpha can inhibit hsa_circ_0045714 expression in chondrocytes so as to upregulate miR-193b expression. Dual-luciferase reporter assay showed that insulin-like growth factor 1 receptor (IGF1R) is a key target gene of miR-193b. Hsa_circ_0045714 over-expression does not influence miR-193b expression, but can inhibit its transcriptional activity, thereby upregulating IGF1R expression. Hsa_circ_0045714 can promote the expression of type II collagen and aggrecan, and upregulate chondrocyte proliferation, while its linear sequences cannot. IGF1R has similar function, while miR-193b can inhibit the expression of type II collagen and aggrecan, and downregulate chondrocyte proliferation but enhance their apoptosis. IGF1R overexpression can reverse the effect of miR-193b, while miR-193b mimics or IGF1R siRNA can inhibit the function of hsa_circ_0045714. Therefore, hsa_circ_0045714 can regulate extracellular matrix synthesis as well as proliferation and apoptosis of chondrocytes by promoting the expression of miR-193b target gene IGF1R. The findings will provide new proofs for studies on the applications of circRNA in OA and other orthopedic diseases.

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Obduktionen im Grenzbereich zwischen Pathologie und Rechtsmedizin

Zusammenfassung

Rechtsmedizin und Pathologie haben viele Unterschiede, aber auch viele Gemeinsamkeiten, und fußen auf demselben Fundament. Im Folgenden werden die Besonderheiten der gerichtlichen Obduktion und ihre gesetzlichen Grundlagen dargestellt und Möglichkeiten zur Zusammenarbeit zwischen den beiden Fächern und zur Erhöhung der Obduktionsquote aufgezeigt. Dies würde der Rechtssicherheit, der klinischen Qualitätssicherung und der Ausbildung, Weiterbildung und Fortbildung aller Ärztinnen und Ärzte dienen.

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DMKN contributes to the epithelial-mesenchymal transition through increased activation of STAT3 in pancreatic cancer

Summary

DMKN was first identified in relation to skin lesion healing and skin carcinoma. Recently, its expression has been associated with pancreatic cancer tumorigenesis, although its involvement remains poorly understood. Herein, we show that DMKN loss of function in Patu-8988 and PANC-1 pancreatic cancer cell lines results in reduced phosphorylation of signal transducer and activator of transcription-3 (STAT3), and increased activation of extracellular signal-regulated kinase (ERK1/2) and AKT serine/threonine kinase. This decreases the proliferation ability of pancreatic ductal adenocarcinoma (PDAC) cells. In addition, DMKN knockdown decreased the invasion and migration of PDAC cells, partially reversed the epithelial-mesenchymal transition, retarded tumor growth in a xenograft animal model by decreasing the density of microvessels, and attenuated the distance metastasis of human PDAC in a mouse model. Taken together, these data suggest that DMKN may be a potential prognostic biomarker and therapeutic target in pancreatic cancer.

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CENP-R acts bilaterally as a tumor suppressor and an oncogene in the two-stage skin carcinogenesis model

Abstract

CENP-R is a component of the CENP-O complex, including CENP-O, CENP-P, CENP-Q, CENP-R, and CENP-U and is constitutively localized to kinetochores throughout the cell cycle in vertebrates. CENP-R deficient chicken DT40 cells are viable and show very minor effect on mitosis. To investigate the functional roles of CENP-R in vivo, we generated CENP-R deficient mice (Cenp-r^-/-). Mice heterozygous or homozygous for Cenp-r null mutation are viable and healthy, with no apparent defect in growth and morphology, indicating Cenp-r is not essential for normal development. Accordingly, to investigate the role of the Cenp-r gene in skin carcinogenesis, we subjected Cenp-r^-/- mice to the DMBA/TPA chemical carcinogenesis protocol and monitored their tumor development. As a result, Cenp-r^-/- mice initially developed significantly more papillomas than control wild type mice. However, papillomas in Cenp-r^-/- mice showed a decrease of proliferative cells and an increase of apoptotic cells. As a result, they did not grow bigger and some papillomas showed substantial regression. Furthermore, papillomas in Cenp-r^-/- mice showed lower frequency of malignant conversion to squamous cell carcinomas. These results indicate Cenp-r functions bilaterally in cancer development: during early developmental stages, Cenp-r behaves as a tumor suppressor, but during the expansion and progression of papillomas it behaves as a tumor-promoting factor.

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The feasibility of prostate-specific membrane antigen positron emission tomography(PSMA PET/CT)-guided radiotherapy in oligometastatic prostate cancer patients

Abstract

Background

To investigate the efficacy and toxicity of 68Ga-PSMA-HBED-CC (⁶⁸Ga-PSMA) PET-CT-guided RT in the treatment of oligometastatic prostate cancer retrospectively.

Methods

A total of 23 prostate cancer patients with biochemical relapse, of which 13 were castration sensitive (CS) and 10 castration resistant (CR), were treated with intensity-modulated and image-guided RT (IMRT-IGRT) on ≤3 metastases detected by ⁶⁸Ga PSMA PET-CT. Androgen deprivation therapy was continued in CR patients.

Results

A total of 38 metastases were treated. The involved sites were pelvic bone (n = 16), pelvic lymph nodes (n = 11), paraaortic lymph nodes (n = 6), ribs (n = 3) and vertebral body (n = 2). The median PSA prior to RT was 1.1 ng/mL (range 0.1–29.0 ng/mL). A median dose of 43.5 Gy (range 30–64 Gy) was delivered by IMRT-IGRT in 12–27 fractions. At a median follow-up of 7 months (range 2–17 months), 19 patients (83%) were in remission. Four patients (17%) developed distant recurrences. The actuarial 1-year LC, PFS and OS rates were 100, 51 (95% CI 8–83%) and 100%. Univariate analysis demonstrated a statistically significantly better PFS in CS patients as compared to CR patients (1-year PFS 67 vs. 0%, p < 0.01). One patient experienced grade 2 acute gastrointestinal toxicity. Grade 3 or more toxicity events were not observed.

Conclusions

By providing optimal LC, low toxicity and a promising PFS in CS patients, the current retrospective study illustrated that ⁶⁸Ga PSMA PET-CT-guided RT may be an attractive treatment strategy in patients with oligometastatic prostate cancer. Validation by randomized trials is eagerly awaited.

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Risk adapted dose-intensified postoperative radiation therapy in prostate cancer patients using a simultaneous integrated boost technique applied with helical Tomotherapy

Abstract

Background

Postoperative adjuvant radiation therapy (ART) in T3 and R1 prostate cancer as well as salvage radiation therapy (SRT) in case of postoperative biochemical failure (BF) are established treatments. Dose-intensified postoperative radiation therapy (RT) schemes have shown superior biochemical control accompanied by increased toxicity rates. In our study we evaluate a novel risk adapted dose-intensified postoperative RT scheme.

Methods

A consecutive series of prostate cancer patients receiving postoperative RT after radical prostatectomy using helical Tomotherapy between 04/2012 and 04/2015 was analyzed retrospectively. RT was administered using a simultaneous integrated boost (SIB) to the area at risk (37 fractions of 1.9 Gy, total dose: 70.3 Gy) being defined based on histopathological findings (T3/R1 region) and in few cases according to additional diagnostic imaging. The whole prostate bed was treated with a dose of 66.6 Gy (37 fractions of 1.8 Gy). Primary endpoints were acute and late genitourinary (GU) and gastrointestinal (GI) toxicities. Secondary endpoints included patient reported outcome as assessed by the International Prostate Symptom Score (IPSS), the International Consultation on Incontinence questionnaire (ICIQ) and prostate cancer specific Quality of Life questionnaire QLQ-PR25, as well as rates of BF.

Results

A total of 69 patients were analyzed. Sixteen patients underwent ART and 53 patients SRT, respectively. The median follow-up was 20 months (range, 8–41 months). Seven (10.1%) and four (5.8%) patients experienced acute grade 2 GU and GI toxicity. Two patients (2.9%) had late grade 2 GU toxicity, whereas no late grade 2 GI nor any grade 3 acute or late GU or GI events were observed. When compared to the baseline IPSS scores (p = 1.0) and ICIQ scores (p = 0.87) were not significantly different at the end of follow-up. Patient reported Quality of life (QoL) showed also no significant difference. A total of seven patients (10.1%) experienced a biochemical recurrence with the 2-year biochemical progression-free survival (bPFS) being 91%.

Conclusions

Postoperative RT for prostate cancer patients with a risk adapted dose-intensified SIB using helical tomotherapy is feasible and associated with favorable acute and late GU and GI toxicity rates, no significant change of IPSS-, ICIQ scores and patient reported QoL and results in promising bPFS rates.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2uqBikA

The feasibility of prostate-specific membrane antigen positron emission tomography(PSMA PET/CT)-guided radiotherapy in oligometastatic prostate cancer patients

Abstract

Background

To investigate the efficacy and toxicity of 68Ga-PSMA-HBED-CC (⁶⁸Ga-PSMA) PET-CT-guided RT in the treatment of oligometastatic prostate cancer retrospectively.

Methods

Results

Conclusions

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(Central) Auditory Processing Disorder Grand Rounds: Multiple Cases, Multiple Causes, Multiple Outcomes

Purpose

The purpose of this article was to provide multiple examples of how (central) auditory processing disorder ([C]APD) is being evaluated and treated at various audiology clinics throughout the United States.

Method

The authors present 5 cases highlighting the diagnosis and treatment of (C)APD in children and adults. Similarities and differences between these cases have been showcased through detailed histories, evaluation protocol, and treatment options. When possible, the rationale for evaluation procedures and intervention processes were described and compared with guidelines and findings within the literature.

Results and Conclusions

These cases illustrate the varied processes and clinical protocols by which children and adults are evaluated, diagnosed, counseled, and treated for (C)APD. In addition, similarities and differences between the referral source, evaluation team, developmental history, comorbidities, test battery, recommendations, and remediations were described. The multiple clinic sites, diversity of clinical philosophies, variety of test measures, and diversity of patient populations make these cases ideal for showcasing the assortment of methodologies used with patients who present with histories and characteristics consistent with (C)APD.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/doi/10.1044/2017_AJA-16-0074/2648889/Central-Auditory-Processing-Disorder-Grand-Rounds

Evaluating Random Error in Clinician-Administered Surveys: Theoretical Considerations and Clinical Applications of Interobserver Reliability and Agreement

Purpose

The purpose of this study is to raise awareness of interobserver concordance and the differences between interobserver reliability and agreement when evaluating the responsiveness of a clinician-administered survey and, specifically, to demonstrate the clinical implications of data types (nominal/categorical, ordinal, interval, or ratio) and statistical index selection (for example, Cohen's kappa, Krippendorff's alpha, or interclass correlation).

Methods

In this prospective cohort study, 3 clinical audiologists, who were masked to each other's scores, administered the Practical Hearing Aid Skills Test–Revised to 18 adult owners of hearing aids. Interobserver concordance was examined using a range of reliability and agreement statistical indices.

Results

The importance of selecting statistical measures of concordance was demonstrated with a worked example, wherein the level of interobserver concordance achieved varied from "no agreement" to "almost perfect agreement" depending on data types and statistical index selected.

Conclusions

This study demonstrates that the methodology used to evaluate survey score concordance can influence the statistical results obtained and thus affect clinical interpretations.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/doi/10.1044/2017_AJA-16-0100/2647806/Evaluating-Random-Error-in-ClinicianAdministered

The Effect of RGD/NGR Peptide Modification of Melanoma Differentiation-Associated Gene-7/Interleukin-24 on Its Receptor Attachment, an In Silico Analysis

Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0.

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Subarachnoid small vein occlusion due to inflammatory fibrosis—a possible mechanism for cerebellar infarction in cryptococcal meningoencephalitis: a case report

Cryptococcal meningoencephalitis (CM) causes cerebral infarction, typically, lacunar infarction in the basal ganglia. However, massive cerebral infarction leading to death is rare and its pathophysiology is un...

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Patient satisfaction with ExtaviPro™ 30G, a new auto-injector for administering interferon β-1b in multiple sclerosis: results from a real-world, observational EXCHANGE study

Patients with multiple sclerosis (MS) receiving long-term, subcutaneous interferon β-1b (IFN β-1b; Extavia®) often experience injection-site reactions and injection-site pain, which together with other side-ef...

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Expression of Kallikrein-Related Peptidase 6 in Primary Mucosal Malignant Melanoma of the Head and Neck

Abstract

Mucosal melanomas of the head and neck (MMHN) are aggressive tumors with poor prognosis, different opposed to cutaneous melanoma. In this study, we characterized primary mucosal malignant melanoma for the expression of Kallikrein-related peptidase 6 (KLK6), a member of the KLK family with relevance to the malignant phenotype in various cancer types including cutaneous melanoma. Paraffin-embedded MMHN of 22 patients were stained immunohistochemically for KLK6 and results were correlated with clinical and pathological data. In 77.3% (17/22) of MMHN cases, positive KLK6 staining was found. Staining pattern for tumor cells showed a predominant cytoplasmic staining. However, in six cases we also observed a prominent nuclear staining. MMHN with a high KLK6 expression showed significantly better outcome concerning local recurrence-free survival (p = 0.013) and nuclear KLK6 staining was significantly associated with the survival status (p = 0.027). Overexpression of KLK6 was detected in more than 70% of MMHN and approximately 40% of tumors showed a strong expression pattern. Correlation between clinical outcome of MMHN patients and overexpression of KLK6 has not been addressed so far. Our data demonstrate for the first time increased levels of KLK6 in MMHN and strengthen the hypothesis that there might be a context-specific regulation and function of KLK6 in mucosal melanoma.

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The Great Mimicker: Metastatic Breast Carcinoma to the Head and Neck with Emphasis on Unusual Clinical and Pathologic Features

Abstract

Distant metastases are relatively common in breast cancer, but spread to the head and neck region is uncommon and can be diagnostically challenging. Pathology databases of two academic hospitals were searched for patients. The diagnoses were by morphologic comparison with the primary breast specimen (when available) or through the use of immunohistochemical stains characteristic of breast carcinoma (cytokeratin 7, mammaglobin, GCDFP15, and/or GATA3 positive—excluding new primary tumors at the respective head and neck sites). Of the 25 patients identified, only 22 (88.0 %) had a known history of breast carcinoma. Time from primary diagnosis to head and neck metastasis was highly variable, ranging from 1 to 33 years (mean = 10.9 years). The most common locations were neck lymph nodes (8 cases), orbital soft tissue (5), oral cavity (3), skull base (3), mastoid sinus (2), nasal cavity (1), palatine tonsil (1), and facial skin (1). Clinical presentations were highly variable, ranging from cranial nerve palsies without a mass lesion to oral cavity erythema and swelling to bone pain. Histologically, two cases showed mucosal (or skin)-based mass lesions with associated pagetoid spread in the adjacent epithelium, a feature normally associated with primary carcinomas. Three tumors were misdiagnosed pathologically as new head and neck primary tumors. This series demonstrates the extreme variability in clinical and pathologic features of breast cancer metastatic to the head and neck, including long time intervals to metastasis.

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Head and Neck Rhabdomyosarcoma: Clinical and Pathologic Characterization of Seven Cases

Abstract

Head and neck rhabdomyosarcoma occurs frequently in children and adolescents, and has been well studied in that population. In contrast, it is rare in adults and is not as well characterized clinically and pathologically. Seven cases of adult rhabdomyosarcoma occurring in head and neck were retrieved from the archives of Department of Pathology and Division of Oral Pathology at University of Washington. Radiologic findings and clinical history, as well as pathologic findings from hematoxylin and eosin slides and immunohistochemistry for myogenic markers were reviewed. A total of seven cases of rhabdomyosarcoma (two embryonal, three alveolar and two pleomorphic subtype) were reviewed. Patient ages ranged from 18 to 57 years (median 21 years). Classic and unique histologic features for each subtype, including post-treatment morphologic changes, were identified. Clinical follow-up information was available for 4 patients. 3 of 4 patients experienced recurrence, including two with distant metastasis. One patient died of disease progression 41 months after presentation. Head and neck rhabdomyosarcoma in adults can manifest both classic and unique histologic features for each subtype. In addition, recurrence and distant metastasis were observed, suggesting aggressive clinical behavior regardless of subtype.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vFrzGU

Transcriptionally Active High-Risk Human Papillomavirus is Not a Common Etiologic Agent in the Malignant Transformation of Inverted Schneiderian Papillomas

Abstract

The role of human papillomavirus (HPV) as an etiologic and transformational agent in inverted Schneiderian papilloma (ISP) is unclear. Indeed, reported detection rates of HPV in ISPs range from 0 to 100%. The true incidence has been confounded by a tendency to conflate high- and low-risk HPV types and by the inability to discern biologically relevant from irrelevant HPV infections. The recent development of RNA in situ hybridization for high-risk HPV E6/E7 mRNA now allows the direct visualization of transcriptionally active high-risk HPV in ISP, providing an opportunity to more definitively assess its role in the development and progression of ISPs. We performed p16 immunohistochemistry and high-risk HPV RNA in situ hybridization on 30 benign ISPs, 7 ISPs with dysplasia, 16 ISPs with carcinomatous transformation, and 7 non-keratinizing squamous cell carcinomas (SCCs) with inverted growth that were unassociated with ISP. Transcriptionally active HPV was not detected in any of the 52 ISPs including those that had undergone carcinomatous transformation, but it was detected in two of seven (29%) non-keratinizing SCCs that showed inverted growth. There was a strong correlation between high-risk HPV RNA in situ hybridization and p16 immunohistochemistry (97%; p < 0.01). These results indicate that transcriptionally active high-risk HPV does not play a common role in either the development of ISP or in its transformation into carcinoma.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2kTVyoP

Human Papillomavirus Associated Cancers of the Head and Neck: An Australian Perspective

Abstract

Human papillomavirus (HPV) associated head and neck squamous cell carcinomas (HNSCCs), have become a serious global health problem. Despite decreases in HPV-negative HNSCCs, the prevalence of HPV-positive HNSCCs has significantly increased. HPV-positive cancers are associated with superior survival outcomes when compared to HPV-negative cancers, which appears likely to be associated with differences in the molecular pathogenesis of the two diseases. While therapies are still problematic, the current HPV vaccine programs hold a promise for the primary prevention of HPV-related HNSCCs and since Australia was the first to introduce a nationwide HPV vaccine program, it is in a unique position to observe the effects of the vaccine on HNSCCs. This review discusses the epidemiological trends associated with HPV in HNSCC, with reference to the differences between HPV-positive and HPV-negative HNSCCs and the prevention potential of HPV vaccines.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2kipxDL

Higher TSH and Lower FT4 Levels in Pregnant Women Are Associated with Higher Pregestational BMI and Greater Gestational Weight Gain

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 310-311.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2uqpdrx

Parathyroid Lesions Can Be Distinguished from Thyroid Lesions on FNA but May Require Ancillary Studies and Molecular Analysis

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 291-293.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vOHmCL

Older Age and Advanced Disease Are Risk Factors for Complications after Thyroid Cancer Surgery

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 294-296.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2uqhrhq

How Does the Thyroid Hormone Level Affect the Level of the Apoptosis Regulator TRAIL?

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 315-317.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vPeYAv

The Merits of Ultrasound Screening for Familial Nonmedullary Thyroid Cancer Are Strongly Dependent on the Number of Affected Family Members

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 297-300.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2uqBbBu

TSH-Based Levothyroxine Dosage Adjustment Is Superior to Fixed Dosage Adjustments in Pregnant Women with Preexisting Hypothyroidism

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 307-309.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vmXSYt

18F-FDOPA-PET Is More Sensitive than F-18-FDG-PET in Persistent or Recurrent Medullary Thyroid Cancer

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 301-304.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vG7bW5

Thyroid Dysfunction Was Associated with Dyslipidemia, but Not Incident Myocardial Infarction or Stroke in a Large U.S. General Population–Based Cohort

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 312-314.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vneoI1

Fatal Nonanaplastic Thyroid Cancers Harbor Multiple Oncogenic Mutations

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 305-306.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vGgGEK

CASE REPORT: Two Cases of Impaired Sensitivity to Thyroid Hormone with Wild-Type THRβ Gene

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 318-321.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vng8Ba

Language Samples From Children Who Use Speech-Generating Devices: Making Sense of Small Samples and Utterance Length

Purpose

Mean length of utterance in morphemes (MLUm) is underreported in people who use augmentative and alternative communication (AAC). MLUm is difficult to measure in people who use AAC because of 2 challenges described in literature: the challenge of small language samples (difficulty collecting representative samples) and the challenge of transcribing short utterances (difficulty transcribing 1-morpheme utterances). We tested solutions to both challenges in a corpus of language samples from children who use speech-generating devices.

Method

The first challenge was addressed by adjusting the length of the sampling window to obtain representative language samples. The second challenge was addressed by using mean syntactic length (MSL) as an alternative to MLUm.

Results

A 24-hour sample window consistently failed to yield representative samples. An extended 1-month sample window consistently yielded representative samples. A significant positive prediction of MLUm by MSL was found in a normative sample. Observed measures of MSL were used to predict MLUm in representative language samples from children who use AAC.

Conclusions

Valid measures of utterance length in people who use AAC can be obtained using extended sampling windows and MSL. Research is needed to characterize the strengths and limitations of both solutions.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/doi/10.1044/2017_AJSLP-16-0114/2648883/Language-Samples-From-Children-Who-Use

A Collaborative Model for Return to Academics After Concussion: Athletic Training and Speech-Language Pathology

Purpose

In this article, we describe an academic concussion management protocol designed for grades Pre-K to 12, called Cognitive Return to Exertion (CoRTEx). Collaboration between the speech-language pathologist (SLP) and athletic trainer (AT) is highlighted.

Method

A description of CoRTEx is provided, and the need for collaboration is emphasized. A case study illustrates an example of how CoRTEx can be implemented at the individual student level.

Results

A total of 165 students went through CoRTEx from the pilot in April 2014 through December 2016. Referrals to CoRTEx were highest for football, blows to the head, and soccer. Anecdotal evidence suggests that CoRTEx provided necessary support for students and their families, although research is needed to provide objective data.

Conclusions

CoRTEx and other similar protocols can be used as models for SLPs to create their own academic concussion management protocols. For cases in which the injured student is an athlete, the SLP–AT collaboration is critical to carefully coordinate return to academics and return to play so that students are successful in school, as well as ready to safely return to sport. Suggestions are made for designing research studies that can provide empirical evidence for the efficacy of such academic concussion management protocols.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/doi/10.1044/2017_AJSLP-16-0138/2648884/A-Collaborative-Model-for-Return-to-Academics

Higher TSH and Lower FT4 Levels in Pregnant Women Are Associated with Higher Pregestational BMI and Greater Gestational Weight Gain

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 310-311.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2uqpdrx

Parathyroid Lesions Can Be Distinguished from Thyroid Lesions on FNA but May Require Ancillary Studies and Molecular Analysis

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 291-293.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vOHmCL

Older Age and Advanced Disease Are Risk Factors for Complications after Thyroid Cancer Surgery

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 294-296.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2uqhrhq

How Does the Thyroid Hormone Level Affect the Level of the Apoptosis Regulator TRAIL?

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 315-317.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vPeYAv

The Merits of Ultrasound Screening for Familial Nonmedullary Thyroid Cancer Are Strongly Dependent on the Number of Affected Family Members

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 297-300.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2uqBbBu

TSH-Based Levothyroxine Dosage Adjustment Is Superior to Fixed Dosage Adjustments in Pregnant Women with Preexisting Hypothyroidism

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 307-309.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vmXSYt

18F-FDOPA-PET Is More Sensitive than F-18-FDG-PET in Persistent or Recurrent Medullary Thyroid Cancer

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 301-304.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vG7bW5

Thyroid Dysfunction Was Associated with Dyslipidemia, but Not Incident Myocardial Infarction or Stroke in a Large U.S. General Population–Based Cohort

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 312-314.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vneoI1

Fatal Nonanaplastic Thyroid Cancers Harbor Multiple Oncogenic Mutations

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 305-306.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vGgGEK

CASE REPORT: Two Cases of Impaired Sensitivity to Thyroid Hormone with Wild-Type THRβ Gene

Clinical Thyroidology Aug 2017, Vol. 29, No. 8: 318-321.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vng8Ba

Expression of Kallikrein-Related Peptidase 6 in Primary Mucosal Malignant Melanoma of the Head and Neck

Abstract

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vFS9Q1

The Great Mimicker: Metastatic Breast Carcinoma to the Head and Neck with Emphasis on Unusual Clinical and Pathologic Features

Abstract

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vns6ug

Head and Neck Rhabdomyosarcoma: Clinical and Pathologic Characterization of Seven Cases

Abstract

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vFrzGU

Atopy and prostate cancer: Is there a link between circulating levels of IgE and PSA in humans?

Abstract

Background

Atopy has been investigated as a potential risk factor for prostate cancer. IgE antibodies may be major players in protective responses against tumours, through engendering antigen presentation and enhancing adaptive immune responses targeted towards a specific allergen, but potentially also against tumour-associated antigens such as prostate-specific antigen (PSA). We therefore cross-sectionally investigated associations between circulating levels of PSA and IgE in the National Health and Nutrition Examination Survey 2005–2006.

Methods

We focused on all men aged 40+ years with measurements for PSA and IgE, and no previous diagnosis of prostate cancer (n = 1312). We estimated the association between total and specific IgE concentration and levels of PSA with logistic regression models, adjusted for age, ethnicity/race, education, smoking status, body mass index (BMI), physical activity status, and history of asthma.

Results

Both total IgE and the sum of specific IgE were inversely associated with the risk of having PSA levels ≥10 ng/mL, though most findings were not statistically significant. The odds ratios for the second and third tertile of total IgE as compared to the first were 0.21 (95% CI 0.06–0.72) and 0.42 (0.08–2.31). The odds ratio for sum of abnormal specific IgE measurements was 0.77 (0.44–1.34).

Conclusion

Despite statistical insignificance, the observed trend warrants further research given the increasing evidence of the role of atopy and IgE antibodies in protective responses against tumours. A lifecourse approach of measuring IgE, specific subtypes, and other markers of the humoral immune system (i.e. IgG) could shed more light on its potential anti-cancer characteristics.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vnlHzt

Atopy and prostate cancer: Is there a link between circulating levels of IgE and PSA in humans?

Abstract

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Methods

Results

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from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vnlHzt

The mean corpuscular volume as a prognostic factor for colorectal cancer

Abstract

Purpose

The aim of the present study was to identify the factors investigated during routine blood examinations which can predict the disease outcome independent of the tumor stage.

Methods

Data from 1174 patients with stage I, II, and III CRC who underwent R0 resection were included. We investigated the correlations between the preoperative routine blood examination data, and clinicopathological factors, and disease-free survival (DFS) using univariate and multivariate analyses.

Results

The univariate analysis showed that tumor location, tumor stage, CRP, serum albumin, creatine kinase, neutrophil-to-lymphocyte ratio, red blood cell count, mean corpuscular volume (MCV), and the administration of postoperative adjuvant chemotherapy were significantly correlated with the DFS. The multivariate analysis of the factors associated with the DFS showed that stage and MCV were significant factors; an MCV of <80 fL was associated with a superior DFS in comparison to an MCV of 80–100 fL (hazard ratio: 0.31, 95% confidence interval: 0.13–0.61, p = 0.0003). The DFS in patients with an MCV of <80 fL was superior to that in patients with an MCV of ≥80 fL, irrespective of whether the patients underwent postoperative adjuvant chemotherapy.

Conclusion

MCV was a prognostic factor for the DFS, independent of the tumor stage, in CRC patients who underwent R0 resection.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vPREDs

Chronology of gastrointestinal cancer

Abstract

The "chronology of cancer" is a concept that describes the nature of cancers through the measure of time. The field extends from carcinogenesis to development, progression, and metastasis. Carcinogenesis is a multi-step process, which results from the accumulation of multiple genetic or epigenetic alterations. Various chronologies of gastrointestinal cancers have been reported for carcinogenesis caused by different risk factors. These chronologies are useful for developing cancer prevention strategies. The tumor growth rate is one of the most important factors in this field. Combining the factors of time and tumor growth enables us to estimate the time at which cancer or metastasis occurred, retrospectively, and to predict the survival of cancer patients, prospectively. It is noteworthy that these chronologies differ significantly among individual cases, even of cancers derived from the same organ. Thus, they are useful for individualization. We can apply the knowledge obtained in this field to the basic research and the diagnosis and treatment of cancers. The chronology of cancer is a classical but interesting field, which helps us consider and explore the essence of cancer. We review the topics related to the chronology of gastrointestinal cancer, ranging from carcinogenesis to metastasis.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2wJkm5q

An analysis of 97 previously diagnosed de novo adult acute erythroid leukemia patients following the 2016 revision to World Health Organization classification

Abstract

Background

The incidence of acute erythroid leukemia subtype (AEL) is rare, accounting for 5% of cases of acute myeloid leukemia (AML), and the outcome is dismal. However, in 2016 revision to the WHO classification, the subcategory of AEL has been removed. Myeloblasts are redefined as the percentage of total marrow cells, not non-erythroid cells. Therefore, the previously diagnosed AEL cases are currently diagnosed as AML or myelodyspalstic syndrome (MDS) according to new criteria.

Methods

We respectively reviewed cases of 97 de novo previously diagnosed AEL and all the patients were diagnosed as AML or MDS according to the new classification scheme, and then the clinical characteristics of these two subtypes were compared. Statistical analyses were performed by SPSS software version 18.0.

Results

The median age was 37 years-old, the two-thirds of previous AEL cases were diagnosed as MDS, and there was no obvious difference between two subtypes except for male/female ratio and age. Cytogenetic, rather than MDS/AML subtypes, can better represent the prognostic factor of previously diagnosed AEL patients. When the cytogenetic risk of patients belonged to MRC intermediate category and age were below 40 years-old in previous AEL cases, the patients who received induction chemotherapy without transplantation had a similar survival compared with the patients who underwent transplantation (3-year OS: 67.2% vs 68.5%).

Conclusions

Cytogenetic, rather than MDS/AML subtypes, can better represent the prognostic factor of previously diagnosed AEL patients. Transplantation was a better choice for those whose cytogenetic category was unfavorable.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2vFBXy5

Αρχειοθήκη ιστολογίου

Τετάρτη 9 Αυγούστου 2017

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