Cricotracheal resection for adult subglottic stenosis : Factors predicting treatment failure

Objectives/Hypothesis Identify predictors of decannulation failure after cricotracheal resection (CTR) and thyrotracheal anastomosis (TTA) in patients with subglottic stenosis (SGS). Study Design Retrospective cohort study. Methods Charts of patients undergoing CTR and TTA for SGS at the University Health Network, Toronto, Ontario, Canada between 1988 and 2017 were reviewed. Patient, pathology, treatment, and outcome data were collected. The end points for statistical analysis were development of restenosis and permanent tracheostomy. Results One hundred fourteen patients (n = 114) were eligible for inclusion in this review. The mean age at primary resection was 46.9 years, 95 (83%) were females, and 19 (17%) were males. The rate of restenosis and permanent tracheostomy was 13% and 5%, respectively. Sixty-two patients (54%) underwent a CTR and TTA, and 52 patients (46%) underwent a CTR, laryngofissure, and TTA. Traumatic stenosis (odds ratio [OR] = 10.3, P = .017), longer T-tube duration (OR = 1.2, P = .011), combined glottic/subglottic stenosis (OR = 10.47, P = .010), start of the stenosis at the vocal cords (OR = 6.6, P = .029), postoperative minor complications (OR = 13.6, P = .028), and need for repeat surgery (OR = 44.1, P <.001) were associated with an increased risk of requiring permanent tracheostomy. Conclusions CTR and TTA are excellent surgical approaches for adult patients with subglottic stenosis. In this study, 5% of patients required permanent tracheostomy. Factors predicting treatment failure include traumatic stenosis, longer T-tube duration, combined glottic/subglottic stenosis, start of stenosis at the level of vocal cords, postoperative minor complications, and need for repeat surgery. Level of Evidence 4 Laryngoscope, 2019Peer reviewe

Analysis of clinically relevant somatic mutations in high-risk head and neck cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma is the second most prevalent malignancy, most frequently occurring in the head and neck (head and neck cutaneous squamous cell carcinoma). Treatment of locally advanced or metastatic disease is associated with functional morbidity and disfigurement. Underlying genetic mechanisms are poorly understood. Targeted sequencing of 48 clinically relevant genes was performed on DNA extracted from formalinfixed and paraffin-embedded high-risk primary head and neck cutaneous squamous cell carcinomas that remained non-metastatic at minimum follow-up of 24 months. Associations of somatic mutations with clinicopathologic characteristics were evaluated and compared with those described in the literature for metastatic disease. Alterations in 44 cancer-associated genes were identified. TP53 was mutated in 100% of cases; APC, ATM, ERBB4, GNAQ, KIT, RB1 and ABL1 were altered in 60% of cases. FGFR2 mutations (40%) were exclusively seen in patients with perineural invasion. MLH1 mutations were exclusively seen in the two younger patients (\u3c45 \u3eyears). Lower incidences of NOTCH1 mutations were observed compared with that described in metastatic head and neck cutaneous squamous cell carcinoma in the literature. Somatic mutations susceptible to EGFR inhibitors, and other small molecular targeted therapeutics were seen in 60% of cases. This study provides insights into somatic mutations in non-metastatic, high-risk head and neck cutaneous squamous cell carcinoma and identifies potential therapeutic targets. Alterations in FGFR2 and NOTCH1 may have roles in local and distant disease progression

Somatic mutations in salivary duct carcinoma and potential therapeutic targets

Background: Salivary duct carcinomas (SDCa) are rare highly aggressive malignancies. Most patients die from distant metastatic disease within three years of diagnosis. There are limited therapeutic options for disseminated disease. Results: 11 cases showed androgen receptor expression and 6 cases showed HER2 amplification. 6 Somatic mutations with additional available targeted therapies were identified: EGFR (p. G721A: Gefitinib), PDGFRA (p. H845Y: Imatinib and Crenolanib), PIK3CA (p. H1047R: Everolimus), ERBB2 (p. V842I: Lapatinib), HRAS (p. Q61R: Selumetinib) and KIT (p. T670I: Sorafenib). Furthermore, alterations in PTEN, PIK3CA and HRAS that alter response to androgen deprivation therapy and HER2 inhibition were also seen. Materials and Methods: Somatic mutation analysis was performed on DNA extracted from 15 archival cases of SDCa using the targeted Illumina TruSeq Amplicon Cancer Panel. Potential targetable genetic alterations were identified using extensive literature and international somatic mutation database (COSMIC, KEGG) search. Immunohistochemistry for androgen receptor and immunohistochemistry and fluorescent in situ hybridization for HER2 were also performed. Conclusions: SDCa show multiple somatic mutations, some that are amenable to pharmacologic manipulation and others that confer resistance to treatments currently under investigation. These findings emphasize the need to develop testing and treatment strategies for SDCa. © Khoo et al

Neck Surgery for Non-Well Differentiated Thyroid Malignancies: Variations in Strategy According to Histopathology

Lymph node metastases in non-well differentiated thyroid cancer (non-WDTC) are common, both in the central compartment (levels VI and VII) and in the lateral neck (Levels II to V). Nodal metastases negatively affect prognosis and should be treated to maximize locoregional control while minimizing morbidity. In non-WDTC, the rate of nodal involvement is variable and depends on the histology of the tumor. For medullary thyroid carcinomas, poorly differentiated thyroid carcinomas, and anaplastic thyroid carcinomas, the high frequency of lymph node metastases makes central compartment dissection generally necessary. In mucoepidermoid carcinomas, malignant peripheral nerve sheath tumors, sarcomas, and malignant thyroid teratomas or thyroblastomas, central compartment dissection is less often necessary, as clinical lymphnode involvement is less common. We aim to summarize the medical literature and the opinions of several experts from different parts of the world on the current philosophy for managing the neck in less common types of thyroid cancer

PD-L1 expression predicts longer disease free survival in high risk head and neck cutaneous squamous cell carcinoma

Programmed cell death (PD-1) and its ligand (PD-L1) inhibitors have shown clinical response in many tumours. PD-L1 data are limited in head and neck cutaneous squamous cell carcinoma (HNcSCC) and no clinical trials of PD-1/PD-L1 inhibitors are published. We performed PD-L1 immunohistochemistry on 74 cases of high risk HNcSCC with 38 matched metastases and evaluated clinicopathological associations, prognostic significance and heterogeneity in matched metastases. We observed PD-L1 expression in \u3e5% of primary tumour cells in 29 cases (39.2%), primary tumour infiltrating lymphocytes (TILs) in 40 cases (70.2%), metastatic tumour cells in 15 cases (39.5%), and metastatic TILs in 18 cases (47.4%). PD-L1 expression in \u3e5% of primary tumour cells was associated with an inflammatory phenotype (p = 0.04), and in primary TILs with clear margins (p = 0.05). PD-L1 expression in \u3e5% of primary tumour cells (p = 0.01), primary TILs (p = 0.001), and metastatic TILs (p = 0.02) was associated with improved disease free survival. PD-L1 expression in \u3e5% of tumour cells was heterogeneous between primary and metastatic tumours in 13 cases (34.2%). PD-L1 expression is common in HNcSCC supporting the rationale for a clinical trial of PD-1/PD-L1 inhibitors. PD-L1 expression in tumour cells or TILs predicts longer disease free survival and demonstrates temperospatial heterogeneity

Mutational Patterns in Metastatic Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma from the head and neck typically metastasize to the lymph nodes of the neck and parotid glands. When a primary is not identified, they are difficult to distinguish from metastases of mucosal origin and primary salivary gland squamous cell carcinoma. UV radiation causes a mutation pattern that predominantly features cytosine to thymine transitions at dipyrimidine sites and has been associated with cutaneous squamous cell carcinoma. In this study, we used whole genome sequencing data from 15 cutaneous squamous cell carcinoma metastases and show that a UV mutation signature is pervasive across the cohort and distinct from mucosal squamous cell carcinoma. The mutational burden was exceptionally high and concentrated in some regions of the genome, especially insulator elements (mean 162 mutations/megabase). We therefore evaluated the likely impact of UV-induced mutations on the dipyrimidine-rich binding site of the main human insulator protein, CCCTC-binding factor, and the possible implications on CCCTC-binding factor function and the spatial organization of the genome. Our findings suggest that mutation signature analysis may be useful in determining the origin of metastases in the neck and the parotid gland. Furthermore, UV-induced DNA damage to insulator binding sites may play a role in the carcinogenesis and progression of cutaneous squamous cell carcinoma

Translaryngeal ultrasound in thyroid surgery: state of the art review

BACKGROUND: Clinical voice assessment prior to thyroid and parathyroid surgery is essential, but the paradigm of indirect laryngoscopy (IDL), when indicated, has been challenged by the risk of aerosolised SARS-Cov-2 during endoscopy of the aerodigestive tract. Translaryngeal ultrasound (TLUS) to assess the vocal cords has been proposed as a safe, non-invasive and sensitive alternative. The aim of this review was to verify TLUS as a viable tool for perioperative laryngeal assessment. METHOD: A literature review was performed using Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials and Scopus with the following search strategy: (vocal cord OR vocal fold OR glottic OR glottis OR vocal ligaments OR rima glottidis) AND (ultras* OR sonograph* OR echography OR echotomography). RESULTS: Fifteen studies were included in this review. All studies compared TLUS to IDL in visualizing the vocal cords in adults. Ten studies compared pre-operative TLUS to IDL where 50.6-100% of vocal cords were successfully visualized. Nine studies compared post-operative TLUS to IDL and reported visualization between 39.6% and 100%. Pre- and post-operative negative predictive values ranged from 60% to 100%. CONCLUSION: Whilst promising, successful visualization of the cords is limited by inter-user variability, older age and male gender. Thus, we see the role of TLUS as an alternative to IDL in the post-operative setting in the young patient following uncomplicated surgery with a normal voice on clinical examination, to confirm recurrent laryngeal nerve integrity while minimizing the risk of aerosolization