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Small extracellular vesicles (sEVs) secreted by various types of cells serve as crucial mediators of intercellular communication within the complex tumour microenvironment (TME). Tumour-derived small extracellular vesicles (TDEs) are massively produced and released by tumour cells, recapitulating the specificity of their cell of origin. TDEs encapsulate a variety of RNA species, especially messenger RNAs, microRNAs, long non-coding RNAs, and circular RNAs, which release to the TME plays multifaced roles in cancer progression through mediating cell proliferation, invasion, angiogenesis, and immune evasion. sEVs act as natural delivery vehicles of RNAs and can serve as useful targets for cancer therapy. This review article provides an overview of recent studies on TDEs and their RNA cargo, with emphasis on the role of these RNAs in carcinogenesis.
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Vesículas Extracelulares , Neoplasias , Microambiente Tumoral , Humanos , Vesículas Extracelulares/metabolismo , Neoplasias/patologia , Neoplasias/genética , Neoplasias/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , RNA Longo não Codificante/genética , RNA Circular/genética , RNA Circular/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Comunicação Celular , RNA/genética , RNA/metabolismoRESUMO
AIM: To evaluate the most important factors of quality of life in patients after vestibular schwannoma surgery. MATERIALS AND METHODS: Patients with unilateral sporadic occurrence of vestibular schwannoma who underwent surgery via suboccipital-retrosigmoid approach were included in the prospective study (2018-2021). Patients after previous Leksell gamma knife irradiation (or other methods of stereotactic radiosurgery) were excluded. Quality of life was assessed using 10 validated questionnaires that were distributed preoperatively, 3 months and 1 year after the surgery. RESULTS: A total of 76 patients were included in the study, complete data were analysed in 43 of them (response rate 57%). Grade III and IV represented up to 70% of all tumors. Patients with larger tumors had a significantly higher risk of postoperative facial nerve paresis, liquorrhea and lower probability of hearing preservation. Patients with smaller tumors and those, who suffered from headaches before surgery had more frequent and severe headaches after surgery. Postoperative headaches were associated with higher incidence of anxiety and tinnitus. More frequent anxiety was also identified in patients with preoperative serviceable hearing who became deaf after surgery. Nevertheless, tinnitus and hearing impairment appeared to have less impact on overall quality of life compared to headaches and facial nerve function. CONCLUSION: According to our results, tumor size, postoperative function of the facial nerve and occurrence of postoperative headaches had the greatest influence on the overall postoperative quality of life in patients after vestibular schwannoma surgery.
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Neuroma Acústico , Zumbido , Humanos , Neuroma Acústico/cirurgia , Qualidade de Vida , Estudos Prospectivos , CefaleiaRESUMO
Introduction: Head and neck paragangliomas (HNPGLs) are rare neuroendocrine tumors, which are mostly benign in nature. Amongst all genes, Succinate Dehydrogenase Subunit D (SDHD) is the most commonly mutated in familial HNPGLs. In about 30% of HNPGLs, germline mutations in SDHD can also occur in the absence of positive family history, thus giving rise to "occult familial" cases. Our aim was to evaluate the pattern of SDHD germline mutations in Czech patients with HNPGLs. Materials and methods: We analyzed a total of 105 patients with HNPGLs from the Otorhinolaryngology departments of 2 tertiary centers between 2006 - 2021. All underwent complex diagnostic work-up and were also consented for genetic analysis. Results: Eighty patients aged 13-76 years were included; around 60% with multiple PGLs were males. Carotid body tumor was the most frequently diagnosed tumor. Germline SDHD mutation was found in only 12% of the Czech patients; approximately 78% of those harboring the mutation had negative family history. The mutation traits had higher affiliation for multiple tumors with nearly 70% patients of ≤ 40 years of age. Conclusion: An SDHD mutation variant was shared amongst unrelated patients but no founder-effect was established. Our findings confirmed that the pattern of SDHD mutation distribution amongst HNPGLs in Czech Republic differs from most studies worldwide.
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Paraganglioma Extrassuprarrenal , Paraganglioma , Adulto , Feminino , Humanos , Masculino , República Tcheca/epidemiologia , Incidência , Mutação , Paraganglioma/epidemiologia , Paraganglioma/genética , Paraganglioma/diagnóstico , Succinato Desidrogenase/genética , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , IdosoRESUMO
OBJECTIVE: To evaluate the safety and efficacy of AM-125 nasal spray (intranasal betahistine) in the treatment of surgery-induced acute vestibular syndrome (AVS). STUDY DESIGN: Prospective, double-blind, randomized, placebo-controlled exploratory phase 2 study with dose escalation (part A) followed by parallel dose testing (part B); open-label oral treatment for reference. SETTING: Twelve European study sites (tertiary referral centers). PATIENTS: One hundred and twenty-four patients 18 to 70 years old undergoing surgery for vestibular schwannoma resection, labyrinthectomy or vestibular neurectomy with confirmed bilateral vestibular function presurgery and acute peripheral vertigo postsurgery. INTERVENTIONS: AM-125 (1, 10, or 20 mg) or placebo or betahistine 16 mg p.o. t.i.d. for 4 weeks, starting 3 days postsurgery; standardized vestibular rehabilitation. MAIN OUTCOME MEASURES: Tandem Romberg test (TRT) for primary efficacy, standing on foam, tandem gait, subjective visual vertical and spontaneous nystagmus for secondary efficacy, Vestibular Rehabilitation Benefit Questionnaire (VRBQ) for exploratory efficacy; nasal symptoms and adverse events for safety. RESULTS: At treatment period end, mean TRT improvement was 10.9 seconds for the 20-mg group versus 7.4 seconds for the placebo group (mixed model repeated measures, 90% confidence interval = 0.2 to 6.7 s; p = 0.08). This was corroborated by nominally higher frequency of complete spontaneous nystagmus resolution (34.5% vs. 20.0% of patients) and improvement in the VRBQ; the other secondary endpoints showed no treatment effect. The study drug was well tolerated and safe. CONCLUSIONS: Intranasal betahistine may help accelerate vestibular compensation and alleviate signs and symptoms of vestibular dysfunction in surgery-induced AVS. Further evaluation in a confirmatory manner appears warranted.
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beta-Histina , Nistagmo Patológico , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , beta-Histina/efeitos adversos , Estudos Prospectivos , Vertigem/tratamento farmacológico , Método Duplo-Cego , Resultado do TratamentoRESUMO
INTRODUCTION: Currently, it is possible to preserve the auditory nerve in a large number of cases, but the preservation of the hearing itself is unpredictable. Apart from wait and scan strategy and stereoradiotherapy, hearing after vestibular schwannoma surgery is considered to remain stable even in long-term follow-up. MATERIALS AND METHODS: Twenty-eight patients had preserved hearing after retrosigmoid suboccipital microsurgery of the vestibular schwannoma between 2008 and 2014. A standard audiological protocol was performed together with an magnetic resonance imaging evaluation of the fluid content of the inner ear. RESULTS: The mean difference in pure-tone average between the direct and final postsurgical examination was 12.758 dB ( p = 2.5E - 06). The word recognition score deteriorated by 17.45% ( p = 0.03516). The mean American Academy of Otolaryngology-Head and Neck Surgery score on the second examination was 2.5, and that on the second examination was 3.111 ( p = 0.00483). There was no significant deterioration in the healthy ear.The signal intensity ratio in the basal turn of the cochlea increased by an average of 0.13 points ( p < 0.05).Patients with persistent tumor or nodular enhancement in the internal acoustic meatus deteriorated significantly in hearing according to the American Academy of Otolaryngology-Head and Neck Surgery scale compared with patients without any finding in the meatus ( p = 0.01299). CONCLUSIONS: There is a discrete but gradual deterioration of the hearing in the postoperative period. Hearing impairment is more pronounced in patients with a nodular process in the internal acoustic meatus, regardless of whether it is growth active. After surgery, the pathological content of the inner ear normalizes (evaluated on T2 magnetic resonance imaging sequences).
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Orelha Interna , Perda Auditiva , Neuroma Acústico , Humanos , Neuroma Acústico/cirurgia , Audição , Orelha Interna/cirurgia , Perda Auditiva/etiologia , Cóclea , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The incidence of sporadic vestibular schwannoma has significantly increased over the past few decades. However, there is no method currently available to accurately predict the risk of subsequent tumor growth. The difference in the management of five patient groups has been evaluated: wait and scan, conversion to microsurgery, conversion to stereoradiotherapy, sterioradiotherapy, and microsurgery. In total, 463 patients with vestibular schwannoma have been consulted in our department from 2010 through 2016. Of the 250 patients initially indicated for observation, 32.4% were later indicated for active treatment. Younger patients were more frequently indicated for surgery (mean age 48 years) compared to older patients, who were more often indicated for stereoradiotherapy (mean age 62 years). Tumor growth was observed more often in patients under 60 years of age and in patients with tumors greater than 10 mm. In elderly patients, including those with larger tumors, a conservative approach is the optimal solution. If tumor growth occurs in the wait-and-scan strategy, it is still possible to continue with a conservative approach in some situations. The duration of follow-up scans is still a matter of debate, as tumors can begin to grow after 5 years from the initial diagnosis.
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Head and neck squamous cell carcinomas (HNSCC) belong among severe and highly complex malignant diseases showing a high level of heterogeneity and consequently also a variance in therapeutic response, regardless of clinical stage. Our study implies that the progression of HNSCC may be supported by cancer-associated fibroblasts (CAFs) in the tumour microenvironment (TME) and the heterogeneity of this disease may lie in the level of cooperation between CAFs and epithelial cancer cells, as communication between CAFs and epithelial cancer cells seems to be a key factor for the sustained growth of the tumour mass. In this study, we investigated how CAFs derived from tumours of different mRNA subtypes influence the proliferation of cancer cells and their metabolic and biomechanical reprogramming. We also investigated the clinicopathological significance of the expression of these metabolism-related genes in tissue samples of HNSCC patients to identify a possible gene signature typical for HNSCC progression. We found that the right kind of cooperation between cancer cells and CAFs is needed for tumour growth and progression, and only specific mRNA subtypes can support the growth of primary cancer cells or metastases. Specifically, during coculture, cancer cell colony supporting effect and effect of CAFs on cell stiffness of cancer cells are driven by the mRNA subtype of the tumour from which the CAFs are derived. The degree of colony-forming support is reflected in cancer cell glycolysis levels and lactate shuttle-related transporters.
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OBJECTIVES: Hearing preservation after vestibular schwannoma (VS) surgery remains a surgical challenge. In some patients with preserved inner ear function, hearing improvement is achievable. As it is currently impossible to determine which patients will present this outcome, predictions must rely on previously published reports. Our case report describes a patient who experienced hearing improvement from an unuseful level to a useful one after vestibular schwannoma surgery. METHODS: Surgery was performed via suboccipital retrosigmoid approach. The patient underwent a basic audiovestibular protocol before and after the surgery - pure tone and speech audiometry, otoacoustic emissions, auditory brainstem responses, electronystagmography - together with a detailed questionnaire study. Usefulness of hearing was evaluated using the AAO-HNS guidelines, supplemented by a frequency of 4 kHz. RESULTS: Hearing was preserved and even improved from an unuseful level to a useful one. Based on the available literature, the most informative predictive factors for such a result seem to be: sudden sensorineural hearing loss prior to surgery, elicitable otoacoustic emissions and the origin from the superior vestibular nerve. CONCLUSION: There are a limited number of studies on this topic and it is still impossible to regularly improve hearing in properly selected patients. Furthermore, the importance of postoperative hearing quality compared to other symptoms and complications remains debatable.
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Neuroma Acústico , Audiometria de Tons Puros , Audição/fisiologia , Humanos , Neuroma Acústico/complicações , Neuroma Acústico/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Vestibular schwannoma is the most common benign neoplasm of the cerebellopontine angle. It arises from Schwann cells of the vestibular nerve. The first symptoms of vestibular schwannoma include hearing loss, tinnitus, and vestibular symptoms. In the event of further growth, cerebellar and brainstem symptoms, along with palsy of the adjacent cranial nerves, may be present. Although hearing impairment is present in 95% of patients diagnosed with vestibular schwannoma, most tumors do not progress in size or have low growth rates. However, the clinical picture has unpredictable dynamics, and there are currently no reliable predictors of the tumor's behavior. The etiology of the hearing loss in patients with vestibular schwannoma is unclear. Given the presence of hearing loss in patients with non-growing tumors, a purely mechanistic approach is insufficient. A possible explanation for this may be that the function of the auditory system may be affected by the paracrine activity of the tumor. Moreover, initiation of the development and growth progression of vestibular schwannomas is not yet clearly understood. Biallelic loss of the NF2 gene does not explain the occurrence in all patients; therefore, detection of gene expression abnormalities in cases of progressive growth is required. As in other areas of cancer research, the tumor microenvironment is coming to the forefront, also in vestibular schwannomas. In the paradigm of the tumor microenvironment, the stroma of the tumor actively influences the tumor's behavior. However, research in the area of vestibular schwannomas is at an early stage. Thus, knowledge of the molecular mechanisms of tumorigenesis and interactions between cells present within the tumor is crucial for the diagnosis, prediction of tumor behavior, and targeted therapeutic interventions. In this review, we provide an overview of the current knowledge in the field of molecular biology and tumor microenvironment of vestibular schwannomas, as well as their relationship to tumor growth and hearing loss.
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INTRODUCTION: The facial nerve surgery belongs to the basic procedures during lateral skull base approaches. Its damage has serious medical and psychological consequences, and therefore mastery of reconstruction and correction techniques should belong to the repertoire of skull base surgeons. The goal of this study was to demonstrate usefulness of electromyographic follow-up in facial nerve reconstruction. MATERIAL AND METHODS: A total of 16 patients underwent hemihypoglossal-facial anastomosis between 2005 and 2017. Most of the primary lesions came from vestibular schwannoma surgery. All patients were examined with electromyography and scored according to the House-Brackmann and IOWA grading scales. Function of the tongue has been evaluated. RESULTS: Ten patients achieved definitive House-Brackmann grade 3 score (62.5%). We did not observe any association with the patient's age, previous irradiation and the etiology of the damage. Electromyography showed pathological spontaneous activity after the first surgery. Incipient regeneration potentials were detected in 4-17 months (average 7.6) and reached maximum in 6.5-18 months (average 16). Electromyographic assessment of the effect of tongue movement showed better mimic voluntary activity by swallowing or by moving the tongue up. There was no relationship between the start of activity and the interval to achieving maximal activity. CONCLUSION: Hemihypoglossal-facial nerve anastomosis is a safe procedure and it is an optimal solution for cases lacking a proximal stump or in the case of reconstruction in the second stage. Electromyography can predict initial reinnervation activity after reconstructive procedures. During subsequent follow-up it can help to discover insufficiently recovering patients, however clinical characteristics are crucial.
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Nervo Facial , Paralisia Facial , Anastomose Cirúrgica , Nervo Facial/cirurgia , Humanos , Nervo Hipoglosso/cirurgia , Resultado do TratamentoRESUMO
Decision making on the treatment of vestibular schwannoma (VS) is mainly based on the symptoms, tumor size, patient's preference, and experience of the medical team. Here we provide objective tools to support the decision process by answering two questions: can a single checkup predict the need of active treatment?, and which attributes of VS development are important in decision making on active treatment? Using a machine-learning analysis of medical records of 93 patients, the objectives were addressed using two classification tasks: a time-independent case-based reasoning (CBR), where each medical record was treated as independent, and a personalized dynamic analysis (PDA), during which we analyzed the individual development of each patient's state in time. Using the CBR method we found that Koos classification of tumor size, speech reception threshold, and pure tone audiometry, collectively predict the need for active treatment with approximately 90% accuracy; in the PDA task, only the increase of Koos classification and VS size were sufficient. Our results indicate that VS treatment may be reliably predicted using only a small set of basic parameters, even without the knowledge of individual development, which may help to simplify VS treatment strategies, reduce the number of examinations, and increase cause effectiveness.
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Tomada de Decisão Clínica , Gerenciamento Clínico , Aprendizado de Máquina , Neuroma Acústico/diagnóstico , Neuroma Acústico/terapia , Adulto , Idoso , Árvores de Decisões , Feminino , Audição , Testes Auditivos , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes , Aprendizado de Máquina Supervisionado , Avaliação de SintomasRESUMO
Cancer-associated fibroblasts (CAFs) are one of the most abundant and critical components of the tumor stroma. CAFs can impact many important steps of cancerogenesis and may also influence treatment resistance. Some of these effects need the direct contact of CAFs and cancer cells, while some involve paracrine signals. In this study, we investigated the ability of head and neck squamous cell carcinomas (HNSCC) patient-derived CAFs to promote or inhibit the colony-forming ability of HNSCC cells. The effect of cisplatin on this promoting or inhibiting influence was also studied. The subsequent analysis focused on changes in the expression of genes associated with cancer progression. We found that cisplatin response in model HNSCC cancer cells was modified by coculture with CAFs, was CAF-specific, and different patient-derived CAFs had a different "sensitizing ratio". Increased expression of VEGFA, PGE2S, COX2, EGFR, and NANOG in cancer cells was characteristic for the increase of resistance. On the other hand, CCL2 expression was associated with sensitizing effect. Significantly higher amounts of cisplatin were found in CAFs derived from patients who subsequently experienced a recurrence. In conclusion, our results showed that CAFs could promote and/or inhibit colony-forming capability and cisplatin resistance in HNSCC cells via paracrine effects and subsequent changes in gene expression of cancer-associated genes in cancer cells.
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Antineoplásicos/farmacologia , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/metabolismo , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Técnicas de Cocultura , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Comunicação Parácrina/efeitos dos fármacos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Ensaio Tumoral de Célula-TroncoRESUMO
AIMS: Total laryngectomy still plays an essential part in the treatment of laryngeal cancer and loss of voice is the most feared consequence of the surgery. Commonly used rehabilitation methods include esophageal voice, electrolarynx, and implantation of voice prosthesis. In this paper we focus on a new perspective of vocal rehabilitation utilizing alternative and augmentative communication (AAC) methods. METHODS AND PATIENTS: 61 consecutive patients treated by means of total laryngectomy with or w/o voice prosthesis implantation were included in the study. All were offered voice banking and personalized speech synthesis (PSS). They had to voluntarily express their willingness to participate and to prove the ability to use modern electronic communication devices. RESULTS: Of 30 patients fulfilling the study criteria, only 18 completed voice recording sufficient for voice reconstruction and synthesis. Eventually, only 7 patients started to use this AAC technology during the early postoperative period. The frequency and total usage time of the device gradually decreased. Currently, only 6 patients are active users of the technology. CONCLUSION: The influence of communication with the surrounding world on the quality of life of patients after total laryngectomy is unquestionable. The possibility of using the spoken word with the patient's personalized voice is an indisputable advantage. Such a form of voice rehabilitation should be offered to all patients who are deemed eligible.
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Neoplasias Laríngeas , Laringe Artificial , Comunicação , Humanos , Neoplasias Laríngeas/cirurgia , Laringectomia , Qualidade de Vida , FalaRESUMO
Multidrug resistance (MDR) is often caused by the overexpression of efflux pumps, such as ABC transporters, in particular, P-glycoprotein (P-gp). Here, we investigate the di- and tri- block amphiphilic polymer systems based on polypropylene glycol (PPO) and copolymers of (N-(2-hydroxypropyl)methacrylamide) (PHPMA) as potential macromolecular inhibitors of P-gp, and concurrently, carriers of drugs, passively targeting solid tumors by the enhanced permeability and retention (EPR) effect. Interestingly, there were significant differences between the effects of di- and tri- block polymer-based micelles, with the former being significantly more thermodynamically stable and showing much higher P-gp inhibition ability. The presence of Boc-protected hydrazide groups or the Boc-deprotection method did not affect the physico-chemical or biological properties of the block copolymers. Moreover, diblock polymer micelles could be loaded with free PPO containing 5-40 wt % of free PPO, which showed increased P-gp inhibition in comparison to the unloaded micelles. Loaded polymer micelles containing more than 20 wt % free PPO showed a significant increase in toxicity; thus, loaded diblock polymer micelles containing 5-15 wt % free PPO are potential candidates for in vitro and in vivo application as potent MDR inhibitors and drug carriers.
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PURPOSE: Vestibular schwannoma removal causes unilateral vestibular deafferentation, which results in dizziness and postural unsteadiness. Vertigo and balance problems together are among the most important aspects affecting quality of life. Intensive vestibular rehabilitation, which starts before surgery, with following postsurgical supervised rehabilitation, using visual biofeedback propose an instrument to accelerate a recovery process. Another option how to accelerate the vestibular compensation, is employment of presurgical gentamicin ablation together with vestibular rehabilitation (prehabilitation) of vestibular function. Purpose of present study was to examine the dynamics of vestibular compensation process using supervised intensive vestibular rehabilitation with visual biofeedback in the short-term postsurgical period. The second aim was to compare both studied groups mainly to evaluate if prehabilitation has potential to accelerate the compensation process in the early postoperative course. METHODS: The study included 52 patients who underwent the retrosigmoid vestibular schwannoma removal. They were divided into two groups. The first group was prehabilitated with intratympanic application of gentamicin before surgery to cause unilateral vestibular loss (14 patients), the second group (38 patients) was treated in standard protocol without prehabilitation. All patients underwent at home vestibular training before surgery to learn new movement patterns. Following the surgery supervised intensive vestibular rehabilitation including visual biofeedback was employed daily in both groups between the 5th and 14th postoperative day. Outcome measurements included an evaluation of subjective visual vertical (SVV), posturography and the Activities-Specific Balance Confidence Scale (ABC). ANOVA for repeated measurements was used for statistical analysis. RESULTS: We observed significant improvement in SVV (p < 0.05), posturography parameters (p < 0.05) and ABC scores (p < 0.05) with postoperative rehabilitation program following surgery in both groups. There was no statistically significant difference between group treated by prehabilitation and group without prehabilitation. CONCLUSIONS: Results of this study showed that intensive postsurgical rehabilitation represents key factor in compensation process following retrosigmoid vestibular schwannoma surgery. Prehabilitation did not speed up recovery process.
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Tontura , Reabilitação Neurológica/métodos , Neuroma Acústico/cirurgia , Procedimentos Cirúrgicos Otológicos/reabilitação , Complicações Pós-Operatórias , Qualidade de Vida , Vertigem , Tontura/etiologia , Tontura/reabilitação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Otológicos/efeitos adversos , Procedimentos Cirúrgicos Otológicos/métodos , Complicações Pós-Operatórias/psicologia , Complicações Pós-Operatórias/reabilitação , Pré-Medicação/métodos , Resultado do Tratamento , Vertigem/etiologia , Vertigem/reabilitaçãoRESUMO
Despite distinctive advances in the field of head and neck squamous cell cancer (HNSCC) biomarker discovery, the spectrum of clinically useful prognostic serum biomarkers is limited. As metabolic activities in highly proliferative transformed cells are fundamentally different from those in non-transformed cells, specific shifts in concentration of different metabolites may serve as diagnostic or prognostic markers. Blood amino acids have been identified as promising biomarkers in different cancers before, but little is known about this field in HNSCC. Blood amino acid profiles of 140 HNSCC patients were examined using high-performance liquid chromatography. Cox proportional hazards regression model was used to assess the prognostic value of amino acid concentrations in serum. Colony forming assay was used to identify the effect of amino acids that were significant in Cox proportional hazards regression models on colony forming ability of FaDu and Detroit 562 cell lines. In the multivariable Cox regression model for overall survival (OS), palliative treatment was associated with an unfavourable prognosis while high serum levels of methionine have had a positive prognostic impact. In the relapse-free survival (RFS) multivariable model, methionine was similarly identified as a positive prognostic factor, along with tumor localization in the oropharynx. Oral cavity localization and primary radio(chemo)therapy treatment strategy have been linked to poorer RFS. 1mM serine was shown to support the forming of colonies in both tested HNSCC cell lines. Effect of methionine was exactly the opposite.
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Aminoácidos/sangue , Neoplasias de Cabeça e Pescoço/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Ensaio Tumoral de Célula-TroncoRESUMO
Metastasis to the head and neck and more specifically to the thyroid gland from distant primary tumors is less common in comparison to the local regional metastasis of squamous cell carcinomas of the upper aero-digestive tract. Preoperative diagnosis of these cases can be difficult. The authors present three cases with distant solitary metastases of clear renal cell carcinoma to the thyroid gland with ambiguous mechanism of tumor spread to the thyroid. Solitary metastases of clear renal cell carcinomas are an uncommon variant of metastasis of this tumor and may imitate thyroid well differentiated carcinoma which most commonly affects the thyroid gland. Therefore, thorough endocrinological investigation of the thyroid gland is necessary. The recommended therapy of renal cell carcinoma metastasis includes surgical removal of all cancerous tissues - i.e. of the gland with the possibly infiltrated adjacent tissues, as well as removal of the affected lymph nodes - selective radical neck dissection. In our study, we discuss the clinical picture, pathology, diagnosis, differential diagnosis and prognosis together with literature review.
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Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Neoplasias da Glândula Tireoide/secundário , Carcinoma Papilar , Humanos , Metástase LinfáticaRESUMO
Skull base tumors and, in particular, vestibular schwannoma (VS) are among the etiological reasons for single-sided deafness (SSD). Patients with SSD have problems in understanding speech in a noisy environment and cannot localize the direction of sounds. Baha is one of the most frequently used systems for SSD compensation. Out of 38 patients with SSD after retrosigmoid removal of VS who underwent testing with Baha softband, 16 were satisfied and were indicated for Baha implantation. Two surgical approaches have been used-the Nijmegen linear incision technique with subdermal thinning (Group I, implant BI300) and fast surgery technique without subdermal thinning (Group II, implant BIA400). The duration of the surgery, the implant stability measured by Ostell, and skin or soft tissue reactions in long range follow-up were evaluated and compared between Group I and II. There was a difference in duration of surgery, in Group II procedures averaged significantly faster (p > 0.001). In both groups, there was a similar trend of the gradual increase of implant stability. In the Group I and II, there was comparable rate of the skin or soft tissue reactions grade 0, I, II, or III. We have proved Baha to be a suitable possibility for SSD patients after the removal of VS, regardless of the approach. After the retrosigmoid approach to the VS, the key step of Baha implantation must be to reach intact healthy bone to avoid implantation into scar tissue.
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Auxiliares de Audição , Perda Auditiva Unilateral , Neuroma Acústico , Implantação de Prótese/métodos , Feminino , Perda Auditiva Unilateral/diagnóstico , Perda Auditiva Unilateral/etiologia , Perda Auditiva Unilateral/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Neuroma Acústico/patologia , Neuroma Acústico/cirurgia , Satisfação Pessoal , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/cirurgia , Retenção da Prótese , Resultado do TratamentoRESUMO
Skull base tumors and, in particular, vestibular schwannoma (VS) are among the etiological reasons for single-sided deafness (SSD). Patients with SSD have problems in understanding speech in a noisy environment and cannot localize the direction of sounds. For the majority, this is the handicap for which they try to find a solution. Apart from CROS hearing aids, Baha is one of the most frequently used systems for SSD compensation. 38 patients with single-sided deafness after retrosigmoid removal of a vestibular schwannoma underwent testing with a Baha softband from September 2010 to August 2014. Sixteen patients (42 %) finally decided to accept Baha implantation. Subjective experience with the Baha softband was evaluated by patients using the BBSS questionnaire immediately after testing. Objective evaluation of the effect was performed as a measurement of the sentence discrimination score in noise and side horizontal discrimination without a Baha and 6 weeks and 12 months after a sound processor fitting. There was a significant improvement in sentence discrimination in the 6 week (64.0 %) and 1 year (74.6 %) interval of follow-up in comparison with understanding without Baha (24.0 %, p = 0.001) in situations when sentences are coming from the side of the non-hearing ear and noise contralaterally with SNR -5 dB. Baha can significantly improve sentence discrimination in complex-listening situation in patients with SSD after the VS surgery.
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Auxiliares de Audição , Perda Auditiva Unilateral/cirurgia , Neuroma Acústico/complicações , Próteses e Implantes , Adulto , Idoso , Feminino , Perda Auditiva Unilateral/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Localização de Som , Inteligibilidade da FalaRESUMO
BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. In addition to causal somatic mutations in the BRAF gene and RET/PTC rearrangements, the contribution of single nucleotide polymorphisms (SNPs) in low-penetrance genes in the development of PTC has been proposed. METHODS: Four SNPs in the XRCC1 (Arg399Gln, Arg280His, Arg194Trp and T-77C) and one SNP from each of three other genes participating in DNA repair pathways and/or cell cycle regulation (ATM Asp1853Asn, TP53 Arg72Pro, CDKN1B Val109Gly) were selected. The allelic and genotypic distributions of these variants as well as haplotypes of the XRCC1 were examined in 583 individuals comprising well-characterized cohorts of 209 PTC patients and 374 healthy volunteers. Correlations of polymorphism with clinical-pathological data and mutation status were performed. RESULTS: XRCC1 T-77C polymorphism affects the genetic susceptibility for PTC development in men, the specific combination of XRCC1 haplotypes correlates with RET/PTC incidence, CDKN1B Val109Gly significantly influences the risk of developing PTC regardless of gender and in PTC cases, selected genotypes of TP53 Arg72Pro and ATM Asp1853Asn were significantly associated with monitored tumour characteristics. CONCLUSION: It seems that SNPs in studied regulating genes contribute to the development of PTC and modify the tumour behaviour or characteristics.