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Item does not contain fulltext The projected increase in life expectancy over the next few decades is expected to result in a rise in age-related diseases, including cancer. Head and neck cancer (HNC) is a worldwide health problem with high rates of morbidity and mortality. In this report, we have critically reviewed the literature reporting the management of older patients with HNC. Older adults are more prone to complications and toxicities secondary to HNC treatment, especially those patients who are frail or have comorbidities. Thus, this population should be screened prior to treatment for such predispositions to maximize medical management of comorbidities. Chronologic age itself is not a reason for choosing less intensive treatment for older HNC patients. Whenever possible, also older patients should be treated according to the best standard of care, as nonstandard approaches may result in increased treatment failure rates and mortality. The treatment plan is best established by a multidisciplinary tumor board with shared decision-making with patients and family. Treatment modifications should be considered for those patients who have severe comorbidities, evidence of frailty (low performance status), or low performance status or those who refuse the recommendations of the tumor board.

Abstract The difficulty of getting a correct distribution of the reinforcement in the metal matrix and the complexity for achieving a good-metallurgy matrix-reinforcement bonding has limited the development of additive manufacturing of metal matrix composites. This research proposes the use of a reactive atmosphere during the fabrication process to obtain titanium matrix composites reinforced with TiN. The relation between the carrying gas and the process parameters used with the presence of porous and defects, the microstructure, and microhardness has been obtained. Nitrogen was used as the carrying gas of the titanium powder. Under laser irradiation, the particles melt and react with nitrogen, resulting in the formation of a titanium matrix composite highly reinforced with TiN. The composite obtained had a microhardness increase between 50 and 100% in comparison with titanium samples fabricated in the same conditions in an argon atmosphere. Three reaction mechanisms have been proposed to take place in the microstructure, depending on the amount of nitrogen in the titanium particles, and its diffusion in them during the manufacture. Graphic abstract

Nowadays, research on additive manufacturing of Ti6Al4V alloy is growing exponentially but there are just a few studies about additive manufacturing of metal matrix composite components. In this work, highly reinforced Ti6Al4V matrix composites with SiC particles have been additively manufactured by direct laser deposition (DLD). Ti6Al4V powder and SiC particles have been deposited layer by layer to form an additive thin wall structure. The geometry, microstructure, and microhardness of the samples are strongly influenced by the laser scanning speed used during de fabrication process. In addition, the effect of the SiC increment in reinforcement concentrations and the influence of SiC particle sizes in the microstructure have been evaluated, and the reaction mechanisms have been established. The percentage of reinforcement measured is lower than expected due to the reinforcement-matrix reactivity that results in partially dissolved SiC particles and the formation of a TiC and Si5Ti3 ring around them. The size and number of particles and reaction products depend on the initial size and percentage of reinforcement and the DLD scanning speed. The higher the size and percentage of SiC particles and reaction products in the matrix, the higher the hardening effect of the composite matrix. Graphic Abstract

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The TINCR (Terminal differentiation-Induced Non-Coding RNA) gene is selectively expressed in epithelium tissues and is involved in the control of human epidermal differentiation and wound healing. Despite its initial report as a long non-coding RNA, the TINCR locus codes for a highly conserved ubiquitin-like microprotein associated with keratinocyte differentiation. Here we report the identification of TINCR as a tumor suppressor in squamous cell carcinoma (SCC). TINCR is upregulated by UV-induced DNA damage in a TP53-dependent manner in human keratinocytes. Decreased TINCR protein expression is prevalently found in skin and head and neck squamous cell tumors and TINCR expression suppresses the growth of SCC cells in vitro and in vivo. Consistently, Tincr knockout mice show accelerated tumor development following UVB skin carcinogenesis and increased penetrance of invasive SCCs. Finally, genetic analyses identify loss-of-function mutations and deletions encompassing the TINCR gene in SCC clinical samples supporting a tumor suppressor role in human cancer. Altogether, these results demonstrate a role for TINCR as protein coding tumor suppressor gene recurrently lost in squamous cell carcinomas.

Head and neck squamous cell carcinomas (HNSCCs) arising in the mucosal linings of the upper aerodigestive tract are highly heterogeneous, aggressive, and multifactorial tumors affecting more than half a million patients worldwide each year. Classical etiological factors for HNSCC include alcohol, tobacco, and human papillomavirus (HPV) infection. Current treatment options for HNSCCs encompass surgery, radiotherapy, chemotherapy, or combinatorial remedies. Comprehensive integrative genomic analysis of HNSCC has identified mutations in TP53 gene as the most frequent of all somatic genomic alterations. TP53 mutations are associated with either loss of wild-type p53 function or gain of functions that promote invasion, metastasis, genomic instability, and cancer cell proliferation. Interestingly, disruptive TP53 mutations in tumor DNA are associated with aggressiveness and reduced survival after surgical treatment of HNSCC. This review summarizes the current evidence and impact of TP53 mutations in HNSCC.

Introduction Nasopharyngeal carcinoma (NPC) is endemic to Eastern and South-Eastern Asia, and, in 2020, 77% of global cases were diagnosed in these regions. Apart from its distinct epidemiology, the natural behavior, treatment, and prognosis are different from other head and neck cancers. With the growing trend of artificial intelligence (AI), especially deep learning (DL), in head and neck cancer care, we sought to explore the unique clinical application and implementation direction of AI in the management of NPC. Methods The search protocol was performed to collect publications using AI, machine learning (ML) and DL in NPC management from PubMed, Scopus and Embase. The articles were filtered using inclusion and exclusion criteria, and the quality of the papers was assessed. Data were extracted from the finalized articles. Results A total of 78 articles were reviewed after removing duplicates and papers that did not meet the inclusion and exclusion criteria. After quality assessment, 60 papers were included in the current study. There were four main types of applications, which were auto-contouring, diagnosis, prognosis, and miscellaneous applications (especially on radiotherapy planning). The different forms of convolutional neural networks (CNNs) accounted for the majority of DL algorithms used, while the artificial neural network (ANN) was the most frequent ML model implemented. Conclusion There is an overall positive impact identified from AI implementation in the management of NPC. With improving AI algorithms, we envisage AI will be available as a routine application in a clinical setting soon.

Contains fulltext : 273922.pdf (Publisher’s version ) (Closed access) Benign peripheral non-cranial nerve sheath tumors are rare lesions, including both schwannomas and neurofibromas. These tumors arise from Schwann cells, and may originate from any peripheral, cranial, or autonomic nerve. Most of them are localized and sporadic but multifocal systemic forms can occur. Cervical sympathetic chain, brachial plexus, cervical plexus and spinal roots and nerves are the major nerve systems commonly affected. Dumbbell-shaped intra- and extradural tumors occur most commonly in the cervical spine, as well as purely extradural and paravertebral tumors. The management of these tumors has improved greatly owing to the developments in imaging techniques and surgical innovations such as endoscopically assisted approaches and robotic surgery. Microsurgical intracapsular excision of the tumor helped by the use of intraoperative fluorescent dyes and intraoperative neurophysiological monitoring minimize postoperative neural deficit, since most schwannomas are encapsulated. Most tumors can be removed with a low rate of complications and recurrence. Radiotherapy should be considered for growing lesions that are not amenable to surgery. In asymptomatic patients, observation and serial scans is an option for elderly infirm patients.

Contains fulltext : 290876.pdf (Publisher’s version ) (Open Access) Inadequate resection margins in head and neck squamous cell carcinoma surgery necessitate adjuvant therapies such as re-resection and radiotherapy with or without chemotherapy and imply increasing morbidity and worse prognosis. On the other hand, taking larger margins by extending the resection also leads to avoidable increased morbidity. Oropharyngeal squamous cell carcinomas (OPSCCs) are often difficult to access; resections are limited by anatomy and functionality and thus carry an increased risk for close or positive margins. Therefore, there is a need to improve intraoperative assessment of resection margins. Several intraoperative techniques are available, but these often lead to prolonged operative time and are only suitable for a subgroup of patients. In recent years, new diagnostic tools have been the subject of investigation. This study reviews the available literature on intraoperative techniques to improve resection margins for OPSCCs. A literature search was performed in Embase, PubMed, and Cochrane. Narrow band imaging (NBI), high-resolution microendoscopic imaging, confocal laser endomicroscopy, frozen section analysis (FSA), ultrasound (US), computed tomography scan (CT), (auto) fluorescence imaging (FI), and augmented reality (AR) have all been used for OPSCC. NBI, FSA, and US are most commonly used and increase the rate of negative margins. Other techniques will become available in the future, of which fluorescence imaging has high potential for use with OPSCC.

Most cases of thyroid carcinoma are classified as low risk. These lesions have been treated with open surgery, remote access thyroidectomy, active surveillance, and percutaneous ablation. However, there is lack of consensus and clear indications for a specific treatment selection. The objective of this study is to review the literature regarding the indications for management selection for low-risk carcinomas. Systematic review exploring inclusion and exclusion criteria used to select patients with low-risk carcinomas for treatment approaches. The search found 69 studies. The inclusion criteria most reported were nodule diameter and histopathological confirmation of the tumor type. The most common exclusions were lymph node metastasis and extra-thyroidal extension. There was significant heterogeneity among inclusion and exclusion criteria according to the analyzed therapeutic approach. Alternative therapeutic approaches in low-risk carcinomas can be cautiously considered. Open thyroidectomy remains the standard treatment against which all other approaches must be compared.

Genetic, symptomatic, and biochemical heterogeneity of patients with primary hyperparathyroidism (PHPT) has become apparent in recent years. An in-depth, evidence-based review of the phenotypes of PHPT was conducted. This review was intended to provide the resulting information to surgeons who operate on patients with hyperparathyroidism. This review revealed that the once relatively clear distinction between familial and sporadic PHPT has become more challenging by the finding of various germline mutations in patients with seemingly sporadic PHPT. On the one hand, the genetic and clinical characteristics of some syndromes in which PHPT is an important component are now better understood. On the other hand, knowledge is emerging about novel syndromes, such as the rare multiple endocrine neoplasia type IV (MEN4), in which PHPT occurs frequently. It also revealed that, currently, the classical array of symptoms of PHPT is seen rarely upon initial presentation for evaluation. More common are nonspecific, nonclassical symptoms and signs of PHPT. In areas of the world where serum calcium levels are checked routinely, most patients today are "asymptomatic" and they are diagnosed after an incidental finding of hypercalcemia; however, some of them have subclinical involvement of bones and kidneys, which is demonstrated on radiographs, ultrasound, and modern imaging techniques. Last, the review points out that there are three distinct biochemical phenotypes of PHPT. The classical phenotype in which calcium and parathyroid hormone levels are both elevated, and other disease presentations in which the serum levels of calcium or intact parathyroid hormone are normal. Today several, distinct phenotypes of the disease can be identified, and they have implications in the diagnostic evaluation and treatment of patients, as well as possible screening of relatives.

Allograft survival of deceased donor kidneys with suboptimal histology (DRTx/suboptimal histology: >10% glomerulosclerosis, >10% tubulointerstitial scarring, or >mild vascular sclerosis) is inferior to both DRTx with optimal histology (DRTx/optimal histology) and living donor kidneys irrespective of histologic changes (LRTx). In this report, we explored the reasons behind this guarded outcome with a special focus on the role of alloimmunity. We initially assessed gene expression in 39 time-zero allograft biopsies using the Nanostring 770 genes PanCancer Immune Profiling Panel. Subsequently, we studied 696 consecutive adult kidney allograft recipients that were grouped according to allograft type and histology at time-zero biopsy [DRTx/suboptimal histology (n = 194), DRTx/optimal histology (n = 166), and LRTx (n = 336)]. Part-1: Several immune pathways were upregulated in time-zero biopsies from DRTx/suboptimal histology (n = 11) compared to LRTx (n = 17) but not to DRTx/optimal histology (n = 11). Part-2: Amongst the three groups of recipients, DRTx/suboptimal histology had the highest incidence of acute rejection episodes, most of which occurred during the first year after transplantation (early rejection). This increase was mainly attributed to T cell mediated rejection, while the incidence of antibody-mediated rejection was similar amongst the three groups. Importantly, early acute T cell mediated rejection was a strong independent predictor for allograft failure in DRTx/suboptimal histology (adjusted HR: 2.13, P = 0.005) but not in DRTx/optimal histology nor in LRTx. Our data highlight an increased baseline immunogenicity in DRTx/suboptimal histology compared to LRTx but not to DRTx/optimal histology. However, our results suggest that donor chronic histologic changes in DRTx may help transfer such increased baseline immunogenicity into clinically relevant acute rejection episodes that have detrimental effects on allograft survival. These findings may provide a rationale for enhanced immunosuppression in recipients of DRTx with baseline chronic histologic changes to minimize subsequent acute rejection and to prolong allograft survival.

Hurthle cell carcinoma (HCC) comprises about 5% of thyroid carcinoma cases. Partly because of its rarity there is much we still need to know about HCC as compared to other histological cancer subtypes. We conducted a systematic literature review following PRISMA guidelines and meta-analysis, from 2000 to 2020, to investigate the main characteristics of HCC and clarify information concerning tumor behavior and treatment. Our review included data from 9638 patients reported in 27 articles over the past 20 years. This tumor occurred more frequently in women (67.5%). The mean age was 57.6 years, and the mean size of the neoplasm at diagnosis was 30 mm. Extrathyroidal extension was common (24%) but lymph node metastasis was not (9%). Total thyroidectomy was the most common surgical approach, with neck dissection usually performed in cases with clinically apparent positive neck nodes. Radioiodine therapy was frequently applied (54%), although there is no consensus about its benefits. The mean 5- and 10-year overall survival was 91% and 76%, respectively. This review serves to further elucidate the main characteristics of this malignancy. HCC of the thyroid is rare and most often presents with a relatively large nodule, whereas lymph node metastases are rare. Given the rarity of HCC, a consensus on their treatment is needed, as doubts remain concerning the role of specific tumor findings and their influence on management.

Introduction: Nasopharyngeal carcinoma (NPC) is an endemic malignancy in Southeast Asia, particularly Southern China. The classical non-keratinising cell type is almost unanimously associated with latent Epstein-Barr virus (EBV) infection. Circulating plasma EBV DNA can be a useful biomarker in various clinical aspects, but comprehensive recommendations and international guidelines are still lacking. We conducted a systematic review of all original articles on the clinical application of plasma EBV DNA for NPC; we further evaluated its strengths and limitations for consideration as standard recommendations. Methods: The search terms 'nasopharyngeal OR nasopharynx', and 'plasma EBV DNA OR cell-free EBV OR cfEBV' were used to identify full-length articles published up to December 2020 in the English literature. Three authors independently reviewed the article titles, removed duplicates and reviewed the remaining articles for eligibility. Results: A total of 81 articles met the eligibility criteria. Based on the levels of evidence and grades of recommendation assessed, it is worth considering the inclusion of plasma EBV DNA in screening, pre-treatment work-up for enhancing prognostication and tailoring of treatment strategy, monitoring during radical treatment, post-treatment surveillance for early detection of relapse, and monitoring during salvage treatment for recurrent or metastatic NPC. One major limitation is the methodology of measurement requiring harmonisation for consistent comparability. Conclusions: The current comprehensive review supports the inclusion of plasma EBV DNA in international guidelines in the clinical aspects listed, but methodological issues must be resolved before global application. 2021 Elsevier Ltd. All rights reserved.

The inherent variability in performing specific surgical procedures for head and neck cancer remains a barrier for accurately assessing treatment outcomes, particularly in clinical trials. While non-surgical modalities for cancer therapeutics have evolved to become far more uniform, there remains the challenge to standardize surgery. The purpose of this review is to identify the barriers in achieving uniformity and to highlight efforts by surgical groups to standardize selected operations and nomenclature. While further improvements in standardization will remain a challenge, we must encourage surgical groups to focus on strategies that provide such a level.

Patients with advanced laryngeal and hypopharyngeal cancer are often treated with chemo-radiotherapy to avoid total laryngectomy. Subclinical swallowing disorders could be present in these patients even though patients do not complain of any symptoms. We sought to evaluate the impact of chemoradiation on swallowing and quality of life. We studied 21 patients undergoing chemo-radiotherapy for advanced laryngeal and hypopharyngeal cancer. All patients were tumor-free and none reported symptoms related to dysphagia during follow-up or showed altered routine screening tests (EAT-10) to detect it. Swallowing functions were assessed using volume–viscosity swallow test (V–VST) and fiberoptic endoscopic evaluation of swallowing (FEES). Quality of life was assessed with the EORT-H&N35, and SWAL-QOL scales. Frequent alterations in swallowing efficacy (100%) and safety (85.5%) were detected with V–VST and FEES. Quality-of-life scales showed a reduction in their scores between 12 and 17%, mainly in the areas of symptoms. Swallowing disorders are common after chemo-radiotherapy, even in patients who do not clinically manifest these disorders, contributing to a decrease in patients' quality of life. FEES and V–VST are useful procedures to detect asymptomatic swallowing disorders.

This study aimed to investigate the clinical and prognostic relevance of the Hippo-YAP transactivators YAP1 and TAZ in oral squamous cell carcinoma, and their possible relationship with PI3K/mTOR pathway activation.Immunohistochemical analysis of YAP1, TAZ, PIK3CA (p110α), p-AKT (Ser473), and p-S6 (Ser235) was performed in paraffin-embedded tissue specimens from 165 OSCC patients. Correlations between protein expression and clinical data were further assessed.YAP1 expression was detected in both cytoplasm and nucleus of tumor cells, whereas TAZ expression was only found in the nucleus. Nuclear YAP1 was significantly associated with tumor size (p = 0.03), neck lymph node metastasis (p = 0.02), TNM stage (p = 0.02), and poor differentiation (p = 0.04). Nuclear TAZ was associated with tobacco (p = 0.03) and alcohol consumption (p = 0.04), and poor tumor differentiation (p = 0.04). There was a positive significant correlation between nuclear and cytoplasmic YAP1, nuclear TAZ, p110α expression, and mTORC1 activation p-S6 (S235). Combined expression of nuclear and cytoplasmic YAP1 was prognostic in both univariate and multivariate analyses. Active nuclear YAP1 was significantly and independently associated with poor disease-specific (p = 0.005, HR = 2.520; 95% CI = 1.319-4.816) and overall survival (p = 0.015, HR = 2.126; 95% CI = 1.155-3.916).Nuclear YAP1 is an independent predictor of poor survival in oral squamous cell carcinoma.

Vascular perfusion research has been dedicated to identify inexpensive, effective, and easy to use methods to assess free flap perfusion for both buried and non-buried flaps.Systematic review of complications in patients underwent Head and Neck microsurgical reconstruction and vascular implantable Doppler monitoring.Sixteen articles were included for qualitative analysis. 2535 (92.2%) patients received IDP monitorization. Venous thrombosis was the most common vascular complication effecting 28 (1.1%). Regarding complications potentially related to the use of the IDP, just one study described the presence of granuloma formation along the suture line in 2 (0.07%) patients.Our findings indicated that Cook-Swartz IDP will represents a safe and effective device for FF monitoring in HN reconstructive micro-surgery. A detailed prospective registration of the results and complications related to the use of IDP remains mandatory to precisely estimate results, cost, and complications.

Introduction The factors that influence deceased donor kidney procurement biopsy reliability are not well established. We examined the impact of biopsy technique and pathologist training on procurement biopsy accuracy. Methods We retrospectively identified all deceased donor kidney-only transplants at our center from 2006 to 2016 with both procurement and reperfusion biopsies performed and information available on procurement biopsy technique and pathologist (n = 392). Biopsies were scored using a previously validated system, classifying “suboptimal” histology as the presence of at least 1 of the following: glomerulosclerosis ≥11%, moderate/severe interstitial fibrosis/tubular atrophy, or moderate/severe vascular disease. We calculated relative risk ratios (RRR) to determine the influence of technique (core vs. wedge) and pathologist (renal vs. nonrenal) on concordance between procurement and reperfusion biopsy histologic classification. Results A total of 171 (44%) procurement biopsies used wedge technique, and 221 (56%) used core technique. Results of only 36 biopsies (9%) were interpreted by renal pathologists. Correlation between procurement and reperfusion glomerulosclerosis was poor for both wedge (r2 = 0.11) and core (r2 = 0.14) biopsies. Overall, 34% of kidneys had discordant classification on procurement versus reperfusion biopsy. Neither biopsy technique nor pathologist training was associated with concordance between procurement and reperfusion histology, but a larger number of sampled glomeruli was associated with a higher likelihood of concordance (adjusted RRR = 1.12 per 10 glomeruli, 95% confidence interval = 1.04−1.22). Conclusions Biopsy technique and pathologist training were not associated with procurement biopsy histologic accuracy in this retrospective study. Prospective trials are needed to determine how to optimize procurement biopsy practices., Graphical abstract

Introduction and objectives dysfunction of the E-cadherin/catenin complex is directly related to carcinogenesis and metastases development. The aim of this paper is to investigate the prognostic significance of E-cadherin and β-catenin expression in surgically treated laryngeal and hypopharyngeal squamous cell carcinomas. Material and methods Tumour tissue samples were obtained from 133 consecutive patients with squamous cell carcinomas of the head and neck: 68 of the larynx and 65 hypopharyngeal carcinomas, who underwent surgical treatment in our hospital between 2000 and 2005. E-cadherin and β-catenin expression was analysed by immunohistochemistry, quantifying the percentage of stained cells and the intensity of staining. Results E-cadherin and β-catenin expression was evaluable in 59 laryngeal carcinomas and in 58 cases of hypopharyngeal carcinomas. In the laryngeal tumours, a significant association was found between the low expression of membrane β-catenin with T4 tumours and tumour recurrence. In the hypopharynx there was a significant association between positive expression of nuclear β-catenin and poor histological differentiation (P = .02). In the multivariate analysis, only the presence of lymph node metastases was an independent predictive factor of decreased disease-specific survival in laryngeal squamous cell carcinomas. Conclusions The expression of E-cadherin and β-catenin does not show prognostic significance in laryngeal and hypopharyngeal squamous cell carcinomas over the TNM classification.

Resumen Introduccion y objetivos La disfuncion del complejo E-cadherina/catenina esta relacionada directamente con la carcinogenesis y el desarrollo de metastasis. El objetivo de este trabajo es investigar el significado pronostico de la expresion de E-cadherina y β-catenina en carcinomas de celulas escamosas de laringe e hipofaringe tratados quirurgicamente. Material y metodos Se obtuvieron muestras de tejido tumoral de 133 pacientes consecutivos con carcinomas escamosos de cabeza y cuello (68 de laringe y 65 carcinomas de hipofaringe), que fueron sometidos a tratamiento quirurgico en nuestro hospital entre 2000 y 2005. La expresion de E-cadherina y β-catenina se analizo mediante inmunohistoquimica, cuantificando el porcentaje de celulas tenidas y la intensidad de la tincion. Resultados La expresion de E-cadherina y β-catenina fue evaluable en 59 muestras de carcinomas de laringe y en 58 de hipofaringe. En tumores de laringe se observo una asociacion significativa entre la baja expresion de β-catenina de membrana y tumores avanzados T4 y la recidiva tumoral. A nivel de hipofaringe se encontro una asociacion significativa de la expresion positiva de β-catenina nuclear con pobre diferenciacion histologica (p = 0,02). En el analisis multivariante solo la presencia de metastasis ganglionares era factor predictor independiente de disminucion de la supervivencia especifica para enfermedad en carcinoma de celulas escamosas de laringe. Conclusiones La expresion de E-cadherina y β-catenina no parece tener utilidad pronostica superior al TNM en los carcinomas epidermoides de laringe e hipofaringe.

INTRODUCTION: Aggressive variants of papillary thyroid cancer (PTC) have been described with increasing frequency. These variants include diffuse sclerosing variant, tall cell variant, columnar cell variant, solid variant, and hobnail variant. METHODS: We have performed a review of the more aggressive variants of PTC with respect to main characteristics, histological and molecular features, and the consequences that the knowledge of these variants should have in the treatment of the patients. RESULTS: At the present time, we do not know the prognostic value of these aggressive PTC variants. The extent of the surgical treatment and adjuvant therapy necessary should be decided on the basis of the extent of the tumor at presentation and the opinion of experienced clinicians. CONCLUSION: These aggressive variants should be known by clinicians, to avoid underdiagnosis, and treated according to the latest recommendations in the literature. ispartof: ADVANCES IN THERAPY vol:37 issue:7 pages:3112-3128 ispartof: location:United States status: published

The as-cast Mg–3Zn–0.4Ca alloy shows a great potential to be used in biomedical applications due to its composition, mechanical properties and biodegradability. Zn and Ca appear naturally in the organism accomplishing vital functions. The alloy consists of an α-Mg matrix and a eutectic composed of α-Mg + Ca2Mg6Zn3. The eutectic product enhances the mechanical properties of the studied alloy, causing strengthening and providing superior hardness values. In this alloy, cracks initiate at the intermetallic compounds and progress through the matrix because of the open network formed by the eutectics. Attending to the corrosion results, the eutectic product presents a noble potential compared to the α-Mg phase. For this reason, the corrosion progresses preferentially through the matrix, avoiding the (α-Mg + Ca2Mg6Zn3) eutectic product, when the alloy is in direct contact to Hank's solution.

The importance of immune tumor microenvironment in the prognosis of patients with head and neck squamous carcinomas (HNSCC) is increasingly recognized. We analyzed the prognostic relevance of PD-L1 and PD-1 expressions in relation to the infiltration by CD8+ and FOXP3+ tumor-infiltrating lymphocytes (TILs). Samples from 372 surgically treated HPV-negative HNSCC patients were evaluated by immunohistochemistry for PD-L1 expression [both tumor proportion score (TPS) and combined proportion score (CPS)], PD-1 expression in immune cells, and density of infiltrating CD8+ and FOXP3+ TILs. PD-L1 expression and CD8+ TIL density were combined to establish the type of tumor microenvironment. 29.5% cases exhibited PD-L1 TPS positivity (≥ 1%), whereas PD-L1 CPS positivity (≥ 1%) was observed in 40% cases. 47.5% cases showed positive PD-1 expression (≥ 1%). PD-L1 and PD-1 positivity correlated with a high density of both CD8+ and FOXP3+ TILs. In univariate analysis, PD-L1 TPS positivity (P = 0.026), PD-L1 CPS positivity (P = 0.004), high density of CD8+ TIL (P = 0.001), and high density of FOXP3+ TIL (P = 0.004) were associated with a better disease-specific survival (DSS). However, in multivariate analysis, only high density of CD8+ TIL was associated with a better DSS (P = 0.002). The type of tumor microenvironment correlated with DSS (P = .008), with the better DSS observed in cases with type I (PD-L1 CPS positivity and high density of CD8+ TIL). High infiltration by CD8+ TIL is associated with better survival outcomes. Positive PD-L1 expression correlates with a high infiltration by TILs, explaining its association with better prognosis.

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. 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. 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. 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.

Chemotherapy has been the basis of advanced cancer treatment for decades. This therapy has largely been considered immunosuppressive, yet accumulated preclinical and clinical evidence shows that certain chemotherapeutic drugs, under defined conditions, may stimulate antitumor immunity and potentiate immune checkpoint inhibitor (ICI)-based therapy. Its effectiveness has been highlighted by recent regulatory approvals of various combinations of chemotherapy with ICIs in several tumors, particularly in some difficult-to-treat cancers. This review discusses the immune modulatory properties of chemotherapy and how they may be harnessed to develop novel chemo-immunotherapy combinations. It also highlights the key determinants of the success of chemo-immunotherapy and provides an overview of the combined chemo-immunotherapies that have been clinically approved.

Introduccion: La ulcera por presion mas frecuente es la sacra. Si compromete el hueso puede provocar osteomielitis por lo que requiere aseo quirurgico y colgajo miocutaneo de Gluteus Maximus por deslizamiento en V-Y. Material y metodo: En el servicio de cirugia plastica del hospital del Salvador entre 2011 y 2020 se han operado 82 pacientes con ulceras sacras grado 4 que requirieron cobertura con colgajo miocutaneo de gluteus maximus en V-Y. De ellas se analizaron los ultimos 37 pacientes. Resultados: De los 37 pacientes, 12 fueron mujeres, 25 hombres, 17 paraplejicos, 12 tetraplejicos, y 8 deambulaban. 6 pacientes presentaron Covid-19. 24 fueron bilaterales y 13 unilaterales. Los colgajos cicatrizaron bien en 30 pacientes. Las complicaciones fueron de 16% consistente en 2 hematomas, 2 dehiscencias, 2 celulitis, y 1 seroma, todas resueltas sin problemas. Seguimiento de entre 3 y 6 meses. Discusion: El tratamiento quirurgico con colgajo miocutaneo de gluteus maximus en V-Y, aparte de aportar volumen para ocluir la ulcera, aporta irrigacion excelente con oxigeno, nutrientes y antibioticos que aseguran una optima cicatrizacion. Dependiendo del diametro de la ulcera el colgajo puede ser uni o bilateral. Dado lo complejo del tratamiento, en general, el porcentaje de complicaciones de 16% se considera bajo. Conclusion ; El tratamiento quirurgico de las ulceras por presion sacras con colgajos miocutaneos deslizantes de Gluteus Maximus ha sido exitoso con buenos resultados quirurgicos con buen flujo sanguineo y buena evolucion.

Contains fulltext : 251733.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Patients with head and neck cancer (HNC) are usually confronted with functional changes due to the malignancy itself or its treatment. These factors typically affect important structures involved in speech, breathing, chewing, swallowing, and saliva production. Consequently, the intake of food will be limited, which further contributes to loss of body weight and muscle mass, anorexia, malnutrition, fatigue, and anemia. This multifactorial condition can ultimately lead to cancer cachexia syndrome. This study aims to examine the treatment of cachexia in HNC patients. METHODS: We systematically searched OvidMedline, PubMed, Scopus, and Web of Science for articles examining the treatment of cachexia in HNC. RESULTS: A total of nine studies were found, and these suggested interventions including nutritional, pharmacologic, therapeutic exercise, and multimodal approaches. The nutritional intervention includes essential components such as dietary counseling, oral nutritional supplements, and medical nutritional support. Individualized nutritional interventions include oral, enteral (feeding tubes i.e., percutaneous endoscopic gastrostomy [PEG], nasogastric tube [NGT]) and parenteral nutrition. The pharmacologic interventions aim at increasing the appetite and weight of cachectic patients. Therapeutic exercise and increased physical activity can help to enhance the synthesis of muscle protein, reducing inflammation and the catabolic effects of cachexia syndrome. CONCLUSION: Owing to the multifactorial nature of this syndrome, it is expected that the management approach should be multi-interventional. Early implementation of these interventions may help to improve survival and quality of health and life of cachectic HNC patients.

Contains fulltext : 251734.pdf (Publisher’s version ) (Open Access) In head and neck cancer (HNC) there is a need for more personalized treatment based on risk assessment for treatment related adverse events (i.e. toxicities and complications), expected survival and quality of life. Sarcopenia, defined as a condition characterized by loss of skeletal muscle mass and function, can predict adverse outcomes in HNC patients. A review of the literature on the measurement of sarcopenia in head and neck cancer patients and its association with frailty was performed. Skeletal muscle mass (SMM) measurement only is often used to determine if sarcopenia is present or not. SMM is most often assessed by measuring skeletal muscle cross-sectional area on CT or MRI at the level of the third lumbar vertebra. As abdominal scans are not always available in HNC patients, measurement of SMM at the third cervical vertebra has been developed and is frequently used. Frailty is often defined as an age-related cumulative decline across multiple physiologic systems, with impaired homeostatic reserve and a reduced capacity of the organism to withstand stress, leading to increased risk of adverse health outcomes. There is no international standard measure of frailty and there are multiple measures of frailty. Both sarcopenia and frailty can predict adverse outcomes and can be used to identify vulnerable patients, select treatment options, adjust treatments, improve patient counselling, improve preoperative nutritional status and anticipate early on complications, length of hospital stay and discharge. Depending on the definitions used for sarcopenia and frailty, there is more or less overlap between both conditions. However, it has yet to be determined if sarcopenia and frailty can be used interchangeably or that they have additional value and should be used in combination to optimize individualized treatment in HNC patients.

El nuevo coronavirus (SARS-CoV-2) apareció en China en diciembre de 2019. Desde su inicio hasta abril de 2020 se ha expandido por todo el mundo, afectando a más de tres millones de personas. Su ascenso exponencial sigue creciendo, generando miles de muertes. Su contagiosidad es persona a persona por gotitas, pudiendo llegar a generar un cuadro clínico de infección respiratoria conocido como COVID-19. Algunos pacientes tienen más riesgos de tener un curso desfavorable; adultos mayores, pacientes con enfermedad cardiovascular, hipertensos y diabéticos. Nuestros pacientes con enfermedad inflamatoria intestinal son un grupo de pacientes con características particulares, muchos de ellos reciben tratamiento inmunosupresor por largos períodos, lo que pudiese suponer un riesgo específico. Las sociedades científicas de Europa y Norteamérica han realizado un esfuerzo conjunto para generar datos, compartir experiencias y dictar recomendaciones de buen manejo clínico. Esta es una revisión de la evidencia disponible, opiniones de expertos y formas de trabajo propuestos durante la pandemia.

Additive manufacturing has revolutionized the manufacturing industry. Researchers have investigated various techniques for increasing the reliability of the metal Additive Manufacturing processes. However, there are few studies about Additive Manufacturing of metal matrix composite components, so, it is necessary increase the research about this topic. In situ Al/AlN composite was synthesized using Direct Laser Deposition equipment in which aluminum powder was deposited through a laser beam using N2 as carrying and reactive gas. This composite powder has been melted and directly deposited layer by layer to form an additive structure. The effect of the laser parameters on the geometry, microstructure and properties of the fabricated structures have been analysed. This allowed the development of a process map for Al and Al/AlN pieces fabricated by Direct Laser Deposition. In situ Al/AlN samples have higher mechanical properties than Al samples.

Resumen Introduccion y objetivos El tratamiento principal de los carcinomas diferenciados de tiroides es la cirugia seguida de radioyodo. El proposito de este estudio es exponer nuestra experiencia en el manejo de estos tumores. Material y metodo Se presenta un estudio retrospectivo de los 55 pacientes intervenidos quirurgicamente de un carcinoma diferenciado de tiroides en nuestro hospital entre los anos 2007 y 2011. Resultados La edad media al diagnostico fue de 49 anos, con un predominio femenino (78% de los casos). El 78% de los pacientes se encontraban en fases iniciales (estadios i y ii ). El diagnostico histopatologico definitivo fue de carcinoma papilar en el 84% y folicular en el 16% restante. A todos, salvo a 2 pacientes (4%), se les realizo una tiroidectomia total, acompanada de linfadenectomia en el 58% de los casos. Un 9% de los pacientes presento hipoparatiroidismo permanente y aunque un 18% sufrio paralisis recurrencial unilateral transitoria, un 40% de ellos se recupero completamente a los 6 meses. Se administro radioyodo en el postoperatorio al 89% de los pacientes. Se produjo un 40% de recidivas, la mayor parte de las cuales (29% de los pacientes) se localizaron a nivel cervical. La supervivencia a los 5 anos fue del 87%, siendo del 95% en el subtipo papilar y descendiendo al 56% en el folicular (p = 0,001). Discusion/conclusiones Los carcinomas diferenciados de tiroides son tumores con un pronostico excelente tras un tratamiento quirurgico adecuado previa valoracion preoperatoria exhaustiva y seguimiento postoperatorio estricto debido a las tasas significativas de recidiva.

Objective The objective was to determine the results of the treatment of severe and/or refractory epistaxis requiring hospital admission. In addition, the results of arterial ligation versus embolisation were compared. Material and method Sixty-three patients with severe and/or refractory epistaxis requiring hospital admission between August 2014 and December 2016 were included prospectively. Results Eleven patients (17%) underwent embolisation, 5 (8%) endoscopy ligation and the remaining 47 (75%) underwent conservative treatment with tamponade. The mean age of the patients in which conservative measures were sufficient was 72 years, while the age of those treated with embolisation was 71 years and of those who underwent surgery was 53 years. For the patients who underwent conservative treatment or surgery, the average stay was 6 days, compared to 9 days for those who underwent embolisation. One patient suffered a hemispheric stroke after embolisation. No post-surgical complications were observed. Conclusions Most cases of severe and/or refractory epistaxis are resolved by conventional tamponade. Endoscopy ligation is associated with a decrease in hospital stay, without serious complications. It is advisable to have all the possible therapeutic options available, for which the presence of interventional radiologists and experienced surgeons is essential to avoid complications and decide the treatment to be performed individually for each patient.

Resumen Introduccion y objetivos El objetivo fue determinar los resultados del tratamiento de las epistaxis graves y/o refractarias que requirieron ingreso hospitalario. Ademas se compararon los resultados del tratamiento mediante ligadura arterial o embolizacion. Material y metodo Se incluyeron de forma prospectiva 63 pacientes con epistaxis grave y/o refractaria que requirieron ingreso hospitalario entre agosto de 2014 y diciembre de 2016. Resultados En 11 pacientes (17%) se realizo embolizacion, 5 (8%) fueron intervenidos mediante endoscopia y en los 47 restantes (75%) se realizo tratamiento conservador. La edad media de los pacientes en los que las medidas conservadoras fueron suficientes fue de 72 anos, mientras que la edad de aquellos tratados con embolizacion fue de 71 anos y de los que fueron intervenidos quirurgicamente fue de 53 anos. En los pacientes sometidos a tratamiento conservador o a cirugia la estancia media fue de 6 dias, frente a 9 dias en aquellos en los que se realizo embolizacion. Un paciente sufrio un ictus hemisferico tras la embolizacion. No se observaron complicaciones posquirurgicas. Conclusiones La mayoria de los pacientes con epistaxis graves y/o refractarias se resuelven mediante taponamiento convencional. El tratamiento mediante ligadura arterial esta asociado a una disminucion de la estancia hospitalaria, sin observarse complicaciones graves. Es aconsejable disponer de todas las opciones terapeuticas posibles para lo cual la presencia de radiologos intervencionistas y cirujanos experimentados es fundamental para evitar complicaciones y decidir el tratamiento a realizar de forma individual en cada paciente.

Activation of WNT/β-catenin signaling has been associated with a non-T-cell-inflamed tumor microenvironment (TME) in several cancers. The aim of this work was to investigate the relationship between β-catenin signaling and TME inflammation in head and neck squamous cell carcinomas (HNSCCs). Membrane and nuclear β-catenin expression, PD-L1 expression, and CD8+ tumor-infiltrating lymphocyte (TIL) density were jointly evaluated by immunohistochemistry in a series of 372 HPV-negative HNSCCs. Membrane β-catenin levels decreased in carcinomas compared to the normal epithelium. Positive nuclear β-catenin was detected in 50 tumors (14.3%) and was significantly associated with a low CD8+ TIL density (168 cells/mm2 versus 293 cells/mm2 in nuclear-β-catenin-negative cases; p = 0.01) and a tendency for a lower expression of PD-L1, resulting in association with a noninflamed TME (i.e., type II, immunological ignorance). Multivariate Cox analysis further demonstrated that low infiltration by CD8+ TILs (HR = 1.6, 95% CI = 1.19–2.14, p = 0.002) and nuclear β-catenin expression (HR = 1.47, 95% CI = 1.01–2.16, p = 0.04) were both independently associated with a poorer disease-specific survival. In conclusion, tumor-intrinsic nuclear β-catenin activation is associated with a non-inflamed TME phenotype and a poorer prognosis, thereby suggesting a possible implication as an immune exclusion mechanism for a subset of HNSCC patients.

Hürthle cell carcinoma (HCC) comprises about 5% of thyroid carcinoma cases. Partly because of its rarity there is much we still need to know about HCC as compared to other histological cancer subtypes.We conducted a systematic literature review following PRISMA guidelines and meta-analysis, from 2000 to 2020, to investigate the main characteristics of HCC and clarify information concerning tumor behavior and treatment.Our review included data from 9638 patients reported in 27 articles over the past 20 years. This tumor occurred more frequently in women (67.5%). The mean age was 57.6 years, and the mean size of the neoplasm at diagnosis was 30 mm. Extrathyroidal extension was common (24%) but lymph node metastasis was not (9%). Total thyroidectomy was the most common surgical approach, with neck dissection usually performed in cases with clinically apparent positive neck nodes. Radioiodine therapy was frequently applied (54%), although there is no consensus about its benefits. The mean 5- and 10-year overall survival was 91% and 76%, respectively.This review serves to further elucidate the main characteristics of this malignancy. HCC of the thyroid is rare and most often presents with a relatively large nodule, whereas lymph node metastases are rare. Given the rarity of HCC, a consensus on their treatment is needed, as doubts remain concerning the role of specific tumor findings and their influence on management.

Carotid blowout syndrome (CBS) is defined as a rupture of common carotid artery or its branches. Endovascular intervention has been advocated as first line of treatment for CBS. This Case Report describes 5 patients with prior history of head and neck cancer who presented with CBS. Two patients presented as acute, 2 as impending, and one as threatened CBS. The lesions found were pseudoaneurysm and focal vascular irregularities involving the common carotid artery, cervical internal carotid artery and lingual artery. Embolization and occlusion with detachable coils of the artery was used in all patients. Technical success and immediate hemostasis were achieved in all patients. One patient presented transient cranial nerve palsy. No recurrent CBS was reported during the follow-up. In our experience, coil embolization, if possible, is a safe and efficient technique in treatment of CBS secondary to head and neck cancers.

Tonsillectomy performed on an outpatient basis in adult patients presents bleeding and pain as main postoperative complications. Following rules such as cold surgical technique, analgesic protocols, preoperative interview, and postoperative follow-up help to better control the process. However, there are patient-dependent factors such as sex, age, indication for tonsillectomy and the time elapsed between the last tonsil infection and surgical intervention that can influence postoperative complications and should be considered. The objective of this work is to evaluate the influence of age, sex, the indication for tonsillectomy and the period elapsed between the last tonsil infection and surgery on bleeding and pain control.A prospective, descriptive, and observational study was carried out in 96 adult patients who underwent outpatient surgery under general anaesthesia, using cold surgical technique, evaluating these complications based on age, sex, indication for tonsillectomy and time elapsed after the last tonsillitis.The patients operated on during the 4 weeks after an episode of tonsillitis presented more postoperative pain. No relationship was found between this period and postoperative bleeding.Male patients had a higher incidence of bleeding than women. The period elapsed between the last tonsil infection and the surgical procedure was associated with greater postoperative pain, but not with greater postoperative bleeding.

The past decade has seen growing interest in marine natural pigments for biotechnological applications. One of the most abundant classes of biological pigments is the tetrapyrroles, which are prized targets due their photodynamic properties, porphyrins are the best known examples of this group. Many animal porphyrinoids and other tetrapyrroles are produced through heme metabolic pathways, the best known of which are the bile pigments biliverdin and bilirubin. Eulalia is a marine Polychaeta characterized by its bright green coloration resulting from a remarkably wide range of greenish and yellowish tetrapyrroles, some of which have promising photodynamic properties. The present study combined metabolomics based on HPLC-DAD with RNA-seq transcriptomics to investigate the molecular pathways of porphyrinoid metabolism by comparing the worm’s proboscis and epidermis, which display distinct pigmentation patterns. The results showed that pigments are endogenous and seemingly heme-derived. The worm possesses homologs in both organs for genes encoding enzymes involved in heme metabolism such as ALAD, FECH, UROS, and PPOX. However, the findings also indicate that variants of the canonical enzymes of the heme biosynthesis pathway can be species- and organ-specific. These differences between molecular networks contribute to explain not only the differential pigmentation patterns between organs, but also the worm’s variety of novel endogenous tetrapyrrolic compounds.