Multiple endocrine neoplasia type 2: A review.

Multiple endocrine neoplasias are rare hereditary syndromes some of them with malignant potential. Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant hereditary cancer syndrome due to germline variants in the REarranged during Transfection (RET) proto-oncogene. There are two distinct clinical entities: MEN 2A and MEN 2B. MEN 2A is associated with medullary thyroid carcinoma (MTC), phaeochromocytoma, primary hyperparathyroidism, cutaneous lichen amyloidosis and Hirschprung's disease and MEN 2B with MTC, phaeochromocytoma, ganglioneuromatosis of the aerodigestive tract, musculoskeletal and ophthalmologic abnormalities. Germline RET variants causing MEN 2 result in gain-of-function; since the discovery of the genetic variants a thorough search for genotype-phenotype associations began in order to understand the high variability both between families and within family members. These studies have successfully led to improved risk classification of prognosis in relation to the genotype, thus improving the management of the patients by thorough genetic counseling. The present review summarizes the recent developments in the knowledge of these hereditary syndromes as well as the impact on clinical management, including genetic counseling, of both individual patients and families. It furthermore points to future directions of research for better clarification of timing of treatments of the various manifestations of the syndromes in order to improve survival and morbidity in these patients.

Missed cancer in the Danish head and neck cancer fast-track program: results from a tertiary cancer center.

BACKGROUND: The Danish head and neck cancer fast-track program is a national standardized pathway aiming to reduce waiting time and improve survival for patients suspected of cancer in the head and neck (HNC). Until now, the frequency of missed cancer in the fast-track program has not been addressed. A missed cancer leads to treatment delay and may cause disease progression and worsening of prognosis. The study objective was to estimate the frequency of patients with missed cancers in the Danish HNC fast-track program and to evaluate the accuracy of the program. MATERIALS AND METHODS: Patients who were rejected from the HNC fast-track program because cancer was not found between 1 July 2012 and 31 December 2018 at Odense University Hospital, Denmark were included and followed for three years. Patients were categorized into groups depending on the diagnostic evaluation. Group 1 included patients evaluated with standard clinical work-up without imaging and biopsy. Group 2 included patients evaluated with imaging and/or biopsy in addition to the standard clinical work-up. The local cancer database and electronic patient records were reviewed to determine if a missed cancer had occurred within the follow-up period. RESULTS: A total of 8345 HNC fast-track courses were initiated during the study period. 1499 were patients suspected of recurrent cancer and were excluded leaving 6846 patients to be assessed for eligibility. Of these, 3752 patients were rejected because cancer was not found. Ten patients were subsequently diagnosed with cancer within the follow-up period resulting in an overall frequency of 0.15%. For group 1 and 2, the frequency was 0.04% and 0.10%, respectively. The sensitivity of the fast-track program was 99.67% and the negative predictive value was 99.73%. CONCLUSION: The frequency of missed cancer in a tertiary HNC center following the Danish fast track program is low.

Epidemiology, outcomes, and prognostic factors in submandibular gland carcinomas: a national DAHANCA study.

PURPOSE: The aim of this study is to present incidence, histological subtypes, survival rates, and prognostic factors based on a national cohort of patients with salivary gland carcinoma. METHODS: All Danish patients with submandibular gland carcinoma diagnosed from 1990 to 2015 (n = 206) were included and analyzed following histological re-evaluation. Data were collected by the Danish Head and Neck Cancer Group (DAHANCA). Overall, disease-specific and recurrence-free survival were evaluated. Prognostic factors were analyzed with multivariate Cox Hazard Regression. RESULTS: The study population consisted of 109 (53%) men and 97 (47%) women, median age 62 years (range 11-102). Adenoid cystic carcinoma was the most frequent subtype (50%). Tumour classification T1/T2 (75%) and N0 (78%) was most frequent. The mean crude incidence was 0.17/100,000/year. Most patients (n = 194, 94%) were treated with primary surgery, and 130 (67%) received postoperative radiotherapy. The 5- and 10-year survival rates were for overall survival 64% and 41%, disease-specific survival 74% and 61%, and recurrence-free survival 70% and 56%, respectively. Survival rates were higher for adenoid cystic carcinoma compared to other subtypes, but the difference was not significant in multivariate analysis. Recurrence occurred in 69 patients, and 37 (53.6%) of them had recurrence in a distant site. Advanced T-classification and regional lymph-node metastases had significant negative impact on survival rates. CONCLUSION: The incidence of submandibular gland carcinoma in Denmark was 0.17/100,000/year and stable during the time period. The most frequent subtype was adenoid cystic carcinoma. Half of the recurrences presented in a distant site, and multivariate analysis confirmed that advanced stage was independent negative prognostic factor for recurrence and survival.

A history of occupational noise exposure is associated with steep-slope audiograms and poorer self-reported hearing-aid outcomes.

OBJECTIVE: To investigate the effects of previous occupational noise exposure in older adults with hearing loss on (1) audiometric configuration and acoustic reflex (AR) thresholds and (2) self-reported hearing abilities and hearing aid (HA) effectiveness. DESIGN: A prospective observational study. STUDY SAMPLE: The study included 1176 adults (≥60 years) with bilateral sensorineural hearing loss. Pure-tone audiometry, AR thresholds, and responses to the abbreviated version of the Speech, Spatial, and Qualities of Hearing Scale (SSQ12) and the International Outcome Inventory for Hearing Aids (IOI-HA) questionnaire were obtained, along with information about previous occupational noise exposure. RESULTS: Greater occupational noise exposure was associated with a higher prevalence of steeply sloping audiograms in men and women and a 0.32 (95% CI: -0.57; -0.06) scale points lower mean SSQ12 total score among noise-exposed men. AR thresholds did not show a significant relation to noise-exposure status, but hearing thresholds at a given frequency were related to elevated AR thresholds at the same frequency. CONCLUSIONS: A noise exposure history is linked to steeper audiograms in older adults with hearing loss as well as to poorer self-reported hearing abilities in noise-exposed men. More attention to older adults with previous noise exposure is warranted in hearing rehabilitation.

Nasal vestibule squamous cell carcinoma: a population-based cohort study from DAHANCA.

BACKGROUND: Cancer of the nasal vestibule is a rare type of malignancy dominated by squamous cell carcinoma (SCC), and with poor survival. The treatment is either radiotherapy, surgery or a combination of both. Previous studies have shown a 5-year disease-specific survival of 74% and overall survival (OS) of 50%.Our objective was to describe the consecutive cohort of patients diagnosed with SCC of the nasal vestibule in Denmark from 2008 until 2018 and evaluate prognostic factors and treatment outcome using locoregional failure (LRF), disease-specific mortality (DSM), and OS as endpoints. METHODS: All patients diagnosed with SCC of the nasal vestibule from 2008 until 2018 were identified in the nationwide clinical database, DAHANCA and were followed for LRF and death (DSM and OS) until March 2021. OS was analysed using Kaplan-Meier estimator, and cumulative incidence of LRF and DSM were analysed using the Aalen-Johansen estimator. Analysis of prognostic factors was performed using Cox proportional hazard models. RESULTS: A total of 162 patients were identified. The median age was 71 years and 54% were male. Disease stage at the time of diagnosis were stage I (70%), II (17%), III (2%) and IV (11%). Curatively intended treatment was performed in 146 patients (90%), of which treatment failure occurred in 42 patients (29%). Most failures occurred at the primary tumour site (64%). Cancer Patient Pathways recommended time to treatment was fulfilled in 71% of patients. The 5-year OS and DSM in patients treated with curative intent were 65% and 11%, respectively. Stage was a significant independent prognostic factor. No difference in LRF, DSM or OS were shown between the applied treatments. CONCLUSIONS: Stage is the main independent prognostic factor, and failure most commonly appear at the primary tumour site.

The Impact of Post-Thyroidectomy Neck Stretching Exercises on Neck Discomfort, Pressure Symptoms, Voice and Quality of Life: A Randomized Controlled Trial.

BACKGROUND: Following surgery for benign nodular goiter, patients may experience neck and shoulder pain, neck pressure and tightness, choking sensation, altered voice function, and dysphagia leading to decreased short-term quality of life (QoL). This single-blinded randomized controlled trial investigated the effect of post-thyroidectomy rehabilitative neck stretching and movement exercises on these variables including QoL. METHODS: Patients undergoing thyroid lobectomy or total thyroidectomy were randomized to perform neck stretching and movement exercises three times daily in four weeks following surgery (intervention group) or conventional follow-up without exercises (control group). Outcome measures were scores in the following questionnaires: Disease-specific Thyroid-Related Patient-Reported Outcome (ThyPRO-39) involving symptoms of "sense of fullness in the neck," "pressure in the throat," and "discomfort swallowing" combined in the multi-item Goiter Symptom Scale, the Voice Handicap-Index-10 (VHI-10), neck and shoulder pain measurement by a numeric rating scale (NRS), and General measure of health (EQ-5D-5L). All scores were assessed prior to surgery and one, two, four weeks, and three months after surgery. Data were analyzed using a linear mixed model. RESULTS: Eighty-nine patients were included and randomized to the control (n = 45) or the intervention group (n = 44). At three months after surgery, both the control and the intervention group experienced large to moderate improvements in the Goiter symptom and Hyperthyroid symptom scale of the ThyPRO questionnaire (p < 0.004). No significant between-group differences were found in any of the other applied scales. CONCLUSIONS: This study confirms that patients experience profound improvements in QoL after surgery for benign nodular goiter. However, early post-thyroidectomy neck stretching and movement exercises did not result in further QoL improvement, reduction in pain or less impacted subjective voice function for patients primarily undergoing thyroid lobectomy. Trial Registration Number NCT04645056 ( https://clinicaltrials.gov ).

Diagnosis of possible nasopharyngeal malignancy in adults with isolated serous otitis media; a systematic review and proposal of a management algorithm.

PURPOSE: The objective of this study was (1) to systematically review the evidence of routine post-nasal space blind biopsies and/or imaging of adults with isolated serous otitis media (SOM) of unknown cause for detection nasopharyngeal malignancy (NPM), and (2) to design a clinical management algorithm for these patients. METHODS: A systematic search was conducted in the databases PubMed, Embase and Cochrane Library guided by the study question "Should adults with isolated SOM of unknown cause undergo routine biopsies of the post-nasal space and/or diagnostic imaging for detection of NPM?". All retrieved studies were reviewed and quantitatively analyzed. RESULTS: The systematic literature search identified 552 publications accessible for title-abstract screening. This yielded 23 studies for full text assessment, of which 6 were found eligible for inclusion. All six studies dealt with nasopharyngeal blind biopsies, whereas no studies on cross-sectional imaging were identified. The derived summarized results of the included studies showed that 5.5% (31/568) of patients with isolated SOM of unknown cause were diagnosed with NPM. Of these, 6.5% (2/31) had normal nasopharyngeal endoscopy (i.e., malignancy was discovered by blind biopsies). Finally, 0.35% (2/568) of patients with isolated SOM of unknown cause diagnosed with NPM had normal nasopharyngeal endoscopy findings (i.e., nasopharyngeal endoscopy ruled-out malignancy in 99.65% of patients). CONCLUSIONS: We found no evidence supporting routine use of blind biopsies or cross-sectional imaging in adults with isolated serous otitis media of unknown cause. We propose a pragmatic management algorithm for workup of adults with persistent secretory otitis media.

Sinonasal cancer in Denmark 2008-2015: a population-based phase-4 cohort study from DAHANCA.

BACKGROUND: Sinonasal cancer is considered a rare disease with poor survival. Its treatment has changed profoundly in recent years, primarily following the introduction of intensity-modulated radiation therapy (IMRT) and minimally invasive endoscopic surgery. Danish national guidelines on treatment of patients diagnosed with sinonasal carcinoma were introduced in 2007. The aim of this phase-4 study was to assess the effect of the implementation of guidelines by describing treatment outcomes in a consecutive nationwide cohort. METHODS: All patients diagnosed with sinonasal carcinoma in Denmark from 2008 to 2015 were identified in the nationwide clinical database, DAHANCA, and were followed until May 2020. Overall survival (OS) was analysed using Kaplan-Meier estimator. Cumulative incidence of locoregional failure (LRF) and disease-specific mortality (DSM) were analysed using the Aalen-Johansen estimator. Competing risks were death from other causes (DSM) and distant failure and death (LRF). Analysis of prognostic factors was performed using Cox proportional hazard analysis. Start of follow-up was time of diagnosis. The results are presented as estimates with 95% confidence intervals (95% CIs). RESULTS: A total of 331 patients were identified. Curatively intended treatment was performed in 264 patients (80%). Non-compliance with treatment guidelines was registered in 24 patients (9%). Non-compliance was associated with LRF (hazard ratio [HR], 2.0 [95% CI: 1.1-3.5]). Among patients qualified for curative treatment, failure occurred in 109 patients (41%), primarily at the primary tumour site (81%). Anatomical tumour site and disease stage were independent prognostic factors. The 5-year OS was 56% in patients treated with curative intent, and a combined treatment strategy showed reduced LRF (HR, 0.53 [95% CI: 0.30-0.92]) in a multivariate analysis. CONCLUSIONS: Guideline compliance and a combined treatment approach reduced the incidence of LRF and thereby increased OS. Our results confirm those of international studies. Treatment of sinonasal carcinoma remains a challenge that requires multidisciplinary team coordination.

Salivary gland carcinoma in Denmark: a national update and follow-up on incidence, histology, and outcome.

PURPOSE: Salivary gland carcinoma is a rare disease and studies on epidemiology and outcome require data collection over many years. The aim of this study is to present an update of incidence rates, anatomical sites, histological subtypes, and survival rates based on the Danish national cohort of salivary gland carcinoma patients. METHODS: Data from all Danish patients with salivary gland carcinoma diagnosed from 1990 to 2015 (n = 1601) were included and analyzed following histological reevaluation and reclassification. Overall, disease-specific, and recurrence-free survival were evaluated. Prognostic factors were analyzed with multivariate Cox Hazard Regression. RESULTS: The study population consisted of 769 men and 832 women, median age 62 years (range 6-102). The most frequent anatomic site was the parotid gland (51.8%). Adenoid cystic carcinoma was the most common subtype (24.7%). The majority had tumor classification T1/T2 (65.3%). The mean crude incidence was 1.2/100.000/year with an increase of 1.5% per year. There was no increase in age-adjusted incidence. The 5-, 10-, and 20-year survival rates were for overall survival 68, 52, and 35%, for disease-specific survival, 77, 69, and 64%, and for recurrence-free survival, 75, 64, and 51%, respectively. Age, high-grade histological subtype, advanced T-classification, cervical lymph node metastases, vascular invasion, and involved surgical margins had significantly negative impact on survival rates. CONCLUSION: The age-adjusted incidence has been stable for a period of 26 years. Multivariate analysis confirmed that histological grade, advanced stage, involved surgical margins and vascular invasion are independent negative prognostic factors. Survival rates were stationary compared to earlier reports.

Recommendations for head and neck surgical oncology practice in a setting of acute severe resource constraint during the COVID-19 pandemic: an international consensus.

The speed and scale of the global COVID-19 pandemic has resulted in unprecedented pressures on health services worldwide, requiring new methods of service delivery during the health crisis. In the setting of severe resource constraint and high risk of infection to patients and clinicians, there is an urgent need to identify consensus statements on head and neck surgical oncology practice. We completed a modified Delphi consensus process of three rounds with 40 international experts in head and neck cancer surgical, radiation, and medical oncology, representing 35 international professional societies and national clinical trial groups. Endorsed by 39 societies and professional bodies, these consensus practice recommendations aim to decrease inconsistency of practice, reduce uncertainty in care, and provide reassurance for clinicians worldwide for head and neck surgical oncology in the context of the COVID-19 pandemic and in the setting of acute severe resource constraint and high risk of infection to patients and staff.

Incidence and malignant transformation of glottic precursor lesions in Denmark.

Objectives: Glottic precursor lesion (GPL) is a well-known premalignant condition, but the existing knowledge of incidence and malignant potential is based on subpopulation studies. In this first, nationwide study we report data from all verified cases of GPL in Denmark during a 10-year period with focus on incidence and malignant transformation of GPL.Methods: Patients were identified by a search for GPL in the time period from 01.01.2000 to 31.12.2009 using the Danish Pathology Data Base, Patobank, which is a nationwide source of all cyto- and histopathological data obtained in Denmark. Data were validated and supplemented by medical chart review.Results: A 10-year national cohort of 965 patients (median age 60 years, male-female ratio 2:1) with histologically verified GPL was analyzed. The overall malignant transformation rate was 18.3% (mild dysplasia 7.7%, moderate dysplasia 19.8%, severe dysplasia 28.5%, and carcinoma in situ 40.3%) with a median progression time of 29 months. Eighty-eight percent of patients were active or former smokers. A significantly larger proportion of male patients (24.1%) experienced malignant transformation compared to females (6.6%) (p < .001).Conclusion: This nationwide population-based study of GPL patients confirmed a stable incidence of GPL in Denmark from January 2000 to December 2009 and a considerable malignant potential, correlated to the grading of GPL according to the World Health Organization classification of laryngeal precursor lesions from 2005, WHOC2005. The recent update, WHOC2017, of low-grade versus high-grade lesions may thus contain less nuanced prognostic information than WHOC2005.Level of evidence: 2b retrospective cohort study.

Elective neck dissection in patients with salivary gland carcinoma: A systematic review and meta-analysis.

OBJECTIVE: Elective neck dissection in patients with salivary gland carcinoma and clinically negative lymph nodes is controversial. Reported proportion of occult nodal metastases vary with histological subtype, tumour classification and preoperative diagnostic methods. This is a systematic review and meta-analysis on the role of END in salivary gland carcinoma. METHODS: A search in PubMed, Embase and Cochrane was performed. Original articles in English with data on tumour characteristics, clinical and pathological N-classification, and neck dissection were included. Reporting Items for Systematic Reviews and Meta-analyses were followed. Random effect modelling was performed to pool the data. Meta-analysis of proportions was performed for occult metastases overall, for T3/T4 versus T1/T2 tumours and for tumours with high-grade versus low-grade histology. Heterogeneity across studies was assessed with I-squared statistics. RESULTS: We included 22 articles in the qualitative synthesis and meta-analysis. The pooled proportion of occult metastases was 21%. In patients with T3/T4 tumour, the pooled proportion of occult metastases was 36%, and in patients with high-grade histology, it was 34%. Most studies concluded that END should be performed in patients with advanced T-classification and high-grade histology tumours. Nine studies assessed occult metastases per level. CONCLUSION: The overall occult metastases proportion does not require END in all patients with salivary gland carcinoma. We recommend END in patients with high-grade or unknown histology or T3/T4 tumours. END should involve level II and III, and level I should be included in tumours in the submandibular gland, sublingual gland and minor oral salivary glands.

Definition of locally recurrent head and neck squamous cell carcinoma: a systematic review and proposal for the Odense-Birmingham definition.

PURPOSE: The objectives of this study were (1) to systematically review current definitions of head and neck squamous cell carcinoma (HNSCC) recurrence and (2) to propose a definition of locally recurrent HNSCC. METHODS: A systematic literature review was performed according to the 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' statement in Medline, Embase, and Cochrane databases guided by the study question "What is the definition of local recurrence for patients with HN:SCC?". All retrieved studies were reviewed and qualitatively analyzed. RESULTS: The systematic literature search resulted in 3467 publications after removal of duplicates. Forty studies were examined as full text, and a total of five were found suitable for inclusion. All five included studies dealt with definitions of second primary HNSCC and were based on the Warren and Gates Criteria; (1) each of the tumors are malignant, (2) each must be distinct, and (3) the probability of one being a metastasis of the other must be excluded. Each of the included studies added specific anatomical and/or temporal separation measures to the criteria of second primary HNSCC. We propose the definition of locally recurrent HNSCC to be: (1) Same anatomical subsite or adjacent subsite within 3 cm of the primary lesion, (2) time-interval no more than 3 years (from completed treatment of the primary lesion), and (3) same p16-status for oropharyngeal carcinomas. CONCLUSIONS: No uniform definition of locally recurrent HNSCC currently exists. We propose the Odense-Birmingham definition based on the anatomical subsite combined with a specific measurable distance and a temporal separation of three years.

Interrater variation of vascular classifications used in enhanced laryngeal contact endoscopy.

PURPOSE: Combined use of contact endoscopy (CE) and Narrow Band Imaging (NBI, Olympus®) is suggested for the visualization of specific vascular changes indicative of glottic neoplasia. We investigated the interrater reliability and agreement in 3 recognized classification systems of vascular changes applied to images from CE + NBI in patients suspected for glottic neoplasia. METHODS: Six experienced head and neck surgeons familiar with NBI rated 120 images obtained by CE + NBI by 3 classification systems of vascular changes as suggested by Ni et al. (N-C), Puxeddu et al. (P-C), and the European Laryngological Society (ELS-C). Three raters were experienced in CE, and three raters had only limited experience with CE. Crude agreement and Fleiss' kappa with 95% confidence interval were estimated for all 6 raters, and for the 2 levels of expertise for each original classification system and for dichotomized versions of the N-C and the P-C based on suggested neoplastic potential. RESULTS: The interrater crude agreement and the corresponding kappa values for the ELS-C were good and significantly higher than those for the N-C and P-C for all raters, irrespective of the level of experience with CE (p < 0.0001). There were no significant differences between the N-C and the P-C (p = 0.16). Kappa was considerably improved for both the N-C and the P-C to a level not different from the ELS-C (p = 0.21-0.71) when their 5 original categories were pooled into dichotomized classifications. CONCLUSION: Difficulties in reliably classifying vascular changes in CE + NBI are evident. Two-tier classification systems are the most reliable.

Value of pre- and intraoperative diagnostic methods in suspected glottic neoplasia.

PURPOSE: To evaluate the individual and combined ability of videostroboscopy (VS), high-speed digital imaging (HSDI), enhanced endoscopy (EE) and saline infusion (SI) to predict neoplasia, defined as glottic precursor lesion (GPL) or T1a glottic cancer, in patients suspected for glottic neoplasia. METHODS: A nationwide prospective cohort study of patients treated by cordectomy for suspected GPL or T1a glottic cancer from August 1st 2016 to October 31st 2018 was conducted in the five Danish University Departments of Head and Neck surgery. Sensitivity, specificity, negative and positive predictive values, and area under Receiver Operating Curves (AUC-ROC) were calculated with 95% confidence intervals with respect to the histological diagnosis. Logistic regression with an imputation model for missing data was applied. RESULTS: 261 patients aged 34-91 years participated; 79 (30.3%) with non-neoplasia (i.e., inflammation, papilloma, hyperkeratosis) and 182 (69.7%) neoplasia, hereof 95 (36.4%) with GPL and 87 (33.3%) with T1a glottic cancer. Data from 188 VS, 60 HSDI, 100 preoperative EE, 209 intraoperative EE, and 234 SI were analyzed. In the complete case analysis the AUC-ROC of each diagnostic test was low, but increased when the tests were combined and especially if the combination included EE. However, multinomial logistic regression with imputation showed significant association (p < 0.05) only between age, male gender, and perpendicular vasculature in intraoperative EE, and the endpoint neoplasia. CONCLUSIONS: Intraoperative EE was the most accurate diagnostic method in detecting neoplasia. The prediction ability of methods applied preoperatively was more limited, but improved when test modalities were combined.

Therapeutic Use of the Human Papillomavirus Vaccine on Recurrent Respiratory Papillomatosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Recurrent respiratory papillomatosis is a benign condition caused by human papillomavirus (HPV). Surgery is the mainstay of treatment, but numerous adjuvant therapies have been applied to improve surgical outcome. Recently, HPV vaccination has been introduced, but only smaller studies of its effect have been published. The present meta-analysis is intended as a possible substitute for a proposed but not yet realized multicenter randomized controlled trial. METHODS: A systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. PubMed, Embase, and Cochrane were systematically searched. All retrieved studies (n = 593) were reviewed and qualitatively assessed. In addition, 2 previously unpublished data sets were included. The systematic review included 11 studies, comprising 133 patients, of whom 63 patients from 5 studies were eligible for meta-analysis. A random-effects meta-analysis was conducted for the mean difference in number of surgical procedures per month before and after vaccination. RESULTS: The number of surgical procedures per month was significantly reduced after HPV vaccination compared with before vaccination (estimated mean, 0.06 vs 0.35). The mean intersurgical interval increased from 7.02 months (range, 0.30-45 months) before to 34.45 months (2.71-82 months) after HPV vaccination. CONCLUSION: The present study supports the continued use of the HPV vaccine as an adjuvant treatment for recurrent respiratory papillomatosis.

Risk of Malignancy in FDG-Avid Thyroid Incidentalomas on PET/CT: A Prospective Study.

BACKGROUND: Due to a substantial risk of malignancy, patients with focal FDG-avid thyroid incidentalomas (FFTIs) on PET/CT are in most of Denmark referred to Head and Neck Cancer (HNC) fast track programs. The aim of this study was to determine the risk of malignancy in FFTI managed in a HNC fast track program. METHODS: A prospective cohort study including all patients with FFTI referred to the HNC fast track program, Odense University Hospital between September 1, 2016 and August 31, 2017. Ultrasonography (US) and fine-needle aspiration biopsy (FNAB) were intended to be done in all patients. Nodules with cytology of Bethesda 1, 3, 4, 5, or 6 were planned for surgical removal. RESULTS: A total of 104 patients were included. All patients had US and 101 patients (97%) had FNAB. Forty-two patients had benign cytology classified as Bethesda 2. The remaining 62 patients underwent surgery except from 11 patients, mainly due to comorbidity. The overall risk of malignancy for patients with FFTI referred to our HNC fast track program was calculated to be 24% (23/95) based on patients with unequivocal cytology and/or histology. The only statistically significant US characteristic to predict malignancy was the appearance of irregular margins with a sensitivity of 47% and specificity of 96%. CONCLUSION: The risk of malignancy of FFTIs handled in our HNC fast track program is 24%.

Up-front PET/CT changes treatment intent in patients with head and neck squamous cell carcinoma.

PURPOSE: In patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), we wanted to examine the differences in overall treatment decisions, i.e. curative versus palliative treatment intent, reached by a multidisciplinary team conference (MDTC) based on 18F-fluoro-deoxy-glucose-positron emission tomography/computed tomography (PET/CT) or chest X-ray + MRI of the head and neck (CXR/MRI). PATIENTS AND METHODS: This was a prospective blinded cohort study based on paired data. Consecutive patients with histologically verified primary HNSCC were invited to participate. All included patients underwent CXR/MRI and PET/CT before diagnostic biopsy. An ordinary MDTC using all available imaging was conducted as per standard practice. After at least 3 months (to eliminate recall bias in the team), the first project MDTC was conducted, based on either CXR/MRI or PET/CT, and the tumor board drew conclusions regarding treatment. After an additional 3 months, a second project MDTC was conducted using the complementary imaging modality. RESULTS: A total of 307 patients were included. Based on CXR/MRI, 303 patients (99%) were recommended for curative treatment and only four patients (1%) for palliative treatment. Based on PET/CT, the MDTC concluded that 278 (91%) patients were suitable for curative treatment and 29 (9%) patients for palliative treatment. The absolute difference of 8% was statistically significant (95% CI: 4.8%-11.5%, p < 0.001). CONCLUSIONS: A PET/CT-based imaging strategy significantly changed the decisions regarding treatment intent made by a MDTC for patients diagnosed with HNSCC, when compared with the standard imaging strategy of CXR/MRI.

Changes in Swallowing Symptoms and Esophageal Motility After Thyroid Surgery: A Prospective Cohort Study.

INTRODUCTION: Swallowing difficulties, the pathophysiology behind which is incompletely understood, have been reported in 47-83% of goiter patients referred for thyroidectomy. We aimed at examining the influence of thyroid surgery on swallowing symptoms and esophageal motility. METHODS: Thirty-three patients with benign nodular goiter undergoing thyroid surgery were included. All completed high-resolution esophageal manometry examinations and the goiter symptom scale score, assessed by the thyroid-specific patient-reported outcome measure. The evaluations were performed before and 6 months after surgery. RESULTS: Before surgery, the goiter symptom score was median 39 points (range 2-61), which improved to median five points (range 1-52) after surgery (p < 0.001). The motility parameters were within the limits of normal swallowing physiology, both before and after surgery. Only the upper esophageal sphincter (UES) pressure increased significantly from 70.6 ± 27.7 to 87.7 ± 43.2 mmHg after surgery (p = 0.04). Using regression analyses, there was no significant correlation between change in goiter symptoms and weight of the removed goiter, motility parameters, or motility disturbances. However, patients undergoing total thyroidectomy experienced a larger reduction in pressure in the area of the UES and former thyroid gland after surgery in comparison with patients undergoing less extensive surgery. CONCLUSIONS: Goiter symptoms improved significantly after thyroidectomy, but without correlation to esophageal motility disturbances. This information is essential when interpreting dysphagia in patients with nodular goiter, and when balancing patients' expectations to surgical goiter therapy. REGISTRATION NUMBER: NCT03100357 ( www.clinicaltrials.org ).