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.

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.

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.

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.

Associations between voice quality and swallowing function in patients treated for oral or oropharyngeal cancer.

PURPOSE: The purpose of this study was to investigate associations between voice quality and swallowing function in patients treated for oral or oropharyngeal cancer. METHODS: Recordings of speech and videofluoroscopy of 51 patients after treatment for oral or oropharyngeal cancer were analysed. Acoustic voice parameters (fundamental frequency (F0), perturbation (jitter %, shimmer %), harmonics-to-noise ratio (HNR), and intensity (extracted from the vowels /a/, /i/, and /u/)) were compared to swallowing function parameters as assessed via videofluoroscopy (oral, oropharyngeal, and total transit time; estimated percent of oral, oropharyngeal, and total residue; oropharyngeal swallowing efficiency (OPSE), and the penetration/aspiration (PA-) scale). RESULTS: Stepwise multivariate regression analyses revealed that jitter, shimmer, and HNR were not associated with swallowing function. Higher voice intensity in all three vowels /a/, /i/, and /u/ was significantly associated with a higher score on the PA-scale (more penetration and aspiration). Higher voice intensity and F0 were significantly associated with lower OPSE. CONCLUSION: Higher voice intensity was significantly associated with higher amount of penetration/aspiration, and higher voice intensity and fundamental frequency were significantly associated with swallowing inefficiency. Possible explanations may be found in overcompensation by increased laryngeal muscular strength resulting in increased intensity and pitch during phonation. However, the physiology of associated voice and swallowing function is yet unclear, and more research is recommended.

Computerized monitoring of patient-reported speech and swallowing problems in head and neck cancer patients in clinical practice.

PURPOSE: The purpose of this study is to evaluate computerized monitoring of speech and swallowing outcomes and its impact on quality of life (QoL) and emotional well-being in head and neck cancer patients in an outpatient clinic. METHODS: Sixty-seven patients, treated by single or multimodality treatment, completed the EORTC QLQ-C30 and QLQ-H&N35 questionnaires and the Hospital Anxiety and Depression Scale in an outpatient clinic, using a touch screen computer system (OncoQuest), at baseline (at time of diagnosis) and first follow-up (1 month after end of treatment). RESULTS: Tumor sites included oral cavity (n = 12), oropharynx (n = 18), hypopharynx (n = 8), and larynx (n = 29). Tumor stage included carcinoma in situ (n = 3), stage I (n = 21), stage II (n = 7), stage III (n = 15), and IV (n = 21). No speech or swallowing problems at baseline or follow-up were noted in 23 % (speech) and 41 % (swallowing) of patients. Twenty-one percent (speech) and 19 % (swallowing) had problems at baseline and returned to normal scores at follow-up, while 16 % (speech) and 19 % (swallowing) had normal scores at baseline and developed problems at follow-up. Forty percent (speech) and 21 % (swallowing) had persistent problems from baseline to follow-up. At baseline, speech problems were significantly related to tumor site and emotional distress. At baseline and follow-up, swallowing problems were significantly related to QoL and emotional distress. At follow-up, speech problems were significantly related to QoL, emotional distress, and swallowing problems. CONCLUSIONS: Monitoring speech and swallowing problems through OncoQuest in an outpatient clinic is feasible. Many patients report speech and swallowing problems, negatively affecting their QoL and emotional well-being.

Irinotecan-induced dysarthria.

Colorectal carcinomas are among the most common tumor types and are generally treated with palliative chemotherapy in case of metastatic disease. Here, we describe the case of a 46-year-old patient with metastatic rectal carcinoma who received second-line therapy with irinotecan and developed isolated transient dysarthria (with normal MR imaging of the brain) following each administration of irinotecan. Neurological and logopedical evaluation revealed that the dysarthria predominantly resulted from a reduced capacity in fine-tuning of motor functions of the tip of the tongue and a minimal reduction in the power of speech at labiodental contact. As hypoglossal nerve activity has been reported to be especially susceptible to cholinergic stimulation and irinotecan can cause cholinergic side effects by binding to and inactivating acetylcholinesterase, we suspect this mechanism to be responsible for irinotecan-induced dysarthria.

Predictive modelling for swallowing dysfunction after primary (chemo)radiation: results of a prospective observational study.

BACKGROUND AND PURPOSE: The purpose of this large multicentre prospective cohort study was to identify which dose volume histogram parameters and pre-treatment factors are most important to predict physician-rated and patient-rated radiation-induced swallowing dysfunction (RISD) in order to develop predictive models for RISD after curative (chemo) radiotherapy ((CH) RT). MATERIAL AND METHODS: The study population consisted of 354 consecutive head and neck cancer patients treated with (CH) RT. The primary endpoint was grade 2 or more swallowing dysfunction according to the RTOG/EORTC late radiation morbidity scoring criteria at 6 months after (CH) RT. The secondary endpoints were patient-rated swallowing complaints as assessed with the EORTC QLQ-H&N35 questionnaire. To select the most predictive variables a multivariate logistic regression analysis with bootstrapping was used. RESULTS: At 6 months after (CH) RT the bootstrapping procedure revealed that a model based on the mean dose to the superior pharyngeal constrictor muscle (PCM) and mean dose to the supraglottic larynx was most predictive. For the secondary endpoints different predictive models were found: for problems with swallowing liquids the most predictive factors were the mean dose to the supraglottic larynx and radiation technique (3D-CRT versus IMRT). For problems with swallowing soft food the mean dose to the middle PCM, age (18-65 versus >65 years), tumour site (naso/oropharynx versus other sites) and radiation technique (3D-CRT versus IMRT) were the most predictive factors. For problems with swallowing solid food the most predictive factors were the mean dose to the superior PCM, the mean dose to the supraglottic larynx and age (18-65 versus >65 years). And for choking when swallowing the V60 of the oesophageal inlet muscle and the mean dose to the supraglottic larynx were the most predictive factors. CONCLUSIONS: Physician-rated and patient-rated RISD in head and neck cancer patients treated with (CH) RT cannot be predicted with univariate relationships between the dose distribution in a single organ at risk and an endpoint. Separate predictive models are needed for different endpoints and factors other than dose volume histogram parameters are important as well.

Patient reported voice outcome in recurrent respiratory papillomatosis.

OBJECTIVES/HYPOTHESIS: To assess the impact of patient reported voice outcome on quality of life and emotional functioning in patients treated for recurrent respiratory papillomatosis (RRP). STUDY DESIGN: Cross-sectional. METHODS: All adult patients treated for RRP between 1984 and 2008 were asked to participate. Outcome measures were obtained from questionnaires including VHI (Voice Handicap Index), HADS (Hospital Anxiety and Depression Scale), 36-Item Short Form Health Survey (SF-36), and Utrechtse Coping List. RESULTS: Out of 45 included patients, 34 (22 males,12 females) participated (76%). Mean age was 52 years (range, 25-85 years). RRP was located only in the larynx in 90% of the cases. Adult onset RRP was diagnosed in 29 cases, juvenile onset RRP in 5. Median number of surgical procedures was five (range, 1-17). In this study cohort, 68% scored above the VHI cutoff point, and 18% had an increased risk for depression or anxiety disorders (HADS). VHI scores were related to age, time between consecutive surgeries, time since last surgery, and passive coping. They were not related to gender, onset of RRP, or location. VHI scores were related to the SF-36 subscales social functioning (r = -0.43) and mental health (r = -0.43). CONCLUSIONS: Patients with RRP often report voice problems in daily life, and this is related to (a passive) coping style, social functioning, and mental health. Psychosocial intervention targeting an adaptive coping style may be beneficial in selected cases.