A systematic review of endotracheal stenting in patients with locally advanced thyroid cancer.

OBJECTIVE: Locally aggressive thyroid cancer can result in airway obstruction secondary to tracheal compression or vocal cord palsy. A tracheal stent provides an alternative to surgical resection, tracheostomy or conservative management in patients with compressive symptoms. This systematic review synthesises the current evidence associated with tracheal stenting in locally advanced thyroid cancer. DESIGN, SETTING AND PARTICIPANTS: We conducted a systematic review of tracheal stenting in locally advanced thyroid cancers. We searched MEDLINE, Embase and Web of Science for studies until 22 September 2020. Inclusion criteria were studies involving patients who had received tracheal stents to treat laryngotracheal stenosis secondary to locally advanced thyroid cancer. Single case reports or single cases were not included. MAIN OUTCOME MEASURES: We assessed studies for data on the performance of tracheal stenting; defined as symptomatic relief, spirometry data, complication rates and mortality. We also extracted data pertaining to the use of different types of stent. RESULTS: We identified eight full-text articles from 325 titles found in our search. These were all single-centre retrospective studies that lacked homogeneity of thyroid cancer histotypes. The number of patients in each study ranged from 4 to 35 patients. Stenting improved performance status (two of two studies), symptoms (five of five studies) and spirometry (two of three studies). The most common complications were tracheal granulation, tumour overgrowth, stent migration and sputum retention. CONCLUSION: There is a lack of evidence in the literature of tracheal stents in locally advanced thyroid cancer. However, the evidence available suggests tracheal stenting may be a useful treatment adjunct in advanced thyroid cancer-causing symptomatic airway obstruction.

Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: demonstrating the natural progression of a rare and misunderstood disease.

Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid in a 46-year-old woman.

A randomised trial to assess the educational benefit of a smartphone otoscope in undergraduate medical training.

PURPOSE: Competent otoscopy is a key otolaryngology skill for a broad range of medical careers, yet undergraduate's confidence to perform otoscopy is reported as low. Smartphone otoscopes have been suggested to improve undergraduates learning of normal eardrum anatomy because unlike the traditional otoscope, the learner and educator share the same image. This study aimed to evaluate whether a smartphone otoscope could enhance medical undergraduates recognition of common ear pathology. METHODS: 52 medical students were randomised into a standard group that used a traditional otoscope and an intervention group that used a smartphone otoscope. Both groups received a short didactic presentation on the recognition of common ear pathologies and were asked to diagnose four simulated pathologies. Both groups received feedback and guidance on how to better visualise the tympanic membrane. Force response items and 5-point Likert scales loaded on an electronic platform recorded their diagnosis and their perceptions towards the otoscope. RESULTS: The smartphone-group (n = 20) had higher overall rates of correct diagnosis compared to control (n = 22) (84% vs. 39%, p = < 0.001). Only the grommet station did not show a significant improvement between the two groups (100% vs. 91%, p = 0.49). 90% (n = 20) of participants felt the smartphone otoscope was preferential for their learning. The same number expressed that they want to use it in future learning. The remainder were indifferent. CONCLUSIONS: The smartphone otoscope enabled learners to better observe and recognise middle ear pathology. This popular learning tool has the potential to accelerate the learning curve of otoscopy and therefore improve the proficiency of future doctors at recognising middle ear diseases.

Non-sebaceous lymphadenoma of the submandibular gland: diagnostic challenges in the head and neck cancer pathway.

Non-sebaceous lymphadenoma (NSLA) is a rare benign salivary gland tumour with lymphoid and epithelial components and without sebaceous differentiation. The large majority of the reported cases arise within the parotid gland. We present an NSLA arising from the submandibular gland. The tumour presented as a painless longstanding neck lump. Ultrasound, fine needle aspiration, MRI and positron emission tomography found features supportive of squamous cell carcinoma. The patient was treated with surgery for oropharyngeal carcinoma of unknown origin, in accordance with local and national guidelines. The final histological assessment revealed the level Ib neck lesion to be NSLA. Although a rare occurrence, these lesions may pose a diagnostic challenge in the head and neck cancer pathway.

Royal Society of Medicine Surgical Innovation Day Adrian Tanner Prize Winner 2019: Multidisciplinary care and surgical innovation for the benefit of the patient with head and neck cancer of unknown primary.

Head and neck carcinoma of unknown primary accounts for approximately 1-5% of all head and neck cancers and presents a genuine diagnostic and therapeutic dilemma. Despite advanced investigations, the primary tumour location remains unknown in up to 40% of these cases. Transoral robotic surgery presents a viable diagnostic and therapeutic option in these patients. This surgical innovation alongside advances in the understanding of head and neck cancer biology means that a multidisciplinary approach in the management of these complex patients is of utmost importance to ensure optimal therapeutic outcomes.

The emerging role of trans-oral robotic surgery for the detection of the primary tumour site in patients with head-neck unknown primary cancers: A meta-analysis.

The identification of the site in head neck unknown primary (HNUP) tumour is of utmost importance to help select best treatment while decreasing treatment-related morbidity and mortality. The primary purpose of this study is to demonstrate that TORS may be a valuable tool in detecting primary tumour. Studies were systematically searched in the PubMed, EMBASE, the Cochrane Library and CENTRAL electronic databases. A total of 12 selected studies (349 patients) were analyzed. The primary tumour detection and positive surgical margins rates were 70.8% and 19.4%, respectively. The rate of HPV-related tumour was 71.3%. The primary tumour was mainly in base of tongue (64%). In conclusion, TORS seems to be an effective surgical approach both in terms of detection of primary tumour site and in terms of therapeutic perspective for HNUP. In particular, a subset of HPV-related tumours might benefits all advantages from this surgical modality.

Transoral Robotic Surgery and the Unknown Primary.

Carcinoma of unknown primary (CUP) comprises approximately 1%-5% of all head and neck malignancies. Primary site detection rates for metastatic cervical squamous cell carcinoma (SCC) remain variable, with current diagnostic imaging unable to identify all tumours. Prevailing evidence suggests that most head and neck CUP are located in the oropharynx. Diagnostic surgical efforts have been directed at sampling the entire oropharynx. Present techniques that make this possible include transoral robotic surgery (TORS). TORS Lingual tonsillectomy or tongue base mucosectomy performed in the setting of head and neck CUP increases the detection rate of occult tumour. The indication, surgical technique, evidence base, and controversies of performing TORS in the context of the unknown primary are presented.

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.

Transoral robotic surgery base of tongue mucosectomy for head and neck cancer of unknown primary.

BACKGROUND: Head and neck cancer of unknown primary (HNCUP) is a source of diagnostic uncertainty. Patients presenting with cytologically positive neck lumps without a clinically identifiable primary, require extensive investigation including imaging, tonsillectomy, panendoscopy and tissue biopsy. Treatment typically involves neck dissection, wide field radiotherapy and chemotherapy. Transoral robotic surgery (TORS) has emerged as an expanding surgical technique for resecting tumours of the oropharynx. Its role in base of tongue (BOT) mucosectomy for HNCUP can alleviate diagnostic uncertainty and provide an adjunct treatment modality with few complications. METHODS: We conducted a 7-year chart review of consecutive patients presenting with HNCUP that were treated with TORS BOT mucosectomy. We examined the efficacy, diagnostic rates and complications associated with TORS BOT mucosectomy when used for treating HNCUP. RESULTS: TORS BOT mucosectomy was performed in seven cases of squamous cell carcinoma of unknown primary. Robotic mucosectomy diagnosed BOT as the primary tumour site in five cases (71.4%). All five cases were p16 positive. Average time before return to normal swallowing function was 2.7 days. There were no major surgical complications. CONCLUSION: TORS BOT mucosectomy is an expanding surgical technique with a key role in head and neck surgery. It can be utilized to good effect where head and neck cancer is diagnosed without an identifiable primary. Incorporating robotic surgery in the diagnostic and treatment pathway offers low complication rates, reduced morbidity and improved tumour identification.

Quantification of lymph nodes in the central compartment of the neck: a cadaveric study.

Differentiated thyroid cancer (DTC) accounts for over 90 % of thyroid malignancies, and is frequently associated with central neck compartment nodal metastasis that requires a therapeutic central compartment neck dissection (CCND) for clinically evident nodes. Current knowledge on the expected lymph node yield from a CCND is limited, compared with data on the lateral neck. The aim of our study was to accurately quantify nodal yield from the cadaveric central neck compartment. Twenty-eight cadaveric necks were dissected and the central neck compartment was subdivided into four regions: pre-laryngeal (delphian), pre-tracheal, right and left para-tracheal regions. Each cadaver had a thyroid gland, which was also removed, and the CCND tissue in each compartment was processed and examined by a consultant histopathologist. Only lymphoid tissue with a defined microscopic fibrous capsule and subcapsular sinus was included in the node count. The median total lymph node count per cadaver was four (range 1-16), with a median of one node detectable in each para-tracheal region (range 0-7) and the pre-tracheal region (range 0-8). The median pre-laryngeal node count was 0 (range 0- 2). The average lymph node size across all compartments was 2.9 mm. This is the first European study to assess cadaveric central neck lymph nodes and establish baseline counts for nodal yield. If a prophylactic or therapeutic CCND is required during thyroid surgery, those involved in DTC management must recognise that there is a wide range, and low median yield of central neck compartment lymph nodes.

Imaging tumour heterogeneity of the consequences of a PKCα-substrate interaction in breast cancer patients.

Breast cancer heterogeneity demands that prognostic models must be biologically driven and recent clinical evidence indicates that future prognostic signatures need evaluation in the context of early compared with late metastatic risk prediction. In pre-clinical studies, we and others have shown that various protein-protein interactions, pertaining to the actin microfilament-associated proteins, ezrin and cofilin, mediate breast cancer cell migration, a prerequisite for cancer metastasis. Moreover, as a direct substrate for protein kinase Cα, ezrin has been shown to be a determinant of cancer metastasis for a variety of tumour types, besides breast cancer; and has been described as a pivotal regulator of metastasis by linking the plasma membrane to the actin cytoskeleton. In the present article, we demonstrate that our tissue imaging-derived parameters that pertain to or are a consequence of the PKC-ezrin interaction can be used for breast cancer prognostication, with inter-cohort reproducibility. The application of fluorescence lifetime imaging microscopy (FLIM) in formalin-fixed paraffin-embedded patient samples to probe protein proximity within the typically <10 nm range to address the oncological challenge of tumour heterogeneity, is discussed.

Renal cell carcinoma metastasis to the parathyroid gland: A very rare occurrence.

INTRODUCTION: Metastases to the parathyroid gland are very uncommon. Although renal cell carcinoma metastasis to the head and neck region is well recognised, with a predilection for unpredictable metastasis to unusual sites such as the thyroid gland, nose, paranasal sinuses, and cranial bones, there are no reports of parathyroid gland involvement. PRESENTATION OF CASE: We describe an unusual case of renal cell carcinoma metastasis to a parathyroid gland in a 69-year-old male who had been treated 8 years previously for a pT3b N0 M1 clear cell carcinoma of the right kidney with a right nephrectomy, and interferon immunotherapy for 18 months. The patient had originally presented to the plastic surgeons with a rapidly enlarging 3cm superficial lesion on the ventral aspect of the left forearm, which was excised with histology revealing metastatic renal (clear) cell carcinoma. DISCUSSION: Renal cell carcinoma has a reputation for unpredictable patterns of metastasis, and our case highlights this, with the first description in the literature of parathyroid gland metastasis. Despite the poor prognosis associated with metastatic renal cell carcinoma, our patient is still alive 10 years following original presentation, despite having metastasis to two different extra-renal sites and a shortened course of initial adjuvant systemic therapy. CONCLUSION: In parathyroid gland metastasis, metastectomy can offer excellent local long term local control.

Systematic review of cochlear implantation in children with developmental disability.

OBJECTIVE: To perform a systematic review comparing the xoutcome of cochlear implantation in children with developmental disability with children without developmental disability. DATA SOURCES: MEDLINE, EMBASE, and Cochrane databases were searched from 1950 or the start date of each database. The search was performed on 1st November 2012, and included articles published ahead of print with no language restrictions. STUDY SELECTION: The initial search presented 441 articles of which 13 met the inclusion criteria. The articles studied children with cochlear implants and developmental disability where expressive and/or receptive language outcomes were compared with children with cochlear implants and normal development. DATA EXTRACTION: Study quality assessment included whether ethical approval was gained, prospective design, eligibility criteria specified, appropriate controls used, adequate follow-up achieved, and defined outcome measures. Cochlear implant outcome analysis included expressive/receptive speech and language development in addition to quality of life and behavior. DATA SYNTHESIS: Because of heterogeneity in postoperative follow-up periods and outcome measures reported, it was not possible to pool the data and perform meta-analysis. Comparisons were made by structured review. CONCLUSION: Seven studies demonstrated a worse outcome for children with developmental disability. Six articles showed no difference in the outcome between the 2 groups. Children with developmental disability may not benefit from cochlear implantation based on traditional assessment tools but appear to improve their environmental awareness and quality of life. More work is needed to define the term benefit when used in this context for this vulnerable group. Autistic children consistently had a negative outcome.

A multi-functional imaging approach to high-content protein interaction screening.

Functional imaging can provide a level of quantification that is not possible in what might be termed traditional high-content screening. This is due to the fact that the current state-of-the-art high-content screening systems take the approach of scaling-up single cell assays, and are therefore based on essentially pictorial measures as assay indicators. Such phenotypic analyses have become extremely sophisticated, advancing screening enormously, but this approach can still be somewhat subjective. We describe the development, and validation, of a prototype high-content screening platform that combines steady-state fluorescence anisotropy imaging with fluorescence lifetime imaging (FLIM). This functional approach allows objective, quantitative screening of small molecule libraries in protein-protein interaction assays. We discuss the development of the instrumentation, the process by which information on fluorescence resonance energy transfer (FRET) can be extracted from wide-field, acceptor fluorescence anisotropy imaging and cross-checking of this modality using lifetime imaging by time-correlated single-photon counting. Imaging of cells expressing protein constructs where eGFP and mRFP1 are linked with amino-acid chains of various lengths (7, 19 and 32 amino acids) shows the two methodologies to be highly correlated. We validate our approach using a small-scale inhibitor screen of a Cdc42 FRET biosensor probe expressed in epidermoid cancer cells (A431) in a 96 microwell-plate format. We also show that acceptor fluorescence anisotropy can be used to measure variations in hetero-FRET in protein-protein interactions. We demonstrate this using a screen of inhibitors of internalization of the transmembrane receptor, CXCR4. These assays enable us to demonstrate all the capabilities of the instrument, image processing and analytical techniques that have been developed. Direct correlation between acceptor anisotropy and donor FLIM is observed for FRET assays, providing an opportunity to rapidly screen proteins, interacting on the nano-meter scale, using wide-field imaging.

The potential of optical proteomic technologies to individualize prognosis and guide rational treatment for cancer patients.

Genomics and proteomics will improve outcome prediction in cancer and have great potential to help in the discovery of unknown mechanisms of metastasis, ripe for therapeutic exploitation. Current methods of prognosis estimation rely on clinical data, anatomical staging and histopathological features. It is hoped that translational genomic and proteomic research will discriminate more accurately than is possible at present between patients with a good prognosis and those who carry a high risk of recurrence. Rational treatments, targeted to the specific molecular pathways of an individual's high-risk tumor, are at the core of tailored therapy. The aim of targeted oncology is to select the right patient for the right drug at precisely the right point in their cancer journey. Optical proteomics uses advanced optical imaging technologies to quantify the activity states of and associations between signaling proteins by measuring energy transfer between fluorophores attached to specific proteins. Förster resonance energy transfer (FRET) and fluorescence lifetime imaging microscopy (FLIM) assays are suitable for use in cell line models of cancer, fresh human tissues and formalin-fixed paraffin-embedded tissue (FFPE). In animal models, dynamic deep tissue FLIM/FRET imaging of cancer cells in vivo is now also feasible. Analysis of protein expression and post-translational modifications such as phosphorylation and ubiquitination can be performed in cell lines and are remarkably efficiently in cancer tissue samples using tissue microarrays (TMAs). FRET assays can be performed to quantify protein-protein interactions within FFPE tissue, far beyond the spatial resolution conventionally associated with light or confocal laser microscopy. Multivariate optical parameters can be correlated with disease relapse for individual patients. FRET-FLIM assays allow rapid screening of target modifiers using high content drug screens. Specific protein-protein interactions conferring a poor prognosis identified by high content tissue screening will be perturbed with targeted therapeutics. Future targeted drugs will be identified using high content/throughput drug screens that are based on multivariate proteomic assays. Response to therapy at a molecular level can be monitored using these assays while the patient receives treatment: utilizing re-biopsy tumor tissue samples in the neoadjuvant setting or by examining surrogate tissues. These technologies will prove to be both prognostic of risk for individuals when applied to tumor tissue at first diagnosis and predictive of response to specifically selected targeted anticancer drugs. Advanced optical assays have great potential to be translated into real-life benefit for cancer patients.

Integrating receptor signal inputs that influence small Rho GTPase activation dynamics at the immunological synapse.

The Rho GTPase Cdc42 regulates cytoskeletal changes at the immunological synapse (IS) that are critical to T-cell activation. By imaging fluorescent activity biosensors (Raichu) using fluorescence lifetime imaging microscopy, Cdc42 activation was shown to display kinetics that are conditional on the specific receptor input (through two IS-associated receptors, CD3 and beta1 integrin). CD3-triggered Cdc42 activity is dependent on the cyto-2 (NPIY) motif of the beta1 integrin cytoplasmic domain. Perturbations of the ezrin-radixin-moesin (ERM) function blocked CD3- and beta1-dependent increases in Cdc42 activity. Both IS-associated receptors probably lie on a serial molecular pathway and transduce signals through the ERM-dependent machinery that is responsible for the remodeling and stabilization of the synapse. Cdc42 activity is impaired in beta1 integrin-deficient T cells that form conjugates with antigen-presenting cells but is partially restored in the context of an antigen-specific synapse. This restoration of Cdc42 activity is due, at least in part, to the recruitment and activation of beta2 integrin.