Algorithm of genetic diagnosis for patients with head and neck paraganglioma-update.

Paragangliomas are rare tumors originating from the paraventricular bodies of the autonomic nervous system located in the adrenal glands, chest, abdomen, pelvis and head and neck. Tumors of this type account for 0.5% of head and neck cancers, 0.03% of all cancers and their incidence is estimated at 1-30/100,000 per year. Head and Neck Paragangliomas (HNPGL) are localized in carotid body, tympanic cavity or jugular foramen. It is established that HNPGL may be associated with mutations of the SDH complex, with SDHD being the most prevalent. However, SDHB, SDHC and SDHAF are also potential causes. The aforementioned mutations are influenced by various risk factors, including young age, a positive family history of paraganglioma, the presence of metastases and gender The purpose of this study is to summarize the results of genetic testing performed on patients with head and neck paraganglioma and to create an up-to-date genetic diagnosis algorithm for patients with HNPGL based on previous studies published in the literature that can be used in daily practice. Several papers observed that among SDHD mutation carriers, most or all of those studied had HNPGL, and SDHB mutations were more frequently found in the presence of metastasis. Based on the results, it was concluded that there is no basis for genetic testing for VHL in patients without a positive family history. In each algorithm proposed by different authors, proposals for rational genetic diagnosis were analyzed based on the studies cited by the author and the analyses included in our paper. For the analysis of the treatment algorithms, the following were included: Martin, Mannelli, Neumann, Gupta. Subsequently, publications related to the genetic diagnosis of HNPGL were analyzed to verify the proposed algorithms in light of the latest genetic studies and to establish an updated diagnostic management scheme.

Optic Neuritis Related to Chronic Sphenoid Sinusitis as an Uncommon Cause of Vision Loss: A Case Report and Literature Review.

BACKGROUND Optic neuritis is a rare but possible complication of sphenoid sinusitis. CASE REPORT We present a case of a young woman with recurrent optic neuritis associated with chronic sphenoid sinusitis. A 29-year-old woman with visual impairment of the left eye to Snellen distance best-corrected visual acuity (DBCVA) of 0.5 and migraine headaches accompanied by vomiting and dizziness reported to the ophthalmic emergency room. The preliminary diagnosis was demyelinating optic neuritis. On head computed tomography, a polypoid lesion of the sphenoid sinus was found and qualified for elective endoscopic treatment. During a 4-year follow-up, evaluation of DBCVA, fundus appearance, visual field, ganglion cells layer (GCL), peripapillary retinal nerve fiber layer (RNFL) thickness, and ganglion cells and visual pathway function (pattern electroretinogram - PERG, pattern visual evoked potentials - PVEPs) were performed. Four years after the occurrence of the initial symptoms, surgical drainage of the sphenoid sinus was performed, which revealed a chronic inflammatory infiltrate and a sinus wall defect on the left side around the entrance to the visual canal. After surgery, headaches and other neurological symptoms resolved, but DBCVA deteriorated in the left eye to finger counting/hand motion, partial atrophy of the optic nerve developed, the visual field defect progressed to 20 central degrees, GCL and RNFL atrophy appeared, and deterioration of ganglion cells and visual pathway function were observed. CONCLUSIONS In patients with optic neuritis and atypical headaches, sphenoid sinusitis should be considered in the differential diagnosis. Delayed laryngological intervention can cause irreversible damage to the optic nerve.

Survival of Laryngeal Cancer Patients Depending on Zinc Serum Level and Oxidative Stress Genotypes.

Stress contributes to various aspects of malignancy and could influence survival in laryngeal cancer patients. Among antioxidant mechanisms, zinc and the antioxidant enzymes superoxide dismutase 2, catalase and glutathione peroxidase 1 play a major role. The aim of this study was a prospective evaluation of the survival of patients with laryngeal cancer in relation to serum levels of zinc in combination with functional genotype differences of three key antioxidant enzymes. The study group consisted of 300 patients treated surgically for laryngeal cancer. Serum zinc levels and common polymorphisms in SOD2, CAT and GPX1 were analyzed. The risk of death in patients with the lowest zinc levels was increased in comparison with patients with the highest levels. Polymorphisms of antioxidant genes by themselves were not correlated with survival, however, serum zinc level impact on survival was stronger for SOD2 TC/TT and CAT CC variants. GPX1 polymorphisms did not correlate with zinc levels regarding survival. In conclusion, serum zinc concentration appears to be an important prognostic factor for survival of patients diagnosed with laryngeal cancer. When higher zinc levels were correlated with polymorphisms in SOD2 and CAT a further increase in survival was observed.

Correction: Serum selenium levels and the risk of progression of laryngeal cancer.

[This corrects the article DOI: 10.1371/journal.pone.0184873.].

Serum selenium levels and the risk of progression of laryngeal cancer.

BACKGROUND: Observational studies have reported an inverse relationship between selenium status (blood or toenail) and the risk of laryngeal cancer; however, the impact of low serum selenium level on survival has not been evaluated. METHODS: We conducted a prospective study of 296 patients diagnosed with laryngeal cancer in Szczecin, Poland. Serum selenium was measured at diagnosis and prior to treatment. Patients were followed from the date of diagnosis to death at five years. Vital status was obtained by linkage to the Polish National Death Registry. RESULTS: The five-year survival after diagnosis was 82.0% (95% CI: 68% to 91%) for individuals in the highest quartile of serum selenium (> 66.8 µg/L) and was 28.6% (95% CI 19% to 42%) for individuals in the lowest quartile (<50.0 µg/L). In an age- and sex-adjusted analysis, the hazard ratio (HR) for death from all causes was 7.01 (95% CI 3.81 to 12.9) for patients in the lowest quartile of serum selenium, compared to those in the highest quartile. The corresponding multivariate HR was 3.07 (95% CI 1.59 to 5.94). CONCLUSIONS: This study suggests that a selenium level in excess of 70 µg/L is associated with improved outcome among patients undergoing treatment for laryngeal cancer. Further studies are needed to evaluate if selenium supplementation to achieve this level might improve overall prognosis.

Selenium as a marker of cancer risk and of selection for control examinations in surveillance.

Publication is summarization of existing data being results of literature review and our experience on usefulness of selenium as a diagnostic marker selection for control examinations in surveillance and as a marker of patients with high risk of cancers.

A low selenium level is associated with lung and laryngeal cancers.

PURPOSE: It has been suggested that selenium deficiency is a risk factor for several cancer types. We conducted a case-control study in Szczecin, a region of northwestern Poland, on 95 cases of lung cancer, 113 cases of laryngeal cancer and corresponding healthy controls. METHODS: We measured the serum level of selenium and established genotypes for four variants in four selenoprotein genes (GPX1, GPX4, TXNRD2 and SEP15). Selenium levels in the cases were measured after diagnosis but before treatment. We calculated the odds of being diagnosed with lung or laryngeal cancer, conditional on selenium level and genotype. RESULTS: Among lung cancer cases, the mean selenium level was 63.2 µg/l, compared to a mean level of 74.6 µg/l for their matched controls (p<0.0001). Among laryngeal cancer cases, the mean selenium level was 64.8 µg/l, compared to a mean level of 77.1 µg/l for their matched controls (p<0.0001). Compared to a serum selenium value below 60 µg/l, a selenium level above 80 µg/l was associated with an odds ratio of 0.10 (95% CI 0.03 to 0.34; p = 0.0002) for lung cancer and 0.23 (95% CI 0. 09 to 0.56; p = 0.001) for laryngeal cancer. In analysis of four selenoprotein genes we found a modest evidence of association of genetic variant in GPX1 with the risk of lung and laryngeal cancers. CONCLUSION: A selenium level below 60 µg/l is associated with a high risk of both lung and laryngeal cancer.

[Mucoepidermoid cancer of parotid gland in 14-years-old girl--case report]. / Rak sluzowo-naskórkowy slinianki przyusznej u 14-letniej dziewczynki - opis przypadku.

INTRODUCTION: Malignant tumors of salivary glands are rare, especially in children. MATERIAL AND METHOD: We present a case report of 14-years-old girl affected by mucoepidermoid cancer of parotid gland. RESULTS: Patient was admitted to our Department in May 2007 due to small, hard, moveable tumor localized in right mandibular angle. The VII nerve function was normal. Fine needle aspiration revealed inflammatory cells without atypical cytologic features. Intraoperative tumor was hard, with irregular surface, surrounded by capsule, connected with the main trunk of facial nerve and cartilaginous part of external auditory meatus. Tumor was excised together with superficial part of parotid gland and surrounding lymph nodes. After operation no signs of facial nerve damage were observed. Postoperative histopathological examination revealed mucoepidermoid cancer, in 2 out of 6 specimens neoplasmatic cells were seen in border of excised tissue. In June 2007 the second operation was performed. Remain part of parotid gland was removed with right facial nerve and conservative lymph node resection. Facial nerve and its branches were reconstructed with sural and great auricular nerve as donor grafts. The symptoms of nerve damage were observed in early postoperative days adequate to 5th degree of House-Brackman scale (HB5). 4 years after operation function of facial nerve is estimated on HB3. The girl is under regular oncological and laryngological control free of neoplasm recurrence. CONCLUSIONS: Diagnostics and treatment of malignant parotid tumors in children are difficult and clinical picture must be always taken into consideration as the most important factor.

Smoking related cancers and loci at chromosomes 15q25, 5p15, 6p22.1 and 6p21.33 in the Polish population.

Genetic factors associated with the risk of smoking related cancers have until recently remained elusive. Since the publication of a genome-wide association study (GWAS) on lung cancer new genetic loci have been identified that appear to be associated with disease risk. In this replication study we genotyped 14 single nucleotide polymorphisms (SNPs) located at the 5p12.3-p15.33, 6p21.3-p22.1, 6q23-q27 and 15q25.1 loci in 874 lung, 450 bladder, 418 laryngeal cancer cases and cancer-free controls, matched by year of birth and sex to the cases. Our results revealed that loci in the chromosome region 15q25.1 (rs16969968[A], rs8034191[G]) and 5p15 (rs402710[T]) are associated with lung cancer risk in the Polish population (smoking status adjusted OR = 1.45, 1.35, 0.77; p ≤ 0.0001, 0.0005, 0.002; 95%CI 1.23-1.72, 1.14-1.59, 0.66-0.91 respectively). None of the other regions analyzed herein were implicated in the risk of lung, bladder or laryngeal cancer. This study supports previous findings on lung cancer but fails to show association of SNPs located in 15q25.1 and 5p15 region with other smoking related cancers like bladder and laryngeal cancer.

[Pharyngeal constrictor muscles closure after total laryngectomy is that really beneficial?]. / Czy zszywanie zwieracza gardla dolnego po laryngektomii calkowitej jest korzystne?

UNLABELLED: High pressure of pharyngo-esophageal segment is the most important factor of impaired development of alaryngeal speech (esophageal speech, tracheoesophageal speech) after total laryngectomy. To prevent pharyngo-esophageal spasm in Department of Otolaryngology in Szczecin are used: pharyngoesophageal plastic surgery with interposition of vascular thyroid flap, two-layer (only mucosa) non-muscular pharyngeal closure and tree-layer closure (mucosa and muscle layer leaving inferior pharyngeal constrictor unsutured). AIM OF STUDY: The aim of this study was to compare the pharyngo-esophageal pressure between patients after pharyngo-esophageal plastic surgery and following the non-muscular pharyngeal closure. MATERIAL AND METHODS: One hundred eighty two subjects after total laryngectomy were enrolled in this study, and included 108 patients subjected to the pharyngo-esophageal plastic surgery, 44 patients who underwent the two-layer pharyngeal closure, and 30 patients with the tree-layer closure. To evaluate the pharyngo-esophageal pressures manometric tests were performed, and to asses the pharynx morphology videopharyngoscopy was used. RESULTS: The average pharyngo-esophageal pressure in the group after the pharyngo-esophageal plastic surgery was 32 (min.-5, max. 50) mmHg. After the two-layer non-muscular pharyngeal closure mean pressure was 35 (min.-17, max.-40) mmHg, and after the tree-layer non-muscular pharyngeal closure the average pressure was 22,42 (min. 5, max. 40) mmHg. The average pharyngo-esophageal pressure was significantly lower (p < 0.01) among patients after the tree-layer non-muscular closure. CONCLUSION: The study suggests that the tree-layer non-muscular pharyngeal closure with inferior pharyngeal constrictor unsutured is the preferable method to prevent pharyngo-esophageal spasm after total laryngectomy. However, the efficacy and safety of this surgical procedure should be explored in further multicenter studies.

Clinical characteristics of laryngeal cancer in BRCA-1 mutation carriers.

BACKGROUND: The aim of this study was to analyze the occurrence of clinical features characteristic of breast cancer type 1 susceptibility protein (BRCA-1)-dependent tumors in a series of BRCA-1 mutation carriers with laryngeal cancer. PATIENTS AND METHODS: The clinical features of five laryngeal cancer patients with BRCA-1 mutations registered in our center were analyzed for: sex, age at diagnosis, age at operation, tumor size and localization, histopathological subtype and grading, lymph node and distant metastases, mode of treatment and long term results of the therapy. RESULTS: The five patients were all men, with an average age at diagnosis of 52.4 years. The majority of the patients had clinical features typical of BRCA-1-dependent tumors: four out of the five patients had advanced staging at the time of diagnosis and in three of them the disorder disseminated within one year of follow-up. CONCLUSION: Since laryngeal carcinomas in men with BRCA-1 mutations show clinical features characteristic of BRCA-1 dependent tumors, it is reasonable to consider treatment modifications appropriate for this sub-group of tumors.

[Morphology of the glottis and perceptiv-acoustic characteristic of the voice and speech after extended fronto-lateral epiglotttoplasty]. / Morfologia glosni i charakterystyka percepcyjno-akustyczna glosu i mowy po laryngektomii fronto-lateralnej poszerzonej z nastepowa epiglotoplastyka.

UNLABELLED: For optimalisation glottis morphology and its phonatory function after frontolateral laryngectomy (FLL) the reconstruction of larynx is made; in Clinic of Otolaryngology the most common is using epiglottis wit or without its vertical incision. AIM OF THE STUDY: the influence of widening laryngeal resection and epiglottis incision on shape of reconstructed glottis, level and degree of phonatory closure and perceptive--acoustic characteristic of voice and speech. MATERIAL: 39 patients (38 M and 1 F) after FLL widened of false vocal cord (n = 11), false vocal cord and part of cricoid cartilage (n = 22), whole cricoid cartilage (n = 6). Vertical incision of epiglottis was made in 31 cases. Mean age was 52 (min.-39, max.-70) years. METHODICS: videolaryngoscopic examination, subjective voice estimation using GRBAS scale, objective phonetic--acoustic voice analysis. RESULTS: In videolaryngoscopic examination the most common shape of glottis was irregular triangle (n = 24), rhombus (n = 7), half--moon (n = 2), irregular (n = 6). 2 patients were using whisper. In spectrographic recordings (n = 39) only noise character of stimulation source was in 2 patients, noise--periodic with noise component present in whole acoustic spectrum in 37. F0 for single word and sentence vocalized in affirmative and interrogative form had the value of male voices and its changes during speaking were well noted. In subjective and objective estimation, the worse voice quality was after FLL widened of false vocal cord, part or whole cricoid cartilage. CONCLUSION: 1) FLL with subsequent epiglottoplasty in 94% of patients makes satisfactory morphologic and biophysical conditions for production of voice and sociological efficient speech. 2) Widening resection of false vocal cord, part or whole cricoid cartilage has unbeneficial influence on perceptive--acoustic characteristic of voice and speech.

Pleomorphic adenoma of salivary glands does not appear to be a BRCA-1-dependent tumour in a Polish cohort.

BACKGROUND: The aim of the study was to examine whether pleomorphic adenoma of salivary glands can occur on the basis of constitutional BRCA-1 mutations. MATERIALS AND METHODS: Two hundred and sixty-eight patients affected by mixed tumour of salivary glands were examined for occurrence of three BRCA-1 mutations dominating in Poland. RESULTS: BRCA-1 mutation was detected in only one of the patients, a female affected by breast cancer and pleomorphic adenoma of parotid gland. Parotid gland tumour showed clinical and histopathological features of typical pleomorphic adenoma with no morphological features of high-grade malignancy, which are characteristic of BRCA-1-dependent tumours. CONCLUSION: Considering the low frequency of BRCA-1 mutation in the examined group and also the absence of features characterizing BRCA-1-dependent tumours in the only BRCA-1-positive case, pleomorphic adenoma of salivary glands should not be recognized as a BRCA-1 dependent tumour.

Familial association of laryngeal, lung, stomach and early-onset breast cancer.

This study analyzes the incidence of different types of cancer among 2839 first-degree relatives of 760 consecutive, unselected laryngeal cancer patients, compared with the general population. A statistically significant excess was seen for other cancers of the larynx (SIR: 400), lung (SIR: 135) and stomach (SIR: 271), and early-onset breast cancer (SIR: 287). Familial laryngeal cancer may not be a single site-specific cancer syndrome.

Clinical and epidemiological features of familial laryngeal cancer in Poland.

BACKGROUND: Laryngeal cancer has one of the worst recurrence rates for any malignancy, is known to be influenced by several environmental factors, and it is significantly more common in males than females. Familial clusterings of laryngeal cancer have been reported but no systematic evaluation of the clinical feature of the disease or an in-depth analysis of familial forms of the disease has been made. In this study we wished to determine if there are any clinical features of the disease that may be useful for the identification of genetic susceptibility loci associated with the disorder. METHODS: Seven hundred and fifty-three unselected consecutive laryngeal cancer patients were analyzed depending on sex, age, smoking behavior, and clinical features (localization, tumor size, lymph node metastases, grading, and staging) and the presence of cancer among first-degree relatives. The presence of at least a second relative affected by laryngeal cancer was considered to be a Familial Larynx Cancer (FLC) case (44 patients). RESULTS: Women in the FLC group had larger tumors, higher proportion of lymph node metastases, higher grading, staging, and a tendency towards supraglottic localization than the sporadic larynx cancer cases. The aggressive pattern characterized by presence of metastases, tumor size >2, and grading=3 revealed to be significantly associated with FLC (OR=10.02, p=0.0003). CONCLUSIONS: The study revealed a distinct clinical pattern of disease in familial cases of laryngeal cancer, which may provide a valuable basis for the identification of genetic determinants of this malignancy.