Current Practice, Safety and Efficacy of Interventions for Recurrent Respiratory Papillomatosis: Evidence From a UK Registry.

OBJECTIVES: To determine the current practice, safety and efficacy of interventions used in the management of recurrent respiratory papillomatosis (RRP) in the UK NHS. DESIGN: Prospective registry (recruitment between 1st April 2018 and 31st August 2022, retrospective data from 1st January 2015 permitted with consent). Sub-group data-linked to Hospital Episode Statistics for additional follow-up (until 31st July 2022). SETTING: UK NHS hospitals treating RRP patients. PARTICIPANTS: Children and adults diagnosed with RRP and managed in an NHS hospital. MAIN OUTCOME MEASURES: Disease severity (Derkay, voice handicap and GRBAS scores), management (type and frequency of surgical and adjuvant intervention) and complications (cancer, death). RESULTS: Three hundred and thirty patients were entered into the registry; 304 (including 65 children) were eligible for analysis. Children had more severe disease than adults (median Derkay score 10 vs. 5). Microdebrider was the most common surgical intervention, particularly in children (86% of children, 49% of adults). Additionally, lasers (CO2, KTP and pulsed dye) were used in 34% of adults. Gardasil was the most common adjuvant therapy (21 children, 23 adults). Procedural complications were rare (10.8% children, 5.9% adults). Five patients developed laryngeal malignancy; there were six deaths during follow-up period. CONCLUSIONS: This is the largest UK RRP study to date. RRP is more aggressive in children than adults, and treatment choice differs between age groups. Overall, management was safe with minimal complications reported, and generally effective in maintaining a safe airway. Standardised reporting is required to objectively monitor disease progression and safety over time. TRIAL REGISTRATION: NCT03465280, ISRCTN36100560.

Analysis of the interactions between small pulmonary nodules, clinical factors and the risk of malignancy in the chest following diagnosis of head and neck cancer.

BACKGROUND: This study aims to investigate radiological and clinical factors which predict malignancy in indeterminate pulmonary nodules in patients with head and neck cancer (HNC). METHODS: Prospective data were collected in 424 patients who were reviewed in the NHS Lothian HNC multidisciplinary meeting from May 2016 to May 2018. Staging and follow-up CT chest imaging were reviewed to identify and assess pulmonary nodules in all patients. RESULTS: About 61.8% of patients had at least one pulmonary nodule at staging CT. In total, 25 patients developed malignancy in the chest. Metastatic disease in the chest was significantly associated with unknown or negative p16 status (p < .0005). Pleural indentation and spiculation were associated with indeterminate nodules, subsequently being shown to represent metastatic disease (p > .0005 and p = .046, respectively). CONCLUSION: Negative or unknown p16 status was associated with an increased propensity to develop metastatic disease in the chest in patients with HNC.

Microscopic positive surgical margins in thyroid carcinoma: a proposal for thyroid oncology teams.

PURPOSE: In the case of well-differentiated thyroid cancer, the importance of microscopic margin status remains controversial. We discuss the relevance of the effect of microscopic positive surgical margins in the early stages of differentiated thyroid cancer. METHODS: A comprehensive literature search and review of available evidence in English literature was undertaken. RESULTS: A previous meta-analysis did not find an association between microscopic positive surgical margins and local recurrence. Heterogeneity of definitions and differences between microscopic surgical margins and extrathyroid extension are discussed. Impact on clinical decision-making is explored. CONCLUSION: The finding of microscopic positive surgical margins in a patient with a thyroid tumor without intraoperative evidence of macroscopic invasion to adjacent structures, with complete resection made by the surgeon and without pathological report of extrathyroid extension, does not have a worse prognostic effect. We present a classification of surgical margins that may help thyroid oncology teams to tailor further management in patients with thyroid cancer.

Transoral endoscopic vestibular approach for thyroidectomy and parathyroidectomy - From promise to practice.

OBJECTIVES: To describe the evolution and recent series on transoral endoscopic vestibular approach thyroidectomy and parathyroidectomy (TOET/PVA). DATA SOURCES: PubMed, Google Scholar. REVIEW METHODS: Review of the available English literature. RESULTS: TOET/PVA may offer several advantages over other remote access thyroidectomy approaches and has been adopted by many centers worldwide with excellent success rates. Indications include benign disease and early thyroid cancer patients. Complication rate is comparable to the trans-cervical approach. The suggested framework has been validated in recent studies and its feasibility confirmed. CONCLUSION: TOET/PVA has now been used to treat thousands of patients worldwide due to low cost, short learning curve and excellent cosmetic outcomes. Further studies will be necessary to demonstrate oncologic non-inferiority and also the true value that is added by the approach.

Management of the Neck in Well-Differentiated Thyroid Cancer.

PURPOSE OF REVIEW: In this narrative review, we discuss the indications for elective and therapeutic neck dissections and the postoperative surveillance and treatment options for recurrent nodal disease in patients with well-differentiated thyroid cancer. RECENT FINDINGS: Increased availability of advanced imaging modalities has led to an increased detection rate of previously occult nodal disease in thyroid cancer. Nodal metastases are more common in young patients, large primary tumors, specific genotypes, and certain histological types. While clinically evident nodal disease in the lateral neck compartments has a significant oncological impact, particularly in the older age group, microscopic metastases to the central or the lateral neck in well-differentiated thyroid cancer do not significantly affect outcome. As patients with clinically evident nodal disease are associated with worse outcomes, they should be treated surgically in order to reduce rates of regional recurrence and improve survival. The benefit of elective neck dissection remains unverified as the impact of microscopic disease on outcomes is not significant.

Considerations for environmentally sustainable head and neck surgical oncology practice.

OBJECTIVE: To evaluate the potential role of head and neck oncologic surgeons in environmental protection, sustainability of health-care systems and avoidance of procedures contributing to climate change in the future. REVIEW METHODS: This literature review searched for relevant literature about the relevance of waste in surgical head and neck oncology practice and the innovative alternatives to decrease its effect on environment. CONCLUSIONS: Head and neck oncologic surgeons have a role in environmental protection, sustainability of health-care systems and avoidance of procedures contributing to climate change in the future. However, there exist only limited data on waste management and other procedures in surgical oncology to promote these practices. IMPLICATIONS FOR PRACTICE: By increasing awareness of the corresponding issues of waste production within the healthcare environment, head and neck surgeons can have a pioneering role in considering how to reduce, recycle and reuse in a more efficient manner. As research in this field accumulates, healthcare providers can engage both managers and clinicians in this process. It remains imperative to provide these professionals opportunities for their work force to rethink current practices in a manner that prioritizes environmentally sustainable head and neck surgical practices.

An analysis of waiting times in patients with thyroid cancer.

BACKGROUND: Scottish guidelines suggest that following a referral with a suspicion of cancer, patients should have a diagnosis within 31 days and commence treatment within 62 days. Thyroid cancer is not included in these targets. This study investigates the timelines of management of thyroid cancer, looking at factors that affect time to treatment and diagnosis in our network. METHODS: The study was a review of a prospectively held database of patients discussed at MDT meetings between January 2016 and September 2018. Of the 153 potentially suitable thyroid cancer patients in NHS Lothian, 62 were eligible for inclusion in the study, having been referred to secondary care by their general practitioner (GP) and diagnosed with differentiated thyroid cancer (DTC). RESULTS: At present only 10% and 16% of patients would meet the 62-day treatment and 31-day diagnosis targets respectively. The time to both diagnosis (p=<0.0005) and treatment (p = 0.022) is significantly improved in patients that have a diagnostic biopsy or FNA (Thy5) or a highly suggestive FNA (Thy4), compared with those that do not. There is no significant effect of GP referral type on time to diagnosis or management of thyroid cancer. With a median follow-up of 33 weeks, only one patient had died. CONCLUSIONS: Thyroid cancer does not fit the classical cancer targets well. It is a relatively indolent form of cancer, with many cases diagnosed either incidentally or after undergoing treatment. It is important to balance the resource implications of providing rapid treatment with the psychological effects of the diagnosis.

Head and neck cancer risk calculator (HaNC-RC)-V.2. Adjustments and addition of symptoms and social history factors.

OBJECTIVES: Head and neck cancer (HNC) diagnosis through the 2-week wait, urgent suspicion of cancer (USOC) pathway has failed to increase early cancer detection rates in the UK. A head and neck cancer risk calculator (HaNC-RC) has previously been designed to aid referral of high-risk patients to USOC clinics (predictive power: 77%). Our aim was to refine the HaNC-RC to increase its prediction potential. DESIGN: Following sample size calculation, prospective data collection and statistical analysis of referral criteria and outcomes. SETTING: Large tertiary care cancer centre in Scotland. PARTICIPANTS: 3531 new patients seen in routine, urgent and USOC head and neck (HaN) clinics. MAIN OUTCOME MEASURES: Data collected were as follows: demographics, social history, presenting symptoms and signs and HNC diagnosis. Univariate and multivariate regression analysis were performed to identify significant predictors of HNC. Internal validation was performed using 1000 sample bootstrapping to estimate model diagnostics included the area under the receiver operator curve (AUC), sensitivity and specificity. RESULTS: The updated version of the risk calculator (HaNC-RC v.2) includes age, gender, unintentional weight loss, smoking, alcohol, positive and negative symptoms and signs of HNC. It has achieved an AUC of 88.6% with two recommended triage referral cut-offs to USOC (cut-off: 7.1%; sensitivity: 85%, specificity: 78.3%) or urgent clinics (cut-off: 2.2%; sensitivity: 97.1%; specificity of 52.9%). This could redistribute cancer detection through USOC clinics from the current 60.9%-85.2%, without affecting total numbers seen in each clinical setting. CONCLUSIONS: The use of the HaNC-RC v.2 has a significant potential in both identifying patients at high risk of HNC early thought USOC clinics but also improving health service delivery practices by reducing the number of inappropriately urgent referrals.

Surgical management of intrathoracic goitres.

BACKGROUND: Intrathoracic goitres (ITG) often present with compressive symptoms and require specialised care by experienced surgical teams. Most ITG can be accessed by a transcervical approach (TCA) and only between 1 and 15% will require an extracervical approach (ECA). Many controversies exist regarding the clinical presentation, evaluation, selection of cases for ECA, surgical technique and outcomes. This paper reviews the recent literature on the management, outcomes and evidence-based treatment strategies of ITG. METHODS: We conducted a review of the literature on the evaluation, management and outcomes of surgery for ITGs. RESULTS: The incidence of cancer in the ITGs ranges between 4 and 20%. Multiplanar CT scanning offers the best preoperative evaluation and aids to determine the approach. Most ITG can be accessed by TCA and ECA are only needed in maximum 15% of cases. In experienced hands, the outcome of these surgeries is comparable to thyroid surgery for non-ITG. CONCLUSIONS: Surgery for ITG is challenging. The experienced surgeon however, with few exceptions can address ITG via TCA, with outcomes comparable to those of uncomplicated thyroid surgery.

Evaluating the predicted impact of changes to the AJCC/TMN staging system for differentiated thyroid cancer (DTC): A prospective observational study of patients in South East Scotland.

OBJECTIVES: To assess the impact of the eighth edition AJCC/TMN staging system on patients with new diagnoses of differentiated thyroid cancers presenting to our regional multidisciplinary team meetings. DESIGN: We analysed Endocrine Cancer MDT meeting records from 2009 to 2015 to identify all patients in the region presenting with a new diagnosis of differentiated thyroid cancer. We re-staged patients according to the eighth edition AJCC/TNM staging classification and analysed the survival outcomes of patients in each stage under the seventh and eighth systems. SETTING: Tertiary referral centre in South East Scotland (NHS Lothian). PARTICIPANTS: Three hundred and sixty-one patients were newly diagnosed with DTC within South East Scotland during the study period and met our inclusion criteria. MAIN OUTCOME MEASURES: Disease-specific mortality at any time during follow-up. RESULTS: In total, 119 of 361 (33%) patients were re-staged when the eighth edition AJCC/TMN system was applied. The number of patients classified as having advanced stage (III/IV) disease fell from 76 (21%) to 8 (2%). The most common reason for down-staging was re-classification of tumour size, a factor in 96 (80.7%) down-staged patients. The five-year disease-specific survival of the cohort overall was 98%. Overall, 7 (1.9%) thyroid cancer-related deaths occurred during follow-up, three of whom were down-staged. CONCLUSIONS: On implementation of the eighth edition of the AJCC/TMN staging system, we expect many patients who would previously have been considered to have advanced thyroid cancer will now be classified as early stage. This will accurately reflect their excellent survival outcomes.

Molecular markers in well-differentiated thyroid cancer.

PURPOSE: Thyroid nodules are of common occurrence in the general population. About a fourth of these nodules are indeterminate on aspiration cytology placing many a patient at risk of unwanted surgery. The purpose of this review is to discuss various molecular markers described to date and place their role in proper perspective. This review covers the fundamental role of the signaling pathways and genetic changes involved in thyroid carcinogenesis. The current literature on the prognostic significance of these markers is also described. METHODS: PubMed was used to search relevant articles. The key terms "thyroid nodules", "thyroid cancer papillary", "carcinoma papillary follicular", "carcinoma papillary", "adenocarcinoma follicular" were searched in MeSH, and "molecular markers", "molecular testing", mutation, BRAF, RAS, RET/PTC, PAX 8, miRNA, NIFTP in title and abstract fields. Multiple combinations were done and a group of experts in the subject from the International Head and Neck Scientific Group extracted the relevant articles and formulated the review. RESULTS: There has been considerable progress in the understanding of thyroid carcinogenesis and the emergence of numerous molecular markers in the recent years with potential to be used in the diagnostic algorithm of these nodules. However, their precise role in routine clinical practice continues to be a contentious issue. Majority of the studies in this context are retrospective and impact of these mutations is not independent of other prognostic factors making the interpretation difficult. CONCLUSION: The prevalence of these mutations in thyroid nodule is high and it is a continuously evolving field. Clinicians should stay informed as recommendation on the use of these markers is expected to evolve.

Metastasis to the Thyroid Gland: A Critical Review.

BACKGROUND: Metastasis to the thyroid gland from nonthyroid sites is an uncommon clinical presentation in surgical practice. The aim of this review was to assess its incidence management and outcomes. METHODS: A literature review was performed to identify reports of metastases to the thyroid gland. Both clinical and autopsy series were included. RESULTS: Metastases to the gland may be discovered at the time of diagnosis of the primary tumor, after preoperative investigation of a neck mass, or on histologic examination of a thyroidectomy specimen. The most common primary tumors in autopsy studies are from the lung. In clinical series, renal cell carcinoma is most common. For patients with widespread metastases in the setting of an aggressive malignancy, surgery is rarely indicated. However, when patients present with an isolated metastasis diagnosed during follow-up of indolent disease, surgery may achieve control of the central neck and even long-term cure. Other prognosticators include features of the primary tumor, time interval between initial diagnosis and metastasis, and extrathyroid extent of disease. CONCLUSIONS: In patients with thyroid metastases, communication among clinicians treating the thyroid and the index primary tumor is essential. The setting is complex, and decisions must be made considering the features of the primary tumor, overall burden of metastases, and comorbidities. Careful balancing of these factors influences individualized approaches.

Do salivary bypass tubes lower the incidence of pharyngocutaneous fistula following total laryngectomy? A retrospective analysis of predictive factors using multivariate analysis.

Salivary bypass tubes (SBT) are increasingly used to prevent pharyngocutaneous fistula (PCF) following laryngectomy and pharyngolaryngectomy. There is minimal evidence as to their efficacy and literature is limited. The aim of the study was to determine if SBT prevent PCF. The study was a multicentre retrospective case control series (level of evidence 3b). Patients who underwent laryngectomy or pharyngolaryngectomy for cancer or following cancer treatment between 2011 and 2014 were included in the study. The primary outcome was development of a PCF. Other variables recorded were age, sex, prior radiotherapy or chemoradiotherapy, prior tracheostomy, type of procedure, concurrent neck dissection, use of flap reconstruction, use of prophylactic antibiotics, the suture material used for the anastomosis, tumour T stage, histological margins, day one post-operative haemoglobin and whether a salivary bypass tube was used. Univariate and multivariate analysis were performed. A total of 199 patients were included and 24 received salivary bypass tubes. Fistula rates were 8.3% in the SBT group (2/24) and 24.6% in the control group (43/175). This was not statistically significant on univariate (p value 0.115) or multivariate analysis (p value 0.076). In addition, no other co-variables were found to be significant. No group has proven a benefit of salivary bypass tubes on multivariate analysis. The study was limited by a small case group, variations in tube duration and subjects given a tube may have been identified as high risk of fistula. Further prospective studies are warranted prior to recommendation of salivary bypass tubes following laryngectomy.

How phenotype guides management of non-conventional squamous cell carcinomas of the larynx?

Although the majority of laryngeal malignancies are the conventional squamous cell carcinomas (SCC), a wide variety of malignant epithelial tumors can affect the larynx. Current treatment guidelines are designed to guide clinicians in management of conventional laryngeal SCC. Less is known about the biological behavior and responsiveness to therapy and overall outcomes of other malignant epithelial lesions. Because a spectrum of disease biology is represented by these rare phenotypes, an understanding of the basic biology can help direct management to optimize clinical outcome in this group of patients. This review provides a critical analysis of literature relating to the diagnosis, management, and outcome of patients with non-conventional squamous malignant epithelial neoplasms of the larynx. Particular attention is paid to features which are at variance with the conventional SCC and how these impact on management of these rare tumors.

Management of pulmonary nodules in head and neck cancer patients - Our experience and interpretation of the British Thoracic Society Guidelines.

BACKGROUND: and purpose of the study: The frequency of lung nodules in the head and neck cancer population is unknown, currently the only guidance available recommends following local policy. The aim of this study was to determine the incidence of pulmonary nodules in our head and neck cancer group and interpret the recently updated British Thoracic Society (BTS) Lung Nodule Guidelines in a head and neck cancer setting. METHODS: 100 patients were diagnosed with head and neck cancer between July 2013-March 2014, clinico-pathological, demographic and radiological data was extracted from the electronic records. Images with lung findings were re-reviewed by a single consultant radiologist for patients with lung pathology on the initial staging CT report. RESULTS: Twenty patients (20%) had discreet pulmonary findings on CT. Eleven (11%) had lung nodules, 6 (6%) had lesions suspicious for metastasis and 3 (3%) had co-incidental bronchogenic primary cancers. These patients were re-imaged between 6 and 18 months and in 1 patient the previously identified 7 mm nodule had progressed to 16 mm at 1 year. There was no set follow up imaging protocol used. CONCLUSION: The MDT in NHS Lothian has reviewed the BTS guidance and now has a local policy for the management of lung nodules in head and neck cancer patients. Lung Nodules in the head and neck cancer population are common >10%. Higher risk patients with larger nodules should be risk assessed with validated assessment tools. PET-CT has a place in the assessment of lung nodules when risk of malignancy is high.

Defining a Valid Age Cutoff in Staging of Well-Differentiated Thyroid Cancer.

BACKGROUND: Age 45 years is used as a cutoff in the staging of well-differentiated thyroid cancer (WDTC) as it represents the median age of most datasets. The aim of this study was to determine a statistically optimized age threshold using a large dataset of patients treated at a comprehensive cancer center. METHODS: Overall, 1807 patients with a median follow-up of 109 months were included in the study. Recursive partitioning was used to determine which American Joint Committee on Cancer (AJCC) variables were most predictive of disease-specific death, and whether a different cutoff for age would be found. From the resulting tree, a new age cutoff was picked and patients were restaged using this new cutoff. RESULTS: The 10-year disease-specific survival (DSS) by Union for International Cancer Control (AJCC/UICC) stage was 99.6, 100, 96, and 81 % for stages I-IV, respectively. Using recursive partitioning, the presence of distant metastasis was the most powerful predictor of DSS. For M0 patients, age was the next most powerful predictor, with a cutoff of 56 years. For M1 patients, a cutoff at 54 years was most predictive. Having reviewed the analysis, age 55 years was selected as a more robust age cutoff than 45 years. The 10-year DSS by new stage (using age 55 years as the cutoff) was 99.2, 98, 100, and 74 % for stages I-IV, respectively. CONCLUSION: A change in age cutoff in the AJCC/UICC staging for WDTC to 55 years would improve the accuracy of the system and appropriately prevent low-risk patients being overstaged and overtreated.

Role of RAI in the management of incidental N1a disease in papillary thyroid cancer.

BACKGROUND: Following total thyroidectomy (TT) for papillary thyroid cancer (PTC), pathological assessment can occasionally reveal incidental perithyroidal lymph nodes (LNs) with occult metastases. These cN0pN1a patients often receive radioactive iodine (RAI) therapy for this indication alone. The aim of this study was to determine the central compartment nodal recurrence-free survival in patients treated without RAI compared to those who received RAI treatment. METHODS: An institutional database of 3664 previously untreated patients with differentiated thyroid cancer operated between 1986 and 2010 was reviewed. A total of 232 pT1-3 patients managed with TT and no neck dissection were subsequently found to have incidental level 6 LNs on pathology. Patients with other indications for RAI, such as extrathyroidal extension and close or positive margins, were excluded. One hundred and four patients remained for analysis. Kaplan-Meier method was used to determine central neck LN recurrence-free survival (RFS). RESULTS: The median age of the cohort was 40 years (range 17-83). The median follow-up was 53 months (range 1-211). The median number of positive LNs removed and maximum LN diameter were 1 (range 1-8) and 5 mm (range 1-16 mm), respectively. A total of 67 (64%) patients had adjuvant RAI and 37 (36%) did not. Patients with vascular invasion (P = 0·01), LNs >2 mm (P = 0·07) and >2 positive nodes (P = 0·06) were more likely to be selected for adjuvant RAI therapy. Patients without RAI therapy had similar 5-year central neck LN RFS compared to those treated with RAI: 96·2% vs 94·6%, respectively (P = 0·92). CONCLUSION: There is no difference in the 5-year central compartment nodal recurrence-free survival in patients treated without RAI compared to those who received RAI treatment.

The surgical approach to managing differentiated thyroid cancer.

In recent decades, our understanding of thyroid cancer has improved significantly with the recognition that differentiated thyroid cancer (DTC) has good survival and oncological outcomes. Along with the recent rise in the detection of otherwise subclinical tumours due to improved diagnostics, there has been much debate on how aggressive one should be when performing thyroid and lymph node surgery. The use of risk stratification to categorize patients into low, intermediate and high risk has led to a more tailored approach to treating differentiated thyroid cancer. This ensures patients are not subject to preventable morbidity from overtreatment while maintaining good outcomes. We discuss the approach to primary thyroid and lymph node surgery by reviewing the current literature.