Experiences and preferences of patients visiting a head and neck oncology outpatient clinic: a qualitative study.

The objective of this study is to report on an in-depth evaluation of patient experiences and preferences at a Head and Neck Oncology outpatient clinic. A qualitative research design was used to determine the experiences and preferences of Head and Neck Cancer patients in an Oncology Outpatient Clinic, Maastricht University Medical Center, The Netherlands. Head and Neck Cancer Patients, treated for at least 6 months at the Oncology Clinic, were included. A qualitative research design with patient interviews was used. All interviews were recorded and transcribed verbatim to increase validity. Analysis was done with use of the template approach and qualitative data analysis software. Three of the six dimensions predominated in the interview: (1) respect for patients' values, preferences and expressed need, (2) information, communication and education and (3) involvement of family and friends. The dimensions physical comfort; emotional support; coordination and integration of care were considered to be of less significance. The findings from this study resulted in a deeper understanding of patients' experiences and preferences and can be useful in the transition towards a more patient-centered approach of health care.

Differentiating head and neck carcinoma from lung carcinoma with an electronic nose: a proof of concept study.

Disease specific patterns of volatile organic compounds can be detected in exhaled breath using an electronic nose (e-nose). The aim of this study is to explore whether an e-nose can differentiate between head and neck, and lung carcinoma. Eighty-seven patients received an e-nose measurement before any oncologic treatment. We used PARAFAC/TUCKER3 tensor decomposition for data reduction and an artificial neural network for analysis to obtain binary results; either diagnosed as head and neck or lung carcinoma. Via a leave-one-out method, cross-validation of the data was performed. In differentiating head and neck from lung carcinoma patients, a diagnostic accuracy of 93 % was found. After cross-validation of the data, this resulted in a diagnostic accuracy of 85 %. There seems to be a potential for e-nose as a diagnostic tool in HNC and lung carcinoma. With a fair diagnostic accuracy, an e-nose can differentiate between the two tumor entities.

Can Epstein-Barr virus DNA load in nasopharyngeal brushings or whole blood predict recurrent nasopharyngeal carcinoma in a non-endemic region? A prospective nationwide study of the Dutch Head and Neck Oncology Cooperative Group.

This study estimated the value of quantitative measurements of EBV markers in the clinical management of nasopharyngeal carcinoma in a non-endemic area. The aim was to predict prognosis and detect recurrent and residual disease. In 72 patients, EBV DNA load in blood and nasopharyngeal brushes, and IgA VCA-p18 and EBNA1 in plasma were measured at different time points. At diagnosis and post-treatment, a cut-off value was used for detecting disease [positive (PPV) and negative (NPV) predictive value]. The markers were correlated as a continuous variable with tumor stage, disease-free survival (DFS) and overall survival (OS). The Cox hazard ratio model assessed hazard ratios. At diagnosis, the markers were above the COV in 45, 92, 85 and 83 % of the patients, respectively. Post-treatment, DNA load test in blood and brush had the best discriminating power (blood DNA load test: PPV 39 % and NPV 97 %, brush for local disease: PPV 75 % and NPV 99 %). Post-treatment, DNA load in blood was the best predictor for OS and DFS [hazard ratio 3.2 (95 % CI 1.51-3.5) and 2.3 (95 % CI 1.72-5.8)]. Assessing the EBV DNA load in blood has significant prognostic value, although the clinical value is for discussion. The EBV DNA load in the brush might improve early detection of local failures post-treatment.

Cost-Effectiveness of Reduced Waiting Time for Head and Neck Cancer Patients due to a Lean Process Redesign.

BACKGROUND: Compared with new technologies, the redesign of care processes is generally considered less attractive to improve patient outcomes. Nevertheless, it might result in better patient outcomes, without further increasing costs. Because early initiation of treatment is of vital importance for patients with head and neck cancer (HNC), these care processes were redesigned. OBJECTIVES: This study aimed to assess patient outcomes and cost-effectiveness of this redesign. METHODS: An economic (Markov) model was constructed to evaluate the biopsy process of suspicious lesion under local instead of general anesthesia, and combining computed tomography and positron emission tomography for diagnostics and radiotherapy planning. Patients treated for HNC were included in the model stratified by disease location (larynx, oropharynx, hypopharynx, and oral cavity) and stage (I-II and III-IV). Probabilistic sensitivity analyses were performed. RESULTS: Waiting time before treatment start reduced from 5 to 22 days for the included patient groups, resulting in 0.13 to 0.66 additional quality-adjusted life-years. The new workflow was cost-effective for all the included patient groups, using a ceiling ratio of €80,000 or €20,000. For patients treated for tumors located at the larynx and oral cavity, the new workflow resulted in additional quality-adjusted life-years, and costs decreased compared with the regular workflow. The health care payer benefited €14.1 million and €91.5 million, respectively, when individual net monetary benefits were extrapolated to an organizational level and a national level. CONCLUSIONS: The redesigned care process reduced the waiting time for the treatment of patients with HNC and proved cost-effective. Because care improved, implementation on a wider scale should be considered.

Feasibility of a Portable Electronic Nose for Detection of Oral Squamous Cell Carcinoma in Sudan.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is increasing at an alarming rate particularly in low-income countries. This urges for research into noninvasive, user-friendly diagnostic tools that can be used in limited-resource settings. This study aims to test and validate the feasibility of e-nose technology for detecting OSCC in the limited-resource settings of the Sudanese population. METHODS: Two e-nose devices (Aeonose™, eNose Company, Zutphen, The Netherlands) were used to collect breath samples from OSCC (n = 49) and control (n = 35) patients. Patients were divided into a training group for building an artificial neural network (ANN) model and a blinded control group for model validation. The Statistical Package for the Social Sciences (SPSS) software was used for the analysis of baseline characteristics and regression. Aethena proprietary software was used for data analysis using artificial neural networks based on patterns of volatile organic compounds. RESULTS: A diagnostic accuracy of 81% was observed, with 88% sensitivity and 71% specificity. CONCLUSIONS: This study demonstrates that e-nose is an efficient tool for OSCC detection in limited-resource settings, where it offers a valuable cost-effective strategy to tackle the burden posed by OSCC.

Detecting head and neck squamous carcinoma using a portable handheld electronic nose.

INTRODUCTION: Detecting volatile organic compounds in exhaled breath enables the diagnosis of cancer. We investigated whether a handheld version of an electronic nose is able to discriminate between patients with head and neck squamous cell cancer (HNSCC) and healthy controls. METHODS: Ninety-one patients with HNSCC and 72 controls exhaled through an e-nose. An artificial neural network based model was built to separate between HNSCC patients and healthy controls. Additionally, three models were created for separating between the oral, oropharyngeal, and glottic subsites respectively, and healthy controls. RESULTS: The results showed a diagnostic accuracy of 72% at a sensitivity of 79%, specificity of 63%, and area under the curve (AUC) of 0.75. Results for the subsites showed an AUC of 0.85, 0.82, and 0.83 respectively for oral, oropharyngeal, and glottic HNSCC. CONCLUSION: This feasibility study showed that this portable noninvasive diagnostic tool can differentiate between HNSCC patients and healthy controls.

Detecting recurrent head and neck cancer using electronic nose technology: A feasibility study.

BACKGROUND: The aim of this feasibility study was to assess the diagnostic performance of an electronic nose (e-nose) as a noninvasive diagnostic tool in detecting locoregional recurrent and/or second (or third) primary head and neck squamous cell carcinoma (HNSCC) after curative treatment. METHODS: Using an e-nose (Aeonose, The eNose Company, Zutphen, The Netherlands), breath samples were collected from patients after curative treatment of an HNSCC with a locoregional recurrence or second (or third) primary tumor (N = 20) and from patients without evidence of recurrent disease (N = 20). Analyses were performed utilizing artificial neural networking based on patterns of volatile organic compounds. RESULTS: A diagnostic accuracy of 83% was observed in differentiating follow-up patients with locoregional recurrent or second (or third) primary HNSCC from those without evidence of disease. CONCLUSION: This study has demonstrated the feasibility of using an e-nose to detect locoregional recurrent and/or second (or third) primary HNSCC.

Gene expression profiles of head and neck carcinomas from Sudanese and Norwegian patients reveal common biological pathways regardless of race and lifestyle.

PURPOSE: To explore possible range of gene expression profiles in head and neck squamous cell carcinomas (HNSCC) and pairwised normal controls from Sudanese (n = 72) and Norwegian (n = 45) patients using a 15K cDNA microarray and to correlate the findings with clinicopathologic variables. EXPERIMENTAL DESIGN: Samples from Sudan were grouped according to anatomic location/patients' habit of toombak (snuff) use, and 37 pools of 2 to 11 tumors matched to 37 pools of their normal controls from the same patients, respectively, were prepared. For Norway, eight pools of 3 to 11 tumors matched to eight pools of their normal controls from the same patients, respectively, were prepared according to anatomic location. Pools (n = 45) were hybridized to microarrays. For controls, 33 of the pools were hybridized against Human Reference RNA. Scanned array images were recorded, and data analysis was done in groups. For verification, results for selected genes were analyzed using quantitative real-time PCR/immunohistochemistry. RESULTS: We identified 136 genes from Sudan and 154 from Norway as differentially expressed between tumors and controls. Changes of the genes found were confirmed in >70% of the pools by hybridization against Reference RNA. Seventy-three genes and three main pathways (signal transduction, cell communication, and ligand-receptor interaction) were of relevance to the HNSCCs from both countries. Hierarchical clustering of the 73 genes identified subclasses of mixed tumors from the two populations, two independent subgroups for Norwegian tumors by their anatomic sites, and five subgroups for Sudanese tumors by their toombak habits. Quantitative real-time PCR/immunohistochemistry validated the microarray-based data. CONCLUSIONS: Differences in gene expression between tumor and nontumor tissues were identified in HNSCCs. Analysis of the two population groups revealed a common set of 73 genes within three main biological pathways. This indicates that the development of HNSCCs is mediated by similar biological pathways regardless of differences related to race, ethnicity, lifestyle, and/or exposure to environmental carcinogens. Of particular interest, however, was the valuable association of gene expression signature found with toombak use and anatomic site of the tumors.

Tumour-associated macrophages secrete IL-6 and MCP-1 in head and neck squamous cell carcinoma tissue.

Conclusion. Tumour-associated macrophages (TAMs) in head and neck squamous cell carcinomas (HNSCCs) secrete interleukin 6 (IL-6) and monocyte chemotactic protein (MCP-1) that can be down-regulated by L-leucine-methylester (LLME); however, there is no qualitative difference between function of TAMs and tissue macrophages in mucosa as measured by IL-6 and MCP-1 secretion. Objectives. TAMs play an important role in the interaction with tumour cells in malignant tumours. The cells in the tumours that are the main sources of the various signal substances need to be further elucidated. The aim of this investigation was to reveal whether TAMs in HNSCCs secrete IL-6 and MCP-1. These cytokines influence tumour cell growth and macrophage influx in tumours, respectively. Materials and methods. In order to inhibit macrophage function in F-spheroids, in some experiments the tissue fragments were initially incubated with LLME, a substance that selectively inhibits function of phagocytes. IL-6 and MCP-1 secretion from untreated F-spheroids was compared to cytokine secretion from LLME-treated F-spheroids as measured by ELISA. Results. LLME did not affect the viability of F-spheroids and reduced IL-6 and MCP-1 secretion from monocyte-derived macrophages in vitro. F-spheroids from LLME-treated tissue fragments showed lower IL-6 and MCP-1 secretion compared with F-spheroids from tissue fragment untreated with LLME.

Head and neck squamous cell carcinoma spheroid- and monocyte spheroid-stimulated IL-6 and monocyte chemotactic protein-1 secretion are related to TNM stage, inflammatory state and tumor macrophage density.

Monocyte fragment (F)-spheroid-stimulated and F-spheroid IL-6 and monocyte chemotactic protein (MCP)-1 secretion are related to inflammatory state, macrophage density and the TNM stage of patients with head and neck squamous cell carcinoma (HNSCC). Fragment (F)-spheroids from HNSCC patients in vitro secrete and stimulate autologous monocytes to secrete IL-6 and MCP-1. The aim of this investigation was to study this cytokine secretion in relation to other cytokines, spheroid composition and host factors.In series I (n=14) the densities of epithelial cells, fibroblasts and macrophages were determined in sections from F-spheroids and donor tissue. In series II (n=17) the TNM stage, donor inflammatory state, macrophage density and the secretion of F-spheroid- and monocyte F-spheroid-stimulated IL-6, MCP-1 and tumor necrosis factor (TNF)-alpha were determined. Epithelial cells were partly replaced by interstitial tissue during spheroid formation. Malignant (M) F-spheroids secreted more MCP-1 than benign (B) F-spheroids. No F-spheroid secreted measurable amounts of TNF-alpha. Monocytes secreted more IL-6 when co-cultured with MF- compared to BF-spheroids. Monocyte IL-6 MF- and MCP-1 MB-spheroid-stimulated secretion correlated with macrophage density. In addition, there was an association between MF- and BF-spheroid-stimulated monocyte cytokine secretion, as well as between BF- and MF-spheroid-stimulated MCP-1 secretion. An inverse relation was also noted between the erythrocyte sedimentation rate at monocyte harvest and the monocyte MCP-1 F-spheroid responses.

Supracricoid laryngectomy and dysphagia: A systematic literature review.

OBJECTIVES/HYPOTHESIS: Perform a systematic literature search to provide an overview of today's literature regarding the different aspects that can cause dysphagia after supracricoid laryngectomy. STUDY DESIGN: A systematic literature review. REVIEW METHODS: The inclusion criteria were laryngeal cancer, supracricoid laryngectomy, and swallowing. Thirty-one qualifying articles were included and analyzed describing swallowing after supracricoid laryngectomy. RESULTS: Included studies examined the incidence of dysphagia and discussed various factors that will or will not contribute to dysphagia after supracricoid laryngectomy, type of reconstruction, swallow training, radiation, arytenoid cartilage resection, extended procedures, and age. CONCLUSION: A high incidence of dysphagia was reported after supracricoid laryngectomy. However, good recovery rates were observed with low incidence of severe complications. The included studies used different methods and standards to start oral intake, remove the nasogastric feeding tube, and observe swallow function. Homogenous study population and standardized guidelines on how to handle the pre- and postoperative course after supracricoid laryngectomy and how to measure swallow function could improve further research.

Determinants of treatment waiting times for head and neck cancer in the Netherlands and their relation to survival.

INTRODUCTION: Waiting to start treatment has been shown to be associated with tumor progression and upstaging in head and neck squamous cell carcinomas (HNSCCs). This diminishes the chance of cure and might lead to unnecessary mortality. We investigated the association between waiting times and survival in the Netherlands and assessed which factors were associated to longer waiting times. METHODS: Patient (age, sex, socioeconomic status (SES), tumor (site, stage) and treatment (type, of institute of diagnosis/treatment) characteristics for patients with HNSCC who underwent treatment were extracted from the Netherlands Cancer Registry (NCR) for 2005-2011. Waiting time was defined as the number of days between histopathological diagnosis and start of treatment. Univariable and multivariable Cox regression was used to evaluate survival. RESULTS: In total, 13,140 patients were included, who had a median waiting time of 37days. Patients who were more likely to wait longer were men, patients with a low SES, oropharynx tumors, stage IV tumors, patients to be treated with radiotherapy or chemoradiation, and patients referred for treatment to a Head and Neck Oncology Center (HNOC) from another hospital. The 5-year overall survival was 58% for all patients. Our multivariable Cox regression model showed that longer waiting time, was significantly related to a higher hazard of dying (p<0.0001). CONCLUSION: This is the first large population-based study showing that longer waiting time for surgery, radiotherapy or chemoradiation is a significant negative prognostic factor for HNSCC patients.

Peripheral blood monocyte and T-lymphocyte activation levels at diagnosis predict long-term survival in head and neck squamous cell carcinoma patients.

This study was performed to determine whether peripheral blood (PB) monocyte and/or lymphocyte activation at diagnosis were associated with long-term prognosis in patients with head and neck squamous cell carcinoma (HNSCC), and to what extent such prognostic properties relate to human papilloma virus (HPV)-associated tumor infection of the included patients. This was a long-term prospective study describing patient survival in relation to PB T lymphocyte and monocyte activation in patients observed for up to 14 years following diagnosis. Sixty-four patients from a consecutive cohort of newly diagnosed HNSCC patients along with 16 non-cancer control patients were included over a period of almost 2 years. Monocyte responsiveness was assessed at diagnosis (N = 56 HNSCC/16 non-cancer controls) by measuring net levels of spontaneous vs lipopolysaccharide-induced monocyte chemotactic protein (MCP)-1 secretion in vitro. PB T lymphocyte activation was determined (N = 58 HNSCC/16 controls) by measuring the percentage of T cells expressing CD69 by flow cytometry. Whether HPV infection or not was determined by PCR analysis on formalin fixed paraffin-embedded tumor tissue. Tumor HPV-positive patients had better prognosis than HPV-negative patients. A low net MCP-1 response in monocytes predicted increased survival (Relative risk (RR) = 2.1; Confidence interval (CI): 1.1-4.0; p < 0.05). A low percentage of CD69 positive T lymphocytes also predicted better prognosis (RR = 2.6; CI: 1.3-5.0; p = 0.005). The predictive power of MCP-1 monocyte and CD69 T lymphocyte measures were retained when adjusted for age and gender of the patients and shown to be independent of each other (N = 50 HNSCC/16 controls). The results were similar in HPV tumor-positive and -negative patients. Patients with high monocyte- and/or T lymphocyte activation status had low survival with 8% 5 year overall survival (OS) compared to 65% 5 year OS for patients with dual low activation levels (RR = 0.27; CI: 0.14-0.56; p < 0.001), mostly secondary to disease-specific survival. Both tumor HPV-positive and -negative HNSCC patients with high percentage of CD69 positive T lymphocytes and/or high monocyte MCP-1 secretion had low long-term survival. The data suggest that the general inflammatory and adaptive immune systems are independently linked to the clinical aggressiveness of both tumor HPV-negative and -positive HNSCC patients.

Application of an electronic nose in the diagnosis of head and neck cancer.

OBJECTIVES/HYPOTHESIS: Electronic nose (E-nose) technology has various applications such as the monitoring of air quality and the detection of explosive and chemical agents. We studied the diagnostic accuracy of volatile organic compounds (VOC) pattern analysis in exhaled breath by means of an E-nose in patients with head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Cohort study. Exhaled breath samples from patients with HNSCC were analyzed by using an E-Nose. METHODS: Thirty-six patients diagnosed with HNSCC exhaled into a 5-litre Tedlar bag. The control group consisted of 23 patients visiting the outpatient clinic for other (benign) conditions. Air samples were analyzed using an E-nose. RESULTS: Logistic regression showed a significant difference (P < 0.05) in VOC resistance patterns between patients diagnosed with HNSCC and the control group, with a sensitivity of 90% and a corresponding specificity of 80%. CONCLUSIONS: E-nose application holds a promising potential for application in the diagnosis of HNSCC due to its rapid, simple, and noninvasive nature. LEVEL OF EVIDENCE: 3b.

The expression of estrogen and progesterone receptors in the human larynx.

OBJECTIVES: The human female voice changes in quality during the menstrual cycle and during pregnancy and menopause. The underlying pathophysiological mechanisms are as yet not known. The aim of this study, therefore, was to evaluate the existence of estrogen receptors (ERs) and progesterone receptors (PRs) in the human vocal fold. MATERIAL AND METHODS: Biopsies of benign vocal fold lesions from 37 female patients were obtained during surgery. Immunohistochemistry for expression of ERs and PRs was performed and evaluated on a semiquantitative scale by two independent pathologists. RESULTS: In series 1, immunohistochemical staining showed six sections positive for ER and three sections for PR. One section had positive staining for both receptors. In series 2, immunohistochemical staining showed 10 of the 15 edema biopsies were positive for ER and six for PR. Six biopsies expressed both receptors. Four of the 10 laryngocele biopsies were positive for ER and two for PR. One was positive for both receptors. CONCLUSION: Our study demonstrates that ERs and PRs are expressed in the larynx of the female human vocal fold in conjunction with edema. The function of these receptors has to be elucidated in future studies.

Laryngeal tuberculosis presenting as a supraglottic carcinoma: a case report and review of the literature.

INTRODUCTION: Laryngeal tuberculosis used to be a common complication in advanced pulmonary tuberculosis. However, it has become a rare occurrence in developed countries since the introduction of antituberculous agents. Moreover, the pattern of the disease has changed over the years. Nowadays, it more closely resembles a laryngeal carcinoma than any other laryngeal illness. CASE PRESENTATION: We describe the case of a 50-year-old Caucasian man who presented with the clinical picture of laryngeal cancer, but which turned out to be tuberculosis. We illustrate the difficulty of recognizing laryngeal tuberculosis both clinically and even with radiological examination. CONCLUSION: Although laryngeal tuberculosis is uncommon, especially in developed countries, it still occurs and should be considered as a differential diagnosis in any laryngeal disease, in particular in the case of a laryngeal carcinoma.

Viable head and neck tumor spheroids stimulate in vitro autologous monocyte MCP-1 secretion through soluble substances and CD14/lectin-like receptors.

Biopsies from carcinoma tissue and benign control mucosa from head and neck squamous cell carcinoma (HNSCC) patients were used to establish fragment (F)-spheroids in vitro. We have previously shown that autologous monocytes co-cultured with F-spheroids in vitro augment their secretion of monocyte chemotactic protein-1 (MCP-1). Presently, the aims of the present work were to study whether the metabolic activity, secreted products and/or specific receptor/ligand on the surface of the F-spheroids and monocytes are necessary for stimulation of the monocyte MCP-1 secretion upon F-spheroid co-culture. Actinomycin D (1 mug/ml for 24 h) pre-treatment of the F-spheroids abolished the monocyte MCP-1 co-culture response. Co-culture of monocytes and F-spheroids separated by a semi-permeable membrane showed a decreased, but still present, monocyte MCP-1 co-culture response. Conditioned medium from F-spheroids stimulated allogenous monocytes to secrete MCP-1. The addition of glucose or galactose, but not mannose, to co-cultures partially inhibited the monocyte MCP-1 co-culture response. The addition of anti-CD14 antibody diminished the MCP-1 co-culture response. In conclusion, the monocyte MCP-1 co-culture response is dependent on metabolically active spheroids, secreted stimuli, and is augmented by direct contact with F-spheroids, possibly via lectin-like receptors and the CD14 receptor.