Loss of p16 expression is a risk factor for recurrence in sinonasal inverted papilloma.

BACKGROUND: The purpose of this study was to evaluate p16, p53, EGFR, pEGFR protein expression and HPV infection as possible markers of tumor progression in a series of sinonasal inverted papilloma (SNIP) and sinonasal squamous cell carcinoma (SNSCC). METHODS: A series of 49 SNIP, 11 SNSCC associated with SNIP (SNIP-SNSCC) and 52 SNSCC not associated with SNIP were analyzed for p16, p53, EGFR, and phosphorylated EGFR (pEGFR) expression by immunohistochemistry. Human papillomavirus (HPV) infection status was evaluated by DNA-PCR. Results were correlated to clinical and follow-up data. RESULTS: Reduced or loss of p16 expression was observed in 18% SNIP, 64% SNIP-SNSCC and 87% of SNSCC. Reduced or loss p16 staining in SNIP correlated with shorter recurrent SNIP-free follow-up. In contrast, p16 expression was not predictive of recurrent SNSCC in cases with SNIP-SNSCC and SNSCC. P53, EGFR, and pEGFR expression did not differ between the tumor groups, nor were they related to recurrent SNIP-free follow-up or recurrent SNSCC. Oncogenic HPV types 16 and 18 were detected in 5% of SNIP and 18% of SNIP-SNSCC, but not in SNSCC. There was no correlation between HPV infection and >70% p16 immunostaining. CONCLUSIONS: HPV infection appears to play a minor role in SNIP and SNSCC and p16 immunostaining does not appear a valid surrogate marker for HPV. However, reduced or loss p16 expression may have prognostic value as a risk marker for recurrent SNIP.

Understanding the Associations across Fibromyalgia-Related Fatigue, Depression, Anxiety, Self-Esteem Satisfaction with Life and Physical Activity in Portuguese and Brazilian Patients: A Structural Equation Modeling Analysis.

Background and Objectives: Fibromyalgia are heterogeneous and differ from patient to patient; however, the most reported are general myalgia and at specific points associated with fatigue and certain psychological adversities. Physical activity can mitigate the effects of the symptoms. However, the associations between fibromyalgia-related fatigue, self-esteem, anxiety, depression, satisfaction with life and physical activity are unclear. Therefore, the aim of the present study was to understand the associations between these symptoms and whether there are differences between these associations across two distinct cultures. Materials and Methods: A total of 473 women aged between 28 and 75 years (M = 49.27; SD ± 8.28) completed five questionnaires about fibromyalgia-related fatigue, physical activity, anxiety, depression, self-esteem, and satisfaction with life. Results: Fibromyalgia-related fatigue was positively associated with depression and anxiety, depression and anxiety were negatively associated with self-esteem, self-esteem was positively associated with satisfaction with life, satisfaction with life was positively associated with physical activity and there were no differences in terms of the perceptions and associations of these variables between Portuguese and Brazilian patients. Conclusions: Our results showed the significant role of associations between these variables and a similarity in the perception and relationship of the variables between the two cultures.

Differences between Portuguese and Brazilian Patients with Fibromyalgia Syndrome: Exploring the Associations across Age, Time of Diagnosis, and Fatigue-Related Symptoms.

Background and Objectives: The current literature demonstrates that different cultures have different perceptions of the symptoms of Fibromyalgia Syndrome (FM). The aim of the study was to explore the differences between Brazilian and Portuguese patients with FM in their fatigue experience and to measure the differences in the perception of fatigue according to age and duration of diagnosis. Materials and Methods: In total, 209 Portuguese women aged between 21 and 75 years old (M = 47.44; SD = 10.73) and 429 Brazilian women aged between 18 and 77 years old (M = 46.51; SD = 9.24) were recruited to participate in the present study. Participants filled out the items in the Multidimensional Daily Fatigue-Fibromyalgia-17 Diary (MDF-Fibro-17), a specific tool to measure the level of five components of FM-related fatigue. Results: The results showed a greater perception of all of the components of fatigue in the Brazilian sample. No significant differences were found related to the age and duration of FM diagnosis. Conclusions: Overall, there are significant differences in fatigue symptoms between Portuguese and Brazilian women with FM, suggesting that cultural and geographical differences should be considered when describing fatigue-related symptoms in women with FM.

Closing of large pharyngostomes with free flaps and proposal of a new classification.

PURPOSE: Large pharyngocutaneous fistulas or pharyngostomes are difficult complications to solve, which generate high morbidity and mortality, a poor quality of life and an increase in health costs. Its management must be comprehensive according to general, local and regional factors. We review our experience in treating these pharyngostomes with free flaps. METHODS: Retrospective study analyzing the results of the reconstruction of 50 patients using free flaps during the period 1991-2019. We exclude patients who required free-flap reconstruction due to primary tumor or those who resolved in other ways. The different types of reconstruction were classified into three types. RESULTS: The 86% (43) were men, and the mean age was 57 years (25-76). In 48% (24/50) the flaps performed were anterolateral thigh (ALT), in 24% (12/50) forearm, in 22% (11/50) parascapular, in 4% (2/50) jejunum and in 2% (1/50) ulnar. A salivary by-pass was placed in 74% (37/50) of the cases. Four cases (8%) presented flap necrosis and two patients died due to treatment. In 86% (43/50) there was some type of complication and 34% (17/50) required surgical revision. 94% (45/48) were able to reintroduce oral feeding. CONCLUSION: According to our experience, we proposed a regardless size classification: type 1 when only a mucous closure (pharynx) are required (6%), type 2 exclusively skin for cutaneous coverage (10%) and mixed type 3 (mucous and skin) (84%). The treatment of large pharyngostomes with free flaps, despite its complexity, is in our experience the best option for its management.

EGFR mutation and HPV infection in sinonasal inverted papilloma and squamous cell carcinoma.

BACKGROUND: To evaluate the involvement of EGFR signalling and HPV infection in a cohort of inverted sinonasal papilloma (ISP) and sinonasal squamous cell carcinoma (SNSCC) and their value for prognosis and clinical treatment. METHODS: We analysed 55 ISP, 14 SNSCC associated with ISP (SNSCC-isp) and and 60 SNSCC not associated with ISP (SNSCC-novo) for EGFR gene mutation and copy number gain, protein expression of EGFR and phosporylated EGFR (pEGFR), and HPV-infection and KRAS mutation. Findings were correlated to clinico-pathological and follow-up data. RESULTS: We found EGFR exon 20 mutations in 38% (7/18) ISP, in 50% (6/12) SNSCC-isp and in 5% (1/19) SNSCC-novo. EGFR was expressed in 92% of ISP, while pEGFR was observed in 54% (21/39). SNSCC-isp and SNSCC-novo demonstrated comparable expression of EGFR (57% and 33%) and of pEGFR (44% and 38%). We observed an inverse relation between EGFR exon 20 mutation and pEGFR expression. Four of 39 (10%) ISP carried HPV-16. Oncogenic HPV was detected in 3/12 (25%) SNSSC-isp and in 1/8 (13%) SNSCC-novo. KRAS mutations were not detected in any of the samples. HPV infection was inversely correlated with pEGFR expression but not with EGFR mutation. ISP with EGFR activation by mutation or by phosphorylation had longer ISP-free survival, however, neither EGFR exon 20 mutation, pEGFR expression nor HPV infection demonstrated prognostic value in SNSCC. CONCLUSIONS: EGFR exon 20 mutation is frequent in ISP and SNSCC-isp, while activation of EGFR through phosphorylation also plays an important role. Our data indicate that a large proportion of SNSCC patients could benefit from therapy with modern EGFR inhibitors.

Effects of strength training in fibromyalgia on balance, neuromuscular performance, and symptomatic analysis: a 12-week study protocol.

Fibromyalgia affects skeletal muscles presenting with muscle stiffness, pain, and fatigue. The exercise practice is wellstabilized and suggested for the reduction of symptoms. However, there are some gaps in the literature related to balance and neuromuscular performance in a strength training protocol. The aim of this study is to structure a protocol to verify the effects of strength training applied over a short period, on balance, neuromuscular performance, and fibromyalgia symptoms. Additionally, we intend to analyze the effects of a short period of cessation of training. Participants will be recruited through flyers, internet advertisements, clinical referrals, health professionals, and email outreach. Volunteers will be randomly assigned to the control group or experimental group. Before the training period, symptoms (Fibromyalgia Impact Questionnaire, Visual Analog Scale), balance (force plate), and neuromuscular performance (medicine ball throw and vertical jump) will be assessed. Participants in the experimental group will perform strength training twice a week (50 min each), on alternate days, for 8 weeks (16 sessions). Then, 4 weeks of detraining will be completed. This training program will be carried out online, using real-time videos, and the participants will be divided into two groups with different schedules. The Borg scale will be used to monitor perceived effort in each session. There is a gap in the literature about exercise prescriptions for fibromyalgia. The supervised online intervention enables a wide range of participation. The strength exercises used (without the use of external materials and/or machines) and load (few repetitions per set) represent a novelty to training programming. Moreover, this training program respects the limitations and individuality of the volunteers, providing exercise adaptations. With positive results, the present protocol could be an easy-to-apply guideline with clear instructions on the details related to exercise prescription. Also, ensure the effectiveness of a low-cost and feasible treatment, especially for fibromyalgia patients. Clinical trial registration: https://clinicaltrials.gov/, identifier: NCT05646641.

Exploring the Relationship between Fibromyalgia-Related Fatigue, Physical Activity, and Quality of Life.

The symptoms of fibromyalgia are varied, including general muscle pain and pain at specific points (also called tender points), excessive fatigue, anxiety, depression, and some psychological problems that can have a negative impact on quality of life. Physical activity is a widely used option by health professionals to alleviate the effects of this syndrome. However, there is no clear information on the possible mediating role of physical activity in the relationship between fibromyalgia-related fatigue and quality of life. Therefore, this study aims to evaluate the relationship between fibromyalgia-related fatigue and quality of life, and to investigate the mediating role of physical activity in patients with this syndrome. METHODS: In a cross-sectional study, 237 Portuguese women aged 28 to 75 years (M = 49.12; SD ± 8.87) and 117 Brazilian women aged 20 to 69 years (M = 46.72; SD ± 8.38) were recruited to participate in this study. These patients completed three valid and reliable questionnaires related to the assessment of fibromyalgia-related fatigue (MDF-Fibro-17), physical activity (IPAQ), and quality of life (SF-36). RESULTS: Both samples had scores above the midpoint for all dimensions of fibromyalgia-related fatigue and scores below the midpoint for quality of life. Physical activity had no mediating effect in either sample, as the total indirect effect was not significant. CONCLUSIONS: Physical activity does not mediate the relationship between fatigue and quality of life. However, the results also show that the fatigue dimensions associated with fibromyalgia had a negative and significant association with physical and mental health indicators in both samples. Thus, patients with FM with higher scores on fatigue-related symptoms might suffer more from physical and mental health, both of which are related to quality of life.

The Multidimensional Daily Diary of Fatigue-Fibromyalgia-17 Items (MDF-Fibro-17): Evidence from Validity, Reliability and Transcultural Invariance between Portugal and Brazil.

The Multidimensional Daily Diary of Fatigue-Fibromyalgia-17 (MDF-fibro-17) is an instrument that measures the different components of fibromyalgia-related fatigue symptoms. The current study aims to examine the factor structure of the MDF-fibro-17 in a sample of Portuguese and Brazilian patients diagnosed with fibromyalgia. Additionally, a cross-cultural analysis was carried out on these samples to understand the multidimensional complexity of examining the different dimensions of fatigue in patients with different cultural backgrounds and how fibromyalgia impacts patients with this syndrome. A confirmatory factor analysis was performed to examine the psychometric properties of the measure. Additionally, a multigroup analysis was carried out on the samples of these two cultures to examine measurement invariance. In total, 209 Portuguese women aged between 21 and 75 years (M = 47.44; SD = 10.73) and 429 Brazilians women aged between 16 and 77 years (M = 46.51; SD = 9.24) participated in this study. The results revealed that the measurement model provided an acceptable fit to the data in both the Portuguese and Brazilian samples, also displaying acceptable convergent and discriminant validity. In addition, the model showed acceptable internal consistency and was invariant between cultures. In sum, the MDF-fibro-17 is a valid measure that offers a unique assessment of fatigue symptoms in Portuguese and Brazilian women with fibromyalgia.

[Unusual cervical cyst. Adenocarcinoma ex-pleomorphic adenoma of a minor salivary gland]. / Quiste cervical inusual. adenocarcinoma ex-adenoma pleomorfo de glándula salival menor.

Cysts with an origin in a malignant tumour of the cervical region are rare. It is even more uncommon that the malignant tumour has its origin in a minor salivary gland as it is the malignant transformation of a pleomorphic adenoma. Some considerations are made regarding its localization, histopathology, diagnosis and therapeuthic attitude, as well as some advices to take into account in order to arrive to the diagnosis and correct treatment in similar cases to the one shown.

[Distant metastases in head and neck cancer]. / Metástasis a distancia en el cáncer de cabeza y cuello.

INTRODUCTION: The presence of distant metastasis (DM) after the initial treatment of head and neck squamous cell carcinoma (HNSCC) is not considered a common event and it is associated to a poor outcome. PURPOSE: To investigate the prevalence and risk factors associated with the diagnosis of distant metastasis in SCC. METHODS AND MATERIALS: A retrospective study of 633 patients with HNSCC to describe the clinical characteristics of the DM. RESULTS: During the follow-up period after the initial treatment, 6.2% of the patients were diagnosed of having distant metastasis. The site of primary tumor was hypopharynx in 14.4%, unknown origin in 11.8% and oropharynx in 8.5%. The most common sites of DM were the lungs (58%) and the bone (22%). Three year overall survival in patients with DM was 2.5% (versus 49,5% in the control group). CONCLUSIONS: This study confirms that DM have an adverse impact in survival. There is a need of guidelines for screening of distant metastases in patients with HNSCC in order to get an early diagnosis and a more effective treatment. Because of the poor prognosis of DM, protocols including adjuvant chemotherapy should be investigated.

[Second primary tumors in head and neck cancer]. / Segundos tumores primarios en el cáncer escamoso de cabeza y cuello.

INTRODUCTION: The development of second primary tumors (SPT) in patients with head and neck squamous cell carcinoma (HNSCC) has become an increasingly important factor in clinical treatment decisions. PURPOSE: To define favourable clinical characteristics for overall survival, in patients with SP head and neck cancer. MATERIAL AND METHOD: Records of 633 patients with SCC treated from 1984 to 2004 were reviewed to describe clinical characteristics of the SPT. RESULTS: The overall incidence of SPT was 11%. The incidence of the index tumors was as follows: supraglottic cancer 21% and oral cancer 16%. The most common SPT occurred in head and neck area in 47%, lung in 32% and esophagus in 11%. Second primary was associated with a poor 5 years survival in patients with HN-SCC (23 versus 53% in control group). CONCLUSION: Because of the high rate of second primary tumors, protocols including chemoprophylaxis should be investigated. Prevention and early detection are indicated.

[Otorhinolaryngological consultation material in PDA: SEORL-PDA]. / Material de Consulta de Otorrinolaringología en PDA: SEORL-PDA.

OBJECTIVES: Occasionally, the Otolaryngologist needs to accede quickly to medical information in order to retrieve data or to solve doubts. In this way, it seems to be of interest to design a clinical guide that could be consulted as a PDA program (Pocket PC and Palm versions), in a personal computer or Internet. MATERIAL AND METHODS: Clinical contents of protocols, guides, and articles, preferably based on the evidence and the clinical experience of 102 authors. Implementation of a program that allows the guide to be used in a PDA, to update it or to add notes using tools that could be downloaded from a web page. RESULTS: A clinical practice guide SEORL-PDA version 1.1, with thirteen ENT's topics, calculation algorithms, internal links and possibility of update the content and to add notes. DISCUSSION: SEORL-PDA is a clinical guide in PDA format, with enough information and possibilities. Its downloading and installation is easily done following the instructions of the web created with these purposes.

[Multimedia educational material. A tool of support to the Otolaryngology training]. / Material educativo multimedia. Una herramienta de apoyo a la enseñanza de la Otorrinolaringología.

Due to multimedia technologies, the medical information has taken an extraordinary growing. Nevertheless, the education at University will turn out to be a more complex pedagogic process. We present a multimedia educational material (MEM), developed as an online course to "Seminars of Otolaryngology", and available free at the University website. MEM was designed and edited by, ENT teachers, pedagogues, and image and computer experts. It has been structured as a series of modules that integrate texts, images, movie clips, video, audio and animations. The schematic presentation stands out with progressive access to the topics through internal and external links. The pedagogic resources give additional support by learning objectives, glossary, references, index and searcher. Finally, the activities and instrumental simulations complete the training in diagnosis and treatment. The MEM is an interactive useful software program for medical training in Otolaryngology, without avoiding the key figure of the teacher.

Circulating IgG response to stromelysin-3, collagenase-3, galectin-3 and mesothelin in patients with pharynx/larynx squamous cell carcinoma.

With the aim of identifying tumor-associated antigens that could be potential markers and/or targets of diagnostic and/or therapeutic approaches, we studied the occurrence of circulating IgG antibodies to human stromelysin-3, collagenase-3, galectin-3 and mesothelin, by Western blot against their purified recombinant forms, in the sera of 50 patients with pharynx/larynx squamous cell carcinoma (PLSCC), as well as in the sera of 50 healthy blood donors. Overall, antibodies to collagenase-3 were detected in 50% of all the cancer patients and 16% of the blood donors examined; this percentage difference was statistically significant (p = 0.00066). With respect to anti-galectin-3 antibodies, the percentages were 32% and 18%, respectively, but they were not statistically different (p = 0.16). Low levels of antibodies to stromelysin-3 and to mesothelin were detected in sera from only two cancer patients. No significant correlations were found in the present study between the presence of antibodies to these proteins and tumor site, clinical and T stages, lymph node involvement, DNA ploidy and histological grade of differentiation of the primary tumors. To our knowledge, this is the first report on the detection of circulating IgG to collagenase-3 in cancer patients. Some of the percentages found here in certain groups of patients are among the highest reported of circulating antibodies to any tumor component studied so far. The monitoring and the use of human antibodies to collagenase-3 could be of diagnostic and therapeutic interest.

[DNA ploidy and S phase in relation to metastases of pharyngolaryngeal epidermoid carcinoma]. / Ploidía de ADN y fase S en relación con las metástasis de los carcinomas epidermoides faringolaríngeos.

Lymph node metastases in pharyngolaryngeal squamous-cell carcinoma are the clinical finding that most precisely condition prognosis. Sometimes the presence of subclinical metastases modifies the initial therapeutic strategy because they are not detected by physical exploration or imaging techniques. We tried to establish a relationship between the tumor's intrinsic aggressiveness and the development of metastases through tumoral DNA damage. Aneuploidy and the S phase were more frequent in tumors of the larynx, particularly supraglottic tumors, that developed lymph node metastases (72%) than in diploid tumors with a normal S phase (18%). In pharyngeal tumors, no differences could be established because most were aneuploid with a high S phase and metastases. Flow cytometry is highly sensitive, but not sufficiently specific for routine clinical use. However, it is a useful point of departure for our line of research, which will continue with a search for more specific genetic or molecular markers of metastases among the general DNA abnormalities.

[Internal jugular thrombophlebitis: complications of the cervical oncological surgery. A case report]. / Tromboflebitis de la yugular interna: complicación de la cirugía oncológica cervical. Presentación de un caso.

Internal jugular vein thrombophlebitis is an infrequent complications, associated in the past to pharyngeal and amygdaline infections but related today to the use of catheters and intravenous drugs. The present paper reports the case of a patient who underwent total laryngectomy and functional neck dissection, developing recurrent neumonias and sepsis in the postoperative period which were secondary to an homolateral jugular thrombophlebitis. A physical exploration with no findings and the poor resolution of CT scan and ultrasound due to postsurgical alterations, lead to a late diagnosis and fatal evolution, in spite of the medical and surgical treatment.

[Follicular adenoma in lingual thyroid: report of a case]. / Adenoma folicular en tiroides lingual: a propósito de un caso.

We present a case of follicular adenoma which has its origin in a unique lingual thyroid. The interest lies in the oddity of this pathology and in the unusual clinical form of dysphagia. In spite of the fact that the thyroid ectopy is a congenital anomaly in the development of the thyroid, the history of previous administration of cervical radiotherapy and the diagnosis in an elderly person makes us suppose, in this case, that there is a different etiopathology.

[Epidermal growth factor receptor gene amplification and E-cadherin expression in head and neck carcinomas]. / Amplificación del gen del receptor del factor de crecimiento epidérmico y expresión de la E-cadherina en los carcinomas de cabeza y cuello.

INTRODUCTION: The E-cadherin adhesion molecule is fundamentally involved in the maintenance of normal epithelial morphology and differentiation. The scattering and invasion of cancer cells induced by epidermal growth factor receptor (EGFR) activation has been suggested to be probably by affecting E-cadherin function. The aim of this study is to confirm whether EGFR amplification is related to E-cadherin expression in head and neck squamous cell carcinomas. MATERIAL AND METHODS: Fifty patients with head and neck squamous cell carcinoma were studied. EGFR amplification was analyzed by semiquantitative PCR. E-cadherin expressión was determined by immunohistochemistry. RESULTS: EGFR amplification was found in 9 cases (18%). E-cadherin expression was generally weaker in tumors than in adjacent normal epithelium. No relationship was found between EGFR amplification and E-cadherin expression. CONCLUSION: EGFR amplification did not affect the level of E-cadherin expression, suggesting a complementary role of both of these molecules in reduction of cellular adhesion in head and neck squamous cell carcinomas.

[Clinico-histological scale for identifying preinvasive lesions of the larynx]. / Escala clínico-histológica en el pronóstico de las lesiones preinvasivas de laringe.

Preinvasive laryngeal lesions progress to infiltrating carcinoma in 7-15% of cases. Clinical manifestations and histological findings are not reliably predictive of progression. Quantitative cytometry improves predictive effectiveness, but is not a routine procedure. A clinico-histological scale consisting of 13 variables which were combined and used prospectively had a predictive value of 0.8 sensitivity and 0.9 specificity for progression of preinvasive laryngeal lesions.