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Immunotherapy has a crucial role in the treatment of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, only a small percentage of patients achieve long-term benefit in terms of overall response and survival. It was shown that HNSCC has an immunosuppressive microenvironment due to high levels of regulatory T cells and immunosuppressive molecules, such as LAG3 and CD73. The aim of our study was to investigate if the expression of CD73 by neoplastic and immune cells could affect the efficacy of anti-PD-1 immunotherapy. We reviewed data from 50 patients with R/M HNSCC receiving first line immunotherapy with or without chemotherapy based on a combined positive score (CPS). CD73 expression by cancer and immune cells was evaluated on pre-treatment and the percentage of stained cells was recorded. We analysed the association between CD73 expression on neoplastic and immune cells and early progression (EP), defined as progression occurring within 3 months. In 88â¯% of patients the primary tumour site was in the oral cavity or larynx. All patients received pembrolizumab associated in 40â¯% of cases to chemotherapy. CD73 was positive in 82â¯% and 96â¯% of cases on neoplastic and immune cells, respectively. The median value of CD73 was 32â¯% for neoplastic cells and 10â¯% for the immune ones. We observed a significant association between the CD73 expression on neoplastic cells over the median value and EP disease. We didn't record a correlation between the expression of CD73 on immune cells and early progression. Our findings suggest that higher expression of CD73 on neoplastic cells could predict resistance to immunotherapy in patients with CPS positive R/M HNSCC. The addition of this biomarker to routine evaluation of CPS could help to select the patients primary resistant to anti-PD-1 immunotherapy.
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5'-Nucleotidase , Neoplasias de Cabeça e Pescoço , Imunoterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Idoso , Imunoterapia/métodos , 5'-Nucleotidase/metabolismo , Adulto , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Proteínas Ligadas por GPI/metabolismo , Proteínas Ligadas por GPI/análise , Microambiente Tumoral/imunologia , Idoso de 80 Anos ou mais , Inibidores de Checkpoint Imunológico/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Radical prostatectomy (RP) is recommended in case of localized or locally advanced prostate cancer (PCa), but it can lead to side effects, including urinary incontinence (UI) and erectile dysfunction (ED). Magnetic resonance imaging (MRI) is recommended for PCa diagnosis and staging, but it can also improve preoperative risk-stratification. PURPOSE: This nonsystematic review aims to provide an overview on factors involved in RP side effects, highlighting anatomical and pathological aspects that could be included in a structured report. EVIDENCE SYNTHESIS: Considering UI evaluation, MR can investigate membranous urethra length (MUL), prostate volume, the urethral sphincter complex, and the presence of prostate median lobe. Longer MUL measurement based on MRI is linked to a higher likelihood of achieving continence restoration. For ED assessment, MRI and diffusion tensor imaging identify the neurovascular bundle and they can aid in surgery planning. Finally, MRI can precisely describe extra-prostatic extension, prostate apex characteristics and lymph-node involvement, providing valuable preoperative information for PCa treatment. CONCLUSIONS: Anatomical principals structures involved in RP side effects can be assessed with MR. A standardized MR report detailing these structures could assist urologists in planning optimal and tailored surgical techniques, reducing complications, and improving patients' care.
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Disfunção Erétil , Imageamento por Ressonância Magnética , Prostatectomia , Neoplasias da Próstata , Incontinência Urinária , Humanos , Masculino , Prostatectomia/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/diagnóstico por imagem , Incontinência Urinária/diagnóstico por imagem , Incontinência Urinária/etiologia , Incontinência Urinária/prevenção & controle , Disfunção Erétil/etiologia , Disfunção Erétil/diagnóstico por imagem , Disfunção Erétil/prevenção & controle , Cuidados Pré-Operatórios/métodosRESUMO
PURPOSE: Otology and neuro-otology surgeries pose significant challenges due to the intricate and variable anatomy of the temporal bone (TB), requiring extensive training. In the last years 3D-printed temporal bone models for otological dissection are becoming increasingly popular. In this study, we presented a new 3D-printed temporal bone model named 'SAPIENS', tailored for educational and surgical simulation purposes. METHODS: The 'SAPIENS' model was a collaborative effort involving a multidisciplinary team, including radiologists, software engineers, ENT specialists, and 3D-printing experts. The development process spanned from June 2022 to October 2023 at the Department of Sense Organs, Sapienza University of Rome. Acquisition of human temporal bone images; temporal bone rendering; 3D-printing; post-printing phase; 3D-printed temporal bone model dissection and validation. RESULTS: The 'SAPIENS' 3D-printed temporal bone model demonstrated a high level of anatomical accuracy, resembling the human temporal bone in both middle and inner ear anatomy. The questionnaire-based assessment by five experienced ENT surgeons yielded an average total score of 49.4 ± 1.8 out of 61, indicating a model highly similar to the human TB for both anatomy and dissection. Specific areas of excellence included external contour, sigmoid sinus contour, cortical mastoidectomy simulation, and its utility as a surgical practice simulator. CONCLUSION: We have designed and developed a 3D model of the temporal bone that closely resembles the human temporal bone. This model enables the surgical dissection of the middle ear and mastoid with an excellent degree of similarity to the dissection performed on cadaveric temporal bones.
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BACKGROUND: The KEYNOTE-048 trial showed that pembrolizumab-based first-line treatment for R/M HNSCC led to improved OS in the PD-L1 CPS ≥ 1 population when compared to the EXTREME regimen. However, the R/M HNSCC real-world population is generally frailer, often presenting with multiple comorbidities, worse performance status and older age than the population included in phase III clinical trials. METHODS: This is a retrospective, single-centre analysis of patients with R/M HNSCC treated with pembrolizumab-based first-line treatment. RESULTS: From February 2021 to March 2023, 92 patients were treated with pembrolizumab-based first-line treatment. Patients treated with pembrolizumab-based chemoimmunotherapy had better ECOG PS and younger age than those treated with pembrolizumab monotherapy. Median PFS and OS were 4 months and 8 months, respectively. PFS was similar among patients treated with pembrolizumab-based chemoimmunotherapy and pembrolizumab monotherapy, while patients treated with pembrolizumab monotherapy had worse OS (log-rank p =.001, HR 2.7). PFS and OS were improved in patients with PD-L1 CPS > = 20 (PFS: log-rank p =.005, HR 0.50; OS: log-rank p =.04, HR 0.57). Patients with higher ECOG PS scores had worse PFS and OS (PFS, log-rank p =.004; OS, log-rank p = 6e-04). In multivariable analysis, ECOG PS2 was associated with worse PFS and OS. CONCLUSIONS: PFS in our real-world cohort was similar to the KEYNOTE-048 reference while OS was numerically inferior. A deeper understanding of clinical variables that might affect survival outcomes of patients with R/M HNSCC beyond ECOG PS and PD-L1 CPS is urgently needed.
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Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Antígeno B7-H1 , Estudos Retrospectivos , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/induzido quimicamenteRESUMO
BACKGROUND AND INTRODUCTION: Lung cancer is a prevalent and deadly disease globally. Non-small cell lung cancer (NSCLC) is the most common subtype, comprising 85% of cases. CASE REPORT: A 65-year-old male ex-smoker presented to our facility with a nocturnal cough. Various investigations revealed that he had metastatic NSCLC, for which he underwent chemotherapy with cisplatin and gemcitabine, followed by immunotherapy with Nivolumab. He achieved a complete response to the therapy and has remained free from recurrence for over 7 years since the initial diagnosis. DISCUSSION AND CONCLUSIONS: The treatment of metastatic NSCLC remains a significant therapeutic challenge, but the implementation of new therapeutic techniques has expanded the possibilities of achieving complete and durable eradication of the disease.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Masculino , Humanos , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Intervalo Livre de Doença , Nivolumabe/uso terapêutico , ImunoterapiaRESUMO
Background: Hearing can be impaired in many neurological conditions and can even represent a forme fruste of specific disorders. Auditory function can be measured by either subjective or objective tests. Objective tests are more useful in identifying which auditory pathway (superior or inferior) is most affected by disease. The inner ear's perilymphatic fluid communicates with the cerebrospinal fluid (CSF) via the cochlear aqueduct representing a window from which pathological changes in the contents of the CSF due to brain inflammation could, therefore, spread to and cause inflammation in the inner ear, damaging inner hair cells and leading to hearing impairment identifiable on tests of auditory function. Methods: A systematic review of the literature was performed, searching for papers with case-control studies that analyzed the hearing and migraine function in patients with neuro-inflammatory, neurodegenerative disorders. With data extracted from these papers, the risk of patients with neurological distortion product otoacoustic emission (DPOAE) was then calculated. Results: Patients with neurological disorders (headache, Parkinson's disease, and multiple sclerosis) had a higher risk of having peripheral auditory deficits when compared to healthy individuals. Conclusion: Existing data lend credence to the hypothesis that inflammatory mediators transmitted via fluid exchange across this communication window, thereby represents a key pathobiological mechanism capable of culminating in hearing disturbances associated with neuroimmunological and neuroinflammatory disorders of the nervous system.
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Laryngeal adenoid cystic carcinoma (LACC) is a sporadic neoplasm, especially if supraglottic. The COVID-19 pandemic worsened the presenting stage of many cancers and impacted their prognosis negatively. Here, a case of a patient with adenoid cystic carcinoma (ACC) with delayed diagnosis and a rapid deterioration with distant metastasis due to the COVID-19 pandemic is illustrated. Next, we present a literature review of this rare glottic ACC. The COVID-19 pandemic worsened the stage of presentation of many cancers and adversely affected their prognosis. The present case had a rapidly lethal course, undoubtedly due to the diagnosis delay caused by the COVID-19 pandemic, which impacted the prognosis of this rare glottic ACC. Strict follow-up is recommended for any suspicious clinical findings, as an early diagnosis will improve the disease prognosis, and to consider the influence of the COVID-19 pandemic, especially on the timing of common diagnostic and therapeutic procedures for oncological diseases. In the post-COVID-19 era, it is important to generate new diagnostic scenarios to achieve an increasingly rapid diagnosis of oncological diseases, especially the rare ones, through screening or similar procedures.
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The manuscript aims to clarify the origins of Western rhinosurgery through the ancient texts of the greatest physicians of the past, up to the Byzantine Era, focusing on the "exchange of knowledge" between peoples. This excursus is carried out by quoting the texts of the greatest doctors of the past, such as Hippocrates, Galen and Celsus and by analysing the works of Byzantine authors such as Oribasius, Aetius, Antillus, which, more than others, represent the moment of fusion and interpenetration of Ancient Medical knowledge, paving the way for the Medieval Scholae Medicae in the West. The aim, therefore, is to fill that sort of "great gap" (from the foundation of Constantinople in the 4th century AD to the early Arab culture in the 11th century AD) due to the fact that figures such as Branca, Vianeo and, finally, Tagliacozzi, are considered direct actors of a recovery of the "ancient knowledge" of classic authors. This literature tends to less evaluate, instead, that important and huge cultural exchange -literally osmotic- in medical and surgical knowledge between peoples and civilizations, that find a trait d'union in the application of medical knowledge and surgical practical techniques matured in the Byzantine, Arab and Early Medieval period. In final analysis, through the History of Rhinosurgery, this paper aims to highlight how Western medical knowledge is made up of the ensemble of cultures which are apparently distant and different from each other, which merge themselves in a truly universal and transcultural knowledge: the Medical knowledge. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Procedimentos Cirúrgicos Nasais , Humanos , História Antiga , Grécia AntigaRESUMO
This paper deals with the literary debate on the first experiments regarding blood transfusion on human beings between 1667 and 1668 in Europe, with particular attention to the less-known experimental research, carried out in Italy. The authors examine the details of the experimental developments, focusing on the techniques and instruments used by physicians involved in this new surgical approach, with special attention to the Italian debate and experimentations. The article suggests that transfusion was considered a part of what we could call "emergency surgery". In this framework, Italian transfusional pioneers played a central role in the improvement and transmission of a discipline that was still in its dawning throughout Europe. Moreover, the manuscript highlights the contribution of the "chirurgia infusoria" as an innovative therapeutic system for an immediate and rapid recovery. From this perspective, blood transfusion represents a surgical practice for reanimation and resuscitation. The objective of this work was to analyze the importance of foreign literature and the English and French disputes presented by Davia in Italy, which made them known. Despite foreign prohibition in Italy, experiments with animal-to-human transfusions continued after 1648. A papal bull excommunicating scientists for conducting such research has never been found.
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Transfusão de Sangue , Médicos , Animais , Humanos , Europa (Continente) , Itália , InternacionalidadeRESUMO
PURPOSE: A single-institution prospective pilot study was conducted to the assess correlation between salivary amylase and xerostomia in patients with head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Serum saliva amylase, clinician-reported xerostomia (using Common Terminology Criteria for Adverse Events), and patient-reported xerostomia (using 8-item self-reported xerostomia-specific questionnaire) were prospectively collected at baseline, during treatment and thereafter. Correlations between variables were assessed by correlation matrices. RESULTS: Twelve patients with locally advanced HNSCC formed the cohort. Eighty-three percent were male, 75% were smokers, 100% had clinical positive lymph nodes at diagnosis, and 42% received induction chemotherapy. All patients received IMRT with concurrent cisplatin-based chemotherapy. No grade ≥4 xerostomia was observed. Severe (G3) acute and late xerostomia occurred in five cases (41.7%) and two cases (16.7%), respectively. Patient-reported xerostomia scores were highly correlated with the clinician-reported scores (ρ = 0.73). A significant correlation was recorded between the concentration of amylase and the acute (ρ = -0.70) and late (ρ = -0.80) xerostomia. CONCLUSION: Preliminary results are encouraging. Prospective clinical trials are needed to define the value of salivary amylase in the management of HNSCC tumors.
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Amilases , Neoplasias de Cabeça e Pescoço , Radioterapia de Intensidade Modulada , Carcinoma de Células Escamosas de Cabeça e Pescoço , Xerostomia , Amilases/análise , Cisplatino/uso terapêutico , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Glândula Parótida , Projetos Piloto , Estudos Prospectivos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Saliva/enzimologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Xerostomia/etiologiaRESUMO
Attempts to analyze clinical unexpected cases of laryngeal fractures based on mild symptoms and physical findings. Even though a laryngeal fracture is rare in a living patient and when happens it is related to severe airways emergency, this case reported seems important to offer a possible differential diagnosis in patients who present with the same symptoms, if no other causes have been detected, like another one benign laryngeal disease.
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Chronic rhinosinusitis with nasal polyps (CRSwNP) and Severe Eosinophilic Asthma (SEA) are both frequently sustained by eosinophilic inflammation and are probably the manifestation of a unique disease of upper and lower respiratory tract. We retrospectively observed 11 patients with severe CRSwNP and concomitant SEA under add-on therapy with benralizumab evaluating symptoms using Sino Nasal Outcome Test-22 (SNOT-22), Visual Analogue Scale (VAS), and Asthma Control Test (ACT) and Nasal polyp size by endoscopic and radiological score by Nasal Polyp Score (NPS) and Lund-Mackay Score (LMS). At 6 and 12 months, the expression of cationic eosinophil protein (ECP), Interleukin 17 (IL-17), Interferon gamma (INF-γ), and vascular endothelial growth factor (VEGF) was measured by nasal scraping to assess mucosal inflammation. After 12 months of benralizumab treatment, SNOT-22 decreased from 45 (23-97) to 14 (5-53) (p < 0.05), total VAS of rhinologic symptoms decreased from 30 (17-44) to 9 (5-37) (p ≤ 0.01) and ACT score increased from 10 (5-15) to 24 (20-25) (p ≤ 0.01). NPS decreased from 5 (3-6) to 3 (2-4) after 6 months (p < 0.05) and to 2 (2-3) after one year respectively (p < 0.05) and LMS total score from 21 (15-24) to 17 (8-21) (p ≤ 0.01) after 12 months from starting treatment. Nasal mucosa scraping found differences in INF-γ and VEGF expression in patients compared to 10 healthy subjects, with a normalization of these markers during eosinophils depletion induced by benralizumab. This is the first pilot real-life study conducted with an anti-IL5R monoclonal antibody in severe eosinophilic asthma and severe CRSwNP patients showing that this treatment can induce benefit both diseases not only from the clinical, but also from the inflammatory point of view. Moreover, our research pointed out that INF-γ and VEGF may represent potential response biomarker.
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Asma , Pólipos Nasais , Rinite , Sinusite , Anticorpos Monoclonais Humanizados , Asma/diagnóstico , Asma/tratamento farmacológico , Biomarcadores , Doença Crônica , Eosinófilos , Humanos , Inflamação , Pólipos Nasais/complicações , Pólipos Nasais/tratamento farmacológico , Estudos Retrospectivos , Rinite/complicações , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , Fator A de Crescimento do Endotélio VascularRESUMO
Neurofibroma (NF) rarely arises in the retropharyngeal space (RPS) of patients with or without Neurofibromatosis type I (NF-I). The diffuse subtype of NF (DNF) is characterized by an infiltrative growth pattern and typically involves the skin and subcutaneous tissue of the head and neck. We describe the clinic-pathologic features of a DNF involving the RPS of an adult without NF-I. To date, this subtype of NF has never been reported at this site.
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Labyrinthine fistula (LF) is one of the most important complications of cholesteatoma and is defined as an abnormal communication between the inner and the middle ear. This study aims to describe our experience with the partial labyrinthectomy evaluating the post-operative hearing results. Twenty-one patients who presented labyrinthine fistula in the semicircular canals were included in the present study. Hearing impairment was present in 48% of patients (10/21). A pre-operative assessment using the Gardner-Robertson hearing classification showed the following: 52%, Class I; and 48%, Class II. A post-surgical Gardner-Robertson hearing classification evidenced the following: 43%, Class I; and 57%, Class II. The presence of LF is usually considered a negative prognostic factor for hearing preservation. The key point of partial labyrinthectomy surgery is the preservation of structures, keeping them wet with Ringer's solution throughout the procedures, and not performing suction that is close to the opened LF. The bony labyrinth is drilled underwater without suction, removing the entire cholesteatoma matrix and quickly plugging the site before and after the LF. This faster plugging of the labyrinth makes it possible to preserve the peri-lymph and the endo-lymph fluid and the hearing function. This study showed that a partial labyrinthectomy is useful for maintaining serviceable hearing in patients with LF.
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Hemangiomas are developmental vascular abnormalities that are common in the head and neck (60%), rare in the oral cavity, and uncommon in the tongue. A patient performed a multi-parametric MRI, which characterized the lesion of his tongue, providing relevant information for diagnostic, therapeutic orientation, and realization of slight aggressive surgery with consequent excellent recovery.
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Hand, foot, and mouth disease (HFMD) is a childhood febrile disease. Oral lesions and papulovesicular lesions on the hands and feet are the clinical signs of the disease. In our case, a 17-year-old boy presented to the emergency department, where he was diagnosed with HFMD. After 6 days, he felt intense pain in his right testicle, and therefore an ultrasound (US) examination was performed. US detected a hypoechoic mass-like area in the right testis. Viral etiology was suspected, and no therapy was prescribed. After a little more than 3 months, US examination showed a reduced lesion size. Viral epididymo-orchitis should be suspected in young men with a recent history of HFMD and testicular pain.