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1.  Repair of Temporal Bone Encephalocele following Canal Wall Down Mastoidectomy 
Case Reports in Otolaryngology  2014;2014:271824.
We report a rare case of a temporal bone encephalocele after a canal wall down mastoidectomy performed to treat chronic otitis media with cholesteatoma. The patient was treated successfully via an intracranial approach. An enhanced layer-by-layer repair of the encephalocele and skull base deficit was achieved from intradurally to extradurally, using temporalis fascia, nasal septum cartilage, and artificial dural graft. After a 22-month follow-up period the patient remains symptom free and no recurrence is noted.
doi:10.1155/2014/271824
PMCID: PMC4189909  PMID: 25328738
2.  Identification and Validation of a Multigene Predictor of Recurrence in Primary Laryngeal Cancer 
PLoS ONE  2013;8(8):e70429.
Purpose
Local recurrence is the major manifestation of treatment failure in patients with operable laryngeal carcinoma. Established clinicopathological factors cannot sufficiently predict patients that are likely to recur after treatment. Additional tools are therefore required to accurately identify patients at high risk for recurrence. This study attempts to identify and independently validate gene expression models, prognostic of disease-free survival (DFS) in operable laryngeal cancer.
Materials and Methods
Using Affymetrix U133A Genechips, we profiled fresh-frozen tumor tissues from 66 patients with laryngeal cancer treated locally with surgery. We applied Cox regression proportional hazards modeling to identify multigene predictors of recurrence. Gene models were then validated in two independent cohorts of 54 and 187 patients (fresh-frozen and formalin-fixed tissue validation sets, respectively).
Results
We focused on genes univariately associated with DFS (p<0.01) in the training set. Among several models comprising different numbers of genes, a 30-probe set model demonstrated optimal performance in both the training (log-rank, p<0.001) and 1st validation (p = 0.010) sets. Specifically, in the 1st validation set, median DFS as predicted by the 30-probe set model, was 34 and 80 months for high- and low-risk patients, respectively. Hazard ratio (HR) for recurrence in the high-risk group was 3.87 (95% CI 1.28–11.73, Wald's p = 0.017). Testing the expression of selected genes from the above model in the 2nd validation set, with qPCR, revealed significant associations of single markers, such as ACE2, FLOT1 and PRKD1, with patient DFS. High PRKD1 remained an unfavorable prognostic marker upon multivariate analysis (HR = 2.00, 95% CI 1.28–3.14, p = 0.002) along with positive nodal status.
Conclusions
We have established and validated gene models that can successfully stratify patients with laryngeal cancer, based on their risk for recurrence. It seems worthy to prospectively validate PRKD1 expression as a laryngeal cancer prognostic marker, for routine clinical applications.
doi:10.1371/journal.pone.0070429
PMCID: PMC3739775  PMID: 23950933
3.  Hybrid Carcinoma of the Larynx: A Case Report (Adenoid Cystic and Adenocarcinoma) and Review of the Literature 
Case Reports in Otolaryngology  2013;2013:385405.
Introduction. The nonsquamous carcinomas of the larynx are considered rare with the majority of malignant tumors in this area, reaching the rate of 95%, to be squamous cell neoplasms. Case Report. The case refers to a 53-year-old man that presented with symptomatology of motor nerve disease. During the evaluation of the neurologic disease, a subglottic mass of the larynx was revealed accidentally in the imaging examination. Under general anesthesia, we performed direct laryngoscopy and biopsy of the mass. The histopathologic examination revealed a hybrid carcinoma coexistence of two different carcinomas, an adenoid cystic carcinoma and an adenocarcinoma, not otherwise specified with poor differentiation. Regarding the therapeutic plan, the mass was considered inoperable due to its expansion to trachea and the patient received radiotherapy. Conclusions. Both the adenocarcinoma and adenoid cystic carcinoma are extremely rare types of malignant tumors in the larynx. The special interest of the present case is the coexistence of these two rare tumors in the same region of the larynx, being a hybrid tumor of the salivary glands in the larynx, which is the second reported case, based on our systematic literature review.
doi:10.1155/2013/385405
PMCID: PMC3638498  PMID: 23691396
4.  Insulin-Like Growth Factor 1 Receptor (IGF1R) Expression and Survival in Operable Squamous-Cell Laryngeal Cancer 
PLoS ONE  2013;8(1):e54048.
Introduction
Prognosis of patients with operable laryngeal cancer is highly variable and therefore potent prognostic biomarkers are warranted. The insulin-like growth factor receptor (IGFR) signaling pathway plays a critical role in laryngeal carcinogenesis and progression.
Patients and Methods
We identified all patients with localized TNM stage I–III laryngeal cancer managed with potentially curative surgery between 1985 and 2008. Immunohistochemical (IHC) expression of IGF1R-alpha, IGF1R-beta and IGF2R was evaluated using the immunoreactive score (IRS) and mRNA levels of important effectors of the IGFR pathway were assessed, including IGF1R, IGF-binding protein 3 (IGFBP3), suppressor of cytokine signaling 2 (SOCS2) and members of the MAP-kinase (MAP2K1, MAPK9) and phosphatidyl-inositol-3 kinase (PIK3CA, PIK3R1) families. Cox-regression models were applied to assess the predictive value of biomarkers on disease-free survival (DFS) and overall survival (OS).
Results
Among 289 eligible patients, 95.2% were current or ex smokers, 75.4% were alcohol abusers, 15.6% had node-positive disease and 32.2% had received post-operative irradiation. After a median follow-up of 74.5 months, median DFS was 94.5 months and median OS was 106.3 months. Using the median IRS as the pre-defined cut-off, patients whose tumors had increased IGF1R-alpha cytoplasm or membrane expression experienced marginally shorter DFS and significantly shorter OS compared to those whose tumors had low IGF1R-alpha expression (91.1 vs 106.2 months, p = 0.0538 and 100.3 vs 118.6 months, p = 0.0157, respectively). Increased mRNA levels of MAPK9 were associated with prolonged DFS (p = 0.0655) and OS (p = 0.0344). In multivariate analysis, IGF1R-alpha overexpression was associated with a 46.6% increase in the probability for relapse (p = 0.0374). Independent predictors for poor OS included node-positive disease (HR = 2.569, p<0.0001), subglottic/transglottic localization (HR = 1.756, p = 0.0438) and IGF1R-alpha protein overexpression (HR = 1.475, p = 0.0504).
Conclusion
IGF1R-alpha protein overexpression may serve as an independent predictor of relapse and survival in operable laryngeal cancer. Prospective evaluation of the IGF1R-alpha prognostic utility is warranted.
doi:10.1371/journal.pone.0054048
PMCID: PMC3554755  PMID: 23365645
5.  Duplication of the External Auditory Canal: Two Cases and a Review of the Literature 
Case Reports in Otolaryngology  2012;2012:924571.
The objective of the present paper is to describe the clinical presentation, diagnostic process, surgical treatment, and outcome of 2 patients with first branchial cleft anomaly. The first case was an 8-year-old girl presented with an elastic lesion located in the left infra-auricular area, in close relation with the lobule, duplicating the external auditory canal. The magnetic resonance imaging revealed a lesion, appearing as a rather well-circumscribed mass within the left parotid gland and duplicating the ear canal. A superficial parotidectomy was subsequently performed, with total excision of the cyst. The second patient was a 15-year-old girl presented with a congenital fistula of the right lateral neck. At superficial parotidectomy, a total excision of the fistula was performed. During the operation the tract was recorded to lay between the branches of the facial nerve, extending with a blind ending canal parallel to the external acoustic meatus. Conclusively, first branchial cleft anomalies are rare malformations with cervical, parotid, or auricular clinical manifestations. Diagnosis of first branchial cleft lesions is achieved mainly through careful physical examination. Complete surgical excision with wide exposure of the lesion is essential in order to achieve permanent cure and avoid recurrence.
doi:10.1155/2012/924571
PMCID: PMC3507044  PMID: 23213587
6.  Association between primary nocturnal enuresis and habitual snoring in children with obstructive sleep apnoea-hypopnoea syndrome 
Introduction
Nocturnal enuresis (NE) and obstructive sleep apnoea-hypopnoea syndrome (OSAHS) are common problems during childhood, and population studies have reported a significant correlation between them. This study aimed to assess whether habitual snoring, mouth breathing and daytime sleepiness are associated with increased incidence of NE in children with OSAHS.
Material and methods
Polysomnography was performed in 42 children (66.7% males), 3.5-14.5 years old, who were evaluated for sleep-disordered breathing (SDB).
Results
Fourteen out of 42 children (33.3%) presented mild, 16 out of 42 (38.1%) moderate and 12 out of 42 (28.6%) severe degree of OSAHS. Apnea hypopnea index (AHI) ranged between 1.30-94.20 (10.54 ±15.67) events per hour of sleep. Nocturnal enuresis was reported in 7/42 (16.7%) of them. The main observed symptoms were snoring (90.5%), restless sleep (81%), mouth breathing (71.4%), nasal congestion (76.2%), and difficulty in arousal (52.4%). A statistically significant association was found between NE and mouth breathing (p = 0.014) or nasal congestion (p = 0.005). Children with OSAHS and NE had a higher arousal index (8.14 ±8.05) compared with OSAHS children without NE (4.61 ±7.95) (p = 0.19, z = –1.28). Snorers had higher levels of AHI (11.02 ±16.37) compared with non-snorers (6.05 ±4.81) (p = 0.33, z = –0.96), and habitually snorers (23/42, 54.76%) were at greater risk of having NE (4/23) than were non-snorers (0/4, p = 0.36). However, the prevalence of enuresis was not related to the severity of OSAHS, expressed as AHI (p = 0.70).
Conclusions
Mouth breathing, nasal congestion and high threshold of arousal during sleep should be more carefully evaluated in cases of children with NE who do not respond to standard treatment and present SDB.
doi:10.5114/aoms.2012.28809
PMCID: PMC3400898  PMID: 22852010
nocturnal enuresis; sleep apnoea syndrome
7.  Glomus Tumor of the Cheek: A Case Report 
Case Reports in Medicine  2012;2012:307294.
Glomus tumors are benign, subcutaneous neoplasms of the perivasculature. Though facial location is rare, the diagnosis of a glomus tumor should be considered in cases of undiagnosed painful facial nodules or chronic facial pain. Imaging aids in defining the tumor and planning a complete excision in order to avoid recurrence. Histological examination is mandatory after every attempted excision. A case of glomus tumor of the cheek along with the possible pitfalls of diagnosis and treatment and a brief review of the limited associated literature are presented.
doi:10.1155/2012/307294
PMCID: PMC3395378  PMID: 22811718
8.  Synchronous Presence of Nasopharyngeal Carcinoma and Marginal Zone (MALT-Type) B-Cell Lymphoma in the Pharynx 
Synchronous malignancy of squamous cell carcinoma and malignant lymphoma in the head and neck region is extremely rare. Nasopharyngeal carcinoma is a nonlymphomatous, squamous cell carcinoma that occurs in the nasopharyngeal epithelium. Reported herein is a unique case of nasopharyngeal carcinoma occurring simultaneously with MALT-type lymphoma in an 83-year-old woman, who complained of deglutition dysfunction. Endoscopic examination of respective organs revealed a submucosal tumour on the posterior wall of pharynx. Biopsy of the hypopharynx was taken and sent for histological examination, which revealed two different neoplasms. Immunohistochemical and molecular analysis confirmed the diagnosis of nasopharyngeal carcinoma coexisting with a MALT-type lymphoma.
doi:10.4061/2011/340763
PMCID: PMC3108342  PMID: 21660262
9.  STAT-Related Profiles Are Associated with Patient Response to Targeted Treatments in Locally Advanced SCCHN1 
Translational Oncology  2011;4(1):47-58.
The anti-epidermal growth factor receptor antibody cetuximab (Erbitux, CTX) is currently used for the treatment of locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN), as yet with modest effectiveness, prompting for the identification of response predictors to this treatment and for the targeting of additional pathways implicated in this disease. Within this scope, we investigated the effect of SRC/STAT pathway components on LA-SCCHN patient outcome. SRC, STAT1, STAT3, STAT5A, STAT5B, ANXA1, CAV1, IGFBP2, EPHA2, EPHB2, and MSN relative gene expression, as well as Stat protein activation, were assessed on LA-SCCHN tumor tissues from 35 patients treated with combined radiotherapy (RT) and CTX-based regimens. Stat1, Stat3, and Stat5 proteins were usually found activated in neoplastic nuclei (70.4%, 85.7%, and 70.8%, respectively). Activated Stat3 and Stat5 were associated with each other (P = .017) and with a CAV1high/MSNhigh/IGFBP2low profile. All patients with tumors expressing high STAT5A/EPHA2 experienced a complete response on RT-CTX-based treatments (12/15 complete responders, P < .0001) and a longer progression-free survival (P = .024). Few tumors expressed high ANXA1/CAV1/EPHA2 and low IGFBP2, a putative dasatinib response-related profile, whereas high ANXA1 was associated with shorter overall survival (P = .003). In conclusion, Stat activation is common in LA-SCCHN, where overexpression of STAT5A and EPHA2 may predict for response to RT-CTX treatments. The STAT5A/EPHA2 profile seems of particular interest for validation in larger cohorts and in multiple tumor types because markers for the positive selection of patients to benefit from CTX-containing treatments are currently lacking.
PMCID: PMC3026408  PMID: 21286377
10.  MMP9 but Not EGFR, MET, ERCC1, P16, and P-53 Is Associated with Response to Concomitant Radiotherapy, Cetuximab, and Weekly Cisplatin in Patients with Locally Advanced Head and Neck Cancer 
Journal of Oncology  2009;2009:305908.
Concomitant administration of radiotherapy with cisplatin or radiotherapy with cetuximab appear to be the treatment of choice for patients with locally advanced head and neck cancer. In the present retrospective analysis, we investigated the predictive role of several biomarkers in an unselected cohort of patients treated with concomitant radiotherapy, weekly cisplatin, and cetuximab (CCRT). We identified 37 patients treated with this approach, of which 13 (35%) achieved a complete response and 10 (27%) achieved a partial response. Severe side effects were mainly leucopenia, dysphagia, rash, and anemia. Tumor EGFR, MET, ERCC1, and p-53 protein and/or gene expression were not associated with treatment response. In contrast, high MMP9 mRNA expression was found to be significantly associated with objective response. In conclusion, CCRT is feasible and active. MMP9 was the only biomarker tested that appears to be of predictive value in cetuximab treated patients. However, this is a hypothesis generating study and the results should not be viewed as definitive evidence until they are validated in a larger cohort.
doi:10.1155/2009/305908
PMCID: PMC2801452  PMID: 20066159

Results 1-10 (10)