MicroRNA-1225-5p inhibits proliferation and metastasis of gastric carcinoma through repressing insulin receptor substrate-1 and activation of β-catenin signaling.

MicroRNA-1225-5p inhibits proliferation and metastasis of gastric carcinoma through repressing insulin receptor substrate-1 and activation of β-catenin signaling.

Oncotarget. 2015 Dec 14;

Authors: Zheng H, Zhang F, Lin X, Huang C, Zhang Y, Li Y, Lin J, Chen W, Lin X

Abstract
Emerging evidence has linked aberrantly expressed microRNAs (miRNAs) with oncogenesis and malignant development in various human cancers. However, their specific roles and functions in gastric carcinoma (GC) remain largely undefined. In this study we identify and report a novel miRNA, miR-1225-5p, as tumor suppressor in GC development and progression. Microarray analysis revealed that there were fifty-six differentially expressed miRNAs (thirty-two upregulated and twenty-four downregulated) in GC tumor samples compared to their corresponding nontumorous tissues. Downregulation of miR-1225-5p was frequently detected in GC and strongly correlated with more aggressive phenotypes and poor prognosis. Functional assays demonstrated that ectopic overexpression of miR-1225-5p could inhibit cell proliferation, colony formation, migration and invasion in vitro, as well as suppress tumor growth and metastasis in nude mice. Further integrative and functional studies suggested insulin receptor substrate 1 (IRS1) as a downstream effector of miR-1225-5p which acted through β-catenin signaling pathway. These results demonstrate that miR-1225-5p serves to constrain GC growth and metastatic potential via inhibition of IRS1 and β-catenin signaling. Therefore, downregulation of miR-1225-5p is likely to be one of major molecular mechanisms accounting for the development and progression of GC.

PMID: 26684358 [PubMed - as supplied by publisher]

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Low expression of BMPRIB indicates poor prognosis of breast cancer and is insensitive to taxane-anthracycline chemotherapy.

Low expression of BMPRIB indicates poor prognosis of breast cancer and is insensitive to taxane-anthracycline chemotherapy.

Oncotarget. 2015 Dec 14;

Authors: Dai K, Qin F, Zhang H, Liu X, Guo C, Zhang M, Gu F, Fu L, Ma Y

Abstract
Bone morphogenetic protein receptor type IB (BMPRIB) is one osteogenesis factor, which function in breast cancer has been rarely explored until recently. In the clinical study presented here, involving a cohort of 368 invasive ductal carcinoma (IDC) patients, we identified that patients with low expression of BMPRIB exhibited poor prognosis, especially in the luminal B subtype. We also provided the first piece of evidence that low level of BMPRIB was a promoting factor for breast cancer patients to develop bone metastasis, but not lung, liver or brain. The first of its kind, we reported that patients with high expression of BMPRIB exhibited favorable prognosis by a retrospective analysis consisting of 168 patients treated with TE (taxane and anthracycline) regimens. And the patients with high expression of BMPRIB were more sensitive to TE regimens in the detection of 32 paired pre-neoadjuvant and post-neoadjuvant specimens. Overall, our study concluded that low expression of BMPRIB indicated poor prognosis of breast cancer and was insensitive to taxane-anthracycline chemotherapy. Our findings also lay a foundation to help clinicians improve identification of patients for TE regimens by BMPRIB in the era of precision medicine.

PMID: 26684357 [PubMed - as supplied by publisher]

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The B56γ3 regulatory subunit-containing protein phosphatase 2A outcompetes Akt to regulate p27KIP1 subcellular localization by selectively dephosphorylating phospho-Thr157 of p27KIP1.

The B56γ3 regulatory subunit-containing protein phosphatase 2A outcompetes Akt to regulate p27KIP1 subcellular localization by selectively dephosphorylating phospho-Thr157 of p27KIP1.

Oncotarget. 2015 Dec 14;

Authors: Lai TY, Yen CJ, Tsai HW, Yang YS, Hong WF, Chiang CW

Abstract
The B56γ-containing protein phosphatase 2A (PP2A-B56γ) has been postulated to have tumor suppressive functions. Here, we report regulation of p27KIP1 subcellular localization by PP2A-B56γ3. B56γ3 overexpression enhanced nuclear localization of p27KIP1, whereas knockdown of B56γ3 decreased p27KIP1 nuclear localization. B56γ3 overexpression decreased phosphorylation at Thr157 (phospho-Thr157), whose phosphorylation promotes cytoplasmic localization of p27KIP1, whereas B56γ3 knockdown significantly increased the level of phospho-Thr157. In vitro, PP2A-B56γ3 catalyzed dephosphorylation of phospho-Thr157 in a dose-dependent and okadaic acid-sensitive manner. B56γ3 did not increase p27KIP1 nuclear localization by down-regulating the upstream kinase Akt activity and outcompeted a myristoylated constitutively active Akt (Aktca) in regulating Thr157 phosphorylation and subcellular localization of p27KIP1. In addition, results of interaction domain mapping revealed that both the N-terminal and C-terminal domains of p27 and a domain at the C-terminus of B56γ3 are required for interaction between p27 and B56γ3. Furthermore, we demonstrated that p27KIP1 levels are positively correlated with B56γ levels in both non-tumor and tumor parts of a set of human colon tissue specimens. However, positive correlation between nuclear p27KIP1 levels and B56γ levels was found only in the non-tumor parts, but not in tumor parts of these tissues, implicating a dysregulation in PP2A-B56γ3-regulated p27KIP1 nuclear localization in these tumor tissues. Altogether, this study provides a new mechanism by which the PP2A-B56γ3 holoenzyme plays its tumor suppressor role.

PMID: 26684356 [PubMed - as supplied by publisher]

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TGF-β/Smad3 signalling regulates the transition of bone marrowderived macrophages into myofibroblasts during tissue fibrosis.

TGF-β/Smad3 signalling regulates the transition of bone marrowderived macrophages into myofibroblasts during tissue fibrosis.

Oncotarget. 2015 Dec 14;

Authors: Wang S, Meng XM, Ng YY, Ma FY, Zhou S, Zhang Y, Yang C, Huang XR, Xiao J, Wang YY, Ka SM, Tang YJ, Chung AC, To KF, Nikolic-Paterson DJ, Lan HY

Abstract
Myofibroblasts are a main cell-type of collagen-producing cells during tissue fibrosis, but their origins remains controversial. While bone marrow-derived myofibroblasts in renal fibrosis has been reported, the cell origin and mechanisms regulating their transition into myofibroblasts remain undefined. In the present study, cell lineage tracing studies by adoptive transfer of GFP+ or dye-labelled macrophages identified that monocyte/macrophages from bone marrow can give rise to myofibroblasts via the process of macrophage-myofibroblast transition (MMT) in a mouse model of unilateral ureteric obstruction. The MMT cells were a major source of collagen-producing fibroblasts in the fibrosing kidney, accounting for more than 60% of α-SMA+ myofibroblasts. The MMT process occurred predominantly within M2-type macrophages and was regulated by TGF-β/Smad3 signalling as deletion of Smad3 in the bone marrow compartment of GFP+ chimeric mice prevented the M2 macrophage transition into the MMT cells and progressive renal fibrosis. In vitro studies in Smad3 null bone marrow macrophages also showed that Smad3 was required for TGF-β1-induced MMT and collagen production. In conclusion, we have demonstrated that bone marrow-derived fibroblasts originate from the monocyte/macrophage population via a process of MMT. This process contributes to progressive renal tissue fibrosis and is regulated by TGF-β/Smad3 signalling.

PMID: 26684242 [PubMed - as supplied by publisher]

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miR-192, a prognostic indicator, targets the SLC39A6/SNAIL pathway to reduce tumor metastasis in human hepatocellular carcinoma.

miR-192, a prognostic indicator, targets the SLC39A6/SNAIL pathway to reduce tumor metastasis in human hepatocellular carcinoma.

Oncotarget. 2015 Dec 14;

Authors: Lian J, Jing Y, Dong Q, Huan L, Chen D, Bao C, Wang Q, Zhao F, Li J, Yao M, Qin L, Liang L, He X

Abstract
Metastasis is one of the causes of cancer death. Functions and mechanisms of microRNAs (miRNAs) involved in hepatocellular carcinoma (HCC) metastasis are largely unknown. Here, a miRNA microarray analysis was performed in MHCC-97L, MHCC-97H and HCC-LM3 cells with gradually increasing metastatic potential to disclose crucial miRNAs involved in HCC metastasis. miR-192 expression decreased and negatively correlated with vascular invasion in HCC specimens. Gain and loss of function studies revealed that miR-192 significantly suppressed metastasis of HCC cells in vitro and in vivo. Solute carrier family 39 member 6 (SLC39A6) was identified as a direct and functional target of miR-192. In addition, SLC39A6 negatively correlated with miR-192 in HCC samples and promoted HCC cell migration and invasion. Moreover, miR-192 decreased SLC39A6 expression, subsequently downregulating SNAIL and upregulating E-cadherin expression. Suppression of migration and invasion caused by miR-192 overexpression was alleviated by exogenous Snail expression. Intriguingly, lower miR-192 expression and higher SLC39A6 expression significantly contributed to poorer outcomes in HCC patients. Multivariate analysis indicated that miR-192 was an independent and significant predictor of HCC patient overall survival. In conclusion, we newly determined that miR-192 targeted the SLC39A6/SNAIL pathway to reduce tumor metastasis in HCC cells. This axis provided insights into the mechanism underlying miRNA regulation of HCC metastasis and a novel therapeutic target for HCC treatment.

PMID: 26684241 [PubMed - as supplied by publisher]

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Identification of the BRAF V600E mutation in gastroenteropancreatic neuroendocrine tumors.

Identification of the BRAF V600E mutation in gastroenteropancreatic neuroendocrine tumors.

Oncotarget. 2015 Dec 14;

Authors: Park C, Ha SY, Kim ST, Kim HC, Heo JS, Park YS, Lauwers G, Lee J, Kim KM

Abstract
Genomic profiles of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are still insufficiently understood, and the genetic alterations associated with drug responses have not been studied. Here, we performed whole exome sequencing of 12 GEP-NETs from patients enrolled in a nonrandomized, open-labeled, single-center phase II study for pazopanib, and integrated our results with previously published results on pancreas (n = 12) and small intestine NETs (n = 50). The mean numbers of somatic mutations in each case varied widely from 20 to 4682. Among 12 GEP-NETs, eight showed mutations of more than one cancer-related gene, including TP53, CNBD1, RB1, APC, BCOR, BRAF, CTNNB1, EGFR, EP300, ERBB3, KDM6A, KRAS, MGA, MLL3, PTEN, RASA1, SMARCB1, SPEN, TBC1D12, and VHL. TP53 was recurrently mutated in three cases, whereas CNBD1 and RB1 mutations were identified in two cases. Three GEP-NET patients with TP53 mutations demonstrated a durable response and one small intestinal grade (G) 1 NET patient with BRAF V600E mutation showed progression after pazopanib treatment. We found BRAF V600E (G1 NET from rectum and two G3 NETs from colon) and BRAF G593S (G2 NET from pancreas) missense mutations (9.1%) in an independent cohort of 44 GEP-NETs from the rectum (n = 26), colon (n = 7), pancreas (n = 4), small intestine (n = 3), stomach (n = 3) and appendix (n = 1) by Sanger sequencing. All tumor specimens were obtained before chemotherapy. In conclusion, BRAF V600E mutation is likely to result in resistance to pazopanib but may be a potentianally actionable mutation in metastatic GEP-NETs patients.

PMID: 26684240 [PubMed - as supplied by publisher]

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Overcoming melanoma resistance to vemurafenib by targeting CCL2-induced miR-34a, miR-100 and miR-125b.

Overcoming melanoma resistance to vemurafenib by targeting CCL2-induced miR-34a, miR-100 and miR-125b.

Oncotarget. 2015 Dec 14;

Authors: Vergani E, Di Guardo L, Dugo M, Rigoletto S, Tragni G, Ruggeri R, Perrone F, Tamborini E, Gloghini A, Arienti F, Vergani B, Deho P, De Cecco L, Vallacchi V, Frati P, Shahaj E, Villa A, Santinami M, De Braud F, Rivoltini L, Rodolfo M

Abstract
In melanoma, the adaptative cell response to BRAF inhibitors includes altered patterns of cytokine production contributing to tumor progression and drug resistance. Among the factors produced by PLX4032-resistant melanoma cell lines, CCL2 was higher compared to the sensitive parental cell lines and increased upon drug treatment. CCL2 acted as an autocrine growth factor for melanoma cells, stimulating the proliferation and resistance to apoptosis. In patients, CCL2 is detected in melanoma cells in tumors and in plasma at levels that correlate with tumor burden and lactate dehydrogenase. Vemurafenib treatment increased the CCL2 levels in plasma, whereas the long-term clinical response was associated with low CCL2 levels.Increased CCL2 production was associated with miRNA deregulation in the resistant cells. miR-34a, miR-100 and miR-125b showed high expression in both resistant cells and in tumor biopsies that were obtained from treated patients, and they were involved in the control of cell proliferation and apoptosis. Inhibition of CCL2 and of the selected miRNAs restored both the cell apoptosis and the drug efficacy in resistant melanoma cells. Therefore, CCL2 and miRNAs are potential prognostic factors and attractive targets for counteracting treatment resistance in metastatic melanoma.

PMID: 26684239 [PubMed - as supplied by publisher]

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Targeting a novel domain in podoplanin for inhibiting plateletmediated tumor metastasis.

Targeting a novel domain in podoplanin for inhibiting plateletmediated tumor metastasis.

Oncotarget. 2015 Dec 14;

Authors: Sekiguchi T, Takemoto A, Takagi S, Takatori K, Sato S, Takami M, Fujita N

Abstract
Podoplanin/Aggrus is a sialoglycoprotein expressed in various cancers. We previously identified podoplanin as a key factor in tumor-induced platelet aggregation. Podoplanin-mediated platelet aggregation enhances tumor growth and metastasis by secreting growth factors and by forming tumor emboli in the microvasculature. Thus, precise analysis of the mechanisms of podoplanin-mediated platelet aggregation is critical for developing anti-tumor therapies. Here we report the discovery of a novel platelet aggregation-inducing domain, PLAG4 (81-EDLPT-85). PLAG4 has high homology to the previously reported PLAG3 and contributes to the binding of its platelet receptor CLEC-2. Mutant analyses indicated that PLAG4 exhibits a predominant platelet-aggregating function relative to PLAG3 and that conserved Glu81/Asp82/Thr85 residues in PLAG4 are indispensable for CLEC-2 binding. By establishing anti-PLAG4-neutralizing monoclonal antibodies, we confirmed its role in CLEC-2 binding, platelet aggregation, and tumor emboli formation. Our results suggest the requirement of simultaneous inhibition of PLAG3/4 for complete suppression of podoplanin-mediated tumor growth and metastasis.

PMID: 26684030 [PubMed - as supplied by publisher]

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Heterogeneity and chronology of 6q15 deletion and ERG-fusion in prostate cancer.

Heterogeneity and chronology of 6q15 deletion and ERG-fusion in prostate cancer.

Oncotarget. 2015 Dec 14;

Authors: Kluth M, Meyer D, Krohn A, Freudenthaler F, Bauer M, Salomon G, Heinzer H, Michl U, Steurer S, Simon R, Sauter G, Schlomm T, Minner S

Abstract
Prostate cancer is notorious for its heterogeneity, which poses a problem for the applicability of diagnostic molecular markers. However, heterogeneity analysis can provide valuable information on the chronology in which molecular alterations arise. Here, we constructed a heterogeneity tissue microarray (TMA) comprising samples from 10 different tumor areas of 189 prostate cancers each in order to study the sequence of two frequent molecular alterations, i.e. 6q15 deletion and TMPRSS2:ERG fusion. Previous work shows a marked inverse relationship between these alterations, suggesting that presence of one of these alterations might impact development of the other. 6q15 deletion was analyzed by fluorescence in situ hybridization and ERG-expression by immunohistochemistry. Only 6.6% of 334 ERG-positive but 28.4% of 440 ERG-negative TMA spots showed 6q15 deletions (p < 0.0001). A breakdown of these data to the level of tumor foci revealed 6q deletions in 138 tumor foci that were large enough to have at least 3 analyzable TMA spots. These included 42 tumor foci with homogeneous ERG positivity and 16 with homogeneous 6q15 deletions. Remarkably, six of the 42 homogeneously ERG-positive tumor foci (14.3%) harbored small 6q15-deleted areas, but none of the 34 6q15-deleted foci showed areas of ERG positivity (p = 0.022). In conclusion, our data suggest that ERG-fusion can precede 6q15 deletion, but not vice versa. The complete absence of ERG-positive tumor areas in 6q15-deleted tumor foci further suggest that the functional consequences of 6q15 deletions may prevent the development of TMPRSS2:ERG fusions.

PMID: 26684029 [PubMed - as supplied by publisher]

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Adoptive immunotherapy using T lymphocytes redirected to glypican-3 for the treatment of lung squamous cell carcinoma.

Adoptive immunotherapy using T lymphocytes redirected to glypican-3 for the treatment of lung squamous cell carcinoma.

Oncotarget. 2015 Dec 14;

Authors: Li K, Pan X, Bi Y, Xu W, Chen C, Gao H, Shi B, Jiang H, Yang S, Jiang L, Li Z

Abstract
There are unmet medical needs for patients with lung squamous cell carcinoma (LSCC). Therefore, in this study, we explored the antitumor potential of third-generation glypican 3 (GPC3)-redirected chimeric antigen receptor (CAR)-engineered T lymphocytes (CARgpc3 T cells) in tumor models of LSCC. First, we demonstrated by immunohistochemistry (IHC) that GPC3 was expressed in 66.3% of LSCC samples and in 3.3% of lung adenocarcinoma (LAD) samples but not in normal lung tissues. In the presence of GPC3-positive LSCC cells, CARgpc3 T cells were highly activated and increased in number. CARgpc3 T cells could specifically lyse GPC3-positive LSCC cells in vitro. In two established LSCC xenograft models, CARgpc3 T cells could almost completely eliminate the growth of GPC3-positive cells. Additionally, the CARgpc3 T cells were able to persist in vivo and efficiently infiltrate the cancerous tissues. Taken together, these findings indicate that CARgpc3 T cells might be a novel potential therapeutic agent for the treatment of patients with LSCC.

PMID: 26684028 [PubMed - as supplied by publisher]

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Loss of E-cadherin disrupts ovarian epithelial inclusion cyst formation and collective cell movement in ovarian cancer cells.

Loss of E-cadherin disrupts ovarian epithelial inclusion cyst formation and collective cell movement in ovarian cancer cells.

Oncotarget. 2015 Dec 13;

Authors: Choi PW, Yang J, Ng SK, Feltmate C, Muto MG, Hasselblatt K, Lafferty-Whyte K, JeBailey L, MacConaill L, Welch WR, Fong WP, Berkowitz RS, Ng SW

Abstract
Increased inclusion cyst formation in the ovary is associated with ovarian cancer development. We employed in vitro three-dimensional (3D) organotypic models formed by normal human ovarian surface epithelial (OSE) cells and ovarian cancer cells to study the morphologies of normal and cancerous ovarian cortical inclusion cysts and the molecular changes during their transitions into stromal microenvironment. When compared with normal cysts that expressed tenascin, the cancerous cysts expressed high levels of laminin V and demonstrated polarized structures in Matrigel; and the cancer cells migrated collectively when the cyst structures were positioned in a stromal-like collagen I matrix. The molecular markers identified in the in vitro 3D models were verified in clinical samples. Network analysis of gene expression of the 3D structures indicates concurrent downregulation of transforming growth factor beta pathway genes and high levels of E-cadherin and microRNA200 (miR200) expression in the cancerous cysts and the migrating cancer cells. Transient silencing of E-cadherin expression in ovarian cancer cells disrupted cyst structures and inhibited collective cell migration. Taken together, our studies employing 3D models have shown that E-cadherin is crucial for ovarian inclusion cyst formation and collective cancer cell migration.

PMID: 26684027 [PubMed - as supplied by publisher]

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Combined analysis of circulating epithelial cells and serum thyroglobulin for distinguishing disease status of the patients with papillary thyroid carcinoma.

Combined analysis of circulating epithelial cells and serum thyroglobulin for distinguishing disease status of the patients with papillary thyroid carcinoma.

Oncotarget. 2015 Dec 13;

Authors: Lin HC, Liou MJ, Hsu HL, Hsieh JC, Chen YA, Tseng CP, Lin JD

Abstract
Papillary thyroid carcinoma (PTC) accounts for about 80% of the cases in thyroid cancer. Routine surveillance by serum thyroglobulin (Tg) and medical imaging is the current practice to monitor disease progression of the patients. Whether enumeration of circulating epithelial cells (CECs) helps to define disease status of PTC patients was investigated. CECs were enriched from the peripheral blood of the healthy control subjects (G1, n = 17) and the patients at disease-free status (G2, n = 26) or with distant metastasis (G3, n = 22). The number of CECs expressing epithelial cell adhesion molecule (EpCAM) or thyroid-stimulating hormone receptor (TSHR) was determined by immunofluorescence microscopy analyses. The medium number of EpCAM+-CECs was 6 (intequartile range 1-11), 12 (interquartile range 7-16) and 91 (interquartile range 31-206) cells/ml of blood for G1, G2 and G3, respectively. EpCAM+-CEC counts were significantly higher in G3 than in G1 (p < 0.05) and G2 (p < 0.05). The medium number of TSHR+-CECs was 9 (intequartile range 3-13), 16 (interquartile range 10-24) and 100 (interquartile range 31-226) cells/ml of blood for G1, G2 and G3, respectively. The TSHR+-CEC counts also distinguished G3 from G1 (p < 0.05) and G2 (p < 0.05). With an appropriate cut off value of CEC count, the disease status for 97.9% (47/48) of the cases was clearly defined. Notably, the metastatic disease for all patients in G3 (22/22) was revealed by combined analysis of serum Tg and CEC. This study implicates that CEC testing can supplement the current standard methods for monitoring disease status of PTC.

PMID: 26684026 [PubMed - as supplied by publisher]

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Prognostic value of high EZH2 expression in patients with different types of cancer: a systematic review with meta-analysis.

Prognostic value of high EZH2 expression in patients with different types of cancer: a systematic review with meta-analysis.

Oncotarget. 2015 Dec 14;

Authors: Jiang T, Wang Y, Zhou F, Gao G, Ren S, Zhou C

Abstract
Enhancer of zeste homologue 2 (EZH2) is a potential independent mechanism for epigenetic silencing of tumor suppressor genes in cancer. We conducted an electronic search on PubMed, EMBASE, Web of Science, and Cochrane library to perform this up-to-date meta-analysis. Fifty-one studies with a total of 9444 patients were included. The prevalence of high EZH2 expression was 0.54 (95% CI: 0.47-0.61). High EZH2 expression was significantly associated with poorer prognosis [overall survival: HR 1.54 (95% CI: 1.30-1.78), P < 0.000; disease free survival: HR 1.35 (95% CI: 1.00-1.71), P < 0.000]. In breast cancer, high EZH2 expression correlated with histological types [OR: 1.53 (95CI: 1.13-2.06); P < 0.006], histological grade [OR: 1.62 (95CI: 1.35-1.95); P < 0.000], estrogen receptor (ER) negativity [OR: 2.05 (95CI: 1.67-2.52); P < 0.000], progesterone receptor (PgR) negativity [OR: 1.42 (95CI: 1.03-1.96); P = 0.034], HER-2 positivity [OR: 1.35 (95CI: 1.08-1.69); P = 0.009], and high p53 expression [OR: 1.66 (95CI: 1.07-2.59); P = 0.024]. These results suggest that high EZH2 expression may be a promising prognostic factor to different cancers. High EZH2 expression tends to correlate with pathological types, histological grade, ER negativity, PgR negativity, HER-2 positivity and p53 high expression in breast cancer.

PMID: 26683709 [PubMed - as supplied by publisher]

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Small Cell Lung Cancer Accompanied by Tonsillar Metastasis and Anti-Hu Antibody-Associated Paraneoplastic Neuropathy: A Rare Case Report With Long-Term Survival.

Small Cell Lung Cancer Accompanied by Tonsillar Metastasis and Anti-Hu Antibody-Associated Paraneoplastic Neuropathy: A Rare Case Report With Long-Term Survival.

Medicine (Baltimore). 2015 Dec;94(50):e2291

Authors: Ni J, Weng L, Liu M, Yang H, Wang Y

Abstract
Tonsillar metastatic small cell lung cancer (SCLC) is rare, while anti-Hu antibodies are frequently found in SCLC.A 66-year-old man was admitted to our hospital with painful dysesthesia and muscle weakness in the distal extremities for over 1 year, progressive dysphagia for over 1 month, and severe cough and dyspnea for over 1 week. He was diagnosed with SCLC accompanied by tonsillar metastasis and anti-Hu antibody-associated paraneoplastic sensory neuropathy (PSN). The patient tolerated 6 cycles of sequential chemoradiotherapy and gradually recovered. The patient's disease remained in remission 2 years after the diagnosis with a remarkable reduction of tumor burden and a persisting high titer of anti-Hu antibodies. To our knowledge, this is the first case of tonsillar metastatic SCLC accompanied by anti-Hu antibody-associated PSN, whereby the anticancer immune response was presumed to play a vital role in disease control.Unilateral tonsillar metastasis of SCLC accompanied by anti-Hu antibody-associated PSN can occur and in certain circumstances, may have a favorable prognosis.

PMID: 26683964 [PubMed - in process]

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Esophageal Involvement of Immunoglobulin G4-Related Disease: A Case Report and Literature Review.

Esophageal Involvement of Immunoglobulin G4-Related Disease: A Case Report and Literature Review.

Medicine (Baltimore). 2015 Dec;94(50):e2122

Authors: Oh JH, Lee TH, Kim HS, Jung CS, Lee JS, Hong SJ, Jin SY

Abstract
ABSTARCT: Immunoglobulin G4 (IgG4)-related disease is characterized by the typical histopathological features of a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, a high ratio of IgG4- to IgG-positive cells, storiform fibrosis (cellular fibrosis organized in an irregular whorled pattern), obliterative phlebitis, and variable presence of eosinophils. The disease exhibits systemic involvement but very rarely involves the esophagus.A 33-year-old man was admitted to our hospital for evaluation of a 1-year history of progressive dysphagia. Neck imaging revealed a 3.9-cm mass in the cervical esophagus and multifocal calcified lymph nodes in the lower neck and mediastinum. Two previous tertiary hospitals failed to diagnose the patient's condition despite the use of ultrasound-guided needle biopsy of the neck tumor. We performed neck imaging studies, a flexible endoscopic swallowing study, high-resolution manometry, upper endoscopy, and a review of the previous pathologic slides. The patient was finally diagnosed with IgG4-related esophagitis and showed a good response to corticosteroid therapy.We herein report a rare case of dysphagia associated with IgG4-related disease and present a review of the literature.

PMID: 26683918 [PubMed - in process]

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Landscape of gene fusions in epithelial cancers: seq and ye shall find.

Landscape of gene fusions in epithelial cancers: seq and ye shall find.

Genome Med. 2015;7(1):129

Authors: Kumar-Sinha C, Kalyana-Sundaram S, Chinnaiyan AM

Abstract
Enabled by high-throughput sequencing approaches, epithelial cancers across a range of tissue types are seen to harbor gene fusions as integral to their landscape of somatic aberrations. Although many gene fusions are found at high frequency in several rare solid cancers, apart from fusions involving the ETS family of transcription factors which have been seen in approximately 50 % of prostate cancers, several other common solid cancers have been shown to harbor recurrent gene fusions at low frequencies. On the other hand, many gene fusions involving oncogenes, such as those encoding ALK, RAF or FGFR kinase families, have been detected across multiple different epithelial carcinomas. Tumor-specific gene fusions can serve as diagnostic biomarkers or help define molecular subtypes of tumors; for example, gene fusions involving oncogenes such as ERG, ETV1, TFE3, NUT, POU5F1, NFIB, PLAG1, and PAX8 are diagnostically useful. Tumors with fusions involving therapeutically targetable genes such as ALK, RET, BRAF, RAF1, FGFR1-4, and NOTCH1-3 have immediate implications for precision medicine across tissue types. Thus, ongoing cancer genomic and transcriptomic analyses for clinical sequencing need to delineate the landscape of gene fusions. Prioritization of potential oncogenic "drivers" from "passenger" fusions, and functional characterization of potentially actionable gene fusions across diverse tissue types, will help translate these findings into clinical applications. Here, we review recent advances in gene fusion discovery and the prospects for medicine.

PMID: 26684754 [PubMed - as supplied by publisher]

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Pathological Characterization of Ovarian Cancer Patients Who Underwent Debulking Surgery in Combination With Diaphragmatic Surgery: A Cross-Sectional Study.

Pathological Characterization of Ovarian Cancer Patients Who Underwent Debulking Surgery in Combination With Diaphragmatic Surgery: A Cross-Sectional Study.

Medicine (Baltimore). 2015 Dec;94(50):e2296

Authors: Nagai T, Oshiro H, Sagawa Y, Sakamaki K, Terauchi F, Nagao T

Abstract
Despite exhaustive efforts to detect early-stage ovarian cancers, greater than two-thirds of patients are diagnosed at an advanced stage. Although diaphragmatic metastasis is not rare in advanced ovarian cancer patients and often precludes optimal cytoreductive surgery, little is known about the mechanisms and predictive factors of metastasis to the diaphragm. Thus, as an initial step toward investigating such factors, the present study was conducted to characterize the pathological status of ovarian cancer patients who underwent debulking surgery in combination with diaphragmatic surgery.This is a retrospective and cross-sectional study of patients who underwent debulking surgery in combination with diaphragmatic surgery at our institution between January 2005 and July 2015. Clinicopathological data were reviewed by board-certified gynecologists, pathologists, and cytopathologists. The rates of various pathological findings were investigated and compared by Fisher exact test between 2 groups: 1 group that was pathologically positive for diaphragmatic metastasis (group A) and another group that was pathologically negative for diaphragmatic metastasis (group B).Forty-six patients were included: 41 patients pathologically positive and 5 pathologically negative for diaphragmatic metastasis. The rates of metastasis to the lymph node (95.8% vs 20%, P = 0.001) and metastasis to the peritoneum except for the diaphragm (97.6% vs 60.0%, P = 0.028) were significantly increased in group A compared with group B. However, no significant differences between the 2 groups were found for rates of histological subtypes (high-grade serous or non-high-grade serous), the presence of ascites, the presence of malignant ascites, exposure of cancer cells on the ovarian surface, blood vascular invasion in the primary lesion, and lymphovascular invasion in the primary lesion.Our study demonstrated that metastasis to the lymph node and nondiaphragmatic metastasis to the peritoneum are significantly associated with metastasis to the diaphragmatic peritoneum, indicating that these factors may be pathological predictors of diaphragmatic metastasis in patients with ovarian cancer. However, as the data available are not sufficient to demonstrate the predictive power of these factors, a further comprehensive, large-scale study should be performed.

PMID: 26683966 [PubMed - in process]

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Pancreas-specific activation of mTOR and loss of p53 induce tumors reminiscent of acinar cell carcinoma.

Pancreas-specific activation of mTOR and loss of p53 induce tumors reminiscent of acinar cell carcinoma.

Mol Cancer. 2015;14(1):212

Authors: Kong B, Cheng T, Qian C, Wu W, Steiger K, Cao J, Schlitter AM, Regel I, Raulefs S, Friess H, Erkan M, Esposito I, Kleeff J, Michalski CW

Abstract
BACKGROUND: Pancreatic acinar cell carcinoma (ACC) is a rare tumor entity with an unfavorable prognosis. Recent whole-exome sequencing identified p53 mutations in a subset of human ACC. Activation of the mammalian target of rapamycin (mTOR) pathway is associated with various pancreatic neoplasms. We thus aimed at analyzing whether activation of mTOR with a concomitant loss of p53 may initiate ACC.
METHODS: We generated transgenic mouse models in which mTOR was hyperactivated through pancreas-specific, homozygous tuberous sclerosis 1 (Tsc1) deficiency, with or without deletion of p53 (Tsc1 (-/-) and Tsc1 (-/-) ; p53 (-/-) ). Activity of mTOR signaling was investigated using mouse tissues and isolated murine cell lines. Human ACC specimens were used to corroborate the findings from the transgenic mouse models.
RESULTS: Hyperactive mTOR signaling in Tsc1 (-/-) mice was not oncogenic but rather induced a near-complete loss of the pancreatic acinar compartment. Acinar cells were lost as a result of apoptosis which was associated with p53 activation. Concomitantly, ductal cells were enriched. Ablation of p53 in Tsc1-deficient mice prevented acinar cell death but promoted formation of acinar cells with severe nuclear abnormalities. One out of seven Tsc1 (-/-) ; p53 (-/-) animals developed pancreatic tumors showing a distinctive tumor morphology, reminiscent of human ACC. Hyperactive mTOR signaling was also detected in a subset of human ACC.
CONCLUSION: Hyperactive mTOR signaling combined with loss of p53 in mice induces tumors similar to human ACC.

PMID: 26683340 [PubMed - as supplied by publisher]

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The natural history of pancreatic lipoma: Does it need observation.

The natural history of pancreatic lipoma: Does it need observation.

Pancreatology. 2015 Nov 27;

Authors: Butler JR, Fohtung TM, Sandrasegaran K, Ceppa EP, House MG, Nakeeb A, Schmidt CM, Zyromski NJ

Abstract
BACKGROUND: Pancreatic lipomas (PL) are a rare, benign mesenchymal neoplasm. Some patients diagnosed with PL are followed radiographically or referred to a second provider, while others are not followed after incidental diagnosis. In this study we describe 74 cases of intrapancreatic lipomas from a single institution over a 12-year period to elucidate the radiologic and clinical natural history of pancreatic lipoma.
METHODS: In the period from January 2001 to December 2013, we selected patients over the age of 18 diagnosed with PL based on Ultrasound, CT, and MR imaging. Clinical data were coupled with review of the radiographic image. These patients were retrospectively followed to establish the significance of PL.
RESULTS: PL was identified in 0.012% of all patients undergoing cross-sectional imaging during the studied interval. Lipomas ranged in size at diagnosis from 0.1 cm to 4.8 cm. The majority of patients were asymptomatic at presentation. No patient required intervention or exhibited a change in lipoma diagnosis over a median follow up interval of 41.5 months (range 2-145). 47 patients underwent subsequent imaging with a median of two additional exams (range 2-113) over 31 months (range 1-18). 46/47 (98%) patients with subsequent images showed no discernible growth; 1/47 (2%) had a resolution of the lipoma.
CONCLUSIONS: Pancreatic lipomas are rare benign mesenchymal neoplasms that exhibit stable size and morphology. They are overwhelmingly asymptomatic. The natural history of pancreatic lipoma is benign. Short-term interval observation is prudent to prove stability and help differentiate from early liposarcoma. Extensive follow-up is not likely necessary for this benign lesion.

PMID: 26682506 [PubMed - as supplied by publisher]

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IMAGE FUSION OF RECONSTRUCTED DIGITAL TOMOSYNTHESIS VOLUMES FROM A FRONTAL AND A LATERAL ACQUISITION.

IMAGE FUSION OF RECONSTRUCTED DIGITAL TOMOSYNTHESIS VOLUMES FROM A FRONTAL AND A LATERAL ACQUISITION.

Radiat Prot Dosimetry. 2015 Dec 18;

Authors: Arvidsson J, Söderman C, Allansdotter Johnsson Å, Bernhardt P, Starck G, Kahl F, Båth M

Abstract
Digital tomosynthesis (DTS) has been used in chest imaging as a low radiation dose alternative to computed tomography (CT). Traditional DTS shows limitations in the spatial resolution in the out-of-plane dimension. As a first indication of whether a dual-plane dual-view (DPDV) DTS data acquisition can yield a fair resolution in all three spatial dimensions, a manual registration between a frontal and a lateral image volume was performed. An anthropomorphic chest phantom was scanned frontally and laterally using a linear DTS acquisition, at 120 kVp. The reconstructed image volumes were resampled and manually co-registered. Expert radiologist delineations of the mediastinal soft tissues enabled calculation of similarity metrics in regard to delineations in a reference CT volume. The fused volume produced the highest total overlap, implying that the fused volume was a more isotropic 3D representation of the examined object than the traditional chest DTS volumes.

PMID: 26683464 [PubMed - as supplied by publisher]

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Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis.

Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis.

Gut. 2015 Dec 18;

Authors: Molina-Infante J, Bredenoord AJ, Cheng E, Dellon ES, Furuta GT, Gupta SK, Hirano I, Katzka DA, Moawad FJ, Rothenberg ME, Schoepfer A, Spechler SJ, Wen T, Straumann A, Lucendo AJ, From the PPI-REE Task Force of the European Society of Eosinophilic Oesophagitis (EUREOS)

Abstract
Consensus diagnostic recommendations to distinguish GORD from eosinophilic oesophagitis (EoE) by response to a trial of proton pump inhibitors (PPIs) unexpectedly uncovered an entity called 'PPI-responsive oesophageal eosinophilia' (PPI-REE). PPI-REE refers to patients with clinical and histological features of EoE that remit with PPI treatment. Recent and evolving evidence, mostly from adults, shows that patients with PPI-REE and patients with EoE at baseline are clinically, endoscopically and histologically indistinguishable and have a significant overlap in terms of features of Th2 immune-mediated inflammation and gene expression. Furthermore, PPI therapy restores oesophageal mucosal integrity, reduces Th2 inflammation and reverses the abnormal gene expression signature in patients with PPI-REE, similar to the effects of topical steroids in patients with EoE. Additionally, recent series have reported that patients with EoE responsive to diet/topical steroids may also achieve remission on PPI therapy. This mounting evidence supports the concept that PPI-REE represents a continuum of the same immunological mechanisms that underlie EoE. Accordingly, it seems counterintuitive to differentiate PPI-REE from EoE based on a differential response to PPI therapy when their phenotypic, molecular, mechanistic and therapeutic features cannot be reliably distinguished. For patients with symptoms and histological features of EoE, it is reasonable to consider PPI therapy not as a diagnostic test, but as a therapeutic agent. Due to its safety profile, ease of administration and high response rates (up to 50%), PPI can be considered a first-line treatment before diet and topical steroids. The reasons why some patients with EoE respond to PPI, while others do not, remain to be elucidated.

PMID: 26685124 [PubMed - as supplied by publisher]

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Sometimes There Is More Than One Puzzle on the Table: Pneumococcal Bacteremia as a New Systemic Lupus Erythematosus Presentation

Infection is common and a leading cause of death in patients with systemic lupus erythematosus (SLE). SLE is associated with a diverse spectrum of immune impairments including humoral defects and hypocomplementemia that contribute to a lupus patient's increased susceptibility to infection with encapsulated bacteria. Nonetheless, there are only few reports of severe invasive bacterial infection as the initial presentation of SLE in the literature. Here, we report a rare case of SLE presenting with pneumococcal bacteremia. Based on the high resolution chest computed tomography and the result of blood cultures, the bacteremia was assumed to be secondary to pneumococcal pneumonia.

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Corrigendum to “Strategy for the Management of Diabetic Macular Edema: The European Vitreo-Retinal Society Macular Edema Study”

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The effects of different environmental pH on healing of tympanic membrane: an experimental study.

The effects of different environmental pH on healing of tympanic membrane: an experimental study.

Eur Arch Otorhinolaryngol. 2015 Dec 18;

Authors: Akkoc A, Celik H, Arslan N, Demirci S, Hucumenoglu S, Caydere M, Oztuna D

Abstract
In this study, we investigated the effect of environmental pH on healing of acute rat tympanic membrane perforations. Twenty Wistar albino rats were divided into four groups and used in the study. A large myringotomy was performed in the posteroinferior quadrants of both tympanic membranes. In left ears, topical pH 4 standard calibration solution was used in groups 1 and 3, and pH 7 standard calibration solution was used in groups 2 and 4. Right ears served as controls, and allowed for spontaneous healing. The solutions were applied for 2 days in groups 1 and 2, and for 7 days in groups 3 and 4. Healing was assessed by macroscopic closure of the tympanic membrane perforation, and histopathological analysis of lamina propria edema, neovascularization, inflammatory cells, and fibroblastic reaction in the temporal bones. pH 7 and pH 4 groups were similar for macroscopic closure of perforation on day 2; however difference was significant on day 7. The fibroblastic activity was significantly less on days 2 and 7 in pH 4 group. On day 7, there were significant differences between pH 4 and pH 7, and pH 7 and control groups for inflammatory cell infiltration. In conclusion, clinical and histopathological results of this study indicated that acidic environmental pH speeded up and shortened wound-healing process. By building up optimum environmental pH, a healthy healing may be achieved in acute tympanic membrane perforations.

PMID: 26683468 [PubMed - as supplied by publisher]

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Functional and anatomical basis for brain plasticity in facial palsy rehabilitation using the masseteric nerve.

Functional and anatomical basis for brain plasticity in facial palsy rehabilitation using the masseteric nerve.

J Plast Reconstr Aesthet Surg. 2015 Oct 30;

Authors: Buendia J, Loayza FR, Luis EO, Celorrio M, Pastor MA, Hontanilla B

Abstract
Several techniques have been described for smile restoration after facial nerve paralysis. When a nerve other than the contralateral facial nerve is used to restore the smile, some controversy appears because of the nonphysiological mechanism of smile recovering. Different authors have reported natural results with the masseter nerve. The physiological pathways which determine whether this is achieved continue to remain unclear. Using functional magnetic resonance imaging, brain activation pattern measuring blood-oxygen-level-dependent (BOLD) signal during smiling and jaw clenching was recorded in a group of 24 healthy subjects (11 females). Effective connectivity of premotor regions was also compared in both tasks. The brain activation pattern was similar for smile and jaw-clenching tasks. Smile activations showed topographic overlap though more extended for smile than clenching. Gender comparisons during facial movements, according to kinematics and BOLD signal, did not reveal significant differences. Effective connectivity results of psychophysiological interaction (PPI) from the same seeds located in bilateral facial premotor regions showed significant task and gender differences (p < 0.001). The hypothesis of brain plasticity between the facial nerve and masseter nerve areas is supported by the broad cortical overlap in the representation of facial and masseter muscles.

PMID: 26683008 [PubMed - as supplied by publisher]

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Assessment of bioabsorbable hydroxyapatite for secondary bone grafting in unilateral alveolar cleft.

Assessment of bioabsorbable hydroxyapatite for secondary bone grafting in unilateral alveolar cleft.

J Plast Reconstr Aesthet Surg. 2015 Nov 14;

Authors: Takemaru M, Sakamoto Y, Sakamoto T, Kishi K

Abstract
AIM: The aim of this study was to evaluate the utility and efficacy of bioabsorbable hydroxyapatite and collagen complex for secondary bone graft in unilateral alveolar cleft.
PATIENTS AND METHODS: From August 2013 to January 2014, 15 patients with unilateral cleft lip and alveolar cleft were enrolled and randomly assigned to two blinded groups. In group I, a cancellous iliac bone graft was placed at the alveolar cleft. In group II, 0.5 ml of HA/Col was placed at the alveolar cleft, and the cancellous iliac bone was positioned in the remaining space. All patients underwent bone grafting with particulate cancellous bone and marrow taken from the anterior iliac crest.
RESULTS: No complications were observed in any patient. The groups did not differ in age, cleft volume, or surgical duration. Intraoperative blood loss and patient-controlled intravenous analgesia (PCA) use were significantly lower in group II (p < 0.05) in comparison to group I. The 1-month volume was 0.895 ml in group I and 0.482 ml in group II (p < 0.05). When the 1-month volume in group II was adjusted for 0.5-ml volume of HA/Col, there was no significant difference in the 1-month volumes (p = 0.32). The 6- and 12-month volumes did not differ significantly between the groups (p = 0.768 and p = 0.165, respectively).
CONCLUSION: The autogenous bone was gradually absorbed, while the HA/Col was absorbed and replaced by the autogenous bone. Thus, HA/Col can be used as an iliac graft in alveolar bone graft procedures to reduce the amount of autogenous bone required from the crest, patient stress, and morbidity.

PMID: 26683007 [PubMed - as supplied by publisher]

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Adrenohepatic fusion: Adhesion or invasion in primary virilizant giant adrenal carcinoma? Implications for surgical resection. Two case report and review of the literature.

Adrenohepatic fusion: Adhesion or invasion in primary virilizant giant adrenal carcinoma? Implications for surgical resection. Two case report and review of the literature.

Int J Surg Case Rep. 2015 Nov 27;18:24-29

Authors: Alastrué Vidal A, Navinés López J, Julián Ibáñez JF, De la Ossa Merlano N, Botey Fernandez M, Sampere Moragues J, Sánchez Torres MD, Barluenga Torres E, Fernández-Llamazares Rodríguez J

Abstract
INTRODUCTION: Adrenohepatic fusion means union between the adrenal gland and the liver, intermingling its parenchymas. It is not possible to identify this condition by image tests. Its presence implies radical and multidisciplinar approach.
PRESENTATION OF CASES: We report two female cases of 45 and 50 years old with clinical virilization and palpable mass on the abdominal right upper quadrant corresponding to adrenocortical carcinoma with hepatic fusion. The contrast-enhanced tomography showed an indistinguishable mass involving the liver and the right adrenal gland. In the first case, the patient had a two-time operation, the former removing only the adrenal carcinoma, and the second performing a radical surgery after an early relapse. In the second case, a radical right en bloc adrenohepatectomy was performed. Both cases were pathologically reported as liver-infiltrating adrenal carcinoma. Only in the second case the surgery was radical effective as first intention to treat, with 3 years of disease-free survival.
DISCUSSION: ACC is a rare entity with poor prognosis. The major indicators of malignancy are tumour diameter over 6cm, local invasion or metastasis, secretion of corticosteroids, virilization and hypertension and hypokalaemia. The parenchymal fusion of the adrenal cortical layer can be misdiagnosed as hepatocellular carcinoma with adhesion with the Glisson capsule. AHF in such cases may be misinterpreted during surgery, what may impair its resectability, and therefore the survival. The surgical treatment must be performed en bloc, often using liver vascular control. Postoperative treatment must be offered immediately after surgery.
CONCLUSION: We report two consecutive rare cases of adrenohepatic fusion in giant right adrenocortical carcinoma, not detectable by imaging, what has important implications for the surgical decision-making. As radical surgery is the best choice to offer a curative treatment, it has to be performed by a multidisciplinary well-assembled team, counting with endocrine and liver surgeons, and transplant surgeons in case of vena cava involvement, in order to maximize the disease-free survival.

PMID: 26684865 [PubMed - as supplied by publisher]

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Xantogranulomatous pyelonephritis: The missed diagnosis.

Xantogranulomatous pyelonephritis: The missed diagnosis.

Int J Surg Case Rep. 2015 Nov 30;18:21-23

Authors: El Abiad Y, Dehayni Y, Qarro A, Balla B, Ammani A, Alami M

Abstract
INTRODUCTION: Xantogranulomatous pyelonephritis (XGPN) is a rare chronic inflammatory disease of the kidney that can be focal or diffuse with the focal form imitating greatly renal cell carcinoma (RCC).
PRESENTATION OF CASE: We report a challenging clinical case of a 38-year old male with right flank pain persisting for 3-months, imaging showed an 8cm heterogenous mass of the upper pole of the right kidney and invading the liver. A right radical nephrectomy including the adrenal in the resection was performed under the tentative diagnosis of renal cell carcinoma (RCC) whereas histology revealed focal XGPN.
DISCUSSION: Preoperative diagnosis of focal XGPN was difficult because of radiological similarities to RCC and lack of history of stone disease or urinary tract infection.
CONCLUSION: This case highlights the need to include XGPN in the differential diagnosis of RCC even in the era of modern imaging.

PMID: 26684864 [PubMed - as supplied by publisher]

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Widespread lytic lesions-A metastatic or vasculitic process?

Widespread lytic lesions-A metastatic or vasculitic process?

Int J Surg Case Rep. 2015 Nov 27;18:18-20

Authors: Khan F, Srirangan S, El-Miedany Y, Madaan S

Abstract
INTRODUCTION: This case highlights the complexities in the initial diagnosis and investigations of widespread lytic lesions initially perceived to be a widespread metastatic process and the consideration of alternative diagnosis.
PRESENTATION OF CASE: A 57 year-old man with a background of psoriatic arthritis presented to the rheumatology department with lumbar back pain and sensory disturbance over L4/5. Magnetic resonance imaging (MRI) and bone scan identified lesions consistent with bony metastases at L5. The patient previously had a raised prostate specific antigen (PSA) of 10.8μg/L (normal<4) but prostate biopsy was benign. Multiple metastatic deposits in the liver and kidneys (confirmed necrotic tissue on biopsy) were identified through further investigations. The initial diagnosis of malignancy was challenged after a positron emission tomography (PET) scan showed lesions highly suggestive of polyarteritis nodosa (PAN) and subsequent magnetic resonance angiogram (MRA) revealed stenosis and aneurysm in the renal artery in keeping with PAN. Therefore what was initially thought to be a widespread metastatic disease process was in fact the manifestation of a systemic vasculitic disease.
DISCUSSION: PAN is a vasculitis that predominantly involves small to medium-sized vessels. The disease can affect any site in the body, but holds a predisposition for organs such as kidneys, heart and the gastrointestinal tract. Differential diagnosis of PAN should be considered in patients with widespread lytic lesions.
CONCLUSION: Due to the pathological nature of PAN and its variable clinical manifestations that add to the challenges of its diagnosis, one must hold a high clinical suspicion, even in urological conditions.

PMID: 26684863 [PubMed - as supplied by publisher]

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The Bactericidal Effect of 2780 and 940 nm Laser Irradiation on Enterococcus faecalis in Bovine Root Dentin Slices of Different Thicknesses.

The Bactericidal Effect of 2780 and 940 nm Laser Irradiation on Enterococcus faecalis in Bovine Root Dentin Slices of Different Thicknesses.

Photomed Laser Surg. 2015 Dec 18;

Authors: Gutknecht N, Al-Karadaghi TS, Al-Maliky MA, Conrads G, Franzen R

Abstract
OBJECTIVE: The aim of this in vitro study was to investigate the antibacterial effect of the dual wavelength (2780 nm Er,Cr:YSGG and 940 nm diode) laser in elimination of Enterococcus faecalis in comparison with a 2780 nm Er,Cr:YSGG laser alone.
BACKGROUND DATA: Various laser wavelengths have been introduced as an adjunct in root canal treatment because of laser's bactericidal effect.
MATERIALS AND METHODS: Seventy- five slices of dentin with thicknesses of 300, 500, and 1000 μm (n = 25 each) obtained from caries-free bovine teeth were inoculated with 1 μL of E. faecalis suspension [1.67 × 10(7) colony-forming units (CFU)] and divided randomly into three groups: (A) samples indirectly irradiated with power settings of 1.06 W, 50 Hz, and 50 μs for Er,Cr:YSGG laser; (B) samples indirectly irradiated with Er,Cr:YSGG laser with the same power settings as group A and simultaneously with a 940 nm diode laser of 0.51 W in pulsed mode; and five samples from each thickness that were chosen as an unirradiated control group (Co). After irradiation, the CFU of E. faecalis were counted and the bacterial reduction was analyzed using Kruskal-Wallis nonparametric and post-hoc Dunnett tests.
RESULTS: There were statistical differences between groups A and B compared with the control group over all the three dentin slice thicknesses (p < 0.001). However, there was no statistical difference between groups A and B in killing of E. faecalis on 500 μm dentin slices. There were significantly more viable bacteria in group A than in group B in 300 μm and 1000 μm dentin slices (p < 0.01).
CONCLUSIONS: The results of this in vitro study showed that the dual wavelength laser system obtained a significantly higher bactericidal effect on E. faecalis than Er,Cr:YSGG laser, reaching a depth of 1000 μm of dentin.

PMID: 26685038 [PubMed - as supplied by publisher]

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Neurofibromas of the Oral Cavity: Clinical Aspects, Treatment, and Outcome.

Neurofibromas of the Oral Cavity: Clinical Aspects, Treatment, and Outcome.

Photomed Laser Surg. 2015 Dec 18;

Authors: Angiero F, Ferrante F, Ottonello A, Maltagliati A, Crippa R

Abstract
OBJECTIVE: This study aimed to evaluate the efficacy of diode laser for the surgical treatment of neurofibromas (NF), in terms of clinical outcome and therapeutic success.
BACKGROUND DATA: The NF is a benign tumor of the peripheral nerve sheath, characterized by the proliferation of Schwann cells, perineural cells, and endoneural fibroblasts. NF may occur as a solitary lesion, or as part of a generalized neurofibromatosis syndrome; much more rarely it occurs in the form of multiple neurofibromas with no associated syndrome. Two distinct variants of neurofibromatosis have been described: types I and II.
METHODS: Ten cases are reported (6 women and 4 men, age range 43-70 years) with smooth, painful, or painless lesions of the oral mucosa. Lesions were completely excised using a diode laser at 980 nm wavelength, average power 2.0 W, in continuous wave mode, with 320 μm optical fibers, for 45 sec average time.
RESULTS: Complete healing occurred within 20 days. There were no adverse effects; patients were carefully followed up and there have been no recurrences after an interval of 3 months to 3 years.
CONCLUSIONS: The results of this diode laser treatment of NF demonstrate good effectiveness of this novel therapy, which may replace conventional surgical procedures.

PMID: 26684917 [PubMed - as supplied by publisher]

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Effectiveness of Sonic, Ultrasonic, and Photon-Induced Photoacoustic Streaming Activation of NaOCl on Filling Material Removal Following Retreatment in Oval Canal Anatomy.

Effectiveness of Sonic, Ultrasonic, and Photon-Induced Photoacoustic Streaming Activation of NaOCl on Filling Material Removal Following Retreatment in Oval Canal Anatomy.

Photomed Laser Surg. 2015 Dec 18;

Authors: Jiang S, Zou T, Li D, Chang JW, Huang X, Zhang C

Abstract
OBJECTIVE: This study aimed to assess the effectiveness of sonic, ultrasonic and laser [photon-induced photoacoustic streaming (PIPS)] irrigation activation in removing filling remnants from oval root canals after standard canal retreatment procedures with the ProTaper universal rotary retreatment system.
METHODS: Twenty-eight maxillary first premolars were instrumented with ProTaper NiTi rotary instruments and obturated with gutta-percha and AH Plus sealer using the continuous wave of condensation technique. After storage at 37°C and 100% humidity for 1 week, the specimens were retreated with the ProTaper universal retreatment system for the removal of filling material. Teeth were then randomly assigned into four groups (n = 7): group 1, positive control; group 2, retreated with sonic irrigation; group 3, retreated with ultrasonic irrigation; and group 4, retreated with laser irradiation. The specimens were scanned using micro-CT before instrumentation, after obturation and mechanical retreatment, and after additional activation procedures. The percentage volume of the filling remnants was measured. Specimens were split longitudinally after micro-CT scan, canal walls were examined using scanning electron microscopy (SEM), and the amount of residual filling material was scored.
RESULTS: The filling materials' removal efficacy in the three experimental groups was higher than that of the control group (p < 0.05), whereas filling materials ranging from 1.46 ± 0.30 to 2.21 ± 0.46 mm(3) remained in the canal in all three experimental groups. Additionally, there was a significantly greater reduction in the amount of filling remnants in the PIPS group than in the sonic and ultrasonic groups (both p < 0.05), and significantly greater reduction in the ultrasonic group than the sonic group (p < 0.05).
CONCLUSIONS: Activation of NaOCl with PIPS showed significantly better performance than sonic and ultrasonic techniques in removing the filling remnants following mechanical retreatment of oval root canals. The ultrasonic technique also performed better than the sonic technique. However, none of the additional activation procedures was able to completely eliminate the filling remnants.

PMID: 26682489 [PubMed - as supplied by publisher]

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Angiostrongylus cantonensis cathepsin B-like protease (Ac-cathB-1) is involved in host gut penetration.

Angiostrongylus cantonensis cathepsin B-like protease (Ac-cathB-1) is involved in host gut penetration.

Parasite. 2015;22:37

Authors: Long Y, Cao B, Yu L, Tukayo M, Feng C, Wang Y, Luo D

Abstract
Although the global spread of the emerging zoonosis, human angiostrongyliasis, has attracted increasing attention, understanding of specific gene function has been impeded by the inaccessibility of genetic manipulation of the pathogen nematode causing this disease, Angiostrongylus cantonensis. Many parasitic proteases play key roles in host-parasite interactions, but those of A. cantonensis are always expressed as the inactive form in prokaryotic expression systems, thereby impeding functional studies. Hence, a lentiviral system that drives secreted expression of target genes fused to a Myc-His tag was used to obtain recombinant Ac-cathB-1 with biological activity. Although this class of proteases was always reported to function in nutrition and immune evasion in parasitic nematodes, recombinant Ac-cathB-1 was capable of hydrolysis of fibronectin and laminin as well as the extracellular matrix of IEC-6 monolayer, so that the intercellular space of the IEC-6 monolayer increased 5.15 times as compared to the control, while the shape of the adherent cells partly rounded up. This suggests a probable role for this protease in intestinal epithelial penetration. The inhibition of Ac-cathB-1 enzymatic activity with antiserum partly suppressed larval penetration ability in the isolated intestine. Thus, an effective system for heterologous expression of parasite proteases is presented for studying gene function in A. cantonensis; and Ac-cathB-1 was related to larval penetration ability in the host small intestine.

PMID: 26682577 [PubMed - as supplied by publisher]

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Proteomic Characterization of Head and Neck Cancer Patient-Derived Xenografts.

Proteomic Characterization of Head and Neck Cancer Patient-Derived Xenografts.

Mol Cancer Res. 2015 Dec 18;

Authors: Li H, Wheeler S, Park YS, Ju Z, Thomas SM, Fichera M, Egloff AM, Lui VW, Duvvuri U, Bauman JE, Mills GB, Grandis JR

Abstract
Despite advances in treatment approaches for head and neck squamous cell carcinoma (HNSCC), survival rates have remained stagnant due to the paucity of preclinical models that accurately reflect the human tumor. Patient-derived xenografts (PDXs) are an emerging model system where patient tumors are implanted directly into mice. Increased understanding of the application and limitations of PDXs will facilitate their rational use. Studies to date have not reported protein profiles of PDXs. Therefore, we developed a large cohort of HNSCC PDXs and found that tumor take rate was not influenced by the clinical, pathologic or processing features. Protein expression profiles, from a subset of the PDXs, were characterized by reverse phase protein array (RPPA) and the data was compared to The Cancer Genome Atlas (TCGA) HNSCC data. Cluster analysis revealed that HNSCC PDXs were more similar to primary HNSCC than to any other tumor type. Interestingly, while a significant fraction of proteins were expressed similarly in both primary HNSCC and PDXs, a subset of proteins/phosphoproteins were expressed at higher (or lower) levels in PDXs compared to primary HNSCC. These findings indicate that the proteome is generally conserved in PDXs, but mechanisms for both positive and negative model selection and/or differences in the stromal components exist.
IMPLICATIONS: Proteomic characterization of HNSCC PDXs demonstrates potential drivers for model selection and provides a framework for improved utilization of this expanding model system.

PMID: 26685214 [PubMed - as supplied by publisher]

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CIC-rearranged Sarcomas: A Study of 20 Cases and Comparisons With Ewing Sarcomas.

CIC-rearranged Sarcomas: A Study of 20 Cases and Comparisons With Ewing Sarcomas.

Am J Surg Pathol. 2015 Dec 17;

Authors: Yoshida A, Goto K, Kodaira M, Kobayashi E, Kawamoto H, Mori T, Yoshimoto S, Endo O, Kodama N, Kushima R, Hiraoka N, Motoi T, Kawai A

Abstract
The CIC gene rearrangement exists in a subset of small round cell sarcomas. As the nosologic relationship of these sarcomas to Ewing sarcomas remains undetermined, we examined 20 CIC-rearranged sarcomas to compare their clinicopathologic features with those of Ewing sarcomas. The CIC-rearranged sarcomas were from a group of 14 men and 6 women with a median age of 24.5 years. The primary tumor sites included the limbs, trunk wall, internal trunk, lung, cerebrum, and pharynx. A comparison of the demographic and clinical characteristics of the 20 patients with CIC-rearranged sarcomas with those of the 53 near-consecutive patients with EWSR1-rarranged Ewing sarcomas showed that there were no differences with respect to their ages and sexes. Although none of the CIC-rearranged sarcomas arose in the bone, 40% of the Ewing sarcomas primarily affected the skeleton. The overall survival of patients with Ewing sarcomas was significantly better than that for patients with CIC-rearranged sarcomas. A histologic comparison of the CIC-rearranged sarcomas with 20 EWSR1-rearranged Ewing sarcomas showed significantly higher degrees of lobulation, nuclear pleomorphism, the prominence of the nucleoli, spindle cell elements, and myxoid changes in the CIC-rearranged sarcomas. Distinguishing immunohistochemical features included heterogenous CD99 reactivity, nuclear WT1 expression, and calretinin expression in the CIC-rearranged sarcomas and NKX2.2 expression in the Ewing sarcomas. CIC-rearranged sarcomas are distinct from Ewing sarcomas clinically, morphologically, and immunohistochemically, and they should be considered a separate entity rather than being grouped within the same family of tumors.

PMID: 26685084 [PubMed - as supplied by publisher]

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Metabolic syndrome and health-related behaviours associated with pre-oral cancerous lesions among adults aged 20-80 years in Yunlin County, Taiwan: a cross-sectional study.

Metabolic syndrome and health-related behaviours associated with pre-oral cancerous lesions among adults aged 20-80 years in Yunlin County, Taiwan: a cross-sectional study.

BMJ Open. 2015;5(12):e008788

Authors: Chang CC, Lin MS, Chen YT, Tu LT, Jane SW, Chen MY

Abstract
OBJECTIVES: To explore the associations of health-related behaviours, metabolic syndrome and risk factors in adults with pre-oral cancerous (POC) lesions in rural, disadvantaged communities with a high prevalence of oral cancer.
DESIGN: A cross-sectional observational study.
SETTING: Community-based health survey in the western coastal area of Yunlin County, Taiwan.
PARTICIPANTS: 5161 adult residents participated in this study.
OUTCOME MEASURES: Assessed parameters included oral leukoplakia, oral submucous fibrosis, fasting blood glucose, triglycerides, high-density lipoprotein cholesterol, blood pressure and waist circumference. Statistical analyses included descriptive statistics, χ(2) tests and multivariate binary logistic regression.
RESULTS: A high percentage of participants were found to have metabolic syndrome (40%) and POC lesions (7.3%). Participants with POC lesions tended to be male (p<0.001), betel nut chewers (p<0.001) and cigarette smokers (p<0.001); have a low level of education (p<0.001); seldom undergo dental check-ups (p<0.01); irregularly participate in physical activity (p<0.01) and have metabolic syndrome (p<0.01).
CONCLUSIONS: Although male sex and disadvantaged socioeconomic status are non-modifiable factors associated with POC and metabolic syndrome in adults, several factors, notably health behaviours, are modifiable. Clinicians can reduce the incidence and consequences of POC by developing programmes for early detection, encouraging regular dental check-ups, and initiating individualised, health-promoting behaviour modification programmes for reducing risky behaviours associated with oral cancer.

PMID: 26685025 [PubMed - as supplied by publisher]

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Clinic manifestations in granulomatosis with polyangiitis.

Clinic manifestations in granulomatosis with polyangiitis.

Int J Immunopathol Pharmacol. 2015 Dec 18;

Authors: Greco A, Marinelli C, Fusconi M, Macri GF, Gallo A, De Virgilio A, Zambetti G, de Vincentiis M

Abstract
Granulomatosis with polyangiitis (GPA), formerly Wegener's granulomatosis (WG), is an uncommon immunologically mediated systemic small-vessel vasculitis that is pathologically characterised by an inflammatory reaction pattern (necrosis, granulomatous inflammation and vasculitis) that occurs in the upper and lower respiratory tracts and kidneys. Although the aetiology of GPA remains largely unknown, it is believed to be autoimmune in origin and triggered by environmental events on a background of genetic susceptibility.In Europe, the prevalence of GPA is five cases per 100,000 population, with greater incidence in Northern Europe. GPA can occur in all racial groups but predominantly affects Caucasians. Both sexes are affected equally. GPA affects a wide age range (age range, 8-99 years).Granulomatosis with polyangiitis is characterised by necrotising granulomatous lesions of the respiratory tract, vasculitis and glomerulonephritis. Classically, the acronym ELK is used to describe the clinical involvement of the ear, nose and throat (ENT); lungs; and kidneys. Because the upper respiratory tract is involved in 70-100% of cases of GPA, classic otorhinolaryngologic symptoms may be the first clinical manifestation of disease. The nasal cavity and the paranasal sinuses are the most common sites of involvement in the head and neck area (85-100%), whereas otological disease is found in approximately 35% (range, 19-61%) of cases.Diagnosis of GPA is achieved through clinical assessment, serological tests for anti-neutrophil cytoplasmic antibodies (ANCA) and histological analysis. The 10-year survival rate is estimated to be 40% when the kidneys are involved and 60-70% when there is no kidney involvement.The standard therapy for GPA is a combination of glucocorticoids and cyclophosphamide. In young patients, cyclophosphamide should be switched to azathioprine in the maintenance phase.A multidisciplinary approach, involving otorhinolaryngologists, oral and maxillofacial surgeons, oral physicians, rheumatologists, renal and respiratory physicians, and ophthalmologists, is necessary for the diagnosis and therapeutic treatment of GPA. ENT physicians have a determining role in recognising the early onset of the disease and starting an appropriate therapy.

PMID: 26684637 [PubMed - as supplied by publisher]

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Discordance in routine second opinion pathology review of head and neck oncology specimens: A single-center five year retrospective review.

Discordance in routine second opinion pathology review of head and neck oncology specimens: A single-center five year retrospective review.

Oral Oncol. 2015 Dec 9;

Authors: Zhu GA, Lira R, Colevas AD

Abstract
OBJECTIVES: Second opinion review of pathology specimens is a common institutional practice, supported by large retrospective studies demonstrating significant histologic discordance. Since the most recent study of head and neck-specific pathology review was conducted, routine HPV and EBV testing is now recommended for certain specimens. We describe the frequency of and reasons for discordant reports and their potential impact on treatment recommendations and prognosis in a five-year retrospective cohort study at a single academic referral institution from 2005 to 2010.
MATERIALS AND METHODS: Following institutional review board review, 1003 cases referred to the Head and Neck Oncology Service were identified using a retrospective database search. Discordance between outside and second review pathology report was assessed by a board-certified medical oncologist.
RESULTS: 667 cases were included, of which 22% were discordant. Discordance was associated with adenocarcinomas (AOR [adjusted odds ratio] 0.09, 95% CI 0.03-0.31; p<0.001), poorly differentiated carcinomas (AOR 0.14, 95% CI 0.06-0.39; p<0.001), and specimens of uncommon histology (AOR 0.18, 95% CI 0.07-0.45; p<0.001) but not biopsy site in a multivariate model. The most common reasons for discordance included histology (61%), followed by the results of special studies (36%), and the presence or absence of stromal invasion (14%). Differences in tumor HPV status comprised 16% of discordant cases and were associated with better prognosis (p<0.001) following second opinion review.
CONCLUSIONS: Routine second opinion pathology review may lead to clinically significant differences in treatment recommendations and prognosis.

PMID: 26684543 [PubMed - as supplied by publisher]

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Oral microbiome, periodontitis and risk of head and neck cancer.

Oral microbiome, periodontitis and risk of head and neck cancer.

Oral Oncol. 2015 Dec 9;

Authors: Galvão-Moreira LV, da Cruz MC

Abstract
A wide range of studies has been successfully exploring the association between the human microenvironment, sustained inflammation, and cancer. Growing evidence has then emerged in this field over the past few years. Nevertheless, reliable data addressing the impact of the oral microbiome and periodontitis on the pathogenesis and risk of head and neck malignancies remain scarce. Hence, this communication focuses on briefly discuss the relationship between the oral microbiome, periodontitis and head and neck cancer based on the current understanding of such a disease-associated scenario.

PMID: 26684542 [PubMed - as supplied by publisher]

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Application of platelet rich fibrin for management of an electrosurge induced osteonecrosis involving maxillary alveolus.

Application of platelet rich fibrin for management of an electrosurge induced osteonecrosis involving maxillary alveolus.

Singapore Dent J. 2015 Dec;36:39-43

Authors: Suresh N, Chandrasekaran B, Muthusamy S, Kannan S, Muthu K

Abstract
BACKGROUND: Application of principles of electrocautery for hemostasis dates back to prehistoric times. Its modern implementation in various fields of general and head and neck surgeries have been well documented. However its usage in minor oral surgical procedures has gained popularity only recently. Complications associated with electro-surgery in the dental field are relatively rare and there is insufficient literature on its management.
CASE REPORT: We present a case report on management of an electrosurgery induced osteonecrosis involving maxillary alveolus of left premolars.
DISCUSSION: Inadvertent contact of the electrosurgery tip on bone can result in necrosis making it necessary to remove the sequestrum and graft the defect. Platelet rich fibrin in combination with bone grafts have been well documented to provide successful periodontal regeneration.
CLINICAL IMPLICATIONS: Our aim of presenting this report is to create awareness among the health care providers regarding electrosurgical injuries. To our knowledge, this is the first time platelet rich fibrin has been used in the management of intraoral electrosurgical injury. Combining bone grafts with platelet rich fibrin is a good alternative as it can be done with relative ease and predictable outcome.

PMID: 26684495 [PubMed - as supplied by publisher]

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Early-onset dropped head syndrome after radiotherapy for head and neck cancer: dose constraints for neck extensor muscles.

Early-onset dropped head syndrome after radiotherapy for head and neck cancer: dose constraints for neck extensor muscles.

J Radiat Res. 2015 Dec 18;

Authors: Inaba K, Nakamura S, Okamoto H, Kashihara T, Kobayashi K, Harada K, Kitaguchi M, Sekii S, Takahashi K, Murakami N, Ito Y, Igaki H, Uno T, Itami J

Abstract
Dropped head syndrome (DHS) is a famous but unusual late complication of multimodality treatment for head and neck carcinoma. We reported this early-onset complication and analyzed the dose to the neck extensor muscles. We examined the records of three patients with DHS after radiotherapy. The doses to the neck extensor muscles were compared between three patients with DHS and nine patients without DHS. The mean dose to the neck extensor muscles of the three patients with DHS were 58.5 Gy, 42.3 Gy and 60.9 Gy, while the dose was <50 Gy in all nine patients in the control group. The onset of this syndrome was 5 months, 6 months and 15 months. The early-onset DHS may have something to do with dose to the neck extensor muscles. The proposed dose to the neck extensor muscles might be <46 Gy (or at least <50 Gy).

PMID: 26684338 [PubMed - as supplied by publisher]

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Genomic Copy Number Variations Characterize the Prognosis of Both P16-Positive and P16-Negative Oropharyngeal Squamous Cell Carcinoma After Curative Resection.

Genomic Copy Number Variations Characterize the Prognosis of Both P16-Positive and P16-Negative Oropharyngeal Squamous Cell Carcinoma After Curative Resection.

Medicine (Baltimore). 2015 Dec;94(50):e2187

Authors: Rhie A, Park WS, Choi MK, Kim JH, Ryu J, Ryu CH, Kim JI, Jung YS

Abstract
Recently increasing high-risk HPV+ OSCC exhibits unique clinical and molecular characteristics compared to HPV-unrelated (HPV-) counterpart. Genomic copy number variations (CNVs), unique in HPV+ OSCCs, and their role for the prognosis prediction remains poorly studied. Here, we analyzed the distinct genomic copy number variations (CNVs) in human papillomavirus-related (HPV+) oropharyngeal squamous cell carcinoma (OSCC) and their role as a prognosticator after curative resection.For 58 consecutive, Korean OSCC patients that underwent surgery-based treatment with median 10 years of follow-up, HPV-related markers, and genome-wide CNV analysis were analyzed. Clinical associations between the CNV profile and survival analyses were followed.p16 expression predicted the overall survival (OS) (hazard ratio [HR] = 0.27, confidence interval [CI]: 0.39-0.80, P = 0.0006) better than HPV L1 PCR (HR = 0.83, CI: 0.66-1.29, P = 0.64), smoking, or other variables. Although the overall number of CNVs was not significantly different, 30 loci showed unique CNV patterns between the p16 and p16- groups. A region containing PRDM2 was amplified only in the p16 group, whereas EGFR and 11q13.3 showed increased amplification in p16- counterpart. Loss of a locus containing FGF18 led to a worse, but gain of region including CDK10 and RAD18 led to better overall survival (OS) in all OSCC patients. Meanwhile, subgroup analysis of p16 OSCC revealed that amplification of regions harboring HRAS and loss of locus bearing KDR led to better OS.p16 OSCC exhibit distinct CNV patterns compared with p16- counterpart. Specific patterns of CNVs predict better survival, especially in p16 OSCC. This might allow better insights of the outcome after curative resection for HPV+ and HPV- OSCC.

PMID: 26683928 [PubMed - in process]

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Qualitative development of the sinus control test: a survey evaluating sinus symptom control.

Qualitative development of the sinus control test: a survey evaluating sinus symptom control.

Int Forum Allergy Rhinol. 2015 Dec 18;

Authors: Banglawala SM, Schlosser RJ, Morella K, Chandra R, Khetani J, Poetker DM, Rayar M, Rudmik L, Sautter NB, Sommer DD, Smith TL, Soler ZM

Abstract
BACKGROUND: Ideal management of chronic rhinosinusitis (CRS) requires ongoing monitoring of disease and its control. Existing control instruments are limited in their correlation to patient reported outcomes, the need for endoscopy, or lack of validation from a multidisciplinary group. The goal of this study was to develop a patient-based Sinus Control Test (SCT) for determining CRS control.
METHODS: A systematic literature review and focus groups consisting of 20 patients and 11 medical experts in CRS from various medical specialties were used to generate items. A draft 13-item questionnaire was administered to 50 patients with CRS in a prospective fashion. Patients were evaluated using the 22-item Sino-Nasal Outcome Test (SNOT-22) instrument, Lund-Mackay computed tomography (CT) score, and Lund-Kennedy endoscopy score. A rhinologist blinded to the questionnaire results also provided an overall control of the disease for each patient. A regression model was generated to identify which subset of items showed the greatest discriminate ability in relation to specialist's and patient's global rating of disease control.
RESULTS: Four questions were included in the final questionnaire (p < 0.05), each with a scale of 0 to 4, with an overall total score ranging from 0 to 16. Optimal classification resulted in patients with a score from 1 to 3 (well controlled), 4 to 11 (partially controlled), and 12 to 16 (uncontrolled). SCT scores correctly classified control levels 72% of the time when compared to physician's assessment.
CONCLUSION: The SCT is a simple, patient generated questionnaire that can measure the control of CRS without requirement of endoscopy or CT evaluation.

PMID: 26683532 [PubMed - as supplied by publisher]

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Postoperative antibiotic prophylaxis in clean-contaminated head and neck oncologic surgery: a retrospective cohort study.

Postoperative antibiotic prophylaxis in clean-contaminated head and neck oncologic surgery: a retrospective cohort study.

Eur Arch Otorhinolaryngol. 2015 Dec 18;

Authors: Busch CJ, Knecht R, Münscher A, Matern J, Dalchow C, Lörincz BB

Abstract
Antibiotic prophylaxis is commonly used in head and neck oncologic surgery, due to the clean-contaminated nature of these procedures. There is a wide variety in the use of prophylactic antibiotics regarding the duration of application and the choice of agent. The purpose of this study was to determine whether short-term or long-term antibiotic prophylaxis has an impact on the development of head and neck surgical wound infection (SWI). Retrospective chart review was carried out in 418 clean-contaminated head and neck surgical oncology cases at our department. More than 50 variables including tumour type and stage, type of surgical treatment, co-morbidities, duration and choice of antibiotic prophylaxis, and the incidence of SWI were analysed. Following descriptive data analysis, Chi square test by Pearson and Fisher's exact test were used for statistical evaluation. Fifty-eight of the 418 patients (13.9 %) developed SWI. Patients with advanced disease and tracheotomy showed a significantly higher rate of SWI than those with early stage disease and without tracheotomy (p = 0.012 and p = 0.00017, respectively). However, there was no significant difference between the SWI rates in the short term and long term treatment groups (14.6 and 13.2 %, respectively; p = 0.689). Diabetes and body weight were not found to be risk factors for SWI. Long-term antibiotic prophylaxis was not associated with a decrease in SWI in the entire cohort of patients undergoing clean-contaminated major head and neck oncologic surgery. Our data confirmed the extent of surgery and tracheotomy as being risk factors for postoperative SWI.

PMID: 26683471 [PubMed - as supplied by publisher]

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Comparison of three different concurrent chemoradiation regimens for treatment of laryngeal cancer.

Comparison of three different concurrent chemoradiation regimens for treatment of laryngeal cancer.

Eur Arch Otorhinolaryngol. 2015 Dec 18;

Authors: Aydil U, Akmansu M, Gumusay Ö, Bakkal FK, Yazıcı Ö, Kızıl Y, Köybaşıoğlu A, Yıldız R, Büyükberber S, İnal E

Abstract
During last decades, laryngeal organ preservation strategies have emerged. The data about the oncological outcomes mainly come from multi-institutional prospective studies. In this study, we aimed to determine the oncological outcomes of different organ preservation regimens applied in routine practice. Patients who had definitive concurrent chemoradiation (CRT) for treatment of laryngeal cancer between January 2001 and June 2013 were retrospectively reviewed. There were 139 subjects who met the inclusion criteria. Three groups were defined: group A (n = 59) consisted of subjects who had concurrent cisplatin and radiotherapy (RT), group B (n = 47) consisted of subjects who had cisplatin/docetaxel-based concurrent CRT, and group C (n = 33) had induction chemotherapy before concurrent cisplatin and RT. The Kaplan-Meier estimated 5-year overall survival, disease-specific survival, disease-free survival, and local recurrence-free survival (LRFS) rates for the whole study group were 66.5, 69.2, 69.6, and 88.9 %, respectively. None of these survival rates were statistically different when the treatment arms were compared. The 3- and 5-year LRFS rates were significantly lower in subjects with a T4a tumor (p = 0.030). According to our results, the oncological outcomes of three different platinum-based concurrent chemotherapy schemes were similar and high local control rates could be achieved with the use of these protocols. Neoadjuvant chemotherapy before concurrent CRT was not superior to conventional concurrent treatment.

PMID: 26683470 [PubMed - as supplied by publisher]

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Clinical and surgical implications regarding morphometric variations of the medial wall of the orbit in relation to age and gender.

Clinical and surgical implications regarding morphometric variations of the medial wall of the orbit in relation to age and gender.

Eur Arch Otorhinolaryngol. 2015 Dec 18;

Authors: Morales-Avalos R, Santos-Martínez AG, Ávalos-Fernández CG, Mohamed-Noriega K, Sánchez-Mejorada G, Montemayor-Alatorre A, Martínez-Fernández DA, Espinosa-Uribe AG, Mohamed-Noriega J, Cuervo-Lozano EE, Mohamed-Hamsho J, Quiroga-García O, Lugo-Guillen RA, Guzmán-López S, Elizondo-Omaña RE

Abstract
The ethmoidal foramens are located on the medial wall of the orbit and are key reference points for intraoperative orientation. Detailed knowledge of the anatomy, bony landmarks and morphometric characteristics of the medial wall of the orbit is essential for various surgical procedures. The aim of this study was to determine the morphometric variations in the medial wall of the orbit and establish significant variations regarding age and gender. A total of 110 orbits were analyzed and subdivided by age (over or under 40 years) and gender. The distances of the medial wall of the orbit between the anterior lacrimal crest, the ethmoidal foramen, the optic canal and the interforamina were determined. Safe surgical areas were sought. Statistical tests were used to determine the differences between groups. In men, there is a safe surgical area proximal to the anterior and posterior ethmoidal foramen. In women, this area is in the posterior third of the medial wall of the orbit between the posterior ethmoidal foramen and the optic canal. Regarding variation according to age, the results of this study suggested that the anteroposterior diameter of the medial wall increases with age. This study showed that the anteroposterior total length of the medial orbit wall is similar between genders of similar age, increases with age, and has significant variations in the distances between the various structures that make up the medial orbit wall with regard to gender and age.

PMID: 26683469 [PubMed - as supplied by publisher]

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Cingulo-Opercular Function During Word Recognition in Noise for Older Adults with Hearing Loss.

Cingulo-Opercular Function During Word Recognition in Noise for Older Adults with Hearing Loss.

Exp Aging Res. 2016 Jan-Feb;42(1):86-106

Authors: Vaden KI, Kuchinsky SE, Ahlstrom JB, Teubner-Rhodes SE, Dubno JR, Eckert MA

Abstract
BACKGROUND/STUDY CONTEXT: Adaptive control, reflected by elevated activity in cingulo-opercular brain regions, optimizes performance in challenging tasks by monitoring outcomes and adjusting behavior. For example, cingulo-opercular function benefits trial-level word recognition in noise for normal-hearing adults. Because auditory system deficits may limit the communicative benefit from adaptive control, we examined the extent to which cingulo-opercular engagement supports word recognition in noise for older adults with hearing loss (HL).
METHODS: Participants were selected to form groups with Less HL (n = 12; mean pure tone threshold, pure tone average [PTA] = 19.2 ± 4.8 dB HL [hearing level]) and More HL (n = 12; PTA = 38.4 ± 4.5 dB HL, 0.25-8 kHz, both ears). A word recognition task was performed with words presented in multitalker babble at +3 or +10 dB signal-to-noise ratios (SNRs) during a sparse acquisition fMRI experiment. The participants were middle-aged and older (ages: 64.1 ± 8.4 years) English speakers with no history of neurological or psychiatric diagnoses.
RESULTS: Elevated cingulo-opercular activity occurred with increased likelihood of correct word recognition on the next trial (t(23) = 3.28, p = .003), and this association did not differ between hearing loss groups. During trials with word recognition errors, the More HL group exhibited higher blood oxygen level-dependent (BOLD) contrast in occipital and parietal regions compared with the Less HL group. Across listeners, more pronounced cingulo-opercular activity during recognition errors was associated with better overall word recognition performance.
CONCLUSION: The trial-level word recognition benefit from cingulo-opercular activity was equivalent for both hearing loss groups. When speech audibility and performance levels are similar for older adults with mild to moderate hearing loss, cingulo-opercular adaptive control contributes to word recognition in noise.

PMID: 26683042 [PubMed - in process]

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Task-Related Vigilance During Word Recognition in Noise for Older Adults with Hearing Loss.

Task-Related Vigilance During Word Recognition in Noise for Older Adults with Hearing Loss.

Exp Aging Res. 2016 Jan-Feb;42(1):64-85

Authors: Kuchinsky SE, Vaden KI, Ahlstrom JB, Cute SL, Humes LE, Dubno JR, Eckert MA

Abstract
BACKGROUND/STUDY CONTEXT: Vigilance refers to the ability to sustain and adapt attentional focus in response to changing task demands. For older adults with hearing loss, vigilant listening may be particularly effortful and variable across individuals. This study examined the extent to which neural responses to sudden, unexpected changes in task structure (e.g., from rest to word recognition epochs) were related to pupillometry measures of listening effort.
METHODS: Individual differences in the task-evoked pupil response during word recognition were used to predict functional magnetic resonance imaging (MRI) estimates of neural responses to salient transitions between quiet rest, noisy rest, and word recognition in unintelligible, fluctuating background noise. Participants included 29 older adults (M = 70.2 years old) with hearing loss (pure tone average across all frequencies = 36.1 dB HL [hearing level], SD = 6.7).
RESULTS: Individuals with a greater average pupil response exhibited a more vigilant pattern of responding on a standardized continuous performance test (response time variability across varying interstimulus intervals r(27) = .38, p = .04). Across participants there was widespread engagement of attention- and sensory-related cortices in response to transitions between blocks of rest and word recognition conditions. Individuals who exhibited larger task-evoked pupil dilation also showed even greater activity in the right primary auditory cortex in response to changes in task structure.
CONCLUSION: Pupillometric estimates of word recognition effort predicted variation in activity within cortical regions that were responsive to salient changes in the environment for older adults with hearing loss. The results of the current study suggest that vigilant attention is increased amongst older adults who exert greater listening effort.

PMID: 26683041 [PubMed - in process]

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Angioleiomyoma of the larynx: beware the subglottic lesion.

Angioleiomyoma of the larynx: beware the subglottic lesion.

BMJ Case Rep. 2015;2015

Authors: Hope N, Smith CP, McCluney N

Abstract
Angioleiomyomas are a benign group of tumours rarely documented in the head and neck region. We present a case of a 47-year-old man attending the ear, nose and throat outpatient clinic, with a history of hoarseness over many years. Investigation revealed a left-sided subglottic lesion. He underwent microlaryngoscopy and biopsy, and the lesion was sent for histological analysis. Postoperatively, the patient began to expectorate fresh red blood that continued for several hours, requiring surgical intervention. Haemostatic control was achieved and a tracheostomy was sited for airway protection. Histopathology identified angioleiomyoma as the cause of his symptoms. Following multidisciplinary team discussion, this was managed with injection of bleomycin and subsequent surgical excision. This case is a reminder that subglottic lesions are often vascular in nature, and should be investigated with imaging and angiography prior to surgery, to avoid complications.

PMID: 26682845 [PubMed - as supplied by publisher]

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Mechanisms of magnesium-induced vasodilation in cerebral penetrating arterioles.

Publication date: Available online 19 December 2015
Source:Neuroscience Research
Author(s): Takahiro Murata, Hans H. Dietrich, Tetsuyoshi Horiuchi, Kazuhiro Hongo, Ralph G. Dacey
We investigated in cerebral penetrating arterioles the signaling mechanisms and dose-dependency of extracellular magnesium-induced vasodilation and also its vasodilatory effects in vessels preconstricted with agonists associated with delayed cerebral vasospasm following SAH. Male rat penetrating arterioles were cannulated. Their internal diameters were monitored. To investigate mechanisms of magnesium-induced vasodilation, inhibitors of endothelial function, potassium channels and endothelial impairment were tested. To simulate cerebral vasospasm we applied several spasmogenic agonists. Increased extracellular magnesium concentration produced concentration-dependent vasodilation, which was partially attenuated by non-specific calcium-sensitive potassium channel inhibitor tetraethylammonium, but not by other potassium channel inhibitors. Neither the nitric oxide synthase inhibitor L-NNA nor endothelial impairment induced by air embolism reduced the dilation. Although the magnesium-induced vasodilation was slightly attenuated by the spasmogen ET-1, neither application of PF2α nor TXA2 analog effect the vasodilation. Magnesium induced a concentration- and smooth muscle cell-dependent dilation in cerebral penetrating arterioles. Calcium-sensitive potassium channels of smooth muscle cells may play a key role in magnesium-induced vasodilation. Magnesium also dilated endothelium-impaired vessels as well as vessels preconstricted with spasmogenic agonists. These results provide a fundamental background for the clinical use of magnesium, especially in treatment against delayed cerebral ischemia or vasospasm following SAH.



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