A Consensus Statement on the Administration of Systemic Bevacizumab in Patients with Recurrent Respiratory Papillomatosis.

OBJECTIVE: To provide detailed guidance on the administration of systemic bevacizumab in patients with recurrent respiratory papillomatosis (RRP) based on a detailed review of the scientific literature and a consensus of experts with real-world clinical experience. METHODS: A bevacizumab consensus working group (N = 10) was composed of adult and pediatric otolaryngologists, adult and pediatric oncologists, and a representative from the RRP Foundation (RRPF), all with experience administering systemic bevacizumab in patients with RRP. After extensive review of the medical literature, a modified Delphi method-based survey series was utilized to establish consensus on the following key areas: clinical and patient characteristics ideal for treatment candidacy, patient perspective in treatment decisions, treatment access, initial dosing, monitoring, guidelines for tapering and discontinuation, and reintensifying therapy. RESULTS: Seventy-nine statements were identified across nine critical domains, and 45 reached consensus [clinical benefits of bevacizumab (3), patient and disease characteristics for treatment consideration (7), contraindications for treatment (3), shared decision-making (incorporating the patient perspective) (5), treatment access (3), initial dosing and administration (8), monitoring (7), tapering and discontinuation (6), and reintensification (3)]. CONCLUSION: This consensus statement provides the necessary guidance for clinicians to initiate systemic administration of bevacizumab and represents a potential paradigm shift toward nonsurgical treatment options for patients with RRP. LEVEL OF EVIDENCE: 5 Laryngoscope, 2024.

Quality of Life in Recurrent Respiratory Papillomatosis Patients after Vocal Fold Surgery: An In-Depth Exploration.

INTRODUCTION: This study explores the quality of life among patients with recurrent respiratory papillomatosis (RRP) after vocal fold surgery as measured by the outcome scores of the Voice Handicap Index (VHI) and the Distress Thermometer and Problem List in Patients with Recurrent Respiratory Papillomatosis (DT&PL). Differences in quality of life were explored within the independent variables age, surgical frequency, weeks since last vocal fold operation, gender, HPV type, surgical location, vaccination with Gardasil©, and a patient's request to speak with a speech-language pathologist. METHODS: A single-center, observational cohort study was conducted using VHI and DT&PL scores and demographic and clinical data obtained from patient files. Inclusion criteria were a confirmed HPV type, age 18 years or older, the ability to fill in both questionnaires in Dutch, and having undergone at least one surgical procedure to remove laryngeal papilloma. Relationships of the independent variables with VHI and Distress Thermometer (DT) scores were explored using univariable and multivariable regressions and linear regression models. RESULTS: Of 271 RRP patients, 100 met the inclusion criteria and responded to requests to fill in both questionnaires with a minimum of 12 weeks after their last operation. Our study showed a statistically significant negative relationship between age and VHI scores (p = 0.02) in the univariable, and multiple linear regressions (p = 0.01), indicating that patients experienced fewer self-perceived functional voice disabilities with each increase in age. A parallel negative relationship is seen between the variables age (p = 0.03) and DT scores. Our results showed a statistically significant positive relationship between the number of vocal fold surgeries and DT scores (p = 0.03). CONCLUSION: The results of this study show a significant relationship between age, surgical frequency, and quality of life in patients with RRP. Older patients have lower Voice Handicap Index (VHI) and Distress Thermometer (DT) scores, indicating fewer self-perceived voice and disease-related quality of life problems. Conversely, a rise in surgical frequency is significantly associated with higher DT scores, reflecting greater disease-related distress.

Erratum: Missed Proximal Tracheoesophageal Fistula (TEF) in a Neonate with Type D Esophageal Atresia.

[This corrects the article DOI: 10.1055/a-2227-6389.].

Missed Proximal Tracheoesophageal Fistula (TEF) in a Neonate with Type D Esophageal Atresia.

We present the case of a patient with the rare type D esophageal atresia (EA), diagnosed after correction of an EA initially diagnosed as type C. Routine postoperative contrast esophagogram showed a missed proximal tracheoesophageal fistula. This case report illustrates the potential difficulties to diagnose type D EA.

Mobile Phone Applications Voice Tools and Voice Pitch Analyzer Validated With LingWAVES to Measure Voice Frequency.

OBJECTIVES: Voice frequency can be measured to assess the voice change in transgender men and women during treatment. There are many applications that can analyze voice frequency. This validation study aimed to compare the ability to measure voice frequency of the mobile phone applications "Voice Tools" and "Voice Pitch Analyzer" with the registration program LingWAVES as the gold standard. STUDY DESIGN: Prospective validation study. METHODS: A total of 45 participants of whom 20 transgender individuals were included. They were asked to read "The North Wind and the Sun" twice. The first measurement compared voice frequency measured by Voice Tools with LingWAVES while the second measurement compared Voice Pitch Analyzer with LingWAVES. The two applications that were being compared simultaneously measured the voice frequency. Pearson's regression correlations were performed to test for correlation between the mobile phone applications and LingWAVES. RESULTS: Significant correlations were demonstrated between the measurements of Voice Tools and LingWAVES (P < 0.001) and between Voice Pitch Analyzer and LingWAVES (P < 0.001). Voice Tools overestimated voice frequency with a median deviation of 2Hz (range -4 to 20). The overestimation was more pronounced in the high ranges. Voice Pitch Analyzer showed underestimation of voice frequency in high ranges. Median deviation was -2Hz (range -16 to 14). CONCLUSIONS: This validation study shows that voice frequency can be reliably measured with the mobile phone applications "Voice Tools" and "Voice Pitch Analyzer". Combined with the ease of use, these applications can be used to measure voice frequency in clinical practice and for research purposes.

Informed consent for suspension microlaryngoscopy: what should we tell the patient? A consensus statement of the European Laryngological Society.

INTRODUCTION: Informed consent for any surgical intervention is necessary, as only well-informed patients can actively participate in the decision-making process about their care, and better understand the likely or potential outcomes of their treatment. No consensus exists on informed consent for suspension microlaryngoscopy (SML). MATERIALS AND METHODS: Informed consent procedures in nine countries on five continents were studied. RESULTS: Several risks can be discerned: risks of SML as procedure, anesthesiologic risks of SML, specific risks of phonosurgery, risks of inadequate glottic exposure or unexpected findings, risks of not treating. SML has recognized potential complications, that can be divided in temporary (minor) complications, and lasting (major) complications. CONCLUSION: SML is a safe procedure with low morbidity, and virtually no mortality. Eleven recommendations are provided.

Bevacizumab as treatment option for recurrent respiratory papillomatosis: a systematic review.

PURPOSE: To this day, there is no cure for recurrent respiratory papillomatosis (RRP). Multiple surgical procedures are performed to achieve symptom relief and prevention of airway obstruction. A promising drug for RRP is the vascular endothelial growth factor (VEGF) binding antibody bevacizumab. This chemotherapeutic agent has an angiogenesis-inhibiting effect which inhibits tumor growth. The objective of this review was to investigate the efficacy of bevacizumab as treatment option for RRP, and to explore the difference of its effects between intralesional and systemic treatment. METHODS: A systematic search was conducted in Cochrane, PubMed, and Embase. Articles were included if bevacizumab treatment was given intralesionally and/or systemically. The methodological quality of the studies was assessed using the CAse REport (CARE) guidelines. RESULTS: Of 585 unique articles screened by title and abstract, 15 studies were included, yielding a total of 64 patients. In 95% of the patients treated with systemic bevacizumab, the post-bevacizumab surgical interval was considerably prolonged. More than half of them did not need any surgical intervention during mean follow-up of 21.6 months. Treatment with intralesional bevacizumab showed a lower efficacy: in 62% of the patients, the post-bevacizumab surgical interval (mean, 1.8 months follow-up) was extended when compared to the interval before the treatment. CONCLUSION: Systemically and intralesionally administered bevacizumab are effective treatment options for severe RRP. A systemic administration might be the treatment of first choice. Further prospective research with long term follow-up is advocated to elucidate this important topic.

Validation and Psychometric Evaluation of the Kannada Version of the Speech Handicap Index in Individuals with Oral and Oropharyngeal Cancer.

The current study aimed to adapt and validate the speech handicap index into the Kannada language, and also to investigate its psychometric properties in Kannada speaking individuals with oral and oropharyngeal cancers. This is a cross-sectional study and it was carried out in two phases. The first phase dealt with the translation of the English version of SHI into the Kannada language, and its validation on 95 healthy individuals and 25 individuals with oral or oropharyngeal cancer. The second phase dealt with the investigation of speech-related quality of life among 50 Kannada speaking individuals with oral and oropharyngeal cancers. The SHI-K has very good internal consistency (Cronbach's Alpha is 0.98) and exhibited good test-retest reliability (ICC = 0.94). The mean scores of the disordered group, for the psychosocial scores (t (118) = 25.87, p < 0.01), for speech scores (t (118) = 19.74, p < 0.01), for total SHI scores (t (188) = 26.45, p < 0.01), for overall rating (t (118) = 16.81, p < 0.01) were statistically significant and greater than the healthy group (p < 0.01). A statistically significant association was found between clinical-stage, total SHI scores, and rating [χ2 (4, N = 50) = 3.82, p = 0.02], but not for sex, tumor site, and type of treatment received. SHI-K is a valid and reliable tool to assess the speech-related quality of life of individuals with speech disorders. This tool can allow clinicians to plan better rehabilitation, and it can be used as an outcome tool for any treatment studies. The findings of the study emphasize the importance of considering patient priorities before commencing surgical or therapeutic interventions.

Relationship between videofluoroscopic and subjective (physician- and patient- rated) assessment of late swallowing dysfunction after (chemo) radiation: Results of a prospective observational study.

BACKGROUND AND PURPOSE: Primary (chemo)radiation (CHRT) for HNC may lead to late dysphagia. The purpose of this study was to assess the pattern of swallowing disorders based on prospectively collected objective videofluoroscopic (VF) assessment and to assess the correlations between VF findings and subjective (physician- and patient-rated) swallowing measures. MATERIAL AND METHODS: 189 consecutive HNC patients receiving (CH)RT were included. Swallowing evaluation at baseline and 6 months after treatment (T6) encompassed: CTCAE v.4.0 scores (aspiration/dysphagia), PROMs: SWAL QOL/ EORTC QLQ-H&N35 (swallowing domain) questionnaires and VF evaluation: Penetration Aspiration Scale, semi-quantitative swallowing pathophysiology evaluation, temporal measures and oral/pharyngeal residue quantification. Aspiration specific PROMs (aPROMs) were selected. Correlations between late penetration/aspiration (PA_T6) and: clinical factors, CTCAE and aPROMs were assessed using uni- and multivariable analysis. RESULTS: Prevalence of PA increased from 20% at baseline to 43% after treatment (p < 0.001). The most relevant baseline predictors for PA_T6 were: PA_T0, age, disease stage III-IV, bilateral RT and baseline aPROM 'Choking when drinking' (AUC: 0.84). In general aPROMs correlated better with VF-based PA than CTCAE scores. The most of physiological swallowing components significantly correlated and predictive for PA (i.e. Laryngeal Vestibular Closure, Laryngeal Elevation and Pharyngeal Contraction) were prone to radiation damage. CONCLUSION: The risk of RT-induced PA is substantial. Presented prediction models for late penetration/aspiration may support patient selection for baseline and follow-up VF examination. Furthermore, all aspiration related OARs involved in aforementioned swallowing components should be addressed in swallowing sparing strategies. The dose to these structures as well as baseline PROMs should be included in future NTCP models for aspiration.

Recommended Maximum Laryngeal Prominence Size in Adult Females: A Cross-Sectional Study Proposing a Laryngeal Prominence Size Standard for Chondrolaryngoplasty in Male-to-Female Transgender Individuals.

BACKGROUND: Although the World Professional Association for Transgender Health has provided international, multidisciplinary, evidence-based standards of care for various aspects of transgender health care, there is a lack of evidence-based guidelines for facial feminization surgery, including chondro laryngoplasty. The aim of this study was to define the recommended maximum laryngeal prominence size in adult females to propose an evidence-based laryngeal prominence size standard for chondrolaryngoplasty in male-to-female transgender individuals. METHODS: This cross-sectional study was conducted in a tertiary care hospital. The study sample consisted of cisgender patients aged 18 to 60 years old with no history of surgery or radiotherapy in the head and neck area who visited the Otolaryngology/Head and Neck Surgery outpatient clinic. Laryngeal prominence size data were collected using three-dimensional scanning of the head and neck area. RESULTS: Seventy-nine participants, 43 males and 36 females, were included in data analysis. Laryngeal prominence size was larger in male participants (median, 0.16 mm; range, 0 to 9.40 mm) than in female participants (median, 0.00 mm; range, 0 to 1.24 mm) (p < 0.001). The proportion of participants with a laryngeal prominence size larger than 0 mm was greater in male participants (55.81 percent) than in female participants (22.22 percent) (p = 0.002). CONCLUSIONS: To the authors' knowledge, this is the first study to assess laryngeal prominence size in the general population. Their results suggest that 2 mm would be the recommended maximum laryngeal prominence size in females. Therefore, a laryngeal prominence size standard of 2 mm could be considered for chondrolaryngoplasty in male-to-female transgender individuals.

A clicking larynx: Diagnostic and therapeutic challenges.

A clicking larynx can be described as a clicking sensation in the neck on swallowing or when moving the head, often associated with a tender or painful area in the neck. Diagnosis and therapy are challenging. In this article, we present a case report and overview of the current literature. The clicking larynx most often is reported to be a result of a displaced cornu superior of the thyroid cartilage, an enlarged greater cornu of the hyoid bone, or a short distance between the thyroid cartilage and hyoid bone. If a possible cause is identified, surgery can be offered to the patient, although an explanation of the possible underlying anatomical cause also could be satisfying for the patient and avert surgery. Laryngoscope, 128:697-700, 2018.

Evaluation of vascular features of vocal cords proposed by the European Laryngological Society.

A newly proposed classification by the European Laryngological Society (ELS) of glottic lesions by narrow-band imaging (NBI) divides their vascular patterns into longitudinal and perpendicular ones. The latter are further subdivided into the wide and narrow patterns. The longitudinal, wide, and narrow patterns are characteristic of benign disease, papilloma, and malignancy, respectively. The aim of the study was to investigate the diagnostic effectiveness of the classification. Forty patients with glottic lesions underwent microlaryngoscopy. The vascular patterns of all vocal cords were defined with NBI. The affected vocal cords were histologically analysed and comprised the arm (A). Unaffected vocal cords were not histologically analysed but followed-up and comprised the arm (B) and were regarded as true negatives if no suspicious changes appeared during the follow-up. The vocal cords from the arm A were categorised into the benign and malignant group according to the histologic result. The ratio of vascular patterns was determined and the groups were statistically compared using the Chi-square test and Fisher's exact test. Perpendicular changes were observed in 36.6% (9/26) of benign diseases and in 100% (23/23) of cancer conditions (p < 0.001). Wide perpendicular changes appeared only in papillomas (6/6) while narrow ones mostly in malignancies (23/26) and also in benign conditions (3/26) (p < 0.001). The sensitivity, specificity, positive and negative predictive values, and accuracy were 100, 95, 88, 100 and 96%, respectively. The new ELS classification can be used effectively and safely to differentiate malignant from benign disease.

The influence of closure technique in total laryngectomy on the development of a pseudo-diverticulum and dysphagia.

OBJECTIVE: In total laryngectomy, the neopharynx can be closed in several ways. It is suggested that a pseudo-diverticulum is seen more frequently in patients closed with vertical closure than with "T"-shaped closure, causing postoperative dysphagia. We report the results of patients treated with vertical closure and "T"-shaped closure with regard to the formation of a pseudo-diverticulum and postoperative dysphagia. METHODS: In our retrospective cohort study, we identified 117 consecutive laryngectomized patients treated in the VU University Medical Center of Amsterdam between March 2009 and December 2013. Evaluations with statistical analysis of postoperative outcome measures (the formation of a pseudo-diverticulum and dysphagia), qualitative and quantitative variables were conducted. RESULTS: Patient demographics were similar between the vertical-shaped closure and the "T"-shaped closure groups. In 84.6% of patients with vertical closure, a pseudo-diverticulum was seen compared to 18.5% with "T"-shaped closure (p < 0.001). Dysphagia was increasingly seen in patients with a pseudo-diverticulum (60.5%) compared to patients without a pseudo-diverticulum (39.5%) (p = 0.090). CONCLUSION: Formation of a pseudo-diverticulum is more frequently seen in laryngectomy patients closed with vertical closure than in patients closed with "T"-shaped closure of the neopharynx. It is favorable to implement "T"-shaped closure in laryngectomy.

Sensing of latent EBV infection through exosomal transfer of 5'pppRNA.

Complex interactions between DNA herpesviruses and host factors determine the establishment of a life-long asymptomatic latent infection. The lymphotropic Epstein-Barr virus (EBV) seems to avoid recognition by innate sensors despite massive transcription of immunostimulatory small RNAs (EBV-EBERs). Here we demonstrate that in latently infected B cells, EBER1 transcripts interact with the lupus antigen (La) ribonucleoprotein, avoiding cytoplasmic RNA sensors. However, in coculture experiments we observed that latent-infected cells trigger antiviral immunity in dendritic cells (DCs) through selective release and transfer of RNA via exosomes. In ex vivo tonsillar cultures, we observed that EBER1-loaded exosomes are preferentially captured and internalized by human plasmacytoid DCs (pDCs) that express the TIM1 phosphatidylserine receptor, a known viral- and exosomal target. Using an EBER-deficient EBV strain, enzymatic removal of 5'ppp, in vitro transcripts, and coculture experiments, we established that 5'pppEBER1 transfer via exosomes drives antiviral immunity in nonpermissive DCs. Lupus erythematosus patients suffer from elevated EBV load and activated antiviral immunity, in particular in skin lesions that are infiltrated with pDCs. We detected high levels of EBER1 RNA in such skin lesions, as well as EBV-microRNAs, but no intact EBV-DNA, linking non-cell-autonomous EBER1 presence with skin inflammation in predisposed individuals. Collectively, our studies indicate that virus-modified exosomes have a physiological role in the host-pathogen stand-off and may promote inflammatory disease.

Prevalence of swallowing and speech problems in daily life after chemoradiation for head and neck cancer based on cut-off scores of the patient-reported outcome measures SWAL-QOL and SHI.

The objective of this study is to assess swallowing and speech outcome after chemoradiation therapy for head and neck cancer, based on the patient-reported outcome measures Swallowing Quality of Life Questionnaire (SWAL-QOL) and Speech Handicap Index (SHI), both provided with cut-off scores. This is a cross-sectional study. Department of Otolaryngology/Head and Neck Surgery of a University Medical Center. Sixty patients, 6 months to 5 years after chemoradiation for head and neck squamous cell carcinoma. Swallowing Quality of Life Questionnaire (SWAL-QOL) and SHI, both validated in Dutch and provided with cut-off scores. Associations were tested between the outcome measures and independent variables (age, gender, tumor stage and site, and radiotherapy technique, time since treatment, comorbidity and food intake). Fifty-two patients returned the SWAL-QOL and 47 the SHI (response rate 87 and 78 %, respectively). Swallowing and speech problems were present in 79 and 55 %, respectively. Normal food intake was noticed in 45, 35 % had a soft diet and 20 % tube feeding. Patients with soft diet and tube feeding reported more swallowing problems compared to patients with normal oral intake. Tumor subsite was significantly associated with swallowing outcome (less problems in larynx/hypopharynx compared to oral/oropharynx). Radiation technique was significantly associated with psychosocial speech problems (less problems in patients treated with IMRT). Swallowing and (to a lesser extent) speech problems in daily life are frequently present after chemoradiation therapy for head and neck cancer. Future prospective studies will give more insight into the course of speech and swallowing problems after chemoradiation and into efficacy of new radiation techniques and swallowing and speech rehabilitation programs.

A Participatory Design Approach to Develop a Web-Based Self-Care Program Supporting Early Rehabilitation among Patients after Total Laryngectomy.

AIM: To develop a Web-based self-care program for patients after total laryngectomy according to a participatory design approach. METHODS: We conducted a needs assessment with laryngectomees (n = 9) and their partners (n = 3) by means of a focus group interview. In 4 focus group sessions, a requirement plan was formulated by a team of health care professionals (n = 10) and translated into a prototype. An e-health application was built including illustrated information on functional changes after total laryngectomy as well as video demonstrations of skills and exercises. Usability of the prototype was tested by end users (n = 4) and expert users (n = 10). Interviews were held to elicit the intention to use and the desired implementation strategy. RESULTS: Six main self-care topics were identified: (1) nutrition, (2) tracheostomy care, (3) voice prosthesis care, (4) speech rehabilitation, (5) smell rehabilitation, and (6) mobility of head, neck, and shoulder muscles. Expert users expressed concerns regarding tailored exercises, indicated a positive intent to implement the intervention in routine care, and expressed a need for guidance when implementing the intervention. End users and expert users appreciated the content completeness and multimedia-based information built into the application. CONCLUSION: The participatory design is a valuable approach to develop a self-care program to help meet users' needs.

Multimodal guided self-help exercise program to prevent speech, swallowing, and shoulder problems among head and neck cancer patients: a feasibility study.

BACKGROUND: During a 6-week course of (chemo)radiation many head and neck cancer patients have to endure radiotherapy-induced toxicity, negatively affecting patients' quality of life. Pretreatment counseling combined with self-help exercises could be provided to inform patients and possibly prevent them from having speech, swallowing, and shoulder problems during and after treatment. OBJECTIVE: Our goal was to investigate the feasibility of a multimodal guided self-help exercise program entitled Head Matters during (chemo)radiation in head and neck cancer patients. METHODS: Head and neck cancer patients treated with primary (chemo)radiation or after surgery were asked to perform Head Matters at home. This prophylactic exercise program, offered in three different formats, aims to reduce the risk of developing speech, swallowing, shoulder problems, and a stiff neck. Weekly coaching was provided by a speech and swallowing therapist. Patients filled out a diary to keep track of their exercise activity. To gain insight into possible barriers and facilitators to exercise adherence, reports of weekly coaching sessions were analyzed by 2 coders independently. RESULTS: Of 41 eligible patients, 34 patients were willing to participate (83% uptake). Of participating patients, 21 patients completed the program (64% adherence rate). The majority of participants (58%) had a moderate to high level of exercise performance. Exercise performance level was not significantly associated with age (P=.50), gender (P=.42), tumor subsite (P=1.00) or tumor stage (P=.20), treatment modality (P=.72), or Head Matters format (Web-based or paper) (P=1.00). Based on patients' diaries and weekly coaching sessions, patients' perceived barriers to exercise were a decreased physical condition, treatment-related barriers, emotional problems, lack of motivation, social barriers, and technical problems. Patients' perceived facilitators included an increased physical condition, feeling motivated, and social and technical facilitators. CONCLUSIONS: Head Matters, a multimodal guided self-help exercise program is feasible for head and neck cancer patients undergoing (chemo)radiation. Several barriers (decreased physical condition, treatment-related barriers) and facilitators (increased physical condition, feeling motivated) were identified providing directions for future studies. The next step is conducting a study investigating the (cost-)effectiveness of Head Matters on speech, swallowing, shoulder function, and quality of life.