Review Allergy
. 2019 Jul;74(7):1219-1236. doi: 10.1111/all.13701. Epub 2019 Apr 30.
ARIA Pharmacy 2018 "Allergic Rhinitis Care Pathways for Community Pharmacy": AIRWAYS ICPs Initiative (European Innovation Partnership on Active and Healthy Ageing, DG CONNECT and DG Santé) POLLAR (Impact of Air POLLution on Asthma and Rhinitis) GARD Demonstration Project
Sinthia Bosnic-Anticevich 1, Elisio Costa 2, Enrica Menditto 3, Olga Lourenço 4, Ettore Novellino 5, Slawomir Bialek 6, Vitalis Briedis 7, Roland Buonaiuto 8, Henry Chrystyn 9, Biljana Cvetkovski 1, Stefania Di Capua 10, Vicky Kritikos 1, Alpana Mair 11, Valentina Orlando 3, Ema Paulino 12, Johanna Salimäki 13, Rojin Söderlund 14, Rachel Tan 1, Dennis M Williams 15, Piotr Wroczynski 6, Ioana Agache 16, Ignacio J Ansotegui 17, Josep M Anto 18 19 20 21, Anna Bedbrook 22, Claus Bachert 23, Mike Bewick 24, Carsten Bindslev-Jensen 25, Jan L Brozek 26, Giorgio Walter Canonica 27, Victoria Cardona 28, Warner Carr 29, Thomas B Casale 30, Niels H Chavannes 31, Jaime Correia de Sousa 32 33, Alvaro A Cruz 34 35, Wienczyslawa Czarlewski 36, Giuseppe De Carlo 37, Pascal Demoly 38 39, Philippe Devillier 40, Mark S Dykewicz 41, Mina Gaga 42, Yehia El-Gamal 43, João Fonseca 44 45, Wytske J Fokkens 46, Maria Antonieta Guzmán 47, Tari Haahtela 48 49, Peter W Hellings 50, Maddalena Illario 51, Juan Carlos Ivancevich 52, Jocelyne Just 53, Igor Kaidashev 54, Musa Khaitov 55, Nikolai Khaltaev 56, Thomas Keil 57 58, Ludger Klimek 59, Marek L Kowalski 60, Piotr Kuna 61, Violeta Kvedariene 62, Désirée E Larenas-Linnemann 63, Daniel Laune 64, Lan T T Le 65, Karin C Lodrup Carlsen 66 67, Bassam Mahboub 68, Dieter Maier 69, Joao Malva 70 71, Patrick J Manning 72, Mário Morais-Almeida 73, Ralph Mösges 74 75, Joaquim Mullol 76, Lars Münter 77, Ruth Murray 78, Robert Naclerio 79, Leyla Namazova-Baranova 80, Kristof Nekam 81, Tshipukane Dieudonné Nyembue 82, Kimi Okubo 83, Robyn E O'Hehir 84 85, Ken Ohta 86, Yoshitaka Okamoto 87, Gabrielle L Onorato 22, Susanna Palkonen 37, Petr Panzner 88, Nikolaos G Papadopoulos 89 90, Hae-Sim Park 91, Ruby Pawankar 92, Oliver Pfaar 93, Jim Phillips 94, Davor Plavec 95, Todor A Popov 96, Paul C Potter 97, Emmanuel P Prokopakis 98, Regina E Roller-Wirnsberger 99, Menachem Rottem 100, Dermot Ryan 101, Bolesław Samolinski 102, Mario Sanchez-Borges 103 104, Holger J Schunemann 26, Aziz Sheikh 105, Juan Carlos Sisul 106, David Somekh 107, Cristiana Stellato 108, Teresa To 109, Ana Maria Todo-Bom 110 111, Peter Valentin Tomazic 112, Sanna Toppila-Salmi 48 49, Antonio Valero 113, Arunas Valiulis 114 115, Errka Valovirta 116, Maria Teresa Ventura 117, Martin Wagenmann 118, Dana Wallace 119, Susan Waserman 120, Magnus Wickman 121, Panayiotis K Yiallouros 122 123, Arzu Yorgancioglu 124, Osman M Yusuf 125, Heather J Zar 126, Mario E Zernotti 127, Luo Zhang 128, Mihaela Zidarn 129, Torsten Zuberbier 130, Jean Bousquet 22 130 131 132 133 134
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PMID: 30565275 DOI: 10.1111/all.13701
Abstract
Pharmacists are trusted health care professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact for allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The Allergic Rhinitis and its Impact on Asthma (ARIA)-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses), and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of allergic rhinitis. However, the ARIA-pharmacy ICP should be adapted to local healthcare environments/situations as regional (national) differences exist in pharmacy care.

Keywords: Allergic Rhinitis and its Impact on Asthma; Asthma; Care pathways; Pharmacist; Rhinitis.

© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Cited by 8 articles
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2
Biomed Res Int
. 2019 Dec 28;2019:9379864. doi: 10.1155/2019/9379864. eCollection 2019.
Combined Analysis of the Aberrant Epigenetic Alteration of Pancreatic Ductal Adenocarcinoma
Rui Xu # 1, Qiuyan Xu # 2, Guanglei Huang # 2, Xinhai Yin 2, Jianguo Zhu 3, Yikun Peng 4, Jukun Song 2
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PMID: 31956659 PMCID: PMC6949667 DOI: 10.1155/2019/9379864
Free PMC article
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most fatal malignancies due to its high morbidity and mortality. DNA methylation exerts a vital part in the development of PDAC. However, a mechanistic role of mutual interactions between DNA methylation and mRNA as epigenetic regulators on transcriptomic alterations and its correlation with clinical outcomes such as survival have remained largely uncovered in cancer. Therefore, elucidation of aberrant epigenetic alteration in the development of PDAC is an urgent problem to be solved. In this work, we conduct an integrative epigenetic analysis of PDAC to identify aberrant DNA methylation-driven cancer genes during the occurrence of cancer.

Methods: DNA methylation matrix and mRNA profile were obtained from the TCGA database. The integration of methylation and gene expression datasets was analyzed using an R package MethylMix. The genes with hypomethylation/hypermethylation were further validated in the Kaplan-Meier analysis. The correlation analysis of gene expression and aberrant DNA methylation was also conducted. We performed a pathway analysis on aberrant DNG methylation genes identified by MethylMix criteria using ConsensusPathDB.

Results: 188 patients with both methylation data and mRNA data were considered eligible. A mixture model was constructed, and differential methylation genes in normal and tumor groups using the Wilcoxon rank test was performed. With the inclusion criteria, 95 differential methylation genes were detected. Among these genes, 74 hypermethylation and 21 hypomethylation genes were found. The pathway analysis revealed an increase in hypermethylation of genes involved in ATP-sensitive potassium channels, Robo4, and VEGF signaling pathways crosstalk, and generic transcription pathway.

Conclusion: Integrated analysis of the aberrant epigenetic alteration in pancreatic ductal adenocarcinoma indicated that differentially methylated genes could play a vital role in the occurrence of PDAC by bioinformatics analysis. The present work can help clinicians to elaborate on the function of differentially methylated expressed genes and pathways in PDAC. CDO1, GJD2, ID4, NOL4, PAX6, TRIM58, and ZNF382 might act as aberrantly DNA-methylated biomarkers for early screening and therapy of PDAC in the future.

Copyright © 2019 Rui Xu et al.

Conflict of interest statement
The authors declare that they have no conflicts of interest.

55 references5 figures
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3
Allergy
. 2019 Jul;74(7):1307-1316. doi: 10.1111/all.13677. Epub 2018 Dec 17.
Increased Expression of L-plastin in Nasal Polyp of Patients With Nonsteroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease
Tetsuji Takabayashi 1, Yukie Tanaka 2, Dai Susuki 1, Kanako Yoshida 1, Kaori Tomita 1, Masafumi Sakashita 1, Yoshimasa Imoto 1, Yukinori Kato 1, Norihiko Narita 1, Tsugihisa Nakayama 3, Shinichi Haruna 3, Robert P Schleimer 4, Shigeharu Fujieda 1
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PMID: 30479022 PMCID: PMC6890232 DOI: 10.1111/all.13677
Free PMC article
Abstract
Background: Most patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD) suffer from recurrence of nasal polyps. However, little is known about the specific cellular and molecular mechanisms contributing to the pathogenesis of nasal polyp development in patients with NERD in particular, especially at baseline when cyclooxygenase 1 inhibitors are not present. The objectives of this study were to identify proteins involved in the pathogenesis of nasal polyps in patients with NERD.

Methods: We collected nasal polyp tissue from patients with NERD and from patients with aspirin-tolerant chronic rhinosinusitis with nasal polyps (CRSwNP). Protein profiles were analyzed by 2-dimensional electrophoresis and identified several proteins, including L-plastin, as highly expressed. We examined L-plastin and tissue factor (TF) expression by immunohistochemical and immunofluorescence analyses. To examine the role of L-plastin in eosinophils, we knocked down L-plastin expression in Eol-1 cells by using siRNA transfection.

Results: L-plastin protein levels in nasal polyp tissue were increased in patients with NERD relative to those in patients with aspirin tolerant CRSwNP. Immunofluorescence analysis revealed that L-plastin was dominantly expressed in eosinophils and L-plastin and TF were co-expressed in eosinophils in NERD nasal polyp tissue. Knockdown of L-plastin in Eol-1 cells disrupted the cell surface distribution of TF by stimulation with granulocyte macrophage colony-stimulating factor.

Conclusion: Increased expression of L-plastin by eosinophils may contribute to abnormal fibrin deposition through TF translocation to the eosinophil cell surface in NERD nasal polyp tissue, which in turn may contribute to the pathogenesis of NERD.

© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Conflict of interest statement
CONFLICT OF INTEREST

The authors declare that they have no conflicts of interest.

Comment in
Do NERDy eosinophils accelerate nasal polyp growth?
Tan BK, Wang Y.
Allergy. 2019 Dec;74(12):2291-2292. doi: 10.1111/all.13855.
PMID: 31067351 No abstract available.
Cited by 2 articles6 figures
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4
Oral Oncol
. 2019 Aug;95:52-58. doi: 10.1016/j.oraloncology.2019.06.002. Epub 2019 Jun 7.
Polymorphous Adenocarcinoma of Salivary Glands
Ximena Mimica 1, Nora Katabi 2, Marlena R McGill 3, Ashley Hay 4, Daniella Karassawa Zanoni 5, Jatin P Shah 6, Richard J Wong 7, Marc A Cohen 8, Snehal G Patel 9, Ian Ganly 10
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PMID: 31345394 PMCID: PMC6698324 (available on 2020-08-01) DOI: 10.1016/j.oraloncology.2019.06.002
Free PMC article
Abstract
Objective: Polymorphous adenocarcinoma of salivary gland (PAC) is rare. Despite being described as a low risk histology, some patients develop regional and distant metastasis. More aggressive behavior has been attributed to a PAC subcategory called cribriform adenocarcinoma of minor salivary glands (CAMSG). We examined oncological outcomes of PAC.

Patients and methods: Fifty-seven patients with PAC were identified from an institutional database of 884 patients surgically treated for salivary gland malignancies from 1985 to 2015. Detailed histopathological analysis was performed. Survival outcomes were calculated using the Kaplan-Meier method. Factors predictive of recurrence were identified using the Cox proportional hazard method.

Results: Fifty-four (95%) had tumors of minor salivary gland origin; the most frequent location was the oral cavity in 41 (76%), specifically the hard palate in 32 (55%). Forty-six patients (81%) were clinical T1-T2; 3 (5%) had a clinically positive neck. Thirty-two patients (56%) were classified as PAC and 14 (25%) as CAMSG. Forty-four patients (77%) had surgery alone; 13 (23%) had surgery and postoperative radiotherapy. The 5- and 10-year overall survival and disease-specific survival were 88% and 79% and 98% and 94%, respectively (median follow up 84 [1-159] months); 5- and 10-year recurrence-free survival were 93% and 88%, respectively. Univariate analysis showed male sex, III/IV stage, and CASMG variant had increased incidence of recurrence but were not statistically significant.

Conclusion: PAC of the salivary glands is an indolent disease with good survival outcomes. Recurrence is uncommon and tends to occur late. Long-term follow-up is indicated in patients with this disease.

Keywords: Cribriform adenocarcinoma of minor salivary glands; Minor salivary gland; Polymorphous low-grade adenocarcinoma; Prognosis; Salivary gland neoplasm; Treatment.

Copyright © 2019 Elsevier Ltd. All rights reserved.

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5
Oral Oncol
. 2019 Aug;95:194-201. doi: 10.1016/j.oraloncology.2019.06.026. Epub 2019 Jun 28.
Establishment of Syngeneic Murine Model for Oral Cancer Therapy
Yi-Fen Chen 1, Kuo-Wei Chang 2, I-Ting Yang 1, Hsi-Feng Tu 3, Shu-Chun Lin 4
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PMID: 31345390 DOI: 10.1016/j.oraloncology.2019.06.026
Abstract
Oral carcinoma (OSCC) is one of the most important causes of cancer death worldwide. OSCC cell lines and preclinical rodent models are crucial to addressing the mechanisms of OSCC and helping the development of new therapeutic strategies and interventions. The establishment of murine OSCC cell lines and syngeneic models are necessary to allow concordant investigation of both in vitro and in vivo pathogenesis. In this study, we established two murine tongue squamous cell carcinoma cell lines, designated MTCQ1 and MTCQ2, from 4NQO-induced OSCC using C57BL/6 mice. These cell lines express a variety of epithelial markers but produce only a tiny amount of E-cadherin. The expression of mesenchymal and stemness regulators are evident, and this is associated with the high mobility in these cell lines. MTCQ1 also shows high Ki67 and PCNA expression, and complicated alterations in p53 expression, which may underlie its high clonogenic potential and rapid orthotopic tumor induction. Using the MTCQ1 cell subclone tagged with GFP (MTCQ1-GFP), extensive neck nodal metastasis and lung metastasis were identified by immunostaining and fluorescence imaging. Inhibition of oncogenic miRNAs, particularly miR-134, was able to attenuate the oncogenicity of MTCQ1-GFP. Cisplatin treatment inhibited both in vitro and in vivo growth of MTCQ1-GFP, and it was found to decrease miR-134 expression in this subclone. The anti-PD-L1 treatment enhanced the inhibitory effects of cisplatin against tumorigenesis. This syngeneic preclinical model should help provide valuable mechanistic insights into OSCC, as well as helping with the development of new approaches to treating this disease.

Keywords: Cancer; Cisplatin; Keratinocyte; Mouth; PD-L1; Preclinical model; Squamous; Therapy; miR-134; microRNA.

Copyright © 2019 Elsevier Ltd. All rights reserved.

Cited by 2 articles
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6
Clinical Trial Oral Oncol
. 2019 Aug;95:170-177. doi: 10.1016/j.oraloncology.2019.06.021. Epub 2019 Jun 25.
Standard of Care vs Reduced-Dose Chemoradiation After Induction Chemotherapy in HPV+ Oropharyngeal Carcinoma Patients: The Quarterback Trial
K Misiukiewicz 1, V Gupta 2, B A Miles 3, R Bakst 4, E Genden 5, I Selkridge 6, J T Surgeon 6, H Rainey 6, N Camille 6, E Roy 6, D Zhang 7, F Ye 7, R Jia 8, E Moshier 8, M Bonomi 9, M Hwang 10, P Som 11, M R Posner 12
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PMID: 31345387 DOI: 10.1016/j.oraloncology.2019.06.021
Abstract
Background: Human Papillomavirus oropharyngeal carcinoma (HPVOPC) has better progression free (PFS) and overall survival (OS) than non-HPVOPC. Standard-dose chemoradiotherapy (sdCRT) results in significant acute toxicity and late morbidity. We hypothesized that after induction chemotherapy (IC), reduced dose chemoradiation (rdCRT) would result in equivalent PFS and OS compared to sdCRT plus IC in HPVOPC and would reduce toxicity.

Methods: Patients with p16+, previously untreated, locally advanced HPVOPC and ≤20 pack years smoking history received 3 cycles of IC with docetaxel, cisplatin and fluorouracil (TPF). Clinical responders who were HPV positive by type-specific PCR were randomized 1:2 to sdCRT (7000 cGy) or rdCRT (5600 cGy) with weekly carboplatin. The endpoints of the study were 3 year PFS and OS.

Results: 23 patients were enrolled, 22 were evaluable for TPF toxicity and 20 were randomized, 8 to sdCRT and 12 to rdCRT. Sixteen (80%) were HPV 16+ and 4 (20%) were other high risk (HR) variants. Fourteen (70%) had high risk features: T4, N2c, or N3. Median follow up was 56 months (range 42-70). Three-year PFS/OS for sdCRT and rdCRT are 87.5% vs 83.3% (log-rank test p = 0.85), respectively. All 3 failures are locoregional within 4 months of completion of CRT; 2 were in HR variants (50%).

Conclusions: rdCRT after IC resulted in similar PFS/OS compared sdCRT. These data support Phase 3 clinical trials of radiation dose reduction after IC as a treatment strategy in HPVOPC. Molecular HPV with variant testing and smoking history are necessary for de-escalation trials.

Keywords: De-escalation; Human papillomavirus; Oropharynx cancer; Sequential therapy.

Copyright © 2019 Elsevier Ltd. All rights reserved.

Cited by 2 articles
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7
Oral Oncol
. 2019 Aug;95:65-73. doi: 10.1016/j.oraloncology.2019.06.012. Epub 2019 Jun 10.
A Histopathological Evaluation and Potential Prognostic Implications of Oral Squamous Cell Carcinoma With Adverse Features
Wei-Chin Chang 1, Ching-Fen Chang 2, Yu-Hsuan Li 1, Cheng-Yu Yang 3, Ruei-Yu Su 4, Chih-Kung Lin 5, Yuan-Wu Chen 6
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PMID: 31345396 DOI: 10.1016/j.oraloncology.2019.06.012
Abstract
Objectives: This study aimed to evaluate the adverse clinicopathologic features of oral squamous cell carcinoma (OSCC), including margin status, depth of invasion, lymphovascular invasion, perineural invasion, and extranodal extension that significantly affect survival outcomes.

Materials and methods: This retrospective cross-sectional study included 341 patients with OSCC who underwent therapeutic surgical treatment in Taiwan. The Kaplan-Meier method was used to estimate survival outcomes. A multivariable Cox regression model was used to evaluate the associations of various clinicopathologic features with 5-year overall survival (OS) outcomes in patients with pN0 and pN+ tumors.

Results: Overall, the patients had 5-year OS and progression-free survival rates of 60.0 and 47.9%, respectively. In the pN0 group, the multivariate analysis identified a positive margin (odds ratio [OR] = 16.3, 95% confidence interval [95% CI]: 3.7-72.3; P = 0.001), depth of invasion >5 mm (OR = 2.1, 95% CI: 1.2-3.7; P = 0.012), presence of lymphovascular space invasion (OR = 5.4, 95% CI: 1.3-22.0; P = 0.018), and presence of perineural invasion (OR = 4.3, 95% CI: 1.7-11.1; P = 0.002) as independent and significant prognosticators of OS. In the pN+ group, only the presence of extranodal extension independently predicted OS (OR = 1.7, 95% CI: 1.1-2.7; P = 0.0026).

Conclusions: When determining survival prognosis for patients with a pN0 status, we recommended including all adverse features. In contrast, extranodal extension was the most important prognostic factor for patients with a pN+ status.

Keywords: Adverse feature; Depth of invasion; Extranodal extension; Lymphovascular invasion; Oral squamous cell carcinoma; Perineural invasion; Prognosis; Surgical margins.

Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cited by 1 article
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8
Oral Oncol
. 2019 Aug;95:43-51. doi: 10.1016/j.oraloncology.2019.05.021. Epub 2019 Jun 6.
Prognostic Determinants of Locally Advanced Buccal Mucosa Cancer: Do We Need to Relook the Current Staging Criteria?
Vijay Pillai 1, Vishal Yadav 1, Vikram Kekatpure 1, Nirav Trivedi 1, Naveen Hedne Chandrashekar 1, Vivek Shetty 1, Vidyabhushan Rangappa 1, Narayana Subramaniam 1, Venkatraman Bhat 2, Nisheena Raghavan 3, Trupti Kolur 1, Nivya George 4, Tinku Thomas 4, Moni Abraham Kuriakose 5
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PMID: 31345393 DOI: 10.1016/j.oraloncology.2019.05.021
Abstract
Objectives: Current guidelines advocate non-surgical treatment for T4b buccal mucosa carcinoma with surgery preferred in other stages. We investigated oncologic outcomes of this cohort in comparison with T4a cohort, treated by similar multi-modality approach of primary surgery followed by adjuvant treatment and identified prognostic determinants of survival.

Materials and methods: Oncologic outcome of prospectively accrued 282 patients with cT4a and cT4b buccal mucosa squamous cell carcinoma were evaluated for overall survival (OS) and disease free survival (DFS) at 2 years of the whole cohort and for the subgroups of T4a and T4b patients. Multivariate Cox proportional hazards regression analysis was performed to identify prognostic determinants.

Results: Of 277 eligible patients treated and followed for a median period of 21 months, the OS was comparable between T4a and T4b as 64% vs 58%, (p = 0.354). The DFS between the two subgroups was 64% vs 61%, (p = 0.316). Although there was 47% pathologic down staging from the clinical stage, there was no significant difference in oncologic outcome between pT4a and pT4b (OS, 57% vs 58% for T4a and T4b, p = 0.687; DFS, 58% vs 60% for T4a and T4b, p = 0.776). On multivariate analysis, extra capsular spread (p = 0.042), lateral pterygoid muscle involvement (p = 0.035) and defaulting adjuvant treatment (p < 0.001) were independent predictors of outcome for the T4b cohort when other factors were controlled.

Conclusions: Primary surgery followed by adjuvant chemo-radiotherapy offers comparable results in selected T4b gingiva and buccal mucosal cancer, suggesting the need to relook the staging criteria for oral cavity cancer.

Keywords: Advanced buccal cancer; Chemoradiation; Compartment resection; Disease free survival; Infratemporal fossa; Masticatory space; Oral cancer, T4b; Overall survival; Radiation; Surgery.

Copyright © 2019 Elsevier Ltd. All rights reserved.

Comment in
Prognostic determinants of locally advanced buccal mucosa cancer: Do we need to relook the current staging criteria? - Needs to be interpreted carefully.
Thiagarajan S, Nair SV.
Oral Oncol. 2019 Nov;98:158-159. doi: 10.1016/j.oraloncology.2019.09.021. Epub 2019 Sep 24.
PMID: 31561949 No abstract available.
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9
Review Curr Opin Allergy Clin Immunol
. 2019 Aug;19(4):365-372. doi: 10.1097/ACI.0000000000000540.
Use of Biologics in Chronic Sinusitis With Nasal Polyps
Chengshuo Wang 1, Luo Zhang 1 2 3
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PMID: 31082822 DOI: 10.1097/ACI.0000000000000540
Abstract
Purpose of review: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory condition with different endotypes between patients from eastern or western countries. Targeted biologics are currently used to treat CRSwNP, but the outcomes widely vary. This review focuses on the present use of biologics for treating CRSwNP.

Recent findings: Monoclonal biologics have been used as an innovative therapy for multiple allergic diseases and comorbid allergic conditions. Over the past several decades, numerous biomarkers have been investigated and were found to be closely correlated with CRSwNP, improving the understanding of inflammatory patterns and endotype classifications for CRSwNP and prompting discussion regarding the use of biologics in CRSwNP. Efficacies vary in reports of different research groups, but it has been found that patients with TH-2-driven inflammatory patterns respond better to the use of biologics than those with non-TH-2-driven CRSwNP. These findings suggest the importance and urgency of developing criteria for biologics in CRSwNP.

Summary: Precisely determining patient criteria, identifying treatment biomarkers based on endotyping for CRSwNP and determinations of contraindications for long-term utilization may be useful for optimizing treatment strategies and improving the therapeutic efficacy of biologics to achieve long-term control starting at early stages.

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10
Oral Oncol
. 2019 Aug;95:143-149. doi: 10.1016/j.oraloncology.2019.06.018. Epub 2019 Jun 22.
Laryngo-esophageal Dysfunction Free Survival and Propensity Score Matched Analysis Comparing Organ Preservation and Total Laryngectomy in Hypopharynx Cancer
J F Petersen 1, C R Arends 1, V van der Noort 2, A Al-Mamgani 3, J P de Boer 4, M M Stuiver 5, M W M van den Brekel 6
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PMID: 31345382 DOI: 10.1016/j.oraloncology.2019.06.018
Abstract
Aims: To assess the functional outcomes of patients treated for hypopharynx cancer and to obtain an unbiased estimate of survival difference between patients treated with chemoradiotherapy (CRT) or total laryngectomy (TL).

Methods: Retrospective cohort study of all patients treated with curative intent for T1-T4 squamous cell carcinoma of the hypopharynx in The Netherlands Cancer Institute (1990-2013). Functional outcome following radiotherapy (RT) or CRT was measured using laryngo-esophageal dysfunction free survival rate (LDFS). Using propensity score (PS) matched analysis, we compared survival outcome of TL to CRT in T2-T4 patients.

Results: We included 343 patients with T1T4 hypopharynx cancer. LDFS 2 and 5-years following CRT was respectively 44 and 32%. Following RT this was 39 and 30%. Patients were matched on the following variables: age, gender, TNM classification, subsite of tumor, decade of diagnosis, prior cancer, smoking, ACE27 score, BMI hemoglobin, albumin, and leukocyte level. With PS matching, we were able to match 26 TL patients with 26 CRT patients. The OS rates for TL and CRT in this matched cohort were respectively 56% and 46% at 5 years and 35% and 17% at 10 years.

Conclusion: In conclusion, functional outcomes following RT or CRT are suboptimal and require improved treatment strategies or rehabilitation efforts. The OS results challenge the preposition that CRT and TLE are equivalent in terms of survival.

Keywords: Chemotherapy; Hypopharynx cancer; Laryngectomy; Laryngo-esophageal dysfunctional free survival rate; Propensity score matching; Radiotherapy; Survival.

Copyright © 2019 Elsevier Ltd. All rights reserved.

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11
Oral Oncol
. 2019 Aug;95:74-78. doi: 10.1016/j.oraloncology.2019.06.007. Epub 2019 Jun 11.
Impact of Chemotherapy Regimen on Treatment Outcomes in Patients With HPV-associated Oropharyngeal Cancer With T4 Disease Treated With Definitive Concurrent Chemoradiation
Onita Bhattasali 1, Joan J Ryoo 1, Lester D R Thompson 2, Iman A Abdalla 3, Jergin Chen 1, Shawn Iganej 4
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PMID: 31345397 DOI: 10.1016/j.oraloncology.2019.06.007
Abstract
Objectives: Although human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is typically associated with a good prognosis, patients with T4 disease experience relatively high rates of treatment failure. Our aim was to identify predictors of relapse among patients with clinical T4 disease.

Material & methods: A retrospective review was conducted of 93 consecutive patients who underwent definitive concurrent chemoradiation for HPV-associated OPSCC with clinical T4 disease from July 2006 to December 2015. Three-year outcomes, including locoregional recurrence (LRR), distant metastasis (DM), overall survival (OS), and cancer-specific survival (CSS), were examined and reported from the date of treatment completion. Multivariable analysis using a Cox proportional hazards model was performed to test associations between outcome and patient and disease characteristics as well as chemotherapy regimen (high-dose cisplatin (HDC) vs. other).

Results: Median follow-up for surviving patients was 50 months (range 18-133). For all-comers, 3-year rates of LRR, DM, OS, and CSS were 15%, 19%, 79%, and 86%, respectively. On multivariable analysis, the only factor prognostic for patient outcomes was the chemotherapy regimen. For patients who received HDC vs. an alternative regimen, 3-year LRR, DM, OS, and CSS, were 9% vs. 20% (p = 0.09), 10% vs. 28% (p = 0.04), 89% vs. 67% (p = 0.04), and 96% vs. 77% (p = 0.02), respectively.

Conclusion: In patients with HPV-associated OPSCC bearing clinical T4 disease, receipt of a concurrent systemic agent other than HDC resulted in increased treatment failure and inferior survival. This analysis suggests that HDC should remain the preferred concurrent regimen for these patients.

Keywords: Carboplatin; Cetuximab; Chemoradiation; Cisplatin; Human papilloma virus; Oropharyngeal cancer; P16-positive; Radiotherapy; Squamous cell carcinoma; T4 disease.

Copyright © 2019 Elsevier Ltd. All rights reserved.

Cited by 1 article
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12
J Sex Med
. 2019 Nov;16(11):1721-1733. doi: 10.1016/j.jsxm.2019.08.015. Epub 2019 Oct 1.
Sildenafil Protects Endothelial Cells From Radiation-Induced Oxidative Stress
R C Wortel 1, A Mizrachi 2, H Li 3, E Markovsky 3, B Enyedi 4, J Jacobi 5, O Brodsky 6, J Cao 7, A R Lippert 7, L Incrocci 8, J P Mulhall 9, A Haimovitz-Friedman 10
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PMID: 31585804 PMCID: PMC7269093 DOI: 10.1016/j.jsxm.2019.08.015
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Abstract
Introduction: The etiology of radiation-induced erectile dysfunction (ED) is complex and multifactorial, and it appears to be mainly atherogenic.

Aim: To focus on vascular aspects of radiation-induced ED and to elucidate whether the protective effects of sildenafil are mediated by attenuation of oxidative stress and apoptosis in the endothelial cells.

Methods: Bovine aortic endothelial cells (BAECs), with or without pretreatment of sildenafil (5 μM at 5 minutes before radiation), were used to test endothelial dysfunction in response to external beam radiation at 10-15 Gy. Generation of reactive oxygen species (ROS) was studied. Extracellular hydrogen peroxide (H2O2) was measured using the Amplex Red assay and intracellular H2O2 using a fluorescent sensor. In addition, ROS superoxide (O2•-) was measured using a O2•- chemiluminescence enhancer. Both H2O2 and O2•- are known to reduce the bioavailability of nitric oxide, which is the most significant chemical mediator of penile erection. Generation of cellular peroxynitrite (ONOO-) was measured using a chemiluminescence assay with the PNCL probe. Subsequently, we measured the activation of acid sphingomyelinase (ASMase) enzyme by radioenzymatic assay using [14C-methylcholine] sphingomyelin as substrate, and the generation of the proapoptotic C16-ceramide was assessed using the diacylglycerol kinase assay. Endothelial cells apoptosis was measured as a readout of these cells' dysfunction.

Main outcome measures: Single high-dose radiation therapy induced NADPH oxidases (NOXs) activation and ROS generation via the proapoptotic ASMase/ceramide pathway. The radio-protective effect of sildenafil on BAECs was due to inhibition of this pathway.

Results: Here, we demonstrate for the first time that radiation activated NOXs and induced generation of ROS in BAECs. In addition, we showed that sildenafil significantly reduced radiation-induced O2•- and as a result there was reduction in the generation of peroxynitrite in these cells. Subsequently, sildenafil protected the endothelial cells from radiation therapy-induced apoptosis.

Strengths and limitations: This is the first study demonstrating that single high-dose radiation therapy induced NOXs activation, resulting in the generation of O2•- and peroxynitrite in endothelial cells. Sildenafil reduced ROS generation by inhibiting the ASMase/ceramide pathway. These studies should be followed in an animal model of ED.

Conclusions: This study demonstrated that sildenafil protects BAECs from radiation-induced oxidative stress by reducing NOX-induced ROS generation, thus resulting in decreased endothelial dysfunction. Therefore, it provides a potential mechanism to better understand the atherogenic etiology of postradiation ED. Wortel RC, Mizrachi A, Li H, et al. Sildenafil Protects Endothelial Cells From Radiation-Induced Oxidative Stress. J Sex Med 2019;16:1721-1733.

Keywords: Endothelial Damage; Erectile Dysfunction; Oxidative Stress; Radiation; Reactive Oxygen Species.

Published by Elsevier Inc.

Conflict of interest statement
Conflicts of Interest: A.R.L. declares a financial stake in BioLum Sciences, LLC.

Cited by 1 article58 references7 figures
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13
Review Otolaryngol Head Neck Surg
. 2020 Jun;162(6):839-852. doi: 10.1177/0194599820913533. Epub 2020 Mar 24.
Transoral Robotic Surgery Versus Plasma Ablation for Tongue Base Reduction in Obstructive Sleep Apnea: Meta-analysis
Joshua A Lee 1, Young Jae Byun 1 2, Shaun A Nguyen 1, Eric J Lentsch 1, M Boyd Gillespie 3
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PMID: 32204654 DOI: 10.1177/0194599820913533
Abstract
Objectives: To compare the effectiveness of transoral robotic surgery (TORS) versus plasma ablation (PA) in tongue base reduction surgery for obstructive sleep apnea (OSA).

Data sources: PubMed, Scopus, Cochrane Library, OVID.

Review methods: Keywords searched included OSA, tongue base surgery, TORS, and coblation. Outcomes included pre- to postoperative apnea-hypopnea index, Epworth Sleepiness Scale (ESS), and lowest oxygen saturation. Additional outcomes included surgical success rate, postoperative bleeding, operative time, and length of stay.

Results: A total of 690 unique articles were identified, of which 60 underwent full-text review. Twenty-six articles were included in final analysis, comprising 18 studies on TORS (834 patients) and 11 studies on PA (294 patients). Mean differences of apnea-hypopnea index, ESS, and lowest oxygen saturation for TORS were -23.92, -7.6, and 5.83% (all P < .01). Corresponding values for PA were -22.07, -4.14, and 5.48% (all P < .00001). TORS had greater ESS reduction than PA (P = .02). Follow-up duration was shorter in TORS than PA (mean ± SD: 4.2 ± 2.6 vs 4.6 ± 1.4 months, P = .0482). Surgical success rates in TORS and PA were similar (57.6% vs 60.3%, P = .4474). Postoperative bleeding occurred less frequently in TORS versus PA (3.3% vs 7.5%, P = .0103). Operative time was longer for TORS than PA (77.9 ± 16.4 minutes vs 44.0 ± 12.9 minutes, P < .0001). Length of stay was similar between TORS and PA (3.9 ± 1.6 days vs 3.9 ± 2.5 days, P = .9047).

Conclusion: Tongue base reduction with TORS or PA each effectively treats OSA and provides comparable results. The choice between techniques might depend on patient factors, availability of technology, and associated costs.

Keywords: base of tongue; coblation; glossectomy; lingual tonsillectomy; obstructive sleep apnea; plasma ablation; sleep disordered breathing; transoral robotic surgery.

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14
Ann Otol Rhinol Laryngol
. 2020 Jul 4;3489420939582. doi: 10.1177/0003489420939582. Online ahead of print.
Comparison of Open and Endoscopic Approaches in the Resection of Esthesioneuroblastoma
Gregory L Barinsky 1, Monica C Azmy 1, Suat Kilic 1, Jordon G Grube 1, Soly Baredes 1 2, Wayne D Hsueh 1 2, Jean Anderson Eloy 1 2 3 4 5
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PMID: 32627574 DOI: 10.1177/0003489420939582
Abstract
Background: Olfactory neuroblastoma, or esthesioneuroblastoma (ENB), is an uncommon sinonasal malignancy arising from olfactory neuroepithelium that is optimally treated with surgical resection. The objective of this study is to determine preoperative predictors of undergoing open versus endoscopic approach for ENB and to investigate significant postoperative survival outcomes between the two surgical approaches.

Methods: The National Cancer Database (NCDB) was queried for cases of ENB histology that were treated surgically from 2010 to 2015. Groups were stratified into open or endoscopic approach cohorts. Patient demographics, tumor characteristics, treatment modality, and 5-year overall survival were compared between the two groups using Chi-Square analysis and Kaplan-Meier survival analysis. Cases were classified as Kadish stage A, B, C, or D based on the "Collaborative Stage-Extension" codes in NCDB.

Results: Of 533 patients meeting inclusion criteria, 276 (51.8%) patients underwent open, and 257 (48.2%) patients underwent endoscopic surgical approaches. Patients undergoing endoscopic surgery were more likely to be Kadish stages A and B and less likely to be stages C and D (P = .020). Those undergoing endoscopic approach overall had a shorter mean hospital stay postoperatively (3.8 vs. 7.0 days, P < .001). Endoscopic cases had a greater 5-year overall survival (81.9% vs. 75.6%, P = .030); after multivariate regression, there was a trend toward survival benefit to endoscopic surgery that did not reach clinical significance (HR 0.644, [0.392-1.058], P = .083).

Conclusion: Although not statistically significant, there is a trend toward increased overall survival with an endoscopic approach in patients undergoing surgery for ENB as compared to an open approach, regardless of Kadish stage. An endoscopic approach is an adequate alternative to an open approach for the surgical treatment of ENB.

Keywords: endoscopic sinus surgery; esthesioneuroblastoma; olfactory neuroblastoma; sinonasal cancer.

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15
J Laryngol Otol
. 2020 May;134(5):387-397. doi: 10.1017/S0022215120001012. Epub 2020 May 29.
Hearing Loss and Employment: A Systematic Review of the Association Between Hearing Loss and Employment Among Adults
A Shan 1, J S Ting 1, C Price 2, A M Goman 1, A Willink 1 3, N S Reed 1 4, C L Nieman 1 5
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PMID: 32468973 DOI: 10.1017/S0022215120001012
Abstract
Background: Hearing loss affects over 1.3 billion individuals worldwide, with the greatest burden among adults. Little is known regarding the association between adult-onset hearing loss and employment.

Methods: Seven databases (PubMed, Embase, Cochrane Library, ABI/Inform Collection, Business Source Ultimate, Web of Science and Scopus) were searched through to October 2018. The key word terms used related to hearing loss and employment, excluding paediatric or congenital hearing loss and deaf or culturally deaf populations.

Results: The initial search resulted in 13 144 articles. A total of 7494 articles underwent title and abstract screening, and 243 underwent full-text review. Twenty-five articles met the inclusion criteria. Studies were set in 10 predominantly high-income countries. Seven of the 25 studies analysed regionally or nationally representative datasets and controlled for key variables. Six of these seven studies reported associations between hearing loss and employment.

Conclusion: The highest quality studies currently available indicate that adult-onset hearing loss is associated with unemployment. However, considerable heterogeneity exists, and more rigorous studies that include low- and middle-income countries are needed.

Keywords: Employment; Hearing Disorders; Hearing Loss; Presbycusis; Underemployment; Unemployment.

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16
Otolaryngol Head Neck Surg
. 2020 Jun;162(6):954-958. doi: 10.1177/0194599820913605. Epub 2020 Mar 24.
Maxillary Frenulum in Newborns: Association With Breastfeeding
Reena Razdan 1, Sarah Callaham 1, Renee Saggio 2, Mary Chafin 2, Michele M Carr 3
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PMID: 32204658 DOI: 10.1177/0194599820913605
Abstract
Objective: To relate maxillary and lingual frenulum configuration to breastfeeding success.

Study design: Cross-sectional study.

Setting: Newborn nursery in tertiary care academic hospital.

Subjects and methods: Newborns were observed between 24 and 72 hours after birth. Mothers were asked a series of questions relating to their breastfeeding experience. The maxillary and lingual frenula were examined and scored. Corresponding LATCH scores were recorded.

Results: A total of 161 mothers with newborns participated. The mean gestational age of newborns was 38.81 weeks (95% CI, 38.65-38.98); 82 (50.9%) male and 79 (49.1%) female newborns were included. In sum, 70.8% had the maxillary frenulum attached to the edge of the alveolar ridge; 28.6%, attached to the fixed gingiva; and 0.6%, attached to mobile gingiva. In addition, 3.7% had anterior ankyloglossia, and 96.3% had no obvious anterior ankyloglossia. There was no significant correlation between maxillary frenulum scores or lingual frenulum scores and LATCH scores (P > .05). Of the mothers included in the study, 56.5% were first-time mothers. Overall, 43.5% of the mothers had other biological children, with 70.0% of those mothers having previously breastfed. Experienced mothers who had breastfed for >3 months had significantly higher LATCH scores. Those who had previously breastfed had a mean LATCH score of 9.16 (95% CI, 8.80-9.52), as compared with those who had not, with a mean of 8.14 (95% CI, 7.43-8.85).

Conclusion: We did not find that maxillary frenulum configuration correlated with LATCH scores. Mothers experienced with breastfeeding had better LATCH scores. Attention toward breastfeeding education, particularly in new mothers, should precede maxillary frenotomy in neonates with breastfeeding difficulties.

Keywords: LATCH score; ankyloglossia; breastfeeding; lingual frenulum; maxillary frenulum; neonatal feeding.

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17
Review Otolaryngol Head Neck Surg
. 2020 Jun;162(6):826-838. doi: 10.1177/0194599820913507. Epub 2020 Mar 31.
Cost-effectiveness of School Hearing Screening Programs: A Scoping Review
Michael Yong 1 2, Jiahe Liang 2, Jeromie Ballreich 2, Jane Lea 1, Brian D Westerberg 1, Susan D Emmett 3 4 5
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PMID: 32228135 DOI: 10.1177/0194599820913507
Abstract
Objective: School hearing screening is a public health intervention that can improve care for children who experience hearing loss that is not detected on or develops after newborn screening. However, implementation of school hearing screening is sporadic and supported by mixed evidence to its economic benefit. This scoping review provides a summary of all published cost-effectiveness studies regarding school hearing screening programs globally. At the time of this review, there were no previously published reviews of a similar nature.

Data sources: A structured search was applied to 4 databases: PubMed (Medline), Embase, CINAHL, and Cochrane Library.

Review methods: The database search was carried out by 2 independent researchers, and results were reported in accordance with the PRISMA-ScR checklist and the JBI methodology for scoping reviews. Studies that included a cost analysis of screening programs for school-aged children in the school environment were eligible for inclusion. Studies that involved evaluations of only neonatal or preschool programs were excluded.

Results: Four of the 5 studies that conducted a cost-effectiveness analysis reported that school hearing screening was cost-effective through the calculation of incremental cost-effectiveness ratios (ICERs) via either quality- or disability-adjusted life years. One study reported that a new school hearing screening program dominated the existing program; 2 studies reported ICERs ranging from 1079 to 4304 international dollars; and 1 study reported an ICER of £2445. One study reported that school-entry hearing screening was not cost-effective versus no screening.

Conclusion: The majority of studies concluded that school hearing screening was cost-effective. However, significant differences in methodology and region-specific estimates of model inputs limit the generalizability of these findings.

Keywords: cost-effectiveness; hearing loss; hearing screening; pediatric; school children.

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18
Oral Oncol
. 2019 Aug;95:91-94. doi: 10.1016/j.oraloncology.2019.05.026. Epub 2019 Jun 11.
'Doing as Little as Possible and as Much as Necessary' - Oncological Efficacy of Marginal Mandibulectomy in Resection of Oral Cavity Cancers
Sandeep Suresh 1, Shaji Thomas 2, Deepak Janardhan 1, Shirish Patil 1, Nebu Abraham George 1, Bipin T Varghese 1, Elizabeth Mathew Iype 1, Malu Rafi 3, Ciju K George 1
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PMID: 31345400 DOI: 10.1016/j.oraloncology.2019.05.026
Abstract
Background: In carefully selected oral cavity cancers, marginal mandibulectomy is an adequate procedure which achieves good disease control adhering to the principle of "doing as little as possible and as much as necessary".

Methodology: This was a retrospective study done by reviewing the medical records of all patients who underwent marginal mandibulectomy for resection of oral cavity cancers in our institution during a period of 5 years. Data was collected from medical case records and analyzed.

Results: 125 cases underwent marginal mandibulectomy for resection of oral cavity cancers. 88.5% of advanced oral cavity cancers that underwent neoadjuvant chemotherapy followed by marginal mandibulectomy are still disease free. The local recurrence rate was 10.4%. Among cases which recurred, 61.5% were in T2 stage of the disease and 30.8% recurred in buccal mucosa. For lesions on the mandible (26/125), the final histopathology showed bone infiltration in only 12% cases and among them only one recurred. Among 88/125 cases where the lesion was abutting mandible even after stretching mucosa, recurrence was noted only in 11.4% with 3-year overall survival of 79.3%.

Conclusions: The low recurrence rate following marginal mandibulectomy in our study shows good locoregional control when performed for a lesion close to or abutting alveolar periosteum. In management of advanced oral cavity cancers, neoadjuvant chemotherapy followed by marginal mandibulectomy was effective in achieving significant locoregional control. For superficial lesions on the mandible, marginal mandibulectomy gives adequate margin clearance resulting in long term survival.

Keywords: Cancer of mouth; Mandible; Mandibular osteotomy; Recurrence; Survival.

Copyright © 2019 Elsevier Ltd. All rights reserved.

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19
Ann Otol Rhinol Laryngol
. 2020 Jul 4;3489420938817. doi: 10.1177/0003489420938817. Online ahead of print.
Systematic Review of Negative Pressure Pulmonary Edema in Otolaryngology Procedures
Corina Din-Lovinescu 1, Usha Trivedi 1, Kathy Zhang 1, Gregory L Barinsky 1, Jordon G Grube 1, Jean Anderson Eloy 1 2, Wayne D Hsueh 1 2
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PMID: 32627567 DOI: 10.1177/0003489420938817
Abstract
Objective(s): Negative pressure pulmonary edema (NPPE) is a rare perioperative complication with a potentially fatal outcome. The aim of this study was to perform a systematic review of NPPE in adult otolaryngology procedures with the goal of identifying risk factors, clinical presentation, diagnosis, management and outcomes.

Methods: Systematic review performed using PubMed, Scopus, Web of Science, and Cochrane databases.

Results: Sixty-nine studies including data from 87 individual patients were included in this review. Fifty-six (68%) patients were male and the average patient age was 37 years old. Type 1 NPPE occurred in 63 (72%) cases, while type 2 NPPE accounted for 20 (23%) cases. The most common procedures leading to NPPE were septoplasty, rhinoplasty or sinus surgery (n = 22, 25%), directly laryngoscopy or bronchoscopy (n = 13, 15%), and tracheostomy or cricothyroidotomy (n = 11, 13%). The most employed treatment options included diuretics (n = 55, 63%) and mechanical ventilation (n = 54, 62%). Seventy-eight (90%) patients made a full recovery with an average time to NPPE resolution of 33 hours and an average length of hospitalization of 5.6 days. Five (6%) patients had a long-term morbidity and four (5%) patients died, with age and ICU stay increasing risk for death and long-term morbidity (OR 1.044 and 7.42, respectively, P < .05).

Conclusion: Septoplasty, rhinoplasty and sinus surgery account for the majority of NPPE cases in adult otolaryngology procedures. Young, healthy patients are the most commonly involved with a slight male predominance. The vast majority of patients recover fully, however there is a significant risk for morbidity and mortality.

Keywords: negative pressure pulmonary edema; otolaryngology procedures; systematic review.

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20
Cell Death Dis
. 2019 Jun 3;10(6):433. doi: 10.1038/s41419-019-1637-7.
A Novel lncRNA n384546 Promotes Thyroid Papillary Cancer Progression and Metastasis by Acting as a Competing Endogenous RNA of miR-145-5p to Regulate AKT3
Jiajia Feng 1 2 3, Qinyi Zhou 1 2 3 4, Hongliang Yi 1 2 3, Shiyin Ma 5, Dawei Li 1 2 3, Yanan Xu 4, Jiadong Wang 6, Shankai Yin 7 8 9
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PMID: 31160577 PMCID: PMC6547665 DOI: 10.1038/s41419-019-1637-7
Free PMC article
Abstract
Long noncoding RNAs (lncRNAs) are emerging as important regulators in the development of cancer cells. However, the role and mechanisms of most lncRNAs in papillary thyroid carcinoma (PTC) remain unknown. In this study, we investigated lncRNA expression profiles of PTC using RNA-seq in two groups of PTC tissues and adjacent normal tissues, and validated by real-time PCR analysis in another 53 pairs of tissues. We identified a novel lncRNA, n384546, which is highly expressed in PTC tissues and cell lines. n384546 expression was associated with clinicopathological features of PTC patients, such as tumor size, lymph node metastasis, and TNM stage. Functionally, knockdown of n384546 inhibited PTC cell proliferation, invasion, and migration both in vitro and in vivo. In addition, we identified miR-145-5p as a key miRNA target of n384546 using online bioinformatics tools. Anti-miR-145 could partially reverse the effects of n384546 knockdown. Furthermore, we found that n384546 could regulate the expression of AKT3 by sponging miR-145-5p, which was confirmed using an in vitro luciferase assay. In conclusion, we validated n384546 as a novel oncogenic lncRNA in PTC and determined that the n384546/miR-145-5p/AKT3 pathway contributes to PTC progression, which might be used as potential therapeutic targets for PTC patients.

Conflict of interest statement
The authors declare that they have no conflict of interest.

Cited by 6 articles47 references6 figures
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21
Shanghai Kou Qiang Yi Xue
. 2020 Apr;29(2):138-145.
[Effect of Disulfiram on Epithelial-Mesenchymal Transformation of Oral Squamous Cell Carcinoma Cells]
[Article in Chinese]
Xue-Mei Wang 1, Yong Jiang
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PMID: 32626875
Abstract
Purpose: To investigate the effect of disulfiram on epithelial-mesenchymal transformation(EMT) in oral squamous cell carcinoma(OSCC) cells based on Smad4 mutation.

Methods: The cancer tissues and adjacent normal tissues of 46 patients with OSCC who underwent tumor resection in the Affiliated Stomatological Hospital of Anhui Medical University from June 2017 to June 2018 were included in the study. Immunohistochemical staining was used to observe the expression of Smad4 in tissues, Western blot was used to determine the expression of Smad4 in tumor cells. The effects of disulfiram on TGF-β1-induced cell EMT migration, invasion, morphology and expression of p38, JNK and ERK were analyzed. SPSS 20.0 software package was used to analyze the data.

Results: The positive expression rate of Smad4 in cancer tissues was significantly lower than that in adjacent normal tissues (P<0.05). The survival rates of human tongue cancer SCC-25 and CAL-27 cells were not significantly different from those of the control group at disulfiram concentrations of 5, 10, and 20 μmol/L(P>0.05). The survival rate of human tongue cancer SCC-25 and CAL-27 cells was significantly lower than that of the control group at disulfiram concentrations ≥30 μmol/L(P<0.05). After treatment with TGF-β1, the morphology of SCC-25 and CAL-27 cells changed from epithelial to mesenchymal. E-cadherin expression was significantly reduced, Vimentin and Snail expression were significantly increased, and migration and invasion were enhanced (P<0.05). After disulfiram + TGF-β1 treatment, as the concentration of disulfiram increased, the morphological changes of SCC-25 and CAL-27 cells gradually decreased, the expression of E-cadherin protein gradually increased, the expression of Vimentin and Snail protein gradually decreased, and migration ability gradually weakened (P<0.05). After 5 minutes of TGF-β1 stimulation, p-ERK levels in SCC-25 and CAL-27 cells gradually increased, reached a maximum at 15 minutes, and then gradually decreased (P<0.05). After 20 μmol/L disulfiram + TGF-β1 treatment, p-ERK levels in SCC-25 and CAL-27 cells gradually decreased with the increase of the treatment time(P<0.05).

Conclusions: Disulfiram can inhibit EMT of Smad4 mutant and Smad4 non-mutated OSCC cells by blocking ERK phosphorylation in the MAPK signaling pathway.

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22
Anat Rec (Hoboken)
. 2019 Jun;302(6):1024-1038. doi: 10.1002/ar.24098. Epub 2019 Mar 15.
Establishment of a Large Animal Model for Eustachian Tube Functional Study in Miniature Pigs
Feng-Wei An 1 2, Hu Yuan 1 2, Weiwei Guo 1 2, Zhao-Hui Hou 1 2, Jian-Ming Cai 3, Chun-Cai Luo 3, Ning Yu 1 2, Qing-Qing Jiang 1 2, Wei Cheng 1 2, Wei Liu 4 5, Shi-Ming Yang 2
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PMID: 30779320 DOI: 10.1002/ar.24098
Free article
Abstract
This study was performed to investigate whether miniature pigs are a suitable animal model for studies of the Eustachian tube (ET). Sixteen Chinese experimental miniature pigs were used in this investigation. Ten animals were used for anatomical and morphometric analyses to obtain qualitative and quantitative information regarding the ET. Three animals were used for histological analysis to determine the fine structure of ET cross-sections. Three animals were used to investigate the feasibility of balloon dilation of the Eustachian tube (BDET). The anatomical study indicated that the pharyngeal orifice and tympanic orifice of the miniature pig ET are located at the posterior end of the nasal lateral wall and anterior wall of the middle ear cavity, respectively. The cartilaginous tube was seen to pass through the whole length of the ET, the length of the cartilaginous part of the ET and the diameter of the isthmus were similar between humans and miniature pigs. The inclination of the ET in miniature pigs was larger than that in humans. The gross histology seemed to be slightly different between miniature pig and human, but the fine structures were essentially the same in both species. BDET experiments verified that the miniature pig model is suitable as a model for clinical operations. The miniature pig ET corresponds very well to that of humans. In addition, the miniature pig ET is suitable as a model for clinical operations. Therefore, the miniature pig is a valid animal model for ET study. Anat Rec, 302:1024-1038, 2019. © 2019 Wiley Periodicals, Inc.

Keywords: Eustachian tube (ET); balloon dilation of the Eustachian tube (BDET); miniature pig.

© 2019 Wiley Periodicals, Inc.

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23
Ann Otol Rhinol Laryngol
. 2020 Jul 4;3489420938100. doi: 10.1177/0003489420938100. Online ahead of print.
KTP Laser Treatment of Early Glottic Cancer: A Multi-Institutional Retrospective Study
Noah P Parker 1, Mark S Weidenbecher 2, Aaron D Friedman 3, Brian A Walker 4, David G Lott 4
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PMID: 32627613 DOI: 10.1177/0003489420938100
Abstract
Objectives: The primary objectives were to report oncologic outcomes of transoral laser microsurgery with potassium-titanyl-phosphate (KTP) laser (TLM-KTP) ablation of early glottic cancer (EGC). The secondary objectives were to report vocal outcomes and to analyze factors that might influence outcomes.

Methods: A multi-institutional, retrospective analysis of consecutive patients treated for T1 or T2 glottic squamous cell carcinoma undergoing TLM-KTP ablation with at least 2 years of follow-up was performed. Patients with prior radiation or surgery for laryngeal disease were excluded.

Primary outcome measures included: surgical failures requiring radiation or laryngectomy, disease-specific survival (DSS), and overall survival (OS). Secondary outcome measures included: pre- and postoperative Voice Handicap Index-10 (VHI-10) scores. The effects of smoking status, stage, and anterior commissure involvement on outcomes were analyzed.

Results: Overall 88 patients met inclusion criteria (83% male, 79.5% current or former smokers). Mean age was 68 (standard deviation (SD): 12). Mean follow-up was 39.5 months (SD: 15.3). Staging included 50 T1a, 21 T1b, and 20 T2 tumors, including three metachronous second primaries. Radiation and/or laryngectomy avoidance was achieved in 87/88 (98.9%) of patients, inclusive of 24 patients requiring KTP re-treatments. Two patients had biopsy-proven recurrence (2.3%), but only 21 of 24 re-treated patients received a formal biopsy. No patients died from laryngeal cancer. DSS and OS were 100% and 92.3%, respectively. The mean VHI-10 scores were 19.3 preoperatively, 3.8 at 6-months postop, and 3.8 at 2-years postop. Smokers had a longer interval to re-treatment (P = .03), patients with T2 lesions had a shorter interval to re-treatment (0.02), and patients with T2 lesions presented with worse initial VHI-10 scores (0.002).

Conclusions: A multi-institutional, retrospective case series of TLM-KTP ablation of EGC demonstrated excellent oncologic outcomes when close surveillance and proactive re-treatments were utilized. Disease-specific survival, overall survival, and vocal function were excellent. Additional studies are necessary to further analyze the merits and risks of this treatment approach.

Keywords: KTP laser; glottic cancer; larynx; vocal cord cancer.

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24
Laryngoscope
. 2020 Jul 6. doi: 10.1002/lary.28879. Online ahead of print.
Emotional and Personality Traits Are Determinants of Activity Avoidance in Chronic Rhinosinusitis Patients
Madison V Epperson 1, Katie M Phillips 1, Marlene M Speth 2, David S Caradonna 3 4, Stacey T Gray 3 5, Ahmad R Sedaghat 1
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PMID: 32628769 DOI: 10.1002/lary.28879
Abstract
Objectives: Chronic rhinosinusitis (CRS), like other sinonasal diseases, may be associated with avoidance of daily activities. Our goal was to identify characteristics associated with avoidance of activities due to CRS.

Materials and methods: A total of 194 CRS patients were recruited. CRS symptom burden was assessed with the 22-item Sinonasal Outcome Test (SNOT-22). SNOT-22 nasal, sleep, ear/facial discomfort and emotional/psychological subdomain scores were calculated. Depressed mood was assessed using the two-item Patient Health Questionnaire (PHQ-2). Personality traits including conscientiousness, neuroticism, agreeableness, openness, and extraversion were assessed using the Big Five Inventory-10 (BFI-10) questionnaire. As the primary outcome, participants rated how often in the prior week that they had avoided any activities in day-to-day life due to their nasal or sinus symptoms on a scale of "never," "rarely," "sometimes," "often," or "extremely often." Ordinal regression models, with bootstrap validation, were used to identify associations between activity avoidance and participants' characteristics.

Results: On multivariable analysis, SNOT-22 score (odds ratio [OR] = 1.03, 95% CI, 1.01-1.04, P = .026), and conscientiousness personality trait (OR = 1.38, 95% CI, 1.05-1.81, P = .019) were positively associated with activity avoidance while age (OR = 0.98, 95% CI, 0.96-0.99, P = .049) was negatively associated with activity avoidance. Of CRS symptom burden/SNOT-22 subdomains, only the emotional/psychological subdomain score (OR = 1.28, 95% CI, 1.12-1.46, P < .001) was associated with activity avoidance.

Conclusion: Younger age and the conscientiousness personality trait were associated with activity avoidance in CRS patients. Of CRS-associated symptomatology, sadness and embarrassment were associated with activity avoidance. Emotional traits and personality most strongly predict avoidance of activities in CRS patients.

Level of evidence: 2c. Laryngoscope, 2020.

Keywords: chronic rhinosinusitis, personality, mood, activity avoidance, productivity, BFI-10, SNOT-22, PHQ-2.

© 2020 The American Laryngological, Rhinological and Otological Society, Inc.

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25
J Vis Exp
. 2019 Sep 12;(151). doi: 10.3791/59340.
An Orthotopic Endometrial Cancer Model With Retroperitoneal Lymphadenopathy Made From In Vivo Propagated and Cultured VX2 Cells
Lauren Philp 1, Harley Chan 2, Marjan Rouzbahman 3, Ariana Rostami 4, Lili Ding 5, Scott V Bratman 6, Margarete K Akens 7, Jonathan C Irish 8, Marcus Q Bernardini 9, Gang Zheng 10
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PMID: 31566617 DOI: 10.3791/59340
Abstract
Endometrial cancer is the most common gynecologic malignancy in North America and the incidence is rising worldwide. Treatment consists of surgery with or without adjuvant therapy depending on lymph node involvement as determined by lymphadenectomy. Lymphadenectomy is a morbid procedure, which has not been shown to have a therapeutic benefit in many patients, and thus a new method to diagnose lymph node metastases is required. To test novel imaging agents, a reliable model of endometrial cancer with retroperitoneal lymph node metastases is needed. The VX2 endometrial cancer model has been described frequently in the literature; however, significant variation exists with respect to the method of model establishment. Furthermore, no studies have reported on the use of cultured VX2 cells to create this model as only cells propagated in vivo have been previously used. Herein, we present a standardized surgical method and post-operative monitoring method for the establishment of the VX2 endometrial cancer model and report on the first use of cultured VX2 cells to create this model.

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26
Biochem Biophys Res Commun
. 2019 Aug 27;516(3):784-789. doi: 10.1016/j.bbrc.2019.06.074. Epub 2019 Jun 26.
Isoprenylcysteine Carboxylmethyltransferase Is Associated With Nasopharyngeal Carcinoma Chemoresistance and Ras Activation
Yongbo Zhu 1, Qiyan Hu 2, Hui Li 3
Affiliations expand
PMID: 31253403 DOI: 10.1016/j.bbrc.2019.06.074
Abstract
Development of chemo-resistance in nasopharyngeal carcinoma (NPC) poses the therapeutic challenge and its mechanisms are still poorly understood. In this work, we demonstrate that targeting isoprenylcysteine carboxylmethyltransferase (Icmt) is a therapeutic strategy to overcome NPC chemo-resistance. We found that Icmt mRNA and protein levels were increased in NPC cells after prolonged exposure to chemotherapy. Using pharmacological inhibitor cysmethynil or genetic siRNA approaches, we showed that Icmt inhibition was more effective against chemoresistant compared to chemosensitive NPC cells, suggesting that chemoresistant NPC cells is more dependent on Icmt function. The combination of Icmt inhibition with 5-FU or cisplatin resulted in greater efficacy than single chemotherapeutic agent alone in NPC. Notably, we demonstrated that the in vitro observations were translatable to in vivo NPC cancer xenograft mouse model. Mechanism analysis indicated that Icmt inhibition decreased Ras and RhoA activities, leading to the suppression of Ras and RhoA-mediated downstream signaling in NPC cells. The reverse of the inhibitory effects of cysmethynil by constitutively active Ras suggests that Ras is the critical effector of Icmt in NPC cells. Our work is the first to show that Icmt plays an important role in the development of NPC chemoresistance. Our findings also suggest that targeting Icmt represents a promising strategy to inhibit Ras function.

Keywords: Chemoresistance; Cysmethynil; Icmt; Nasopharyngeal carcinoma.

Copyright © 2019 Elsevier Inc. All rights reserved.

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27
Ann Otol Rhinol Laryngol
. 2020 Jul 4;3489420938820. doi: 10.1177/0003489420938820. Online ahead of print.
Prospective Evaluation of a Smartphone Otoscope for Home Tympanostomy Tube Surveillance: A Pilot Study
Debra M Don 1, Jeffrey A Koempel 1, Laurel M Fisher 2, Choo Phei Wee 3, Beth Osterbauer 1
Affiliations expand
PMID: 32627572 DOI: 10.1177/0003489420938820
Abstract
Objectives: Recent technological advances have led to the capability of performing high resolution imaging of the tympanic membrane. Smartphone technologies and applications have provided the opportunity to capture digital images and easily share them. The smartphone otoscope device was developed as a simple system that can convert a smartphone into a digital otoscope. This device has the prospective ability to improve physician-patient communication and assist with the diagnosis and management of ear disease. Our objective was to evaluate the feasibility and physician/parental satisfaction using the Cellscope® smartphone attachment for at home tympanostomy tube monitoring.

Methods: Children between 6 months and 15 years of age at an urban tertiary children's hospital that were scheduled for bilateral tympanostomy tube insertion or underwent bilateral tympanostomy tube surgery were prospectively enrolled in the study. Comparisons were made between parental home-recorded videos and findings during in-office otoscopy. Two independent otolaryngologists reviewed the videos and concordance between inter-rater agreements was calculated. Acceptability and use questionnaires were administered to physicians and parents.

Results: There was good intra-rater agreement between traditional otoscopy and video-otoscopy for tube extruding, tube blocked and tube extruded with at least 80% agreement (P < .05) and excellent inter-rater agreement between physicians for nearly all tube variables (P < .0001) There was a high degree of satisfaction with this mode of surveillance. Parents and physicians agreed that the CellScope® smartphone was easy to use, helpful with the occurrence of acute events, and appeared to improve quality of care.

Conclusions: The CellScope® smartphone is feasible for use in tympanostomy tube surveillance. Use of the device may allow otolaryngologists to easily follow a child's tympanostomy tube remotely over time and offer greater parental satisfaction.

Keywords: pediatric; smartphone otoscope; tympanostomy tubes.

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28
Jpn J Clin Oncol
. 2020 Jun 10;50(6):653-660. doi: 10.1093/jjco/hyaa034.
Long-term Outcomes of Trans-Oral Robotic Surgery-Assisted Total Laryngectomy for Recurrent Laryngeal Cancers
Chen-Chi Wang 1 2 3 4, Wen-Jiun Lin 4, Armando De Virgilio 5, Shih-An Liu 1 4, Sheng-Hwa Chen 3, Jia-Shiou Liao 2 6
Affiliations expand
PMID: 32236415 DOI: 10.1093/jjco/hyaa034
Abstract
Objective: For recurrent laryngeal cancers, trans-oral robotic surgery has been used to perform total laryngectomy, but limited cases had been reported without long-term outcome follow-up. This study aims at presenting the largest longitudinal retrospective cohort in a single tertiary referral medical center.

Methods: From November 2013 to August 2017, seven patients with recurrent laryngeal cancers without evidence of neck metastasis were selected to receive trans-oral robotic surgery-assisted TL without neck dissection. The para-operative details including the surgical success rates, surgical methods, resection extent, drainage tube placement, pharyngeal wound closure, console surgical time, pathologic findings and long-term complications were reviewed and described. The study end points include survival rates and preservation of swallowing function without tube feeding.

Results: Trans-oral robotic surgery-assisted total laryngectomy was successfully performed on all seven patients with mean surgical console time of 111 ± 66 min. Strap muscles and hyoid bone were resected like open surgery in six and five patients, respectively. For all the seven patients, there was no severe pharyngo-cutaneous fistula formation requiring repair in a second surgery, but tracheostoma stenosis was not uncommon (57%). Three patients received adjuvant chemotherapy/radiotherapy. After follow-up of 36.1 ± 15.8 months, two patients had neck recurrence, and one patient died 19 months after surgery, but the other five patients were alive without disease recurrence. The overall survival rate was 85.7% (6/7), and all patients had good swallowing function without tube feeding.

Conclusions: Trans-oral robotic surgery-assisted total laryngectomy is a feasible approach for selected patients with recurrent laryngeal cancers. The oncologic and functional outcomes were satisfactory. Further larger cohort study is worthwhile to further elucidate the value of trans-oral robotic surgery-assisted total laryngectomy.

Keywords: laryngeal cancer; robotic surgery; swallowing; total laryngectomy; trans-oral.

© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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29
Facial Plast Surg
. 2020 Jul 6. doi: 10.1055/s-0040-1713790. Online ahead of print.
Lower Blepharoplasty Three-Dimensional Volume Assessment After Fat Pad Transposition and Concomitant Fat Grafting
Robert T Cristel 1, Benjamin P Caughlin 2
Affiliations expand
PMID: 32629483 DOI: 10.1055/s-0040-1713790
Abstract
Lower blepharoplasty is a commonly performed procedure to improve the aesthetic of the lower eyelid and upper midface. Combined fat pad transposition and fat grafting has not been previously studied using three-dimensional (3D) analysis. The aim of the study is to demonstrate the benefits of fat pad transposition with concomitant autologous fat grafting in lower blepharoplasty and to determine quantitative volumetric effects on the tear trough and lower periorbital region using VectraXT 3D imaging and analysis. A retrospective review was performed to identify patients undergoing primary lower blepharoplasty with combined fat pad transposition and fat grafting. The study time period was from September 2017 to March 2019 with a mean 6.5-month postoperative follow-up. This study was performed in a private practice institution (Kovac Cosmetic Center, Oakbrook Terrace, IL). Nine subjects were enrolled in the study with four males and five females. All subjects underwent lower blepharoplasty with combined fat pad transposition and fat grafting without any additional procedures. Preoperative and postoperative photographs were taken with the VectraXT 3D camera system and software. 3D photographs were then compared to assess the volume changes in the periorbital region. The volume in the lower periorbital region was assessed using 3D analysis. All subjects were found to have an increase in volume in the periorbital region. There was a mean volume gain of 2.84 mL on the right and 2.87 mL on the left. There was no statistical difference among volume gains between sides (p = 0.95). Combined fat pad transposition and autologous fat grafting is an effective procedure for improving the tear trough deformity and periorbital area. The use of 3D volume assessment is able to accurately measure and quantify the volume changes of the postoperative results.

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Conflict of interest statement
No funding sources were obtained to support this work. The authors claim no conflict of interests.

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30
Otolaryngol Head Neck Surg
. 2020 Jun;162(6):942-949. doi: 10.1177/0194599820911720. Epub 2020 Mar 24.
Audiometric Outcomes and Middle Ear Disease Following Cerebrospinal Fluid Leak Repair
Kristen L Yancey 1, Nauman F Manzoor 1, David S Haynes 1, Marc L Bennett 1, Matthew O'Malley 1, Alejandro Rivas 1
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PMID: 32204657 DOI: 10.1177/0194599820911720
Abstract
Objective: To investigate audiometric outcomes and incidence of chronic ear disease following lateral skull base repair (LSBR) of cerebrospinal fluid (CSF) leaks.

Study design: Retrospective review.

Setting: Tertiary skull base center.

Subjects and methods: Consecutive adults undergoing LSBR of CSF leaks between 2012 and 2018 were reviewed. Audiometric data included mean air conduction pure-tone average (PTA), air-bone gap (ABG), speech recognition threshold (SRT), and word recognition score (WRS). The incidence and management of the following were collected: effusion, retraction, otitis media and externa, perforation, and cholesteatoma.

Results: Seventy-three patients underwent transmastoid (n = 5), middle cranial fossa (n = 2), or combined approach (n = 67) for repair of spontaneous leaks (sCSFLs, n = 41) and those occurring in the setting of chronic ear disease (ceCSFLs, n = 32). ABG decreased 7.23 dB (P = .01) in sCSFL patients. Perforations (P = .01) were more likely in ceCSFL. No sCSFL patient developed a cholesteatoma, perforation, or infection. Effusions (n = 7) were transient, and retractions (n = 2) were managed conservatively in the sCSFL cohort. Eight ceCSFL patients required tubes, 3 underwent tympanoplasties with (n = 2) and without (n = 1) ossicular chain reconstruction (OCR), and 1 had tympanomastoidectomy with OCR.

Conclusion: Lateral skull base repair of CSF leaks maintained or improved hearing. Patients with preexisting chronic ear disease were more likely to require additional intervention to sustain adequate middle ear aeration compared to the sCSFL cohort. LSBR of sCSFL does not appear to increase risk for developing chronic ear disease.

Keywords: audiometry; lateral skull base repair; middle ear disease; spontaneous cerebrospinal leak.

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31
Review J Cancer
. 2020 Jun 8;11(16):4884-4896. doi: 10.7150/jca.44506. eCollection 2020.
Immune Microenvironment of Thyroid Cancer
Hongyu Yin 1 2, Yemei Tang 1 2, Yujia Guo 1 2, Shuxin Wen 3 4
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PMID: 32626535 PMCID: PMC7330689 DOI: 10.7150/jca.44506
Free PMC article
Abstract
Thyroid cancer (TC) is a highly heterogeneous endocrine malignancy with an increased incidence in women than in men. Previous studies regarding the pathogenesis of TC focused on the pathological changes of the tumor cells while ignoring the importance of the mesenchymal cells in tumor microenvironment. However, more recently, the stable environment provided by the interaction of thyroid cancer cells with the peri-tumoral stroma has been widely studied. Studies have shown that components of an individual's immune system are closely related to the occurrence, invasion, and metastasis of TC, which may affect response to treatment and prognosis of the patients. This article presents a comprehensive review of the immune cells, secreted soluble mediators and immune checkpoints in the immune microenvironment, mechanisms that promoting TC cells immune evasion and existing immunotherapy strategies. Besides it provides new strategies for TC prognosis prediction and immunotherapy.

Keywords: Immune Evasion; Immune Microenvironment; Immunotherapy; Thyroid Cancer (TC).

© The author(s).

Conflict of interest statement
Competing Interests: The authors have declared that no competing interest exists.

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32
PLoS One
. 2020 Apr 3;15(4):e0228122. doi: 10.1371/journal.pone.0228122. eCollection 2020.
Peritonsillar Abscess May Not Always Be a Complication of Acute Tonsillitis: A Prospective Cohort Study
Enni Sanmark 1, Johanna Wikstén 1, Hannamari Välimaa 2 3, Leena-Maija Aaltonen 1, Taru Ilmarinen 1, Karin Blomgren 1
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PMID: 32243441 PMCID: PMC7122714 DOI: 10.1371/journal.pone.0228122
Free PMC article
Abstract
The present study aimed to specify diagnostics for peritonsillar abscesses (PTAs) and to clarify the role of minor salivary glands. This prospective cohort study included 112 patients with acute tonsillitis (AT) and PTA recruited at a tertiary hospital emergency department between February and October 2017. All patients completed a questionnaire concerning their current disease. Serum amylase (S-Amyl) and C-reactive protein (S-CRP) levels, tonsillar findings, and pus aspirate samples and throat cultures were analyzed. Eight of 58 PTA patients (13.8%) had no signs of tonsillar infection. The absence of tonsillar erythema and exudate was associated with low S-CRP (p<0.001) and older age (p<0.001). We also observed an inverse correlation between S-Amyl and S-CRP levels (AT, r = -0.519; PTA, r = -0.353). Therefore, we observed a group of PTA patients without signs of tonsillar infection who had significantly lower S-CRP levels than other PTA patients. These findings support that PTA may be caused by an etiology other than AT. Variations in the S-Amyl levels and a negative correlation between S-Amyl and S-CRP levels may indicate that minor salivary glands are involved in PTA development.

Conflict of interest statement
The authors have declared that no competing interests exist.

30 references2 figures
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33
Am J Rhinol Allergy
. 2020 Jul 5;1945892420939814. doi: 10.1177/1945892420939814. Online ahead of print.
miR-30a-5p Inhibits Epithelial-to-Mesenchymal Transition by Targeting CDK6 in Nasal Polyps
Ting Zhang 1 2, Yong Zhou 1 2, Bo You 1 2, Yiwen You 1 2, Yongbing Yan 1 2, Jie Zhang 1 2, Yinyin Pei 1 2, Wei Zhang 1 2, Jing Chen 1 2
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PMID: 32623901 DOI: 10.1177/1945892420939814
Abstract
Background: Epithelial-to-Mesenchymal Transition (EMT) is considered as a crucial event in disease development and dysregulation of microRNAs (miRNAs) is involved in the regulation of EMT in various human diseases. Emerging evidences congregated over the years have demonstrated that miR-30a-5p was decreased in diseases and its overexpression inhibited the process of diseases via attenuating EMT. Although aberrant expression of miRNAs and occurrence of EMT were previously reported in Nasal Polyps (NPs), the role of miR-30a-5p in EMT of NPs is still remains unclear.

Objective: The purpose of our present study was to explore the expression and potential function of miR-30a-5p in EMT of NPs.

Methods: The expression of miR-30a-5p and mRNA expression level were detected by quantitative real-time PCR (qRT-PCR) in transforming growth factor β1 (TGF-β1) - induced EMT model and NPs patients. Western Blot (WB) and immunohistochemistry (IHC) were performed to evaluate the protein expression level of EMT markers. The cells mobility was assessed by Wound-Healing assay. Luciferase reporter assay was utilized to verify the relationship between Cyclin-dependent kinase 6 (CDK6) and miR-30a-5p.

Results: Firstly, we observed that miR-30a-5p was down-regulated notably, accompanying with the alteration of EMT markers expression in NPs tissues and EMT model induced by TGF-β1 in primary Human Nasal Epithelial Cells (pHNECs) and A549 cells in vitro. Moreover, the functional assays demonstrated that overexpression of miR-30a-5p significantly inhibited EMT and cells mobility. Subsequently, CDK6 was validated as a direct target of miR-30a-5p. Finally, we performed the rescue experiments indicating that overexpression of CDK6 eliminated the suppressive effects of miR-30a-5p in TGF-β1-induced EMT in pHNECs and A549 cells.

Conclusion: Taken together, our results suggested that EMT was involved in NPs, and overexpression of miR-30a-5p could attenuate EMT via repressing the expression of the CDK6 in pHNECs and A549 cells.

Keywords: CDK6; epithelial-to-mesenchymal transition; inhibition; miR-30a-5p; nasal polyps; primary human nasal epithelial cells; transforming growth factor β1.

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34
Review Trends Pharmacol Sci
. 2019 Sep;40(9):613-623. doi: 10.1016/j.tips.2019.07.001. Epub 2019 Jul 20.
Tumor Vasculatures: A New Target for Cancer Immunotherapy
Zhigang Liu 1, Yifan Wang 2, Yuhui Huang 3, Betty Y S Kim 4, Hong Shan 5, Depei Wu 6, Wen Jiang 7
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PMID: 31331639 DOI: 10.1016/j.tips.2019.07.001
Abstract
Immune cells rely on a functional vascular network to enter tissues. In solid tumors, blood vessels are abnormal and dysfunctional and, thus, immune effector cell infiltration is impaired. Although normalizing the tumor vasculature has been shown to improve the efficacy of cancer immunotherapies, recent studies suggest that enhanced immune stimulation also, in turn, improves tumor vascular normalization. Thus, this new paradigm of immune system-tumor vasculature mutual reprogramming opens the possibility of identifying new cancer treatment strategies that combine vascular targeting and immunotherapies. Here, we highlight current evidence supporting immune system-tumor vasculature crosstalk and outline how this relationship can provide new rationales for developing more effective combination immunotherapy strategies for treating human cancers.

Keywords: cancer immunotherapy; immune checkpoint blockade; tumor microenvironment; tumor vasculature; vascular normalization.

Copyright © 2019 Elsevier Ltd. All rights reserved.

Cited by 2 articles
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35
Otolaryngol Head Neck Surg
. 2020 Jun;162(6):867-872. doi: 10.1177/0194599820914275. Epub 2020 Mar 31.
Effect of Electrocautery Settings on Particulate Concentrations in Surgical Plume During Tonsillectomy
Michele M Carr 1, Vijay A Patel 2, Jhy-Charm Soo 3, Sherri Friend 3, Eun Gyung Lee 3
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PMID: 32228131 PMCID: PMC7323892 DOI: 10.1177/0194599820914275
Free PMC article
Abstract
Objectives: To describe the effect of monopolar electrocautery (EC) settings on surgical plume particulate concentration during pediatric tonsillectomy.

Study design: Cross-sectional study.

Setting: Tertiary medical center.

Subjects and methods: During total tonsillectomy exclusively performed with EC, air was sampled with a surgeon-worn portable particle counter. The airborne mean and maximum particle concentrations were compared for tonsillectomy performed with EC at 12 W vs 20 W, with smoke evacuation system (SES) and no smoke evacuation (NS).

Results: A total of 36 children were included in this analysis: 9 cases with EC at 12 W and SES (12SES), 9 cases with EC at 20 W and SES (20SES), 9 cases with EC at 12 W without SES (12NS), and 9 cases with EC at 20 W without SES (20NS). Mean particle number concentration in the breathing zone during tonsillectomy was 1661 particles/cm3 for 12SES, 5515 particles/cm3 for 20SES, 8208 particles/cm3 for 12NS, and 78,506 particles/cm3 for 20NS. There was a statistically significant difference in the particle number concentrations among the 4 groups. The correlation between the particle number concentration and EC time was either moderate (for 12SES) or negative (for remaining groups).

Conclusion: Airborne particle concentrations during tonsillectomy are over 9.5 times higher when EC is set at 20 W vs 12 W with NS, which is mitigated to 3.3 times with SES. Applying lower EC settings with SES during pediatric tonsillectomy significantly reduces surgical plume exposure for patients, surgeons, and operating room personnel, which is a well-known occupational health hazard.

Keywords: electrocautery; pediatric otolaryngology; surgical plume; tonsillectomy.

Conflict of interest statement
Competing interests: None.

Cited by 1 article2 figures
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36
Otolaryngol Head Neck Surg
. 2020 Jun;162(6):873-880. doi: 10.1177/0194599820914298. Epub 2020 Apr 14.
Trends in Ambulatory Surgery Center Utilization for Otolaryngologic Procedures Among Medicare Beneficiaries, 2010-2017
Neil S Kondamuri 1, Ashley L Miller 2 3, Vinay K Rathi 2 4, Lauren Miller 2 3, Regan W Bergmark 5 6 7, Tushar S Patel 8, Stacey T Gray 2 3
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PMID: 32283985 DOI: 10.1177/0194599820914298
Abstract
Objective: Surgical care is increasingly shifting to freestanding ambulatory surgical centers (ASCs). The extent to which otolaryngologists use ASCs has implications for patient safety and health care spending. This study characterizes trends in utilization and resultant financial implications for common otolaryngologic procedures performed at ASC and hospital outpatient departments (HOPDs).

Study design: Retrospective cross-sectional analysis.

Setting: ASCs, HOPDs.

Subjects and methods: Subjects included Medicare beneficiaries undergoing outpatient otolaryngologic procedures between 2010 and 2017. Procedures included the 20 highest-volume procedures performed by otolaryngologists at ASCs in 2017. Main outcomes included absolute and relative percentage difference in the proportion of procedures furnished at ASCs and HOPDs and estimated Medicare cost savings resulting from increased ASC utilization between 2011 and 2017.

Results: The proportion of outpatient otolaryngologic procedures performed at ASCs increased by 1.8% (relative difference: 10.0%; mean annual relative increase: 1.60%), and the proportion located at HOPDs decreased by 6.0% (relative difference: -11.8%; mean annual relative decrease: -1.6%) between 2010 and 2017. Rhinoplasty accounted for the largest absolute increase in ASC utilization over the study period (absolute [relative] 8.9% [33.5%]). Increased ASC utilization resulted in an estimated $7.1 million in cost savings to Medicare between 2011 and 2017.

Conclusion: Otolaryngologists shifted outpatient surgical care from HOPDs to ASCs between 2010 and 2017, with resultant reductions in Medicare expenditures. Further research is necessary to examine the impact of this shift on patient safety.

Keywords: ambulatory surgery centers; otolaryngology; patient safety; payment reform.

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37
Otolaryngol Head Neck Surg
. 2020 Jun;162(6):969-978. doi: 10.1177/0194599820915472. Epub 2020 Apr 14.
Patterns in Pain and Opiate Use After Endoscopic Sinus Surgery
Sifon Ndon 1, Todd Spock 2, Sina J Torabi 3, R Peter Manes 3
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PMID: 32284006 DOI: 10.1177/0194599820915472
Abstract
Objective: To evaluate postoperative opiate use and patients' opinions regarding pain management after endoscopic sinus surgery (ESS).

Study design: Case series with planned data collection.

Setting: Tertiary referral medical center.

Subjects and methods: We prospectively evaluated postoperative opiate utilization in adults undergoing ESS over a 2-year period at an academic medical facility. Exclusion criteria included use of nasal packing, intracranial or orbital procedures, tumor surgery, and any use of endoscopic drills. All patients underwent bilateral maxillary antrostomy, total ethmoidectomy, sphenoidotomy, and frontal sinusotomy with or without septoplasty. Patients were discharged with 30 oxycodone-acetaminophen (5-325 mg) and a survey assessing pain and narcotic/nonnarcotic use on postoperative days 0 to 7.

Results: A total of 64 patients completed surveys. Mean ± SD narcotic use over the 7-day postoperative period was 7.7 ± 7.6 pills. Patients with high narcotic use (>6 pills total) had no differences in demographic or surgical factors from those with low use (≤6 pills) but did report a higher level of postoperative day 1 pain (4.8 ± 1.1 vs 2.0 ± 1.4, P < .001). Narcotic use declined during this period, with <30% of patients requiring narcotics by postoperative day 3.

Conclusion: Our results support reduced opiate prescription and encouragement of nonnarcotic use after ESS without compromising effective pain management.

Keywords: adult; narcotics; otolaryngology; postoperative period; surveys and questionnaires.

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38
Case Reports Medicine (Baltimore)
. 2020 May 29;99(22):e20392. doi: 10.1097/MD.0000000000020392.
Thyroglossal Duct Lipoma: A Rare Case Report
Ming-Shao Tsai 1 2 3 4, Geng-He Chang 1 2 3 4, Huei-Chieh Chuang 4 5, Wan-Ni Lin 4 6, Yao-Te Tsai 1 2
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PMID: 32481427 DOI: 10.1097/MD.0000000000020392
Free article
Abstract
Rationale: Thyroglossal duct cyst (TGDC), the most common midline neck mass, has several histological diagnoses other than cyst in the literature. We present the first case of thyroglossal duct lipoma.

Patient concerns: A 63-year-old woman presented with a painless soft midline neck mass for more than 3 years, which enlarged in size and caused a lump sensation during swallowing.

Diagnoses: Sonography revealed a 3.5 × 3.0 × 3.0-cm homogenous isoechoic oval lesion without an acoustic shadow beyond the thyroid glands. An ultrasound-guided biopsy revealed abundant sheets of fat cells with infiltration of some lymphocytes and histiocytes. Computed tomography revealed a 3.5 × 3.0 × 3.0-cm well-circumscribed ovoid mass with Hounsfield unit (HU) between -50 and -100 and a thyroglossal duct remnant. All these findings supported the diagnosis of thyroglossal duct lipoma.

Interventions: The patient underwent Sistrunk operation for excision of the neck tumor, and pathological examination revealed an adipose tumor surrounded by benign thyroid tissue, confirming the diagnosis of thyroglossal duct lipoma.

Outcomes: Neither postoperative complication nor recurrence was noted at the 18-month follow-up.

Lessons: This is the first case of thyroglossal duct lipoma in the literature. Our study extends the disease spectrum of thyroglossal duct mass and suggests that clinicians should consider thyroglossal duct lipoma in the differential diagnosis of a midline neck mass.

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39
Randomized Controlled Trial Otolaryngol Head Neck Surg
. 2020 Jun;162(6):853-859. doi: 10.1177/0194599820912030. Epub 2020 Mar 17.
Influence of Sevoflurane-Based Anesthesia Versus Total Intravenous Anesthesia on Intraoperative Neuromonitoring During Thyroidectomy
Xiaoxi Li 1, Bin Zhang 2, Ling Yu 1, Jiaonan Yang 1, Hongyu Tan 1
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PMID: 32178568 DOI: 10.1177/0194599820912030
Abstract
Objective: To examine the influence of sevoflurane-based combined intravenous and inhaled anesthesia versus propofol-based total intravenous anesthesia (TIVA) on intraoperative neuromonitoring (IONM) during thyroidectomy.

Study design: A randomized controlled trial.

Setting: The present study was conducted in a tertiary hospital.

Subjects and methods: Forty patients were randomly assigned to a sevoflurane-based combined intravenous and inhalation group (group S) or a propofol-based total intravenous group (group P). Anesthesia was induced with midazolam, sufentanil, propofol, and cisatracurium in both groups and was maintained with sevoflurane and remifentanil in group S and with TIVA with propofol and remifentanil in group P. IONM was performed intermittently according to the IONM formula standard.

Results: The time until detection of the first positive electromyographic (EMG) signal was significantly longer in group S (median, 41.0 minutes [interquartile range, 37.5-49.3]) than in group P (37.0 minutes [33.3-41.5], P = .028). All patients in group P had a positive EMG signal at initial monitoring, whereas 8 patients (40.0%) in group S did not. The rate of positive EMG signal at initial monitoring was significantly higher in group P than in group S (P = .006). The amplitude of the evoked potentials at V1, R1, R2, and V2 were similar between the groups.

Conclusion: Combined intravenous and inhaled anesthesia based on sevoflurane-remifentanil prolonged the time until detection of a positive EMG signal during IONM as compared with TIVA with propofol-remifentanil in patients undergoing thyroidectomy.

Keywords: combined intravenous and inhaled anesthesia; intraoperative neuromonitoring; propofol; sevoflurane; thyroidectomy; total intravenous anesthesia.

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40
Otolaryngol Head Neck Surg
. 2020 Jun;162(6):985-992. doi: 10.1177/0194599820917147. Epub 2020 Apr 28.
Contralateral Tongue Muscle Activation During Hypoglossal Nerve Stimulation
Joshua J Sturm 1, Oleg Modik 2, Ioannis Koutsourelakis 1, Maria V Suurna 1
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PMID: 32343198 DOI: 10.1177/0194599820917147
Abstract
Objective: The effectiveness of upper airway stimulation via hypoglossal nerve stimulation for obstructive sleep apnea depends upon the pattern of tongue muscle activation produced. This study investigated the nature of contralateral tongue muscle activation by unilateral hypoglossal nerve stimulation using intraoperative nerve integrity monitoring in conjunction with electromyography and explored the relationship between contralateral tongue muscle activation and polysomnographic measures of obstructive sleep apnea severity.

Study design: Prospective case series.

Setting: Tertiary care medical center.

Subjects and methods: Fifty-one patients underwent unilateral (right) hypoglossal nerve stimulator implantation for obstructive sleep apnea. Neurophysiological data included electromyographic responses in ipsilateral (right) and contralateral (left) genioglossus muscles in response to intraoperative bipolar probe stimulation (0.3 mA) of medial hypoglossal nerve branches. Clinical data included pre- and postoperative apnea-hypopnea indices and oxygen desaturation levels.

Results: A subset of patients (20/51, 39%) exhibited electromyographic responses in both the ipsilateral and contralateral genioglossus (bilateral), whereas the remaining patients (31/51, 61%) exhibited electromyographic responses only in the ipsilateral genioglossus (unilateral). The baseline characteristics of bilateral and unilateral responders were similar. Both groups exhibited significant and comparable improvements in apnea-hypopnea index and oxygen desaturations after hypoglossal nerve stimulation. Neither the amplitude nor the latency of contralateral genioglossus responses was predictive of clinical outcomes.

Conclusion: A subset of patients undergoing unilateral hypoglossal nerve stimulation exhibits activation of contralateral genioglossus muscles. Patients with unilateral and bilateral genioglossus responses exhibit comparable, robust improvements in apnea-hypopnea index and oxygen desaturation levels.

Keywords: hypoglossal nerve stimulation; neurostimulation; obstructive sleep apnea; sleep surgery.

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41
Br J Cancer
. 2020 Jul 6. doi: 10.1038/s41416-020-0964-x. Online ahead of print.
Evaluation of p16 INK4a Expression as a Single Marker to Select Patients With HPV-driven Oropharyngeal Cancers for Treatment De-Escalation
Steffen Wagner 1, Elena-Sophie Prigge 2 3, Nora Wuerdemann 4 5, Henrike Reder 4, Ayman Bushnak 4, Shachi Jenny Sharma 4 5, Theresa Obermueller 2 3, Magnus von Knebel Doeberitz 2 3, Thomas Dreyer 6, Stefan Gattenlöhner 6, Gregor Wolf 4, Jörn Pons-Kühnemann 7, Claus Wittekindt 4, Jens Peter Klussmann 4 5
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PMID: 32624580 DOI: 10.1038/s41416-020-0964-x
Abstract
Background: A remarkably better prognosis is associated with oropharyngeal squamous cell carcinomas (OPSCC) driven by human papillomaviruses (HPV) compared with HPV-negative OPSCC. Consequently, de-escalation of standard treatment has been suggested. Due to modest specificity rates, debates are ongoing, whether p16INK4a, a surrogate marker for HPV-driven OPSCC, is sufficient to correctly identify those tumours and avoid substantial HPV misattribution and thus undertreatment of patients by de-escalation. Robust data estimating the proportion of potentially undertreated patients are missing.

Methods: We assessed a large-scale cohort of consecutively included OPSCC diagnosed between 2000 and 2017 for HPV-DNA, HPV genotypes, p16INK4a expression and multiple tumour- and patient-related risk factors, and investigated their impact on patients' survival in comprehensive uni- and multivariate analyses.

Results: Aetiological relevance of HPV (p16INK4a- and high-risk HPV-DNA-positivity) was detected in 27.1% (n = 192) of OPSCC, with HPV16 being the most abundant HPV type (94.6%). In 5.5% patients (n = 39), p16INK4a overexpression but no HPV-DNA was detected. Principal component and survival analyses revealed that 60.6% of these p16INK4a-positive OPSCC lacking HPV-DNA did not resemble HPV16-driven but HPV-negative OPSCC regarding risk-factor profile and overall survival. Notably, this group represented 10.6% of all p16INK4a-overexpressing OPSCC.

Conclusions: p16INK4a as a single marker appears insufficient to indicate OPSCC patients suitable for treatment de-escalation.

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42
Clinical Trial Otolaryngol Head Neck Surg
. 2020 Jun;162(6):933-941. doi: 10.1177/0194599820911716. Epub 2020 Mar 17.
Subjective Benefits of Bimodal Listening in Cochlear Implant Recipients With Asymmetric Hearing Loss
Nicholas J Thompson 1, Margaret T Dillon 1, Emily Buss 1, Meredith A Rooth 1, English R King 2, Andrea L Bucker 2, Sarah A McCarthy 2, Ellen J Deres 2, Brendan P O'Connell 1, Harold C Pillsbury 3rd 1, Kevin D Brown 1
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PMID: 32182164 PMCID: PMC7268952 DOI: 10.1177/0194599820911716
Free PMC article
Abstract
Objective: To investigate the influence of cochlear implant (CI) use on subjective benefits in quality of life in cases of asymmetric hearing loss (AHL).

Study design: Prospective clinical trial.

Setting: Tertiary academic center.

Subjects and methods: Subjects included CI recipients with AHL (n = 20), defined as moderate-to-profound hearing loss in the affected ear and mild-to-moderate hearing loss in the contralateral ear. Quality of life was assessed with the Speech, Spatial, and Qualities of Hearing Scale (SSQ) pragmatic subscales, which assess binaural benefits. Subjective benefit on the pragmatic subscales was compared to word recognition in quiet and spatial hearing abilities (ie, masked sentence recognition and localization).

Results: Subjects demonstrated an early, significant improvement (P < .01) in abilities with the CI as compared to preoperative abilities on the SSQ pragmatic subscales by the 1-month interval. Perceived abilities were either maintained or continued to improve over the study period. There were no significant correlations between results on the Speech in Quiet subscale and word recognition in quiet, the Speech in Speech Contexts subscale and masked sentence recognition, or the Localization subscale and sound field localization.

Conclusions: CI recipients with AHL report a significant improvement in quality of life as measured by the SSQ pragmatic subscales over preoperative abilities. Reported improvements are observed as early as 1 month postactivation, which likely reflect the binaural benefits of listening with bimodal stimulation (CI and contralateral hearing aid). The SSQ pragmatic subscales may provide a more in-depth insight into CI recipient experience as compared to behavioral sound field measures alone.

Keywords: asymmetric hearing loss; binaural hearing; cochlear implant; quality of life; single sided deafness.

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43
Ear Nose Throat J
. 2020 Jul 5;145561320937238. doi: 10.1177/0145561320937238. Online ahead of print.
T1b Glottic Tumor and Anterior Commissure Involvement: Is the Transoral CO 2 Laser Microsurgery a Safe Option?
Juan Antonio Cabrera-Sarmiento 1, Juan Carlos Vázquez-Barro 1 2, Jesús Herranz González-Botas 1 3, Carlos Chiesa-Estomba 4, Miguel Mayo-Yáñez 1 5
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PMID: 32627619 DOI: 10.1177/0145561320937238
Abstract
Objectives: Transoral CO2 laser therapy represents the treatment of choice for early-stage laryngeal tumors. The anterior commissure involvement (ACI) is related to a worse local control and a lower rates of organ preservation. The objective of this study is to analyze the differences in survival, local control, and organ preservation in T1b glottic patients according to the presence of ACI.

Methods: Observational prospective study in pT1b treated with transoral CO2 laser between 2009 and 2014.

Results: Forty patients (37 male and 3 female) with a mean age of 66.43 ± 8.16 years were recruited. Anterior commissure involvement was present in 70% of the patients. The 5-year specific cause survival was 91.66%, with 32.50% of local recurrences. Laryngeal preservation was 80%, being lower in the group with local recurrence (P < .000). The involvement of the anterior commissure does not influence the organ preservation (P = .548), the appearance of local recurrences (P = .391), or the survival (P = .33).

Conclusions: Transoral CO2 laser therapy is an effective and reproducible treatment for early-stage laryngeal tumors. The results obtained are similar to previous studies, although they present discrepancies in relation to the role of the ACI. Prospective randomized trials are required focusing also on the patients' quality of life and functional outcome in order to clarify the role of the ACI and the need to implement changes in its evaluation, staging, and evolution.

Keywords: TNM staging; anterior commissure; early glottic cancer; larynx tumor; transoral laser microsurgery.

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44
Innovations (Phila)
. 2020 Jul 5;1556984520935535. doi: 10.1177/1556984520935535. Online ahead of print.
Negative-Pressure Vacuum Therapy for High-Output Chyle Leak Following Neck Dissection
Guy Pines 1 2, Liron Malka Yosef 2 3, Li Or Lazar 1 2, Ilan Bar 1 2, Doron Schindel 2 3
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PMID: 32628079 DOI: 10.1177/1556984520935535
Abstract
Chyle fistula is a challenging complication following neck dissection carrying a high morbidity and mortality rate. Herein we present a challenging case of successful management of high-output left-sided cervical chyle fistula with negative-pressure vacuum (VAC) therapy in a case where all conservative treatments failed. A 40-year-old man with lymphoma and supraglottic carcinoma underwent endoscopic resection and bilateral neck dissections. He developed high-output chyle fistula, nonresponsive to conservative treatments. Double-layered Vicryl mesh was placed between the sponge and the jugular vein to prevent vascular injury. Immediately after initiation of the VAC therapy, the output decreased, and completely stopped after 3 days. The VAC therapy was continued for additional 5 days to ensure complete seal of the fistula by granulation tissue, by which time the wound was primarily closed. VAC therapy seems to be a safe and effective treatment for high-output cervical chyle fistula following neck dissection, avoiding complex surgical interventions. Thoracic surgeons should be aware of this low-morbidity and potentially effective treatment modality for this challenging complication.

Keywords: VAC therapy; chylous fistula; neck dissection.

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45
Jpn J Clin Oncol
. 2020 Jun 10;50(6):701-711. doi: 10.1093/jjco/hyaa016.
MUC5AC Enhances Tumor Heterogeneity in Lung Adenocarcinoma With Mucin Production and Is Associated With Poor Prognosis
Yujie Dong 1 2, Lijuan Zhou 2, Dan Zhao 2, Kun Li 2, Zichen Liu 2, Nanying Che 2, Honggang Liu 1
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PMID: 32083303 DOI: 10.1093/jjco/hyaa016
Abstract
Objective: The clinicopathological significance of Mucin5AC (MUC5AC) in lung adenocarcinoma with mucin production is still unclear. This study aimed to explore MUC5AC expression in lung adenocarcinoma with mucin production and its correlation with histological subtypes, common driver mutations and its impact on prognosis.

Methods: MUC5AC and thyroid transcription factor 1 immunohistochemistry was performed on surgical samples from 90 patients with lung adenocarcinoma with mucin production. Common driver mutations including EGFR and KRAS mutations and ALK rearrangement were detected by established methods.

Results: MUC5AC was significantly associated with lymphovascular invasion (P = 0.023) and tumors with intra-cytoplasmic mucin (P < 0.001). Moreover, MUC5AC was more significant in invasive mucinous adenocarcinoma (P < 0.001), as well as in tumors with KRAS mutations (P = 0.005) and a lack of thyroid transcription factor 1 expression (P < 0.001). Conversely, MUC5AC was less significantly detected in acinar predominant adenocarcinoma (P = 0.036) and tumors with EGFR mutations (P = 0.001). Notably, MUC5AC in non-pure mucinous subtype of lung adenocarcinoma with mucin production showed more aggressive behavior, distinct expression pattern and a lack of significant correlation with thyroid transcription factor 1 (P = 0.113) when compared with pure mucinous subtype. MUC5AC-positive tumors were significantly associated with a worse prognosis compared to MUC5AC-negative tumors (P < 0.001). A multivariate survival analysis showed that MUC5AC was an independent prognosis factor for poor prognosis (P = 0.006).

Conclusions: The clinicopathological features of non-pure mucinous subtype of lung adenocarcinoma with mucin production were distinct and should be distinguished from pure mucinous subtype. MUC5AC was associated with poor prognosis and could be a potential therapeutic target for this distinct type of lung adenocarcinoma that has few effective treatments.

Keywords: MUC5AC; heterogeneity; lung adenocarcinoma with mucin production; prognosis.

© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

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46
Ear Nose Throat J
. 2020 Jul 5;145561320936963. doi: 10.1177/0145561320936963. Online ahead of print.
Computed Tomography Image Analysis and Clinical Correlations of Retromaxillary Cells
Cheng Cao 1, Fangwei Zhou 1, ZhiYan Song 2, Zezhang Tao 1 3, Yu Xu 1 3
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PMID: 32627620 DOI: 10.1177/0145561320936963
Abstract
Objective: This study aimed to investigate and analyze the anatomic characteristics of the retromaxillary cell (RMC) by using computed tomography (CT) images of paranasal sinuses and to improve its identification with ethmomaxillary sinus (EMS).

Methods: The paranasal sinus CT scans of 441 outpatients or inpatients in our hospital from January 2018 to October 2018 were analyzed. The incidence of RMC, EMS, Haller cell, imaging anatomical characteristics, and morphological manifestations were observed via sinus CTs. The relationship of RMC and ipsilateral maxillary sinusitis was analyzed.

Results: The incidence of RMC is 83.90% (740/882). The incidence of males and females was 83.81% (414/494) and 84.02% (326/388), respectively. The incidence of bilateral (72.79%, 321/441) was much higher than that of unilateral (22.22%, 98/441). The lateral extension of the RMC ranged from 1.18 to 13.31 mm, with an average of 6.10 ± 2.03 mm. The incidence of ipsilateral maxillary sinus opacification on the RMC sides and non-RMC sides has no significance difference (χ2 = .054, P = .459). The incidence of Haller cell and EMS decreased significantly in the presence of RMC (P < .01).

Conclusion: The RMC is an anatomical variation originating from posterior ethmoid cells, which is commonly encountered in the clinic. The pneumatization of RMC is highly variable, and a bilateral is common. During endoscopic sinus surgery, it is necessary to carefully identify such an air cell to ensure the complete opening of the paranasal sinus during surgery.

Keywords: anatomical variation; computed tomography image; identification; retromaxillary cells (RMCs).

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47
Lancet Oncol
. 2019 Nov;20(11):1485-1486. doi: 10.1016/S1470-2045(19)30651-5.
Developing an Independent Palestinian Cancer Care Capacity
Ziv Gil 1, Fadi Atrash 2, Suliman Za'aroura 3, Salem Billan 4, Walid Nammour 5
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PMID: 31674309 DOI: 10.1016/S1470-2045(19)30651-5
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48
Otolaryngol Head Neck Surg
. 2020 Jun;162(6):959-968. doi: 10.1177/0194599820915468.
Postoperative Outcomes of Branchial Cleft Cyst Excision in Children and Adults: An NSQIP Analysis
Annie E Moroco 1, Robert A Saadi 2, Vijay A Patel 2, Erik B Lehman 3, Meghan N Wilson 2
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PMID: 32484763 DOI: 10.1177/0194599820915468
Abstract
Objective: Identify risk factors and perioperative morbidity for patients undergoing branchial cleft cyst (BCC) excision.

Study design: Cross-sectional analysis.

Setting: American College of Surgeons National Surgical Quality Improvement Program adult and pediatric databases (NSQIP and NSQIP-P).

Subject and methods: Patients who underwent BCC excision (Current Procedural Terminology 42810, 42815) were queried via NSQIP (2005-2016) and NSQIP-P (2012-2016). Outcomes analyzed include patient demographics, medical comorbidities, admission type, operative characteristics, length of hospital stay, postoperative complications, and readmission.

Results: A total of 1775 children and 677 adults were identified. Mean age at time of surgery was 4.6 years for children and 38.6 years for adults. Outpatient procedures were performed in 87.1% of adults and 94.0% of children (P < .001). Postoperative complications were uncommon, occurring in <1% of adults and 3.9% of children (P < .001). Similarly, readmission occurred in 1.2% of adults and 1.1% of children. In adults, smoking status was shown to have a significant effect on postoperative complications (odds ratio, 6.25; P = .037). Age group did not have an effect on the complication rate in the pediatric population. Pediatric otolaryngologists had higher rates of postoperative complications (P = .001), prolonged operative times (P < .001), and fewer outpatient procedures (P < .001). Conversely, in adults, otolaryngologists had fewer postoperative complications.

Conclusion: Postoperative complications following BCC excision are relatively uncommon, demonstrating procedural safety when performed at any age.

Keywords: NSQIP; adult; branchial cleft cyst; complications; pediatric.

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49
J Laryngol Otol
. 2020 May;134(5):447-452. doi: 10.1017/S0022215120000961. Epub 2020 Jun 3.
Short-term Results of Upper Airway Stimulation in Obstructive Sleep Apnoea Patients: The Amsterdam Experience
P E Vonk 1 2, M J L Ravesloot 1 3, J P van Maanen 1, N de Vries 1 4 5
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PMID: 32493527 DOI: 10.1017/S0022215120000961
Abstract
Objectives: This paper aimed to: retrospectively analyse single-centre results in terms of surgical success, respiratory outcomes and adverse events after short-term follow up in obstructive sleep apnoea patients treated with upper airway stimulation; and evaluate the correlation between pre-operative drug-induced sleep endoscopy findings and surgical success.

Methods: A retrospective descriptive cohort study was conducted, including a consecutive series of obstructive sleep apnoea patients undergoing implantation of an upper airway stimulation system.

Results: Forty-four patients were included. The total median Apnoea-Hypopnea Index and oxygen desaturation index significantly decreased from 37.6 to 8.3 events per hour (p < 0.001) and from 37.1 to 15.9 events per hour (p < 0.001), respectively. The surgical success rate was 88.6 per cent, and did not significantly differ between patients with or without complete collapse at the retropalatal level (p = 0.784). The most common therapy-related adverse event reported was (temporary) stimulation-related discomfort.

Conclusion: Upper airway stimulation is an effective and safe treatment in obstructive sleep apnoea patients with continuous positive airway pressure intolerance or failure. There was no significant difference in surgical outcome between patients with tongue base collapse with or without complete anteroposterior collapse at the level of the palate.

Keywords: Hypoglossal Nerve; Sleep Apnea, Obstructive.

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50
Clinical Trial Lancet Oncol
. 2020 Feb;21(2):294-305. doi: 10.1016/S1470-2045(19)30728-4. Epub 2020 Jan 14.
Cemiplimab in Locally Advanced Cutaneous Squamous Cell Carcinoma: Results From an Open-Label, Phase 2, Single-Arm Trial
Michael R Migden 1, Nikhil I Khushalani 2, Anne Lynn S Chang 3, Karl D Lewis 4, Chrysalyne D Schmults 5, Leonel Hernandez-Aya 6, Friedegund Meier 7, Dirk Schadendorf 8, Alexander Guminski 9, Axel Hauschild 10, Deborah J Wong 11, Gregory A Daniels 12, Carola Berking 13, Vladimir Jankovic 14, Elizabeth Stankevich 15, Jocelyn Booth 15, Siyu Li 15, David M Weinreich 14, George D Yancopoulos 14, Israel Lowy 14, Matthew G Fury 14, Danny Rischin 16
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PMID: 31952975 DOI: 10.1016/S1470-2045(19)30728-4
Abstract
Background: Cemiplimab has shown substantial antitumour activity in patients with metastatic cutaneous squamous cell carcinoma. Patients with locally advanced cutaneous squamous cell carcinoma have poor prognosis with conventional systemic therapy. We present a primary analysis of the safety and antitumour activity of cemiplimab in patients with locally advanced cutaneous squamous cell carcinoma.

Methods: This pivotal open-label, phase 2, single-arm trial was done across 25 outpatient clinics, primarily at academic medical centres, in Australia, Germany, and the USA. Eligible patients (aged ≥18 years with histologically confirmed locally advanced cutaneous squamous cell carcinoma and an Eastern Cooperative Oncology Group performance status of 0-1) received cemiplimab 3 mg/kg intravenously over 30 min every 2 weeks for up to 96 weeks. Tumour measurements were done every 8 weeks. The primary endpoint was objective response, defined as the proportion of patients with complete or partial response, according to independent central review as per Response Evaluation Criteria in Solid Tumors version 1.1 for radiological scans and WHO criteria for medical photography. Data cutoff was Oct 10, 2018, when the fully enrolled cohort reached the prespecified timepoint for the primary analysis. Analyses were done as per the intention-to-treat principle. The safety analysis comprised all patients who received at least one dose of cemiplimab. This study is registered with ClinicalTrials.gov, number NCT02760498.

Findings: Between June 14, 2016, and April 25, 2018, 78 patients were enrolled and treated with cemiplimab. The median duration of study follow-up was 9·3 months (IQR 5·1-15·7) at the time of data cutoff. An objective response was observed in 34 (44%; 95% CI 32-55) of 78 patients. The best overall response was ten (13%) patients with a complete response and 24 (31%) with a partial response. Grade 3-4 treatment-emergent adverse events occurred in 34 (44%) of 78 patients; the most common were hypertension in six (8%) patients and pneumonia in four (5%). Serious treatment-emergent adverse events occurred in 23 (29%) of 78 patients. One treatment-related death was reported that occurred after onset of aspiration pneumonia.

Interpretation: Cemiplimab showed antitumour activity and an acceptable safety profile in patients with locally advanced cutaneous squamous cell carcinoma for whom there was no widely accepted standard of care.

Funding: Regeneron Pharmaceuticals and Sanofi.

Copyright © 2020 Elsevier Ltd. All rights reserved.

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