The activity level of a particular gene in lung tumours might identify lung-cancer patients who will likely be helped by a particular chemotherapy regimen given to prevent recurrence after surgery. The finding comes from a study led by researchers at The…
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Timing may not be everything, but it could be important in understanding why an anticancer treatment like radiation produces different results against cancer cells, according to a new study by Sheng-hong Chen and colleagues. The cells respond…
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Some patients with breast cancer, lung cancer and leukaemia seem to fare poorly after treatment because of the effects of a particular gene, a new study finds. The gene, called CYP3A7, is normally only active in infancy, but in some people it continues…
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Wnt activation protects against neomycin-induced hair cell damage in the mouse cochlea.:
Cell Death Dis. 2016;7:e2136
Authors: Liu L, Chen Y, Qi J, Zhang Y, He Y, Ni W, Li W, Zhang S, Sun S, Taketo MM, Wang L, Chai R, Li H
Abstract
Recent studies have reported the role of Wnt/β-catenin signaling in hair cell (HC) development, regeneration, and differentiation in the mouse cochlea; however, the role of Wnt/β-catenin signaling in HC protection remains unknown. In this study, we took advantage of transgenic mice to specifically knockout or overactivate the canonical Wnt signaling mediator β-catenin in HCs, which allowed us to investigate the role of Wnt/β-catenin signaling in protecting HCs against neomycin-induced damage. We first showed that loss of β-catenin in HCs made them more vulnerable to neomycin-induced injury, while constitutive activation of β-catenin in HCs reduced HC loss both in vivo and in vitro. We then showed that loss of β-catenin in HCs increased caspase-mediated apoptosis induced by neomycin injury, while β-catenin overexpression inhibited caspase-mediated apoptosis. Finally, we demonstrated that loss of β-catenin in HCs led to increased expression of forkhead box O3 transcription factor (Foxo3) and Bim along with decreased expression of antioxidant enzymes; thus, there were increased levels of reactive oxygen species (ROS) after neomycin treatment that might be responsible for the increased aminoglycoside sensitivity of HCs. In contrast, β-catenin overexpression reduced Foxo3 and Bim expression and ROS levels, suggesting that β-catenin is protective against neomycin-induced HC loss. Our findings demonstrate that Wnt/β-catenin signaling has an important role in protecting HCs against neomycin-induced HC loss and thus might be a new therapeutic target for the prevention of HC death.
PMID: 26962686 [PubMed – as supplied by publisher]
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This study was designed to comparatively assess laryngeal function and quality of life (QOL) of patients after laser surgery (LS) or radiotherapy (RT) for early glottic cancer.
Sixty-four patients with T1 glottic cancer treated with RT or type II cordectomy underwent both subjective and objective vocal assessments. The LS group was divided into the following: (1) vaporization with defocused mode (laser surgery [LS]-Vap); and (2) excision with focused mode using lower power (LS-Ex).
Auditory-perceptual evaluation and videostroboscopic images in the LS-Ex group worsened shortly after treatment and time-dependent recovery was quicker than in the LS-Vap group. The LS-Ex group showed equivalent posttherapeutic vocal function with the RT group by acoustics, aerodynamics, and self-assessment questionnaire analysis, whereas the LS-Vap group showed statistically significant worse function.
The multidimensional assessment showed that early glottic cancer could be successfully treated by either RT or LS-Ex with equivalent posttherapeutic laryngeal function and QOL. © 2016 Wiley Periodicals, Inc. Head Neck, 2016
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The exotic physical properties of graphene have led to intense research activities on the synthesis and characterization of graphene composites during the last decade. The methods developed for preparation of such materials and the different application areas are reviewed. Mainly the inorganic nanostructure/graphene composites have been discussed. The techniques of ex-situ and in-situ hybridization respectively, have been pointed out. Some of the application areas such as batteries, ultracapacitors for energy storage, fuel cells and solar cells for energy generation are discussed. The possible future directions of research are highlighted.
Keratin-producing odontogenic cysts (KPOCs) are a group of cystic lesions that are often aggressive, with high rates of recurrence and multifocality. KPOCs included orthokeratinised odontogenic cyst (OOC) and parakeratotic odontogenic cysts, which are now considered true tumours denominated keratocystic odontogenic tumours (KCOTs). GLUT1 is a protein transporter that is involved in the active uptake of glucose across cell membranes and that is overexpressed in tumours in close correlation with the proliferation rate and positron emission tomography (PET) imaging results.
A series of 58 keratin-producing odontogenic cysts was evaluated histologically and immunohistochemically in terms of GLUT1 expression. Different data were correlated using the beta regression model in relation to histological type and immunohistochemical expression of GLUT1, which was quantified using two different morphological methods.
KPOC cases comprised 12 OOCs and 46 KCOTs, the latter corresponding to 6 syndromic and 40 sporadic KCOTs. GLUT1 expression was very low in OOC cases compared with KCOT cases, with statistical significant differences when quantification was considered. Different GLUT1 localisation patterns were revealed by immunostaining, with the parabasal cells showing higher reactivity in KCOTs. However, among KCOTs cases, GLUT1 expression was unable to establish differences between syndromic and sporadic cases.
GLUT1 expression differentiated between OOC and KCOT cases, with significantly higher expression in KCOTs, but did not differentiate between syndromic and sporadic KCOT cases. However, given the structural characteristics of KCOTs, we hypothesised that PET imaging methodology is probably not a useful diagnostic tool for KCOTs. Further studies of GLUT1 expression and PET examination in KCOT series are needed to confirm this last hypothesis.
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Publication date: May 2016
Source:Atmospheric Environment, Volume 132
Author(s): Chuen-Meei Gan, Christian Hogrefe, Rohit Mathur, Jonathan Pleim, Jia Xing, David Wong, Robert Gilliam, George Pouliot, Chao Wei
The objective of this study is to determine the adequacy of using a relatively coarse horizontal resolution (i.e. 36 km) to simulate long-term trends of pollutant concentrations and radiation variables with the coupled WRF-CMAQ model. WRF-CMAQ simulations over the continental United State are performed over the 2001 to 2010 time period at two different horizontal resolutions of 12 and 36 km. Both simulations used the same emission inventory and model configurations. Model results are compared both in space and time to assess the potential weaknesses and strengths of using coarse resolution in long-term air quality applications. The results show that the 36 km and 12 km simulations are comparable in terms of trends analysis for both pollutant concentrations and radiation variables. The advantage of using the coarser 36 km resolution is a significant reduction of computational cost, time and storage requirement which are key considerations when performing multiple years of simulations for trend analysis. However, if such simulations are to be used for local air quality analysis, finer horizontal resolution may be beneficial since it can provide information on local gradients. In particular, divergences between the two simulations are noticeable in urban, complex terrain and coastal regions.
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Fentanyl iontophoretic transdermal system (ITS) [Ionsys®] is indicated for the management of acute postoperative pain in adults requiring opioid analgesia in the hospital setting. This article reviews the clinical use of fentanyl ITS for postoperative pain management, and summarizes the pharmacology of fentanyl and the characteristics of the two-component fentanyl ITS (Ionsys®) device. In well-designed, multicentre clinical trials, fentanyl ITS was an effective and generally well tolerated method for managing acute postoperative pain in inpatients who had undergone major abdominal, thoracic or orthopaedic surgery. Overall, fentanyl ITS provided equivalent analgesic efficacy to that with morphine patient-controlled intravenous analgesia (PCIA), but was perceived to be more convenient/easier to use than morphine PCIA by patients, nurses and physical therapists. Patients receiving fentanyl ITS also had a greater ability to mobilize after surgery than patients receiving morphine PCIA. In addition, relative to morphine PCIA, fentanyl ITS offers advantages in terms of the noninvasive administrative route (i.e. transdermal needle-free administration), pre-programmed delivery (no risk of programming errors/incorrect dosing) and improved tolerability with regard to the overall incidence of opioid-related adverse events (ORAEs) and some individual ORAEs. Hence, fentanyl ITS is a useful option for the management of acute postoperative pain in adults requiring opioid analgesia in the hospital setting.
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Metallic dental implants cause severe streaking artifacts in computed tomography (CT) data, which affect the accuracy of dose calculations in radiation therapy. The aim of this study was to investigate the benefit of the metal artifact reduction algorithm iterative metal artifact reduction (iMAR) in terms of correct representation of Hounsfield units (HU) and dose calculation accuracy.
Heterogeneous phantoms consisting of different types of tissue equivalent material surrounding metallic dental implants were designed. Artifact-containing CT data of the phantoms were corrected using iMAR. Corrected and uncorrected CT data were compared to synthetic CT data to evaluate accuracy of HU reproduction. Intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans were calculated in Oncentra v4.3 on corrected and uncorrected CT data and compared to Gafchromic™ EBT3 films to assess accuracy of dose calculation.
The use of iMAR increased the accuracy of HU reproduction. The average deviation of HU decreased from 1006 HU to 408 HU in areas including metal and from 283 HU to 33 HU in tissue areas excluding metal. Dose calculation accuracy could be significantly improved for all phantoms and plans: The mean passing rate for gamma evaluation with 3 % dose tolerance and 3 mm distance to agreement increased from 90.6 % to 96.2 % if artifacts were corrected by iMAR.
The application of iMAR allows metal artifacts to be removed to a great extent which leads to a significant increase in dose calculation accuracy.
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Integrative analysis of microRNA and mRNA expression profiles in non-small-cell lung cancer
Cancer Gene Therapy advance online publication, March 11 2016. doi:10.1038/cgt.2016.5
Authors: C Yang, C Sun, X Liang, S Xie, J Huang & D Li
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Sfilate | Chiede una ricarica sulla Poste Pay ma non paga: fermato dai Finanzieri AlessandriaNews Dopo aver ottenuto una ricarica di 600 euro in una nota sala nei pressi della sede del Comune, l'uomo ha raggirato il dipendente, affermando di non avere al seguito denaro e/o carte di pagamento. Chiamati immediatamente in causa dal titolare dell … Sexy, provocante e super chic! Alessia Marcuzzi divina in VersaceSfilate Terremoto in Calabria: Scossa di Magnitudo 3.7 tra Reggio e CataniaNotizie.it |
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Osteoarthritis is the most common human arthritis characterized by degeneration of articular cartilage. Several studies reported that levels of human cartilage glycoprotein chitinase 3-like-1 (CHI3L1) are known as a potential marker for the activation of chondrocytes and the progression of Osteoarthritis (OA), whereas lubricin appears to be chondroprotective. The aim of this study was to investigate the co-expression and co-localization of CHI3L1 and lubricin in normal and osteoarthritic rat articular cartilage to correlate their modified expression to a specific grade of OA. Samples of normal and osteoarthritic rat articular cartilage were analyzed by the Kellgren–Lawrence OA severity scores, the Kraus' modified Mankin score and the Histopathology Osteoarthritis Research Society International (OARSI) system for histomorphometric evaluations, and through CHI3L1 and lubricin gene expression, immunohistochemistry and double immuno-staining analysis. The immunoexpression and the mRNA levels of lubricin increased in normal cartilage and decreased in OA cartilage (normal vs. OA, p < 0.01). By contrast, the immunoexpression and the mRNA levels of CHI3L1 increased in OA cartilage and decreased in normal cartilage (normal vs. OA, p < 0.01). Our findings are consistent with reports suggesting that these two glycoproteins are functionally associated with the development of OA and in particular with grade 2/3 of OA, suggesting that in the future they could be helpful to stage the severity and progression of the disease.
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The early cysteine-labeled metallothionein (MT) from Triticum aestivum (common wheat), denoted Ec-1, features two structurally well-defined domains, γ and βE, coordinating two and four Zn(II) ions, respectively. While the protein is currently assumed to function mainly in zinc homeostasis, a low amount of copper ions was also recently detected in a native Ec-1 sample. To evaluate the observed copper binding in more detail, the recombinant Zn6Ec-1 form was exposed to different amounts of Cu(I) ions and the resulting species characterized with spectroscopic methods. Data reveal that the first Cu(I) equivalent coordinates exclusively to the N-terminal γ-domain of the protein and replaces one Zn(II) ion. To analyze the ability of the γ-domain for coordination of monovalent metal ions in more detail, the γ-Ec-1 peptide fragment was incubated with increasing amounts of Cu(I) and the process monitored with UV–VIS, circular dichroism, and luminescence spectroscopy. Closely similar spectra are observed regardless if the apo- or the metal ion-loaded and, hence, pre-folded forms, were used for the titration experiments with Cu(I). The results indicate that low amounts of Cu(I) ions displace the two metal ions subsequently and stoichiometrically, despite the different coordination geometry requirements of Cu(I) and Zn(II).
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The tricho-rhino-phalangeal syndrome 1 gene (TRPS1), which was initially found to be associated with tricho-rhino-phalangeal syndrome, is critical for the development and differentiation of bone, hair follicles and kidney. However, its role in cancer progression is largely unknown. In this study, we demonstrated that down-regulation of TRPS1 correlated with distant metastasis, tumour recurrence and poor survival rate in cancer patients. TRPS1 was frequently down-regulated in high-metastatic cancer cell lines from breast, colon and nasopharynx. Silencing of TRPS1 stimulated epithelial-mesenchymal transition (EMT), migration and invasion in vitro and metastasis in vivo, while TRPS1 over-expression exhibited the opposite effects. Using quantitative proteomics, FOXA1 a negative regulator of epithelial-mesenchymal transition (EMT) was shown to be down-regulated by TRPS1 knockdown. Ectopic expression of FOXA1 blocked the enhancement of EMT, migration and invasion induced by TRPS1 silencing. Mechanistically, TRPS1, acting as a transcription activator, directly induced FOXA1 transcription by binding to the FOXA1 promoter. We further showed that down-regulation of TRPS1 was induced by miR-373 binding to the 3'UTR of TRPS1. Over-expression of TRPS1, but not TRPS1-3'UTR, blocked the enhancement of migration and invasion induced by miR-373. Taken together, we consider that down-regulation of TRPS1 by miR-373, acting as a transcriptional activator, promotes EMT and metastasis by repressing FOXA1 transcription, expanding upon its previously reported role as a transcription repressor.
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Cutaneous cylindroma is an adnexal tumour with apocrine differentiation. A predisposition to multiple cylindromas is seen in patients with Brooke-Spiegler syndrome, who carry germline mutations in the tumour suppressor gene CYLD. Previous studies of inherited cylindromas have highlighted the frequent presence of biallelic truncating CYLD mutations as a recurrent driver mutation. We have previously shown that sporadic cylindromas express either MYB-NFIB fusion transcripts, or show evidence of MYB activation in the absence of such fusions. Here, we investigated inherited cylindromas from several families with germline CYLD mutations for the presence of MYB activation. Strikingly, none of the inherited CYLD-defective (n = 23) tumours expressed MYB-NFIB fusion transcripts. However, MYB expression was increased in the majority of tumours (69%) and global gene expression analysis revealed that well-established MYB target genes were upregulated in CYLD-defective tumours. Moreover, knock-down of MYB expression caused a significant reduction in cylindroma cell proliferation, suggesting that MYB is also a key player and oncogenic driver in inherited cylindromas. Taken together, our findings suggest molecular heterogeneity in the pathogenesis of sporadic and inherited cutaneous cylindromas, with convergence on MYB activation.
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Most patients with acquired pure red cell aplasia (PRCA) and some with acquired aplastic anemia (AA) respond well to cyclosporine (CsA), but thereafter often show CsA dependency. The mechanism underlying this dependency remains unknown. We established a reliable method for measuring the regulatory T cell (Treg) count using FoxP3 and Helios expression as markers and determined the balance between Tregs and other helper T cell subsets in 16 PRCA and 29 AA patients. The ratios of interferon-γ-producing CD4+ (Th1) T cells to Tregs in untreated patients and CsA-dependent patients were significantly higher (PRCA 5.77 ± 1.47 and 7.38 ± 2.58; AA 6.18 ± 2.35 and 8.94 ± 4.06) than in healthy volunteers (HVs; 3.33 ± 0.90) due to the profound decrease in the percentage of Tregs. In contrast, the ratios were comparable to HVs in convalescent CsA-treated AA patients (4.74 ± 2.10) and AA patients in remission after the cessation of CsA treatment (4.24 ± 1.67). Low-dose CsA (100 ng/ml) inhibited the proliferation of conventional T cells (Tconv) to a similar degree to the inhibition by Tregs in a co-culture with a 1:1 Treg/Tconv ratio. The data suggest that CsA may reverse the hematopoietic suppression in PRCA and AA patients by compensating for the inadequate immune regulatory function that occurs due to a profound decrease in the Treg count.
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Although the importance of the epigenetic changes in tumors, including oral squamous cell carcinomas (OSCCs), is now becoming apparent, the mechanisms that trigger or cause aberrant DNA methylation in cancer are still unrevealed. DNA methylation is regulated by a family of enzymes, DNA methyltransferases (DNMTs). DNMT gene expression analysis, as well as genetic polymorphisms, has not been previously evaluated in OSCC.
In 65 OSCC patients, SYBR Green real-time PCR method was assessed for relative quantification of DNMT1, DNMT3A, and DNMT3B mRNAs, normalized to TATA-binding protein (TBP) mRNA. The expression levels of all three genes were dichotomized as high or low, with a twofold change of normalized mRNA expression used as the cutoff value. Polymorphisms in DNMT1 (rs2228612) and DNMT3B (rs406193) were analyzed in 99 OSCCs by TaqMan SNPs genotyping assays.
DNMT1, DNMT3A, and DNMT3B were overexpressed in 36.9, 26, and 23 % of the OSCC patients, respectively. DNMT1 overexpression was significantly associated with the overall survival, p = 0.029, and relapse-free survival of OSCC patients, p = 0.003. Patients with DNMT1 overexpression, as an independent prognostic factor, had a 2.385 times higher risk to relapse than those with lower expression. The DNMT1 A201G gene polymorphism was associated with a reduced overall survival in OSCC patients, p = 0.036.
Our results suggest that DNMT1 could play an important role in modulating OSCC patient survival.
DNMT gene expression could be a potential prognostic marker that might lead to an improvement in diagnosis, prognosis, and prospective use of epigenetic-targeted therapy of OSCC.
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Quantifying the multiple processes which control and modulate the extent of oral bioavailability for drug candidates is critical to accurate projection of human pharmacokinetics (PK). Understanding how gut wall metabolism and hepatic elimination factor into first-pass clearance of drugs has improved enormously. Typically, the cytochrome P450s, uridine 5′-diphosphate-glucuronosyltransferases and sulfotransferases, are the main enzyme classes responsible for drug metabolism. Knowledge of the isoforms functionally expressed within organs of first-pass clearance, their anatomical topology (e.g. zonal distribution), protein homology and relative abundances and how these differ across species is important for building models of human metabolic extraction. The focus of this manuscript is to explore the parameters influencing bioavailability and to consider how well these are predicted in human from animal models or from in vitro to in vivo extrapolation. A unique retrospective analysis of three AstraZeneca molecules progressed to first in human PK studies is used to highlight the impact that species differences in gut wall metabolism can have on predicted human PK. Compared to the liver, pharmaceutical research has further to go in terms of adopting a common approach for characterisation and quantitative prediction of intestinal metabolism. A broad strategy is needed to integrate assessment of intestinal metabolism in the context of typical DMPK activities ongoing within drug discovery programmes up until candidate drug nomination.
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The Independent | Scarlet fever outbreak fears: What are the symptoms, what treatment is available and how is it spread? The Independent A spike in scarlet fever cases in the south of England has raised fears that it could signal an outbreak in the UK. Authorities in Surrey have recorded 33 suspected cases of the bacterial illness in the past four weeks: 43.5 per cent higher than during … |
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Intraosseous lipoma of the iliac: case report.
Rev Bras Ortop. 2016 Jan-Feb;51(1):113-7
Authors: de Moraes FB, Paranahyba RM, do Amaral RA, Bonfim VM, Jordão ND, Souza RD
Abstract
Lipomas are benign tumors that attack fat cells and most often affecting soft tissues in adulthood. On rare occasions, they may affect bones, preferentially the metaphyses of the long bone. They are generally asymptomatic and radiography shows radiolucent lesions with a thin sclerotic rim or radiodense lesions with a thick sclerotic rim. Malignant transformation of these tumors is rare, as is their recurrence, and there is no need for surgery in most cases. In this report, we present a rare case of intraosseous lipoma in the iliac bone.
PMID: 26962507 [PubMed]
Muir-Torre Syndrome: A Case Associated with an Infrequent Gene Mutation.
J Clin Aesthet Dermatol. 2016 Jan;9(1):56-9
Authors: Grob A, Feser C, Grekin S
Abstract
Muir-Torre syndrome is a rare, autosomal dominant genodermatosis characterized by the presence of at least one sebaceous gland neoplasm, associated with an underlying visceral malignancy. Muir-Torre syndrome is believed to be a subtype of Lynch Syndrome. Affected individuals are found to have germline mutations predominantly in DNA mismatch repair gene MSH2, and much less frequently, MLH1. The authors report the case of a 55-year-old woman presenting with multiple cutaneous neoplasms including sebaceoma, basal cell carcinoma, and squamous cell carcinoma; personal history of colorectal and endometrial cancer; and family history of colorectal cancer; found to have a deletion at mismatch repair gene MLH1. It is important to recognize the role of these less common gene deletions in producing the Muir-Torre syndrome phenotype, and consider the correlation of cutaneous manifestations with internal disease. The authors discuss the clinical presentation of Muir-Torre syndrome, methods of diagnosis, and the importance of regular medical surveillance to detect and prevent disease progression in Muir-Torre syndrome patients and their family members.
PMID: 26962393 [PubMed]
Atypical teratoid rhabdoid tumor of the lateral ventricle.
J Pediatr Neurosci. 2015 Oct-Dec;10(4):382-5
Authors: Darmoul M, Nsir AB, Chabchoub I, Hattab MN
Abstract
Atypical teratoid/rhabdoid tumors (AT/RTs) are rare and highly malignant embryonal central nervous system neoplasms, usually seen in very young children with rapid fatal outcome despite aggressive treatment. They are most commonly located in the posterior fossa. Intraventricular location is extremely rare. To the best of our knowledge, only 4 cases of lateral ventricle location were reported in the literature. We report the fifth case of lateral ventricle AT/RT in a 2-month-old male who presented with rapid increase of his head circumference. Brain computed tomography scan and magnetic resonance imaging showed heterogeneous huge mass within the left lateral ventricle extending to the parieto-occipital parenchyma and markedly enhancing by contrast. The baby underwent left transparietal approach with complete removal of the tumor. Histological examination confirmed the diagnosis of AT/RT. An aggressive chemotherapy was administrated postoperatively. The outcome is good without neurological deficit or recurrence after 3 years and half of follow-up.
PMID: 26962351 [PubMed]
5-HT1A receptors (HTR1As) in the insular cortex are thought to be related with the generation of stress-induced functional gastrointestinal disorders (FGIDs), but its mechanism is not clear. Visceral hypersensitivity is one important pathophysiological mechanism of FGIDs. This study aimed to explore the role of HTR1As in mediating stress-induced visceral hypersensitivity and its mechanism in the insular cortex.
Visceral hypersensitivity rat model was established by water avoidance stress (WAS) and the visceral sensitivity was measured by electromyogram. The activities of HTR1As were regulated by microinjecting the HTR1A agonist and antagonist into the insular cortex. The expression levels of 5-HT, HTR1A, N-methyl-d-aspartic acid receptor subtype 2B (NR2B) and c-fos were observed by RT-PCR, Western Blot and immunohistochemical staining.
In WAS rats, the expression levels of 5-HT and HTR1As in the insular cortex were significantly lower (p < 0.05) than that in sham WAS and normal rats, but the levels of c-fos and NR2B were significantly higher (p < 0.05). After microinjecting HTR1As agonist into the insular cortex of WAS rats, the visceral sensitivity and the expression levels of NR2B and c-fos in insular cortex significantly decreased (p < 0.05).
The HTR1As-NR2B signal pathway of insular cortex plays an important role in regulating stress-induced visceral hypersensitivity.
This study aimed to explore the role of 5-HT1A receptors (HTR1As) in mediating stress-induced visceral hypersensitivity and its mechanism in the insular cortex. The results indicated that HTR1A in the insular cortex plays an important role in mediating chronic stress-induced visceral hypersensitivity in rats. N-methyl-d-aspartic acid receptor subtype 2B may be one of the important downstream signaling molecules of HTR1A mediating the visceral hypersensitivity.
Hirschsprung disease (HSCR) is a congenital bowel disease caused by the absence of nerve cells in portions of the intestine. Our recent genome-wide association study has identified a variant (rs1254900) of vesicle-associated membrane protein 5 (VAMP5) as a potential risk locus for total colonic aganglionosis (TCA) in HSCR. In addition, VAMP5 is a member of the VAMP/synaptobrevin protein complex, which participates in nerve signal transduction by regulating the vesicular fusion of the neurotransmitter in synaptic transmission.
A total of 11 single nucleotide polymorphisms (SNPs), including those in the functionally important coding region, were selected on the basis of linkage disequilibrium and genotyped in 187 HSCR patients and 283 unaffected controls by using a TaqMan assay. Logistic analysis was conducted to investigate the possible association between VAMP5 SNPs and the risk of HSCR.
Genetic variants of VAMP5 showed increased association signals in the TCA subgroup of HSCR patients (minimum p = 9.69 × 10−5, OR = 3.93 at rs10206961) compared to other subgroups, even after Bonferroni correction (pcorr = 0.002). In haplotype analysis, three haplotypes (BL1_ht1, BL2_ht1, and BL2_ht2) were associated with the risk of TCA (minimum pcorr = 0.005). In additional combined analysis after imputation based on our previous GWAS, five SNPs still retained significant associations with the TCA subtype (minimum pcorr = 0.006 at rs10206961).
Considering that differential genetic effects on the development of the enteric nervous system, our results suggest that VAMP5 may be associated with the TCA of HSCR. However, further replications and functional evaluations are required.
We examine the association between VAMP5 SNPs and the risk of Hirschsprung disease in a Korean population. Five genetic variants (rs1561198, rs55971080, rs10206961, rs1254900, and rs14242) were associated with risk of TCA (minimum p = 9.69 × 10−5, pcorr = 0.002 at rs10206961). Results indicating increased association signals in the TCA subgroup compared to other subgroups suggest that VAMP5 may have an effect on the extent of the aganglionic segment in ENS development.
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Postoperative Cerebrospinal Fluid Leakage Associated With Total En Bloc Spondylectomy.
Orthopedics. 2015 Jul 1;38(7):e561-6
Authors: Yokogawa N, Murakami H, Demura S, Kato S, Yoshioka K, Hayashi H, Ishii T, Igarashi T, Fang X, Tsuchiya H
Abstract
Cerebrospinal fluid (CSF) leakage is a serious postoperative complication associated with total en bloc spondylectomy. The authors examined the risk factors for CSF leakage after this procedure. A total of 72 patients underwent total en bloc spondylectomy at the authors' institution between May 2010 and April 2013. Postoperative CSF leakage was observed in 17 of the 72 patients (23.6%). The results of univariate analysis suggested that age 54 years or older, preoperative surgical site irradiation, resection of 3 or more vertebral bodies, and dural injury were significant risk factors for postoperative CSF leakage after total en bloc spondylectomy. Multivariate analysis showed that preoperative surgical site irradiation was the only significant risk factor for postoperative CSF leakage (adjusted odds ratio, 5.22; 95% confidence interval, 1.03-26.45, P=.046). The authors also assessed the course of treatment for postoperative CSF leakage in each patient. Of 17 patients with postoperative CSF leakage, 13 recovered without further complications, but 4 required reoperation (2 for wound dehiscence, 1 for surgical site infection, and 1 for severe intracranial hypotension). All 4 patients who required reoperation had a history of surgical site irradiation. Thus, this study suggests that careful consideration should be given to postoperative CSF leakage in patients with a history of surgical site irradiation. These findings may contribute to the management of postoperative CSF leakage associated with total en bloc spondylectomy and supplement the information given to the patient in the process of obtaining informed consent.
PMID: 26186316 [PubMed - indexed for MEDLINE]
Efficacy of octreotide against chylothorax following lateral neck dissection for thyroid cancer: A case report.
Int J Surg Case Rep. 2016 Feb 27;21:107-110
Authors: Hayashibara N, Ogawa T, Tsuji E, Ishizuna K
Abstract
INTRODUCTION: Postsurgical chylothorax is a rare complication of cervical dissection for thyroid cancer. We report that octreotide, a synthetic analog of somatostatin, is effective in treating chylothorax after thyroid carcinoma surgery.
PRESENTATION OF CASE: The patient was a 48-year-old woman who presented to our institution complaining of a left anterior cervical mass. We diagnosed this as thyroid papillary carcinoma and performed a subtotal excision of the thyroid gland with left cervical lymph node dissection. The patient developed dyspnea, and a chest X-ray revealed bilateral chylothorax on Day 4 post-surgery. Octreotide was administered since bilateral chylothorax was noted. A marked decrease in chyle effusion was noted just 3 days after starting octreotide, and after a total of 9 days of treatment, there were no further signs of chylous effusion.
DISCUSSION: Octreotide is effective against postsurgical chylothorax; however, if there are no signs of improvement, we believe surgical treatment should be considered.
CONCLUSION: Octreotide should be administered first to treat postsurgical chylothorax before surgical treatment is considered.
PMID: 26963261 [PubMed - as supplied by publisher]
Case report of non-traumatic spontaneous intrahepatic bile duct rupture in an adult.
Int J Surg Case Rep. 2016 Feb 20;21:104-106
Authors: Sumer F, Kayaalp C, Karagül S, Ertugrul I, Yagci MA, Onur A
Abstract
INTRODUCTION: Spontaneous rupture of the biliary duct, a rare condition in adults, is difficult to diagnose preoperatively and presents with acute abdominal symptoms. The treatment of this rare condition should be based on the individual's clinical status. We present peripheric biliary duct rupture (segment three) treated with external segment III drainage and postoperative endoscopic removal of the stones.
PRESENTATION OF CASE: An 82-year-old male patient presented with abdominal pain and fever. An ultrasound (US) revealed a solid gall stone lesion, 3cm in diameter, in liver segments three and four with additional intra-abdominal fluid accumulation without coexisting free air. A diagnostic laparotomy was then performed because the patient had signs of peritonitis. Exploration revealed a biliary leakage from the posterior surface of segment three. An external biliary drainage catheter was inserted to the perforated segment III duct via a 6 French (6F) feeding catheter. He was discharged after 10 days and his intracholedocal stent was removed postoperative after three months. The patient continues to be monitored.
DISCUSSION: Spontaneous rupture of the intrahepatic biliary duct is a rare condition. Although occurrence is frequently reported as spontaneous, the majority of cases are related to choledocholithiasis. The role of surgical treatment in cases of spontaneous bile duct rupture is unclear. When biliary peritonitis is present, drainage of contaminated biliary fluid, T-tube drainage, closure of the biliary duct, as well as primary disease conditions, should be reviewed prior to treatment.
CONCLUSION: Surgical treatment of spontaneous biliary duct rupture should be indicated only after careful consideration of the patient's clinical and comorbidity status.
PMID: 26963260 [PubMed - as supplied by publisher]
Gene and pathway level analyses of germline DNA-repair gene variants and prostate cancer susceptibility using the iCOGS-genotyping array.
Br J Cancer. 2016 Mar 10;
Authors: Saunders EJ, Dadaev T, Leongamornlert DA, Olama AA, Benlloch S, Giles GG, Wiklund F, Grönberg H, Haiman CA, Schleutker J, Nordestgaard BG, Travis RC, Neal D, Pasayan N, Khaw KT, Stanford JL, Blot WJ, Thibodeau SN, Maier C, Kibel AS, Cybulski C, Cannon-Albright L, Brenner H, Park JY, Kaneva R, Batra J, Teixeira MR, Pandha H, Govindasami K, Muir K, UK Genetic Prostate Cancer Study Collaborators, UK ProtecT Study Collaborators, PRACTICAL Consortium, Easton DF, Eeles RA, Kote-Jarai Z
Abstract
BACKGROUND: Germline mutations within DNA-repair genes are implicated in susceptibility to multiple forms of cancer. For prostate cancer (PrCa), rare mutations in BRCA2 and BRCA1 give rise to moderately elevated risk, whereas two of ∼100 common, low-penetrance PrCa susceptibility variants identified so far by genome-wide association studies implicate RAD51B and RAD23B.
METHODS: Genotype data from the iCOGS array were imputed to the 1000 genomes phase 3 reference panel for 21 780 PrCa cases and 21 727 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. We subsequently performed single variant, gene and pathway-level analyses using 81 303 SNPs within 20 Kb of a panel of 179 DNA-repair genes.
RESULTS: Single SNP analyses identified only the previously reported association with RAD51B. Gene-level analyses using the SKAT-C test from the SNP-set (Sequence) Kernel Association Test (SKAT) identified a significant association with PrCa for MSH5. Pathway-level analyses suggested a possible role for the translesion synthesis pathway in PrCa risk and Homologous recombination/Fanconi Anaemia pathway for PrCa aggressiveness, even though after adjustment for multiple testing these did not remain significant.
CONCLUSIONS: MSH5 is a novel candidate gene warranting additional follow-up as a prospective PrCa-risk locus. MSH5 has previously been reported as a pleiotropic susceptibility locus for lung, colorectal and serous ovarian cancers.British Journal of Cancer advance online publication 10 March 2016. doi:10.1038/bjc.2016.50 www.bjcancer.com.
PMID: 26964030 [PubMed - as supplied by publisher]
Primary Retroperitoneal Mucinous Cystadenoma.
Ann Coloproctol. 2016 Feb;32(1):33-7
Authors: Lee SY, Han WC
Abstract
Mucinous cystadenomas and cystadenocarcinomas of the ovary are clinically and histopathologically well-established common tumors. However, primary retroperitoneal mucinous cystic tumors are extremely rare, and although their histopathogenesis is still uncertain, several theories have been proposed. Most authors suggest that they develop through mucinous metaplasia in a preexisting mesothelium-lined cyst. An accurate preoperative diagnosis of these tumors is difficult because no effective diagnostic measures have been established. Delay in diagnosis and treatment of this tumor may be fatal for the patient because of complications such as rupture, infection, and malignant transformation. We describe the case of a 31-year-old woman with abdominal pain and a palpable mass. Computed tomography of the abdomen revealed a retroperitoneal cystic mass, which was resected successfully through laparoscopy. Histopathological examination of the resected mass confirmed the diagnosis of a primary retroperitoneal mucinous cystadenoma. The patient was discharged on postoperative day 5 without any complications.
PMID: 26962534 [PubMed]
Intraosseous lipoma of the iliac: case report.
Rev Bras Ortop. 2016 Jan-Feb;51(1):113-7
Authors: de Moraes FB, Paranahyba RM, do Amaral RA, Bonfim VM, Jordão ND, Souza RD
Abstract
Lipomas are benign tumors that attack fat cells and most often affecting soft tissues in adulthood. On rare occasions, they may affect bones, preferentially the metaphyses of the long bone. They are generally asymptomatic and radiography shows radiolucent lesions with a thin sclerotic rim or radiodense lesions with a thick sclerotic rim. Malignant transformation of these tumors is rare, as is their recurrence, and there is no need for surgery in most cases. In this report, we present a rare case of intraosseous lipoma in the iliac bone.
PMID: 26962507 [PubMed]
Review Articles
N Jufas, N Patel
The Journal of Laryngology & Otology,FirstView Article(s), 6 pages
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Muir-Torre Syndrome: A Case Associated with an Infrequent Gene Mutation.
J Clin Aesthet Dermatol. 2016 Jan;9(1):56-9
Authors: Grob A, Feser C, Grekin S
Abstract
Muir-Torre syndrome is a rare, autosomal dominant genodermatosis characterized by the presence of at least one sebaceous gland neoplasm, associated with an underlying visceral malignancy. Muir-Torre syndrome is believed to be a subtype of Lynch Syndrome. Affected individuals are found to have germline mutations predominantly in DNA mismatch repair gene MSH2, and much less frequently, MLH1. The authors report the case of a 55-year-old woman presenting with multiple cutaneous neoplasms including sebaceoma, basal cell carcinoma, and squamous cell carcinoma; personal history of colorectal and endometrial cancer; and family history of colorectal cancer; found to have a deletion at mismatch repair gene MLH1. It is important to recognize the role of these less common gene deletions in producing the Muir-Torre syndrome phenotype, and consider the correlation of cutaneous manifestations with internal disease. The authors discuss the clinical presentation of Muir-Torre syndrome, methods of diagnosis, and the importance of regular medical surveillance to detect and prevent disease progression in Muir-Torre syndrome patients and their family members.
PMID: 26962393 [PubMed]
Atypical teratoid rhabdoid tumor of the lateral ventricle.
J Pediatr Neurosci. 2015 Oct-Dec;10(4):382-5
Authors: Darmoul M, Nsir AB, Chabchoub I, Hattab MN
Abstract
Atypical teratoid/rhabdoid tumors (AT/RTs) are rare and highly malignant embryonal central nervous system neoplasms, usually seen in very young children with rapid fatal outcome despite aggressive treatment. They are most commonly located in the posterior fossa. Intraventricular location is extremely rare. To the best of our knowledge, only 4 cases of lateral ventricle location were reported in the literature. We report the fifth case of lateral ventricle AT/RT in a 2-month-old male who presented with rapid increase of his head circumference. Brain computed tomography scan and magnetic resonance imaging showed heterogeneous huge mass within the left lateral ventricle extending to the parieto-occipital parenchyma and markedly enhancing by contrast. The baby underwent left transparietal approach with complete removal of the tumor. Histological examination confirmed the diagnosis of AT/RT. An aggressive chemotherapy was administrated postoperatively. The outcome is good without neurological deficit or recurrence after 3 years and half of follow-up.
PMID: 26962351 [PubMed]
This American Head and Neck Society (AHNS) consensus statement discusses the techniques of laryngeal examination for patients undergoing thyroidectomy and parathyroidectomy. It is intended to help guide all clinicians who diagnose or manage adult patients with thyroid disease for whom surgery is indicated, contemplated, or has been performed. This consensus statement concludes that flexible transnasal laryngoscopy is the optimal laryngeal examination technique, with other techniques including laryngeal ultrasound and stroboscopy being useful in selected scenarios. © 2016 Wiley Periodicals, Inc. Head Neck, 2016
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Delayed diagnosis of Gorlin syndrome: Learning from mistakes!
J Pediatr Neurosci. 2015 Oct-Dec;10(4):359-61
Authors: Ramanathan S, Kumar D, Al Heidous M, Palaniappan Y
Abstract
Gorlin syndrome (GS) is a rare inherited multisystem disorder with predisposition to basal cell carcinomas and various other neoplasms. Characteristic features include falx calcification, multiple odontogenic keratocysts (OKCs), early onset medulloblastoma, craniofacial and skeletal malformations, cardiac and ovarian fibroma. We present a case of GS in a 9-year-old girl with recurrent dental infections which was overlooked for 8 years. Diagnosis was finally suggested by the incidental detection of multiple OKCs and ovarian fibromas on follow-up magnetic resonance imaging performed for surveillance of previous operated brain tumor.
PMID: 26962343 [PubMed]
Solitary plasmacytoma of the mandible: report of two cases.
BMJ Case Rep. 2016;2016
Authors: Kucukkurt S, Karan NB, Senguven B, Kahraman S
Abstract
Plasma cell neoplasms (plasmacytoma) are discrete, solitary masses of lymphoid neoplastic proliferations of B cells. Plasmacytomas comprise three groups: multiple myeloma, solitary plasmacytoma (SP) and extramedullary plasmacytoma. SP originates as a clone of transformed malignant plasma cells in the bone marrow. SP of the jaw is a rare condition; therefore diagnosis is quite difficult and often results in misdiagnosis. MM is a lymphoproliferative disease the prognosis of which is worse than SP. SP can progress to MM in a few months to years after diagnosis. In this regard, early diagnosis of the disease is of utmost importance. This article presents two cases of SP diagnosed in the mandible and documented with clinical, radiographic and histological findings.
PMID: 26961559 [PubMed - in process]
Treatment for local glottic cancer recurrences after primary transoral laser microsurgery (TLM) has not been standardized.
In 33 consecutive cases of salvage TLM after laser surgery for early glottic carcinoma failed, we retrospectively considered the potential clinicopathological prognostic factors in univariate statistical setting.
Patient age <65 years and pathological involvement of the deep margins were associated with a higher second recurrence rate and shorter disease-free survival.
The age of the patient and the pathological status of surgical margins after salvage TLM could be useful for planning a closer endoscopic/radiological follow-up in selected patients at high risk of recurrence. Other appropriately designed studies are needed to see if an open surgical approach should be considered for younger patients (<65 years old) with recurrent glottic carcinoma after primary TLM. © 2016 Wiley Periodicals, Inc. Head Neck, 2016
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When a patient cannot be intubated or ventilated, cricothyrotomy is indicated. Risks associated with emergent cricothyrotomy are significant, and this procedure typically requires revision. Additional options for establishing an emergent airway are limited. Thus, elective tracheotomy to ensure a safe airway after procedures involving the upper aerodigestive tract is common. Although safe and effective overall, this procedure is not without additional risks, added resources, complex cares, and extended hospitalizations.
We present a case in which exposure of the anterior trachea was performed without tracheotomy in a patient with a high-risk airway undergoing an open partial laryngectomy.
The patient did not develop respiratory distress postoperatively and was able to avoid a tracheostomy and its associated cares.
Pretracheotomy with tracheal exposure simplifies emergent surgical access to the airway. We believe tracheal exposure in the appropriately selected patient is a safe and cost-effective alternative to elective tracheotomy. © 2016 Wiley Periodicals, Inc. Head Neck, 2016
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Patients with cancer undergoing head and neck reconstruction can experience significant distress from alterations in appearance and bodily functioning. We sought to delineate salient dimensions of body image concerns in this patient population preparing for reconstructive surgery.
Participants completed self-report questionnaires evaluating numerous aspects of body image. We used Bayesian factor analysis modeling methods to identify latent factors emerging from the data.
We identified 2 latent factors: appearance distress and functional difficulties. The highest level of preoperative body image concerns were related to distress about appearance changes and its perceived social consequences. Appearance distress items displayed greater variability compared with functional difficulties.
Appearance and functional changes to body image are important areas of concern for patients with head and neck cancer as they prepare for reconstructive surgery. Knowledge regarding specific body image issues can be used to guide psychosocial assessments and intervention to enhance patient care. © 2016 Wiley Periodicals, Inc. Head Neck, 2016
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Anaplastic lymphoma kinase positive inflammatory myofibroblastic tumor of the urachus: A rare neoplasm in an unusual location.
Indian J Pathol Microbiol. 2016 Jan-Mar;59(1):93-5
Authors: Venkatesh K, Madhusudhan HR
Abstract
Inflammatory myofibroblastic tumors (IMTs) are uncommon benign neoplasms in the abdomen, and urachal involvement is very rare. IMT of the urachus is usually mistaken clinically and radiologically for a malignant tumor. The tumor has spindle cell proliferation with a prominent inflammatory infiltrate and myxoid degeneration favoring other designations such as inflammatory pseudotumor and fibromyxoid pseudotumor. Complete excision is the treatment of choice. The case documented here was in a 50-year-old male, with an abdominal mass diagnosed on computed tomography scan as adenocarcinoma of urachus infiltrating the bladder. Histopathology showed a benign spindle cell tumor invading bladder muscle. Immunohistochemistry aided in diagnosing an anaplastic lymphoma kinase (ALK)-1 positive IMT. Approximately, 50% of the IMTs show ALK positivity, and though when present, it indicates neoplastic nature of the spindle cells, the pathogenesis of IMT is still elusive. The urachal IMTs need documentation in literature for their rarity and diagnostic dilemma posed by them.
PMID: 26960648 [PubMed - in process]
This study was designed to comparatively assess laryngeal function and quality of life (QOL) of patients after laser surgery (LS) or radiotherapy (RT) for early glottic cancer.
Sixty-four patients with T1 glottic cancer treated with RT or type II cordectomy underwent both subjective and objective vocal assessments. The LS group was divided into the following: (1) vaporization with defocused mode (laser surgery [LS]-Vap); and (2) excision with focused mode using lower power (LS-Ex).
Auditory-perceptual evaluation and videostroboscopic images in the LS-Ex group worsened shortly after treatment and time-dependent recovery was quicker than in the LS-Vap group. The LS-Ex group showed equivalent posttherapeutic vocal function with the RT group by acoustics, aerodynamics, and self-assessment questionnaire analysis, whereas the LS-Vap group showed statistically significant worse function.
The multidimensional assessment showed that early glottic cancer could be successfully treated by either RT or LS-Ex with equivalent posttherapeutic laryngeal function and QOL. © 2016 Wiley Periodicals, Inc. Head Neck, 2016
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T3 laryngeal cancer encompasses heterogeneous lesions whose treatment is still debated. The purpose of this study was to evaluate transoral laser microsurgery (TLM) in management of selected T3 glottic and supraglottic cancers.
Fifty-six patients with selected T3 glottic and supraglottic squamous cell carcinomas (SCCs) treated by TLM ± selective neck dissection ± adjuvant therapy were evaluated in terms of overall survival (OS), disease-free survival (DFS), and organ preservation rates.
For the entire cohort, 5-year OS and DFS were 63.3% and 72.4%, whereas they were 65.2% and 72.9% for glottic and 59.3% and 76.3% for supraglottic SCC, respectively. No patient required permanent tracheostomy and 1 patient was gastrostomy tube-dependent at last follow-up.
TLM ± selective neck dissection ± adjuvant (chemo)radiotherapy for selected T3 glottic and supraglottic SCC represents an effective alternative treatment to open partial laryngectomies and nonsurgical organ preservation protocols, particularly in elderly and frail patients. © 2016 Wiley Periodicals, Inc. Head Neck, 2016
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Primary endobronchial myxoid leiomyoma in a child: An unusual case report and review of literature.
Indian J Pathol Microbiol. 2016 Jan-Mar;59(1):87-9
Authors: Awasthi A, Dubey S, Sabhikhi AK, Bal S
Abstract
Primary leiomyomas are rare benign tumors of the lung and only 25 cases have been documented in children, most of which are endobronchial. Leiomyomas are benign smooth muscle neoplasms, usually diagnosed on morphological characteristics. However, immunohistochemistry plays a crucial role in the lineage differentiation when these are encountered at unusual sites or with unexpected morphological features. We report a case of endobronchial tumor of a 13-year-old male child who presented with a dry cough and hemoptysis. A mass lesion in the right main bronchus was detected by bronchoscopy and contrast-enhanced computed tomography. On histopathological examination of the resected specimen, a diagnosis of myxoid leiomyoma was made. To the best of our knowledge, this is the first case of myxoid leiomyoma to be reported in the respiratory tract. This case also demonstrates the need for a high index of suspicion and the role of immunomarkers in the diagnosis of such challenging cases.
PMID: 26960646 [PubMed - in process]
Postradiation angiosarcoma of bladder with extensive osseous metaplasia.
Indian J Pathol Microbiol. 2016 Jan-Mar;59(1):78-80
Authors: Rallabandi HB, Swain M, Gowrishankar S, Sinha S
Abstract
Angiosarcomas are rare soft tissue neoplasms accounting for <2% of all sarcomas. Rare cases have been reported in other sites like breast, spleen, liver, bone and bladder. This is a case report of an angiosarcoma of the bladder in a 65 year old lady who came with complaints of haematuria. Ultrasonography and computerized tomography revealed a bladder tumour with calcification, which on cystoscopy also showed a calcified mass. The patient had a past history of carcinoma cervix for which she had undergone surgery and radiotherapy, 22 years ago. Biopsy of the bladder mass showed features of a high grade epithelioid sarcoma with extensive osseous metaplasia. On immune stains,the tumour was positive for CD31 and vimentin and negative for cytokeratin, desmin and CD34. Until now, only sixteen cases of angiosarcoma of the bladder have been reported in english literature, of which 6 occurred secondary to radiation. Our case is the first to occur after 22 years of radiotherapy and have extensive osseous metaplasia.
PMID: 26960643 [PubMed - in process]
