Murat Ulusan

Promoter methylation and loss of p16INK4a gene expression in head and neck cancer

Silencing of tumor suppressor genes plays a vital role in head and neck carcinogenesis. In this study we aimed to evaluate aberrant p16INK4a gene promoter methylation in patients with head and neck cancer.

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, RARβ, 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 role of components of the extracellular matrix and inflammation on oral squamous cell carcinoma metastasis

OBJECTIVES Oral squamous cell carcinoma (OSCC) accounts for about 90% of malignant oral lesions, and is identified as the most frequently occurring malignant tumour of oral structures. We aimed to investigate the genes and pathways related with metastasis on Turkish OSCC patients. MATERIALS AND METHODS We performed whole genome expression profiling array on an Illumina platform. A total of 24 samples with 12 OSCC and 12-paired controls that had no tumour were included in the study. Hierarchic clustering and heat map were used for data visualisation and p-values assessed to identify differentially expressed genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Ingenuity Pathway Systems (IPA) analysis were performed to consider biologic meaning of differential expression of the genes between tumour and control groups. RESULTS We identified 790 probe sets, corresponding to 648 genes that were effective in separating invasive and metastatic OSCC. Consequently, we found statistically relevant expression results on extracellular matrix members on MMPs such as MMP3, MMP10, MMP1 and MMP9; on laminin such as LAMC2, LAMA3 and LAMB3; several genes in the collagen family; and also on chemokines from the inflammation process. CONCLUSION Statistically relevant expression changes for MMPs, laminins, collagens, and chemokines, which are components of the extracellular matrix and inflammation process, may be considered as a molecular biomarker for early prediction. Further studies are necessary to determine and understand the molecular mechanisms that underlie OSCC metastasis.

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.

Persistent cough associated with osteophyte formation and vagus nerve impingement following cervical spinal surgery: case report.

Persistent cough due to irritation of the vagus nerve by osteophytes resulting from cervical spinal surgery is a very rare condition. The authors report the case of a 49-year-old woman who presented with a persistent cough subsequent to cervical spinal surgery. One year after the initial operation, the patient underwent surgery to free the larynx from the prevertebral fascia and cut the pharyngeal plexus, but her symptoms persisted. In order to control the cough, she used a soft cervical collar with padding inserted in the left side so that the larynx would be pushed to the right, a solution she discovered on her own. Without the collar, she coughed uncontrollably. A CT scan was performed and showed an osteophyte that had developed at the level of the prosthesis. Based on these findings, the authors hypothesized that the cough was caused by vagus nerve irritation due to the osteophyte. The osteophyte was resected and the vagus nerve was moved to a position anterior to the carotid artery and was isolated by means of an autogenous tensor fascia lata graft. The patients symptom disappeared immediately after the surgery. At the most recent follow-up visit, 18 months after surgery, the patient was symptom free and was pursuing regular daily activities without using a cervical collar.

The Effect of Arytenoidectomy on Functional and Oncologic Results of Supracricoid Partial Laryngectomy

Objective: The effect of arytenoid resection was investigated in patients who had undergone supracricoid partial laryngectomy (SCPL) by comparing functional and oncologic results between patients with both arytenoids preserved with those with one arytenoid resected. Methods: Patients were divided into 2 groups: (1) both arytenoids preserved SCPL (BASCL) cases and (2) one arytenoid preserved SCPL (OASCL). The functional outcomes of the 2 groups were compared in terms of nasogastric tube removal time, decannulation time, incidence of aspiration pneumonia, and Performance Status Scale Scores for Head and Neck Cancer Patients for the late postoperative period. Additionally, the oncologic outcomes of both groups were compared using the 5-year local control rate, overall survival, disease-specific survival, and larynx preservation rate. Results: Of the 68 patients who were enrolled in the study, 20 of them were in the OASCL group and 48 in BASCL group. There was no statistically significant difference in the early and late functional outcomes, and the oncologic outcomes were also similar. Conclusion: In addition to the proven oncologic safety, arytenoid resection does not increase the functional morbidity of the SCPL.

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

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.

The importance of mold sensitivity in nonallergic rhinitis patients

In recent studies, local specific immunoglobulin E (sIgE) production against allergens in nasal mucosa and a positive response to a nasal allergen provocation test (NAPT) have been demonstrated in some patients initially diagnosed as nonallergic rhinitis (NAR) or idiopathic rhinitis (IR). The aim of this study was to evaluate the presence of local allergic rhinitis (LAR) in patients who experience rhinitis symptoms in indoor and outdoor moldy conditions and to investigate the role of the NAPT in diagnosis.

[The relationship between operation type, adjuvant radiation therapy, spinal accessory nerve and quality of life in patients with laryngeal cancer].

OBJECTIVES In this study, we aimed to investigate the effect of operation type, adjuvant radiation therapy (RT), and preserved spinal accessory nerve on the quality of life in patients with laryngeal cancer. PATIENTS AND METHODS A total of 191 consecutive patients (185 males, 6 females; mean age 59±10 years; range 42 to 79 years) who were operated due to laryngeal cancer were included. The quality of life scores were estimated using the Washington University Quality of Life Questionnaire, version IV. The patients were divided into six groups according to the operation type, the need for postoperative RT and preserved or operated spinal accessory nerve during the neck dissection. Group 1 consisted of patients with total or near total laryngectomy; group 2 consisted of those with partial laryngeal surgery; group 3 consisted of those with postoperative RT; group 4 consisted of those without postoperative RT; group 5 consisted of those with preserved 11th cranial nerve during the neck dissection, and group 6 consisted of those with non-preserved 11th cranial nerve during the neck dissection. The questionnaire scores were compared among the groups. RESULTS The compact quality of life scores were 77.4±11.3 in group 1, 86.2±7.2 in group 2, 79.1±9.5 in group 3, 83.4±10.6 in group 4, 87.3±9.4 in group 5, and 79.4±10.8 in group 6. There was a statistically significant difference in the compact quality of life scores among the surgery groups, neck dissection groups and RT groups (p=0.018, p<0.001, p<0.001, respectively). There was no effect of preserved 11th cranial nerve on daily activity, swallowing, chewing, appearance, recreation, salivation, taste, speech, mood, and anxiety parameters. This nerve was not preserved in 71.9% of the patients who were urged to change their job due to shoulder problems. The difference was statistically significant (p<0.001). CONCLUSION According to our study results, we concluded that partial laryngectomy improved the quality of life, rather than total or near-total laryngectomy, while postoperative RT had an adverse effect on the quality of life and preserved spinal accessory nerve during the neck dissection had a positive impact on the quality of life in patients with laryngeal cancer.

Oncologic and functional outcomes of open surgery in early supraglottic tumors: is it still a valid technique?

OBJECTIVES In this study, we aimed to analyze the oncologic and functional outcomes of supraglottic laryngectomy. PATIENTS AND METHODS Medical records of 91 cases (85 males, 6 females; mean age 55.4 years; range 30 to 75 years) who underwent surgery due to early supraglottic laryngeal cancer in our clinic were retrospectively analyzed. Statistical analysis was performed using chi-square test and Fishers exact test. Mean values were estimated by means of t-test, while survival curves were drawn using Kaplan-Meier method. RESULTS With respect to oncologic assessment, disease-free survival rate was 81%, the rate of regional recurrence was 6%, the rate of local recurrence was 8%, the rate of distant metastasis was 7% and the rate of occult neck metastasis was 25%. Metastatic neck disease and extracapsular invasion in the lymphatic ganglia were found to be the most critical parameters in terms of survival. With respect to functional assessment, the mean time of decannulation was 41 days, while the mean time of nasogastric tube removal was 19 days. It was observed that cases with a Forced Expiratory Volume in 1 second (FEV-1) of <75% experienced more aspiration-related problems. The functional outcomes were worse in the cases who underwent bilateral neck dissection and postoperative radiotherapy. CONCLUSION Open surgery is a more effective treatment modality in the early supraglottic tumors in terms of oncologic and functional outcomes. It should be continued to be use as an alternative method to the novel and expensive technologies including transoral robotic surgery or transoral laser surgery.