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OBJECTIVE: To develop and test the prototypes of a novel post-laryngectomy rehabilitation tool incorporating an obligatory, disposable heat and moisture exchanger (HME) and a reusable, multi-magnet automatic speaking valve (ASV). MATERIAL AND METHODS: The study subjects comprised 20 laryngectomized individuals (15 males, 5 females), 5 of whom were already using an ASV and 15 who were not. Three successive prototypes were tested. Data were collected by means of structured questionnaires, considering for example patient compliance, skin adhesion, voicing and coughing aspects, and voice and speech quality assessments, assessing for example maximum phonation time and dynamic loudness range. RESULTS: Of the 15 non-ASV users, 5 did not comply with the study due to peristomal skin adhesion problems. Of the remaining 15 patients, all 5 ASV users and 6/10 non-users were fully compliant with the new device. The cough-relief valve of the new device functions properly, as does the valve position adjustment for physical exertion. With this new device the maximum phonation time was longer than with a regular ASV (15.2 vs 11.6 s; p = 0.006) and the dynamic range was larger (33.0 vs 24.8 dB; p < 0.001). CONCLUSION: The test results obtained with this new device show that its advanced features (obligatory HME and multi-magnet valve systems) offer additional benefits for further improving vocal and pulmonary rehabilitation after total laryngectomy

Purpose: Predominant causes of head and neck cancer recurrence after radiotherapy are rapid repopulation, hypoxia, fraction of cancer stem cells, and intrinsic radioresistance. Currently, intrinsic radioresistance can only be assessed by ex vivo colony assays. Besides being time-consuming, colony assays do not identify causes of intrinsic resistance. We aimed to identify a biomarker for intrinsic radioresistance to be used before start of treatment and to reveal biologic processes that could be targeted to overcome intrinsic resistance. Experimental Design: We analyzed both microRNA and mRNA expression in a large panel of head and neck squamous cell carcinoma (HNSCC) cell lines. Expression was measured on both irradiated and unirradiated samples. Results were validated using modified cell lines and a series of patients with laryngeal cancer. Results: miRs, mRNAs, and gene sets that correlated with resistance could be identified from expression data of unirradiated cells. The presence of epithelial-to-mesenchymal transition (EMT) and low expression of miRs involved in the inhibition of EMT were important radioresistance determinants. This finding was validated in two independent cell line pairs, in which the induction of EMT reduced radiosensitivity. Moreover, low expression of the most important miR (miR-203) was shown to correlate with local disease recurrence after radiotherapy in a series of patients with laryngeal cancer. Conclusions: These findings indicate that EMT and low expression of EMT-inhibiting miRs, especially miR-203, measured in pretreatment material, causes intrinsic radioresistance of HNSCC, which could enable identification and treatment modification of radioresistant tumors. Clin Cancer Res; 21(24); 5630–8. ©2015 AACR.

Background Management of the N0 neck in patients with head and neck squamous cell carcinoma (SCC) remains controversial. We describe the outcome of patients who underwent transoral tumor excision and a wait-and-see policy for the neck staged N0 by ultrasonography-guided cytology (USgFNAC). Because selection of lymph nodes for USgFNAC is currently based on size criteria, we investigated the additional value of sentinel node (SN) identification. Methods The outcome of 161 patients with T1–T2 oral/oropharyngeal SCC was determined. In a subgroup of 39 patients the SN was identified and aspirated in addition. Results SN identification and aspiration was possible in 38 of 39 patients but without decreasing the false-negative rate of USgFNAC. During follow-up (12–99 months) 34 of 161 (21%) patients developed lymph node metastases. After therapeutic neck dissection and postoperative radiotherapy, 27 of 34 (79%) could be salvaged (88% regional control). Conclusions Wait-and-see seems justified in case of negative USgFNAC. Strict follow-up with USgFNAC is required. SN identification and aspiration is feasible but did not improve lymph node selection. © 2002 Wiley Periodicals, Inc. Head Neck 24: 282–289, 2002; DOI 10.1002/hed.10018

In total, 10-30% of patients with head and neck squamous cell carcinoma (HNSCC) develop local recurrences despite seemingly adequate tumour resection. This may result from minimal residual cancer (MRC): small numbers of tumour cells left behind in the surgical margins, undetectable by routine histopathology. In recent studies, p53 mutations have been considered as selective and sensitive DNA markers of cancer cells. There are two potential problems in using mutated-p53 DNA as a marker. Firstly, p53 mutations occur early in progression and might therefore detect unresected precursor lesions besides tumour cells. Secondly, DNA is a very stable biomolecule that might lead to false-positive results. These two potential problems have been evaluated in this study. Fifty patients with a radical tumour resection were included, of whom 30 showed a p53 mutation in the primary tumour. Histopathologically tumour-free surgical margins were quantitatively analysed for mutated p53 by molecular diagnosis (plaque assay) and subsequent (immuno)histopathology. p53 mutated DNA was detected in the surgical margins of 19/30 patients. Immunohistochemistry confirmed the presence of small tumour foci in 2/19 mutated p53-positive cases. In 7/19 cases, the tumour-specific p53 mutation was found in unresected dysplastic mucosal precursor lesions. Moreover, in a number of cases small p53-immunostained patches were detected, but the mutations found were never tumour-related. By screening contralateral exfoliated cells and plaque assays on RNA it was shown that detection of mutated-p53 DNA is prone to false-positive results. In conclusion, using p53 mutations as a marker, both MRC and unresected mutated p53-positive mucosal precursor lesions are detected within surgical margins. Molecular assessment of surgical margins using p53 mutations enables the selection of HNSCC patients at high risk for tumour recurrence, but tumour RNA seems at present to be a more specific biomolecule for analysis than tumour DNA.

Imaging is playing a major role in the assessment of cervical lymphadenopathy. In infectious disease, the assessment of abscess formation and the relation of the abscess to surrounding vital structures is crucial for its management. In head and neck malignancies, imaging can be helpful for staging. Imaging of the neck for the assessment of nodal metastases can be used to detect occult metastases or to assess operability of palpable metastases. The detection of small occult metastases has limitations, as micrometastases cannot be depicted; however, imaging can fulfill a role in diminishing the risk of occult metastases, and thus influence management. For this purpose a very sensitive technique is necessary. The currently used radiological criteria are not sensitive enough to accomplish enough reduction of the risk of occult metastases; therefore, more sensitive CT and MRI criteria, but especially ultrasound-guided aspiration, should be employed to assess the clinically negative neck.

The purpose of this study was to determine time trends for primary treatment modalities in advanced laryngeal cancer, overall survival (OS), and laryngectomy-free interval (LFI) over the last 2 decades in The Netherlands.We conducted an analysis of T3 to T4 laryngeal cancer data from 2 combined national (population-based and pathology-based) cancer registries.A total of 2072 T3 cases (14.7%) and 1722 T4 cases (12.2%) were identified. Total laryngectomy as primary treatment modality decreased, whereas radiotherapy (RT) increased. For T3 disease, 5-year OS after primary total laryngectomy (+/- adjuvant RT), RT, and chemoradiotherapy (CRT) was 49%, 47%, and 45%, respectively. For T4 disease, this was 48%, 34%, and 42% (overall p .0001), respectively. Five-year LFI for T3 disease was 81% (RT) and 77% (CRT), and for T4 disease it was 81% and 87%, respectively.From 1991 to 2010 total laryngectomy as primary treatment modality for advanced laryngeal cancer decreased and RT increased. T3 disease showed similar survival rates for all primary treatment modalities. For T4 disease, total laryngectomy (+ adjuvant RT) showed the best survival. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1247-E1255, 2016.

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 37 days. 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 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. (C) 2014 Elsevier Ltd. All rights reserved.

Background: Breathing through a tracheostoma results in insufficient warming and humidification of the inspired air. This loss of air conditioning, especially humidification, can be partially restored with the application of a heat and moisture exchanger (HME) over the tracheostoma. For medical professionals, it is not easy to judge differences in water exchange performance of various HMEs owing to the lack of universal outcome measures. This study has three aims: assessment of the water exchange performance of commercially available HMEs for laryngectomized patients, validation of these results with absolute humidity outcomes, and assessment of the role of hygroscopic salt present in some of the tested HMEs. Methods: Measurements of weight and absolute humidity at end inspiration and end expiration at different breathing volumes of a healthy volunteer were performed using a microbalance and humidity sensor. Twenty-three HMEs from 6 different manufacturers were tested. Associations were determined between core weight, weight change, breathing volume, and absolute humidity, using both linear and nonlinear mixed effects models. Results: Water exchange of the 23 HMEs at a breathing volume of 0.5 L varies between 0.5 and 3.6 mg. Both water exchange and wet core weight correlate strongly with the end-inspiratory absolute humidity values (r2 = 0.89/0.87). Hygroscopic salt increases core weight. Conclusions: The 23 tested HMEs for laryngectomized patients show wide variation in water exchange performance. Water exchange correlates well with the end-inspiratory absolute humidity outcome, which validates the ex vivo weight change method. Wet core weight is a predictor of HME performance. Hygroscopic salt increases the weight of the core material. The results of this study can help medical professionals to obtain a more founded opinion about the performance of available HMEs for pulmonary rehabilitation in laryngectomized patients, and allow them to make an informed decision about which HME type to use.

The most frequent cause of voice prosthesis failure is microbial biofilm formation on the silicone valve, leading to destruction of the material and transprosthetic leakage. The Provox ActiValve valve is made of fluoroplastic, which should be insusceptible to destruction. The purpose of this study was to determine if fluoroplastic is insusceptible to destruction by Candida species.Thirty-three dysfunctional Provox ActiValves (collected 2011-2013). Biofilm analysis was performed with Illumina paired-end sequencing (IPES), assessment of biofilm-material interaction with fluorescence in situ hybridization (FISH), and confocal laser scanning microscopy (CLSM).IPES (n = 10) showed that Candida albicans and Candida tropicalis are dominant populations on fluoroplastic and silicone. Microbial diversity is significantly lower on fluoroplastic. Lactobacillus gasseri is the prevalent bacterial strain on most voice prostheses. FISH and CLSM (n = 23): in none of the cases was ingrowth of Candida species present in the fluoroplastic.Fluoroplastic material of Provox ActiValve seems insusceptible to destruction by Candida species, which could help improve durability of voice prostheses. © 2015 Wiley Periodicals, Inc. Head Neck 38: E432-E440, 2016.

Objectives: Our aim was to characterize articulation proficiency and differences between tumor sites before and after chemoradiotherapy for advanced head and neck cancer with the help of acoustic measures. Our further goal was to improve objective speech measures and gain insight into muscle functioning before and after treatment. Methods: In 34 patients with laryngeal or hypopharyngeal, nasal or nasopharyngeal, or oral or oropharyngeal cancer, we acoustically analyzed nasality, vowel space, precision, and strength of articulation in 12 speech sounds (/α/, /i/, /u/, /p/, /s/, /z/, /l/, /t/, /tj/, /k/, /x/, /r/) before treatment and 10 weeks and 1 year after treatment. Outcomes were compared between assessment points and between tumor sites. Results: Nasality in nonlaryngeal sites was significantly reduced by treatment. Most affected in articulation were the oral or oropharyngeal cancer sites, followed by the nasal or nasopharyngeal sites. One year after treatment, vowel space had not recovered and consonant articulation had weakened. Laryngeal sites were less affected in articulation by tumor or treatment. Conclusions: Analyses of articulatory-acoustic features are a useful instrument for assessing articulation and speech quality objectively. Assessment of a number of sounds representing various articulation manners, places, and tongue shapes revealed patterns of speech deterioration after chemoradiotherapy. The results suggest that patients' speech could benefit from articulation exercises to address changes in muscle coordination and/or sensitivity and to counteract side effects and “underexercise” atrophy.

Pharyngocutaneous fistulas (PCFs) following total laryngectomy is a common complication. The standard therapy is conservative management, and if this is not successful, surgical closure. There is a group of patients with limited survival chance who have small PCFs. In these patients who are not candidates for surgery, sealing of the PCF with a voice prosthesis can significantly improve the functionality of these patients allowing them to swallow and phonate.

Imaging is playing a major role in the assessment of cervical lymphadenopathy. In head and neck malignancies, imaging can be helpful for staging, and sometimes in differentiating different types of metastases, such as squamous cell carcinomas, non-hodgkins disease and thyroid carcinomas. This article on imaging of cervical lymph node metastases will describe both radiological and clinical aspects. Computed tomography (CT) and magnetic resonance (MR) are widely used for primary tumor and nodal imaging. However, very seldom these modalities have clinical consequences for the management of the neck, such as a wait-and-see policy if no nodes are depicted. This is caused by the limited accuracy of both modalities caused by the fallibility of radiologic criteria for metastases. Ultrasound (US) is hampered by similar morphologic criteria, and only US-guided fine needle aspiration cytology (FNAC) can offer additional cytologic criteria which are more reliable.

Imaging of the neck for the assessment of nodal metastases can be used to detect occult metastases or to assess operability of palpable metastases. The detection of small occult metastases has limitations, as micrometastases cannot be depicted. However, imaging can diminish the risk of occult metastases and thus influence management; for this purpose a very sensitive technique is necessary. The currently used radiologic criteria are not sensitive enough to accomplish enough reduction in the risk of occult metastases. Therefore, more sensitive CT and MRI criteria, but especially ultrasound guided aspiration, should be used to assess the clinically negative neck.

Lymphatic metastasis is the most important mechanism in the spread of head and neck squamous cell carcinomas. The rate of metastasis probably reflects the aggressiveness of the primary tumor and is an important prognosticator. 55,59,94,128 Not only the presence, but also the number of nodal metastases, the level in the neck, the size of the nodes, and the presence of extranodal spread are important prognostic features. In most institutions throughout the world, the neck is mainly staged by palpation. Although palpation has the advantage of being both easy and inexpensive to perform and repeat, it is generally accepted to be inaccurate. Both the sensitivity and specificity are in the range of 60% to 70%, depending on the tumor site studied. 4,90 As a consequence of the low sensitivity of palpation, a neck side without palpable metastases is at risk of harboring occult metastasis. This risk is to a large extent dependent on the size and site and other characteristics of the primary tumor. 34,56,60,71 For example, in glottic carcinomas and in small sinonasal carcinomas the risk of occult metastases is far below 10%. On the other hand, nasopharyngeal carcinomas, and to a lesser extent other pharyngeal carcinomas, have a risk of occult metastases of 50% or more. For most T1 to T3 oral, oropharyngeal, and supraglottic tumors this risk of occult metastases is in the range of 20% to 50%, with significant differences between different sites and studies. 46,58,64,74,87,93,96 In many head and neck primaries not only the ipsilateral site of the neck is at risk but the contralateral site has a significant risk to harbor metastases as well, especially when the primary has grown close to or extends over the midline. Because of the fallibility of palpation, it is widely accepted to treat the neck electively if the risk of occult metastases is high. The "acceptable" risk to perform elective treatment is very hard to define. As most clinicians do not treat the neck electively in small T1 oral carcinomas that carry a risk of around 15% of occult metastases, this figure is often quoted. Recently a meta-analysis using a decision analysis model on the basis of prognostic literature data was performed. In this study, a risk of occult metastases higher than 20% was calculated to be optimal for elective treatment. 134

Epidemiologic analyses have shown disproportional increases of head and neck squamous cell carcinoma (HNSCC) incidence in a younger age group (younger than 45 years old), compared to patients above 45 years old. Although this group is small (5%), it includes a significant subset of the HNSCC patient population, and is characterized by a distinct clinical and etiological phenotype. HNSCC in young patients often presents without significant exposure to alcohol and tobacco and primarily affects the oropharynx and oral cavity. Exposure to human papilloma virus (HPV) has been identified as a major contributor to the pathogenesis of oropharyngeal carcinomas, and explains part of the observed incidence variation. Specific hereditary influences, including genetic predispositions accounting for an increased mutagen sensibility and inherited syndromes like Fanconi Anemia and Bloom's syndrome, have been identified as causative factors in a subgroup of young-onset HNSCC, but their cumulative influence remains at present likely underestimated. Circumstantial evidence suggests that young-onset HNSCC patients have a clinically different phenotype compared to older patients, however, the true impact of young age on HNSCC clinical behavior will remain difficult to determine unless multi-institutional databases will be combined. The rising incidence of young-onset HNSCC mandates intensification of research endeavors into its etiology, clinical phenotype and optimal management.

Both organ-preserving concurrent (chemo)radiotherapy ((C)RT) and organ-sacrificing surgery (total laryngectomy) are used for treatment of advanced laryngeal cancer. The purpose of this study was to present the assessment of our treatment protocol for T3 (C)RT and T4 disease (total laryngectomy + postoperative RT).We conducted a retrospective cohort study in 182 consecutive patients (1999-2008). The primary outcome was overall survival (OS) in relation to stage and treatment.One hundred two patients received RT (82.4% T3), 20 patients CRT (60.0% T3), and 60 patients total laryngectomy + RT (91.7% T4). Five-year OS: T3 52%, T4 48%, for RT 50%, for CRT 43%, and for total laryngectomy + RT 52%. Five-year laryngectomy-free interval was 72% after RT, and 83% after CRT.There were no differences in survival according to T classification or treatment modality. Because the majority of T3 laryngeal cancers were treated with (C)RT and the majority of T4 with total laryngectomy + RT, this gives food for thought on whether the present protocol for T3 laryngeal cancer is optimal.

Although modern imaging techniques become more accurate for the assessment of lymph node metastases in the neck as criteria and technology evolve, micrometastases remain occult with any technique. Even the routine histopathological examination of neck dissection specimens is unable to detect all micrometastases. Because knowledge on the incidence of micrometastases in the clinically NO neck might be of importance for decision making regarding elective treatment, a retrospective study on 96 elective neck dissections was conducted. Meticulous histopathological examination of the neck dissection specimens yielded 3092 lymph nodes of which 67 (2.2%) were tumor-positive. Twenty-six of these 67 lymph node metastases were micrometastases. Of the 36 tumor-positive neck dissection specimens, 21 contained micrometastases. In 9 tumor-positive specimens only micrometastases were found. This high incidence of micrometastases has important implications for the diagnostic work-up, the treatment, and histopathological examination of the NO neck.

Background Failure of locoregional control is the main cause of recurrence in advanced head and neck cancer. This multi-center trial aims to improve outcome in two ways. Firstly, by redistribution of the radiation dose to the metabolically most FDG-PET avid part of the tumour. Hereby, a biologically more effective dose distribution might be achieved while simultaneously sparing normal tissues. Secondly, by improving patient selection. Both cisplatin and Epidermal Growth Factor Receptor (EGFR) antibodies like Cetuximab in combination with Radiotherapy (RT) are effective in enhancing tumour response. However, it is unknown which patients will benefit from either agent in combination with irradiation. We will analyze the predictive value of biological markers and 89Zr-Cetuximab uptake for treatment outcome of chemoradiation with Cetuximab or cisplatin to improve patient selection. Methods ARTFORCE is a randomized phase II trial for 268 patients with a factorial 2 by 2 design: cisplatin versus Cetuximab and standard RT versus redistributed RT. Cisplatin is dosed weekly 40 mg/m2 for 6 weeks. Cetuximab is dosed 250mg/m2 weekly (loading dose 400 mg/m2) for 6 weeks. The standard RT regimen consists of elective RT up to 54.25 Gy with a simultaneous integrated boost (SIB) to 70 Gy in 35 fractions in 6 weeks. Redistributed adaptive RT consists of elective RT up to 54.25 Gy with a SIB between 64-80 Gy in 35 fractions in 6 weeks with redistributed dose to the gross tumour volume (GTV) and clinical target volume (CTV), and adaptation of treatment for anatomical changes in the third week of treatment. Patients with locally advanced, biopsy confirmed squamous cell carcinoma of the oropharynx, oral cavity or hypopharynx are eligible. Primary endpoints are: locoregional recurrence free survival at 2 years, correlation of the median 89Zr-cetuximab uptake and biological markers with treatment specific outcome, and toxicity. Secondary endpoints are quality of life, swallowing function preservation, progression free and overall survival. Discussion The objective of the ARTFORCE Head and Neck trial is to determine the predictive value of biological markers and 89Zr-Cetuximab uptake, as it is unknown how to select patients for the appropriate concurrent agent. Also we will determine if adaptive RT and dose redistribution improve locoregional control without increasing toxicity. ClinicalTrials.gov Identifier: NCT01504815

Purpose of review: Total laryngectomy rehabilitation (TLR) in Europe is not uniform, with quite some differences in approach and infrastructure between various countries. In, for example, the Netherlands, Switzerland, Scandinavia, and more recently also in the UK, head and neck cancer (HNC) treatment and rehabilitation shows a high level of centralization in dedicated HNC centres. In other European countries, the level of centralization is lower, with more patients treated in low-volume hospitals. This article focusses on the situation in the Netherlands and, where applicable, will discuss the regional variations in Europe.Recent findings: Prosthetic surgical voice restoration (PSVR) presently is the method of choice in Europe, and use of oesophageal and electrolarynx voice has moved to the background. In most European countries (except the UK and Ireland), PSVR is physician driven, with an indispensable role for speech-language pathologists and increasingly for oncology nurses. Indwelling voice prostheses are mostly preferred, also because these devices can be implanted at the time of trachea-oesophageal puncture. Pulmonary rehabilitation is achieved with heat and moisture exchangers, which, based on extensive clinical and basic physiology research, are considered an obligatory therapy measure. In addition to PSVR, also issues such as smoking cessation, dysphagia/swallowing rehabilitation, and olfaction/taste rehabilitation are discussed. Especially, the latter has shown great progress over the last decade and is another example of increasing implementation of evidence-based practice in TLR.Summary: TLR has shown considerable progress over the last decades, and through the intensified collaboration between all clinicians involved, significantly has improved vocal, pulmonary, and olfactory rehabilitation after total laryngectomy.

Development and (pre-) clinical assessment were performed of a novel surgical tool for primary and secondary tracheoesophageal puncture (TEP) with immediate voice prosthesis (VP) insertion in laryngectomized patients, the Provox Vega Puncture Set (PVPS). After preclinical assessment in fresh frozen cadavers, a multicenter prospective clinical feasibility study in two stages was performed. Stage-1 included 20 patients, and stage-2 had 27. Based on observations in stage-1, the PVPS was re-designed (decrease in diameter of the dilator from 23.5 to 18 Fr.) and further used in stage-2. Primary outcome measure was immediate VP insertion without requiring additional instruments. Secondary outcome measures for comparison of the new with the traditional TEP procedure were: appreciation, ease of use, time consumption, estimated surgical risks and overall preference. A mini-max two-stage study design was used to establish the required sample size. In stage-1, dilatation forces were considered too high in patients with a fibrotic TE wall. With the final thinner version of the PVPS, VPs were successfully inserted into the TEP in ‘one-go’ in 24/27 (89%) of TEPs: 20 primary and 7 secondary. Participating surgeons rated appreciation, ease of use, time consumption and estimated surgical risks as better. Related adverse events were few and minor. The new PVPS appeared to be the preferred device by all participating surgeons. This study shows that the novel, disposable PVPS is a useful TEP instrument allowing quick and easy insertion of the VP in the vast majority of cases without requiring additional instruments.

6016Background: Salivary Duct Carcinoma (SDC) is a rare, highly aggressive subtype of salivary gland cancer, which is androgen receptor (AR) positive in most pts. In recurrent disease androgen depr...

AimLocoregional recurrences and distant metastases in adequately treated head and neck squamous cell carcinoma (HNSCC) patients have a dismal effect on survival. Tumor cells that escape histopathological detection might be the prime cause of this effect. We evaluated whether minimal residual cancer (MRC) in deep surgical margins and disseminated tumor cells (DTCs) in bone marrow aspirates are associated with clinicohistopathological parameters and outcome.MethodsSubmucosal samples of deep resection margins of 105 HNSCC patients with histopathologically tumor-free surgical margins were analysed for the presence of MRC using hLy-6D qRT-PCR. Bone-marrow aspirates of 76 of these patients were analysed for DTCs by immunocytochemical staining. Presence of molecular-positive deep surgical margins, presence of DTC in bone marrow aspirates, and clinicohistopathological parameters were tested for associations with survival parameters by univariate and multivariate analyses.ResultsIn addition to lymph node stage, it appeared that vasoinvasive growth and particularly infiltrative growth pattern are significant predictors for locoregional recurrence (p = 0.041 and p = 0.006, respectively) and disease-free survival (p = 0.014 and p = 0.008, respectively). Remarkably, neither the presence of molecular-positive deep surgical margins nor that of DTC in bone marrow aspirates were significantly related to outcome.ConclusionsThe presence of vasoinvasive and infiltrative growth in HNSCC tumor specimens are significant risk-factors for locoregional recurrence and disease-free survival. At present there seems no role for molecular analysis of deep surgical margins and bone marrow aspirates in predicting outcome with the methods used.

Head and neck cancer is relatively rare: in the Netherlands, some 2600 newly diagnosed cases are registered annually. Its treatment is centralised and is actually performed only in Dutch Head and Neck Society (DHNS) accredited medical centres. Although survival rates have improved only marginally, treatment regimens have changed over the past few years. Treatment has become increasingly focused on the preservation of organs and their functionalities. The effects of both a tumour and its treatment can have a serious impact on the functioning and quality of life of a patient. Therefore, sufficient attention to post-treatment rehabilitation is necessary. The Netherlands Cancer Institute has recently collaborated with the Amsterdam Rehabilitation Research Center Reade in developing a structured multidisciplinary rehabilitation programme. This programme has also been made available to other DHNS centres.

Purpose: This study quantifies tumor shape variability in head-and-neck cancer patients during radiation therapy using implanted markers. Methods and Materials: Twenty-seven patients with oropharyngeal tumors treated with (chemo)radiation were included. Helical gold markers (0.35 × 2 mm, 3-10/patient, average 6) were implanted around the tumor. Markers were identified on planning computed tomography (CT) and daily cone beam CT (CBCT). After bony anatomy registration, the daily vector length on CBCT in reference to the planning CT and daily marker movement perpendicular to the gross tumor volume (GTV) surface at planning CT (d normal) of each marker were analyzed. Time trends were assessed with linear regression of the normal> markers. In 2 patients, 2 markers were implanted in normal tissue to evaluate migration by measuring intermarker distances. Results: Marker implantation was feasible without complications. Three-dimensional vectors (4827 measurements, mean 0.23 cm, interquartile ratio 0.24 cm) were highest in base of tongue sublocalization (P

Objectives/Hypothesis:Assessment of a novel adhesive baseplate (Provox StabiliBase) for heat and moisture exchanger (HME) and/or automatic speaking valve (ASV) application.Study Design:Prospective, clinical, multicenter trial.Methods:This was a trial in laryngectomized patients comparing their usual adhesive with the trial adhesive. Primary outcome measure was overall patient preference; additional outcome parameters possibly explaining patients' preferences were 1) patient tolerance and preference with respect to daily handling of the adhesive; 2) adhesive lifespan, and 3) voice and speech with the adhesives. Study specific questionnaires, visual analog scales, patients' diaries, and stoma assessments were used for data collection.Results:In total, 58 of the 65 laryngectomized individuals entered in the study completed the trial. Patients' overall preference for the new device was high (76%; P < .001). Significantly better performance was found for the trial adhesive with respect to ease of application (P = .034), fit (P < .001), and air leakage through the adhesive (P < .001). Comfort and stoma depth correlated weakly (r = 0.297; P = .024; deeper stoma-more comfort with StabiliBase). The adhesive lifespan with HME is significantly increased (1.7 times and 15.7 hours-plus airtight use; P < .001). This longer lifespan coincided with somewhat increased dirtying of the adhesive (P = .02). There were no serious adverse events.Conclusions:The StabiliBase adhesive for peristomal attachment of HMEs and/or ASVs was preferred by 76% of study participants and showed a promising prolonged lifespan. This new device further increases the options for stoma attachment in laryngectomized individuals, and subsequently the availability of optimal voice and pulmonary rehabilitation for a larger proportion of patients.

Objective To evaluate the functional outcomes after total laryngectomy (TLE) for a dysfunctional larynx in patients with head and neck cancer that is in complete remission after (chemo)radiotherapy.Design Retrospective cohort study.Setting Tertiary comprehensive cancer center.Patients The study included 25 patients from a cohort of 217 consecutive patients with TLE who were treated between January 2000 and July 2010. The inclusion criteria for this subgroup analysis were complete remission and functional problems for which TLE was considered to be the only resolution. Quality of life assessment was carried out using the European Organization for Research and Treatment of Cancer Quality of Life C30 and Head and Neck Module 35 questionnaires and an additional study-specific questionnaire covering functional aspects, such as swallowing and dyspnea, in more detail.Intervention Total laryngectomy.Main Outcome Measures Morbidity, mortality, and functional outcomes.Results The indication for TLE was chronic aspiration with or without recurrent pneumonia (n = 15 [60%]), debilitating dyspnea (n = 8 [32%]), and persistent profuse hemorrhage (radiation ulcer) (n = 2 [8%]). After TLE, 14 of the 25 patients (56%) had 20 major postoperative complications, including 11 pharyngocutaneous fistulas, requiring additional treatment. Tube feeding and recurrent pneumonia incidence had decreased from 80% and 28% to 29% and 0%, respectively, 2 years after surgery. Prosthetic voice rehabilitation was possible in 19 patients (76%). Two years after surgery, 10 of 14 patients (71%) still reported TLE-related pulmonary problems despite the consistent use of a heat and moisture exchanger. The 5-year overall survival rate was 35%.Conclusions Total laryngectomy for a dysfunctional larynx tends to have a high complication rate. However, in this study, the initial functional problems (aspiration, recurrent pneumonia, and dyspnea) did not recur. Tube feeding was significantly reduced, and the quality of life of the surviving patients appeared to be reasonable.

Background Extranodal spread (ENS) of tumors is widely used as a prognosticator for patients with head and neck cancer and is used as an indicator for postoperative treatment. However, the histopathologic agreement among pathologists on the assessment of the presence or absence of this criterion has never been studied. Methods The interobserver and intraobserver agreement among 10 pathologists on the diagnosis of ENS in 41 tumor-positive lymph nodes was evaluated. Results The kappa value of the interobserver agreement among pathologists varied between 0.14 and 0.75, the overall kappa value was 0.42 and 0.49 in the 2 scoring sessions. The intraobserver kappa value varied between 0.49 and 0.95. Conclusion The intraobserver and interobserver agreement among pathologists in the assessment of the presence of ENS was low in metastatic lymph nodes in the neck. Because of the widely accepted prognostic significance and therapeutic consequences of ENS, there is a need for internationally accepted reproducible criterion for the histopathologic assessment of ENS in metastatic lymph nodes in the neck. (c) 2011 Wiley Periodicals, Inc. Head Neck, 2011

For oral cavity malignancies, sentinel lymph node (SLN) mapping is performed by injecting a radiocolloid around the primary tumour followed by lymphoscintigraphy. Surgically, SLNs can then be localized using a handheld gamma ray detection probe. The aim of this study was to evaluate the added value of intraoperative fluorescence imaging to the conventional radioguided procedure. For this we used indocyanine green (ICG)-(99m)Tc-nanocolloid, a hybrid tracer that is both radioactive and fluorescent. Fourteen patients with oral cavity squamous cell carcinoma were peritumourally injected with ICG-(99m)Tc-nanocolloid. SLNs were preoperatively identified with lymphoscintigraphy followed by single photon emission computed tomography (SPECT)/CT for anatomical localization. During surgery, SLNs were detected with a handheld gamma ray detection probe and a handheld near-infrared fluorescence camera. Pre-incision and post-excision imaging with a portable gamma camera was performed to confirm complete removal of all SLNs. SLNs were preoperatively identified using the radioactive signature of ICG-(99m)Tc-nanocolloid. Intraoperatively, 43 SLNs could be localized and excised with combined radio- and fluorescence guidance. Additionally, in four patients, an SLN located close to the primary injection site (in three patients this SLN was located in level I) could only be intraoperatively localized using fluorescence imaging. Pathological analysis of the SLNs revealed a metastasis in one patient. Combined preoperative SLN identification and intraoperative radio- and fluorescence guidance during SLN biopsies for oral cavity cancer proved feasible using ICG-(99m)Tc-nanocolloid. The addition of fluorescence imaging was shown to be of particular value when SLNs were located in close proximity to the primary tumour

To the Editor: We would like to take the opportunity to comment on the recently published article by Brannon et al, ‘‘Extracapsular Tumor Extension in Cervical Lymph Nodes: Reconciling the Literature and SEER Data.’’ In the literature, the risk of extracapsular tumor spread (ECS) increases with a larger nodal size; however, ECS can be also be detected in smaller nodes. As the authors discussed, the published literature represents findings from studies consisting only of small numbers of patients and retrospectively obtained data. Therefore, this study analyzed the relationship between nodal size and the frequency of ECS in a larger, more representative, prospectively collected database. For the collection of data, the authors consulted the Surveillance, Epidemiology, and End Results (SEER) registry. A total of 1684 patients eventually could be studied. As the article showed, the association between ECS and nodal size in the current literature was clearly different than the findings after review of the SEER database in this study. Looking for a possible explanation Brannon et al suggested a possible influence of the individual evaluation of the lymph nodes by the pathologist or the lack of a structured protocol for reporting ECS and registration in the SEER. In the literature, the reported incidence of microscopic ECS varies between 21% and 85%, and the incidence of macroscopic ECS varies between 17% and 54%. As the authors discussed, it is unclear whether these different percentages reflect differences between patient populations studied or interobserver variation between pathologists on the interpretation of ECS. Because the presence of ECS is important in determining the treatment protocol, it is important to report on this topic in a universal way. Therefore, we recently performed a study to examine the level of agreement among pathologists on the presence or absence of ECS. The interobserver and intraobserver agreement among 10 pathologists on the diagnosis of ECS in 41 tumor-positive lymph nodes was evaluated. All pathologists evaluated twice the 41 lymph nodes for the presence or absence of ECS. The pathologists were instructed to conduct their evaluation on the basis of their own criteria. The kappa value of the interobserver agreement among pathologists varied between 0.14 and 0.75, and the overall kappa value was 0.42 and 0.49 in the 2 scoring sessions. The intraobserver kappa value varied between 0.49 and 0.95. With respect to these findings, we concluded that the intraobserver and interobserver agreement among pathologists in the assessment of the presence of ECS was low. Taking into account these results, we believe the differences found by Brannon et al probably were caused by interobserver variation between different pathologists determining ECS in the SEER database. In conclusion, because of the widely accepted prognostic significance and therapeutic consequences of ECS, we agree with the authors that there is a need for internationally accepted reproducible criteria for the histopathologic assessment of ECS in metastatic lymph nodes in the neck.

Since 1993, ten multidisciplinary symposia were organized at The Netherlands Cancer Institute on the diagnosis and treatment of malignancies of the head and neck. The symposia are meant to provide up-to-date teaching for physicians by world-renowned speakers. The previous symposia dealt with sarcomas, reconstruction, cancer in young patients, salivary glands, melanoma, unknown primaries, as well as several other topics. This 10th symposium focused on skin cancer of the head and neck. There are many types of skin cancer and the differential diagnosis can often be difficult. In this symposium, diagnosis, molecular biology, epidemiology, staging and the treatment of various skin cancers were discussed by leaders in the field. There were over 200 participants from many different countries in Europe and overseas, representing specialties in the fields of dermatology, maxillofacial surgery, otolaryngology, head and neck surgery, general surgery, plastic and reconstructive surgery, and radiotherapy.

Objectives: To investigate tumour-thickness measurement with an intra-operative ultrasound (US) probe. Methods: A retrospective data analysis was undertaken for a total of 65 patients with a T1-2 oral cavity cancer, who were seen at a tertiary referral centre between 2004 and 2010. The correspondence between tumour thickness measured by ultrasonography and histopathology was assessed by Pearson's correlation coefficient, and also between tumour thickness and the development of neck metastasis. Results: In 11 cases, intra-oral measurement was not optimal due to limited mouth opening (n∈=∈2) or impossibility to depict the lesion (n∈=∈9). Tumour thickness measured by US correlated well with histopathology (n∈=∈23, R∈=∈0.93). Tumour thickness of 7 mm carries a risk of lymph node metastasis of 12%, whereas in tumours exceeding 7 mm this risk is 57% (p∈=∈0.001). Twenty-five percent developed neck metastasis and 19% had local recurrence. Conclusion: Tumour thickness is an important predictive marker for lymph node metastases. As such, it can help in decision-making with regard to management of the primary tumour and neck. Based upon our findings, a wait-and-see policy is only warranted for superficial lesions with tumour thickness of less than 7 mm, but only if regular follow-up using US-guided aspiration of the neck is ensured.

Model systems are irreplaceable to study cancer. Although the best model system is human cancer in man, research in patients is restricted by ethical and financial restraints. Furthermore, experiments cannot be repeated and patient numbers are limited. Tumor cell cultures are the most versatile system to study cancer cells. They allow for repeated experiments in controlled conditions, are relatively inexpensive and are ideal to study genes, pathways, and tumor response. Mouse models enable to study cancer behavior and carcinogenesis in vivo and many different model systems are available. Apart from xenografts in immune compromised mice, transplantation of oral mice tumors in syngeneic mice, animals developing oral cancer using carcinogen exposure and genetically modified mice can be used. All these models, however, have advantages and limitations that will be discussed in this chapter.

Purpose: To find molecular markers from expression profiling data to predict recurrence of laryngeal cancer after radiotherapy. Experimental Design: We generated gene expression data on pre-treatment biopsies from 52 larynx cancer patients. Patients developing a local recurrence were matched for T-stage, subsite, treatment, gender and age with non-recurrence patients. Candidate genes were then tested by immunohistochemistry on tumor material from a second series of 76 patients. Both series comprised early stage cancer treated with radiotherapy alone. Finally, gene expression data of eight larynx cancer cell lines with known radiosensitivity were analyzed. Results: Nineteen patients with a local recurrence were matched with 33 controls. Gene sets for hypoxia, proliferation and intrinsic radiosensitivity did not correlate with recurrence, whereas expression of the putative stem cell marker CD44 did. In a supervised analysis, probes for all three splice variants of CD44 on the array appeared in the top 10 most significantly correlated with local recurrence. Immunohistochemical analysis of CD44 expression on the independent validation series confirmed CD44's predictive potential. In 8 larynx cancer cell lines, CD44 gene expression did not correlate with intrinsic radiosensitivity although it did correlate significantly with plating efficiency, consistent with a relationship with stem cell content. Conclusions: CD44 was the only biological factor tested which significantly correlated with response to radiotherapy in early stage larynx cancer patients, both at the mRNA and protein levels. Further studies are needed to confirm this and to assess how general these findings are for other head and neck tumor stages and sites. Clin Cancer Res; 16(21); 5329–38. ©2010 AACR.

Neuroendocrine carcinomas of the larynx include a range of rare tumors which have variable biologic behavior, affecting treatment and prognosis. Among these, typical carcinoid tumors are the least common type. Prognosis of typical carcinoid tumor is better than atypical carcinoid tumor and small cell carcinoma of the larynx. Conservation surgery is the preferred treatment modality. Transoral CO2 laser surgery can be a good alternative for appropriate cases because of the functional results and less morbidity. In this article, a 71-year-old female presented with complaints of feeling a mass during swallowing. Fiberoptic examination of the larynx revealed a mass located on the right aryepiglottic fold and biopsy revealed the tumor as a typical carcinoid tumor. We describe CO2 laser excision of a typical carcinoid tumor of the larynx in this case report.

Background. The additional value of single photon emission computed tomography with CT (SPECT/CT) for detection and localization of sentinel nodes in patients with a melanoma of the head and neck was determined. Methods. Thirty-eight patients received conventional lymphoscintigraphy followed by hybrid SPECT/CT. The number of sentinel nodes visualized and anatomic information provided were analyzed. Changes in surgical approach due to additional information from the SPECT/CT were evaluated in 20 patients. Results. SPECT/CT visualized a mean of 2.6 sentinel nodes per patient (range, 1–6). SPECT/CT depicted an additional sentinel node in 16% of the patients and clearly showed the anatomic location of the hot nodes in all patients. The surgical approach was adjusted on the basis of SPECT/CT images in 11 patients (55%). Conclusion. SPECT/CT visualizes more sentinel nodes than conventional images and shows their anatomic location. SPECT/CT is recommended in patients with a melanoma in the head or neck. © 2010 Wiley Periodicals, Inc. Head Neck, 2011

Contains fulltext : 88442.pdf (Publisher’s version ) (Closed access) PURPOSE: The purpose of this study was to combine gene expression profiles and clinical factors to provide a better prediction model of local control after chemoradiotherapy for advanced head and neck cancer. MATERIAL AND METHODS: Gene expression data were available for a series of 92 advanced stage head and neck cancer patients treated with primary chemoradiotherapy. The effect of the Chung high-risk and Slebos HPV expression profiles on local control was analyzed in a model with age at diagnosis, gender, tumor site, tumor volume, T-stage and N-stage and HPV profile status. RESULTS: Among 75 patients included in the study, the only factors significantly predicting local control were tumor site (oral cavity vs. Pharynx, hazard ratio 4.2 [95% CI 1.4-12.5]), Chung gene expression status (high vs. Low risk profile, hazard ratio 4.4 [95% CI 1.5-13.3]) and HPV profile (negative vs. Positive profile, hazard ratio 6.2 [95% CI 1.7-22.5]). CONCLUSIONS: Chung high-risk expression profile and a negative HPV expression profile were significantly associated with increased risk of local recurrence after chemoradiotherapy in advanced pharynx and oral cavity tumors, independent of clinical factors. 01 juni 2010

To assess device life of the new Provox Vega 22.5 and 20 Fr prostheses, to establish whether the optimized airflow characteristics of these devices materialize in better voice characteristics in comparison to Provox2, and to assess the feasibility of voice prosthesis replacement with the new Smart Inserter.Prospective clinical phase II study.Prospective clinical phase II study including two patient cohorts (Provox Vega 22.5 Fr: N = 33; Provox Vega 20 Fr: N = 26). Device-life assessment, subjective data collection with study-specific structured questionnaires, perceptual analysis (Comparative Mean Opinion Score), and objective voice analysis (standard Dutch text, maximum phonation time, and dynamic range).Device life of both prostheses appears comparable to Provox2. Several voice characteristics were better in Vega 22.5, which coincides well with patients' preference. Voicing with Vega 20 appears comparable to Provox2. Use of Smart Inserter showed a short learning curve, and was considered an improvement by the clinicians.The new Provox Vega 22.5 and 20 Fr prostheses have a device life comparable to Provox2, whereas voicing is better than (with the 22.5 Fr version) or comparable (with the 20 Fr version) to Provox2. The Smart Inserter, after a short learning curve, turns out to be a further improvement of the anterograde replacement of these indwelling devices.

Background. Critical evaluation of outcome of primary parotid carcinoma treatment is limited by pathologic diversity and low incidence numbers. Scientific evidence for the optimal management of the N0-neck is scarce and was, therefore, investigated in a systematic literature review. Methods. The articles included were published in English between 1997 and 2007 and describe populations with the de- finitive pathology, staging, and treatment. Of 1104 articles, 19 were selected, describing 2703 patients. Results. Of eligible populations, 83% were clinically N0. Pathology reporting of elective lymph node dissection (ELND) had limitations, but 23% showed occult metastases. Regional recurrence occurred in 5% of patients. Conclusion. The discrepancy between the relatively high percentage of occult metastases and reported low regional re- currence rates may indicate the efficacy of treatment, being ei- ther ELND or radiotherapy of the neck. Pooling, standardized collection, and reporting of data are essential in comparing outcomes in populations to determine optimal treatment. V C 2009 Wiley Periodicals, Inc. Head Neck 32: 1402-1411, 2010

Conclusions: Provox Vega prostheses demonstrate good short-term feasibility, and their optimized airflow-resistance design offers laryngectomy patients indwelling voice prostheses with more choices in outer diameters without sacrificing (too) much in voice quality. Objectives: Technological progress enables improvement of in vitro airflow characteristics of voice prostheses and design of voice prostheses with smaller outer diameters. This could potentially improve voice quality in users of Provox2, and avoid diminished voice quality in users of prostheses with smaller outer diameters. Methods: This was a prospective clinical phase I/feasibility study of three newly designed indwelling voice prostheses (Provox Vega 22.5 (Provox2 successor), 20, and 17Fr). Assessments consisted of patients' self-reported voice and speech, perceptual evaluation, acoustic analysis, maximum phonation time, loudness, speech rate, pull-out force and adaptation of the tracheoesophageal (TE) puncture to smaller diameter voice prostheses. Vega 22.5 was assessed in 15 patients (all Provox ActiValve users, observation period 3 weeks), and 16 patients with Vega 20/17 (2 weeks each). Results: No voice prostheses problems were encountered. Half of the patients with Vega 22.5 preferred that for its better voice quality. Voice and speech were considered equal to Provox2 for Vega 20, but slightly less for Vega 17. Most TE punctures adapted well to the smaller diameter voice prostheses.

Background. The objective of this study was to evaluate the effectiveness and safety of our careful observational strategy and neck dissections and the accuracy of ultrasound-guided fine-needle aspiration cytology, and to determine the prognostic factors for outcome and regional control after primary chemoradiation. Diagnostic evaluation of the regional status after concurrent chemoradiation for advanced head and neck cancer remains difficult, and the indications for a salvage neck dissection and its extent are not clearly defined. Methods. In a series of 540 patients, there was suspicion of regional residual or recurrent disease after chemoradiation in 61 patients who underwent 68 salvage neck dissections and 68 patients who were considered unresectable. For the patients with salvage neck dissection, the accuracy of ultrasound-guided fine-needle aspiration cytology was determined. Disease control in the neck, disease-specific and overall survival, and parameters that may have prognostic value for the outcome were evaluated. Results. Neck dissection specimens contained viable tumor in 26 (43%) patients. Of these, 13 had selective neck dissections and 13 modified radical neck dissections. Ultrasound-guided fine-needle aspiration cytology had a sensitivity of 80% and specificity of 42%. Nine patients developed a regional recurrence after salvage neck dissection (5 located in contralateral neck). Five-year regional control and overall survival rates were 79% and 36%, respectively. Significant prognostic factors for overall survival were surgical margins and "residual versus recurrent disease" in multivariate analysis. Conclusion. Considering the good regional control rate and the high rate of unnecessary neck dissections with a theoretical planned neck dissection strategy, we conclude that a careful observational strategy is worthwhile and safe. For the evaluation of radiation treatment response, ultrasound-guided fine-needle aspiration cytology has a low specificity. (C) 2009 Wiley Periodicals, Inc. Head Neck 31: 593-603, 2009

Contains fulltext : 81775.pdf (Publisher’s version ) (Closed access) OBJECTIVES/HYPOTHESIS: To find biomarkers associated with response to radiotherapy in laryngeal cancer that can be used together with clinical parameters to improve outcome prediction. METHODS: In this study, 26 patients irradiated for laryngeal carcinomas with a local recurrence within two years (cases) and 33 patients without recurrence (controls) were included. All pretreatment biopsies were arrayed onto a tissue array. Immunohistochemistry was performed for 13 biomarkers that were selected from the literature as potential predictors for radioresponse in head and neck (HN) cancer: Bcl-2, Bcl-xL, p16, p21, p27, p53, cyclin D1, HIF-1alpha, CA9, COX-2, EGFR, ki-67, and pRB. RESULTS: Univariate logistic regression models showed borderline statistically significant increased relative risks, with positivity for CA9, COX-2, and p53. Goeman's global testing revealed an overall association between outcome and the 13 markers together with clinical variables. The most important markers were CA9 and COX-2. CONCLUSIONS: In laryngeal carcinoma, hypoxia and COX-2 overexpression provide a stronger contribution to an increased risk of local recurrence after radiotherapy compared with the well-known candidate markers p53, Bcl-2, and cyclin D1. However, no robust expression profile for the prediction of radioresistance was found.

Objectives: To assess the long-term results of the Provox ActiValve, a prosthesis for voice rehabilitation after total laryngectomy that was designed to lessen the need for frequent replacements caused by Candida and "underpressure."Patients and Methods: Retrospective assessment of device lifetime, indications for replacement, voice quality, and maintenance issues, measured by a structured trial specific questionnaire, in a cohort of 42 laryngectomized patients, experiencing a short Provox2 device lifetime (median, 21 days).Results: The median device lifetime of Provox ActiValve, replaced for leakage through the device and those still in situ at the date of data collection (N = 32), was 337 days (mean 376 days): a statistically significant 16-fold increase compared to the Provox2 prosthesis (P < .001). In 10 patients, replacement was fistula-related (median after 86 days): esophageal pouch (N = 4), fistula granulation (N = 3), extrusion of the device (N = 2), and periprosthetic leakage (N = 1). Eighty-six percent of the patients used a special lubricant to diminish "stickiness" of the valve. Provox ActiValve was preferred by 90% of the patients who completed the trial-specific questionnaire.Conclusions: For patients requiring frequent device-related replacements, Provox ActiValve, also long-term, provides a true solution and thereby is a valuable addition to prosthetic voice rehabilitation.

Contains fulltext : 53443.pdf (Publisher’s version ) (Closed access) PURPOSE: The goal of the present study was to improve prediction of outcome after chemoradiation in advanced head and neck cancer using gene expression analysis. MATERIALS AND METHODS: We collected 92 biopsies from untreated head and neck cancer patients subsequently given cisplatin-based chemoradiation (RADPLAT) for advanced squamous cell carcinomas (HNSCC). After RNA extraction and labeling, we performed dye swap experiments using 35k oligo-microarrays. Supervised analyses were performed to create classifiers to predict locoregional control and disease recurrence. Published gene sets with prognostic value in other studies were also tested. RESULTS: Using supervised classification on the whole series, gene sets separating good and poor outcome could be found for all end points. However, when splitting tumors into training and validation groups, no robust classifiers could be found. Using Gene Set Enrichment analysis, several gene sets were found to be enriched in locoregional recurrences, although with high false-discovery rates. Previously published signatures for radiosensitivity, hypoxia, proliferation, "wound," stem cells, and chromosomal instability were not significantly correlated with outcome. However, a recently published signature for HNSCC defining a "high-risk" group was shown to be predictive for locoregional control in our dataset. CONCLUSION: Gene sets can be found with predictive potential for locoregional control after combined radiation and chemotherapy in HNSCC. How treatment-specific these gene sets are needs further study.