Matrix-based molecular mechanisms, targeting and diagnostics in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a head and neck cancer (HNC) with a high mortality rate. OSCC is developed in the oral cavity and it is triggered by many etiologic factors and can metastasize both regionally and distantly. Recent research advances in OSCC improved our understanding on the molecular mechanisms involved in and the initiation of OSCC metastasis. The key roles of the extracellular matrix (ECM) in OSCC are an emerging area of intensive research as the ECM macromolecular network is actively involved in events that regulate cellular morphological and functional properties, transcription and cell signaling mechanisms in invasion and metastasis. The provisional matrix that is formed by cancer cells is profoundly different in composition and functions as compared with the matrix of normal tissue. Fibroblasts are mainly responsible for matrix production and remodeling, but in cancer, the tumor matrix in the tumor microenvironment (TME) also originates from cancer cells. Even though extensive research has been conducted on the role of ECM in regulating cancer pathogenesis, its role in modulating OSCC is less elucidated since there are several issues yet to be fully understood. This critical review is focused on recent research as to present and discuss on the involvement of ECM macromolecular effectors (i.e., proteoglycans, integrins, matrix metalloproteinases) in OSCC development and progression.

Insights into metastatic roadmap of head and neck cancer squamous cell carcinoma based on clinical, histopathological and molecular profiles.

The incidence of head and neck cancer (HNC), constituting approximately one in ten cancer cases worldwide, affects approximately 644,000 individuals annually. Managing this complex disease involves various treatment modalities such as systemic therapy, radiation, and surgery, particularly for patients with locally advanced disease. HNC treatment necessitates a multidisciplinary approach due to alterations in patients' genomes affecting their functionality. Predominantly, squamous cell carcinomas (SCCs), the majority of HNCs, arise from the upper aerodigestive tract epithelium. The epidemiology, staging, diagnosis, and management techniques of head and neck squamous cell carcinoma (HNSCC), encompassing clinical, image-based, histopathological and molecular profiling, have been extensively reviewed. Lymph node metastasis (LNM) is a well-known predictive factor for HNSCC that initiates metastasis and significantly impacts HNSCC prognosis. Distant metastasis (DM) in HNSCC has been correlated to aberrant expression of cancer cell-derived cytokines and growth factors triggering abnormal activation of several signaling pathways that boost cancer cell aggressiveness. Recent advances in genetic profiling, understanding tumor microenvironment, oligometastatic disease, and immunotherapy have revolutionized treatment strategies and disease control. Future research may leverage genomics and proteomics to identify biomarkers aiding individualized HNSCC treatment. Understanding the molecular basis, genetic landscape, atypical signaling pathways, and tumor microenvironment have enhanced the comprehension of HNSCC molecular etiology. This critical review sheds light on regional and distant metastases in HNSCC, presenting major clinical and laboratory features, predictive biomarkers, and available therapeutic approaches.

The interplay between tumor and nodal microenvironments for the formation of nodal premetastatic niche in head and neck cancer.

Head and neck cancer (HNC) encompasses a number of malignancies originating in the head and neck area. In patients with HNC, cervical lymph nodes constitute metastatic sites for cancer cells that escape primary tumors. The premetastatic niche (PMN) is a crucial concept in understanding metastatic disease. PMN refers to the microenvironment resulting mainly from primary tumor cells to foster metastatic tumor cell growth at a distant organ. Tumor microenvironment (TME) plays an important part in the pathogenesis of PMN. A significant prognostic factor is the close association between metastases of lymph nodes and organ dissemination in many different malignancies. The nodal premetastatic niche (NPMN) is a particular type of PMN located within the lymph nodes. NPMN formation is specifically important in HNC as regional lymph node metastasis commonly occurs. The formation happens when tumor cells create a supportive microenvironment within lymph nodes, facilitating their survival, growth, spread, and invasion. This complex mechanism involves multiple steps and cellular interactions between the primary tumor and tumor microenvironment. Several extracellular matrix (ECM) macromolecules, cytokines, and growth factors are implicated in this process. The aim of this article is to present the most recent data on the regulation of the lymph node PMN at molecular and cellular levels in HNC, as well as insights with respect to the relationship between primary tumor cells and the microenvironment of lymph nodes, and the formation of NPMN. We also critically discuss on potential targets for preventing or disrupting nodal metastases and identify potential biomarkers for predicting HNC outcomes.

Early detecting cervical necrotizing fasciitis from deep neck infections: a study of 550 patients.

PURPOSE: The aim of this retrospective review study is to evaluate Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score as an indicative parameter in early detecting cervical necrotizing fasciitis (CNF) from deep neck infections (DNI). METHODS: We reviewed 12 cases of CNF and 538 cases of non-necrotizing deep neck infection hospitalized in our hospital over the last decade. Cervical necrotizing fasciitis was histologically confirmed. RESULTS: Using an LRINEC score of 6 as a cutoff sensitivity was calculated at 100% (95% CI 99.9-100) and specificity 72.5% (95% CI 72.4-72.6). Negative predicted value (NPV) was 100% and positive predicted value (PPV) was 7.5%. C-reactive protein (CRP), white blood count (WBC), and glucose (Glu) levels have a higher correlation. Haemoglobin (Hb), sodium (Na), and creatinine (Cr) do not seem to have a big impact in our study. CONCLUSION: LRINEC score proves to be a useful "rule-out" tool that works on the safe side with high sensitivity and poor specificity. WBC, CRP, and Glu seem to be the most significant variables of the LRINEC score. Hb, Na, and Cr make the score safer. Decision for surgery must be based on medical history, clinical symptoms and signs, imaging findings, and laboratory tests and not according to the LRINEC score itself.

Gigantic paranasal sinuses osteomas: clinical features, management considerations, and long-term outcomes.

PURPOSE: Paranasal sinus osteomas are slow-growing, benign bony tumours that when larger than 30 mm, they are termed 'gigantic'. Special considerations apply for tumours of this calibre, and their rarity renders their management fairly controversial. This study seeks to contribute to an increased understanding concerning their management by presenting a 12-year experience from a single institution. METHODS: Retrospective review of files of patients treated for a gigantic paranasal sinus osteoma from January 2008 to December 2019. Additionally, all patients were prospectively reexamined in early 2020 for late complications or clinical recurrence. RESULTS: Ten patients were included, with a mean age of 53.8 years (range: 23-77 years). The leading presenting findings were proptosis (80%) and diplopia (70%). Transient visual impairment was remarkably frequent (30%). Five patients were managed with an open approach, two with an endoscopic, and three with a combined technique. The most common adverse characteristics that dictated the use of an open approach, alone or in combination with an endoscopic approach, were the involvement of the anterior wall of the frontal sinus (40%), erosion of its posterior wall (30%), and a far-anterior intraorbital extension (30%). No major postoperative complications were observed, and also no recurrences. CONCLUSION: Our study illustrates that these tumours may require a different management attitude. Despite substantial advances in the endoscopic management of benign sinonasal tumours, managing these massive tumours solely endoscopically could, in many cases, be inefficacious or impossible. Open approaches remain valuable, representing a safe and straightforward method for adequate exposure.

Cervical necrotizing fasciitis affects only immunocompromized patients? Diagnostic challenges, treatment outcomes and clinical management of eleven immunocompetent adult patients with a still fatal disease.

PURPOSE: Cervical Necrotizing fasciitis (CNF) has been reported as an unusual rapidly progressive, life-threatening, inflammatory disease that is known to affect predominately immunocompromised patients. Few case reports have been sporadically published involving immunocompetent adults. This is the first study presents a series of immunocompetent CNF patients. MATERIALS AND METHODS: A retrospective chart review study was performed on immunocompetent adults with CNF from January 2003 to December 2019. The diagnosis was histologically confirmed. We analyzed epidemiological, clinical, laboratory and imaging findings and discussed them along with the treatment plan. RESULTS: A total of eleven adult patients were included in the study. The average age was 43 years, ranging from 17 to 62 years. The average hospitalization time was 28 days, ranging from 10 to 129 days. All patients presented with cervical erythema and odynophagia. The causative factors are known in nine patients. Tissue cultures demonstrated mixed flora in six patients. Seven underwent a temporary tracheostomy. Wide neck exploration incisions were performed in all patients as the diagnosis was established after imaging findings. In nine cases the anterior-upper mediastinum was affected but only in two patients extension of the surgical planes to the mediastinum was performed. Four patients developed polyserositis. Nine patients survived and two developed multiorgan failure and died. CONCLUSION: There seem to be no differences between immunocompetent and immunocompromised CNF patients, in regards to clinical, imaging and laboratory findings as well as their treatment plan.

Short-Term Follow-Up of Self-Isolated COVID-19 Patients with Smell and Taste Dysfunction in Greece: Two Phenotypes of Recovery.

INTRODUCTION: The course of anosmia and ageusia in COVID-19 patients is not yet clearly known. We present short-term follow-up data concerning mild to moderate disease in home-quarantined COVID-19 patients in Greece. METHODS: We provided a symptom questionnaire and instructions for a self-administered home smell-and-taste test to 79 positive COVID-19 patients from 2 tertiary hospitals in Greece. The patients recorded their subjective symptoms before and during infection as well as 4 weeks after the diagnosis. The patients also underwent the home test during infection and 4 weeks later. RESULTS: Twenty-nine patients (36.7%) reported a loss of smell, and 21 (27.8%) reported a loss of taste, with equal prevalences between genders. We observed 2 types of recovery, i.e., a rapid, almost complete recovery, and a second slower and partial recovery. The type of recovery was not age related. A rapid recovery was observed in two thirds of the patients, with their olfactory ratings presenting a trend towards significance in correlation with nasal obstruction. A slow recovery in olfaction was correlated with low intensity ratings in odors with a trigeminal compound. The loss of taste was more pronounced in sweet and salty intensity ratings. CONCLUSION: Chemosensory deficits associated with COVID-19 infection were quite frequent among the Greek patients with mild or moderate disease who, in most cases, returned to normal within 4 weeks. However, 1 in 3 patients presented with persistent olfactory and gustatory dysfunction in the short term.

Dysphagia Caused by Chronic Laryngeal Edema.

A rare case of a young female with chronic diffuse laryngeal edema causing severe swallowing difficulty is presented. The patient was previously treated with antibiotics and steroids with no improvement. Diagnosis was made with biopsy of the epiglottis under local anesthesia in the office.

Fiberoptic Endoscopic Evaluation of Swallowing Findings in Children With Rett Syndrome.

Feeding abnormalities, swallowing dysfunction, and gastrointestinal issues cause poor weight gain, oral motor dysfunction, and air swallowing in children with Rett syndrome (RTT). Pneumonia is the leading cause of death. Our study describes fiberoptic endoscopic swallowing findings in 11 female RTT children. Each patient was evaluated using the 8-point Penetration/Aspiration Scale (PAS). The average age was 7 years. All patients had tongue dyskinesis and prolonged oral stage. Eight girls exhibited liquid entering the airway without coughing, whereas 6 did well with pureed meal. Three girls had pneumonia. Age was not correlated with pneumonia episodes (P = .18). Pureed material was related with pneumonia (P = .006), whereas liquids were not. Pureed PAS was positively correlated with Liquid PAS (P = .008) and age (P = .004). All aspiration/penetration incidents occurred before the pharyngeal phase. No patient under 7 years experienced pneumonia episodes. Silent aspiration can occur early in infancy, although pneumonia episodes can occur later.

Holmium:YAG laser-assisted intraductal sialendoscopic lithotripsy under local anesthesia.

OBJECTIVES: This retrospective multi-institutional chart review study aims to present results from patients treated with Holmium:YAG laser-assisted sialendoscopic intraductal lithotripsy under local anesthesia. METHODS: Preoperative ultrasound and/or CT were used for location and measurement of the stones. Local anesthesia was applied in all patients, Marchal all-in- one 1.3 mm and Erlangen 1.6 sialendoscopes were used. The laser was used with power settings limited by discomfort or pain. Inclusion criteria were stone size (all >5 mm) and fixed stones. RESULTS: 42 patients, 48 stones were treated (30 males/12 females), 21 submandibular and 21 parotid. Ages ranged from 20 to 70 years (95 % CI: 43.37-51.58). Mean size was 6.2 mm (95 % CI: 5.71-6.72). Complete fragmentation was achieved in 66.7 % and incomplete in 33.3 %. Out of the incomplete fragmented 14 cases, seven (50 %) remained symptom free on follow-up. Maximum duration was 120 min. Minimum power settings of the laser was 4.8 Watts and maximum 18 Watts. Six patients expressed pain or discomfort that limited power increase and duration of the procedure. Total follow up time was 10 years. There were no major complications such as hemorrhage, nerve paresis or skin ulceration. CONCLUSION: The procedure is safe under local anesthesia, well tolerated by most patients and should be used in cases of small fixed and "intermediate-sized" stones as a single modality. Discomfort may limit power settings and duration. The later is the major disadvantage of the method.

Translation and Cross-Cultural Adaptation of the Thyroidectomy-Related Voice Questionnaire (TVSQ) in Greek Population.

OBJECTIVES: The Thyroidectomy-Related Voice Questionnaire (TVSQ) is a useful tool in the detection of voice changes and dysfunctions and the diagnosis of other symptoms related to transient or permanent laryngeal nerve damage in patients after thyroidectomy. The aim of our study is the translation and validation of (TVSQ) in the Greek language and in Greek population for the first time. METHODS: The TVSQ was translated from English to Greek and vice versa by two independent researchers, while before the application of the TVSQ in clinical practice, a control group of 20 people was used. The following methods were used for the weighting and analysis of the TVSQ: Polychoric correlation, Cronbach's alpha, confirmatory factor analysis, and item response theory (IRT). RESULTS: Polychoric correlations revealed that questions 1-10 have a strong positive correlation with each other, while the correlation of the rest of the TVSQ items is positive. Subsequently, for the first subgroup of questions ("voice change") Cronbach's alpha was equal to 0.950, while for the second ("throat and neck discomfort") Cronbach's alpha was equal to 0.846. Thus, we conclude that the internal consistency reliability is high for both subgroups of TVSQ questions. With the IRT method we showed that for the first subgroup of questions ("voice change"), the item with the least predictive value is question 5, while for the second subgroup of questions ("throat and neck discomfort"), the item with the least educational value was question 15. CONCLUSIONS: Our team translated and validated the TVSQ with the above statistical methods in the Greek language, so that it can be used as a valuable tool in clinical practice, and more specifically in patients undergoing thyroidectomy. TVSQ can play a significant role on the diagnosis of either postoperative voice disorders and other symptoms related to thyroidectomy.

Lymphoma presenting as preauricular tumor in unilateral parotid gland agenesis: a case report and review of literature.

BACKGROUND: Parotid gland agenesis is a rare, congenital, usually asymptomatic disorder. Until now, only 24 cases with unilateral, incidentally found, parotid gland agenesis have been described. Here, we present the first reported case of an ipsilateral preauricular neoplasm in a patient with unilateral parotid gland agenesis. During surgery, the position of the greater auricular- and facial nerves was documented. Furthermore, we performed the first sialendoscopy for this rare disorder to assess the number of duct branches, which might be indicative of the abundance of parotid tissue. Moreover, we looked for sialendoscopic characteristic features that could aid in identifying these patients in the ambulatory setting. CASE PRESENTATION: A 50-year-old Greek man presented with a painless, slowly enlarging mass in the right parotid space. Magnetic resonance imaging revealed a complete absence of the right parotid gland without accessory parotid tissue. The right parotid gland was replaced by fatty tissue and the radiologist suggested a benign parotid tumor. Fine needle aspiration was indicative of a reactive lymph node. Sialendoscopy revealed only two branches within the right parotid duct. Surgical resection was performed through a conventional lateral parotidectomy. This revealed typical anatomic position of the greater auricular- and facial nerves despite the parotid tissue agenesis. Histopathology revealed a small lymphocytic lymphoma. CONCLUSIONS: Surgeons should feel confident to resect tumors of the parotid space in patients with parotid gland agenesis. Reduced branching observed during sialendoscopy might indicate parotid gland agenesis. Physicians should be even more cautious than usual with the watch and wait strategy in patients with tumors of parotid gland agenesis, since the probability of a tumor being a benign salivary gland tumor might be lower than usual.

Unsupervised Screen Exposure and Poor Language Development: A Scoping Review to Assess Current Evidence and Suggest Priorities for Research.

Screen exposure has both negative and positive effects on the level of language skills a child acquires. The purpose of this review is to address current literature on the possible relationship between unsupervised screen exposure and language development in children and to provide recommendations to caregivers regarding screen exposure of children, taking into consideration the possible effects. A scoping review was conducted using the PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online) database. A total of 590 articles were retrieved and considered for inclusion. Twenty-one articles were finally included and reviewed with an emphasis on language, communication, and executive skills as well as cognitive development. The negative effects of screen exposure for children outweigh the positive effects. The largest number of studies demonstrate that unsupervised screen exposure may negatively impact a child's language usage and cognitive and executive skills, disrupt playtime, and affect the quality of sleep. On the other hand, supervised screen use is associated with improved language skills. More evidence is needed on unsupervised exposure in children to new types of screens. As technology could play a significant role in schools in the future, additional research is required to create educational media for schoolchildren with specific guidelines.

Neuroendocrine and undifferentiated sinonasal and skull base tumors: An up-to-date narrative review.

Tumors located in the nasal cavity, paranasal sinuses and the skull base comprise a wide range of histologic subtypes. Among them, neuroendocrine and undifferentiated tumors are rare but noteworthy, because of their distinctive features, aggressive nature, and diagnostic complexities. A literature search was conducted in the PubMed/MEDLINE and the Scopus databases from 2019 until inception. The keywords "neuroendocrine", "undifferentiated", "nose", "sinonasal", "paranasal", "skull base" were used. Thirty-eight articles referring to neuroendocrine and undifferentiated tumors of the nose, paranasal sinuses and the skull base were finally included and analyzed. Neuroendocrine and undifferentiated tumors of the nose, paranasal sinuses and the skull base are infrequent malignancies, most commonly affecting middle-aged men. They usually present with non-specific symptoms, even though ocular or neurologic manifestations may occur. Prognosis is generally poor; however, novel targeted and immunological therapies have shown promising results. Sinonasal Neuroendocrine Carcinomas (SNECs) carry distinct histological and immunohistochemical features. Management consists of surgical resection coupled with systematic therapy. Sinonasal Undifferentiated Carcinomas (SNUCs) lack specific squamous or glandular features. They typically stain positive for pancytokeratin and INI1 antibody. Treatment includes induction chemotherapy, followed by a combination of chemotherapy and radiotherapy. Olfactory neuroblastomas (ONBs) have neuroepithelial or neuroblastic features. They show diffuse positivity for various markers, including synaptophysin, chromogranin, and neuron-specific enolase (NSE). Surgical resection plus radiotherapy is considered the treatment of choice. In conclusion, neuroendocrine and undifferentiated tumors arising from the nose, paranasal sinuses and the skull base represent a unique group of malignancies. A thorough understanding of their clinical features, molecular changes, diagnostic approaches, treatment modalities, and prognostic factors is critical for providing optimal patient care. Still, continued research efforts and multidisciplinary collaboration are warranted, in order to improve outcomes for patients diagnosed with these rare and aggressive tumors.

A Systematic Review of Intracranial Complications in Adults with Pott Puffy Tumor over Four Decades.

The purpose of this study is to investigate the risk factors of intracranial complications in adult patients with Pott Puffy Tumor (PPT). A systematic review was conducted of clinical studies from January 1983 to December 2022 that reported on PPT adult patients. The full-text articles were reviewed for the patients' ages, sex, cultured organisms, surgical procedures, clinical sequalae, and underlying diseases that may affect the onset of intracranial complications in PPT adult patients. A total of 106 studies were included. Medical data were reviewed for 125 patients (94 males, 31 females). The median age was 45 years. A total of 52% had comorbidities, mostly head trauma (24.5%), sinus/neurosurgical operations (22.4%), immunosuppression conditions (13.3%), diabetes mellitus (9.1%), cocaine use (7.1%), or dental infections (6.1%). A total of 28 cultures revealed Streptococcus (22.4%), 24 contained staphylococci (19.2%), and 22 cultures contained other pathogens (17.6%). An amount of 30.4% developed intracranial complications, with the most common being epidural abscesses or empyemas (55.3%), as well as subdural (15.7%) and extradural lesions (13.2%). Age, DM, and immunosuppression conditions are significantly associated with intracranial complications (p < 0.001, p = 0.018 and p = 0.022, respectively). Streptococcus infection is associated with intracranial complications (p = 0.001), although Staphylococcus and other microorganisms are not. Surgical intervention, mainly ESS, and broad-spectrum antibiotics remain the cornerstones of treatment.

Sinonasal Neuroendocrine Carcinoma in Adult Proteus Syndrome.

Introduction: Proteus syndrome (PS) is a rare genetic disorder usually caused by mutations in AKT1 or PTEN genes, characterized by multiple, asymmetric tissue overgrowth with high clinical variability. Sinonasal neuroendocrine carcinomas (SNEC) are exceptionally rare tumors encountered in the ethmoid sinus, nasal cavity, or maxillary sinus. Case Report: We report a 35-year-old patient with PS, who underwent successful surgical removal of a well-differentiated SNEC obstructing his nasal cavity and highlight the role of the otolaryngologist for safe airway management, minimal surgical intervention and coordination of the multidisciplinary care. Histologically, focally hyperplastic mucosal epithelium of respiratory type of the nasal chamber was noticed along with seromucinous glands and capillary congestion of the subepithelial fibrovascular tissue. The limited presence of neoplastic tissue with histomorphological and immunophenotypic features of a neuroendocrine neoplasm was focally observed. Tumor cells grow in the form of islets within a vascular stroma; these neoplastic cells are immunohistochemically positive for synaptophysin, CD56, EMA, Ki67 (low expression, cell proliferation rate: 2%), CD31, chromogranin and pancytokeratin AE1 / AE3 as well as for S-100 protein (weak intensity). Conclusions: This first description of a SNEC in a PS patient, might hint towards a common basis between the two conditions, due to the mosaic AKT1 variant and an activated AKT/PIK3CA/PTEN pathway.

Pediatric Laryngopharyngeal Reflux in the Last Decade: What Is New and Where to Next?

BACKGROUND: Laryngopharyngeal reflux may affect people of any age; still, most of the accumulated knowledge concerns adults, and evidence regarding pediatric populations remains relatively restricted. This study aims to review the most recent and emerging aspects of pediatric laryngopharyngeal reflux from the last ten years. It also attempts to identify gaps in knowledge and highlight discrepancies that future research should urgently address. METHODS: An electronic search of the MEDLINE database was conducted, limited to January 2012 through December 2021. Non-English language articles, case reports, and studies that concerned a purely or predominantly adult population were excluded. The information from the articles with the most relevant contribution was initially categorized by theme and subsequently synthesized into a narrative form. RESULTS: 86 articles were included, of which 27 were review articles, eight were surveys, and 51 were original articles. Our review systematically maps the research done in the last decade and provides an updated overview and the current state-of-the-art in this subject. CONCLUSIONS: Despite discrepancies and heterogeneity in accumulating research, evidence gathered so far endorses a need for refining an escalating multiparameter diagnostic approach. A step-wise therapeutic plan appears to be the most reasonable management approach, starting with behavioral changes for mild to moderate, uncomplicated cases and escalating to personalized pharmacotherapy options for severe or nonresponsive cases. Surgical options could be considered in the most severe cases when potentially life-threatening symptoms persist despite maximal medical therapy. Over the past decade, the amount of available evidence has been gradually increasing; however, its strength remains low. Several aspects remain markedly under-addressed, and further adequately powered, multicenter, controlled studies with uniformity in diagnostic procedures and criteria are urgently needed.

The Role of Exosomes in Epithelial-to-Mesenchymal Transition and Cell Functional Properties in Head and Neck Cancer.

Exosomes are nanosized vesicles that are produced in normal and cancer cells, promoting intracellular communication. In head and neck cancer (HNC), exosomes are involved in many undesirable events of cancer development and progression, including angiogenesis, tumor microenvironment (TME) remodeling, invasion, epithelial-to-mesenchymal transition (EMT), metastasis, extracellular matrix (ECM) degradation, and drug resistance. Exosomes are involved in altering the signaling pathways in recipient cells by the cargoes they carry. Proteins, lipids, and nucleic acids such as DNA fragments and RNAs (i.e., mRNAs, miRNAs, and long non-coding RNAs) are carried in the exosomes to promote cell communication. EMT is a critical cellular process in which epithelial cells are forced to become mesenchymal cells by the actions of SNAIL/SLUG, TWIST, and ZEB family transcription factors carried in exosomes that facilitate metastasis. In this critical review, we focused on exosome biogenesis, their cargoes, and their involvement in EMT induction and metastasis during HNC. Insights into exosome isolation and characterization, as well as their key role in ECM remodeling and degradation, are also presented and critically discussed. More importantly, this article addresses the role of exosomes in HNC and drug resistance induced in drug-sensitive cancer cells. In addition, exosomes have a great potential to be used as diagnostic and therapeutic tools. A better understanding on exosome biogenesis, composition, and functions in HNC will aid in developing novel therapeutic strategies to treat HNC, overcome therapy resistance, and avoid metastasis, which is a significant cause of cancer death.

Conservative Otosclerosis Treatment With Sodium Fluoride and Other Modern Formulations: A Systematic Review.

Otosclerosis, also known as otospongiosis, is a primary osteodystrophy of the otic capsule of the inner ear and one of the leading causes of deafness in adults. The rationale for medical therapy for otospongiosis is to slow down and eventually stop the phase of bone resorption. Conservative treatments include sodium fluoride (NaF), bisphosphonates, and other modern medicines. A systematic review of the existing and published articles and books until April 2021 has been conducted in Medscape, Google Scholar, PubMed, and other databases using appropriate terms. According to the results of the research, the administration of NaF for a period of at least six months stabilizes hearing thresholds (HTs), improves vestibular symptoms, and delays the worsening of tinnitus. The administration of bisphosphonates for a period of at least six months showed significant percentage differences in the improvement of hearing loss, dizziness, and tinnitus remission. In the already existing double-blind studies that were evaluated, groups of patients treated with bisphosphonates for at least 24 months showed greater stabilization of the mean air and bone conduction thresholds than groups of patients treated with a placebo. The new modern medications have not yet been widely administered clinically to draw useful conclusions, although the test results of some of their use are quite encouraging.

Phase II Window Study of Olaparib Alone or with Cisplatin or Durvalumab in Operable Head and Neck Cancer.

Purpose: We conducted a phase II randomized noncomparative window of opportunity (WOO) trial to evaluate the inhibition of cellular proliferation and the modulation of immune microenvironment after treatment with olaparib alone or in combination with cisplatin or durvalumab in patients with operable head and neck squamous cell carcinoma (HNSCC). Experimental Design: Forty-one patients with HNSCC were randomized to cisplatin plus olaparib (arm A), olaparib alone (arm B), no treatment (arm C) or durvalumab plus olaparib (arm D). The primary endpoint was to evaluate the percentage of patients in each arm that achieved a reduction of at least 25% in Ki67. Secondary endpoints included objective response rate (ORR), safety, and pathologic complete response (pCR) rate. Paired baseline and resection tumor biopsies and blood samples were evaluated for prespecified biomarkers. Results: A decrease in Ki67 of at least 25% was observed in 44.8% of treated patients, as measured by quantitative immunofluorescence. The ORR among treated patients was 12.1%. pCR was observed in 2 patients. Two serious adverse events occurred in 2 patients.Programmed death ligand 1 (PD-L1) levels [combined positive score (CPS)] were significantly higher after treatment in arms A and D. Expression of CD163 and colony-stimulating factor 1 receptor (CSF1R) genes, markers of M2 macrophages, increased significantly posttreatment whereas the expression of CD80, a marker of M1 macrophages, decreased. Conclusion: Preoperative olaparib with cisplatin or alone or with durvalumab was safe in the preoperative setting and led to decrease in Ki67 of at least 25% in 44.8% of treated patients. Olaparib-based treatment modulates the tumor microenvironment leading to upregulation of PD-L1 and induction of protumor features of macrophages. Significance: HNSCC is characterized by defective DNA repair pathways and immunosuppressive tumor microenvironment. PARP inhibitors, which promote DNA damage and "reset" the inflammatory tumor microenvironment, can establish an effective antitumor response. This phase II WOO trial in HNSCC demonstrated the immunomodulatory effects of PARP inhibitor-induced DNA damage. In this chemo-naïve population, PARP inhibitor-based treatment, reduced tumor cell proliferation and modulated tumor microenvironment. After olaparib upregulation of PD-L1 and macrophages, suggests that combinatorial treatment might be beneficial. Synopsis: Our WOO study demonstrates that preoperative olaparib results in a reduction in Ki67, upregulation of PD-L1 CPS, and induction of protumor features of macrophages in HNSCC.