Acquired Anterior Laryngeal Web in a Shotgun Injury.

We report the first case of an anterior laryngeal web post gunshot wound in the modern literature. A 27 year-old man suffered a close range shotgun injury to his neck. He presented with stridor and a large open neck wound. Emergency tracheostomy was required. A postoperative fibreoptic laryngoscopy revealed anterior glottic web formation. This case report highlights the difficulties in managing acquired anterior laryngeal webs and reviews the only other case in the in the literature from 1915.

Factors influencing nodal yield in neck dissections for head and neck malignancies.

OBJECTIVE: A standard lateral neck dissection should yield at least 18 lymph nodes. The goal of the present study was to examine what factors might influence the number of lymph nodes retrieved during a neck dissection. METHODS: This was a retrospective cohort study in a tertiary academic referral centre for head and neck oncology. Two hundred and nineteen consecutive neck dissections were examined. Age of the patient and primary site were recorded, along with tumour histology, previous radiotherapy and final nodal count. RESULTS: The mean age was 62.2 ± 13.0 years. The most common primary site was the oral cavity (38.8 per cent). The mean number of lymph nodes was 30.63 ± 13.9. In total, 17.8 per cent had undergone previous radiotherapy. The mean number of lymph nodes was 33.26 ± 13.27 in patients with no previous radiation exposure and 18.47 ± 9.46 in those with previous radiation treatment. CONCLUSION: Lymph node yield from a neck dissection is likely multi-factorial in nature. Previous radiotherapy, the only significant contributor, led to a mean reduction of lymph node yield from 33.3 to 18.5.

Optical genome mapping in acute myeloid leukemia: a multicenter evaluation.

Detection of hallmark genomic aberrations in acute myeloid leukemia (AML) is essential for diagnostic subtyping, prognosis, and patient management. However, cytogenetic/cytogenomic techniques used to identify those aberrations, such as karyotyping, fluorescence in situ hybridization (FISH), or chromosomal microarray analysis (CMA), are limited by the need for skilled personnel as well as significant time, cost, and labor. Optical genome mapping (OGM) provides a single, cost-effective assay with a significantly higher resolution than karyotyping and with a comprehensive genome-wide analysis comparable with CMA and the added unique ability to detect balanced structural variants (SVs). Here, we report in a real-world setting the performance of OGM in a cohort of 100 AML cases that were previously characterized by karyotype alone or karyotype and FISH or CMA. OGM identified all clinically relevant SVs and copy number variants (CNVs) reported by these standard cytogenetic methods when representative clones were present in >5% allelic fraction. Importantly, OGM identified clinically relevant information in 13% of cases that had been missed by the routine methods. Three cases reported with normal karyotypes were shown to have cryptic translocations involving gene fusions. In 4% of cases, OGM findings would have altered recommended clinical management, and in an additional 8% of cases, OGM would have rendered the cases potentially eligible for clinical trials. The results from this multi-institutional study indicate that OGM effectively recovers clinically relevant SVs and CNVs found by standard-of-care methods and reveals additional SVs that are not reported. Furthermore, OGM minimizes the need for labor-intensive multiple cytogenetic tests while concomitantly maximizing diagnostic detection through a standardized workflow.

Complexities of revision mastoid surgery in a migratory population cohort.

We present a review of patients from Eastern Europe who have recently immigrated to Ireland with complicated otological disease. We carried out a retrospective chart review of these patients. These are a complicated cohort of 7 patients, 5 (71.4%) of whom had previous ear surgery, none had old notes and there was often a need for interpreters (3 or 42.8%) and challenging surgery. Follow up was also problematic with many of the patients. In summary this is a case series to highlight a relatively new group of patients to emphasize the need for pre-operative CT scans, facial nerve monitoring and the difficult nature of revision surgery with no old notes.

Ectopic olfactory neuroblastoma: report of four cases and a review of the literature.

Our objective is to present a short series of four rare cases of ectopic olfactory neuroblastoma. Our methods present four case reports of ectopic olfactory neuroblastoma and a review of the literature for management and treatment of this disease. The results indicate short case series reports of ectopic olfactory neuroblastoma arising from the anterior ethmoidal sinuses, the nasopharynx, the lateral nasal wall and the floor of the nose. The discussion focuses on likely origins of ectopic olfactory neuroblastoma, its clinical features and management. We conclude that ectopic olfactory neuroblastoma is a rare disease. Treatment principles are the same for non-ectopic disease and guided by extension into adjacent structures such as the orbit or anterior cranial fossa and usually involves surgery with or without adjuvant radiotherapy.

'Out of house' virtual surgical planning for mandible reconstruction after cancer resection: is it oncologically safe?

The purpose of this study was to investigate whether the time delay between 'out of house' proprietary virtual surgical planning (OH-VSP) of the mandibular resection for oral cancer and the actual surgery results in compromised margins and oncological disadvantage for the patient. Outcomes of patients who had OH-VSP of their mandibular resection and reconstruction were compared with those of patients who had the same surgery using a conventional non-VSP approach. The groups were similar in patient demographics, tumour stage and size, nodal status, and reconstruction complexity. VSP resulted in a significant reduction in operating time (P<0.01). VSP did not affect bony (P=0.49) or soft tissue (P=0.22) margin status. In summary, VSP reduced the operating theatre time, and despite the time interval between bony resection planning and surgery, there was no compromise to the oncological safety of the operation.

Tracheostomy stomal seeding following oral cavity resection.

BACKGROUND: Tracheal stoma recurrence following oral cavity surgery is exceedingly rare. Although several different mechanisms for this have been described, the pathogenesis still remains uncertain. METHODS: We present the case of a gentleman who presented 6-months following oral cavity SCC resection with a large fungating mass at his previous tracheostomy site, and also review the reported literature on this rare phenomenon. RESULTS: Four weeks after diagnosis of his recurrence he underwent a total laryngectomy, wide-local skin excision and reconstruction with a pectoralis major pedicled flap. He recovered well initially following his operation, however unfortunately contracted nosocomial SARS-Cov2 and succumbed from respiratory complications during his post-operative recovery. CONCLUSION: Stomal recurrence after temporary tracheostomy for oral cavity malignancies are very rare. Previously reported management of these can vary from surgical to palliative treatment. Methods to prevent these include delaying tracheostomy until after surgical resection, packing the pharynx during resection and adjuvant radiotherapy.

Neutrophil-derived 5'-adenosine monophosphate promotes endothelial barrier function via CD73-mediated conversion to adenosine and endothelial A2B receptor activation.

During episodes of inflammation, polymorphonuclear leukocyte (PMN) transendothelial migration has the potential to disturb vascular barrier function and give rise to intravascular fluid extravasation and edema. However, little is known regarding innate mechanisms that dampen fluid loss during PMN-endothelial interactions. Using an in vitro endothelial paracellular permeability model, we observed a PMN-mediated decrease in endothelial paracellular permeability. A similar decrease was elicited by cell-free supernatants from activated PMN (FMLP 10(-6) M), suggesting the presence of a PMN-derived soluble mediator(s). Biophysical and biochemical analysis of PMN supernatants revealed a role for PMN-derived 5'-adenosine monophosphate (AMP) and its metabolite, adenosine, in modulation of endothelial paracellular permeability. Supernatants from activated PMN contained micromolar concentrations of bioactive 5'-AMP and adenosine. Furthermore, exposure of endothelial monolayers to authentic 5'-AMP and adenosine increased endothelial barrier function more than twofold in both human umbilical vein endothelial cells and human microvascular endothelial cells. 5'-AMP bioactivity required endothelial CD73-mediated conversion of 5'-AMP to adenosine via its 5'-ectonucleotidase activity. Decreased endothelial paracellular permeability occurred through adenosine A2B receptor activation and was accompanied by a parallel increase in intracellular cAMP. We conclude that activated PMN release soluble mediators, such as 5'-AMP and adenosine, that promote endothelial barrier function. During inflammation, this pathway may limit potentially deleterious increases in endothelial paracellular permeability and could serve as a basic mechanism of endothelial resealing during PMN transendothelial migration.

Challenging the use of the lymphocyte to white cell count ratio in the diagnosis of infectious mononucleosis by analysis of a large cohort of Monospot test results.

OBJECTIVE: We investigated the hypothesis that a lymphocyte/white cell count ratio should be used as a diagnostic indicator of infectious mononucleosis. DESIGN: Retrospective study to compare lymphocyte counts and white blood cell counts, against the criterion standard, the mononucleosis spot test. SETTING: Department of Otolaryngology, Mater Misericordiae University Hospital, Dublin, Ireland. PARTICIPANTS: We reviewed 1000 patients who had Monospot assays, 500 positive and 500 negative. MAIN OUTCOME MEASURES: The lymphocyte counts and white blood cell ratio was calculated and compared with the monospot result to calculate the sensitivity and specificity at various ratios. RESULTS: The lymphocyte counts and white blood cell ratio was significantly different in the positive and negative monospot groups (P < 0.05). The mean lymphocyte counts and white blood cell ratio in the positive group was 0.49 and the mean lymphocyte to white cell count ratio in the monospot negative group was 0.29.A ratio of 0.35 had a specificity of 72% and a sensitivity of 84% for the detection of glandular fever. A higher ratio will give a greater specificity, but a lower sensitivity, and vice versa. CONCLUSIONS: The mean lymphocyte to white cell count ratio is not sufficient to diagnose or exclude infectious mononucleosis. Thus, this study does not confirm the conclusions of earlier studies.

Activated endothelial cells elicit paracrine induction of epithelial chloride secretion. 6-Keto-PGF1alpha is an epithelial secretagogue.

Endothelial cells play a central role in the coordination of the inflammatory response. In mucosal tissue, such as the lung and intestine, endothelia are anatomically positioned in close proximity to epithelia, providing the potential for cell-cell crosstalk. Thus, in this study endothelial-epithelial biochemical crosstalk pathways were studied using a human intestinal crypt cell line (T84) grown in noncontact coculture with human umbilical vein endothelia. Exposure of such cocultures to endothelial-specific agonists (LPS) resulted in activation of epithelial electrogenic Cl- secretion and vectorial fluid transport. Subsequent experiments revealed that in response to diverse stimuli (LPS, IL-1alpha, TNF-alpha, hypoxia), endothelia produce and secrete a small, stable epithelial secretagogue into conditioned media supernatants. Further experiments identified this secretagogue as 6-keto-PGF1alpha, a stable hydrolysis product of prostacyclin (PGI2). Results obtained with synthetic prostanoids indicated that 6-keto-PGF1alpha (EC50 = 80 nM) and PGI2 stable analogues (EC50 = 280 nM) activate the same basolaterally polarized, Ca2+-coupled epithelial receptor. In summary, these findings reveal a previously unappreciated 6-keto-PGF1alpha receptor on intestinal epithelia, the ligation of which results in activation of electrogenic Cl- secretion. In addition, these data reveal a novel action for the prostacyclin hydrolysis product 6-keto-PGF1alpha and provide a potential endothelial- epithelial crosstalk pathway in mucosal tissue.

Aggressive medullary thyroid cancer, an analysis of the Irish National Cancer Registry.

BACKGROUND AND OBJECTIVES: Medullary thyroid cancer consists of a spectrum of disease that ranges from extremely indolent tumors to aggressive types associated with a high mortality rate. The objective of our study is to evaluate the prognostic factors and outcomes of patients diagnosed with MTC in a homogenous population, and to examine patients diagnosed with MTC for mutations in the RET proto-oncogene from the same period. METHODS: A retrospective analysis of the National Cancer Registry in Ireland was undertaken, between 1998 and 2007. The Kaplan-Meier method was used to determine overall survival and factors predictive of outcome were determined by univariate and multivariate analysis by cox regression using Stata 13 software. MAIN FINDINGS: Forty-three patients were diagnosed with medullary thyroid cancer, 55.8 % were female and 44.2 % were male. A median age of 52 was found. The overall median survival was 6.32 years and the 1- and 5-year overall survival was 88.37 and 62.79 %, respectively, with 10-year survival calculated at 48.63 %. On univariate analysis age, stage and surgical intervention were statistically significant indicators of prognosis. T stage and age remained statistically significant indicators of prognosis on multivariate analysis. Two patients with no history of MEN syndromes or family history of medullary thyroid cancer had RET proto-onocogene mutations. CONCLUSIONS: Our patient cohort was substantially older and presented at an advanced T status than what is commonly seen in the literature. This may account for poor survival outcomes and the very low pick-up of RET mutations in sporadic medullary thyroid cancer.

Auditory canal exostoses in Irish surfers.

AIM: Surfing is increasing in popularity in Ireland. Exostoses of the external auditory canal are a common finding in those who surf in cold water. The aim of this study was to examine the prevalence of external canal exostoses in a population of Irish surfers. METHODS: A cross-sectional study of Irish surfers was carried out. Patients were examined and questioned on their knowledge of exostoses, surfing routine, use of barrier protection and symptoms experienced. RESULTS: 119 surfers were analysed. 66 % of the surfers examined exhibited exostoses and 88 % were unaware of their diagnosis. Those that developed exostoses had surfed for a mean of 5,028 h, those that did not had surfed for a significantly shorter mean of 1,909 h (p = 0.0002). CONCLUSIONS: This is first study of this nature in the UK or Ireland. With a 5- to 6-year lag phase for exostoses to develop, these patients are likely to become an increasing part of Otolaryngologist's workload.

Total rhinectomy, a clinical review of nine cases.

INTRODUCTION: A large proportion of malignancies involving the external nose can be managed with limited resection and local autologous reconstruction or, in some cases, radiotherapy as primary or adjuvant treatment. We highlight a small cohort of patients undergoing total rhinectomy for advanced nasal malignancies. METHODS: A retrospective review of all patients undergoing total rhinectomy in our institution from 2006 to 2014 was undertaken. We reviewed patient demographics, surgical management, adjuvant treatment, histology, reconstruction and outcomes. RESULTS: Nine patients underwent total rhinectomy over an 8-year period, three of whom were being treated for recurrent disease. Eight patients had squamous cell carcinoma (SCC) and a single patient had an angiosarcoma. Two patients completed adjuvant radiotherapy. Seven patients underwent nasal prosthetic rehabilitation. All nine patients are alive and disease free at latest follow-up. CONCLUSION: Total rhinectomy is an uncommon procedure usually undertaken for extensive nasal malignancy. Nasal prosthetic rehabilitation is a viable method of reconstruction.

Chromosomal microarray provides enhanced targetable gene aberration detection when paired with next generation sequencing panel in profiling lung and colorectal tumors.

The development of targeted therapies based on specific genomic alterations has altered the treatment and management of lung and colorectal cancers. Chromosomal microarray (CMA) has allowed identification of copy number variations (CNVs) in lung and colorectal cancers in great detail, and next-generation sequencing (NGS) is used extensively to analyze the genome of cancers for molecular subtyping and use of molecularly guided therapies. The main objective of this study was to evaluate the utility of combining CMA and NGS for a comprehensive genomic assessment of lung and colorectal adenocarcinomas, especially for detecting drug targets. We compared the results from NGS and CMA data from 60 lung and 51 colorectal tumors. From CMA analysis, 33% were amplified, 89% showed gains, 75% showed losses and 41% demonstrated loss of heterozygosity; pathogenic variants were identified in 81% of colon and 67% lung specimens through NGS. KRAS mutations commonly occurred with loss in TP53 and there was significant loss of BRCA1 and NF1 among male patients with lung cancer. For clinically actionable targets, 23% had targetable CNVs when no pathogenic variants were detected by NGS. The data thus indicate that combining the two approaches provides significant benefit in a routine clinical setting not available by NGS alone.

Ongoing challenges in the treatment of adenoid cystic carcinoma of the head and neck.

BACKGROUND: Adenoid cystic carcinoma is a malignant tumour of major and minor salivary glands. Distant metastasis and poor survival are persistent in the literature, with recent publications aimed at understanding molecular pathogenesis and development of pharmaceutical therapeutic options. AIM: Provide an update of recent studies in the management of adenoid cystic carcinoma of the head and neck. METHODS: Literature search using Medline, Scopus, Google Scholar, the Cochrane Database of Systematic Reviews and the Cochrane central register of controlled trials for articles on adenoid cystic carcinoma from January 2005 to January 2015. CONCLUSION: Adenoid cystic carcinoma is characterized by a slow growing mass, with distant metastasis independent of local or regional control. Primary tumour resection remains the preferred option with radiotherapy having an adjuvant role. Recent advances have been made with novel targeted therapies however, limited to clinical trials and advanced disease.

Structural determinants of haloenol lactone-mediated suicide inhibition of canine myocardial calcium-independent phospholipase A2.

Haloenol lactones are potent mechanism-based inhibitors of a novel class of calcium-independent phospholipases A2 which have been implicated as the enzymic mediators of membrane dysfunction during myocardial ischemia (Hazen, S. L.; et al. J. Biol. Chem. 1991, 266, 7227-7232). Herein we demonstrate that the ring size, hydrophobic group, and cryptic electrophile in the haloenol lactone moiety are important and modifiable determinants of the inhibitory potency of haloenol lactone-mediated inhibition of calcium-independent phospholipase A2. Direct comparisons between haloenol lactone-mediated inhibition of calcium-independent phospholipase A2 and the absence of inhibition with calcium-dependent phospholipase A2 further underscore the marked differences in the catalytic strategy employed by these two classes of intracellular phospholipases A2.