Epigenetic down-regulation of SOX2 is an independent poor prognostic factor for hypopharyngeal cancers.

AIMS: We recently reported that a small subset (7%) of oesophageal squamous cell carcinomas completely lacking SOX2 expression had unique clinicopathological features and a dismal prognosis. The aim of the present study was to elucidate whether the findings obtained in oesophageal cancers are applicable to hypopharyngeal squamous cell carcinomas (HPSCCs) or oropharyngeal squamous cell carcinomas (OPSCCs). METHODS AND RESULTS: The study cohort consisted of consecutive patients with HPSCC (n = 130) and OPSCC (n = 65) who underwent surgery without preoperative therapy. On immunostaining, SOX2 was almost entirely negative in 10 of 130 HPSCCs (8%) and seven of 65 OPSCCs (11%). No significant differences were observed in clinicopathological features, including p16 status, between SOX2-positive and SOX2-negative cancers. However, patients with SOX2-negative HPSCC had significantly worse overall and recurrence-free survival than those with SOX2-positive HPSCC, whereas such a prognostic relationship was not confirmed in patients with OPSCC. In a multivariate analysis, the loss of SOX2 expression appeared to be an independent poor prognostic factor for patients with HPSCC. In a sequencing analysis, no mutation was found in SOX2. As SOX2 is known to contain an extensive CpG island before the transcription start site, methylation-specific polymerase chain reaction for the SOX2 promoter was performed. Methylated alleles were found in nine of 10 SOX2-negative HPSCCs but in none of SOX2-positive HPSCCs. CONCLUSIONS: Similarly to oesophageal cancers, a small subset (8%) of HPSCCs characteristically almost completely lacking SOX2 expression appeared to be aggressive neoplasms with high recurrence rates. Promoter hypermethylation was determined to be a major mechanism underlying epigenetic SOX2 silencing.

The Histopathology of IgG4-Related Disease.

IgG4-related disease is a multi-organ immune-mediated chronic fibroinflammatory condition characterized by elevated serum IgG4 concentrations, tumefaction, and tissue infiltration by IgG4-positive plasma cells. The exact etiology of IgG4-related disease remains unclear with no known role of the IgG4 molecule itself being identified. Although the pancreas and salivary glands are the main organs affected, the involvement of other organs has also been reported. This multi-organ disease mimics a large number of malignant, infectious, and inflammatory disorders; therefore, a prompt differential diagnosis is important for selecting the right therapeutic strategy. Early steroid therapy assists in preventing tissue fibrosis, parenchymal extinction, and severe functional impairments in the affected organs. The definitive and prompt diagnosis of IgG4-related disease requires both histopathological confirmation and clinicopathological correlations. A histopathological examination is mandatory to exclude neoplastic or inflammatory conditions that mimic IgG4-related disease. The histological changes that occur are basically similar in any organ manifestation, with several site-specific findings being recognized. This chapter summarizes general rules for the pathological examination of IgG4-related disease, as well as the histopathological features and differential diagnoses of major organ manifestations.

Modified Mallampati Score Improves Specificity of STOP-BANG Questionnaire for Obstructive Sleep Apnea.

BACKGROUND: An accurate, clinical screening tool for obstructive sleep apnea (OSA) that identifies patients for further diagnostic testing would assist in the diagnosis of this comorbidity. One example, the STOP-BANG questionnaire (SBQ), has been validated as a screening tool with high sensitivity. However, its specificity may result in a high false-positive rate. The aim of this study to determine if addition of the Modified Mallampati score to the SBQ improves its specificity. METHODS: The authors studied 162 patients referred to the Sleep Disorders Clinic at Yedikule Chest Disease Education and Research Hospital. All patients were prospectively screened for risk of OSA using the SBQ, their oral anatomy was assessed by Modified Mallampati scoring, and sleep quality characterized by polysomnography. Polysomnography results were reviewed when available and the predictive performance of the SBQ and the modified SBQ scoring models were compared. RESULTS: In the authors' study an SBQ score ≥3 yielded sensitivities of 0.85, 0.86, and 0.91 for Apnea-Hypopnea Index (AHI) ≥5/h, AHI ≥15/h, and AHI ≥30/h, respectively, and specificities of 0.09, 0.10, and 0.18. The modified SBQ with a cutoff of ≥4 (>3) points for AHI levels of >5, >15, and >30 yielded respective sensitivities of 0.84, 0.86, and 0.91 and specificities of 0.25, 0.26, and 0.27. CONCLUSIONS: The author's results from indicated the modified SBQ with a cutoff of >3 points in this study was more specific than the standard SBQ but no less sensitive, and may be used in identifying OSA patients for further diagnostic evaluation or avoiding unnecessary testing.

Sclerosing mesenteritis: A real manifestation or histological mimic of IgG4-related disease?

We present three cases of sclerosing mesenteritis and review the literature to learn whether or not sclerosing mesenteritis is an IgG4-related disease (IgG4-RD). Our patients were all adult males. Their mesenteric masses ranged from 6.5 to 14.5 cm in the greatest diameter. Tissue specimens showed moderate to severe lymphoplasmacytic infiltration with occasional eosinophils against a background of irregular fibrosis. Both obliterative phlebitis and storiform fibrosis were noted in all cases. IgG4+ plasma cells were moderately increased in number (46 to 85 cells/high-power field). However, unlike IgG4-RD, the IgG4+/IgG+ plasma cell ratio was <40% (28% to 35%). Serum IgG4 concentrations were also within the normal range (43.2 to 105 mg/dL; normal range <135 mg/dL). Two biopsy cases showed spontaneous regression on imaging approximately 5 months later. No sclerosing conditions were found in other organs. The literature review identified 11 additional cases of sclerosing mesenteritis with IgG4+ plasma cell infiltration. However, conclusive cases with four characteristic features (high serum IgG4 levels, tissue IgG4 elevation, multi-organ involvement, and effective response to glucocorticoid therapy) have never been reported. In conclusion, although sclerosing mesenteritis shares histological features with IgG4-RD, most cases are less likely to be IgG4-related. IgG4-RD seemingly seldom, if ever, affects this anatomical site.

Halitosis associated volatile sulphur compound levels in patients with laryngopharyngeal reflux.

Previous reports have suggested that laryngopharyngeal reflux (LPR) may cause halitosis. However, it remains unclear if LPR is a risk factor for halitosis. The aim of this study was to investigate if patients diagnosed with LPR have an increased probability of halitosis compared to a normal population. Fifty-eight patients complaining of LPR symptoms and 35 healthy subjects were included in the study. A LPR diagnosis was made using an ambulatory 24-h double pH-probe monitor, which is the gold standard diagnostic tool for LPR. Additionally, halitosis was evaluated by measuring the levels of volatile sulphur compounds using OralChroma™ and an organoleptic test score. The result of the final diagnosis of the 58 patients after the 24 h ambulatory pH monitoring was that 42 patients had LPR. Significant correlations were observed between the organoleptic test score and hydrogen sulfide (H2S) and methyl mercaptan (CH3SH) levels. These were also significantly correlated with LPR. We found a strong positive association between LPR and volatile sulphur compound levels. The H2S and CH3SH levels differed significantly between the LPR and control groups (p < 0.0001 and p < 0.0001, respectively). Halitosis was significantly associated with the occurrence and severity of LPR. The present study provides clear evidence for an association between halitosis and LPR. Halitosis has a high frequency in patients with LPR and reflux characteristics are directly related to their severity and therefore could be considered as a manifestation of LPR.

The Effects of Nasal Packing and Transseptal Suturing After Septoplasty on Olfactory Function, Patient Comfort, and Mucociliary Clearance.

BACKGROUND: This study compared the effects of nasal packing and transseptal suturing after septoplasty by evaluating olfactory function, pain, and mucociliary clearance. METHODS: The study enrolled 39 patients diagnosed with isolated septal deviation. The patients were randomly assigned to 2 groups. In Group A (n = 21), transseptal sutures were placed for septal stabilization after the septoplasty. In Group B (n = 18), both nasal passages were packed with Merocel tampons after the septoplasty. It was made Sniffin Sticks test, sacchranirine test, and pain and discomfort scales preoperatively, 1 week postoperatively and 3 months postoperatively on all patients. RESULTS: There was no postoperative bleeding, submucoperichondrial haematoma, or abscess formation in either group. The postoperative discomfort and pain scores were increased in Group B (the packing group) in our study, the mucociliary clearance improved after septoplasty in both groups, and there was no significant difference in mucociliary clearance between the 2 groups. The odor threshold, odor identification, and odor discrimination were significantly increased 3 months postoperatively, but not 1 week postoperatively. CONCLUSIONS: Nasal packing causes more discomfort and pain than transseptal suturing, while there was no significant difference in olfactory functions or the mucociliary clearance after septoplasty between nasal packing and transseptal suturing.

Effects of Spreader Grafts on Olfactory Function in Septorhinoplasty.

BACKGROUND: Following rhinoplasty, the cross-sectional parts of the nose may be significantly reduced, and nasal air movement and olfaction may be altered. Studies on olfactory function after surgical procedures are quite limited and have largely focused on sinus surgery or septoplasty. OBJECTIVES: The objective of this study is to assess the consequences of spreader grafts on olfactory function. METHODS: This prospective study was conducted at the Gaziosmanpasa Taksim Education and Research Hospital, Department of Otolaryngology, from January 2014 to June 2015. In total, 68 patients who had undergone an open-technique septorhinoplasty were included. In 35 patients, bilateral spreader grafts were included with the open septorhinoplasty (group 1), and 33 patients underwent open septorhinoplasties without spreader grafts (group 2). RESULTS: The age and gender distributions of the patients in the two groups did not differ (p > 0.05). Preoperative threshold, discrimination, and identification values in both groups did not differ (p > 0.05). In groups 1 and 2, postoperative threshold values were significantly higher than preoperative values (p < 0.05). The change in threshold, discrimination, and identification level was significantly higher postoperatively versus preoperatively in group 1 (p < 0.05); however, the changes in discrimination and identification values did not significantly differ between in group 2 (p > 0.05). CONCLUSIONS: Our study demonstrates the superior widening effect of spreader grafts over the nasal valve and favorable results in olfactory function in primary septorhinoplasty patients. LEVEL OF EVIDENCE IV: This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Oncogenic E6 and/or E7 proteins drive proliferation and invasion of human papilloma virus­positive head and neck squamous cell cancer through upregulation of Ror2 expression.

Ror2 (receptor tyrosine kinase like orphan receptor 2) is highly expressed in various types of cancers; in the majority of these cancers, Ror2 expression is associated with more aggressive disease states. Recently, it has been reported that Ror2 is highly expressed in human papilloma virus (HPV)­positive head and neck squamous cell cancer (HNSCC) cell lines, presumably indicating that Ror2 plays a critical role in HPV­related cancers. However, the function of Ror2 in HPV­positive HNSCC is currently unknown. Here, we first examined the expression levels of Ror2 in clinical specimens from patients with HPV­negative and HPV­positive oropharyngeal squamous cell cancer (OPSCC) via immunohistochemical analysis. We found that Ror2 was expressed in both HPV­negative and HPV­positive OPSCC tissues. We then confirmed that HPV­positive HNSCC cell line, UPCI:SCC152 cells, express Ror2 higher than HPV­negative cell lines as previously reported. Suppressed expression of HPV E6/7 resulted in reduced expression levels of Ror2. We also revealed that Ror2 downregulation significantly inhibited the proliferation of UPCI:SCC152 cells without inducing apoptosis. Moreover, Ror2 knockdown decelerated G1/S phase progression and abrogated invasive migration of UPCI:SCC152 cells. These results provide strong evidence that E6 and/or E7 oncoproteins regulate the progression of HPV­positive HNSCC by upregulating Ror2 expression, suggesting that Ror2 could potentially be a novel target in HPV­related cancers.

Results of free flap reconstruction for patients aged 80 years or older with head and neck cancer.

OBJECTIVE: Free flap reconstruction in elderly patients is one of the most challenging surgeries in the treatment of head and neck cancers. The aim of this study was to examine the oncological and functional outcomes of free flap reconstruction for elderly patients with head and neck cancer. METHODS: We retrospectively reviewed elderly patients who underwent free flap reconstruction for the treatment of head and neck cancers. All patients were 80 years or older. Clinicopathologic features, surgical procedures, oncological and functional outcomes were obtained from medical records. RESULTS: Free flap reconstructions were performed in 13 patients (3 female, 10 male). The mean age was 82.6 ± 3.4 years (range: 80-91). The mean follow-up period was 23.3 months (range 4-41 months). The mean disease-free survival was 49 ± 6 months (range 4-60 months). All patients had been alive more than one year after surgery. Reconstruction was performed using free jejunum in 10 patients and radial forearm flap in 3 patients. Graft necrosis occurred in 2 patients. Other two patients experienced major postoperative medical complications. CONCLUSION: Free flap reconstruction in well-selected older adults is safe and effective. Advanced age should not preclude consideration of free flap reconstruction in those patients.

Effect of Continuous Positive Airway Pressure on Overactive Bladder Symptoms in Patients with Obstructive Sleep Apnea Syndrome.

OBJECTIVE: To evaluate overactive bladder (OAB) in male and female patients with moderate or severe obstructive sleep apnea syndrome (OSAS) and to investigate the impact of three months of continuous positive airway pressure (CPAP) therapy on the symptoms of OAB. METHODS: Twenty-eight female and 45 male patients with moderate and severe OSAS whose obstructive sleep apnea (OSA) severity was evaluated according to the apnea-hypopnea index were included in the study. Patients' voiding symptoms were evaluated using the validated Turkish translations of overactive bladder symptom scores (OAB-V8) and the International Consultation on Incontinence Questionnaire Short-Form (ICIQ-SF) at OSAS diagnosis and at 3-months after the CPAP therapy. RESULTS: Patients with moderate and severe OSAS were more likely to have OAB than the average population, and CPAP therapy improved the symptoms of OAB in both male and female patients. In addition, a positive association was observed between OSA severity and OAB-V8 and ICIQ-SF in female patients and between OSA severity and OAB-V8 in male patients. CONCLUSION: Our findings suggest that CPAP therapy improves the clinical symptoms of OAB. Thus, unnecessary medical or interventional treatment of OAB can be avoided in such patients.

Impact of alcohol dehydrogenase-aldehyde dehydrogenase polymorphism on clinical outcome in patients with hypopharyngeal cancer.

BACKGROUND: The purpose of this research was to investigate the association between alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) polymorphisms and hypopharyngeal squamous cell carcinoma (SCC) survival. METHODS: We genotyped ADH1B (rs1229984) and ALDH2 (rs671) single nucleotide polymorphisms (SNPs) in 85 Japanese male patients with hypopharyngeal SCC. The independent prognostic values of ADH1B-ALDH2 genotypes were analyzed by univariate and multivariate proportional hazard Cox regression, taking well-known clinical risk factors into account. RESULTS: Heavy drinkers with ALDH2*2 allele resulted in significantly worse overall survival (OS; P = .028) and disease-free survival (DFS; P = .029) compared with other patients. Heavy drinkers with ALDH2*2 allele remained statistically significant in multivariate analysis for OS and DFS, indicating independent poor prognostic factor (hazard ratio [HR] 2.251; 95% confidence interval [CI] 1.018-4.975 and HR 2.261; 95% CI 1.021-5.006, respectively). CONCLUSION: We conclude that heavy drinkers with the ALDH2*2 allele are associated with poor outcome in hypopharyngeal SCC.

An assessment of olfactory function in patients with laryngopharyngeal reflux disease.

CONCLUSIONS: The results reported here indicate that there was a statistically significant difference in the olfactory functions of laryngopharyngeal reflux patients vs the healthy group. To the best of the authors' knowledge, this study is the first to evaluate the olfactory function of patients diagnosed with laryngopharyngeal reflux using an objective method, 24-h pH monitoring. OBJECTIVES/HYPOTHESIS: The aim of this study was to investigate olfactory functions in laryngopharyngeal reflux (LPR) patients and compare the results with healthy controls. METHODS: A total of 60 participants; 30 men and women with a diagnosis of laryngopharyngeal reflux and 30 healthy controls, were included in the study. Patients in the laryngopharyngeal reflux group were evaluated by the Reflux Symptom Index (RSI), Reflux Finding Scores (RFS), and finally 24-h pH monitoring to confirm the diagnosis of laryngopharyngeal reflux. The Sniffin' Sticks olfactory test results of the laryngopharyngeal reflux and control groups were compared, and the relationship between the study findings and the olfactory parameters were evaluated. RESULTS: The odor threshold, odor discrimination, odor identification, and TDI scores of the laryngopharyngeal reflux group were significantly lower than those of the control group. Also there was a statistically significant negative correlation detected between the olfactory test and some symptom and finding scores.

First bite syndrome - An 11-year experience.

OBJECTIVE: First bite syndrome is the development of pain in the ipsilateral parotid region after the first few bites of food and can be seen after surgery of the upper cervical region. The aim of this study is to highlight the etiology of this potentially debilitating chronic pain syndrome. MATERIALS AND METHODS: Retrospective review of 53 patients undergoing surgery of the upper neck between 2002 and 2013. RESULTS: FBS developed in 16 patients (30%). Partial resolution of FBS symptoms occurred in 69% and complete resolution in 12%, whereas 15% had no change. FBS was most common in the patients who had tumor arising from deep lobe of parotid gland in comparison with other sites (50% vs 18%, p=0.017). FBS developed in 57% of patients undergoing external carotid artery (ECA) ligation and in 12.5% of patients in whom ECA was preserved (p=0.0008). Among the patients in whom ECA was preserved, FBS developed in 43% of the patients in whom sympathetic chain was sacrificed and in 4% of the patients in whom sympathetic chain was preserved. CONCLUSION: Present results further support the role of sympathetic chain in the development of FBS.

An objective assessment of halitosis in children with adenoid vegetation during pre- and post-operative period.

OBJECTIVES: Although most specialists in otorhinolaryngology and pediatrics find halitosis to be a common problem in children with adenoid hypertrophy, there are no objective data on this topic in the literature. Whether adenoid hypertrophy is a risk factor for halitosis or whether halitosis is a sign of adenoid hypertrophy remains unclear. Thus, the aim of this study was to investigate whether children diagnosed with adenoid hypertrophy have a higher probability of halitosis than do children in the normal population and whether adenoidectomy can decrease oral malodor. METHODS: Forty children with adenoid hypertrophy and 40 healthy subjects aged 5-15 years were included in the study. The children with adenoid hypertrophy underwent adenoidectomy operations and were followed for 3 months. We measured volatile sulfur compounds (VSCs), hydrogen sulfide (H2S), methyl mercaptan (CH3SH), and dimethyl sulfide (CH3)2S using an objective method, a portable gas chromatograph (OralChroma; AbiMedical, Osaka, Japan). RESULTS: The mean CH3SH and (CH3)2S levels were significantly different (p < 0.05) between the adenoid hypertrophy group and the controls. The H2S, CH3SH, and (CH3)2S levels in the third postoperative month were significantly lower (p < 0.05) than those in the preoperative period, and there was no significant difference postoperatively between the patients with adenoid hypertrophy and controls. There was a positive correlation between age and VSC levels, and CH3SH levels were significantly higher in patients with ventilation tube insertion, rather than just adenoidectomy. CONCLUSIONS: There was a statistically significant association between halitosis and adenoid hypertrophy, and a significant improvement in halitosis was obtained following adenoidectomy. The present study provides an association between halitosis and adenoid hypertrophy. If there is no other oral pathology causing halitosis, halitosis can be a sign of adenoid hypertrophy in children.

Effects of topical intranasal doxycycline treatment in the rat allergic rhinitis model.

OBJECTIVES: Allergic rhinitis (AR) is a chronic upper respiratory tract disease that inflames the mucous membranes of the nose and occurs when circulating inflammatory cells including eosinophils and basophils migrate to and accumulate in the inflammation area by passing through the interstitium and capillary walls. To pass through these barriers, the inflammatory cells degrade extracellular matrix proteins. Matrix metalloproteinases (MMPs) released by inflammatory cells mediate the degradation of these proteins. MMPs have synthetic inhibitors and doxycycline, a tetracycline antibiotic, inhibits MMPs. This study investigated the efficiency of intranasal doxycycline in decreasing the symptoms and inflammatory cell infiltration in an animal model of AR. METHODS: AR was created in female Wistar rats by repeated intranasal challenge with ovalbumin by intraperitoneal injection. For 15 days, topical intranasal doxycycline was administered one hour before ovalbumin administration. Following intranasal administration, nasal symptoms were scored and the nasal mucosae of all rats were evaluated histopathologically. To investigate tissue changes, hematoxyline-eosin and Alcian blue/periodic acid Schiff stains were used. As well, cilia loss, goblet cell changes, vascular congestion, vascular proliferation, inflammatory cell infiltration, eosinophil infiltration and the degree of hypertrophy in chondrocytes were evaluated with light microscopy. RESULTS: Typical symptoms of AR were decreased by intranasal doxycycline administration. These effects were stable after repeated intranasal ovalbumin administration. Histological evaluation of doxycycline treated rats did not reveal typical inflammatory changes associated with AR. CONCLUSION: MMPs may have crucial functions in AR and topical intranasal doxycycline, which decreases inflammatory cell infiltration, may offer an alternative therapy for AR.