Copy number profiling of tumor suppressor genes in head and neck cancer.

BACKGROUND: Sensitive and reliable new biomarkers are needed in head and neck cancer to predict the outcome and for therapy that is more effective. Copy number alterations are frequent and play a critical role in cancer. METHODS: Copy number alterations of 24 tumor suppressor genes in head and neck cancer were analyzed simultaneously in matched tumor and normal samples from 93 patients using multiplex ligation-dependent probe amplification (MLPA). RESULTS: Chromosomes 3p and 9p displayed the most common alterations. The gene displaying most frequent losses was the mutL homolog 1 (MLH1) gene, followed by the cyclin-dependent kinase inhibitor 2A (CDKN2A) and CDKN2B genes. A significant correlation was observed between the CDKN2A and CDKN2B genes. The tissue inhibitor of metalloproteinase (TIMP)3 gene alterations were observed in 8 tumors. CONCLUSION: Our data confirm previous observations and suggest that losses of the MLH1 and CDKN2 genes and alterations of the TIMP3 gene play an important role in head and neck carcinogenesis. © 2016 Wiley Periodicals, Inc. Head Neck 39: 341-346, 2017.

Prevalence of allergic fungal rhinosinusitis among patients with chronic rhinosinusitis with or without nasal polyposis who underwent endonasal sinus surgery in northwestern Turkey.

OBJECTIVES: This study aims to evaluate the prevalence of allergic fungal rhinosinusitis in chronic rhinosinusitis patients in the northwest of Turkey. PATIENTS AND METHODS: Eighty-seven patients diagnosed with chronic rhinosinusitis and who were planned endonasal sinus surgery were enrolled in this prospective study. Patients were evaluated by detailed clinical examination, computed tomography, skin test against allergens, total serum immunoglobulin E (IgE) antibody, fungal-specific IgE antibody, and histopathologic and mycologic monitoring. RESULTS: Fungal elements showing tissue invasiveness were detected in only four patients. These patients had specific IgE against Aspergillus fumigatus (4.6%). Skin tests were positive for at least one allergen in 16 patients (18.3%). CONCLUSION: None of the patients met diagnostic criteria for allergic fungal rhinosinusitis. This result may be due to the diversity in disease prevalence based on geographical location or diagnostic methods.

The impact of social and demographic features on comprehensive receptive and expressive performance in cochlear implant patients.

OBJECTIVES: This study aims to observe the effects of social and demographic factors on the language development of prelingual pediatric cochlear implant patients. PATIENTS AND METHODS: Between April 2006 and April 2010, 44 children (26 boys, 18 girls; mean age 81.1±16.9 months; range 54 to 115 months) who were prelingually implanted and who had an implant experience of at least 36 months were retrospectively analyzed. Only the patients without mental-motor retardation, cochlear anomaly and revision surgery and who continued their education without any interruption were selected. Receptive and expressive vocabulary tests were performed on these patients. Social and demographic features including gender, implant age, parents' education status and annual income were recorded. The relationship between language development and socio-demographic factors were investigated. RESULTS: Patients implanted before the age of 36 months showed better levels of receptive and expressive language. Children with higher maternal education levels showed significantly better expressive and receptive equivalent language ages. Annual income of the families had significant positive impacts on the language development of the children who were implanted before the age of 36 months. CONCLUSION: Both expressive and receptive language skills over 36 months of implant experience are significantly associated with age at the time of the implant and socio-economic status of the parents.

[Revision surgery in cochlear implantation]. / Koklear implantasyonda revizyon cerrahisi.

OBJECTIVES: In this study, we evaluated the reasons and management approaches for revision cochlear implant surgery. PATIENTS AND METHODS: Thirty-two patients (20 males, 12 females; mean age 7.4 years; range 15 month to 54 years) who underwent revision cochlear implantation in our clinic were divided into two group, including reimplantation or non-reimplantation group. RESULTS: Of patients who underwent revision surgery, 22 had reimplantation, while remaining 10 were not required reimplantation. The mean time from the first surgery to revision surgery was 17.3±15.2 months (range 1-59 months). In patients who underwent primary surgery in our clinic, the revision and reimplantation rates were 5.2% and 3.4%, respectively. The reasons for revision surgery included software failure of the device (n=7), local flap problems (n=7), reference electrode problems (n=5), magnet displacement (n=2), electrode migration to vestibule (n=2), extracochlear insertion of electrode (n=2), broken electrode (n=2), device failure following head trauma (n=2), facial stimulation and paralysis (n=1), electrode exposition from the external ear canal (n=1), and electrode exposition to the middle ear (n=1). CONCLUSION: The most common reasons for the revision cochlear implant surgery are software failure of the device, local flap problems and electrode failures. In revision surgery, the problems should be solved without damaging the implant, if the implant is running.

Radiation-induced osteosarcoma of the larynx: case report and literature review.

Laryngeal osteosarcoma is an extremely rare disease. Only 23 cases have been published in the literature. Radiation-induced laryngeal osteosarcoma is even rarer; this is only the third such case to be reported. A 59-year-old man underwent radiotherapy for an in situ laryngeal squamous cell carcinoma at another institution. Five years later he developed a laryngeal osteosarcoma, and a total laryngectomy was performed. Although previous reports showed a poor prognosis, our patient was without disease at the 8-year follow-up. To the best of our knowledge, this is the longest disease-free follow-up to be reported in the literature. We also present a review of the world's literature.

Promoter methylation and loss of p16(INK4a) gene expression in head and neck cancer.

BACKGROUND: Silencing of tumor suppressor genes plays a vital role in head and neck carcinogenesis. In this study we aimed to evaluate aberrant p16(INK4a) gene promoter methylation in patients with head and neck cancer. METHODS: Methylation of the gene was investigated by bisulfite modification/methylation-specific polymerase chain reaction and gene expression levels were analyzed by quantitative reverse transcription-polymerase chain reaction in tumors and matched normal tissue samples from Turkish patients with head and neck cancer. RESULTS: The promoter region of the p16(INK4a) gene was methylated in 67.5% and 28.6% of the primary tumors and the corresponding normal tissue, respectively. This difference was highly significant. In concordance, p16(INK4a) gene expression was downregulated in 67.5% of the tumor samples. Methylation and the absence of expression in the tumors were observed in 48% of the patients. CONCLUSIONS: Our data indicate that methylation of the p16(INK4a) gene is a frequent event in primary head and neck cancer and that it plays a major role in the silencing of p16(INK4a) gene expression during tumor development.

Simultaneous methylation profiling of tumor suppressor genes in head and neck cancer.

Head and neck cancer (HNC) is a common cancer, and its prognosis has not changed during the last decades. Detection of the disease at an early stage is crucial for successful treatment, as early diagnosis can significantly increase the survival rate. Methylation of tumor suppressor genes is an early event in cancer responsible for incorrect gene silencing. Since methylation changes are reversible, they also provide a promising target for therapy. So far, only individual genes have been analyzed for aberrant methylation in HNC. In this study, we analyzed the methylation status of 24 tumor suppressor genes simultaneously by methylation-specific multiplex ligation-dependent probe amplification in matched tumor and normal tissue samples from patients with HNC. CHFR, RARß, DAPK1, and RASFF1 genes were the most frequently methylated genes in tumor tissue. Eight genes were not methylated in any sample. The methylation frequencies for individual genes ranged from 0% to 19%. Our results indicate that methylation of tumor suppressor genes is not high as previously reported by methylation-specific polymerase chain reaction and is confined to a smaller but significant fraction of the tumors. Whether this group represents a unique entity in the disease spectrum warrants further studies.

The use of the latissimus dorsi myocutaneous flap in the reconstruction of complex head and neck defects.

OBJECTIVES: To compare and contrast the use of the latissimus dorsi myocutaneous flap in complex head and neck defects requiring major reconstructive surgery with respect to the other reconstruction techniques, and to emphasize the importance of this flap as an life and surgeon-saving reconstruction modality. PATIENTS AND METHODS: In this study, 20 cases (17 males, 3 females; mean age 58.5 years; range 48 to 72 years) of major head and neck operations reconstructed with a latissimus dorsi myocutaneous flap in Istanbul University, Istanbul Medical Faculty, Ear, Nose and Throat Clinic between October 2004 and November 2006 were retrospectively examined. The latissimus dorsi myocutaneous flap was preferred as a primary reconstructive modality in eight of the cases and a secondary reconstructive modality in the remaining 12 cases. The reasons for choosing the latissimus dorsi myocutaneous flap as the reconstructive modality were examined in this study and compared with other reconstruction techniques. RESULTS: Partial flap necrosis was observed in four of the 20 cases. In two of these unsuccessful cases, minor intervention was sufficient to achieve functionally satisfactory results. However, one case with partial flap necrosis was lost due to the uncontrollable primary disease. In the one remaining case who had undergone cranioplasty, partial necrosis of the flap developed after the completion of radiotherapy in the 4th postoperative month. No total flap necrosis was encountered in any of the cases. CONCLUSION: The latissimus dorsi myocutaneous flap is a reconstructive modality with a high success rate and should be considered among reconstruction alternatives.

Analysis of the hMSH2 gene variants in head and neck cancer.

The hMSH2 (human MutS homolog 2) gene plays a central role in DNA mismatch repair. Structural variations in the gene may lead to protein instability and deficient mismatch repair. However, the role of polymorphic variants of the hMSH2 gene have not been defined in head and neck cancer. In this study, the roles of three polymorphic variants in the functional domains of the gene were investigated in 166 patients with head and neck cancer by allele-specific PCR, electronical array addressing, and PCR/RFLP (restriction fragment length polymorphism). This is the first study to investigate the gIVS12-6T --> C polymorphism in head and neck cancer. A significant association between the CC genotype and reduced risk of disease suggests that the gIVS12-6T --> C substitution at the splice-acceptor site may affect the risk of head and neck cancer. We did not observe an association between the Asn127Ser and Gly322Asp polymorphisms and cancer risk. A possible role of the gIVS12-6T --> C substitution warrants further validation in larger cohorts because of low allele frequency.

The effect of tumor width and depth on extracapsular lymp node metastases in tongue tumors.

OBJECTIVES: In this study, we investigate the relationship between the effects of tumor width and depth with the extracapsular nodal spread (ECS) in oral tumors. PATIENTS AND METHODS: In this study we investigate retrospectively data of 107 patients (69 males, 38 females; mean age 45 years; range 25 to 79 years) with tongue tumors, who had undergone surgery in our clinic, between 1994 and 2004. Twenty-one of them had ECS. The effects of tumor width and depth on various parameters such as nodal metastases, survival, grade and ECS are investigated. RESULTS: It was found that tumor width and depth were the most important factors that affect ECS and logistic regression analysis point out tumor width influence more than tumor depth. Receiver operating characteristic (ROC) curve analysis shows us when tumor width exceeds 3.7 cm or tumor depth exceeds 2.4 cm, rate of ECS reaches the maximum sensitivity and specificity. CONCLUSION: Tumor width and depth has affects on survival and prognosis but also they have significant relation with ECS.

Assessment of microsatellite instability in head and neck cancer using consensus markers.

Head and neck cancer is the sixth most common cancer in the world and one of the most lethal cancers. Microsatellite instability is an important characteristic of tumor cells and is observed both in presence and absence of mismatch repair gene mutations. The importance of microsatellite instability in head and neck cancer is not well established due to the lack of a consensus panel and selection of different markers, criteria and methodological variances. The main objective of this study was to investigate the performance of a consensus panel of microsatellite repeats by automated fragment analysis. Matched tumor and normal tissue samples from 99 patients were analyzed using five mononucleotide markers. Following PCR the amplified fragments were analyzed by capillary electrophoresis on an ABI 310 genetic analyzer. Microsatellite instability was observed in 26 patients. In 17 patients instability was detected at multiple loci. NR21 and BAT25 were the most frequently altered targets. These two mononucleotide markers could detect all samples displaying high-instability. In this study we describe a standardized fluorescent multiplex PCR combined with computerized analysis, which allows rapid and accurate analysis of a high number of samples and obviates the need to compare tumors with matching normal tissue.

N-acetyltransferase 1 and 2 gene sequence variants and risk of head and neck cancer.

Polymorphisms that alter the function of genes involved in the activation or detoxification of carcinogenic compounds can influence an individuals risk of developing cancer. Polymorphic changes modulating the acetylation capacity of the N-acetyltransferase (NAT) genes have been implicated in the risk of developing cancer. In this study the role of genetically determined individual NAT1 and NAT2 genotypes, haplotypes and haplotype combinations in the predisposition to head and neck cancer was investigated. Polymorphic regions of the NAT1 and NAT2 genes were analyzed in patients with head and neck cancer and healthy individuals by polymerase chain reaction-restriction fragment length polymorphism. Distribution of the genotypes, allele frequencies, diplotypes and haplotypes and correlation with clinical characteristics were evaluated. No association was observed between the NAT1*3, NAT1*10, NAT1*11, NAT2*5 and NAT2*6 genotypes and risk of head and neck cancer. The NAT2*7 slow genotype was associated with reduced risk of disease. A significant association was observed between the fast acetylator NAT2*4/NAT1*10 diplotype and risk of head and neck cancer. Combined haplotypes harboring the T1088A and C1095A variants characterizing the NAT1*10 allele were associated with increased risk. Our results suggest that NAT1 and NAT2 gene combinations may influence the risk of developing head and neck cancer.

Localization of cerebrospinal fluid leaks by gadolinium-enhanced magnetic resonance cisternography: a 5-year single-center experience.

OBJECTIVE: Intrathecal gadolinium (Gd)-enhanced magnetic resonance (MR) cisternography is a newly introduced imaging method. Two main objectives of this study were to investigate the sensitivity of Gd-enhanced MR cisternography for presurgical localization of cerebrospinal fluid (CSF) leaks in patients with CSF rhinorrhea and to study the potential long-term adverse effects of intrathecal Gd application. METHODS: Fifty-one patients (19 women; mean age, 36.2 yr) with CSF rhinorrhea were included in the study. A total of 0.5 ml of Gd was injected into the lumbar subarachnoid space. T1-weighted MR cisternographic images were obtained to detect CSF leakage. The patient's neurological states and vital signs were recorded for the first 24 hours after the procedure. Neurological evaluations were repeated 1, 3, and 12 months after the procedure. The patients were followed for at least 3 years with annual neurological examinations. RESULTS: Gd-enhanced MR cisternography demonstrated CSF leaks in 43 of the 51 patients. The sensitivity of Gd-enhanced MR cisternography for localization of CSF leaks was 84%. Forty-four patients underwent surgery to repair dural tears. Surgical findings confirmed the results of Gd-enhanced cisternography in 43 of the 44 patients who underwent surgery (98%). Eight patients with negative Gd-enhanced MR cisternography had no active rhinorrhea at the time of procedure, and seven of them did not need surgery. None of the patients developed an acute adverse reaction that could be attributed to the procedure. None of the patients developed any neurological symptoms or signs caused by intrathecal Gd injection during a mean follow-up period of 4.12 years. CONCLUSION: Gd-enhanced MR cisternography is a sensitive and safe imaging method for detection of CSF leaks in patients with rhinorrhea.

Salivary gland choristoma of the middle ear.

Choristoma is a mass of tissue histologically normal for an organ or part of the body other than the site at which it is located. A rare case of ectopic salivary gland choristoma in the middle ear is described in a 14-year-old girl whose only symptom was a 55 dB conductive hearing loss. The left middle ear mass appeared whitish and was located behind the intact tympanic membrane. We first suspected it to be congenital middle ear cholesteatoma. Exploratory tympanotomy, however, revealed a salivary gland choristoma that adhered tightly to the facial nerve. Differential diagnosis and treatment of this rare condition are discussed.

Autologous fat augmentation for voice and swallow improvement after cordectomy.

Surgery for the treatment of early-stage glottic carcinoma still remains a valid option. In most patients, newly formed neocord tissue preserves glottic functions, but in some patients an important glottic gap leading to glottic insufficiency may occur. In our study, 11 patients who had serious glottic insufficiency after endoscopic laser and laryngofissure cordectomy were treated with autologous fat injection (AFI) into the neocord tissue for voice and swallowing rehabilitation. One patient did not attend the first control visit and was excluded from the study. The remaining 10 patients were evaluated in the preoperative and postoperative periods for phonatory functions and efficacy of AFI by videolaryngostroboscopy and computerized acoustic analysis. Phonatory functions showed statistically significant improvement in the shimmer, noise-to-harmonic ratio, maximum phonation time and fundamental frequency. Perceptual ratings (GRBAS scale) also showed statistically significant improvement in all 5 parameters. Despite improvement in glottic closure, the mucosal wave deteriorated. Due to recurrence of symptoms of glottic insufficiency, AFI was repeated in 2 patients at the third and fifth months, respectively. One year later, the AFI resulted in successful rehabilitation of swallowing in all patients. The probability of resorption of autologous fat and the deterioration of the mucosal wave after AFI remain a problem, but re-injection can be done easily. As AFI is an easy, safe and cheap method, we concluded that it is a promising alternative procedure for managing voice problems after laser or laryngofissure cordectomy defects.

Lingual schwannoma.

Schwannomas or neurilemmomas are benign, slow growing, usually solitary and encapsulated tumor, originating from Schwann cells of the nerve sheath. Intraoral schwannoma accounts for 1% of head and neck region and are commonly seen at the base region of tongue. Most of the few such reports in the literature, have described schwannomas that occurred in the tongue. In this article, we report a rare case of lingual schwannoma involving the anterior of tongue, in a young individual, in whom the lesion was completely excised via an intra oral approach.

Simultaneous existence of papillary carcinoma in the thyroid gland and thyroglossal duct cyst in two patients.

Papillary carcinoma of the thyroglossal duct cyst is a rare occurrence. Two patients presenting with medial neck masses were diagnosed as having thyroglossal duct cysts by ultrasonography. The Sistrunk operation was performed. Histopathologic evaluation demonstrated papillary carcinoma in the surgical specimens of both patients. The thyroid glands were examined by ultrasonography, scintigraphy, and fine-needle aspiration biopsy. Biopsy showed papillary carcinoma, and total thyroidectomies were performed. Micropapillary carcinoma was detected in the resected thyroid glands. The patients were asymptomatic without complications after 24 and 32 months of follow-up, respectively.

Polymorphisms of the XRCC1 DNA repair gene in head and neck cancer.

Inherited polymorphisms in the genes controlling the cell cycle or functioning in the DNA repair mechanisms may impair their function and contribute to genetic susceptibility. Abnormalities in the DNA repair have been reported in head and neck cancer. The XRCC1 gene functions in singlestrand break and base excision repair processes. In this study, two polymorphisms of the XRCC1 gene, Arg194Trp and Arg399Gln were investigated in 95 patients with head and neck carcinoma. The polymorphic regions were amplified by PCR followed by digestion with methylation-specific restriction enzymes, and analyzed electrophoretically. Genotype and allele frequencies were calculated, and association with cancer risk or clinical parameters was investigated. No association was observed between the genotypes and head and neck cancer for either polymorphism. Distribution of the alleles did not significantly differ between the patients and the control group. A significant association was only found for the Trp194 allele among the smoking individuals. Our data indicate that the Arg194Trp and Arg399Gln polymorphisms do not confer a significant risk for head and neck carcinogenesis.

Transoral microlaryngoscopic approach for schwannoma of the larynx.

Neurogenous tumors of the larynx are extremely rare. We present a 66-year-old male patient who underwent surgical excision of schwannoma of the larynx, which originated from the left aryepiglottic fold. Excision of the mass was performed through an endolaryngeal approach (suspension microlaryngoscopy). In the early postoperative period, the patient was breathing comfortably and his swallowing and phonation were normal. During a follow-up of three years, no evidence for recurrence was detected and he had no complaints of dysphagia, globus sensation, dyspnea on exertion, or cough.