18F-FDG PET Biomarkers Help Detect Early Metabolic Response to Irreversible Electroporation and Predict Therapeutic Outcomes in a Rat Liver Tumor Model.
Radiology. 2017 Dec 12;:170920
Authors: Wang X, Su Z, Lyu T, Figini M, Procissi D, Shangguan J, Sun C, Wang B, Shang N, Gu S, Ma Q, Gordon AC, Lin K, Wang J, Lewandowski RJ, Salem R, Yaghmai V, Larson AC, Zhang Z
Abstract
Purpose To test the hypothesis that biomarkers of fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) can be used for the early detection of therapeutic response to irreversible electroporation (IRE) of liver tumor in a rodent liver tumor model. Materials and Methods The institutional animal care and use committee approved this study. Rats were inoculated with McA-RH7777 liver tumor cells in the left median and left lateral lobes. Tumors were allowed to grow for 7 days to reach a size typically at least 5 mm in longest diameter, as verified with magnetic resonance (MR) imaging. IRE electrodes were inserted, and eight 100-μsec, 2000-V pulses were applied to ablate the tumor tissue in the left median lobe. Tumor in the left lateral lobe served as a control in each animal. PET/computed tomography (CT) and MR imaging measurements were performed at baseline and 3 days after IRE for each animal. Additional MR imaging measurements were obtained 14 days after IRE. After 14-day follow-up MR imaging, rats were euthanized and tumors harvested for hematoxylin-eosin, CD34, and caspase-3 staining. Change in the maximum standardized uptake value (ΔSUVmax) was calculated 3 days after IRE. The maximum lesion diameter change (ΔDmax) was measured 14 days after IRE by using axial T2-weighted imaging. ΔSUVmax and ΔDmax were compared. The apoptosis index was calculated by using caspase-3-stained slices of apoptotic tumor cells. Pearson correlation coefficients were calculated to assess the relationship between ΔSUVmax at 3 days and ΔDmax (or apoptosis index) at 14 days after IRE treatment. Results ΔSUVmax, ΔDmax, and apoptosis index significantly differed between treated and untreated tumors (P < .001 for all). In treated tumors, there was a strong correlation between ΔSUVmax 3 days after IRE and ΔDmax 14 days after IRE (R = 0.66, P = .01) and between ΔSUVmax 3 days after IRE and apoptosis index 14 days after IRE (R = 0.57, P = .04). Conclusion 18F-FDG PET imaging biomarkers can be used for the early detection of therapeutic response to IRE treatment of liver tumors in a rodent model. © RSNA, 2017.
PMID: 29232185 [PubMed - as supplied by publisher]
Feasibility and Safety of Intrathoracic Biopsy and Repeat Biopsy for Evaluation of Programmed Cell Death Ligand-1 Expression for Immunotherapy in Non-Small Cell Lung Cancer.
Radiology. 2017 Dec 12;:170347
Authors: Tsai EB, Pomykala K, Ruchalski K, Genshaft S, Abtin F, Gutierrez A, Kim HJ, Li A, Adame C, Jalalian A, Wolf B, Garon EB, Goldman JW, Suh R
Abstract
Purpose To determine feasibility and safety of biopsy and repeat biopsy for assessment of programmed cell death ligand-1 (PD-L1) status. Materials and Methods This retrospective analysis reviewed 101 patients who underwent transthoracic core needle biopsy for the KEYNOTE-001 (MK-3475) clinical trial of pembrolizumab, an antiprogrammed cell death-1 therapy for non-small cell lung cancer, from May 2012 to September 2014. Sixty-one male patients (mean age, 66.1 years; range 36-83 years) and 40 female patients (mean age, 66.8 years; age range, 36-90 years) were included. Data collected included population characteristics, treatment history, target location, size, and depth from pleura. Adequacy of the tissue sample for diagnostic testing and rates of biopsy-related complications were assessed. Statistical analysis was performed by using univariate and multivariate generalized linear models to determine significant risk factors for biopsy complications. Results A total of 110 intrathoracic biopsies were performed, and 101 (91.8%) were performed as repeat biopsies subsequent to a previous percutaneous or bronchoscopic biopsy or previous surgical biopsy or resection. More than 84.5% (93 of 110) of biopsies were performed in patients who had undergone previous local or systemic therapy. Specimens were adequate for evaluation of PD-L1 expression in 96.4% of biopsies. Procedure-related complications occurred in 28 biopsies (25.4%); pneumothorax was most common (22.7%). Overall mean number of core needle biopsy samples obtained was 7.9 samples. Conclusion Image-guided transthoracic core needle biopsy is an effective method for obtaining tissue for PD-L1 expression analysis. © RSNA, 2017.
PMID: 29232184 [PubMed - as supplied by publisher]
Loss of Substantia Nigra Hyperintensity at 3.0-T MR Imaging in Idiopathic REM Sleep Behavior Disorder: Comparison with 123I-FP-CIT SPECT.
Radiology. 2017 Dec 12;:162486
Authors: Bae YJ, Kim JM, Kim KJ, Kim E, Park HS, Kang SY, Yoon IY, Lee JY, Jeon B, Kim SE
Abstract
Purpose To examine whether the loss of nigral hyperintensity (NH) on 3.0-T susceptibility-weighted (SW) magnetic resonance (MR) images can help identify high synucleinopathy risk in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD). Materials and Methods Between March 2014 and April 2015, 18 consecutively recruited patients with iRBD were evaluated with 3.0-T SW imaging and iodine 123-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT) single photon emission computed tomography and compared with 18 healthy subjects and 18 patients with Parkinson disease (PD). Two readers blinded to clinical diagnosis independently assessed the images. 123I-FP-CIT uptake ratios were compared by using the Kruskal-Wallis test, and intra- and interobserver agreements were assessed with the Cohen κ. The synucleinopathy conversion according to NH status was evaluated in patients with iRBD after follow-up. Results NH was intact in seven patients with iRBD and lost in 11. The 123I-FP-CIT uptake ratios were comparable between those with intact NH (mean, 3.22 ± 0.47) and healthy subjects (mean, 3.37 ± 0.47) (P = .495). The 123I-FP-CIT uptake ratios in the 11 patients with iRBD and NH loss (mean, 2.48 ± 0.44) were significantly lower than those in healthy subjects (mean, 3.37 ± 0.47; P < .001) but higher than those in patients with PD (mean, 1.80 ± 0.33; P < .001). The intra- and interobserver agreements were excellent (κ > 0.9). Five patients with iRBD and NH loss developed symptoms of parkinsonism or dementia 18 months after neuroimaging. Conclusion NH loss at 3.0-T SW imaging may be a promising marker for short-term synucleinopathy risk in iRBD. © RSNA, 2017 Online supplemental material is available for this article.
PMID: 29232183 [PubMed - as supplied by publisher]
Mesenteriale und peritoneale inflammatorische Prozesse stellen eine große klinische Herausforderung bezüglich der Differenzialdiagnosen dar. In diesem Übersichtsartikel wird ein systematischer Überblick über die häufigsten Ursachen, eingeteilt nach Autoimmunreaktionen, Infarzierung mit Nekrosen und Protozoen bzw. bakteriellen Infektionen, gegeben.
Allen inflammatorischen peritonealen und mesenterialen Prozessen ist eine unspezifische abdominelle Symptomatik der Patienten gemein. Auch radiologisch existieren sehr viele Überschneidungen mit unspezifischen Vergrößerungen von Lymphknoten bzw. nodulären Strukturen im Peritoneum oder Mesenterium. Basierend auf den klinischen Angaben und der Anamnese kann der Radiologe jedoch zu einer Reduktion der Differenzialdiagnosen beitragen und somit durch rechtzeitige Diagnose das therapeutische Outcome positiv beeinflussen.
Beim großen Spektrum der Ätiologie für inflammatorische peritoneale und mesenteriale Prozesse müssen radiologisch Autoimmunerkrankungen (IgG4-assoziierte Erkrankungen), akute Infarzierung mit Nekrosen bzw. Infektionen mit Protozoen oder Bakterien differenzialdiagnostisch in Betracht gezogen werden.
Group A rotaviruses (RVA) are one of the leading causes of gastroenteritis in young children worldwide. The introduction of universal mass vaccination around the world has contributed to a reduction in hospitalizations and outpatient visits associated with rotavirus infection. Continued surveillance of RVA strains is needed to determine long-term effects of vaccine introduction. In the present work, we carried out the analysis of the genotypic diversity of RVA strains isolated in Nizhny Novgorod (Russia) during the 2015–2016 epidemic season. Also we conducted a comparative analysis of the amino acid sequences of T-cell epitopes of wild-type and vaccine (RotaTeq and Rotarix) strains. In total, 1461 samples were examined. RVAs were detected in 30.4% of cases. Rotaviruses with genotype G9P[8] (40.5%) dominated in the 2015-16 epidemic season. Additionally, RVAs with the following genotypes were detected: G4P[8] (25.4%), G1P[8] (13%), G2P[4] (3.2%). Rotaviruses with genotypes G3P[9], G6P[9], and G1P[9] totaled 3%. The number of partially typed and untyped RVA samples was 66 (14.9%). The findings of a RVA of G6P[9] genotype in Russia were an original observation. Our analysis of VP6 and NSP4 T-cell epitopes showed highly conserved amino acid sequences. The found differences seem not to be caused by the immune pressure but were rather related to the genotypic affiliations of the proteins. Vaccination against rotavirus infection is not included in the national vaccination schedule in Russia. Monitoring of the genotypic and antigenic diversity of contemporary RVA will allow providing a comparative analysis of wild-type strains in areas with and without vaccine campaign.
There is growing evidence of a direct influence of vasculature on the development of neurons in the brain. The development of the cranial vasculature has been well described in zebrafish but its anatomical relationship with the adjacent developing sensory ganglia has not been addressed. Here, by 3D imaging of fluorescently labelled blood vessels and sensory ganglia, we describe for the first time the spatial organization of the cranial vasculature in relation to the cranial ganglia during zebrafish development. We show that from 24 h post-fertilization (hpf) onwards, the statoacoustic ganglion (SAG) develops in direct contact with two main blood vessels, the primordial hindbrain channel and the lateral dorsal aortae (LDA). At 48 hpf, the LDA is displaced medially, losing direct contact with the SAG. The relationship of the other cranial ganglia with the vasculature is evident for the medial lateral line ganglion and for the vagal ganglia that grow along the primary head sinus (PHS). We also observed that the innervation of the anterior macula runs over the PHS vessel. Our spatiotemporal anatomical map of the cranial ganglia and the head vasculature indicates physical interactions between both systems and suggests a possible functional interaction during development.
Publication date: Available online 12 December 2017
Source:Radiotherapy and Oncology
Author(s): Marianne C. Aznar, Frances K. Duane, Sarah C. Darby, Zhe Wang, Carolyn W. Taylor
Background and purposeWe report a systematic review of lung radiation doses from breast cancer radiotherapy.Methods and materialsStudies describing breast cancer radiotherapy regimens published during 2010–2015 and reporting lung dose were included. Doses were compared between different countries, anatomical regions irradiated, techniques and use of breathing adaptation.Results471 regimens from 32 countries were identified. The average mean ipsilateral lung dose (MLDipsi) was 9.0 Gy. MLDipsi for supine radiotherapy with no breathing adaption was 8.4 Gy for whole breast/chest wall (WB/CW) radiotherapy, 11.2 Gy when the axilla/supraclavicular fossa was irradiated, and 14.0 Gy with the addition of internal mammary chain irradiation; breathing adaptation reduced MLDipsi by 1 Gy, 2 Gy and 3 Gy respectively (p < 0.005). For WB/CW radiotherapy, MLDipsi was lowest for tangents in prone (1.2 Gy) or lateral decubitus (0.8 Gy) positions. The highest MLDipsi was for IMRT in supine position (9.4 Gy).The average mean contralateral lung dose (MLDcont) for WB/CW radiotherapy was higher for IMRT (3.0 Gy) than for tangents (0.8 Gy).ConclusionsLung doses from breast cancer radiotherapy varied substantially worldwide, even between studies describing similar regimens. Lymph node inclusion and IMRT use increased exposure, while breathing adaptation and prone/lateral decubitus positioning reduced it.
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In total hip arthroplasty, prediction of the optimal implant size is important in order to prevent perioperative complications. However, it is not easy to achieve complete agreement between the planned size and the actual size required appropriate implant fit. No previous report has adequately discussed the factors related to mismatch between predicted and actual implant sizes. The purpose was to report the results of a single surgeon case series of patients undergoing THA using computed tomography (CT)-based templating and the possible factors related to implant size mismatch.
The study included 141 hips of 126 patients who underwent primary total hip arthroplasty with CT-based navigation. We retrospectively reviewed the planned and actual implant sizes used in these patients. Cup position, cup orientation and stem alignment were evaluated as surgical factors that could possibly be related to mismatch in implant size. Cortical index and canal flare index were also evaluated as morphological factors.
The final inclusions in this study were 124 hips of 111 patients including 82% of those were developmental dysplasia of the hip. Agreement in implant size was seen for 94.4% of cups and 85.5% of stems, respectively. No related factors were found for cup size mismatch. Stem alignment in the sagittal and coronal planes showed significant differences between the size-matched stem group and the smaller stem group ( \(p<0.05\) ).
Implant size agreement rates between the three-dimensional plan and the actual implants used intraoperatively were high. However, broach alignment should be checked in the coronal and sagittal planes if the intraoperative broach is smaller than the planned size.
Chemokines are small secreted proteins with chemoattractant properties that play a key role in inflammation. One such chemokine, Stromal cell-derived factor-1 (SDF-1) also known as CXCL12, and its receptor, CXCR4, are expressed and functional in cardiac myocytes. SDF-1 both stimulates and enhances the cellular signal which attracts potentially beneficial stem cells for tissue repair within the ischemic heart. Paradoxically however, this chemokine is known to act in concert with the inflammatory cytokines of the innate immune response which contributes to cellular injury through the recruitment of inflammatory cells during ischemia. In the present study, we have demonstrated that SDF-1 has dose dependent effects on freshly isolated cardiomyocytes. Using Tunnel and caspase 3-activation assays, we have demonstrated that the treatment of isolated adult rat cardiac myocyte with SDF-1 at higher concentrations (pathological concentrations) induced apoptosis. Furthermore, ELISA data demonstrated that the treatment of isolated adult rat cardiac myocyte with SDF-1 at higher concentrations upregulated TNF-α protein expression which directly correlated with subsequent apoptosis. There was a significant reduction in SDF-1 mediated apoptosis when TNF-α expression was neutralized which suggests that SDF-1 mediated apoptosis is TNF-α-dependent. The fact that certain stimuli are capable of driving cardiomyocytes into apoptosis indicates that these cells are susceptible to clinically relevant apoptotic triggers. Our findings suggest that the elevated SDF-1 levels seen in a variety of clinical conditions, including ischemic myocardial infarction, may either directly or indirectly contribute to cardiac cell death via a TNF-α mediated pathway. This highlights the importance of this receptor/ligand in regulating the cardiomyocyte response to stress conditions.
The ex vivo human skin wound model is a widely accepted model to study wound epithelialization. Due to a lack of animal models that fully replicate human conditions, the ex vivo model is a valuable tool to study mechanisms of wound re-epithelialization, as well as for pre-clinical testing of novel therapeutics. The current standard for assessment of wound healing in this model is histomorphometric analysis, which is labor intensive, time consuming, and requires multiple biological and technical replicates in addition to assessment of different time points. Optical Coherence Tomography (OCT) is an emerging non-invasive imaging technology originally developed for non-invasive retinal scans that avoids the deleterious effects of tissue processing. This study investigated OCT as a novel method for assessing re-epithelialization in the human ex vivo wound model. Excisional ex vivo wounds were created, maintained at air-liquid interface, and healing progression was assessed at days 4 and 7 with OCT and histology. OCT provided adequate resolution to identify the epidermis, the papillary and reticular dermis, and importantly, migrating epithelium in the wound bed. We have deployed OCT as a non-invasive tool to produce, longitudinal "optical biopsies" of ex vivo human wound healing process, and we established an optimal quantification method of re-epithelialization based on en face OCT images of the total wound area. Pairwise statistical analysis of OCT and histology based quantifications for the rate of epithelialization have shown the feasibility and superiority of OCT technology for non-invasive monitoring of human wound epithelialization. Furthermore, we have utilized OCT to evaluate therapeutic potential of allogeneic adipose stem cells revealing their ability to promote re-epithelialization in human ex vivo wounds. OCT technology is promising for its applications in wound healing and evaluation of novel therapeutics in both the laboratory and the clinical settings. This article is protected by copyright. All rights reserved.
Changes in contents of sugars, organic acids, limonoids, phenolics contents, and antioxidant capacities of lemon slices dried at different temperatures were evaluated. Air drying (AD) promoted losses of sugars, citric acid, ascorbic acid, extractable phenolics (EPs), and non-extractable phenolics (NEPs), while it introduced an increase in limonoids. Phenolics of lemon were mainly presented in their extractable form. Hesperidin and eriocitrin were the main EPs; protocatechuic acid and poncirin were the predominant NEPs. The decrease in extractable phenolic acid, EP, and NEP content in lemon is lower at low drying temperatures, while the increase in non-extractable phenolic acid content is higher at high drying temperatures. The antioxidant capacity of EP was higher than that of NEP. Phenolics contributed to antioxidant capacities of lemon slices, and flavonoids were the main contributors among phenolics. Considering limonoids contents and the high levels of EP, NEP, and antioxidant capacities, AD at 60 °C could be an appreciate treatment for dehydrating lemon slices.
The aim of the study was to encapsulate resveratrol (RV) in trimethyl chitosan (TMC) nanoparticles cross-linked with tripolyphosphate (TPP) and/or alginate to achieve controlled release and improved cellular uptake. TMC (degree of quaternization of 78%) was prepared by reacting purified chitosan with iodomethane. Three types of RV-loaded TMC nanoparticles were prepared: TMC–TPP (TP-NPs), TMC–alginate (TA-NPs), and TMC–alginate–TPP (TAP-NPs). TA-NPs and TAP-NPs showed lower particle size and encapsulation efficiency (EE), better distribution, and more sustained release than TP-NPs due to the high molecular weight and viscous property of alginate. Caco-2 cellular uptake of RV was improved by TMC nanoencapsulation, and TP-NPs showed the highest uptake due to its significantly higher EE. Compared with TAP-NPs, TA-NPs with higher positive surface charge showed higher cellular uptake. Moreover, Caco-2 cell growth-inhibiting activity of RV was significantly increased by TMC nanoencapsulation and TP-NPs showed the significantly highest activity with a good agreement with the permeability results.
Image segmentation is an essential step in quantifying the extent of reduced or absent lung function. The aim of this study is to develop and validate a new tool for automatic segmentation of lungs in ventilation and perfusion SPECT images and compare automatic and manual SPECT lung segmentations with reference computed tomography (CT) volumes.
A total of 77 subjects (69 patients with obstructive lung disease, and 8 subjects without apparent perfusion of ventilation loss) performed low-dose CT followed by ventilation/perfusion (V/P) SPECT examination in a hybrid gamma camera system. In the training phase, lung shapes from the 57 anatomical low-dose CT images were used to construct two active shape models (right lung and left lung) which were then used for image segmentation. The algorithm was validated in 20 patients, comparing its results to reference delineation of corresponding CT images, and by comparing automatic segmentation to manual delineations in SPECT images.
The Dice coefficient between automatic SPECT delineations and manual SPECT delineations were 0.83 ± 0.04% for the right and 0.82 ± 0.05% for the left lung. There was statistically significant difference between reference volumes from CT and automatic delineations for the right (R = 0.53, p = 0.02) and left lung (R = 0.69, p < 0.001) in SPECT. There were similar observations when comparing reference volumes from CT and manual delineations in SPECT images, left lung (bias was − 10 ± 491, R = 0.60, p = 0.005) right lung (bias 36 ± 524 ml, R = 0.62, p = 0.004).
Automated segmentation on SPECT images are on par with manual segmentation on SPECT images. Relative large volumetric differences between manual delineations of functional SPECT images and anatomical CT images confirms that lung segmentation of functional SPECT images is a challenging task. The current algorithm is a first step towards automatic quantification of wide range of measurements.
For wastewater-related issues (WRI), life cycle assessment (LCA) is often used to evaluate environmental impacts and derive optimization strategies. To promote the application of LCA for WRI, it is critical to incorporate local impact of water pollutants. Organic pollution, a main type of water pollution, has not been given much consideration in current LCA systems. This paper investigates the necessity of setting a regionalized impact category to reflect the local impact of organic pollution. A case study is conducted concerning an upgraded wastewater treatment plant (WWTP) in China, which is assumed to meet different sewage control strategies. Chemical oxygen demand (COD) is selected to represent the organic pollution and treated as an individual impact category. CML 2002 is used to quantify the environmental impacts of different strategies. Results show that abnormal LCA results are generated with the traditional eutrophication impact category, and after the introduction of COD, more reasonable LCA results are obtained, making the entire comparison of different control strategies more meaningful and compelling. Moreover, BEES, Ecovalue 08, and Chinese factors are adopted here as different weighting methods. Different weighting results exhibited various trade-offs for the increasingly strict control strategies; the results of BEES and Ecovalue08 underlined the potential environmental burden, but the results of Chinese factors only emphasized the local environmental improvement. It is concluded that setting regionalized impact category for organic pollution can make LCA results more reasonable in wastewater treatment, especially in evaluating Chinese cases because of the serious water pollution caused by large quantities of COD emission.
Image segmentation is an essential step in quantifying the extent of reduced or absent lung function. The aim of this study is to develop and validate a new tool for automatic segmentation of lungs in ventilation and perfusion SPECT images and compare automatic and manual SPECT lung segmentations with reference computed tomography (CT) volumes.
A total of 77 subjects (69 patients with obstructive lung disease, and 8 subjects without apparent perfusion of ventilation loss) performed low-dose CT followed by ventilation/perfusion (V/P) SPECT examination in a hybrid gamma camera system. In the training phase, lung shapes from the 57 anatomical low-dose CT images were used to construct two active shape models (right lung and left lung) which were then used for image segmentation. The algorithm was validated in 20 patients, comparing its results to reference delineation of corresponding CT images, and by comparing automatic segmentation to manual delineations in SPECT images.
The Dice coefficient between automatic SPECT delineations and manual SPECT delineations were 0.83 ± 0.04% for the right and 0.82 ± 0.05% for the left lung. There was statistically significant difference between reference volumes from CT and automatic delineations for the right (R = 0.53, p = 0.02) and left lung (R = 0.69, p < 0.001) in SPECT. There were similar observations when comparing reference volumes from CT and manual delineations in SPECT images, left lung (bias was − 10 ± 491, R = 0.60, p = 0.005) right lung (bias 36 ± 524 ml, R = 0.62, p = 0.004).
Automated segmentation on SPECT images are on par with manual segmentation on SPECT images. Relative large volumetric differences between manual delineations of functional SPECT images and anatomical CT images confirms that lung segmentation of functional SPECT images is a challenging task. The current algorithm is a first step towards automatic quantification of wide range of measurements.
Osteomas of temporal bone are rare, slow growing benign tumours and they are reported in all parts of temporal bone. This study is a retrospective study of the clinical presentation, management and complications of temporal bone osteoma done from January 1999 through January 2017. The study population is thirteen patients, all who has been radiologically and histopathologically proven to be a case of osteoma. Total number of patients were 13 of which 7 were females and rest 6 were male. Presenting complaints included swelling behind the ear (6 cases), reduced hearing in 4 cases, 2 cases had ear discharge, 3 of them were asymptomatic in whom it was diagnosed accidently. The duration of symptoms ranged from 1 month to 10 years. Of total 13 patients 7 had external auditory canal involvement and 4 cases had mastoid region. Two patients were managed conservatively, one refused surgery and rest ten cases underwent excision. The specimen was sent for histopathological examination and diagnosis of osteoma was confirmed. The decision regarding whether to operate or not depends on each case depending on its size, symptoms and more importantly the complications. Excision of osteoma remains the treatment of choice.
Osteomas of temporal bone are rare, slow growing benign tumours and they are reported in all parts of temporal bone. This study is a retrospective study of the clinical presentation, management and complications of temporal bone osteoma done from January 1999 through January 2017. The study population is thirteen patients, all who has been radiologically and histopathologically proven to be a case of osteoma. Total number of patients were 13 of which 7 were females and rest 6 were male. Presenting complaints included swelling behind the ear (6 cases), reduced hearing in 4 cases, 2 cases had ear discharge, 3 of them were asymptomatic in whom it was diagnosed accidently. The duration of symptoms ranged from 1 month to 10 years. Of total 13 patients 7 had external auditory canal involvement and 4 cases had mastoid region. Two patients were managed conservatively, one refused surgery and rest ten cases underwent excision. The specimen was sent for histopathological examination and diagnosis of osteoma was confirmed. The decision regarding whether to operate or not depends on each case depending on its size, symptoms and more importantly the complications. Excision of osteoma remains the treatment of choice.
Genes, Vol. 8, Pages 384: The Tumor Suppressor p53 in Mucosal Melanoma of the Head and Neck
Genes doi: 10.3390/genes8120384
Authors: Marie Fritsche Andreas Knopf
Despite worldwide prevention programs, the incidence for cutaneous melanoma is continuously increasing. Mucosal melanoma (MM) represents a rare but highly aggressive phenotype of common melanoma with predilection in the sinonasal system. Far away from ultraviolet sun exposure, the molecular mechanisms underlying tumorigenesis and the highly aggressive clinical behavior are poorly understood. In many solid malignomas of the head and neck region, p53 tumor suppressor functions as oncogene due to p53 protein stabilizing mutation. Interestingly, the vast majority of MM demonstrates constitutively expressed p53 protein, with protein stabilizing mutations being rare. Abrogated activation of p53 target genes results in derogation of the apoptotic signal cascade and contributes to the strong resistance against chemotherapeutic agents activating p53 dependent apoptosis. The current review illustrates the role of p53 and its pathway in MM.
The association of dietary factors with urinary bladder cancer prognosis has scarcely been investigated, and results of studies conducted to date are inconsistent. We investigated whether empirically derived dietary patterns are associated with risks of recurrence and progression in non-muscle invasive bladder cancer patients. Data from 595 newly diagnosed non-muscle-invasive bladder cancer patients from an ongoing prospective cohort study were used to derive dietary patterns using exploratory factor analysis. Factor scores were calculated and then categorized in sex-specific tertiles. Multivariable adjusted proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals for the associations between tertiles of adherence to the dietary patterns and risks of recurrence and progression. We identified four dietary patterns: “fruits and vegetables”, “Western”, “low-fat”, and “Tex-Mex”. Patients in the highest tertile of adherence to the Western pattern experienced a 1.48 times higher risk of recurrence (95% CI 1.06-2.06) compared to patients in the lowest tertile. No statistically significant associations of a Western diet with risk of progression, or of the other dietary patterns with risk of recurrence and progression were found. Overall, we found that adherence to a Western diet was associated with a higher risk of recurrence but further studies are needed to confirm our findings. This article is protected by copyright. All rights reserved.
Tumor cells frequently overexpress heat shock protein 70 (Hsp70) and present it on their cell surface, where it can be recognized by pre-activated NK cells. In this retrospective study the expression of Hsp70 was determined in relation to tumor-infiltrating CD56+ NK cells in formalin-fixed paraffin embedded (FFPE) tumor specimens of patients with SCCHN (N=145) as potential indicators for survival and disease recurrence. All patients received radical surgery and postoperative cisplatinum-based radiochemotherapy (RCT). In general, Hsp70 expression was stronger, but with variable intensities, in tumor compared to normal tissues. Patients with high Hsp70 expressing tumors (scores 3-4) showed significantly decreased overall survival (OS; p=0.008), local progression-free survival (LPFS; p=0.034) and distant metastases-free survival (DMFS; p=0.044), compared to those with low Hsp70 expression (scores 0-2), which remained significant after adjustment for relevant prognostic variables. The adverse prognostic value of a high Hsp70 expression for OS was also observed in patient cohorts with p16- (p=0.001), p53- (p=0.0003), and HPV16 DNA-negative (p=0.001) tumors. The absence or low numbers of tumor-infiltrating CD56+ NK cells also correlated with significantly decreased OS (p=0.0001), LPFS (p=0.0009) and DMFS (p=0.0001). A high Hsp70 expression and low numbers of tumor-infiltrating NK cells have the highest negative predictive value (p=0.00004). In summary, a strong Hsp70 expression and low numbers of tumor-infiltrating NK cells correlate with unfavourable outcome following surgery and RCT in patients with SCCHN, and thus serve as negative prognostic markers. This article is protected by copyright. All rights reserved.
Eukaryotic elongation factor 2 kinase (eEF2K) negative regulates the elongation phase of mRNA translation and hence protein synthesis. Increasing evidence indicates that eEF2K plays an important role in the survival and migration of cancer cells and in tumour progression.
As demonstrated by two-dimensional wound-healing and three-dimensional transwell invasion assays, knocking down or inhibiting eEF2K in cancer cells impairs migration and invasion of cancer cells. Conversely, exogenous expression of eEF2K or knocking down eEF2 (the substrate of eEF2K) accelerates wound healing and invasion.
Importantly, using LC-HDMSE analysis, we identify 150 proteins whose expression is decreased and 73 proteins which are increased upon knocking down eEF2K in human lung carcinoma cells. Of interest, 34 down-regulated proteins include integrins and other proteins implicated in cell migration, suggesting that inhibiting eEF2K may help prevent cancer cell mobility and metastasis. Interestingly, eEF2K promotes the association of integrin mRNAs with polysomes, providing a mechanism by which eEF2K may enhance their cellular levels. Consistent with this, genetic knock down or pharmacological inhibition of eEF2K reduces the protein expression levels of integrins.
Notably, pharmacological or genetic inhibition of eEF2K almost completely blocked tumour growth and effectively prevented the spread of tumour cells in vivo. High levels of eEF2K expression were associated with invasive carcinoma and metastatic tumours. These data provide the evidence that eEF2K is a new potential therapeutic target for preventing tumour metastasis. This article is protected by copyright. All rights reserved.
Objective: To evaluate the Turkey's nationwide HPV DNA screening program on the basis of first 1 million screened women.
Methods: Women over age 30 were invited for population based screening via HPV DNA and conventional cytology. Samples were collected by family physicians and the evaluations and reports had been performed in the National Central HPV laboratories.
Results: The acceptance rate for HPV based cervical cancer screening after first invitation was nearly 36.5%. Since HPV DNA tests have been implemented, cervical cancer screening rates have shown 4-5-fold increase in primary level. Through the evaluation of all, HPV positivity was seen in 3,5%. The commonest HPV genotypes were 16, followed by 51, 31, 52 and 18. Among the 37.515 HPV positive cases, cytological abnormality rate was 19,1%. Among HPV positive cases, 16.962 cases had HPV 16 or 18 or other oncogenic HPV types with abnormal cytology (>ASC-US). These patients were referred to colposcopy. The colposcopy referral rate was 1.6%. Among these, final clinico-pathological data of 3.499 patients were normal in 1.985 patients, CIN1 in 708, CIN2 in 285, CIN3 in 436 and cancer in 85 patients and only pap-smear program could miss 45.9% of ≥CIN3 cases
Conclusion: The results of 1 million women including the evaluation of 13 HPV genotypes with respect to prevalence, geographic distribution and abnormal cytology results shows that HPV DNA can be used in primary level settings in order to have a high coverage rated screening program and is very effective compared to conventional pap-smear. This article is protected by copyright. All rights reserved.
The high prevalence of secondary hyperparathyroidism (SHPT) after obesity surgery is a concern for long-term bone health. Limited knowledge exists about optimal vitamin D and suppression of parathyroid hormone (PTH) after these procedures. The aim of this study was to investigate the prevalence of SHPT and its relation to vitamin D status.
A cross-sectional study at Oslo University Hospital, Norway.
502 consecutive patients, age 22-64 years, attending 2-year follow-up after Roux-en-Y gastric bypass.
A serum intact PTH >7.0 pmol/l in the absence of elevated serum ionized calcium (iCa) was considered as SHPT. Vitamin D status was defined by serum concentrations of 25-hydroxyvitamin D (S-25(OH)D).
Altogether, 171 patients (34%) had SHPT. The prevalence of SHPT varied across the range of S-25(OH)D (P<0.001), being highest (71%) with S-25(OH)D <25 nmol/l. Compared with S-25(OH)D <50 nmol/l, the prevalence of SHPT was lower with S-25(OH)D ≥50 nmol/l (29.0%; RR=0.64 (95%-CI:0.50-0.81)) and S-25(OH)D ≥75 nmol/l (27.7%; RR=0.61 (95%-CI:0.44-0.84)). S-25(OH)D ≥100 nmol/l was associated with the lowest PTH and the lowest prevalence of SHPT (16.0%; RR=0.35 (95%-CI:0.14-0.88) compared with S-25(OH)D <50 nmol/l), and the most normal calcium distribution. These associations were most pronounced with iCa in the lower range. A synergistic association was found for S-25(OH)D and iCa on SHPT.
Vitamin D deficient patients had the highest prevalence of SHPT two years after gastric bypass. PTH and the prevalence of SHPT were notably lower with S-25(OH)D ≥100 nmol/l, compared with lower target levels.
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It is recognized that total testosterone (TT) does not sufficiently describe androgen status when sex hormone binding globulin (SHBG) is altered. However, in humans, evidence supporting the existence of a hypogonadism due to low T bioactivity is scanty. The aim of the study was to assess whether changes in SHBG levels, independently of TT, are associated with subjective and objective androgen dependent parameters.
Cross-sectional observation.
2622 men (aged 51.1±13.5 years) attending a Sexual Medicine and Andrology Outpatient Clinic for sexual dysfunctions.
All patients underwent a standardized diagnostic protocol before starting any treatment. Clinical and biochemical parameters have been collected. Higher ANDROTEST score has been used as a comprehensive marker of more severe hypogonadal symptoms. Prostate specific antigen (PSA) and hematocrit have been used as objective surrogate markers of T bioactivity.
After adjusting for TT and lifestyle, SHBG showed a significant positive association with ANDROTEST score (B=0.79 [0.61;0.96], p<0.0001). Conversely, higher SHBG, independently of TT, was negatively related to PSA (B=-0.86 [-0.83;-0.89]; p<0.0001) and hematocrit (B=-0.64 [-0.88;-0.40]; p<0.0001), after adjustment for the aforementioned confounders along with age and body mass index. Furthermore, a relationship between SHBG and lipids or blood pressure was found, with lower SHBG levels associated with a worse metabolic profile, independently of TT.
Higher SHBG, independently of TT, is associated with either subjective or objective androgen deficiency features. This indicates that besides a hypogonadism due to an impaired T production, a hypogonadism due to a lower biological activity of T does exist.
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