Emergency department visits and unplanned hospitalizations in the treatment period for head and neck cancer patients treated with curative intent: A population-based analysis.

BACKGROUND: Mucosal head and neck squamous cell cancers are often managed with multimodality treatment which can be associated with significant toxicity. The objective of this study was to assess emergency department visits and unplanned hospitalizations for these patients during and immediately after their treatment. METHODS: A cohort of patients treated for head and neck squamous cell carcinoma was developed using administrative data. Emergency department visits and hospitalizations in the 90-day post-treatment period was determined. If a second treatment was initiated prior to the completion of 90 days, the attributable risk period was changed to the second treatment. RESULTS: Cohort of 3898 patients (1312 larynx/hypopharynx; 2586 oral cavity/oropharynx) from 2008 to 2012. The number of unplanned hospitalizations or ED visits (per 100 patient days) were 0.69 for surgery, 0.78 for surgery followed by concurrent chemoradiotherapy (CCRT), 0.55 for surgery followed by radiotherapy, 0.86 for CCRT, and 0.50 for radiation. Patients receiving CCRT had a statistically higher likelihood of treatment period events. The larynx/hypopharynx cancer subsite, higher comorbidity and more advanced stage of disease were all independent predictors of events. CONCLUSIONS: Patients undergoing treatment for head and neck cancer have significant unplanned hospitalizations and visits to the emergency department in the treatment period. Rates are higher in patients receiving CCRT. Quality improvement interventions should be used to improve these rates.

Heat and moisture exchanger use reduces in-hospital complications following total laryngectomy: a case-control study.

BACKGROUND: Total laryngectomy (TL) is an appropriate oncologic operation for many patients with laryngeal cancer delivering excellent oncologic outcomes, however it remains beset with significant functional consequences. Following TL, the upper and lower airways are permanently disconnected, which causes unfiltered, cold air with reduced humidity to enter the tracheobronchial tree, resulting in mucus overproduction and an increase in the viscosity of the mucus. In response to this, Heat and moisture exchangers were developed to compensate for the lost functions of the upper respiratory tract and their effect on the patients' respiratory performance in addition to their quality of life. METHODS: The case records of 48 patients undergoing total laryngectomy were reviewed and data concerning demographics, surgical details, post-operative care requirements and adverse events was retrieved. Post hoc analysis of the case patients was undertaken to identify any benefit of using a heat and moisture exchanger (HME) system with particular reference to post-operative respiratory outcomes. RESULTS: There was no significant difference between case and control subjects based on demographics, extent of surgery or need for flap repair. 16 patients had used a HME and 32 patients had used external humidification (EH). Of those experiencing mucous plugging, only 3/24 (12.5 %) had used a HME system, in contrast to 21/24 (87.5 %) who used EH (Chi square = 9.375, p = 0.002). The odds ratio of having an adverse event if not using HME was 8.27 (CI = 1.94 - 35.71). Use of HME also significantly reduced the number of days requiring physiotherapy (1.75 days vs. 3.20 days, p = 0.034). CONCLUSION: Use of an HME system can reduce in-hospital complications, in particular episodes of mucus plugging, and post-operative care requirements. Furthermore, there is a cost benefit to using HME systems that warrants more widespread introduction of these devices in head and neck surgery centers.

Comparison of survival between radiation therapy and trans-oral laser microsurgery for early glottic cancer patients; a retrospective cohort study.

BACKGROUND: The literature reports various treatment methodologies, such as trans-oral laser microsurgery, radiation therapy, total/partial laryngectomies, and concurrent radiation chemotherapy for patients with early larynx cancer. However, at the forefront of early glottis treatment is trans-oral laser microsurgery and radiation therapy, likely due to better functional and survival outcomes. Here we conduct the largest Canadian head-to-head comparison of consecutive patients treated with either radiation therapy or trans-oral laser microsurgery. Additionally, we compare these two treatments and their 5-year survival rates post treatment to add to the existing literature. METHODS: Charts of patients who were diagnosed with early glottic cancer between 2006 and 2013 were reviewed. Seventy-five patients were identified, and split into 2 groups based on their primary treatment, trans-oral laser microsurgery and radiation therapy. Kaplan-Meier survival curves, life-tables, and the log-rank statistic were reported to determine if there was a difference between the two treatment groups and their disease-specific survival, disease-free survival, and total laryngectomy-free survival. Additionally, each different survival analysis was stratified by potential confounding variables, to help conclude which treatment is more efficacious in this population. RESULTS: The 5-year disease-specific survival rate is 93.3 % σ = 0.063 and 90.8 % σ = 0.056 for patients treated with trans-oral laser microsurgery and radiation therapy, respectively (χ (2) < 0.001, p = 0.983). The disease free survival rate is 60.0 % (σ =0.121) for patients treated with trans-oral laser microsurgery, and 67.2 % (σ = 0.074) for those who received RT (χ (2) = 0.19, p = 0.663). Additionally, the total laryngectomy-free survival rate is 84.1 % (σ = 0.1) and 79.1 % (σ = 0.072) for patients' early glottic cancer treated by trans-oral laser microsurgery and radiation therapy, respectively (χ (2) = 0.235, p = 0.628). Chi-square analysis of age-group versus treatment group (χ (2) = 6.455, p = 0.04) and T-stage versus treatment group (χ (2) = 11.3, p = 0.001) revealed a statistically significant relationship, suggesting survival analysis should be stratified by these variables. However, after stratification, there was no statistically significant difference between the trans-oral laser microsurgery and radiation therapy groups in any of the survival analyses. CONCLUSION: No difference was demonstrated in the 5-year disease-specific survival, disease-free survival, and total laryngectomy-free survival, between the RT and TLM treatment groups. Additionally, both groups showed similar 5-year survival after stratifying by confounding variables.

Regulation of gene Expression by 1alpha,25-dihydroxyvitamin D3 and Its analog EB1089 under growth-inhibitory conditions in squamous carcinoma Cells.

Analogs of 1alpha,25-dihydroxyvitamin D(3) (1alpha, 25(OH)2D3) inhibit growth in vitro and in vivo of cells derived from a variety of tumors. Here, we examined the effects of 1alpha,25(OH)2D3 and its analog EB1089 on proliferation and target gene regulation of human head and neck squamous cell carcinoma (SCC) lines SCC4, SCC9, SCC15, and SCC25. A range of sensitivities to 1alpha,25(OH)2D3 and EB1089 was observed, from complete G0/G1 arrest of SCC25 cells to only 50% inhibition of SCC9 cell growth. All lines expressed similar levels of vitamin D3 receptor (VDR) mRNA and protein, and no significant variation was observed in 1alpha,25(OH)2D3-dependent induction of the endogenous 24-hydroxylase gene, or of a transiently transfected 1alpha,25(OH)2D3-sensitive reporter gene. The antiproliferative effects of 1alpha,25(OH)2D3 and EB1089 in SCC25 cells were analyzed by screening more than 4,500 genes on two cDNA microarrays, yielding 38 up-regulated targets, including adhesion molecules, growth factors, kinases, and transcription factors. Genes encoding factors implicated in cell cycle regulation were induced, including the growth arrest and DNA damage gene, gadd45alpha, and the serum- and glucocorticoid-inducible kinase gene, sgk. Induction of GADD45alpha protein in EB1089-treated cells was confirmed by Western blotting. Moreover, while expression of proliferating cell nuclear antigen (PCNA) was reduced in EB1089-treated cells, coimmunoprecipitation studies revealed increased association between GADD45alpha and PCNA in treated cells, consistent with the capacity of GADD45alpha to stimulate DNA repair. While 1alpha,25(OH)2D3 and EB1089 modestly induced transcripts encoding the cyclin-dependent kinase inhibitor p21(waf1/cip1), no changes in protein levels were observed, indicating that p21(waf1/cip1) induction does not contribute to the antiproliferative effects of 1alpha,25(OH)2D3 and EB1089 in SCC cells. Finally, in partially resistant SCC9 cells, there was extensive loss of target gene regulation (10 of 10 genes tested), indicating that resistance arises from widespread loss of 1alpha,25(OH)2D3-dependent gene regulation in the presence of normal levels of functional VDRs.

Occult cervical metastases: immunoperoxidase analysis of the pathologically negative neck.

OBJECTIVES: The purpose of this study is to better estimate the true incidence of occult regional metastases associated with stage I and II squamous cell carcinoma of the oral cavity. The clinical and prognostic significance of micrometastatic disease discovered by cytokeratin immunoperoxidase reactivity in the previously pathologically N0 neck is also evaluated. METHODS: Forty patients treated between 1985 and 1996 with T1 or T2 squamous cell carcinoma of the lip and oral cavity were studied. All had primary surgical treatment including functional neck dissection. No metastases were demonstrated on hematoxylin and eosin microscopy. All specimens were reexamined with immunoperoxidase staining for cytokeratin. RESULTS: Five percent of patients had micrometastatic disease. Retrospective analysis of patients with a minimum follow-up of 2 years has failed to show a statistically significant association between a positive cytokeratin analysis and poor locoregional control or overall survival. CONCLUSIONS: Results suggest that the true incidence of occult metastases with carcinoma of the oral cavity is significantly higher than previously documented. However, the prognostic significance of these findings remains unclear.

Transoral approaches to the clivus and nasopharynx.

This article presents the surgical anatomy of the clivus, nasopharynx, and craniocervical junction as it relates to the transoral approach to the midline basicranium. Particular attention is given to the indications, limitations, and complications of this procedure. The transpalatal approach is discussed in detail. Finally, the transmandibular approach is also briefly discussed.

Management of congenital anomalies of the neck.

This article, although not exhaustive, highlights the most common congenital anomalies of the neck. The diagnostic possibilities for a neck mass are extensive, and congenital malformations account for a minority of neck masses. The misdiagnosis and inappropriate treatment of a neck mass may have serious consequences for the patient. Therefore, a standardized and complete approach to the evaluation of neck masses is required. As stressed in this article, a thorough history and physical examination form the cornerstones of such an evaluation. The fact that congenital lesions of the neck have varied manifestations and may present at any age should always be considered.

Transnasal oesophagoscopy-guided in-office secondary tracheoesophageal puncture.

OBJECTIVE: Tracheoesophageal puncture is recognised as an effective and reliable method for voice restoration following total laryngectomy. Several techniques have been described, ranging from rigid oesophagoscopy under general anaesthesia to more recent endoscopic techniques utilising intravenous sedation or local anaesthetic. We describe our technique for secondary tracheoesophageal puncture utilising unsedated transnasal oesophagoscopy in an office setting. METHOD: Retrospective review of all total laryngectomy patients undergoing in-office transnasal oesophagoscopy-assisted tracheoesophageal puncture between October 1 2004 and December 31 2006. RESULTS: Eleven patients undergoing transnasal oesophagoscopy-guided tracheoesophageal puncture were identified. Successful tracheoesophageal puncture placement was achieved in 10 of 11 patients (91 per cent). In one patient tracheoesophageal puncture could not be performed due to anatomic constraints. One patient had bleeding from the puncture site requiring silver nitrate cautery. All patients tolerated the procedure well. Voice results were satisfactory in all cases. CONCLUSIONS: Transnasal oesophagoscopy-guided tracheoesophageal puncture provides a simple, safe option for secondary voice rehabilitation in laryngectomy patients.

Adenoid cystic carcinoma of the head and neck: a clinicopathologic study of 37 cases.

The records of 37 patients with histopathologically confirmed adenoid cystic carcinoma, who presented to McGill University's Department of Otolaryngology between 1956 and 1990, were reviewed to determine factors influencing local failure, distant metastases, and survival. Of the 37 cases, 12 developed local recurrences. Local failure was seen an average of 3.5 years following initial treatment, 62% of which were seen prior to 2 years. No statistically significant advantage was found for the use of postoperative radiotherapy in the prevention of local recurrences. Thirteen cases presented with or subsequently developed distant metastases. The mean interval between initial treatment and the appearance of distant disease was 8.1 years. A comparison of survival in patients with negative versus positive surgical margins was carried out. Survival at 15 years with negative margins remained 100%, while with positive margins, only 35% survived. Disease-free survival with negative and positive margins at 10 years was 80% and 31.1%, respectively. The effect of positive margins on survival was statistically significant with a p values between .01 and .001. The aim of this study was to demonstrate the importance of negative surgical margins with regard to survival. The results suggest that negative margins at initial resection significantly improve long-term disease-free survival.

The independent and combined effects of RAR-, RXR-, and VDR-selective ligands on the growth of squamous cell carcinoma in vitro.

OBJECTIVE: The purpose of our study was to analyze the independent and combined effects of RAR-, RXR-, and VDR-selective ligands on the growth of squamous cell carcinoma to develop new, more effective, and less toxic chemopreventive therapy. METHOD: The effects of 13-cis retinoic acid (13-cis RA), LG1069 (a highly selective RXR ligand), and vitamin D3 (D3) were analyzed in vitro in the SCC-25 human squamous cell carcinoma cell line. SCC-25 cells were grown in culture medium containing vehicle or hormone at the indicated concentrations. Growth of surviving cells was then assessed using a hemocytometer. The presence of functional vitamin D3 receptor (VDR) was confirmed using gene-transfer experiments with a promoter-lac Z reporter plasmid. RESULTS: D3 and 13-cis RA have equipotent antiproliferative effects on SCC-25 cells. Furthermore, equimolar LG1069 completely blocks the growth-suppressive effects of D3 but has no effect on the action of 13-cis RA. CONCLUSION: D3 and its analogs, administered alone or in combination with 13-cis RA, may provide more effective and less toxic chemopreventive therapy for the prevention of second primary carcinomas of the head and neck.