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Objectives: To examine whether social determinants of health (SDH) factors are associated with time to diagnosis, treatment selection, and time to recurrent surgical intervention in idiopathic subglottic stenosis (iSGS) patients. Methods: Adult patients with diagnosed iSGS were recruited prospectively (2015-2017) via clinical providers as part of the North American Airway Collaborative (NoAAC) and via an online iSGS support community on Facebook. Patient-specific SDH factors included highest educational attainment (self-reported), median household income (matched from home zip code via U.S. Census data), and number of close friends (self-reported) as a measure of social support. Main outcomes of interest were time to disease diagnosis (years from symptom onset), treatment selection (endoscopic dilation [ED] vs cricotracheal resection [CTR] vs endoscopic resection with adjuvant medical therapy [ERMT]), and time to recurrent surgical intervention (number of days from initial surgical procedure) as a surrogate for disease recurrence. Results: The total 810 participants were 98.5% female, 97.2% Caucasian, and had a median age of 50 years (IQR, 43-58). The cohort had a median household income of $62 307 (IQR, $50 345-$79 773), a median of 7 close friends (IQR, 4-10), and 64.7% of patients completed college or graduate school. Education, income, and number of friends were not associated with time to diagnosis via multivariable linear regression modeling. Univariable multinominal logistic regression demonstrated an association between education and income for selecting ED versus ERMT, but no associations were noted for CTR. No associations were noted for time to recurrent surgical procedure via Kaplan Meier modeling and Cox proportional hazards regression. Conclusions: Patient education, income, and social support were not associated with time to diagnosis or time to disease recurrence. This suggests additional patient, procedure, or disease-specific factors contribute to the observed variations in iSGS surgical outcomes.

The association between the indoor environment and lifetime prevalence of otitis media (OM) in Australian children was assessed. We analysed data from a cross-sectional study of children, aged 7–11 years, performed in twelve Australian cities during 2007–2008. The main outcome was a parental report of their child’s diagnosis with OM by a doctor. Information on the indoor environment (energy sources used for heating, cooling, and cooking, pets, and second-hand smoke exposure), in the first year of life and at present, was collected from parents by a questionnaire. Multi-level logistic regression models were used to adjust for individual- and area-level confounders. Our analysis comprised 2872 children (51% female, mean age: 10.0 (SD 1.2)). Of those, 1097 (39%) were reported to have OM. Exposure to gas heating in the first year of life was significantly associated with higher odds of OM in adjusted models (OR:1.22; 95% CI: 1.00,1.47), as was current exposure to reverse-cycle air conditioning (OR: 1.52, 95% CI: 1.27,1.82). Ownership of a cat or dog at any time was also associated with high odds of OM (OR: 1.50; 95% CI: 1.17,1.92). No other significant associations were observed. In this national study of Australian children, indoor environmental exposures associated with the lifetime prevalence of OM were gas heating, reverse-cycle air conditioning and pet ownership. Exposures in both early life and later childhood may both play a role in OM.

A 67-year-old Caucasian male presented with severe contraction of socket lining 8 years after enucleation, dermis fat graft and successful ocular prosthesis fitting. Following two failed attempts at using amniotic membrane grafts to reform the socket lining, a total socket reconstruction was attempted using a novel nasal turbinate mucosal graft technique. This was performed in a staged fashion with lower fornix reconstruction followed by upper fornix reconstruction 3 months later. The patient was stable at 12 months review, with a satisfactory cosmetic outcome. Nasal turbinate mucosa was used as it was surgically accessible, provided natural socket lubrication due to its mucosal surface, and avoided oral mucosa and its associated morbidity. This case report suggests that nasal turbinate mucosa is a suitable autologous grafting material for total socket reconstruction in contracted anophthalmic sockets.

Zellweger syndrome spectrum disorders are caused by mutations in any of at least 12 different PEX genes. This includes PEX16, an important regulator of peroxisome biogenesis. Using whole genome sequencing, we detected previously unreported, biallelic variants in PEX16 [NM_004813.2:c.658G>A, p.(Ala220Thr) and NM_004813.2:c.830G>A, p.(Arg277Gln)] in an individual with leukodystrophy, spastic paraplegia, cerebellar ataxia, and craniocervical dystonia with normal plasma very long chain fatty acids. Using olfactory-neurosphere derived cells, a population of neural stem cells, we showed patient cells had reduced peroxisome density and increased peroxisome size, replicating previously reported findings in PEX16 cell lines. Along with alterations in peroxisome morphology, patient cells also had impaired peroxisome function with reduced catalase activity. Furthermore, patient cells had reduced oxidative stress levels after exposure to hydrogen-peroxide (H2O2), which may be a result of compensation by H2O2 metabolising enzymes other than catalase to preserve peroxisome-related cell functions. Our findings of impaired catalase activity and altered oxidative stress response are novel. Our study expands the phenotype of PEX16 mutations by including dystonia and provides further insights into the pathological mechanisms underlying PEX16-associated disorders. Additional studies of the full spectrum of peroxisomal dysfunction could improve our understanding of the mechanism underlying PEX16-associated disorders. Keywords: Whole genome sequencing, PEX16, Peroxisomes, Leukodystrophy, Dystonia

Background To compare outcomes of high-risk human papilloma virus-related oropharyngeal squamous cell carcinoma (HPV OPSCC) treated with modern radiation treatment (RT) and daily image-guidance, staged with the 7th versus the 8th Edition (Ed) Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) TNM staging systems. Methods All eligible patients with HPV OPSCC treated definitively over a 10-year period (2007–2016) at a single institution were included. Protocols consisting of either RT or chemo-radiation (CRT) (weekly cisplatin or cetuximab) +/− neoadjuvant chemotherapy for those with bulky disease were used. All patients were Fluorine-18-deoxyglucose positron emission tomography (FDG-PET) staged at baseline and at intervals for up to 2 years post-treatment. Patients received parotid-sparing intensity modulated or volumetric modulated arc therapy with simultaneous integrated boost to either 70Gy in 35 fractions or 66Gy in 30 fractions. The overall survival (OS) was determined for each stage using the 7th Ed and subsequently with the updated 8th Ed staging system. Results One hundred fifty-three patients were analysed. Patient stage groupings varied between the 7th and 8th Eds respectively; Stage I (0.7% vs 64.7%), Stage II (8.5% vs 22.2%), stage III (21.6% vs 12.4%) and stage IV (69.3% vs 0.7%). In the 7th Ed, the 5 year probability of OS for stages I to III was 90%, versus stage IV 85.5%. There was no statistically significant difference between the staging groups (p = 0.85). In the 8th Ed there was a statistically significant difference in 5 year OS for stage I and stage II disease (96.9% vs 77.1% respectively; p

Background Tumour thickness is a strong predictor for cervical node involvement in oral cavity squamous cell carcinomas (SCCs), with a recent meta-analysis concluding a 4-mm optimal prognostic cut-off point. No consensus has been reached for the tumour thickness cut-off for oral tongue SCCs. Methods A retrospective review of prospectively collected data from 112 patients by the Northern Sydney Cancer Centre (Australia) with primary oral tongue SCC was conducted. Tumour thickness was measured by standard histopathological techniques and cervical node involvement was determined either from neck dissection histopathology or by clinical and radiological follow-up. Results Neck dissection was performed in 78 patients (70%). Tumour thickness was a significant predictor of cervical node disease (P

Objective:To review our experience with therapeutic sialendoscopy in both the submandibular and parotid glands in order to determine prognostic factors and improve successful outcomes.Study design:Single-centre, retrospective chart review.Method:The medical records of patients who had undergone sialendoscopy for sialolithiasis were reviewed, and demographic details, stone data (location, size, multiplicity, mobility), and operative technique and success were recorded.Results:Eighty-five patients were included: 70 patients with submandibular stones and 15 with parotid stones. Sialendoscopy was successful in all cases. Complete endoscopic removal was successful in 51 per cent of patients with submandibular stones and 47 per cent of those with parotid stones. Size (less than 5 mm) and distance from the papilla (less than 3 cm) were significant factors affecting success for patients with submandibular duct stones. However, this was not the case for patients with parotid duct stones, with neither variable achieving significance; nevertheless, numbers were small.Conclusion:Stone size and location significantly affect the success of therapeutic sialendoscopy in submandibular glands.

Importance Surgical treatment comparisons in rare diseases are difficult secondary to the geographic distribution of patients. Fortunately, emerging technologies offer promise to reduce these barriers for research. Objective To prospectively compare the outcomes of the 3 most common surgical approaches for idiopathic subglottic stenosis (iSGS), a rare airway disease. Design, Setting, and Participants In this international, prospective, 3-year multicenter cohort study, 810 patients with untreated, newly diagnosed, or previously treated iSGS were enrolled after undergoing a surgical procedure (endoscopic dilation [ED], endoscopic resection with adjuvant medical therapy [ERMT], or cricotracheal resection [CTR]). Patients were recruited from clinician practices in the North American Airway Collaborative and an online iSGS community on Facebook. Main Outcomes and Measures The primary end point was days from initial surgical procedure to recurrent surgical procedure. Secondary end points included quality of life using the Clinical COPD (chronic obstructive pulmonary disease) Questionnaire (CCQ), Voice Handicap Index-10 (VHI-10), Eating Assessment Test-10 (EAT-10), the 12-Item Short-Form Version 2 (SF-12v2), and postoperative complications. Results Of 810 patients in this cohort, 798 (98.5%) were female and 787 (97.2%) were white, with a median age of 50 years (interquartile range, 43-58 years). Index surgical procedures were ED (n = 603; 74.4%), ERMT (n = 121; 14.9%), and CTR (n = 86; 10.6%). Overall, 185 patients (22.8%) had a recurrent surgical procedure during the 3-year study, but recurrence differed by modality (CTR, 1 patient [1.2%]; ERMT, 15 [12.4%]; and ED, 169 [28.0%]). Weighted, propensity score–matched, Cox proportional hazards regression models showed ED was inferior to ERMT (hazard ratio [HR], 3.16; 95% CI, 1.8-5.5). Among successfully treated patients without recurrence, those treated with CTR had the best CCQ (0.75 points) and SF-12v2 (54 points) scores and worst VHI-10 score (13 points) 360 days after enrollment as well as the greatest perioperative risk. Conclusions and Relevance In this cohort study of 810 patients with iSGS, endoscopic dilation, the most popular surgical approach for iSGS, was associated with a higher recurrence rate compared with other procedures. Cricotracheal resection offered the most durable results but showed the greatest perioperative risk and the worst long-term voice outcomes. Endoscopic resection with medical therapy was associated with better disease control compared with ED and had minimal association with vocal function. These results may be used to inform individual patient treatment decision-making.

Human ATP13A2 (PARK9), a lysosomal type 5 P-type ATPase, has been associated with autosomal recessive early-onset Parkinson's disease (PD). ATP13A2 encodes a protein that is highly expressed in neurons and is predicted to function as a cation pump, although the substrate specificity remains unclear. Accumulation of zinc and mitochondrial dysfunction are established aetiological factors that contribute to PD; however, their underlying molecular mechanisms are largely unknown. Using patient-derived human olfactory neurosphere cultures, which harbour loss-of-function mutations in both alleles of ATP13A2, we identified a low intracellular free zinc ion concentration ([Zn(2+)]i), altered expression of zinc transporters and impaired sequestration of Zn(2+) into autophagy-lysosomal pathway-associated vesicles, indicating that zinc dyshomeostasis occurs in the setting of ATP13A2 deficiency. Pharmacological treatments that increased [Zn(2+)]i also induced the production of reactive oxygen species and aggravation of mitochondrial abnormalities that gave rise to mitochondrial depolarization, fragmentation and cell death due to ATP depletion. The toxic effect of Zn(2+) was blocked by ATP13A2 overexpression, Zn(2+) chelation, antioxidant treatment and promotion of mitochondrial fusion. Taken together, these results indicate that human ATP13A2 deficiency results in zinc dyshomeostasis and mitochondrial dysfunction. Our data provide insights into the molecular mechanisms of zinc dyshomeostasis in PD and its contribution to mitochondrial dysfunction with ATP13A2 as a molecular link between the two distinctive aetiological factors of PD.

The objective was to assess the feasibility and safety of transoral robotic surgery (TORS)-assisted free flap reconstruction for hypopharyngeal carcinoma after radiation therapy. The study evaluated the feasibility, surgical margins, the need for a tracheotomy, a nasogastric tube as well as surgery-related complications. Two patients underwent TORS-assisted free flap reconstruction after radiation therapy. The resection margins were free of tumor in both patients. A tracheotomy was performed in one patient who had been decannulated on the sixth postoperative day. One patient resumed satisfactory oral feeding in the fourth postoperative month and the second patient on postoperative day 7. No intraoperative complication and one postoperative complication (neck hematoma) were reported. After a follow-up period of 24 and 30 months, no local recurrence was observed. TORS is feasible for hypopharyngeal resection and assisted free flap reconstruction after radiation therapy. It represents a further step in the development of minimally invasive surgery for the treatment of head and neck cancers with laryngeal preservation.

Introduction. Pharyngoesophageal diverticuli are a common cause of dysphagia; they are associated with various morbidities and a decreased quality of life. There are several different types of the diverticuli, and they are divided based on the anatomical location of origin relative to the cricopharyngeal muscle; these include Zenker’s, Killian-Jamieson’s, and Laimer’s diverticula. The authors present a unique case of pharyngoesophageal diverticulum that has not been previously described.Case Presentation. A 65-year-old male presented with a 12-month history of dysphagia and odynophagia for solids. Barium swallow revealed bilateral moderately sized diverticuli that altered in size during the different phases of swallow. CT scan of the neck with oral contrast further identified the anatomy of the diverticuli, arising between the hyoid bone and thyroid cartilage.Discussion. An external transcervical approach was utilised to successfully repair the diverticuli. Subsequent cricopharyngeal spasm was treated with botulinum toxin, and the patient recovered with no ongoing symptoms. The barium swallow study is a commonly utilised initial investigation as it is easy to perform and safe and has good diagnostic value. Definitive management usually involves either endoscopic or open surgery. This case depicts a unique case of a pharyngeal diverticulum arising between the hyoid bone and thyroid cartilage.

Introduction The study aims to report outcomes for patients treated using intensity-modulated radiotherapy (IMRT) with simultaneous-integrated boost and weekly cisplatin for American Joint Committee on Cancer stage III/IV mucosal head and neck squamous cell carcinomas (HNSCCs). Methods Records for 67 patients treated definitively with IMRT for HNSCC were reviewed. By including only those treated with weekly cisplatin, 45 patients were eligible for analysis. Treatment outcomes, effect of patient, tumour and treatment characteristics on disease recurrence were analysed. Results All patients completed IMRT to 7000 cGy in 35 fractions, with concurrent weekly cisplatin 40 mg/m2 (median 6 cycles). Median follow-up was 28 months for living patients. Two-year loco-regional recurrence-free, metastasis-free and overall survival were 85.4, 81.0 and 87.4%, respectively. Local recurrence occurred in three patients, and distant recurrence in eight patients. Conclusions Our results show efficacy of IMRT and weekly cisplatin in the treatment of stage III/IV HNSCC at our institution with respect to loco-regional control.

Objective:To investigate the rate of occult neck disease in patients with metastatic squamous cell carcinoma to the parotid gland following parotidectomy and neck dissection.Methods:A consecutive series of patients treated between 2000 and 2014 for metastatic squamous cell carcinoma to the parotid were analysed. Patients were included if they had no clinical or radiological evidence of neck disease. Pathology of parotidectomy and neck dissection specimens was reviewed. Other variables analysed included patient immune status, surgery type, complications, use of positron emission tomography scanning and treatment with radiotherapy.Results:Sixty-five patients had no clinical or radiological evidence of neck disease initially. Forty-six patients (70.8 per cent) underwent neck dissection. Occult neck disease was only found in 8 of the 46 patients (17.3 per cent). Occult neck disease was found more often in those with immunocompromise (5.7 vs 38.5 per cent, p = 0.003). Patients who were immunocompromised had a significantly worse disease-specific survival rate at five years (0 vs 92 per cent, p = 0.0001).Conclusion:Occult neck disease was seen in 17.3 per cent of patients and immunosuppression was a significant predictor for this.

Background Correctly identifying the aetiology of lateral cervical cysts poses a diagnostic challenge commonly encountered by head and neck surgeons. The aim of this study was to ascertain the effectiveness of current investigatory techniques used in the diagnosis of these masses. Methods A retrospective analysis of all patients presenting to a single Sydney Head and Neck Unit between 2000 and 2010 with the diagnosis of a lateral cervical cyst was performed. Patients with a clinically evident primary malignancy were excluded from the study. Results of their clinical assessment and any investigations performed were compared with pathology after surgical excision. Results Forty-seven patients met the inclusion criteria. Twelve of the 47 masses showed squamous cell carcinoma on histology post-operatively. The remainder of the masses (35 out of 47) were histologically diagnosed as branchial cleft cysts. Of the malignant tumours, 4 of 12 (33%) were correctly identified before cyst removal. Fine-needle aspiration (FNA) was performed in 37 of the 47 patients, with a sensitivity of 25% and a specificity of 96.6%. Notably, a false-positive result was obtained from FNA in a patient who had a final diagnosis of branchial cyst after modified radical neck dissection. The rate of malignancy in patients aged over 40 years (44%) was higher than that of the total group (25.5%) and significantly higher than that of patients aged below 40 years (0%). Conclusions Current techniques in the investigation of cystic neck masses are suboptimal in their accuracy. Clinical evaluation and, in particular, thorough examination of the oropharynx directly and by fibre-optic nasendoscopy will often reveal the presence of a primary cancer when present. Care must always be taken in the evaluation of such lesions to maximize the likelihood of making the correct diagnosis.

Background: To compare the epidemiology and survival outcomes of Australian patients with HPV-positive and -negative oropharyngeal squamous cell carcinoma (OPSCC) using a standalone p16 approach. Methods: A retrospective analysis of medical record data was performed for patients presenting with OPSCC to Royal North Shore Hospital in Sydney, Australia from 2005 to 2017. p16 immunohistochemistry (IHC) was used as a biomarker for HPV status. Epidemiological trends and clinicopathological details were compared between the HPV-positive and -negative cohorts. Three-year overall survival rates and the hazard ratio conferred by HPV positivity were calculated. Results: A total of 244 patients were included with 202 (82.8%) having HPV-positive disease. The yearly incidence of HPV-positive OPSCC increased from 2005 to 2016 (P

Basal cell carcinomas (BCCs) are locally invasive skin neoplasms of cells in the epidermal basal layer. BCC metastasis remains a rare phenomenon, although such an event is associated with high morbidity and mortality. It has been suggested that certain features may be used to predict metastatic spread, including histological subtype, size, and perineural or lymphovascular invasion. We reviewed cases of metastatic BCC seen at Royal North Shore Hospital over a 16 year period. Pathology reports and specimens of both the primaries and metastatic lesions were obtained, and reviewed by an independent pathologist for second opinion on histopathology and confirmation of metastatic BCC. Six cases were found and reviewed (age 60±12, 17% F). Three of the six cases involved primaries located in the head and neck. The most common primary histological subtypes were morpheaform & infiltrative. This was accompanied by perineural and/or lymphovascular invasion in two cases. Three of the cases demonstrated large primaries of greater than 50 mm in diameter. One was found to have squamous differentiation in both the primaries and metastases. The most common site of metastases was the lungs, occurring in three of the cases, whilst other metastatic locations included bone and lymph nodes. We propose that primary BCCs with suspicious clinical/histopathological features be monitored closely, especially those from the head and neck region. We also propose further consideration of immunohistochemical markers as potential metastatic predictors.

Background Currently there are very few biomarkers to identify head and neck squamous cell carcinoma (HNSCC) cancer patients at a greater risk of recurrence and shortened survival. This study aimed to investigate whether a marker of systemic inflammation, the neutrophil-to-lymphocyte ratio (NLR), was predictive of clinical outcomes in a heterogeneous cohort of HNSCC cancer patients. Methods We performed a retrospective analysis to identify associations between NLR and clinicopathological features to recurrence free survival (RFS) and overall survival (OS). Univariate analysis was used to identify associations and selected variables were included in multivariable Cox regression analysis to determine predictive value. Results A total of 145 patients with stage I-IV HNSCC that had undergone radiotherapy were analysed. Seventy-six of these patients had oropharyngeal cancer and 69 had non-oropharyngeal HNSCC and these populations were analysed separately. NLR was not associated to any clinicopathological variable. On univariate analysis, NLR showed associations with RFS and OS in both sub-populations. Multivariable analysis showed patients with NLR > 5 had shortened OS in both sub-populations but NLR > 5 only predicted RFS in oropharyngeal patients. Poor performance status predicted OS in both sub-populations and current smokers had shortened OS and RFS in non-oropharyngeal patients. Conclusions The results show patients with NLR > 5 predict for shorter overall survival. Further prospective validation studies in larger cohorts are required to determine the clinical applicability of NLR for prognostication in HNSCC patients. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2089-4) contains supplementary material, which is available to authorized users.

Tumour thickness is a strong predictor for cervical node involvement in oral cavity squamous cell carcinomas (SCCs), with a recent meta-analysis concluding a 4-mm optimal prognostic cut-off point. No consensus has been reached for the tumour thickness cut-off for oral tongue SCCs.A retrospective review of prospectively collected data from 112 patients by the Northern Sydney Cancer Centre (Australia) with primary oral tongue SCC was conducted. Tumour thickness was measured by standard histopathological techniques and cervical node involvement was determined either from neck dissection histopathology or by clinical and radiological follow-up.Neck dissection was performed in 78 patients (70%). Tumour thickness was a significant predictor of cervical node disease (P0.01), with a median tumour thickness of 5.5 mm. Cervical node metastasis rates for tumours2, 2-3.9 and ≥4 mm thick were 10%, 42.1% and 46.5%, respectively. The rate of cervical node metastasis was significantly higher for patients with tumours thicker than a cut-off of 2 mm (odds ratio: 7.53, P0.01). A 4-mm thickness cut-off was also statistically significant (P0.05); however, the odds ratio was smaller at 2.52.Despite some previous evidence for a 4-mm tumour thickness cut-off in oral tongue SCCs, thinner tumours (2-3.9 mm) can also have a propensity for cervical node metastasis. Patients in this category require close monitoring for regional recurrence if they do not have a neck dissection.

Background:Pharyngeal pouches have been recognised as a cause of dysphagia for centuries and have been treated in a variety of ways over that time.Objective:This article aimed to analyse the results of surgery by a variety of techniques, as performed by one surgeon.Method:A retrospective analysis of a case series was conducted, analysing the variables of patient age, sex, type of surgery, length of hospital stay, leak, recurrence and other complications.Results:A total of 121 patients were treated by 135 operations. There were no leaks in the group treated by endoscopic stapling and this group also had a significantly shorter hospital stay. As for recurrence, the lowest rate appeared to be in the group treated by excision of the pouch.Conclusion:The techniques used by the author all still seem to have a role in the management of pharyngeal pouch, with the endoscopic stapling approach associated with a low rate of complications and short hospital stay.

Background: Cysts, sinuses or abscesses arising from second, third or fourth branchial cleft remnants may lie either within the body of, or in close proximity to the thyroid gland. Given their infrequent nature they may pose both diagnostic and management challenges for the treating surgeon when they occur in association with thyroid disorders. Methods: This is a case series. All patients with concomitant thyroid disorders and a branchial cleft anomaly treated in the University of Sydney Endocrine Surgical Unit in the 10-year period 1994−2003 comprised the study group. Patient demographics, clinical presentation, imaging, surgical management, definitive histology and outcomes were documented. Results: Six patients were identified with an age range of 3−76 years and a male : female ratio of 1:5. Five branchial cleft anomalies were left sided, one was right sided. Two patients had second cleft anomalies, both of which were initially thought to represent metastatic lymph nodes in association with thyroid cancer. A further two patients had third cleft abnormalities presenting as suppurative thyroiditis. The final two patients had fourth cleft abnormalities causing intraoperative management problems. Conclusions: Branchial cleft remnants and anomalies are rare but may occur in association with thyroid disease. They may pose a diagnostic and management dilemma either preoperatively, when mistaken for metastatic thyroid cancer, or intraoperatively when mistaken for a thyroid nodule.

We conducted a retrospective study of 104 cases of salivary gland tumors that were initially assessed by fine-needle aspiration biopsy (FNAB). Based on subsequent histopathologic analysis of excised specimens, we found that preoperative FNAB was highly sensitive and specific for both benign and malignant tumors—including the most common, pleomorphic adenomas and squamous cell carcinomas, respectively. Despite its possible drawbacks, we conclude that preoperative FNAB is a useful tool in the management of salivary gland tumors.

We report 3 cases of rare, life-threatening intracranial and internal jugular vein (IJV) thrombosis that were caused by common ENT infections. These infections included otitis media in a 6-year-old girl, tonsillitis in a 21-year-old woman, and odontogenic sepsis in a 56-year-old woman. All 3 patients were treated with culture-directed systemic antibiotics; 2 of them also required surgical drainage (the child and the older adult). The 2 adults also received therapeutic anticoagulation, which was continued until venous recanalization was documented; the duration of combined antibiotic and anticoagulation treatment was 6 weeks. All 3 patients made uneventful recoveries. Significant morbidities associated with intracranial and IJV thrombosis were avoided as a result of prompt diagnosis and judicious treatment.

We sought to evaluate the swallowing function of 18 patients surviving nasopharyngeal cancer, who had been treated using an intensity-modulated radiotherapy (IMRT) protocol designed to minimise functional impairment. We compared the outcomes of a patient-reported oral function score with fiberoptic endoscopic examination of swallow (FEES), Australian Therapy Outcome Measures (AusTOMs) and a measure of trismus. While all patients returned to a fully oral diet, there was ongoing swallow dysfunction characterised by bolus residue and delay, but no aspiration. Dysphagia was of mild or moderate severity on all measures, generally because of the need for texture modification, impaired bolus transit or dysgeusia. There was xerostomia on self-reported measurement combined with reports of behaviours adaptive to xerostomia on AusTOMs; however, salivary functioning was less impaired on FEES. There was no trismus in this cohort. Our cohort lacked the morbidity experienced by cohorts reported in earlier studies, potentially due to the use of IMRT.

Background Despite the association with more advanced nodal stage, patients with human papillomavirus (HPV) positive oropharyngeal cancers have better outcomes. We examined whether the HPV can modify the effect of known prognostic factors in tonsillar cancer. Patients and methods A total of 489 patients from 10 centres were followed up for recurrence or death for a median of 3.2 years. Determinants of the rate of locoregional recurrence, death from tonsillar cancer and overall survival were modelled using Cox regression. Results The prognostic value of T and N stages were modified by HPV as indicated by statistically significant interaction terms. After adjusting for age, gender and treatment, T stage appeared relevant only for HPV-positive cancers (where a higher T stage was associated with worse outcomes). There was some evidence that N stage was a more relevant prognostic factor for HPV-negative than -positive cancers. There was no evidence that the HPV modifies the effect of age, gender or grade on outcomes. Conclusions This study suggests that the prognostic significance of the conventional staging system in tonsillar cancer is modified by HPV.

Kufor-Rakeb syndrome (KRS) is a rare form of autosomal recessive juvenile or early-onset, levodopa responsive parkinsonism and has been associated with mutations in ATP13A2(also known as PARK9), a lysosomal type 5 P-type ATPase. Recently, we identified novel compound heterozygous mutations, c.3176T>G (p.L1059R) and c.3253delC (p.L1085WfsX1088) in ATP13A2 of two siblings affected with KRS. When overexpressed, wild-type ATP13A2 localized to Lysotracker-positive and LAMP2-positive lysosomes while both truncating and missense mutated ATP13A2 were retained in the endoplasmic reticulum (ER). Both mutant proteins were degraded by the proteasomal but not the lysosomal pathways. In addition, ATP13A2 mRNA with c.3253delC was degraded by nonsense-mediated mRNA decay (NMD), which was protected by cycloheximide treatment. To validate our findings in a biologically relevant setting, we used patient-derived human olfactory neurosphere cultures and fibroblasts and demonstrated persistent ER stress by detecting upregulation of unfolded protein response-related genes in the patient-derived cells. We also confirmed NMD degraded ATP13A2 c.3253delC mRNA in the cells. These findings indicate that these novel ATP13A2 mutations are indeed pathogenic and support the notion that mislocalization of the mutant ATP13A2, resultant ER stress, alterations in the proteasomal pathways and premature degradation of mutant ATP13A2 mRNA contribute to the aetiology of KRS.Hum Mutat 32:1–9, 2011. © 2011 Wiley-Liss, Inc.

Summary Hereditary spastic paraplegia (HSP) leads to progressive gait disturbances with lower limb muscle weakness and spasticity. Mutations in SPAST are a major cause of adult-onset, autosomal-dominant HSP. Spastin, the protein encoded by SPAST, is a microtubule-severing protein that is enriched in the distal axon of corticospinal motor neurons which degenerate in HSP patients. Animal and cell models have identified functions of spastin and mutated spastin but these models lack the gene dosage, mutation variability and genetic background that characterize patients with the disease. In this study, this genetic variability is encompassed by comparing neural progenitor cells derived from biopsies of the olfactory mucosa from healthy controls with similar cells from HSP patients with SPAST mutations, in order to identify cell functions altered in HSP. Patient-derived cells were similar to control-derived cells in proliferation and multiple metabolic functions but had major dysregulation of gene expression, with 57% of all mRNA transcripts affected, including many associated with microtubule dynamics. Compared to control cells, patient-derived cells had 50% spastin, 50% acetylated α-tubulin and 150% stathmin, a microtubule-destabilising enzyme. Patient-derived cells were smaller than control cells. They had altered intracellular distributions of peroxisomes and mitochondria and they had slower moving peroxisomes. These results suggest that patient-derived cells might compensate for reduced spastin, but their increased stathmin expression reduced stabilised microtubules and altered organelle trafficking. Sub-nanomolar concentrations of the microtubule-binding drugs, paclitaxel and vinblastine, increased acetylated α-tubulin levels in patient cells to control levels, indicating the utility of this cell model for screening other candidate compounds for drug therapies.

To present the preliminary results in our institute with supracricoid laryngectomy with cricohyoidoepiglotopexy (CHEP), as well as to evaluate possible short-term complications.This study included eight patients with diagnosis of squamous cell carcinoma of the larynx glottic region (three patients were in stage I, two in II and three in III). Histologic grade was well differentiated in three patients, moderately differentiated in four and poorly differentiated in one.Supracricoid laryngectomy with cricohyoidoepiglotopexy were performed in all cases, and bilateral elective functional neck dissection was done in 6 patients. Both cricoarytenoid units were preserved in 6 patients and only one in the other two cases. Mean time of hospitalization was 11 days. Mean time of decanulation was 12 days for the whole group; however, in those patients that preserved both cricoarytenoid units, the mean time of decanulation was 6 days, and in those that preserved one cricoarytenoid unit it was 31 days. Physiologic phonation was achieved in all patients at the moment of decanulation. Mean time for remotion of nasogastric sonde was 25 days, and it was 17 days for those who preserved both cricoarytenoid units and for patients with one cricoarytenoid unit it was 46 days.Supracricoid laryngectomy with cricohyoidoepiglotopexy allows to preserve the basic functions of the larynx (respiration, degluttion and phonation), as well as the reintegration of affected patients to social life. All patients must be evaluated carefully in order avoid changing the stage or the surgical plan due to substadification of the tumor.

Based on an inception cohort of 35 patients with T1–3N0M0 squamous cell carcinoma of the true vocal cord who had a complete clinical response after a platinum-based induction chemotherapy regimen and a minimum of 3 years of follow-up, the current retrospective study documented the long-term results and consequences of local recurrence following the use of a platinum-based chemotherapy—alone regimen for cure. During the years 1985 to 1996, 231 patients with invasive squamous cell carcinoma of the true vocal cord classified as T1–3N0M0 were managed at our department with a platinum-based induction chemotherapy regimen. A complete clinical response was achieved in 77 patients. Thirty-five of the 77 patients with complete clinical response were managed at our institution with a platinum-based chemotherapy—alone regimen. The statistical analysis of data on survival, local control, nodal control, distant metastasis, and metachronous second primary tumor incidence was based on the Kaplan-Meier product limit method. Univariate analysis was performed for potential statistical relation between local recurrence and various variables. The 3- and 5-year actuarial survival estimates were 91.4% and 88.6%, respectively. Overall, the causes of death were intercurrent disease in 6 patients and metachronous second primary tumor in 4 patients. The 3- and 5-year actuarial local control estimate was 64.8%. No significant statistical relation could be demonstrated between the incidence for local recurrence and the variables under analysis. Salvage treatment in patients with local recurrence yielded a 100% local control rate and laryngeal preservation rate. The 3- and 5-year actuarial lymph node control estimate was 97.1%. The 3- and 5-year actuarial estimate for patients with distant metastasis was 0%. The 5- and 10-year actuarial estimates for patients with metachronous second primary tumor were 9.7% and 28.1%, respectively. Although local recurrence was noted in almost a third of patients with complete clinical response who were managed with a platinum-based chemotherapy-alone regimen, it did not appear to be detrimental, as none of the patients who had local recurrence ultimately died from their disease or lost their larynx.

The current retrospective studies documented the incidence, sites of occurrence, risk factors, and outcome of metachronous second primary cancers (MSPCs) among an inception cohort of 410 patients with invasive squamous cell carcinoma of the true vocal cord successfully treated with partial laryngectomy at a single institution. The Kaplan-Meier actuarial life-table method was used to document the relationship between the incidence of MSPCs and survival data. Univariate analysis was performed for potential statistical relationships among the incidence of MSPCs, the site of occurrence, and different variables. The overall incidence of MSPCs was 23.9% (98/410). The 10-year actuarial survival estimate for MSPCs was 20.4%. The incidence curve of MSPCs was linear, resulting in a 2%/y rate of development for MSPCs. In univariate analysis, the only variable that demonstrated a statistical correlation with the incidence of MSPCs was smoking, with MSPCs being statistically more likely to occur in smokers than in nonsmokers (p = .04). The main sites of origin for MSPCs were the lung (25.5% of cases), other non-upper aerodigestive tract sites (32.7%), and the upper aerodigestive tract (41.8%). The 10-year actuarial estimates for MSPCs were 9.1% in the upper aerodigestive tract, 7.1% in sites other than the lung or upper aerodigestive tract, and 6.6% in the lung. The incidence curve for MSPCs was linear, whatever the site of origin, resulting in 1%/y, 0.7%/y, and 0.6%/y rates of development for MSPCs in the upper aerodigestive tract, sites other than the lung or upper aerodigestive tract, and the lung, respectively. Survival was statistically reduced when an MSPC developed; the 10-year actuarial survival estimates were 76.8% in patients who did not develop an MSPC and 43.7% in patients who developed an MSPC (p < .0001). Overall, 68.4% of patients who developed an MSPC (67/98) died of this disease. The 10-year actuarial survival estimates were 24% for lung MSPCs, 43.7% for non-lung, non-upper aerodigestive tract MSPCs, and 63.4% for upper aerodigestive tract MSPCs.

BACKGROUND The current studies documented the results achieved with chemotherapy alone with curative intent in a series of 67 patients with invasive squamous cell carcinoma of the pharyngolarynx classified as T1–T4N0M0 complete clinical responders after a platin-based induction chemotherapy regimen. METHODS Group I consisted of 36 patients with tumors originating from the glottis. Group II consisted of 31 patients with tumors originating from sites within the pharyngolarynx other than the glottis. A minimum of 3 years of follow-up was achieved. Statistical analyses of survival, local control, lymph node control, distant metastasis, and second primary tumor rates were based on the Kaplan–Meier life-table method. Laryngeal preservation rates and local control rates are presented. RESULTS The 5-year actuarial survival estimate was 85.1% in Group I patients and 54.8% in Group II patients. Survival was statistically more likely to be reduced in Group II patients compared with Group I patients (P = 0.01). The 5-year actuarial local control estimate was 65.7% in Group I patients and 37.5% in Group II patients. Local failure was statistically more likely to occur in Group II patients compared with Group I patients (P = 0.02). Local control rates after salvage treatment were 100% in Group I patients and 83% in Group II patients. Laryngeal preservation rates after salvage treatment were 100% in Group I patients and 64% in Group II patients. The 5-year actuarial lymph node control estimate was 90% in Group I patients and 73.7% in Group II patients. Lymph node failure was statistically more likely to occur in Group II patients compared with Group I patients (P = 0.04). The 5-year actuarial estimate for patients without distant metastasis was 100% in Group I patients and 90% in Group II patients. Distant metastasis was statistically more likely to occur in Group II patients compared with Group I patients (P = 0.03). The 10-year actuarial estimate for patients without metachronous second primary tumors was 56.4% in Group I and 46.1% in Group II. CONCLUSIONS The current report 1) contradicts the old dogma of nonchemocurability for invasive squamous cell carcinoma of the upper aerodigestive tract and 2) suggests that the use of a platin-based chemotherapy-alone regimen with curative intent in patients with invasive squamous cell carcinoma of the pharyngolarynx who are classified as T1–T4N0M0 complete clinical responders after receiving an induction chemotherapy regimen is best indicated when the tumor originates from the glottis. Cancer 2001;92:1504–11. © 2001 American Cancer Society.

The purpose of this study was to review the incidence, risks, management, and outcomes of nontumoral laryngeal stenosis after supracricoid partial laryngectomy (SCPL) in a case series of 376 consecutive SCPLs performed at 1 institution from 1975 to 1995 with a minimum of 3 years of follow-up. Post-SCPL nontumoral symptomatic laryngeal stenosis was defined as an inability to decannulate patients before the 60th postoperative day (group 1) or the development of dyspnea (in patients without local recurrence) after an initial period of prolonged, successful decannulation (group 2). Of 376 SCPLs performed, nontumoral symptomatic laryngeal stenosis developed in 14 (3.7%). There were 7 patients (1.85%) in group 1 and 7 patients (1.85%) in group 2. In univariate analysis, none of the following variables appeared to be statistically related to the risk of immediate stenosis (group 1): age, gender, comorbidity, diabetes mellitus, symptomatic gastroesophageal reflux, arteritis, preoperative radiotherapy, arytenoid cartilage disarticulation, type of reconstruction performed, and postoperative radiotherapy. A delayed laryngeal stenosis (group 2) was statistically more likely to occur if the reconstruction performed at the time of SCPL was a cricohyoidopexy (p = .01). Successful management of the laryngeal stenosis without permanent tracheostomy was achieved in 5 group 1 patients and 3 group 2 patients. We believe that stenosis in group 1 patients arose through technical error, whereas group 2 patients seemed to suffer from problems of healing, mainly cicatricial narrowing of the airway at the site of the cricohyoidal impaction, or pexis. As a result, whereas laryngeal stenosis in group 1 patients was usually more easily correctable through dilation, laser incision, or resection of redundant tissue or revision of the impaction, laryngeal stenosis in group 2 patients presented a more difficult and frustrating complication. The management and outcomes of these patients are presented.

We report 2 cases in which supracricoid partial laryngectomy and cricohyoidoepiglottopexy were used to restore the airway in cases of severe associated glottic and supraglottic laryngeal stenosis.