BMC Palliat Care. 2019 Oct 23;18(1):85. doi: 10.1186/s12904-019-0468-8.
Efficacy and cost-utility of the eHealth application 'Oncokompas', supporting patients with incurable cancer in finding optimal palliative care, tailored to their quality of life and personal preferences: a study protocol of a randomized controlled trial.
Schuit AS1,2, Holtmaat K1,2, Hooghiemstra N1,2, Jansen F1,2,3, Lissenberg-Witte BI4, Coupé VMH4, van Linde ME5, Becker-Commissaris A6, Reijneveld JC7, Zijlstra JM8, Sommeijer DW9,10, Eerenstein SEJ3, Verdonck-de Leeuw IM11,12,13.
Author information
1
Department of Clinical, Neuro and Developmental Psychology, Faculty of Behavioral and Movement Sciences, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, van der Boechorststraat 7, 1081, BT, Amsterdam, The Netherlands.
2
Cancer Center Amsterdam (CCA), Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
3
Amsterdam UMC, Vrije Universiteit Amsterdam, Otolaryngology - Head and Neck Surgery, Cancer Center Amsterdam, De Boelelaan, 1117, Amsterdam, The Netherlands.
4
Department of Epidemiology and Biostatistics, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan, 1117, Amsterdam, The Netherlands.
5
Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan, 1117, Amsterdam, The Netherlands.
6
Department of Pulmonary Diseases, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan, 1117, Amsterdam, The Netherlands.
7
Department of Neurology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan, 1117, Amsterdam, The Netherlands.
8
Department of Hematology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan, 1117, Amsterdam, The Netherlands.
9
Department of Internal Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
10
Department of Internal Medicine, Flevo Hospital, Hospitaalweg 1, Almere, The Netherlands.
11
Department of Clinical, Neuro and Developmental Psychology, Faculty of Behavioral and Movement Sciences, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, van der Boechorststraat 7, 1081, BT, Amsterdam, The Netherlands. im.verdonck@amsterdamumc.nl.
12
Cancer Center Amsterdam (CCA), Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. im.verdonck@amsterdamumc.nl.
13
Amsterdam UMC, Vrije Universiteit Amsterdam, Otolaryngology - Head and Neck Surgery, Cancer Center Amsterdam, De Boelelaan, 1117, Amsterdam, The Netherlands. im.verdonck@amsterdamumc.nl.
Abstract
BACKGROUND:
Patients with incurable cancer have to deal with a wide range of symptoms due to their disease and treatment, influencing their quality of life. Nowadays, patients are expected to adopt an active role in managing their own health and healthcare. Oncokompas is an eHealth self-management application developed to support patients in finding optimal palliative care, tailored to their quality of life and personal preferences. A randomized controlled trial will be carried out to determine the efficacy and cost-utility of Oncokompas compared to care as usual.

METHODS:
136 adult patients with incurable lung, breast, colorectal and head and neck cancer, lymphoma and glioma, will be included. Eligible patients have no curative treatment options and a prognosis of at least three months. Patients will be randomly assigned to the intervention group or the control group. The intervention group directly has access to Oncokompas alongside care as usual, while the waiting list control group receives care as usual and will have access to Oncokompas after three months. The primary outcome measure is patient activation, which can be described as a patient's knowledge, skills and confidence to manage his or her own health and healthcare. Secondary outcome measures comprise self-efficacy, health-related quality of life, and costs. Measures will be assessed at baseline, two weeks after randomization, and three months after the baseline measurement.

DISCUSSION:
This study will result in knowledge on the efficacy and cost-utility of Oncokompas among patients with incurable cancer. Also, more knowledge will be generated into the need for and costs of palliative care from a societal and healthcare perspective.

TRIAL REGISTRATION:
Netherlands Trial Register identifier: NTR 7494 . Registered on 24 September 2018.

KEYWORDS:
Incurable cancer; Palliative care; Patient activation; Self-management; Supportive care; eHealth

PMID: 31647011 DOI: 10.1186/s12904-019-0468-8
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102.
Ann Otol Rhinol Laryngol. 2019 Oct 24:3489419883289. doi: 10.1177/0003489419883289. [Epub ahead of print]
Gene Expression Analysis to Investigate Biological Networks Underlying Nasal Inflammatory Dysfunctions Induced by Diesel Exhaust Particles Using an In Vivo System.
Kim HS1, Kim BG2, Park S2, Kim N2, Jang AS3, Seo YR1, Park MK2.
Author information
1
Institute of Environmental Medicine, Department of Life Science, Dongguk University Biomedi Campus, Goyang-si, Gyeonggi-do, Republic of Korea.
2
Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
3
Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea.
Abstract
OBJECTIVES:
Diesel exhaust particles (DEP)s are notorious ambient pollutants composed of a complex mixture of a carbon core and diverse chemical irritants. Several studies have demonstrated significant relationships between DEP exposure and serious nasal inflammatory response in vitro, but available information regarding underlying networks in terms of gene expression changes has not sufficiently explained potential mechanisms of DEP-induced nasal damage, especially in vivo.

METHODS:
In the present study, we identified DEP-induced gene expression profiles under short-term and long-term exposure, and identified signaling pathways based on microarray data for understanding effects of DEP exposure in the mouse nasal cavity.

RESULTS:
Alteration in gene expression due to DEP exposure provokes an imbalance of the immune system via dysregulated inflammatory markers, predicted to disrupt protective responses against harmful exogenous substances in the body. Several candidate markers were identified after validation using qRT-PCR, including S100A9, CAMP, IL20, and S100A8.

CONCLUSIONS:
Although further mechanistic studies are required for verifying the utility of the potential biomarkers suggested by the present study, our in vivo results may provide meaningful suggestions for understanding the complex cellular signaling pathways involved in DEP-induced nasal damages.

KEYWORDS:
air pollution; diesel exhaust particles; inflammation; microarray; nasal damages

PMID: 31646875 DOI: 10.1177/0003489419883289
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103.
J BUON. 2019 Jul-Aug;24(4):1700-1705.
SPLUNC1 and MLL3 regulate cancer stem cells in nasopharyngeal carcinoma.
Bian S1, Wang Z, Chen Y, Li R.
Author information
1
Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
Abstract
PURPOSE:
Nasopharyngeal carcinoma (NPC) is one of the common types of cancer that originate from the nasopharyngeal region. Recurrence and early metastasis represent major problems associated with NPC mortality. These are mainly caused by various molecular changes that take place during the conversion of normal stem cells into treatment-resistant stem cells. The aim of our study was to investigate the proliferative behavior of cancer stem cells in different stages of NPC and to identify the functional roles of SPLUNC1 and MLL3 associated with cancer stem cells.

METHODS:
We successfully developed a NPC mouse model using C666-1 cells. Immunohistochemistry and Western blotting were used to analyze the expression of SOX2, SPLUNC1 and MLL3.

RESULTS:
Null BALB/c mice developed initial and aggressive stages of NPC in 3 and 10 weeks, respectively. Histological results showed that the proliferative ability of cells increased as the tumor progressed to the next level. The SOX2 protein showed a peculiar pattern of upregulation in aggressive NPC when compared with control tissues and initial NPC. Remarkably, our study found that SPLUNC1 and MLL3 expression showed upregulation in initial NPC, which indicates their role in the tumor resistance mechanism even if their expression was downregulated in aggressive NPC.

CONCLUSIONS:
Our results conclude that SPLUNC1 and MLL3 expression control the resistance mechanism of cancer stem cells in initial NPC, but their downregulation in aggressive stages contributes to developing resistance in nasopharyngeal cancer stem cells.

PMID: 31646828
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104.
Methods Mol Biol. 2020;2041:107-116. doi: 10.1007/978-1-4939-9717-6_7.
Histochemical Approach for Simultaneous Detection of Ectonucleotidase and Alkaline Phosphatase Activities in Tissues.
Losenkova K1, Paul M1, Irjala H2, Jalkanen S1, Yegutkin GG3.
Author information
1
MediCity Research Laboratory, University of Turku, Turku, Finland.
2
Department of Otorhinolaryngology, Head and Neck Surgery, Turku University Hospital and Turku University, Turku, Finland.
3
MediCity Research Laboratory, University of Turku, Turku, Finland. gennady.yegutkin@utu.fi.
Abstract
Studies on pathophysiology and the therapeutic potential of extracellular ATP and other purines represent an important and rapidly evolving field. The integral response of the cell is determined by multiple factors, including the release of endogenous ATP, co-expression of different types of nucleotide- and adenosine-selective receptors, as well as the specific makeup of ectoenzymes governing the duration and magnitude of purinergic signaling. Current findings support the presence of an extensive network of purine-converting ectoenzymes that are co-expressed to a variable extent among the mammalian tissues and share similarities in substrate specificity. Here, we describe a histochemical approach for simultaneous detection of ecto-nucleotidase and tissue-nonspecific alkaline phosphatase (TNAP) activities in the same tissue slice. Further employment of this technique for staining human palatine tonsil cryosections revealed selective distribution of the key ectoenzymes within certain tonsillar structures, including germinal centers and connective tissues (ecto-5'-nucleotidase/CD73), as well as interfollicular area (TNAP and NTPDase1/CD39).

KEYWORDS:
Ecto-5′-nucleotidase/CD73; Enzyme histochemistry; Human tonsils; NTPDase1/CD39; Tissue-nonspecific alkaline phosphatase

PMID: 31646483 DOI: 10.1007/978-1-4939-9717-6_7
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105.
Eur Arch Otorhinolaryngol. 2019 Oct 23. doi: 10.1007/s00405-019-05684-2. [Epub ahead of print]
FDG-PET/CT in the surveillance of head and neck cancer following radiotherapy.
Risør LM1, Loft A2, Berthelsen AK2, Loft FC2, Madsen AR2, Vogelius IR3, Kjær A2, Friborg J3.
Author information
1
Department of Clinical Physiology, Department of Biomedical Sciences, Nuclear Medicine and PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark. louise.madeleine.risoer@regionh.dk.
2
Department of Clinical Physiology, Department of Biomedical Sciences, Nuclear Medicine and PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
3
Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Abstract
PURPOSE:
To examine the time-dependent diagnostic performance of FDG-PET/CT in the follow-up of head and neck cancer (HNC) and to assess the prognostic value of PET-negative and PET-inconclusive findings.

MATERIAL AND METHODS:
279 HNC patients primarily treated with radiotherapy from 2006 to 2012 were included. The follow-up PET/CT scans were categorized as benign, malignant or inconclusive by a radiologist and a nuclear physician. The reference standard was histology or verification by progression on imaging. The outcome measures were positive (PPV) and negative predictive value (NPV), and the PET/CT scans were grouped according to time since treatment and compared. An analysis of the diagnostic accuracy was performed with the inconclusive results categorized as both benign and malignant to create ranges for the diagnostic performance.

RESULTS:
The proportion of inconclusive results declined from 26 to 8.4% and 0% after 0-3, 3-6 and 12-24 months post-treatment. The ranges for diagnostic performance after 0-3, 3-6, 6-12, 12-24 months and overall post-treatment were: PPV 27.3-50, 48.4-58.3, 71.4-100, 100 and 50.5-65.7 and NPV 75.0-84.6, 95.1-96.8, 92.9-100, 100 and 94.8-96.7. Time to recurrence was not statistically different after a PET-negative or a PET-inconclusive result.

CONCLUSION:
The diagnostic accuracy of a surveillance PET/CT scan after HNC improves with time since treatment, and is very reliable after 1 year. However, the NPV is already high 3 months post-treatment supporting the use of PET/CT for early evaluation of head and neck cancer patients.

KEYWORDS:
FDG-PET/CT; Follow-up; Head and neck cancer; Nuclear medicine; Oncology; Radiotherapy; Surveillance

PMID: 31646385 DOI: 10.1007/s00405-019-05684-2
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106.
Clin Transl Radiat Oncol. 2019 Aug 30;19:87-95. doi: 10.1016/j.ctro.2019.08.005. eCollection 2019 Nov.
Identifying organs at risk for radiation-induced late dysphagia in head and neck cancer patients.
Hedström J1,2, Tuomi L1,3, Finizia C1,3, Olsson C4,5.
Author information
1
Department of Otorhinolaryngology, Head and Neck Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, 413 45 Gothenburg, Sweden.
2
Region Västra Götaland, Sahlgrenska University Hospital, Department of Anesthesia and Intensive Care, Area 2, 416 85 Gothenburg, Sweden.
3
Region Västra Götaland, Sahlgrenska University Hospital, Department of Otorhinolaryngology, 413 45 Gothenburg, Sweden.
4
Department of Radiation Physics, Institute of Clinical Sciences, the Sahlgrenska Academy Gothenburg University, 413 45 Gothenburg, Sweden.
5
Regional Cancer Center West, the Western Sweden Healthcare Region, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden.
Abstract
BACKGROUND AND PURPOSE:
Dysphagia is a common, severe and dose-limiting toxicity after oncological treatment of head and neck cancer (HNC). This study aims to investigate relationships between radiation doses to structures involved in normal swallowing and patient-reported as well as clinically measured swallowing function in HNC patients after curative (chemo-) radiation therapy (RT) with focus on late effects.

MATERIALS AND METHODS:
Patients (n = 90) with HNC curatively treated with RT ± chemotherapy in 2007-2015 were assessed for dysphagia post-treatment by telephone interview and videofluoroscopy (VFS). A study-specific symptom score was used to determine patient-reported dysphagia. The Penetration-Aspiration Scale (PAS) was applied to determine swallowing function by VFS (PAS ≥ 4/ ≥ 6 = moderate/severe dysphagia). Thirteen anatomical structures involved in normal swallowing were individually delineated on the patients' original planning CT scans and associated dose-volume histograms (DVHs) retrieved. Relationships between structure doses and late toxicity were investigated through univariable and multivariable logistic regression analysis (UVA/MVA) accounting for effects by relevant clinical factors.

RESULTS:
Median assessment time was 7 months post-RT (range: 5-34 months). Mean dose to the contralateral parotid gland and supraglottic larynx as well as maximum dose to the contralateral anterior digastric muscle predicted patient-reported dysphagia (AUC = 0.64-0.67). Mean dose to the pharyngeal constrictor muscle, the larynx, the supraglottic larynx and the epiglottis, as well as maximum dose to the contralateral submandibular gland predicted moderate and severe dysphagia by VFS (AUC = 0.71-0.80).

CONCLUSION:
The patients in this cohort were consecutively identified pre-treatment, and were structurally approached and assessed for dysphagia after treatment at a specific time point. In addition to established dysphagia organs-at-risk (OARs), our data suggest that epiglottic and submandibular gland doses are important for swallowing function post-RT. Keeping DVH thresholds below V60 = 60% and V60 = 17%, respectively, may increase chances to reduce occurrence of severe late dysphagia. The results need to be externally validated in future studies.

© 2019 The Authors.

KEYWORDS:
3D-CRT, Three Dimensional Conformal Radiation Therapy; AAA, Anisotropic Analytical Algorithm; ACE-27, Adult Comorbidity Evaluation 27; AUC, area under the Receiver Operating Characteristic (ROC) curve; BMI, body mass index; CI, confidence interval; CT, computed tomography; Cc, cubic centimeter; DARS, dysphagia-aspiration-related structures; DESdC, Drinking, Eating, Swallowing difficulties and Coughing when eating/drinking; DVH, dose-volume histogram; Deglutition disorders; Dysphagia-aspiration-related structures; EBRT, external beam radiation therapy; EQD2, equivalent dose in 2Gy fractions; Gy, Gray; HNC, head and neck cancer; Head and neck neoplasms; ICRU, International Commission on Radiation Units and Measurements; IMRT, intensity-modulated radiation therapy; MVA, multivariable logistic regression; N.A, non applicable; OAR, organ-at-risk; OR, odds ratio; PAS, penetration-aspiration scale; PCM, pharyngeal constrictor muscle; PRO, patient-reported outcome; QoL, quality of life; ROC, Receiver Operating Characteristic curve; RT, radiation therapy; Radiation dose; Radiation therapy; SD, standard deviation; SEM, standard error of the mean; SLP, speech-language pathologist; TNM, Tumor location, Nodular engagement, Metastasis; UES, upper esophageal sphincter; UVA, univariable logistic regression; VFS, videofluoroscopy; VMAT, volumetric-modulated radiation therapy; Vx, the volume (%) of a structure receiving ≥xGy.; ρ, Spearman’s Correlation Coefficient

PMID: 31646203 PMCID: PMC6804434 DOI: 10.1016/j.ctro.2019.08.005
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107.
Oncoimmunology. 2019 Jul 19;8(11):e1638207. doi: 10.1080/2162402X.2019.1638207. eCollection 2019.
Enhancing direct cytotoxicity and response to immune checkpoint blockade following ionizing radiation with Wee1 kinase inhibition.
Patel P1, Sun L1, Robbins Y1, Clavijo PE1, Friedman J1, Silvin C2, Van Waes C2, Cook J3, Mitchell J3, Allen C1,4.
Author information
1
Translational Tumor Immunology Program, National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.
2
Tumor Biology Section, National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.
3
Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
4
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Abstract
Tumor cells activate the G2/M cell cycle checkpoint in response to ionizing radiation (IR) and effector immune cell-derived granzyme B to facilitate repair and survival. Wee1 kinase inhibition reverses the ability of tumor cells to pause at G2/M. Here, we hypothesized that AZD1775, a small molecule inhibitor of Wee1 kinase, could sensitize tumor cells to IR and T-lymphocyte killing and improve responses to combination IR and programmed death (PD)-axis immune checkpoint blockade (ICB). Multiple models of head and neck carcinoma, lung carcinoma and melanoma were used in vitro and in vivo to explore this hypothesis. AZD1775 reversed G2/M cell cycle checkpoint activation following IR, inducing cell death. Combination IR and AZD1775 induced accumulation of DNA damage in M-phase cells and was rescued with nucleoside supplementation, indicating mitotic catastrophe. Combination treatment enhanced control of syngeneic MOC1 tumors in vivo, and on-target effects of systemic AZD1775 could be localized with targeted IR. Combination treatment enhanced granzyme B-dependent T-lymphocyte killing through reversal of additive G2/M cell cycle block induced by IR and granzyme B. Combination IR and AZ1775-enhanced CD8+ cell-dependent MOC1 tumor growth control and rate of complete rejection of established tumors in the setting of PD-axis ICB. Functional assays demonstrated increased tumor antigen-specific immune responses in sorted T-lymphocytes. The combination of IR and AZD1775 not only lead to enhanced tumor-specific cytotoxicity, it also enhanced susceptibility to T-lymphocyte killing and responses to PD-axis ICB. These data provide the pre-clinical rationale for the combination of these therapies in the clinical trial setting.

© 2019 Taylor & Francis Group, LLC.

KEYWORDS:
AZD1775; G2/M block; PD-1 immune checkpoint blockade; WEE1 kinase; cell cycle; cytotoxic T lymphocyte; ionizing radiation

PMID: 31646086 PMCID: PMC6791428 [Available on 2020-07-19] DOI: 10.1080/2162402X.2019.1638207
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108.
Biomed Opt Express. 2019 Sep 16;10(10):5198-5206. doi: 10.1364/BOE.10.005198. eCollection 2019 Oct 1.
Enhanced photothermal hemostasis using dual wavelengths in an in vivo leporine kidney model.
Kim SW1, Hwang J2, Xuan J3, Hasenberg T3, Kang HW2,4.
Author information
1
Department of Otolaryngology-Head and Neck Surgery, Kosin University College of Medicine, Busan, South Korea.
2
Interdisciplinary Program of Marine-Bio, Electrical & Mechanical Engineering, Pukyong National University, Busan, South Korea.
3
UroPH R&D, Boston Scientific Corp., San Jose, CA 95134, USA.
4
Department of Biomedical Engineering and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong, National University, Busan, South Korea.
Abstract
The current study investigated the hemostatic effect of dual wavelengths on in vivo leporine kidney tissue using 532-nm and 980-nm laser systems. Three irradiation modes, 532 nm, 980 nm, and dual (532 and 980 nm) modes, were compared to test non-contact photothermal hemostasis on 36 bleeders in the kidney models. Each bleeder was flushed with saline during the irradiation. The dual mode achieved complete hemostasis more rapidly than the single modes (4.0 ± 1.4 s for dual vs. no hemostasis for 532 nm and 10.0 ± 1.3 s for 980 nm; p < 0.001). Application of 60 W from the dual wavelengths expanded the surface area of the thermal lesion (up to 60%). In vivo dual-wavelength irradiation achieved more rapid and complete hemostasis with ∼2 mm coagulation depth than the single-wavelength irradiation.

© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.

PMID: 31646041 PMCID: PMC6788610 DOI: 10.1364/BOE.10.005198
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Select item 31645979
109.
Hum Genome Var. 2019 Aug 30;6:41. doi: 10.1038/s41439-019-0075-5. eCollection 2019.
Rapid screening of copy number variations in STRC by droplet digital PCR in patients with mild-to-moderate hearing loss.
Ito T1, Kawashima Y1, Fujikawa T1, Honda K1, Makabe A1, Kitamura K1,2, Tsutsumi T1.
Author information
1
1Department of Otorhinolaryngology, Tokyo Medical and Dental University, Tokyo, Japan.
2
Department of Otorhinolaryngology, Head and Neck Surgery, Chigasaki Chuo Hospital, Chigasaki, Japan.
Abstract
Copy number variations (CNVs) are commonly reported in STRC, the causal gene for DFNB16. Various techniques are used clinically for CNV detection, and droplet digital PCR (ddPCR) provides highly precise absolute quantification of DNA copy number. We aimed to validate the feasibility and efficiency of ddPCR in combination with long-range PCR (LR-PCR) in identifying CNVs and mutations in STRC. Additionally, we determined the frequency of CNVs and mutations in STRC in Japanese patients with mild-to-moderate hearing loss. We evaluated 84 unrelated Japanese patients with mild-to-moderate bilateral idiopathic or autosomal recessive nonsyndromic sensorineural hearing loss. The ratio of STRC copy number to the copy number of the internal control RPP30 ranged from 0.949 to 1.009 (0.989 ± 0.017) in 77 patients; it ranged from 0.484 to 0.538 (0.509 ± 0.024) in five patients and was 0.000 in two patients, indicating heterozygous and homozygous deletions, respectively. The copy number deletion prevalence rates were 7.7% and 0.9% in the patients and healthy controls, respectively. In combination with LR-PCR, ddPCR revealed that at least three patients (3.6%) had STRC-related hearing loss. Detecting STRC CNVs by ddPCR was rapid, precise, and cost-effective and facilitated the identification of STRC CNVs.

© The Author(s) 2019.

KEYWORDS:
Genetics research; Neurodegenerative diseases

PMID: 31645979 PMCID: PMC6804619 DOI: 10.1038/s41439-019-0075-5
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110.
Hum Genome Var. 2019 Aug 13;6:37. doi: 10.1038/s41439-019-0068-4. eCollection 2019.
Clinical characteristics with long-term follow-up of four Okinawan families with moderate hearing loss caused by an OTOG variant.
Ganaha A#1, Kaname T#2, Yanagi K#2, Tono T#1, Higa T#3, Suzuki M#3.
Author information
1
1Department of Otorhinolaryngology-Head and Neck Surgery, University of Miyazaki, Miyazaki, Japan.
2
2Department of Human Genetics, National Center for Child Health and Development, Tokyo, Japan.
3
3Department of Otorhinolaryngology-Head and Neck Surgery, University of the Ryukyus, Okinawa, Japan.
#
Contributed equally
Abstract
We describe the clinical features of four Japanese families with moderate sensorineural hearing loss due to the OTOG gene variant. We analyzed 98 hearing loss-related genes in patients with hearing loss originally from the Okinawa Islands using next-generation sequencing. We identified a homozygous variant of the gene encoding otogelin NM_001277269(OTOG): c.330C>G, p.Tyr110* in four families. All patients had moderate hearing loss with a slightly downsloping audiogram, including low frequency hearing loss without equilibrium dysfunction. Progressive hearing loss was not observed over the long-term in any patient. Among the three patients who underwent newborn hearing screening, two patients passed the test. OTOG-associated hearing loss was considered to progress early after birth, leading to moderate hearing loss and the later stable phase of hearing loss. Therefore, there are patients whose hearing loss cannot be detected by NHS, making genetic diagnosis of OTOG variants highly useful for complementing NHS in the clinical setting. Based on the allele frequency results, hearing loss caused by the p.Tyr110* variant in OTOG might be more common than we identified. The p.Tyr110* variant was reported in South Korea, suggesting that this variant is a common cause of moderate hearing loss in Japanese and Korean populations.

© The Author(s) 2019.

KEYWORDS:
Diseases; Medical genetics

PMID: 31645975 PMCID: PMC6804730 DOI: 10.1038/s41439-019-0068-4
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Select item 31645882
111.
Ecancermedicalscience. 2019 Jul 29;13:954. doi: 10.3332/ecancer.2019.954. eCollection 2019.
Synchronous peritoneal carcinomatosis from a buccal squamous cell carcinoma: a case report focusing on possible metastatic mechanisms and novel therapeutic modalities.
Fan FS1,2, Yang CF3,4.
Author information
1
Section of Haematology and Oncology, Department of Medicine, Ministry of Health and Welfare Changhua Hospital, 80, Sec. 2, Chung-Jeng Rd, Pu-Shin Township, Chang-Hua County, 51341, Taiwan.
2
https://orcid.org/0000-0002-8123-6941.
3
Department of Pathology, Ministry of Health and Welfare Changhua Hospital, 80, Sec. 2, Chung-Jeng Rd, Pu-Shin Township, Chang-Hua County, 51341, Taiwan.
4
https://orcid.org/0000-0002-7366-4380.
Abstract
A 53-year-old male patient was diagnosed with squamous cell carcinoma of buccal mucosa with synchronous diffuse peritoneal carcinomatosis, a very rare presentation for oral cancer. His disease was highly resistant to intensive systemic chemotherapy and progressed rapidly. So far as we know, there were only five cases with peritoneal involvement by metastatic head and neck cancer reported prior to this patient in the English literature. Immunohistochemistry study revealed that tumour specimens from both oral cavity and peritoneum were negative for tumour necrosis factor alpha and CD24 but positive for CD44 and CD36. These four molecules have been disclosed to be involved in the process of peritoneal metastasis from ovarian cancer. Their roles in the metastatic pathway and possible therapeutic policy targeting at them will be thoroughly discussed.

© the authors; licensee ecancermedicalscience.

KEYWORDS:
CD36; CD44; buccal cancer; metastatic mechanism; peritoneal carcinomatosis; squamous cell carcinoma

PMID: 31645882 PMCID: PMC6759322 DOI: 10.3332/ecancer.2019.954
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Select item 31645603
112.
Sci Rep. 2019 Oct 23;9(1):15198. doi: 10.1038/s41598-019-51599-7.
Combined CT radiomics of primary tumor and metastatic lymph nodes improves prediction of loco-regional control in head and neck cancer.
Bogowicz M1, Tanadini-Lang S2, Guckenberger M2, Riesterer O2.
Author information
1
Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. marta.bogowicz@usz.ch.
2
Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Abstract
Loco-regional control (LRC) is a major clinical endpoint after definitive radiochemotherapy (RCT) of head and neck cancer (HNC). Radiomics has been shown a promising biomarker in cancer research, however closer related to primary tumor control than composite endpoints. Radiomics studies often focus on the analysis of primary tumor (PT). We hypothesize that the combination of PT and lymph nodes (LN) radiomics better predicts LRC in HNC treated with RCT. Radiomics analysis was performed in CT images of 128 patients using Z-Rad implementation (training n = 77, validation n = 51). 285 features were extracted from PT and involved LN. Features were preselected with the maximum relevance minimum redundancy method and the multivariate Cox model was trained using least absolute shrinkage and selection operator. The mixed model was based on the combination of PT and LN radiomics, whereas the PT model included only the PT features. The mixed model showed significantly higher performance than the PT model (p < 0.01), c-index of 0.67 and 0.63, respectively; and better risk group stratification. The clinical nodal status was not a significant predictor in the combination with PT radiomics. This study shows that the LRC can be better predicted by expansion of radiomics analysis with LN features.

PMID: 31645603 PMCID: PMC6811564 DOI: 10.1038/s41598-019-51599-7
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113.
BMJ Case Rep. 2019 Oct 23;12(10). pii: e230768. doi: 10.1136/bcr-2019-230768.
Primary Ewing's sarcoma of the temporal bone: a rare entity and review of the literature.
Vishnoi JR1,2, Kumar V2, Srivastava K3, Misra S4.
Author information
1
Surgical Oncology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India drjvishnoi@gmail.com.
2
Surgical Oncology, King George's Medical University, Lucknow, Uttar Pradesh, India.
3
Radiotherapy, King George's Medical University, Lucknow, Uttar Pradesh, India.
4
Surgical Oncology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.
Abstract
Ewing's sarcoma (ES) is the second most common malignant primary bone tumour in children and adolescents. It primarily affects the diaphysis of long bones and pelvis. ES arising from temporal bone is extremely rare. To date, 43 such cases have been described in the literature. Clinical and radiological features are non-specific. Diagnosis is based mainly on immunohistochemistry. The present article presents an extremely rare case of ES of the temporal bone in a 20-year young man, and he was successfully treated with multiagent chemotherapy and radiotherapy.

© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.

KEYWORDS:
head and neck cancer; head and neck surgery; radiotherapy

PMID: 31645395 DOI: 10.1136/bcr-2019-230768
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Conflict of interest statement
Select item 31645352
114.
Clin Cancer Res. 2019 Oct 23. pii: clincanres.2209.2019. doi: 10.1158/1078-0432.CCR-19-2209. [Epub ahead of print]
Neoadjuvant PD-1 immune checkpoint blockade reverses functional immunodominance among tumor-antigen specific T cells.
Friedman J1, Moore EC2, Zolkind P3, Robbins Y2, Clavijo PE2, Sun L4, Greene S4, Morisada MV5, Mydlarz WK6, Schmitt N7, Hodge JW8, Schreiber H9, Van Waes C10, Uppaluri R11, Allen C12.
Author information
1
National Institute on Deafness and Other Communication Disorders, National Institutes of Health.
2
Head and Neck Surgery Branch, National Institutes of Deafness and Other Communication Disorders, National Institutes of Health.
3
Otolaryngology, Washington University in St. Louis.
4
NIDCD, National Institutes of Health.
5
National Institute on Deafness and Communication Disorders, National Institutes of Health.
6
Otolaryngology - Head and Neck Surgery, Johns Hopkins University School of Medicine.
7
Johns Hopkins University School of Medicine.
8
Laboratory of Tumor Immunology & Biology, National Cancer Institute.
9
Commitee on Cancer Biology, Department of Pathology and Committee on Immunology, University of Chicago.
10
Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH.
11
Head and Neck Surgical Oncology, Dana-Farber/Brigham and Women's Cancer Center.
12
National Institute on Deafness and Other Communication Disorders, National Institutes of Health clint.allen@nih.gov.
Abstract
PURPOSE:
Surgical resection of primary tumor with regional lymphadenectomy remains the treatment of choice for patients with advanced human papillomavirus-negative head and neck squamous cell carcinoma. However, even when pathologic disease-free margins can be achieved, locoregional and/or distant disease relapse remains high. Perioperative immunotherapy may improve outcomes, but mechanistic data supporting the use of neoadjuvant or adjuvant treatment clinically is sparse.

EXPERIMENTAL DESIGN:
Two syngeneic models of oral cavity carcinoma with defined T cell antigens were treated with PD-1 mAb before or after surgical resection of primary tumors, and antigen-specific T cell responses were explored with functional and in vivochallenge assays.

RESULTS:
We demonstrated that functional immunodominance developed among T cells targeting multiple independent tumor antigens. T cells specific for subdominant antigens expressed greater levels of PD-1. Neoadjuvant, but not adjuvant, PD-1 immune checkpoint blockade broke immunodominance and induced T cell responses to dominant and subdominant antigens. Using tumors lacking the immunodominant antigen as a model of antigen escape, neoadjuvant PD-1 immune checkpoint blockade induced effector T cell immunity against tumor cells lacking immunodominant but retaining subdominant antigen. When combined with complete surgical excision, neoadjuvant PD-1 immune checkpoint blockade led to formation of immunologic memory capable of preventing engraftment of tumors lacking the immunodominant but retaining subdominant antigen.

CONCLUSIONS:
Together, these results implicate PD-1 expression by T cells in the mechanism of functional immunodominance among independent T cell clones within a progressing tumor, and support the use of neoadjuvant PD-1 immune checkpoint blockade in patients with surgically resectable carcinomas.

Copyright ©2019, American Association for Cancer Research.

PMID: 31645352 DOI: 10.1158/1078-0432.CCR-19-2209
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115.
Medicine (Baltimore). 2019 Oct;98(42):e16987. doi: 10.1097/MD.0000000000016987.
Tongue base varix as a source of oral bleeding: A case report.
Kim YM1, Kim JW1, Park IS2, Choi JS1.
Author information
1
Department of Otorhinolaryngology-Head and Neck Surgery.
2
Department of Pathology, Inha University School of Medicine, Incheon, Republic of Korea.
Abstract
RATIONALE:
Oral bleeding is usually diagnosed after by referral to other department for the differential diagnosis of hematemesis or hemoptysis. If a patient presents with blood in the oral cavity with no obvious source, generally upper airway, pulmonary, or gastroesophageal lesions are considered likely bleeding foci. The tongue base is an unusual site for laryngopharyngeal varices and only a few cases have been reported.

PATIENT CONCERNS:
Although varix at the tongue base in patients with liver cirrhosis has been rarely described, physicians must consider variceal bleeding from the tongue base when presented with oral bleeding. In such cases, bleeding foci can be identified and controlled by laryngoscopy. We describe the case of a 42-year-old woman complaining of small amount of hemoptysis with variceal bleeding at the tongue base controlled by laryngoscopic excision and cauterization.

DIAGNOSIS:
A diagnosis of tongue base varix was made based on medical history, clinical manifestations, laryngoscopic findings and pathologic features for the patient.

INTERVENTIONS:
The successful laryngoscopic procedures were performed.

OUTCOMES:
The patient has shown no recurrent oral bleeding during follow-up.

LESSONS:
Variceal bleeding in the tongue base is likely to cause serious massive hemorrhage. We need to consider this possibility when presented with a patient with intraoral bleeding but no evidence of hemoptysis or hematemesis.

PMID: 31626079 DOI: 10.1097/MD.0000000000016987
[Indexed for MEDLINE] Free full text
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116.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2019 Sep 7;54(9):717-720. doi: 10.3760/cma.j.issn.1673-0860.2019.09.018.
[The significance and latest progress of extrathyroidal extension of thyroid cancer].
[Article in Chinese; Abstract available in Chinese from the publisher]
Huang L1, Li C1, Wang W1, Cai YC1, Sun RH1, Jiang J1, Zhou YQ1, Shui CY1, Liu W1, Wang X1.
Author information
1
Department of Head and Neck Surgery, Sichuan Cancer Hospital (the Second Renmin Hospital of Sichuan Province, Chengdu 610041, China.
Abstract
Extrathyroidal extension of thyroid cancer has been an important adverse factor affecting the prognosis of patients. According to the latest NCCN (National Comprehensive Cancer Network) guidelines, extrathyroidal extension is the surgical guide fortotal thyroidectomy in newly diagnosed patients, and its incidence in differentiated thyroid cancer is 5%-34%, belonging to T3-T4 stage.In the eighth edition of thyroid cancer AJCC staging, the T3 stage was first divided into T3a (tumor>4 cm and limited to the thyroid) and T3b (gross extrathyroidal extension invading only strap muscles from a tumor of any size), and the "minimal extrathyroidal extension(tumor invasion intoperithyroidal soft tissue or strap muscle invasion)"of the seventh edition was removed from the T stage and changed to the gross extrathyroidal extension invading only strap muscles, but there is still much controversy. It can be seen that different degrees of "extrathyroidal extension" have significant differences in the survival and prognosis of thyroid cancer. This article reviews the latest research progress of extrathyroidal extension, and discusses the significance and clinical research progress of it.

KEYWORDS:
Extrathyroidal extension; Prognosis; Recurrence; Thyroid neoplasms

PMID: 31550771 DOI: 10.3760/cma.j.issn.1673-0860.2019.09.018
[Indexed for MEDLINE]
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Select item 31550770
117.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2019 Sep 7;54(9):712-716. doi: 10.3760/cma.j.issn.1673-0860.2019.09.017.
[Research progress in the establishment of allergic rhinitis mouse model].
[Article in Chinese; Abstract available in Chinese from the publisher]
Ye MY1, Tan GL1.
Author information
1
Department of Otorhinolaryngology Head and Neck Surgery, 3rd Xiangya Hospital, Central South University, Changsha 410013, China.
Abstract
The number of patients with allergic rhinitis (AR) have been increasing in the world. Establishment of AR model in mice is an important method for the study of this disease. However, there is still no consensus standard for the modeling methods, selection of allergens and adjuvants, and evaluation parameter of AR modeling. Here, we introduce the advancement of AR mouse model in recent years from the above, and provide evidence of references for the standardized process of AR mouse model establishment.

KEYWORDS:
Adjuvants, immunologic; Allergens; Mice; Models, animal; Rhinitis, allergic

PMID: 31550770 DOI: 10.3760/cma.j.issn.1673-0860.2019.09.017
[Indexed for MEDLINE]
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Select item 31550769
118.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2019 Sep 7;54(9):708-711. doi: 10.3760/cma.j.issn.1673-0860.2019.09.016.
[The expression and function of acid-sensing ion channels in auditory system and vestibular system].
[Article in Chinese; Abstract available in Chinese from the publisher]
Zhang L1, Xing YZ1, Ye HB1, Shi HB1.
Author information
1
Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Sixth People's Hospital of Shanghai Jiaotong University, Shanghai 200233, China.
Abstract
Acid-sensing ion channels are a class of extracellular H(+) activated cation channels, belonging to the amiloride-sensitive epithelial Na(+) channel/degenerin (ENaC/DEG) superfamily. During extracellular acidification, the channels are activated and produce corresponding action potential. Acid-sensing ion channels are extensively expressed in the peripheral and central nervous system. It plays an important in synaptic plasticity, mechanical sensation, injury sensation related to acidosis of local tissues, acid reception and retinal regulation. This article reviews the expression, biological characteristics and functions of acid-sensing ion channels in cochlea, vestibular tissue and auditory center, so as to improve the understanding of physiology and pathophysiology of auditory system.

KEYWORDS:
Acid-sensing ion channels; Cochlea; Epithelial sodium channel; Vestibule, labyrinth

PMID: 31550769 DOI: 10.3760/cma.j.issn.1673-0860.2019.09.016
[Indexed for MEDLINE]
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Select item 31550759
119.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2019 Sep 7;54(9):676-684. doi: 10.3760/cma.j.issn.1673-0860.2019.09.006.
[The efficacy and safety of salvage surgery for local recurrent nasopharyngeal carcinoma: a systematic review and Meta-analysis].
[Article in Chinese; Abstract available in Chinese from the publisher]
Wang JQ1, Han R2, Li XP2, Zhao YT3, Yu XX3, Wang XW3, Wang K3, Li G2.
Author information
1
Department of Otorhinolaryngology Hend and Neck Surgery, the Third Affiliated Hospital of Southen Medical University, Guangzhou 510360, China.
2
Department of Otorhinolaryngology Head and Neck Surgery, Southen Hospital Affiliated to Southen Medical University, Guangzhou 510515, China.
3
Department of Clinical Medicine, Southen Medical University, Guangzhou 510515, China.
Abstract
Objective: To assess the current evidence regarding the efficacy, safety, and potential advantages of endoscopic compared with open salvage surgery for patients with local recurrent nasopharyngeal carcinoma. Methods: A systematic search of Pubmed/Medline, Embase, and Cochrane databases ranged between 2000 and 2017 was conducted. Included studies reported specific residual or local recurrent nasopharyngeal cancer survival data. Proportional Meta-analysis was performed on both outcomes with a random-effects model and the 95% confidential intervals were calculated by Stata 12.0 software. Results: A total of 24 case series studies were included in the Meta-analysis.The pooled 2-year overall survival rates of endoscopic and open group were 84% (95%CI:72%-93%), 68%(95%CI:59%-77%),respectively.The pooled 2-year disease-free survival rates of endoscopic and open group were 68%(95%CI:53%-81%), 65%(95%CI:54%-75%),respectively. The pooled 5-year overall survival rates of endoscopic and open group were 72%(95%CI:37%-97%), 48% (95%CI:40%-56%),respectively.The pooled 5-year disease-free survival rates of endoscopic and open group were 65%(95%CI:29%-93%), 50%(95%CI:43%-57%),respectively.The combined outcome of endoscopic was higher than open procedure. In addition, less severe complications, lower local recurrence rates(27%vs32%).The 2-year overall survival rates of endoscopic was higher than open procedure in the staging of rT1, rT2, and rT3 (93%vs87%; 77%vs63%; 67%vs53%) , but was equal to open in the staging for rT4 (35%vs35%) .Meta-regression showed that the heterogeneity was correlated with advanced tumor ratio. Conclusions: The present Meta-analysis reveals that endoscopic approach offers a safe and efficient alternative to open approach with better short-term outcome and fewer postoperative complications in selecting patients strictly.

KEYWORDS:
Endoscopic surgery; Meta-analysis; Nasopharyngeal neoplasms; Salvage surgery

PMID: 31550759 DOI: 10.3760/cma.j.issn.1673-0860.2019.09.006
[Indexed for MEDLINE]
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120.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2019 Sep 7;54(9):662-669. doi: 10.3760/cma.j.issn.1673-0860.2019.09.004.
[Clinical study of postoperative adjuvant radiotherapy and postoperative concurrent chemoradiotherapy for locally advanced hypopharyngeal squamous cell carcinoma].
[Article in Chinese; Abstract available in Chinese from the publisher]
Liu K1, Zhang XX1, Liu MB1, Wang JL1, Wu WM1, Huang DL1, Zhao JD1, Ma L2.
Author information
1
Department of Otorhinolaryngology Head and Neck Surgery, Chinese People's Liberation Army General Hospital, Medical School of Chinese People's Liberation Army, Beijing 100853, China.
2
Department of Radiotherapy, Chinese People's Liberation Army General Hospital, Medical School of Chinese People's Liberation Army, Bejing 100853, China.
Abstract
Objective: Using propensity score matching method (PSM) to investigate the clinical effect of postoperative adjuvant radiotherapy and postoperative concurrent chemoradiotherapy for locally advanced hypopharyngeal squamous cell carcinoma. Methods: From July 2007 to July 2018,174 postoperative patients with locally advanced hypopharyngeal squamous cell carcinoma were enrolled in pre-PSM cohort, including 168 males and 6 females, the median age was 60 years old (ranged from 37 to 79 years old).Loco-regional control (LRC),progression-free survival (PFS) and overall survival (OS) were compared and analyzed between the patients treated with postoperative adjuvant radiotherapy and postoperative concurrent chemoradiotherapy (cisplatin was given in a dose of 80 mg/m(2) on days 1, 22, and 43). After the propensity score matching (PSM), 61 sub-pairs of 122 patients were generated in post-PSM cohort. Survival rate were assessed with Kaplan-Meier method and Log-rank test. Results: After the propensity score matching(PSM), 61 sub-pairs of 122 patients were generated in post-PSM cohort.The patients were followed up for 3-135 months, the median follow-up was 42 months. No significant differences in 3-year and 5-year LRC, PFS, OS were observed between the two groups (P>0.05) . For postoperative patients who had high-risk factors (extracapsular extension of nodal disease, and/or vascular embolism, and/or lymph node metastasis≥2, and/or positive surgical margin, and/or perineural infiltration),there were significant differences between the two groups in 3-year PFS (60.99% vs 84.49%,P<0.05), 5-year PFS (35.47% vs 56.97%,P<0.05) and 5-year LRC (41.02% vs 68.50%, P<0.05), but no significant difference was found in OS between the two groups (P>0.05). Conclusion: Postoperative concurrent chemoradiotherapy was more efficacious than postoperative radiotherapy alone in terms of loco-regional control and PFS for high-risk postoperative patients with locally advanced hypopharyngeal squamous cell carcinoma.

KEYWORDS:
Carcinoma, squamous cell; Chemoradiotherapy, adjuvant; Neoplasm staging; Radiotherapy; Survival rate

PMID: 31550757 DOI: 10.3760/cma.j.issn.1673-0860.2019.09.004