OtoRhinoLaryngology News: 12/28/17

Πέμπτη 28 Δεκεμβρίου 2017

Association between investigator-measured body-mass index and colorectal adenoma: a systematic review and meta-analysis of 168,201 subjects

Abstract

The objective of this meta-analysis is to evaluate the odds of colorectal adenoma (CRA) in colorectal cancer screening participants with different body mass index (BMI) levels, and examine if this association was different according to gender and ethnicity. The EMBASE and MEDLINE were searched to enroll high quality observational studies that examined the association between investigator-measured BMI and colonoscopy-diagnosed CRA. Data were independently extracted by two reviewers. A random-effects meta-analysis was conducted to estimate the summary odds ratio (SOR) for the association between BMI and CRA. The Cochran's Q statistic and I² analyses were used to assess the heterogeneity. A total of 17 studies (168,201 subjects) were included. When compared with subjects having BMI < 25, individuals with BMI 25–30 had significantly higher risk of CRA (SOR 1.44, 95% CI 1.30–1.61; I² = 43.0%). Subjects with BMI ≥ 30 had similarly higher risk of CRA (SOR 1.42, 95% CI 1.24–1.63; I² = 18.5%). The heterogeneity was mild to moderate among studies. The associations were significantly higher than estimates by previous meta-analyses. There was no publication bias detected (Egger's regression test, p = 0.584). Subgroup analysis showed that the magnitude of association was significantly higher in female than male subjects (SOR 1.43, 95% CI 1.30–1.58 vs. SOR 1.16, 95% CI 1.07–1.24; different among different ethnic groups (SOR 1.72, 1.44 and 0.88 in White, Asians and Africans, respectively) being insignificant in Africans; and no difference exists among different study designs. In summary, the risk conferred by BMI for CRA was significantly higher than that reported previously. These findings bear implications in CRA risk estimation.

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EZH2 overexpression in head and neck cancer is related to lymph node metastasis

Abstract

Background

Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the polycomb repressive complex 2, plays an important role in tumor development and progression by interacting with histone and non-histone proteins. EZH2 represents a putative therapeutic target and has been suggested as a prognostic marker in several cancer types.

Material and Methods

The present study investigates the prognostic relevance of immunohistochemical EZH2 expression in head and neck squamous cell carcinoma. Tissue microarray sections with 667 cancers of oral cavity, oro- and hypopharynx and larynx were analyzed for EZH2 expression.

Results

Nuclear EZH2 staining was recorded in 322 (81.8%) of 394 cases. Staining was weak in 33 (10.2%), moderate in 128 (39.6%) and strong in 103 (32.0%) cancers. The prevalence of EZH2 expression in tumors of the oral cavity and the orohypopharynx was higher as compared to cancers of the larynx (p=0.0023). EZH2 expression was correlated to presence of lymph node metastasis (p=0.0089) but was unrelated to histological grade, tumor stage, surgical margin or distant metastasis. EZH2 expression had no impact on patient survival.

Conclusion

The high prevalence of EZH2 expression in head and neck squamous cell carcinoma stresses its capability as a therapeutic target.

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Intraoperative objective evaluation of venous congestion in deep epigastric artery perforator flap breast reconstruction: A pilot study

Abstract

Background

In a deep epigastric artery perforator (DIEP) flap breast reconstruction, the necessity of additional anastomosis of the superficial inferior epigastric vein (SIEV) should be determined intraoperatively. The purpose of this pilot study is to propose a method to detect venous congestion intraoperatively using the blood glucose measurement index (BGMI).

Methods

In 70 DIEP flaps of 67 patients for breast reconstruction, the ratio of blood glucose content in the flap to systemic blood glucose (BGMI) was measured immediately after wound closure. Eight flaps in which BGMI was less than 0.8 were categorized into the low BGMI group, and additional venous anastomosis using SIEV was conducted. The other 62 flaps were categorized into the normal BGMI group. Perioperative objective color difference of the flap calculated using the L*a*b* color coordinate scale was recorded simultaneously. Correlation between BGMI and color difference was analyzed.

Results

In all flaps in the low BGMI group, SIEV diameter was increased; after additional anastomosis, the BGMI significantly improved (from 0.71 ± 0.05 to 0.94 ± 0.05, P < .01). There was a significant correlation between BGMI and color difference (P = .04). The determination coefficient was 0.265. When a BGMI of less than 0.8 was assumed to be a true positive, the area under the curve of color difference in the receiver operating characteristic curve was 0.82.

Conclusion

BGMI immediately after wound closure may be useful to detect initial signs of venous congestion. Intraoperative objective color difference also reflects venous congestion; however, it is not highly accurate.

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Identification of genes highly downregulated in pancreatic cancer through a meta-analysis of microarray datasets: implications for discovery of novel tumor-suppressor genes and therapeutic targets

Abstract

Purpose

The lack of specific symptoms at early tumor stages, together with a high biological aggressiveness of the tumor contribute to the high mortality rate for pancreatic cancer (PC), which has a 5-year survival rate of about 7%. Recent failures of targeted therapies inhibiting kinase activity in clinical trials have highlighted the need for new approaches towards combating this deadly disease.

Methods

In this study, we have identified genes that are significantly downregulated in PC, through a meta-analysis of large number of microarray datasets. We have used qRT-PCR to confirm the downregulation of selected genes in a panel of PC cell lines.

Results

This study has yielded several novel candidate tumor-suppressor genes (TSGs) including GNMT, CEL, PLA2G1B and SERPINI2. We highlight the role of GNMT, a methyl transferase associated with the methylation potential of the cell, and CEL, a lipase, as potential therapeutic targets. We have uncovered genetic links to risk factors associated with PC such as smoking and obesity. Genes important for patient survival and prognosis are also discussed, and we confirm the dysregulation of metabolic pathways previously observed in PC.

Conclusions

While many of the genes downregulated in our dataset are associated with protein products normally produced by the pancreas for excretion, we have uncovered some genes whose downregulation appear to play a more causal role in PC. These genes will assist in providing a better understanding of the disease etiology of PC, and in the search for new therapeutic targets and biomarkers.

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Perceptual Changes with Monopolar and Phantom electrode stimulation

Publication date: Available online 28 December 2017
Source:Hearing Research
Author(s): Silke Klawitter, David M. Landsberger, Andreas Büchner, Waldo Nogueira
Phantom electrode (PE) stimulation is achieved by simultaneously stimulating out-of-phase from two adjacent intra-cochlear electrodes with different amplitudes. If the basal electrode stimulates with a smaller amplitude than the apical electrode of the pair, the resulting electrical field is pushed away from the basal electrode producing a lower pitch. There is great interest in using PE stimulation in a processing strategy as it can be used to provide stimulation to regions of the cochlea located more apically than the most apical contact on the electrode array. The result is that even lower pitch sensations can be provided without additional risk of a deeper insertion. However, it is unknown if there are perceptual differences between monopolar (MP) and PE stimulation other than a shift in place pitch. Furthermore, it is unknown if the effect and magnitude of changing from MP to PE stimulation is dependent on electrode location. This study investigates the perceptual differences (including pitch and other sound quality differences) at multiple electrode positions using MP and PE stimulation using both a multidimensional scaling procedure (MDS) and a traditional scaling procedure.10 Advanced Bionics users reported the perceptual distances between 5 single electrode (typically 1, 3, 5, 7, and 9) stimuli in either MP or PE (σ=0.5) mode. Subjects were asked to report how perceptually different each pair of stimuli were using any perceived differences except loudness. Subsequently, each stimulus was presented in isolation and subjects scaled how "high" or how "clean" each sounded.Results from the MDS task suggest that perceptual differences between MP and PE stimulation can be explained by a single dimension. The traditional scaling suggests that the single dimension is place pitch. PE stimulation elicits lower pitch perceptions in all cochlear regions. Analysis of Cone Beam Computer Tomography (CBCT) data suggests that PE stimulation may be more effective at the apical part of the cochlea. PE stimulation can be used for new sound coding strategies in order to extend the pitch range for cochlear implant (CI) users without perceptual side effects.

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Computational modeling of the human auditory periphery: auditory-nerve responses, evoked potentials and hearing loss

Publication date: Available online 28 December 2017
Source:Hearing Research
Author(s): Sarah Verhulst, Alessandro Altoè, Viacheslav Vasilkov
Models of the human auditory periphery range from very basic functional descriptions of auditory filtering to detailed computational models of cochlear mechanics, inner-hair cell (IHC), auditory-nerve (AN) and brainstem signal processing. It is challenging to include detailed physiological descriptions of cellular components into human auditory models because single-cell data stems from invasive animal recordings while human reference data only exists in the form of population responses (e.g., otoacoustic emissions, auditory evoked potentials). To embed physiological models within a comprehensive human auditory periphery framework, it is important to capitalize on the success of basic functional models of hearing and render their descriptions more biophysical where possible. At the same time, comprehensive models should capture a variety of key auditory features, rather than fitting their parameters to a single reference dataset. In this study, we review and improve existing models of the IHC-AN complex by updating their equations and expressing their fitting parameters into biophysical quantities. The quality of the model framework for human auditory processing is evaluated using recorded auditory brainstem response (ABR) and envelope-following response (EFR) reference data from normal and hearing-impaired listeners. We present a model with 12 fitting parameters from the cochlea to the brainstem that can be rendered hearing impaired to simulate how cochlear gain loss and synaptopathy affect human population responses. The model description forms a compromise between capturing well-described single-unit IHC and AN properties and human population response features.

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The 2-anilino-4-amino-5-aroylthiazole-type compound AS7128 inhibits lung cancer growth through decreased iASPP and p53 interaction

Abstract

Lung cancer is the leading cause of cancer-related death worldwide. Thus, developing novel therapeutic agents become urgent demands for lung cancer treatment. In this study, compound AS7128 was selected from a two-million entry chemical library screening and identified as a candidate drug that against non-small cell lung cancer (NSCLC) in vitro and in vivo. Further investigation indicated that AS7128 could induce cell apoptosis and cell cycle arrest, especially in the mitosis stage. In addition, we also found that iASPP, an oncogenic protein that functionally inhibits p53, might be associated with AS7128 through mass identification. Further exploration indicated that AS7128 treatment could restore the transactivation ability of p53 and thus increase the expressions of its downstream target genes, which are related to cell cycle arrest and apoptosis. This occurs via disruption of the interactions between p53 and iASPP in cells. Taken together, AS7128 could bind to iASPP, disrupt the interaction between iASPP and p53, and result in cell cycle arrest and apoptosis. These findings may provide new insights for using iASPP as a therapeutic target for NSCLC treatment.

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C-C chemokine receptor type 1 mediates osteopontin-promoted metastasis in hepatocellular carcinoma

Abstract

In hepatocellular carcinoma (HCC) microenvironment, chemokine receptors have a critical role in tumorigenesis and metastasis. Our previous studies have found that osteopontin (OPN) is a promoter for HCC metastasis. However, the role of chemokine receptors in OPN-induced HCC metastasis still remains unclear. In this study, we demonstrate that OPN is dramatically elevated in HCC tissues with metastasis and high expression of OPN correlates with poorer overall survival and higher recurrence rate. OPN upregulates chemokine receptor expression, migration, invasion, and pulmonary metastasis in HCC. We find that C-C chemokine receptor type 1 (CCR1) and C-X-C chemokine receptor type 6 (CXCR6) are the most upregulated chemokine receptors induced by OPN. CCR1 knockdown results in reduction of migration, invasion and pulmonary metastasis induced by OPN in vitro and in vivo, whereas CXCR6 knockdown does not reverse OPN-promoted migration and invasion. Moreover, OPN up-regulates the expression of CCR1 via activating phosphoinositide 3-kinase (PI3K)/AKT and hypoxia-inducible factor 1α (HIF-1α) in HCC cells. Furthermore, blockade of OPN-CCR1 axis with CCR1 antagonist significantly restrains the promoting effects of OPN on HCC progression and metastasis. In human HCC tissues, OPN expression shows significantly positive correlation with CCR1 expression, and the patients with high levels of both OPN and CCR1 have the most dismal prognosis. Collectively, our results indicate that the OPN-CCR1 axis in HCC is important for accelerating tumor metastasis and CCR1 is a potential therapeutic target for controlling metastasis in HCC patients with high OPN.

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Implementation of “Clinical Sequencing” in Cancer Genome Medicine in Japan

Abstract

In oncology, actionable mutations (alterations) in cancer-associated genes are critical in terms of the selection of therapeutic approaches. Next-generation sequencing (NGS) of tumor sample DNA (i.e., clinical sequencing) can guide clinical management by providing diagnostic or prognostic data, and facilitating the identification of potential treatment regimens, such as molecular-targeted and immune checkpoint blockade therapies. In the U.S., a variety of tumor-profiling multiplex gene panels have been developed and implemented for this purpose. In Japan, several academic institutions have now performed detailed investigations of the feasibility and value of clinical sequencing, and cancer societies have issued consensus clinical practice guidelines for NGS-based gene panel tests. These efforts will facilitate the implementation of cancer genome medicine in Japan.

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Cancer Immunotherapy Targeted Glypican-3 or Neoantigens

Abstract

Immune checkpoint inhibitors have ushered a new era in cancer therapy, although other therapies or combinations thereof are still needed for the many patients for whom these drugs are ineffective. In this light, we have identified in glypican-3 an HLA-24, HLA-A2 restriction peptide with extreme cancer specificity. In this paper, we summarize results from a number of related clinical trials demonstrating that glypican-3 peptide vaccines induce specific cytotoxic T lymphocytes in most patients (UMIN Clinical Trials Registry: UMIN000001395, UMIN000005093, UMIN000002614, UMN000003696, UMIN000006357,). We also describe the current state of personalized cancer immunotherapy based on neoantigens, and assess, based on our own research and experience, the potential of such therapy to elicit cancer regression. Finally, we discuss the future direction of cancer immunotherapy.

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Proposal for Reclassification of N Staging Systems in Penile Cancer Patients: Based on Number of Positive Lymph Nodes

Abstract

In the present study, we aim to compare the rationality of proposed N classification based on the number of metastatic lymph nodes (LNs) with the current one. A total of 509 penile cancer patients at our institute were analyzed. Univariable and multivariable statistical analyses were used to assess cancer-specific survival (CSS) in two staging systems. Harrell's concordance index was applied to evaluate predictive accuracy of the current and proposed N classification in predicting CSS. We propose a new classification: pN1 (metastasis in 1-2 regional LNs), pN2 (metastasis in 3 regional LNs, or three or fewer regional lymph nodes with extranodal extension), and pN3 (metastasis in 4 or more regional LNs). According to the current and proposed N classification, the five-year CSS of penile cancer patients with pN1, pN2 and pN3 was 85.8%, 39.0%, and 19.7%; and with pN1, pN2 and pN3 was 79.8%, 39.3% and 15.3%, which almost all showed significant difference (P < 0.001, P = 0.259) (P < 0.001, P < 0.001). Multivariable predictive accuracy of the proposed and current N staging was 76.48% and 70.92% (5.56% gain; P < 0.001). With a multivariable model of clinical features, both current (hazard ratio [HR], 7.761, 10.612; P < 0.001, P < 0.001) and proposed N stages (HR, 3.792, 3.971; P < 0.001, P < 0.001) exhibited independent effects on survival. The proposed N classification is superior to the current one, which is simpler and provides more accurate prognosis.

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Regulatory mechanisms of HIF-1 activity: Two decades of knowledge

Abstract

Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator of various genes related to cellular adaptive responses to hypoxia. Dysfunctions in the regulatory systems of HIF-1 activity have been implicated in the pathogenesis of various diseases including malignant tumors, and, thus, elucidating the molecular mechanisms underlying the activation of HIF-1 is eagerly desired for the development of novel anti-cancer strategies. The importance of the oxygen-dependent and ubiquitin-mediated proteolysis of the regulatory subunit of HIF-1 (HIF-1α) was first reported in 1997. Since then, accumulating evidence has revealed that HIF-1α may become stable and active, even under normoxic conditions; e.g. when disease-associated genetic and functional alterations in some genes trigger the aberrant activation of HIF-1 regardless of the oxygen conditions. We herein review the last two decades of knowledge, since 1997, on the regulatory mechanisms of HIF-1 activity from conventional oxygen- and proteolysis-dependent mechanisms to up-to-the-minute information on cancer-associated genetic and functional alteration-mediated mechanisms.

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The new metformin derivative HL156A prevents oral cancer progression by inhibiting the IGF/Akt/mTOR pathways

Summary

Metformin is a biguanide widely prescribed as an antidiabetic drug for type 2 diabetes mellitus patients. The purpose of this study was to observe the effects of the new metformin derivative, HL156A, on human oral cancer cell and to investigate its possible mechanisms. It was observed that HL156A significantly decreased FaDu and YD-10B cell viability and colony formation in a dose dependent manner. HL156A also markedly reduced wound closure and migration of FaDu and YD-10B cells. We observed that HL156A decreased mitochondrial membrane potential and induced ROS levels and apoptotic cells with caspase-3 and -9 activation. HL156A inhibited the expression and activation of IGF-1 and its downstream proteins, AKT, mTOR, and ERK1/2. In addition, HL156A activated AMPK-NF-κB signaling of FaDu and YD-10B cells. A xenograft mouse model further revealed that HL156A suppressed AT84 mouse oral tumor growth, accompanied by downregulated p-IGF-1, p-mTOR, PCNA and promoted p-AMPK and TUNEL expression. These results suggest the potential value of the new metformin derivative HL156A as a candidate for a therapeutic modality for the treatment of oral cancer.

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Nimotuzumab combined with concurrent chemoradiotherapy in Japanese patients with esophageal cancer: a phase I study

Summary

Nimotuzumab is a humanized anti-epidermal growth factor receptor IgG1 monoclonal antibody. This phase I study assessed the tolerability, safety, efficacy, and PK of nimotuzumab in combination with chemoradiotherapy in Japanese patients with esophageal cancer. Patients with stage II, III, and IV esophageal cancer were enrolled. Patients were planned to receive nimotuzumab (level 1: 200 mg/week for 25 weeks; or level 2: 400 mg/week in the chemoradiation period, 400 mg biweekly in an additional chemotherapy period [8 weeks after the chemoradiation period] and a maintenance therapy period [after chemotherapy to 25 weeks]) combined with cisplatin (75 mg/m² on day 1) and fluorouracil (1000 mg/m² on days 1 to 4) in the chemoradiation and additional chemotherapy periods. Radiotherapy was administered concurrently at 50.4 Gy. A total of 10 patients were enrolled in level 1. Dose-limiting toxicities were observed in two patients (grade 3 infection and renal disorder). The maximum tolerated dose was estimated to be at least 200 mg/week and the dose was not escalated to level 2. The most common grade ≥3 toxicities were lymphopenia (90%), leukopenia (60%), neutropenia (50%), and febrile neutropenia, decreased appetite, hyponatremia, and radiation esophagitis (30% each). Neither treatment-related death nor grade ≥3 skin toxicity was observed in any patient. Complete response rate was 50%. Progression-free survival was 13.9 months. One- and 3-year survival rates were 75% and 37.5%, respectively. Immunogenicity was not reported in any patient. Nimotuzumab in combination with concurrent chemoradiotherapy was tolerable and effective for Japanese patients with esophageal cancer.

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Altered motor plasticity in an acute relapse of multiple sclerosis

Abstract

In relapsing-remitting MS (RRMS) the symptoms of a clinical relapse subside over time. Neuroplasticity is believed to play an important compensatory role. In this study we assessed excitability-decreasing plasticity during an acute relapse of MS and 12 weeks afterwards. Motor plasticity was examined in 19 patients with clinically isolated syndrome or RRMS during a steroid-treated relapse (t1) and 12 weeks afterwards (t2) using paired-associative stimulation (PAS10). This method combines repetitive electric nerve stimulation with transcranial magnetic stimulation of the contralateral motor cortex to model long-term synaptic depression in the human cortex. Additionally, 19 age-matched healthy controls were assessed. Motor evoked potentials of the abductor pollicis brevis muscle were recorded before and after intervention. Clinical disability was assessed by the Multiple Sclerosis Functional Composite and the subscore of the nine-hole peg test taken as a measure of hand function. The effect of PAS10 was significantly different between controls and patients: At t1, but not at t2, baseline-normalized postinterventional amplitudes were significantly higher in patients (106 [IQR 98 – 137] % post10-15 and 111 [IQR 88-133] % post20-25) compared to controls (92 [IQR 85-111] % and 90 [IQR 75-102] %). Additional exploratory analysis indicated a potentially excitability-enhancing effect of PAS10 in patients as opposed to controls. Significant clinical improvement between t1 and t2 was not correlated with PAS10 effects.

Our results indicate an alteration of PAS10-induced synaptic plasticity during relapse, presumably reflecting a polarity shift due to metaplastic processes within the motor cortex. Further studies will need to elucidate the functional significance of such changes for the clinical course of MS.

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Perceptual Changes with Monopolar and Phantom electrode stimulation

Computational modeling of the human auditory periphery: auditory-nerve responses, evoked potentials and hearing loss

A phenomenological model of the synapse between the inner hair cell and auditory nerve: Implications of limited neurotransmitter release sites

Publication date: Available online 28 December 2017
Source:Hearing Research
Author(s): Ian C. Bruce, Yousof Erfani, Muhammad S.A. Zilany
Peterson and Heil [Hear. Res., In Press] have argued that the statistics of spontaneous spiking in auditory nerve fibers (ANFs) can be best explained by a model with a limited number of synaptic vesicle docking (release) sites (∼4) and a relatively-long average redocking time (∼16–17 ms) for each of the sites. In this paper we demonstrate how their model can be: i) generalized to also describe sound-driven ANF responses and ii) incorporated into a well-established and widely-used model of the entire auditory periphery [Zilany et al., J. Acoust. Soc. Am. 135, 283–286, 2014]. The responses of the new model exhibit substantial improvement in several measures of ANF spiking statistics, and predicted physiological forward-masking and rate-level functions from the new model structure are shown to also better match published physiological data.

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Evaluation of the Supraglottic and Subglottic Activities Including Acoustic Assessment of the Opera-Chant Singers

Publication date: Available online 28 December 2017
Source:Journal of Voice
Author(s): Emine Petekkaya, Ahmet Hilmi Yücel, Özgür Sürmelioğlu
Opera and chant singers learn to effectively use aerodynamic components by breathing exercises during their education. Aerodynamic components, including subglottic air pressure and airflow, deteriorate in voice disorders. This study aimed to evaluate the changes in aerodynamic parameters and supraglottic structures of men and women with different vocal registers who are in an opera and chant education program. Vocal acoustic characteristics, aerodynamic components, and supraglottic structures were evaluated in 40 opera and chant art branch students. The majority of female students were sopranos, and the male students were baritone or tenor vocalists. The acoustic analyses revealed that the mean fundamental frequency was 152.33 Hz in the males and 218.77 Hz in the females. The estimated mean subglottal pressures were similar in females (14.99 cmH2O) and in males (14.48 cmH2O). Estimated mean airflow rates were also similar in both groups. The supraglottic structure compression analyses revealed partial anterior-posterior compressions in 2 tenors and 2 sopranos, and false vocal fold compression in 2 sopranos. Opera music is sung in high-pitched sounds. Attempts to sing high-pitched notes and frequently using register transitions overstrain the vocal structures. This intense muscular effort eventually traumatizes the vocal structures and causes supraglottic activity.

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The Influence of Noise on the Vocal Dose in Women

Publication date: Available online 28 December 2017
Source:Journal of Voice
Author(s): Alessandra Terra Vasconcelos Rabelo, Juliana Nunes Santos, Bárbara Oliveira Souza, Ana Cristina Côrtes Gama, Max de Castro Magalhães
ObjectiveThe objective of this study was to evaluate if noise interferes with the vocal dose in women without vocal complaints.Study designThis is an experimental and comparative study.MethodsData were collected on 27 women between 22 and 50 years of age without vocal complaints in a university classroom. Speech-language pathology evaluation was performed employing auditory-perceptual analysis and a vocal symptom questionnaire. The acoustics of the classroom were evaluated via both observation of the characteristics of the room and the quantification of background noise and reverberation time. Two distinctive acoustic conditions were created for evaluations: condition 1, a room without acoustic treatment and without noise reproduction, and condition 2, a room without acoustic treatment with noise reproduction. Each participant was evaluated individually in both acoustic conditions. To obtain vocal dose data, a vocal dosimeter was used. Subjects were asked to perform two 10-minute readings, one in each acoustic condition. The order of conditions was randomized between subjects. Subjects were instructed to complete the reading tasks at the vocal intensity deemed appropriate to be heard by a listener in the back of the room. t Tests and the Wilcoxon test were employed to compare parameters across subjects and conditions.ResultsFundamental frequency, vocal intensity, percentage of phonation, and cycle dose significantly increased in the background noise condition.ConclusionA positive relation between vocal dose and the presence of excessive noise in the environment was observed.

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The Effectiveness of the EASE Scale in the Development of a Vocal Warm-up Program for an Amateur Choir

Publication date: Available online 28 December 2017
Source:Journal of Voice
Author(s): Daniel Lucas Picanço Marchand, Fernanda Salles Kavaliunas, Mauriceia Cassol
ObjectivesThis study aims to assess the effectiveness of the EASE-BR (Evaluation of the Ability to Sing Easily for Brazil) protocol in the development of a vocal warm-up program for members of an amateur choir.Study DesignThis is a prospective cross-sectional study measuring pre- and postintervention results at two moments.MethodsForty-four subjects filled out a questionnaire to characterize the sample and underwent two major applications of the EASE-BR scale—the first to determine the group's vocal requirements and the second to assess the performance after the application of a customized vocal warm-up routine.ResultsOverall reduction of the scores in the postintervention moment has been determined. The score of 16 of the questions (72.7%) showed a statistically relevant reduction after the intervention.ConclusionsThe EASE-BR scale proved a valuable assessment tool and its use may help develop customized vocal warm-up programs for different types of singers.

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Balance Training Does Not Alter Reliance on Visual Information during Static Stance in Those with Chronic Ankle Instability: A Systematic Review with Meta-Analysis

Abstract

Background

Visual, vestibular, and somatosensory systems contribute to postural control. Chronic ankle instability (CAI) patients have been observed to have a reduced ability to dynamically shift their reliance among sources of sensory information and rely more heavily on visual information during a single-limb stance relative to uninjured controls. Balance training is proven to improve postural control but there is a lack of evidence regarding the ability of balance training programs to alter the reliance on visual information in CAI patients.

Objective

Our objective was to determine if balance training alters the reliance on visual information during static stance in CAI patients.

Methods

The PubMed, CINAHL, and SPORTDiscus databases were searched from their earliest available date to October 2017 using a combination of keywords. Study inclusion criteria consisted of (1) using participants with CAI; (2) use of a balance training intervention; and (3) calculation of an objective measure of static postural control during single-limb stance with eyes open and eyes closed. Sample sizes, means, and standard deviations of single-leg balance measures for eyes-open and eyes-closed testing conditions before and after balance training were extracted from the included studies. Eyes-open to eyes-closed effect sizes [Hedges' g and 95% confidence intervals (CI)] before and after balance training were calculated, and between-study variability for heterogeneity and potential risks of publication bias were examined.

Results

Six studies were identified. The overall eyes-open to eyes-closed effect size difference between pre- and post-intervention assessments was not significant (Hedges' g effect size = 0.151, 95% CI = − 0.151 to 0.453, p = 0.26). This result indicates that the utilization of visual information in individuals with CAI during the single-leg balance is not altered after balance training. Low heterogeneity (Q(5) = 2.96, p = 0.71, I ² = 0%) of the included studies and no publication bias were found.

Conclusion

On the basis of our systematic review with meta-analysis, it appears that traditional balance training protocols do not alter the reliance on visual information used by CAI patients during a single-leg stance.

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Longitudinal clinico-pathological data of the progression of oral mucosal melanoma–report of two cases and literature review

Publication date: Available online 28 December 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Paras B. Patel, John M. Wright, David R. Kang, Yi-Shing Lisa Cheng
Oral mucosal melanoma (OMM) is notorious for having a poor prognosis. Recognition of the early features of OMM by both clinicians and pathologists can play an important role in improving survival. Therefore, the purpose of this report is to increase awareness of the early features of OMM, by presenting two cases with longitudinal clinical and histopathological documentation showing progression of OMM from a deceptively bland pre-malignant (non-invasive) oral melanocytic lesion (POML). Analyzing the clinical and histopathological features of POML in our cases, and those in the literature, we found that the concerning features are: 1) clinically, a pigmented lesion violating the ABCDE criteria or showing multiple recurrences; and 2) histologically, a melanocytic proliferation, in either a lentiginous or pagetoid pattern with or without cellular atypia. Making a diagnosis of POML prospectively is often challenging. Increasing awareness of the clinical and histopathological features, and complete surgical excision of POML is emphasized.

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BTB/POZ domain-containing protein 7 is inversely associated with fibronectin expression in salivary adenoid cystic carcinoma

Publication date: Available online 28 December 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Yunxia Liu, Jiwu Song, Jun Zhang, Liu Yang, Zongxia Liu, Xuxia Wang
ObjectiveThis study was aimed to investigate the relationship between BTB/POZ domain-containing protein 7 (BTBD7) and fibronectin (FN) expression in salivary adenoid cystic carcinoma (SACC) and the function of BTBD7 in proliferation, migration and invasion of SACC cells.MethodsThe BTBD7 and FN expression in SACC and non-tumor salivary tissues as well as SACC cells were characterized by immunohistochemistry and immunofluorescence. The effect of BTBD7 silencing on the proliferation, migration and invasion of SACC-LM cells were determined by wound healing and transwell invasion assays.ResultsThe percentages of SACC with positive BTBD7 expression were significantly higher than that of those with FN expression. BTBD7 silencing significantly increased the relative levels of FN expression and inhibited the proliferation, migration and invasion of SACC-LM cells.ConclusionsThe data indicated that BTBD7 was inversely associated with FN expression in SACC. BTBD7 may inhibit FN expression, but promote proliferation, migration and invasion of SACC-LM cells. Hence, BTBD7 may be associated with metastasis and a new therapeutic target for intervention of SACC.

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Osteonecrosis of the jaw unrelated to medication or radiotherapy

Publication date: Available online 28 December 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Yusuf Gadiwalla, Vinod Patel
Osteonecrosis of the jaw (ONJ) is an increasingly common condition primarily due to the rise of medication related osteonecrosis of the jaw (MRONJ) and osteoradionecrosis (ORN). Apart from MRONJ and ORN there remains a wide and varied range of rare causes and diseases that can lead to a clinical presentation of ONJ. This article aims to highlight alternatives causes of jaw necrosis following review of the literature to aid diagnosis and treatment planning for dental and head and neck specialities.

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Oral lymphangiectasias and Crohn's disease: two case reports

Publication date: Available online 28 December 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Sheila Galvin, Stephen R. Flint, Mary E. Toner, Claire M. Healy, Kumara Ekanayake
Lymphangiectasias, or acquired lymphangiomas, are rare in the oral cavity, more typically occurring on the skin or genital area, and to our knowledge have not been reported previously in association with Crohn's disease. Lymphangiectasias can occur at any age and develop secondary to chronic obstruction of lymphatics. This differentiates them from congenital lymphangiomas which are congenital malformations of the lymphatic system. We present two cases of oral lymphangiectasias associated with Crohn's disease, one of which was treated successfully with cryotherapy.

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Robotic-assisted laparoscopic surgery for pediatric tumors: a bicenter experience

Abstract

Mini-invasive surgery is more and more integrated in pediatric surgery. The robotic-assisted surgery brought new advantages from which the patient and the surgeon could benefit compared to laparoscopy. Its use in oncological surgery is still controversial. 12 robotic-assisted tumor resections with the da Vinci Surgical Robot (Intuitive Surgical, Sunnyvale, CA) were attempted in 11 children (mean age 7.65 years; age range 0.75–16.75 years; mean weight 30.3 kg; weight range 8.6–62 kg) in two centers. Mean total operative time was 145 min (range 72–263 min). 1 procedure (8.3%) was converted. The pathology included renal tumors (n = 2; one nephroblastoma, one metanephric adenoma), adrenal tumors (n = 9; three neuroblastomas, two pheochromocytomas, two adrenocortical adenomas, one cystic lymphangioma, one paraganglioma) and a pancreatic tumor (n = 1; one pancreatic cyst). 4 tumors (33.3%) were malignant. Every patient underwent a R0 resection. 1 child (8.3%) developed a post operative complication. Mean length of hospitalization was 3.0 days (range 2–5 days). Followup averaged 3.3 years with no recurrence. All children are alive. Robot-assisted MIS seems to be safe and feasible in pediatric tumors. The oncological surgical principles were respected in our series with low morbi/mortality and good long-term results. Robotic surgery and its technical advantages bring potential benefits for children with cancer. It has a role to play in pediatric oncological surgery but its place and indications still need to be better defined.

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Phenotype and genotype of muscle ryanodine receptor rhabdomyolysis-myalgia syndrome

Objectives

Rhabdomyolysis and myalgia are common conditions, and mutation in the ryanodine receptor 1 gene (RYR1) is suggested to be a common cause. Due to the large size of RYR1, however, sequencing has not been widely accessible before the recent advent of next-generation sequencing technology and limited phenotypic descriptions are therefore available.

Material & Methods

We present the medical history, clinical and ancillary findings of patients with RYR1 mutations and rhabdomyolysis and myalgia identified in Denmark, France and The Netherlands.

Results

Twenty-two patients with recurrent rhabdomyolysis (CK > 10 000) or myalgia with hyperCKemia (>1.5 × ULN) and a RYR1 mutation were identified. One had mild wasting of the quadriceps muscle, but none had fixed weakness. Symptoms varied from being restricted to intense exercise to limiting ADL function. One patient developed transient kidney failure during rhabdomyolysis. Two received immunosuppressants on suspicion of myositis. None had episodes of malignant hyperthermia. Muscle biopsies were normal, but CT/MRI showed muscle hypertrophy in most. Delay from first symptom to diagnosis was 12 years on average. Fifteen different dominantly inherited mutations were identified. Ten were previously described as pathogenic and 5 were novel, but rare/absent from the background population, and predicted to be pathogenic by in silico analyses. Ten of the mutations were reported to give malignant hyperthermia susceptibility.

Conclusion

Mutations in RYR1 should be considered as a significant cause of rhabdomyolysis and myalgia syndrome in patients with the characteristic combination of rhabdomyolysis, myalgia and cramps, creatine kinase elevation, no weakness and often muscle hypertrophy.

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Subthalamic deep brain stimulation and trunk posture in Parkinson's disease

Objectives

We sought to assess the efficacy of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD)-associated trunk posture abnormalities retrospectively analyzing data from 101 patients reporting mild-to-severe trunk posture abnormalities of a cohort of 216 PD patients treated with STN-DBS at our center.

Methods

Abnormal trunk posture was rated on a scale of 0 (normal) to 4 (marked flexion with an extreme abnormality of posture) as per the grading score reported in the Unified Parkinson's Disease Rating Scale. The independent effect of STN-DBS on trunk posture was assessed comparing Medication-Off (presurgery) vs Stimulation-On/Medication-Off (post-surgery). The combined effect of STN-DBS plus levodopa was evaluated comparing Medication-On (presurgery) vs Stimulation-On/Medication-On (post-surgery). Analyses were conducted considering both the entire cohort of patients and the subgroup with camptocormia (CMC) and Pisa syndrome (PS).

Results

The independent effect of STN-DBS resulted in a 41.4% improvement in abnormal trunk posture severity (P < .001), with 78.2% of patients (n = 79) reporting an improvement of at least 1 point. The combined effect of STN-DBS and levodopa resulted in a 30.9% improvement (P = .061), with 54.5% of patients (n = 55) reporting an improvement of at least 1 point.

The subanalysis of patients with CMC (n = 23) and PS (n = 5) showed a 42.7% improvement in abnormal posture severity when considering the independent effect of STN-DBS (P < .001) and 30.5% when considering the combined effect of STN-DBS and levodopa (P < .001).

Conclusions

STN-DBS may have the potential for improving posture in patients with advanced PD.

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Application of a Skin Adhesive to Maintain Seal in NPWT

A technique using a cyanoacrylate-based tissue adhesive may offer a new method of maintaining an airtight seal in NPWT.
Wounds

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Evaluation of the Supraglottic and Subglottic Activities Including Acoustic Assessment of the Opera-Chant Singers

The Influence of Noise on the Vocal Dose in Women

The Effectiveness of the EASE Scale in the Development of a Vocal Warm-up Program for an Amateur Choir

Formal models and quantitative measures of multisensory integration: a selective overview

Abstract

Multisensory integration (MI) is defined as the neural process by which unisensory signals are combined to form a new product that is significantly different from the responses evoked by the modality-specific component stimuli. In recent years, MI research has seen exponential growth in the number of empirical and theoretical studies. This paper presents a selective overview of formal modeling approaches to MI. Emphasis is on models and measures for behavioral paradigms like, e.g., localization, judgment of temporal order or simultaneity, and reaction times, but some concepts for the modeling of single cell spike rates are treated as well. We identify a number of essential concepts underlying most model classes, like Bayesian causal inference, probability summation, coactivation, and time window of integration. Quantitative indexes for measuring and comparing the strength of MI across different paradigms are also discussed. Whereas progress over the last years is remarkable, we point out some strengths and weaknesses of the modeling approaches and discuss some obstacles towards a unified theory of MI.

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Nanomaterials at the neural interface

Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50
Author(s): Denis Scaini, Laura Ballerini
Interfacing the nervous system with devices able to efficiently record or modulate the electrical activity of neuronal cells represents the underlying foundation of future theranostic applications in neurology and of current openings in neuroscience research. These devices, usually sensing cell activity via microelectrodes, should be characterized by safe working conditions in the biological milieu together with a well-controlled operation-life. The stable device/neuronal electrical coupling at the interface requires tight interactions between the electrode surface and the cell membrane. This neuro-electrode hybrid represents the hyphen between the soft nature of neural tissue, generating electrical signals via ion motions, and the rigid realm of microelectronics and medical devices, dealing with electrons in motion. Efficient integration of these entities is essential for monitoring, analyzing and controlling neuronal signaling but poses significant technological challenges. Improving the cell/electrode interaction and thus the interface performance requires novel engineering of (nano)materials: tuning at the nanoscale electrode's properties may lead to engineer interfacing probes that better camouflaged with their biological target. In this brief review, we highlight the most recent concepts in nanotechnologies and nanomaterials that might help reducing the mismatch between tissue and electrode, focusing on the device's mechanical properties and its biological integration with the tissue.

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COX-2/sEH Dual Inhibitor PTUPB Potentiates the Anti-tumor Efficacy of Cisplatin

Cisplatin-based therapy is highly toxic, but moderately effective in most cancers. Concurrent inhibition of cyclooxygenase-2 (COX-2) and soluble epoxide hydrolase (sEH) results in anti-tumor activity, and has organ protective effects. The goal of this study was to determine the anti-tumor activity of PTUPB, an orally bioavailable COX-2/sEH dual inhibitor, in combination with cisplatin and gemcitabine (GC) therapy. NSG mice bearing bladder cancer patient-derived xenografts were treated with vehicle, PTUPB, cisplatin, GC or combinations thereof. Mouse experiments were performed with two different PDX models. PTUPB potentiated cisplatin and GC therapy, resulting in significantly reduced tumor growth and prolonged survival. PTUPB plus cisplatin was no more toxic than cisplatin single agent treatment as assessed by body weight, histochemical staining of major organs, blood counts and chemistry. The combination of PTUPB and cisplatin increased apoptosis and decreased phosphorylation in the MAPK/ERK and PI3K/AKT/mTOR pathways compared to controls. PTUPB treatment did not alter platinum-DNA adduct levels, which is the most critical step in platinum-induced cell death. The in vitro study using the combination index method showed modest synergy between PTUPB and platinum agents only in 5637 cell line among several cell lines examined. However, PTUPB is very active in vivo by inhibiting angiogenesis. In conclusion, PTUPB potentiated the anti-tumor activity of cisplatin-based treatment without increasing toxicity in vivo, and has potential for further development as a combination chemotherapy partner.

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Prognostic values of the integrated model incorporating the volume of metastatic regional cervical lymph node and pretreatment serum Epstein–Barr virus DNA copy number in predicting distant metastasis in patients with N1 nasopharyngeal carcinoma

Abstract

Background

According to the 7th edition of the American Joint Committee on Cancer (AJCC) staging system, over 50% of patients with nasopharyngeal carcinoma (NPC) have N1 disease at initial diagnosis. However, patients with N1 NPC are relatively under-researched, and the metastasis risk of this group is not well-stratified. This study aimed to evaluate the prognostic values of gross tumor volume of metastatic regional lymph node (GTVnd) and pretreatment serum copy number of Epstein–Barr virus (EBV) DNA in predicting distant metastasis of patients with N1 NPC, and to develop an integrated prognostic model that incorporates GTVnd and EBV DNA copy number for this group of patients.

Methods

The medical records of 787 newly diagnosed patients with nonmetastatic, histologically proven N1 NPC who were treated at Sun Yat-sen University Cancer Center between November 2009 and February 2012 were analyzed. Computed tomography-derived GTVnd was measured using the summation-of-area technique. Blood samples were collected before treatment to quantify plasma EBV DNA. The receiver operating characteristic (ROC) curve analysis was used to evaluate the cut-off point for GTVnd, and the area under the ROC curve was used to assess the predicted validity of GTVnd. The survival rates were assessed by Kaplan–Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model.

Results

The 5-year distant metastasis-free survival (DMFS) rates for patients with GTVnd > 18.9 vs. ≤ 18.9 mL were 82.2% vs. 93.2% (P < 0.001), and for patients with EBV DNA copy number > 4000 vs. ≤ 4000 copies/mL were 83.5% vs. 93.9% (P < 0.001). After adjusting for GTVnd, EBV DNA copy number, and T category in the Cox regression model, both GTVnd > 18.9 mL and EBV DNA copy number > 4000 copies/mL were significantly associated with poor prognosis (both P < 0.05). According to combination of GTVnd and EBV DNA copy number, all patients were divided into low-, moderate-, and high-risk groups, with the 5-year DMFS rates of 96.1, 87.4, and 73.8%, respectively (P < 0.001). Multivariate analysis confirmed the prognostic value of this model for distant metastatic risk stratification (hazard ratio [HR], 4.17; 95% confidence interval [CI] 2.34–7.59; P < 0.001).

Conclusions

GTVnd and serum EBV DNA copy number are independent prognostic factors for predicting distant metastasis in NPC patients with N1 disease. The prognostic model incorporating GTVnd and EBV DNA copy number may improve metastatic risk stratification for this group of patients.

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Choice of postoperative radiation for stage IIIA pathologic N2 non-small cell lung cancer: impact of metastatic lymph node number

Abstract

Background

Postoperative radiation (PORT) is an option for non-small cell lung cancer (NSCLC) patients with resectable stage IIIA pathological N2 status (pN2). For patients with PORT, this study aims to investigate the impact of the exact number of positive lymph nodes (LNs) on overall survival (OS) and lung cancer-specific survival (LCSS).

Methods

Within the Surveillance, Epidemiology, and End Results database, we identified 3373 patients with stage IIIA pathological N2 status (pN2) NSCLC who underwent a lobectomy or pneumonectomy from 2004 to 2013. OS and LCSS were compared among patients coded as receiving PORT or observation. The proportional hazards model was applied for investigation.

Results

OS and LCSS favored PORT for patients with stage IIIA (pN2) NSCLC. Multivariable analyses showed that PORT and the exact number of positive LNs (n ≤ 3) were independently associated with better OS and LCSS. Both better OS and LCSS emerged for positive LNs (n > 3) after the use of PORT in survival analyses, whereas the benefits of OS and LCSS were not observed anymore for positive LNs (n ≤ 3) group. More importantly, multivariable analyses showed that the use of PORT is an independent risk factor of survival for positive LNs (n > 3) but not for positive LNs (n ≤ 3).

Conclusions

In Stage IIIA (pN2) NSCLC, the use of PORT demonstrated better survival results than no PORT for patients with positive LNs (n > 3), but not for patients with positive LNs (n ≤ 3).

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Balloon dilatation of the Eustachian tube in adult patients with chronic dilatory tube dysfunction: a retrospective cohort study

Abstract

Objectives

The aim of this study is to assess the subjective and objective short-term results and safety of transnasal balloon dilatation of the Eustachian tube (BET) in adult patients with chronic dilatory Eustachian tube dysfunction (ETD).

Design

Retrospective cohort study. Data collection was performed preoperatively, 1 and 3 months after BET.

Setting

Tertiary referral hospital.

Participants

A cohort of 42 consecutive patients (66 ears).

Main outcome measures

ETDQ-7 score, bone conduction threshold, air-bone gap, the ability to perform Valsalva's and/or Toynbee's manoeuvre, tympanic membrane and middle ear conditions were collected pre- and postoperatively. Subjective satisfaction and complications were collected postoperatively.

Results

The ETDQ-7 score improved significantly from 4.28 to 3.09 1 month postoperatively and from 4.10 to 2.96 3 months postoperatively. Bone conduction thresholds did not differ significantly postoperatively. A significant improvement of air-bone gap was found postoperatively. The tympanic membrane and middle ear condition showed improvement in 62%. Subjective satisfaction 1 and 3 months postoperatively was around 43 and 48%. A small number of minor (self-limiting) complications did occur.

Conclusions

BET has shown to be a safe intervention, which may have a positive effect on objective and subjective indicators for chronic dilatory ETD in adult patients. We observed subjective positive effects in less than half of the patients. For certain indications, there was a measurable positive effect on the findings of the eardrum and ETDQ-7, whereas in other patients it seemed not to have any effect at all. Careful patient selection may improve this success rate. Randomized controlled trials with a prolonged follow-up are required to assess the value of BET in comparison to grommets.

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The effect of selective internal radiation therapy with yttrium-90 resin microspheres on lung carbon monoxide diffusion capacity

Abstract

Background

Selective internal radiation therapy (SIRT) with embolization of branches of the hepatic artery is a valuable therapeutic tool for patients with hepatic malignancies; however, it is also associated with lung injury risk due to shunting. Diffusion capacity of the lungs for carbon monoxide (DLCO) is a clinically significant lung function test, and worsening in DLCO is suggested to reflect a limited gas exchange reserve caused by the potential toxicity of chemoradiotherapy or it may be a marker of related lung injury. This study aimed to examine the changes in DLCO during SIRT with resin microspheres in newly treated and retreated patients. Forty consecutive patients who received SIRT for a variety of malignant conditions were included. All subjects were treated with Yttrium-90 labelled resin microspheres. DLCO tests were performed after the procedures. In addition, patients were specifically followed for radiation pneumonitis.

Results

The mean DLCO did not significantly change after the first (82.8 ± 19.4 vs. 83.1 ± 20.9, p = 0.921) and the second treatments (87.4 ± 19.7 vs. 88.6 ± 23.2, p = 0.256). Proportion of patients with impaired DLCO at baseline was not altered significantly after the first (37.5 vs. 45.0%, p = 0.581) and the second treatments (27.3 vs. 27.3%, p = 1.000). Also, percent change in DLCO values did not correlate with radiation dose, lung shunt fraction, or lung exposure dose (p > 0.05 for all comparisons). None of the patients developed radiation pneumonitis.

Conclusions

Our results suggest that no significant change in DLCO in association with SIRT occurs, both after the first or the second treatment sessions. Further larger studies possibly with different protocols are warranted to better delineate DLCO changes after SIRT in a larger spectrum of patients.

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Balloon dilatation of the Eustachian tube in adult patients with chronic dilatory tube dysfunction: a retrospective cohort study

Abstract

Objectives

Design

Retrospective cohort study. Data collection was performed preoperatively, 1 and 3 months after BET.

Setting

Tertiary referral hospital.

Participants

A cohort of 42 consecutive patients (66 ears).

Main outcome measures

Results

Conclusions

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Balloon dilatation of the Eustachian tube in adult patients with chronic dilatory tube dysfunction: a retrospective cohort study

Abstract

Objectives

Design

Retrospective cohort study. Data collection was performed preoperatively, 1 and 3 months after BET.

Setting

Tertiary referral hospital.

Participants

A cohort of 42 consecutive patients (66 ears).

Main outcome measures

Results

Conclusions

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Preface

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High CEA levels in a case of resected colorectal cancer: delayed diagnosis of metachronous medullary thyroid cancer

Abstract

Background

Carcinoembryonic antigen (CEA) is one of the most widely used tumor markers, and its value in the surveillance of post-operative colorectal cancer is well established. Fluorodeoxyglucose-positron emission tomography (FDG-PET) has been clinically used in colorectal cancer imaging including preoperative staging, evaluation of therapeutic response, detection of disease recurrence, and investigation of unexplained rising tumor markers.

Case presentation

We report a case of resected colorectal cancer presented with rising CEA levels in 5 years, and FDG-PET revealed no definitive evidence of recurrence except abnormal focal FDG uptake in the right thyroid lobe. However, fine needle aspiration cytology (FNAC) of the thyroid nodule showed negative for malignancy. Progressively rising CEA levels were noted over the following 5 years, but serial follow-up examinations did not find evidence of recurrence. Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) was performed subsequently and again showed focal FDG uptake in the right thyroid lobe. This time, FNAC revealed positive for malignancy, in favor of medullary thyroid carcinoma (MTC). The patient underwent total thyroidectomy and modified radical neck dissection, and MTC with cervical nodal metastasis (pT3N1) was diagnosed. He had cervical lymph nodes recurrence 2 years later, which was resected.

Conclusions

This case reminded us that FDG-PET/CT may detect occult tumors resulting in CEA elevation other than colorectal cancer. Moreover, FNA has a higher false negative rate in detecting MTC than other forms of thyroid cancer. Repeat FNAC for the initial negative cytology result and measure of serum calcitonin for the early MTC detection could be more helpful to avoid the delay in MTC diagnosis.

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Postoperative extracranial metastasis from glioblastoma: a case report and review of the literature

Abstract

Background

Glioblastoma is the most common primary malignant brain tumor. Extraneural metastases are rarely reported in the literature.

Case presentation

We report a case of a 38-year-old patient who was diagnosed with glioblastoma in 2015. Four months after surgery, local relapse was found and the patient received a second surgery. After another 4 months, we found a hard mass in the right posterior neck when she admitted to our department for fourth cycle of adjuvant chemotherapy. Immunohistochemical investigation supported the diagnosis of glioblastoma metastases to the neck after resection of the right neck mass. A few days later, spinal vertebral magnetic resonance imaging (MRI) confirmed multiple metastases in the thoracic, lumbar, sacral, and bilateral iliac bones.

Conclusions

Glioblastoma is the most common primary malignant brain tumor. Whole tumor resection and early radiotherapy and chemotherapy can delay recurrence and prolong survival. Extracranial metastases are extremely rare. We report this case with the aim of bringing attention to extracranial metastasis of brain glioma.

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Bronchoscopic Management of Central Airway Obstruction Secondary to Rheumatoid Arthritis

No abstract available

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Executive Summary of Training and Competence Standards for the Interventional Pulmonology Master Program in Italy

No abstract available

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Clinical Success Stenting Distal Bronchi for “Lobar Salvage” in Bronchial Stenosis

Background: Airway stents are traditionally used in central airway obstructions to maintain airway patency. Historically, distal bronchial stenting within lobar and segmental bronchi has not been amenable to stenting. In addition, there are questionable benefits to stenting small airways. The Atrium iCast stent is a polytetrafluoroethylene covered stainless steel balloon deployed stent which can be deployed through a flexible bronchoscope under direct visualization. The purpose of this study was to assess the feasibility, complications, and long-term impact of using this stent in patients with lobar bronchial stenosis either secondary to malignancy or benign etiologies. Methods: All records of patients who had the placement of an iCast stent were reviewed over 3.5 years. For each patient the age, sex, location, histology, stent size, duration of stent placement, radiographic improvement, and complications were collected. Results: A total of 122 iCast stents were deployed in 38 patients with lobar bronchial stenosis. The average age was 58 years with 50% male. The etiology included 45% malignant and 55% due to benign conditions. In total, 18.5% patients had stents placed in >1 segment. There was an average of 4 procedures per patient with a mean time to stent revision or removal of 85 days. All patients had symptomatic or radiographic improvement. Common complications included migration (10%), granulation tissue formation (5%), deployment malfunction (2%), stent dislodgement immediately after deployment (2%), mucous plugging (1%), and tumor occlusion (1%). Conclusion: Stenting small airways with lobar salvage is feasible and improves symptoms and radiographic outcomes.

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Risk of Jaw Dislocation With Prolonged Endobronchial Ultrasound-guided Transbronchial Needle Aspiration

No abstract available

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Lobar Airway Stents: Proceed With Caution

No abstract available

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Methylene Blue for Bronchopleural Fistula Localization

A bronchopleural fistula (BPF) is a communication between the pleural space and the bronchial tree. BPFs are challenging to diagnose and are associated with a high morbidity and mortality. Sequential balloon occlusion is commonly used for localization of a BPF. We describe our experience with 4 cases of successful localization of the BPF by instillation of methylene blue into the pleural space through a pigtail catheter, with simultaneous bronchoscopic visualization of dye in the tracheobronchial tree. Two patients were treated with endobronchial valves and 3 had a surgical thoracic muscle flap placed.

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From a Silver Lining to the Silver Anniversary: 25 Years of the Journal of Bronchology and Interventional Pulmonology

No abstract available

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Synergistic inhibition of tumor growth by combination treatment with drugs against different subpopulations of glioblastoma cells

Abstract

Background

Glioma stem cells (GSCs) contribute to tumor recurrence and drug resistance. This study characterizes the tumorigenesis of CD133⁺ cells and their sensitivity to pharmacological inhibition.

Methods

GSCs from human U87 and rat C6 glioblastoma cell lines were isolated via magnetic cell sorting using CD133 as a cancer stem cell marker. Cell proliferation was determined using the WST-1 assay. An intracranial mouse model and bioluminescence imaging were used to assess the effects of drugs on tumor growth in vivo.

Results

CD133⁺ cells expressed stem cell markers and exhibited self-renewal and enhanced tumor formation. Minocycline (Mino) was more effective in reducing the survival rate of CD133⁺ cells, whereas CD133⁻ cells were more sensitive to inhibition by the signal transducer and activator of transcription 3 (STAT3) inhibitor. Inhibition of STAT3 decreased the expression of CD133⁺ stem cell markers. The combination of Mino and STAT3 inhibitor synergistically reduced the cell viability of glioma cells. Furthermore, this combination synergistically suppressed tumor growth in nude mice.

Conclusion

The results suggest that concurrent targeting of different subpopulations of glioblastoma cells may be an effective therapeutic strategy for patients with malignant glioma.

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Clinicopathological factors influencing the outcomes of surgical treatment in patients with T4a hypopharyngeal cancer

Abstract

Background

The purpose of this study was to determine prognostic factors influencing outcomes of surgical treatment in patients with T4a hypopharyngeal cancer.

Methods

The present study enrolled 93 patients diagnosed with T4a hypopharyngeal cancer who underwent primary surgery between January 2005 and December 2015 at six medical centers in Korea. Primary tumor sites included pyriform sinus in 71 patients, posterior pharyngeal wall in 14 patients, and postcricoid region in 8 patients. Seventy-two patients received postoperative radio(chemo)therapy.

Results

Five-year disease-free survival (DFS) and disease-specific survival (DSS) rates were 38% and 45%, respectively. In univariate analysis, 5-year DFS was found to have significant and positive correlations with margin involvement (p < 0.001) and extracapsular spread (p = 0.025). Multivariate analysis confirmed that margin involvement (hazard ratio (HR): 2.81; 95% confidence interval (CI): 1.49-5.30; p = 0.001) and extracapsular spread (HR: 2.08; 95% CI: 1.08-3.99; p = 0.028) were significant factors associated with 5-year DFS. In univariate analysis, cervical lymph node metastasis (p = 0.048), lymphovascular invasion (p = 0.041), extracapsular spread (p = 0.015), and esophageal invasion (p = 0.033) were significant factors associated with 5-year DSS. In multivariate analysis, extracapsular spread (HR: 2.98; 95% CI: 1.39-6.42; p = 0.005) and esophageal invasion (HR: 2.87; 95% CI: 1.38-5.98; p = 0.005) remained significant factors associated with 5-year DSS.

Conclusion

Margin involvement and extracapsular spread are factors influencing recurrence while extracapsular spread and esophageal invasion are factors affecting survival in patients with T4a hypopharyngeal cancer treated by primary surgery.

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Reliability and validity study of Sino-nasal outcome test 22 (Thai version) in chronic rhinosinusitis

Abstract

Background

Chronic rhinosinusitis (CRS) is one of common health conditions that affects patients' health-related quality of life. Our purpose is to assess the reliability and validity of Thai-version of Sino-Nasal Outcome Test 22 in chronic rhinosinusitis.

Methods

Permission for translation of SNOT-22 from English language to Thai language was obtained from the developer. The translation process was done based on the international standard of translation method. A total of 80 subjects were recruited into the study and divided into two groups comprising of 50 patients with chronic rhinosinusitis and 30 healthy volunteers. Cronbach's α and Intraclass correlation coefficient were evaluated for its reliability. Validity test was evaluated against VAS score, SF-36 (Thai version) questionnaire and CT scan (based on Lund-Mackay score). Responsiveness was assessed between pre-operative and post-operative scores in 34 patients.

Results

The Thai version of SNOT-22 showed good reliability according to high value of Cronbach's α coefficient (r = 0.929) and intraclass correlation coefficient (r = 0.935). It also showed good validity by its ability to differential the patients with chronic rhinosinusitis from normal (p < 0.001), and different severity of symptoms (p < 0.05). In addition, the SNOT-22 Thai version also showed good responsiveness when compared between pre-operative and post-operative scores (p < 0.001) and also well-performed in effect size calculation (1.37).

Conclusion

We demonstrated that Thai -version of SNOT-22 has good reliability and validity, suitable for evaluation of chronic rhinosinusitis symptoms together with severity of the disease and response to treatment.

Trial registration

Thai clinical trials registry TCTR20170320003. Date of registration 20/03/2017 (retrospectively registered).

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Causes of higher symptomatic airway load in patients with chronic rhinosinusitis

Abstract

Background

Chronic rhinosinusitis display a variety of different phenotypes. The symptoms of disease are characterised by various signs and symptoms such as nasal congestion, nasal discharge, pressure sensation in the face and reduced or complete loss of smell.

In a patient population undergoing functional endoscopic sinonasal surgery (FESS) for chronic rhinosinusitis, we wanted to investigate the clinical features and explore if the presence of biofilm, nasal polyps or other disease characteristic could serve as predictor for the symptomatic load. A patient group undergoing septoplasty without disease of the sinuses was included as control.

Methods

The Sinonasal outcome test (SNOT-20), EPOS visual analogue scale (VAS) and the Lund-Mackey CT score (LM CT score) were used to examine 23 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), 30 patient with nasal polyps (CRSwNP) and 22 patients with septal deviation. Tissue samples were collected prospectively during surgery. The cohort has previously been examined for the presence of biofilm.

Results

Patients with CRSsNP and CRSwNP had significantly higher degree of symptoms compared to the septoplasty group (SNOT-20 scores of 39.8, 43.6 and 29.9, respectively, p = 0.034). There were no significant differences in the total SNOT-20 or VAS symptoms scores between the CRSsNP and CRSwNP subgroups. However patients with nasal polyps showed significantly higher scores of symptoms related to sinonasal discomfort such as cough, runny nose and need to blow nose (p = 0.011, p = 0.046, p = 0.001 respectively). Patients with nasal polyps showed a significantly higher LM CT score compared to patients without polyps (12.06 versus 8.00, p = 0.001). The presence of biofilm did not impact the degree of symptoms.

Conclusion

The presence of nasal polyp formations in CRS patients was associated with a higher symptomatic airway load as compared to patients without polyps. These findings suggest that nasal polyps could be an indicator of more substantial sinonasal disease. The presence of biofilm did not impact the degree of symptoms, however, as biofilm seem to be a common feature of chronic rhinosinusitis (89% in this cohort), it is more likely to be involved in the development of the CRS, rather than being a surrogate marker for increased symptomatic load.

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Editorial Board/Aims & Scope

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Suggestions for surveillance and radiation strategy in nasopharyngeal carcinoma treated with IMRT: Based on hazard-rate and patterns of recurrence

Nasopharyngeal carcinoma (NPC) is highly radiochemosensitive and its locoregional control rate, which had been improved by the multidisciplinary approach, has approximated to 85% [1–3]. Once recurrence, salvage strategy should be administered [4–9] and the location and extent of therecurrentdisease will determine the optimal therapy [10]. Nevertheless, the efficacies of evidence-based re-treatment are yet unsatisfactory for patients suffered recurrent diseases. It may partly due to the delayed diagnosis of recurrence to advanced stage, which made the re-treatment even harder, so it is essential to discover the recurrence in its infancy.

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Altered fractionation radiotherapy combined with concurrent low-dose or high-dose cisplatin in head and neck cancer: A systematic review of literature and meta-analysis

Improving patient outcomes, as the ultimate goal in oncology, greatly depends on concentrated efforts to promote public health programs, overcome challenges in diagnosis and disease management, and expand health care availability. In squamous cell carcinoma of the head and neck (SCCHN), the Surveillance, Epidemiology, and End Results (SEER) database revealed a substantial enhancement of the 5-year overall survival rate from 54.7% in 1990s to 65.9% in 2000s, particularly in patients with tongue (including base of tongue) and tonsil cancers, in whom the proportion of prognostically favourable human papillomavirus (HPV)-positive cases has been on the rise [1–3].

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Pre-Radiation dental considerations and management for head and neck cancer patients

In 2016, there were over 48,000 new cases of head and neck cancer (HNC) resulting in over 9,500 deaths in the United States alone [1]. Approximately 90% of HNC are squamous cell carcinomas [2]. It is widely known that major risk factors such as smoking, alcohol, and use of smokeless tobacco products are associated with head and neck squamous cell carcinoma (HNSCC) [3,4]. HNSCC has been known to have a high incidence of lymph node metastasis, with over two-thirds of patients presenting with regional lymph node involvement, and 10% presenting with distant metastases [5,6].

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Oral cancer-derived exosomal NAP1 enhances cytotoxicity of natural killer cells via the IRF-3 pathway

Oral cancer (OC) is one of the most common cancers in the world, four-fifths of what occurred in developing countries [1,2]. The major treatments for OC are still primarily conventional therapies, i.e., surgery, radiotherapy and chemotherapy. Many patients with OC are diagnosed at locally advanced stages, and OC cases with distant metastasis or recurrence lack effective therapies. Immunotherapy has recently proved effective for several malignant tumor types, including OC. However, a systematic increase in median progression-free survival has not been observed [3,4].

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RACK1 is an organ-specific prognostic predictor in OSCC

OSCC is one of the most common subtypes of HNSCC, with an estimated 300,000 new cases and 140,000 deaths occurring worldwide each year [1]. The five-year survival rate of patients with OSCC is only about 50%, despite recent advances in diagnosis and treatment [2]. Now, the most significant factors to affect outcome of patients with OSCC are still the classical clinic pathological parameters of tumor such as tumor stage, and clinical TNM stage, which are not possible to be good predictors of the risk of death.

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Benzethonium chloride activates ER stress and reduces proliferation in HNSCC

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy in the world, accounting for 650,000 new cancer diagnoses each year with 350,000 deaths [1]. Despite the high mortality rate and increased public interest in the United States, NIH support for head and neck cancer research has been decreasing and progress in treatments has accordingly lagged egregiously behind more generously funded malignancies [2–4]. Management of HNSCC over the past 20 years has moved towards an organ preservation approach with most patients being offered a combination of chemotherapy and radiation treatment.

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Optimising volumetric arc radiotherapy for dental rehabilitation in oropharynx cancer – A retrospective dosimetry review and feasibility planning study

Squamous cell carcinomas (SCC) of the oropharynx are potentially curable cancers with surgery, radiotherapy, chemoradiotherapy or a combination of the same [1]. Three year survival rates up to 82% are reported, and are best in Human Papilloma Virus (HPV) related disease [2], meaning that survivorship issues are now increasingly important. In a UK head and neck cancer follow up clinic almost 30% of patients complained of ongoing dental issues relating to pain as well as poor functional dental consequences, reported by both dentate and edentulous patients [3].

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Differences in incidence and survival of oral cavity and pharyngeal cancers between Germany and the United States depend on the HPV-association of the cancer site

Oral cavity and pharyngeal cancers (OCPC) include cancers of the lip, oral cavity, and pharynx. Together, this group of cancers accounts for over 500,000 new cancer cases per year worldwide [1]. In 2007, the WHO concluded that human papillomavirus (HPV) type 16 is a cause of some subtypes of OCPC [2]. Many epidemiological and molecular studies have meanwhile provided evidence for this causal link, particularly for squamous cell cancers of the oropharynx, the tonsils and parts of the tongue [3]. Consequently, a paradigm shift in the understanding of OCPC has occurred.

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Nanomedicine, an emerging therapeutic strategy for oral cancer therapy

Squamous Cell Carcinoma (SCC) is the most frequently diagnosed oral cancer. It is important to note that while this term is oftentimes used to include both oral cavity and oropharyngeal SCC tumors, these are both separate entities [1,2]. Both are included within the larger group of Head and Neck Squamous Carcinoma (HNSCC), which is the sixth most common form of cancer worldwide [3]. Herein, the term oral SCC (OSCC) is used in reference to both SCC of the oral cavity and oropharynx. OSCC represents ∼2 to 3% of all human cancers [4].

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Abstracts Presented at the Australian and New Zealand Association of Clinical Anatomists (ANZACA) 13th Annual Meeting “Artful Anatomy” 7th–9th December 2016, Australian National University (ANU) Medical School, Canberra, Australian Capital Territory, Australia

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Familial and Somatic BAP1 Mutations Inactivate ASXL1/2-Mediated Allosteric Regulation of BAP1 Deubiquitinase by Targeting Multiple Independent Domains

Deleterious mutations of the ubiquitin carboxy-terminal hydrolase BAP1 found in cancers are predicted to encode inactive truncated proteins, suggesting that loss of enzyme function is a primary tumorigenic mechanism. However, many tumors exhibit missense mutations or in-frame deletions or insertions, often outside the functionally critical UCH domain in this tumor suppressor protein. Thus, precisely how these mutations inactivate BAP1 is unknown. Here, we show how these mutations affect BAP1 interactions with the Polycomb group-like protein ASXL2, using combinations of computational modeling technology, molecular biology, and in vitro reconstitution biochemistry. We found that the BAP1-ASXL2 interaction is direct and high affinity, occurring through the ASXH domain of ASXL2, an obligate partner for BAP1 enzymatic activity. The ASXH domain was the minimal domain for binding the BAP1 ULD domain, and mutations on the surfaces of predicted helices of ASXH abolished BAP1 association and stimulation of BAP1 enzymatic activity. The BAP1-UCH, BAP1-ULD, and ASXH domains formed a cooperative stable ternary complex required for deubiquitination. We defined four classes of alterations in BAP1 outside the UCH domain, each failing to productively recruit ASXH to the wild-type BAP1 catalytic site via the ULD, resulting in loss of BAP1 ubiquitin hydrolase activity. Our results indicate that many BAP1 mutations act allosterically to inhibit ASXH binding, thereby leading to loss of enzyme activity. Small molecule approaches to reactivate latent wild-type UCH activity of these mutants might be therapeutically viable.

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Interhemispheric motor interactions in hemiparetic children with perinatal stroke: Clinical correlates and effects of neuromodulation therapy

Publication date: February 2018
Source:Clinical Neurophysiology, Volume 129, Issue 2
Author(s): Derek Eng, Ephrem Zewdie, Patrick Ciechanski, Omar Damji, Adam Kirton
ObjectiveBrain stimulation and constraint therapy may enhance function after perinatal stroke but mechanisms are unknown. We characterized interhemispheric interactions (IHI) in hemiparetic children and explored their relationship to motor function and neuromodulation.MethodsForty-five hemiparetic perinatal stroke subjects aged 6–19 years completed a clinical trial of repetitive-transcranial magnetic stimulation (rTMS) and constraint therapy. Paired-pulse TMS measured IHI in cases and normal controls. Suprathreshold conditioning stimuli preceded contralateral test stimuli bidirectionally: stroke to non-stroke (SNS) and non-stroke to stroke (NSS). Primary outcome was the interhemispheric ratio (IHR) between conditioned and test only MEP amplitudes X100 (<100 implied inhibition). Motor outcomes at baseline and post-intervention were compared to IHR.ResultsProcedures were well tolerated. IHI occurred bidirectionally in controls. Eighteen stroke participants had complete data. IHR were increased in stroke participants in both directions. SNS IHR was >100 (facilitation) in 39% of measurements and correlated with better motor function. NSS IHR correlated with poorer motor function. Intervention-induced clinical change was not associated with IHR.ConclusionsInterhemispheric interactions are altered and related to clinical function, but not necessarily neuromodulation, in children with perinatal stroke.SignificanceAdding interhemispheric interactions to evolving models of developmental plasticity following early injury may advance neuromodulation strategies.

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Tumor treating fields (TTFields) delay DNA damage repair following radiation treatment of glioma cells

Abstract

Background

Tumor Treating Fields (TTFields) are an anti-neoplastic treatment modality delivered via application of alternating electric fields using insulated transducer arrays placed directly on the skin in the region surrounding the tumor. A Phase 3 clinical trial has demonstrated the effectiveness of continuous TTFields application in patients with glioblastoma during maintenance treatment with Temozolomide. The goal of this study was to evaluate the efficacy of combining TTFields with radiation treatment (RT) in glioma cells. We also examined the effect of TTFields transducer arrays on RT distribution in a phantom model and the impact on rat skin toxicity.

Methods

The efficacy of TTFields application after induction of DNA damage by RT or bleomycin was tested in U-118 MG and LN-18 glioma cells. The alkaline comet assay was used to measure repair of DNA lesions. Repair of DNA double strand breaks (DSBs) were assessed by analyzing γH2AX or Rad51 foci. DNA damage and repair signaled by the activation pattern of phospho-ATM (pS1981) and phospho-DNA-PKcs (pS2056) was evaluated by immunoblotting. The absorption of the RT energy by transducer arrays was measured by applying RT through arrays placed on a solid-state phantom. Skin toxicities were tested in rats irradiated daily through the arrays with 2Gy (total dose of 20Gy).

Results

TTFields synergistically enhanced the efficacy of RT in glioma cells. Application of TTFields to irradiated cells impaired repair of irradiation- or chemically-induced DNA damage, possibly by blocking homologous recombination repair. Transducer arrays presence caused a minor reduction in RT intensity at 20 mm and 60 mm below the arrays, but led to a significant increase in RT dosage at the phantom surface jeopardizing the "skin sparing effect". Nevertheless, transducer arrays placed on the rat skin during RT did not lead to additional skin reactions.

Conclusions

Administration of TTFields after RT increases glioma cells treatment efficacy possibly by inhibition of DNA damage repair. These preclinical results support the application of TTFields therapy immediately after RT as a viable regimen to enhance RT outcome. Phantom measurements and animal models imply that it may be possible to leave the transducer arrays in place during RT without increasing skin toxicities.

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Αρχειοθήκη ιστολογίου

Πέμπτη 28 Δεκεμβρίου 2017

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